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Team recommends melanoma screening in CLL

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Team recommends melanoma screening in CLL

 

Micrograph showing CLL

 

Patients with chronic lymphocytic leukemia (CLL) should be routinely monitored for melanoma, according to researchers.

 

A study of 470 CLL patients showed they have a significantly higher risk of invasive melanoma than the general population.

 

Most of the melanomas reported in this study were detected via routine surveillance, and most were discovered before they reached an advanced stage.

 

Clive Zent, MD, of Wilmot Cancer Institute at the University of Rochester Medical Center in Rochester, New York, and his colleagues described this study in Leukemia Research.

 

The researchers analyzed data on 470 CLL patients followed for 2849 person-years. Eighteen of these patients developed 22 melanomas. This included 14 cases of invasive melanoma in 13 patients.

 

The rate of invasive melanoma was significantly higher in this CLL cohort than the rate observed in the age- and sex-matched general population. The standardized incidence ratio was 6.32.

 

“We do not for sure know why CLL patients are more susceptible to melanoma, but the most likely cause is a suppressed immune system,” Dr Zent noted.

 

“Normally, in people with healthy immune systems, malignant skin cells might be detected and destroyed before they become a problem. But in CLL patients, failure of this control system increases the rate at which cancer cells can grow into tumors and also the likelihood that they will become invasive or spread to distant sites.”

 

Detection and management

 

Fifteen of the 22 melanomas (68.2%) in the CLL cohort were detected via surveillance in a dermatology clinic, and 2 (9.1%) were detected at the CLL/lymphoma clinic.

 

Three cases of melanoma (14.3%) were detected within the first year of a patient’s CLL diagnosis.

 

Seven melanomas (33.3%) were detected at pathologic stage 0, 8 (38.1%) at stage I, 2 (9.5%) at stage II, 3 (14.3%) at stage III, and 1 (4.8%) at stage IV. Detailed data were not available for the remaining case.

 

Melanomas were managed with wide local excision (n=19), sentinel node biopsies (n=6), Mohs surgery (n=1), drugs (n=2), palliative care (n=1), and comfort care (n=1).

 

The 4 patients who received drugs, palliative care, or comfort care had advanced melanoma.

 

The patient who received palliative care was still alive at 2.4 years of follow-up. The patient who received comfort care died of metastatic melanoma 1.4 years after diagnosis.

 

The third patient with advanced melanoma received 2 cycles of dacarbazine and palliative radiation to lung and brain metastases. This patient died 3.6 years after melanoma diagnosis.

 

The fourth patient received ipilimumab for the melanoma while also receiving ibrutinib to treat her CLL. When the ipilimumab failed, the patient proceeded to pembrolizumab and achieved a near-complete response within 3 months. Then, an intensely hypermetabolic abdominal node was detected and successfully treated with radiation.

 

The patient continued on pembrolizumab, and her melanoma was in sustained remission at last follow-up, after 23 cycles of pembrolizumab. Her CLL was still responding to ibrutinib at that point as well.

 

Based on these data, Dr Zent and his colleagues recommend routine melanoma screening for CLL patients. The team believes such surveillance might decrease morbidity and mortality in these patients, although more research is needed to confirm this theory.

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Micrograph showing CLL

 

Patients with chronic lymphocytic leukemia (CLL) should be routinely monitored for melanoma, according to researchers.

 

A study of 470 CLL patients showed they have a significantly higher risk of invasive melanoma than the general population.

 

Most of the melanomas reported in this study were detected via routine surveillance, and most were discovered before they reached an advanced stage.

 

Clive Zent, MD, of Wilmot Cancer Institute at the University of Rochester Medical Center in Rochester, New York, and his colleagues described this study in Leukemia Research.

 

The researchers analyzed data on 470 CLL patients followed for 2849 person-years. Eighteen of these patients developed 22 melanomas. This included 14 cases of invasive melanoma in 13 patients.

 

The rate of invasive melanoma was significantly higher in this CLL cohort than the rate observed in the age- and sex-matched general population. The standardized incidence ratio was 6.32.

 

“We do not for sure know why CLL patients are more susceptible to melanoma, but the most likely cause is a suppressed immune system,” Dr Zent noted.

 

“Normally, in people with healthy immune systems, malignant skin cells might be detected and destroyed before they become a problem. But in CLL patients, failure of this control system increases the rate at which cancer cells can grow into tumors and also the likelihood that they will become invasive or spread to distant sites.”

 

Detection and management

 

Fifteen of the 22 melanomas (68.2%) in the CLL cohort were detected via surveillance in a dermatology clinic, and 2 (9.1%) were detected at the CLL/lymphoma clinic.

 

Three cases of melanoma (14.3%) were detected within the first year of a patient’s CLL diagnosis.

 

Seven melanomas (33.3%) were detected at pathologic stage 0, 8 (38.1%) at stage I, 2 (9.5%) at stage II, 3 (14.3%) at stage III, and 1 (4.8%) at stage IV. Detailed data were not available for the remaining case.

 

Melanomas were managed with wide local excision (n=19), sentinel node biopsies (n=6), Mohs surgery (n=1), drugs (n=2), palliative care (n=1), and comfort care (n=1).

 

The 4 patients who received drugs, palliative care, or comfort care had advanced melanoma.

 

The patient who received palliative care was still alive at 2.4 years of follow-up. The patient who received comfort care died of metastatic melanoma 1.4 years after diagnosis.

 

The third patient with advanced melanoma received 2 cycles of dacarbazine and palliative radiation to lung and brain metastases. This patient died 3.6 years after melanoma diagnosis.

 

The fourth patient received ipilimumab for the melanoma while also receiving ibrutinib to treat her CLL. When the ipilimumab failed, the patient proceeded to pembrolizumab and achieved a near-complete response within 3 months. Then, an intensely hypermetabolic abdominal node was detected and successfully treated with radiation.

 

The patient continued on pembrolizumab, and her melanoma was in sustained remission at last follow-up, after 23 cycles of pembrolizumab. Her CLL was still responding to ibrutinib at that point as well.

 

Based on these data, Dr Zent and his colleagues recommend routine melanoma screening for CLL patients. The team believes such surveillance might decrease morbidity and mortality in these patients, although more research is needed to confirm this theory.

 

Micrograph showing CLL

 

Patients with chronic lymphocytic leukemia (CLL) should be routinely monitored for melanoma, according to researchers.

 

A study of 470 CLL patients showed they have a significantly higher risk of invasive melanoma than the general population.

 

Most of the melanomas reported in this study were detected via routine surveillance, and most were discovered before they reached an advanced stage.

 

Clive Zent, MD, of Wilmot Cancer Institute at the University of Rochester Medical Center in Rochester, New York, and his colleagues described this study in Leukemia Research.

 

The researchers analyzed data on 470 CLL patients followed for 2849 person-years. Eighteen of these patients developed 22 melanomas. This included 14 cases of invasive melanoma in 13 patients.

 

The rate of invasive melanoma was significantly higher in this CLL cohort than the rate observed in the age- and sex-matched general population. The standardized incidence ratio was 6.32.

 

“We do not for sure know why CLL patients are more susceptible to melanoma, but the most likely cause is a suppressed immune system,” Dr Zent noted.

 

“Normally, in people with healthy immune systems, malignant skin cells might be detected and destroyed before they become a problem. But in CLL patients, failure of this control system increases the rate at which cancer cells can grow into tumors and also the likelihood that they will become invasive or spread to distant sites.”

 

Detection and management

 

Fifteen of the 22 melanomas (68.2%) in the CLL cohort were detected via surveillance in a dermatology clinic, and 2 (9.1%) were detected at the CLL/lymphoma clinic.

 

Three cases of melanoma (14.3%) were detected within the first year of a patient’s CLL diagnosis.

 

Seven melanomas (33.3%) were detected at pathologic stage 0, 8 (38.1%) at stage I, 2 (9.5%) at stage II, 3 (14.3%) at stage III, and 1 (4.8%) at stage IV. Detailed data were not available for the remaining case.

 

Melanomas were managed with wide local excision (n=19), sentinel node biopsies (n=6), Mohs surgery (n=1), drugs (n=2), palliative care (n=1), and comfort care (n=1).

 

The 4 patients who received drugs, palliative care, or comfort care had advanced melanoma.

 

The patient who received palliative care was still alive at 2.4 years of follow-up. The patient who received comfort care died of metastatic melanoma 1.4 years after diagnosis.

 

The third patient with advanced melanoma received 2 cycles of dacarbazine and palliative radiation to lung and brain metastases. This patient died 3.6 years after melanoma diagnosis.

 

The fourth patient received ipilimumab for the melanoma while also receiving ibrutinib to treat her CLL. When the ipilimumab failed, the patient proceeded to pembrolizumab and achieved a near-complete response within 3 months. Then, an intensely hypermetabolic abdominal node was detected and successfully treated with radiation.

 

The patient continued on pembrolizumab, and her melanoma was in sustained remission at last follow-up, after 23 cycles of pembrolizumab. Her CLL was still responding to ibrutinib at that point as well.

 

Based on these data, Dr Zent and his colleagues recommend routine melanoma screening for CLL patients. The team believes such surveillance might decrease morbidity and mortality in these patients, although more research is needed to confirm this theory.

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Abstinence and Heavy Drinking May Increase Dementia Risk

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Risk increases in a linear fashion at higher levels of consumption.

People who abstain from alcohol or consume more than 14 units per week during middle age are at increased risk of developing dementia, according to a study published online ahead of print August 1 in BMJ. However, the underlying mechanisms are likely to be different in the two groups.

Continuously increasing life expectancy and, according to World Health Organization estimates, an expected tripling of dementia prevalence by 2050 have increased the importance of understanding the impact of alcohol consumption on aging outcomes. Previous studies have indicated that moderate drinking is associated with a reduced risk of dementia, whereas abstinence and heavy drinking are associated with an increased risk. The evidence is far from conclusive, however, and the reasons underlying these associations remain unclear.

Drinking Patterns Analyzed

A team of researchers from France and the United Kingdom investigated the association between midlife alcohol consumption and risk of dementia into early old age. They also examined whether cardiometabolic disease affects this association. Their findings are based on data from 9,087 British civil servants who were between ages 35 and 55 in 1985 and took part in the ongoing Whitehall II Study, which is looking at the impact of social, behavioral, and biologic factors on long-term health.

Participants’ alcohol consumption and alcohol dependence were assessed at regular intervals between 1985 and 1993 (average age, 50). Alcohol consumption trajectories between 1985 and 2004 were also used to examine the association of long-term alcohol consumption and risk of dementia from midlife to early old age. Admissions for alcohol-related chronic diseases and cases of dementia from 1991 to 2017, and the role of cardiometabolic disease, were identified from hospital records.

Among the 9,087 participants, 397 cases of dementia were recorded over an average follow-up period of 23 years. Average age at dementia diagnosis was 76.

After adjusting for sociodemographic, lifestyle, and health-related factors that could have affected the results, the researchers found that abstinence in midlife or drinking more than 14 units per week was associated with a higher risk of dementia, compared with drinking one to 14 units of alcohol per week. Among those drinking more than 14 units per week of alcohol, every seven-unit-per-week increase in consumption was associated with a 17% increase in dementia risk.

History of hospital admission for alcohol-related chronic diseases was associated with a quadrupled risk of dementia. The researchers showed that some of the excess dementia risk in abstainers resulted from a greater risk of cardiometabolic disease.

Alcohol consumption trajectories showed similar results, with long-term abstainers, those reporting decreased consumption, and long-term consumers of more than 14 units per week at a higher risk of dementia, compared with long-term consumers of one to 14 units per week.

Further analyses to test the strength of the associations produced broadly consistent findings, suggesting that the results are robust. Taken together, these results suggest that abstention and excessive alcohol consumption are associated with an increased risk of dementia, said lead author Séverine Sabia, PhD, a research associate at Inserm, U1018, Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, France and Hôpital Paul Brousse in Villejuif, France, and colleagues.

According to the researchers, no firm conclusions regarding cause and effect can be drawn from this observational study, and the researchers said they cannot rule out the possibility that some of the risk may result from confounding factors. However, the findings “strengthen the evidence that excessive alcohol consumption is a risk factor for dementia” and “encourage use of lower thresholds of alcohol consumption in guidelines to promote cognitive health at older ages,” they said. The findings “should not motivate people who do not drink to start drinking, given the known detrimental effects of alcohol consumption for mortality, neuropsychiatric disorders, cirrhosis of the liver, and cancer,” they added.

 

 

Some Questions Answered, Some Questions Remain

This study fills gaps in knowledge, “but we should remain cautious and not change current recommendations on alcohol use based solely on epidemiologic studies,” said Sevil Yasar, MD, PhD, in a related editorial. Dr. Yasar is an Associate Professor of Medicine at Johns Hopkins School of Medicine in Baltimore.

Dr. Yasar called for further studies and, ideally, a government-funded randomized clinical trial with close monitoring of adverse outcomes to answer pressing questions about the possible protective effects of light-to-moderate alcohol use on risk of dementia and about the mediating role of cardiovascular disease. “Alcohol consumption of one to 14 units per week may benefit brain health; however, alcohol choices must take into account all associated risks, including liver disease and cancer.”

Suggested Reading

Sabia S, Fayosse A, Dumurgier J, et al. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362:k2927.

Yasar S. Relation between alcohol consumption in midlife and dementia in late life. BMJ. 2018;362:k3164.

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Risk increases in a linear fashion at higher levels of consumption.

Risk increases in a linear fashion at higher levels of consumption.

People who abstain from alcohol or consume more than 14 units per week during middle age are at increased risk of developing dementia, according to a study published online ahead of print August 1 in BMJ. However, the underlying mechanisms are likely to be different in the two groups.

Continuously increasing life expectancy and, according to World Health Organization estimates, an expected tripling of dementia prevalence by 2050 have increased the importance of understanding the impact of alcohol consumption on aging outcomes. Previous studies have indicated that moderate drinking is associated with a reduced risk of dementia, whereas abstinence and heavy drinking are associated with an increased risk. The evidence is far from conclusive, however, and the reasons underlying these associations remain unclear.

Drinking Patterns Analyzed

A team of researchers from France and the United Kingdom investigated the association between midlife alcohol consumption and risk of dementia into early old age. They also examined whether cardiometabolic disease affects this association. Their findings are based on data from 9,087 British civil servants who were between ages 35 and 55 in 1985 and took part in the ongoing Whitehall II Study, which is looking at the impact of social, behavioral, and biologic factors on long-term health.

Participants’ alcohol consumption and alcohol dependence were assessed at regular intervals between 1985 and 1993 (average age, 50). Alcohol consumption trajectories between 1985 and 2004 were also used to examine the association of long-term alcohol consumption and risk of dementia from midlife to early old age. Admissions for alcohol-related chronic diseases and cases of dementia from 1991 to 2017, and the role of cardiometabolic disease, were identified from hospital records.

Among the 9,087 participants, 397 cases of dementia were recorded over an average follow-up period of 23 years. Average age at dementia diagnosis was 76.

After adjusting for sociodemographic, lifestyle, and health-related factors that could have affected the results, the researchers found that abstinence in midlife or drinking more than 14 units per week was associated with a higher risk of dementia, compared with drinking one to 14 units of alcohol per week. Among those drinking more than 14 units per week of alcohol, every seven-unit-per-week increase in consumption was associated with a 17% increase in dementia risk.

History of hospital admission for alcohol-related chronic diseases was associated with a quadrupled risk of dementia. The researchers showed that some of the excess dementia risk in abstainers resulted from a greater risk of cardiometabolic disease.

Alcohol consumption trajectories showed similar results, with long-term abstainers, those reporting decreased consumption, and long-term consumers of more than 14 units per week at a higher risk of dementia, compared with long-term consumers of one to 14 units per week.

Further analyses to test the strength of the associations produced broadly consistent findings, suggesting that the results are robust. Taken together, these results suggest that abstention and excessive alcohol consumption are associated with an increased risk of dementia, said lead author Séverine Sabia, PhD, a research associate at Inserm, U1018, Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, France and Hôpital Paul Brousse in Villejuif, France, and colleagues.

According to the researchers, no firm conclusions regarding cause and effect can be drawn from this observational study, and the researchers said they cannot rule out the possibility that some of the risk may result from confounding factors. However, the findings “strengthen the evidence that excessive alcohol consumption is a risk factor for dementia” and “encourage use of lower thresholds of alcohol consumption in guidelines to promote cognitive health at older ages,” they said. The findings “should not motivate people who do not drink to start drinking, given the known detrimental effects of alcohol consumption for mortality, neuropsychiatric disorders, cirrhosis of the liver, and cancer,” they added.

 

 

Some Questions Answered, Some Questions Remain

This study fills gaps in knowledge, “but we should remain cautious and not change current recommendations on alcohol use based solely on epidemiologic studies,” said Sevil Yasar, MD, PhD, in a related editorial. Dr. Yasar is an Associate Professor of Medicine at Johns Hopkins School of Medicine in Baltimore.

Dr. Yasar called for further studies and, ideally, a government-funded randomized clinical trial with close monitoring of adverse outcomes to answer pressing questions about the possible protective effects of light-to-moderate alcohol use on risk of dementia and about the mediating role of cardiovascular disease. “Alcohol consumption of one to 14 units per week may benefit brain health; however, alcohol choices must take into account all associated risks, including liver disease and cancer.”

Suggested Reading

Sabia S, Fayosse A, Dumurgier J, et al. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362:k2927.

Yasar S. Relation between alcohol consumption in midlife and dementia in late life. BMJ. 2018;362:k3164.

People who abstain from alcohol or consume more than 14 units per week during middle age are at increased risk of developing dementia, according to a study published online ahead of print August 1 in BMJ. However, the underlying mechanisms are likely to be different in the two groups.

Continuously increasing life expectancy and, according to World Health Organization estimates, an expected tripling of dementia prevalence by 2050 have increased the importance of understanding the impact of alcohol consumption on aging outcomes. Previous studies have indicated that moderate drinking is associated with a reduced risk of dementia, whereas abstinence and heavy drinking are associated with an increased risk. The evidence is far from conclusive, however, and the reasons underlying these associations remain unclear.

Drinking Patterns Analyzed

A team of researchers from France and the United Kingdom investigated the association between midlife alcohol consumption and risk of dementia into early old age. They also examined whether cardiometabolic disease affects this association. Their findings are based on data from 9,087 British civil servants who were between ages 35 and 55 in 1985 and took part in the ongoing Whitehall II Study, which is looking at the impact of social, behavioral, and biologic factors on long-term health.

Participants’ alcohol consumption and alcohol dependence were assessed at regular intervals between 1985 and 1993 (average age, 50). Alcohol consumption trajectories between 1985 and 2004 were also used to examine the association of long-term alcohol consumption and risk of dementia from midlife to early old age. Admissions for alcohol-related chronic diseases and cases of dementia from 1991 to 2017, and the role of cardiometabolic disease, were identified from hospital records.

Among the 9,087 participants, 397 cases of dementia were recorded over an average follow-up period of 23 years. Average age at dementia diagnosis was 76.

After adjusting for sociodemographic, lifestyle, and health-related factors that could have affected the results, the researchers found that abstinence in midlife or drinking more than 14 units per week was associated with a higher risk of dementia, compared with drinking one to 14 units of alcohol per week. Among those drinking more than 14 units per week of alcohol, every seven-unit-per-week increase in consumption was associated with a 17% increase in dementia risk.

History of hospital admission for alcohol-related chronic diseases was associated with a quadrupled risk of dementia. The researchers showed that some of the excess dementia risk in abstainers resulted from a greater risk of cardiometabolic disease.

Alcohol consumption trajectories showed similar results, with long-term abstainers, those reporting decreased consumption, and long-term consumers of more than 14 units per week at a higher risk of dementia, compared with long-term consumers of one to 14 units per week.

Further analyses to test the strength of the associations produced broadly consistent findings, suggesting that the results are robust. Taken together, these results suggest that abstention and excessive alcohol consumption are associated with an increased risk of dementia, said lead author Séverine Sabia, PhD, a research associate at Inserm, U1018, Centre for Research in Epidemiology and Population Health, Université Paris-Saclay, France and Hôpital Paul Brousse in Villejuif, France, and colleagues.

According to the researchers, no firm conclusions regarding cause and effect can be drawn from this observational study, and the researchers said they cannot rule out the possibility that some of the risk may result from confounding factors. However, the findings “strengthen the evidence that excessive alcohol consumption is a risk factor for dementia” and “encourage use of lower thresholds of alcohol consumption in guidelines to promote cognitive health at older ages,” they said. The findings “should not motivate people who do not drink to start drinking, given the known detrimental effects of alcohol consumption for mortality, neuropsychiatric disorders, cirrhosis of the liver, and cancer,” they added.

 

 

Some Questions Answered, Some Questions Remain

This study fills gaps in knowledge, “but we should remain cautious and not change current recommendations on alcohol use based solely on epidemiologic studies,” said Sevil Yasar, MD, PhD, in a related editorial. Dr. Yasar is an Associate Professor of Medicine at Johns Hopkins School of Medicine in Baltimore.

Dr. Yasar called for further studies and, ideally, a government-funded randomized clinical trial with close monitoring of adverse outcomes to answer pressing questions about the possible protective effects of light-to-moderate alcohol use on risk of dementia and about the mediating role of cardiovascular disease. “Alcohol consumption of one to 14 units per week may benefit brain health; however, alcohol choices must take into account all associated risks, including liver disease and cancer.”

Suggested Reading

Sabia S, Fayosse A, Dumurgier J, et al. Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study. BMJ. 2018;362:k2927.

Yasar S. Relation between alcohol consumption in midlife and dementia in late life. BMJ. 2018;362:k3164.

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Frequent BCCs linked to blood cancers

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Woman sunbathing

 

New research suggests people who develop frequent cases of basal cell carcinoma (BCC) have an increased risk of leukemias, lymphomas, and other cancers.

 

“We discovered that people who develop 6 or more basal cell carcinomas during a 10-year period are about 3 times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, of Stanford University School of Medicine in California.

 

“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

 

Dr Sarin and her colleagues reported their findings in JCI Insight.

 

Stanford cohort

 

The researchers first studied 61 patients treated at Stanford Health Care for unusually frequent BCCs—an average of 11 per patient over a 10-year period. The team investigated whether these patients may have mutations in 29 genes that code for DNA damage repair proteins.

 

“We found that about 20% of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3% of the general population,” Dr Sarin said. “That’s shockingly high.”

 

Specifically, there were 12 BCC patients (19.7%) who had 13 pathogenic mutations in 12 genes—APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. And 3.0% of non-Finnish European subjects in the Exome Aggregation Consortium had pathogenic mutations in these 12 genes.

 

Furthermore, 21 of the 61 BCC patients (64.4%) had a history of additional cancers. This included 5 hematologic malignancies (leukemia/lymphoma), 5 invasive melanomas, and 2 breast, 2 colon, and 5 prostate cancers.

 

When the researchers compared the cancer prevalence in these patients to the Surveillance, Epidemiology, and End Results-estimated prevalence of cancer in the 60- to 69-year-old population of European descent, the BCC cohort had an increased risk of any cancer—a relative risk (RR) of 3.5 (P<0.001).

 

The RR was 3.5 for leukemia and lymphoma (P=0.004), 11.9 for invasive melanoma (P<0.001), 4.5 for colon cancer (P=0.030), 5.6 for breast cancer (P=0.009), and 4.7 for prostate cancer (P<0.001).

 

Insurance cohort

 

To confirm the findings in the Stanford cohort, the researchers applied a similar analysis to a large medical insurance claims database, Truven MarketScan.

 

The database contained 111,562 patients with 1 case of BCC, 13,264 patients with 6 or more BCCs, and 2920 patients with 12 or more BCCs. Truven patients with no history of BCC served as controls.

 

The researchers adjusted for age and sex and found that patients with 1 BCC, 6 or more BCCs, and 12 or more BCCs had an increased risk of any cancer compared to controls.

 

The odds ratio (OR) for any cancer was 1.61 for patients with 1 BCC, 3.12 for those with 6 or more BCCs, and 4.15 for patients with 12 or more BCCs.

 

The OR for Hodgkin lymphoma was 2.27 for patients with 1 BCC, 8.94 for patients with 6 or more BCCs, and 15.41 for patients with 12 or more BCCs.

 

The OR for non-Hodgkin lymphoma was 1.40 for patients with 1 BCC, 2.59 for patients with 6 or more BCCs, and 3.10 for patients with 12 or more BCCs.

 

The OR for leukemia was 1.76 for patients with 1 BCC, 3.23 for patients with 6 or more BCCs, and 5.78 for patients with 12 or more BCCs.

 

The researchers pointed out that, the more BCCs an individual had, the more likely that person was to have had other cancers as well.

 

“I was surprised to see such a strong correlation, but it’s also very gratifying,” Dr Sarin said. “Now, we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers and perhaps suggest that they consider genetic testing and increased screening.”

 

 

 

The researchers are continuing to enroll Stanford patients in their study to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. The team would also like to conduct a similar study in patients with frequent melanomas.

 

The current study was supported by the Dermatology Foundation, the Stanford Society of Physician Scholars, the American Skin Association, and Pellepharm Inc.

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Woman sunbathing

 

New research suggests people who develop frequent cases of basal cell carcinoma (BCC) have an increased risk of leukemias, lymphomas, and other cancers.

 

“We discovered that people who develop 6 or more basal cell carcinomas during a 10-year period are about 3 times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, of Stanford University School of Medicine in California.

 

“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

 

Dr Sarin and her colleagues reported their findings in JCI Insight.

 

Stanford cohort

 

The researchers first studied 61 patients treated at Stanford Health Care for unusually frequent BCCs—an average of 11 per patient over a 10-year period. The team investigated whether these patients may have mutations in 29 genes that code for DNA damage repair proteins.

 

“We found that about 20% of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3% of the general population,” Dr Sarin said. “That’s shockingly high.”

 

Specifically, there were 12 BCC patients (19.7%) who had 13 pathogenic mutations in 12 genes—APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. And 3.0% of non-Finnish European subjects in the Exome Aggregation Consortium had pathogenic mutations in these 12 genes.

 

Furthermore, 21 of the 61 BCC patients (64.4%) had a history of additional cancers. This included 5 hematologic malignancies (leukemia/lymphoma), 5 invasive melanomas, and 2 breast, 2 colon, and 5 prostate cancers.

 

When the researchers compared the cancer prevalence in these patients to the Surveillance, Epidemiology, and End Results-estimated prevalence of cancer in the 60- to 69-year-old population of European descent, the BCC cohort had an increased risk of any cancer—a relative risk (RR) of 3.5 (P<0.001).

 

The RR was 3.5 for leukemia and lymphoma (P=0.004), 11.9 for invasive melanoma (P<0.001), 4.5 for colon cancer (P=0.030), 5.6 for breast cancer (P=0.009), and 4.7 for prostate cancer (P<0.001).

 

Insurance cohort

 

To confirm the findings in the Stanford cohort, the researchers applied a similar analysis to a large medical insurance claims database, Truven MarketScan.

 

The database contained 111,562 patients with 1 case of BCC, 13,264 patients with 6 or more BCCs, and 2920 patients with 12 or more BCCs. Truven patients with no history of BCC served as controls.

 

The researchers adjusted for age and sex and found that patients with 1 BCC, 6 or more BCCs, and 12 or more BCCs had an increased risk of any cancer compared to controls.

 

The odds ratio (OR) for any cancer was 1.61 for patients with 1 BCC, 3.12 for those with 6 or more BCCs, and 4.15 for patients with 12 or more BCCs.

 

The OR for Hodgkin lymphoma was 2.27 for patients with 1 BCC, 8.94 for patients with 6 or more BCCs, and 15.41 for patients with 12 or more BCCs.

 

The OR for non-Hodgkin lymphoma was 1.40 for patients with 1 BCC, 2.59 for patients with 6 or more BCCs, and 3.10 for patients with 12 or more BCCs.

 

The OR for leukemia was 1.76 for patients with 1 BCC, 3.23 for patients with 6 or more BCCs, and 5.78 for patients with 12 or more BCCs.

 

The researchers pointed out that, the more BCCs an individual had, the more likely that person was to have had other cancers as well.

 

“I was surprised to see such a strong correlation, but it’s also very gratifying,” Dr Sarin said. “Now, we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers and perhaps suggest that they consider genetic testing and increased screening.”

 

 

 

The researchers are continuing to enroll Stanford patients in their study to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. The team would also like to conduct a similar study in patients with frequent melanomas.

 

The current study was supported by the Dermatology Foundation, the Stanford Society of Physician Scholars, the American Skin Association, and Pellepharm Inc.

 

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New research suggests people who develop frequent cases of basal cell carcinoma (BCC) have an increased risk of leukemias, lymphomas, and other cancers.

 

“We discovered that people who develop 6 or more basal cell carcinomas during a 10-year period are about 3 times more likely than the general population to develop other, unrelated cancers,” said Kavita Sarin, MD, PhD, of Stanford University School of Medicine in California.

 

“We’re hopeful that this finding could be a way to identify people at an increased risk for a life-threatening malignancy before those cancers develop.”

 

Dr Sarin and her colleagues reported their findings in JCI Insight.

 

Stanford cohort

 

The researchers first studied 61 patients treated at Stanford Health Care for unusually frequent BCCs—an average of 11 per patient over a 10-year period. The team investigated whether these patients may have mutations in 29 genes that code for DNA damage repair proteins.

 

“We found that about 20% of the people with frequent basal cell carcinomas have a mutation in one of the genes responsible for repairing DNA damage, versus about 3% of the general population,” Dr Sarin said. “That’s shockingly high.”

 

Specifically, there were 12 BCC patients (19.7%) who had 13 pathogenic mutations in 12 genes—APC, BARD1, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NBN, and PALB2. And 3.0% of non-Finnish European subjects in the Exome Aggregation Consortium had pathogenic mutations in these 12 genes.

 

Furthermore, 21 of the 61 BCC patients (64.4%) had a history of additional cancers. This included 5 hematologic malignancies (leukemia/lymphoma), 5 invasive melanomas, and 2 breast, 2 colon, and 5 prostate cancers.

 

When the researchers compared the cancer prevalence in these patients to the Surveillance, Epidemiology, and End Results-estimated prevalence of cancer in the 60- to 69-year-old population of European descent, the BCC cohort had an increased risk of any cancer—a relative risk (RR) of 3.5 (P<0.001).

 

The RR was 3.5 for leukemia and lymphoma (P=0.004), 11.9 for invasive melanoma (P<0.001), 4.5 for colon cancer (P=0.030), 5.6 for breast cancer (P=0.009), and 4.7 for prostate cancer (P<0.001).

 

Insurance cohort

 

To confirm the findings in the Stanford cohort, the researchers applied a similar analysis to a large medical insurance claims database, Truven MarketScan.

 

The database contained 111,562 patients with 1 case of BCC, 13,264 patients with 6 or more BCCs, and 2920 patients with 12 or more BCCs. Truven patients with no history of BCC served as controls.

 

The researchers adjusted for age and sex and found that patients with 1 BCC, 6 or more BCCs, and 12 or more BCCs had an increased risk of any cancer compared to controls.

 

The odds ratio (OR) for any cancer was 1.61 for patients with 1 BCC, 3.12 for those with 6 or more BCCs, and 4.15 for patients with 12 or more BCCs.

 

The OR for Hodgkin lymphoma was 2.27 for patients with 1 BCC, 8.94 for patients with 6 or more BCCs, and 15.41 for patients with 12 or more BCCs.

 

The OR for non-Hodgkin lymphoma was 1.40 for patients with 1 BCC, 2.59 for patients with 6 or more BCCs, and 3.10 for patients with 12 or more BCCs.

 

The OR for leukemia was 1.76 for patients with 1 BCC, 3.23 for patients with 6 or more BCCs, and 5.78 for patients with 12 or more BCCs.

 

The researchers pointed out that, the more BCCs an individual had, the more likely that person was to have had other cancers as well.

 

“I was surprised to see such a strong correlation, but it’s also very gratifying,” Dr Sarin said. “Now, we can ask patients with repeated basal cell carcinomas whether they have family members with other types of cancers and perhaps suggest that they consider genetic testing and increased screening.”

 

 

 

The researchers are continuing to enroll Stanford patients in their study to learn whether particular mutations in genes responsible for repairing DNA damage are linked to the development of specific malignancies. The team would also like to conduct a similar study in patients with frequent melanomas.

 

The current study was supported by the Dermatology Foundation, the Stanford Society of Physician Scholars, the American Skin Association, and Pellepharm Inc.

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Increased B-cell lymphoma risk with JAK1/2 inhibitors

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Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19+ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

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Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19+ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

Patients with myeloproliferative neoplasms treated with Janus-kinase (JAK) 1/2 inhibitors may be at significantly increased risk of aggressive B cell non-Hodgkin lymphomas, according to a study published in Blood.

A retrospective cohort study of 626 Viennese patients with myeloproliferative neoplasms – 69 of whom were treated with JAK1/2 inhibitors – found that 4 of the 69 patients (5.8%) developed aggressive B-cell lymphoma, compared with just 2 patients (0.36%) in the rest of the group. This represented a significant, 16-fold higher risk of aggressive B cell lymphoma associated with JAK1/2 inhibitor therapy (P = .0017).

The lymphoma was diagnosed within 13-35 months of starting JAK1/2 inhibitors. In three patients, the disease was in the bone marrow and peripheral blood, one patient had it in mammary tissue, and another had it in mucosal tissue. All four lymphomas showed positive MYC and p53 staining.

All four patients had been treated with ruxolitinib, one was also treated with fedratinib, and three of the four had been pretreated with alkylating agents.

Meanwhile, a second retrospective cohort study in Paris of 929 patients with myeloproliferative neoplasms, reported in the same paper, found that 3.51% of those treated with ruxolitinib developed lymphoma, compared with 0.23% of conventionally-treated patients.

Using archived bone marrow samples from 54 of the 69 patients treated with JAK1/2 inhibitors, researchers discovered that 15.9% of them – including three of the B-cell lymphoma patients (the fourth was not tested) – had a preexisting B cell clone. This was present as early as 47-70 months before the lymphoma diagnosis.

“In patients, the clonal B-cell population was present as long as 6 years before overt lymphoma and preceded JAK1/2 inhibition which offers the opportunity to determine patients at risk,” wrote Edit Porpaczy, MD, of the Comprehensive Cancer Center at the Medical University of Vienna, and her coauthors. “Targeted inhibition of JAK-STAT signaling appears to be required to trigger the appearance of the B-cell clone as other treatments eliminating the myeloid cell load in men do not exert a comparable effect.”

In the Viennese cohort, three of the lymphomas were aggressive CD19+ B-cell type, and the fourth was a nonspecified high-grade B-cell lymphoma.

Researchers also looked at the effects of JAK1/2 inhibition in STAT1-/- mice, and found that two-thirds developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B-cells.

“Upon STAT1-deficiency myeloid hyperplasia is paralleled by the occurrence of a malignant B-cell clone, which evolves into disease upon bone-marrow transplantation and gives rise to a leukemic lymphoma phenotype,” the authors wrote.

The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank and the WWTF Precision Medicine Program. Several authors reported support, funding or advisory board positions with the pharmaceutical industry.

SOURCE: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

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Key clinical point: JAK1/2 inhibition in patients with myeloproliferative neoplasms is linked to a higher risk of aggressive lymphoma.

Major finding: Patients with myeloproliferative neoplasms treated with JAK1/2 inhibitors have a 16-fold higher incidence of lymphoma.

Study details: A retrospective cohort study of 626 patients with myeloproliferative neoplasms.

Disclosures: The study was supported by the Austrian Science Fund, the Anniversary Fund of the Austrian National Bank, and the WWTF Precision Medicine Program. Several authors reported support, funding, or advisory board positions with the pharmaceutical industry.

Source: Porpaczy E et al. Blood. 2018 Jun 14. doi: 10.1182/blood-2017-10-810739.

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New chronic lymphocytic leukemia guidelines from the UK

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Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

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Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

 

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

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Key clinical point: Fludarabine, cyclophosphamide, and rituximab should be first-line therapy for patients with chronic lymphocytic leukemia (CLL) without TP53 disruption.

Major finding: All patients diagnosed with CLL should be tested for TP53 disruption.

Study details: A guideline developed by the British Society for Haematology offering recommendations for CLL treatment outside clinical trials.

Disclosures: The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

Source: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

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Open Clinical Trials for Patients With Renal Cell Carcinoma (FULL)

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Open Clinical Trials for Patients With Renal Cell Carcinoma

Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting from those populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors more than 430 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 24, 2017; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for kidney cancer/renal cell carninoma. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma

This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least 1 line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients’ tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment that targets their tumor’s particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

ID: NCT02465060
Sponsor:
National Cancer Institute
Locations (contact): Naval Medical Center-San Diego, California (Preston S. Gable); VA Connecticut Healthcare System-West Haven Campus (Herta H. Chao); Durham VAMC, North Carolina (Michael J. Kelley); Walter Reed National Military Medical Center, Bethesda, Maryland (Jeremy G. Perkins)

Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer

This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.

ID: NCT00378703
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Jesse Brown VAMC, Chicago, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; VA New Jersey Health Care System East Orange; Dayton VAMC, Ohio; Michael E. DeBakey VAMC, Houston, Texas

Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery (S0931)

Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.

ID: NCT01120249
Sponsor: Southwest Oncology Group
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC Indianapolis, Indiana; VAMC Baltimore, Maryland; Minneapolis VeteransMedical Center, Minnesota; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; Wright-Patterson, Medical Center, Ohio; Michael E.DeBakey VAMC, Houston, Texas; Audie L. Murphy VA Hospital, San Antonio, Texas

Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer

This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.

ID: NCT01835158
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Minneapolis Veterans Medical Center, Minnesota; VAMC Columbia, Missouri; VA Western New York Health Care System, Buffalo

Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

Sponsor: National Cancer Institute
ID: NCT01198158
Locations: Jesse Brown VAMC, Chicago, Illinois; Walter Reed National Military Medical Center, Bethesda, Maryland; VA Western New York Health Care System, Buffalo

 

 

Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery

This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Sponsor: National Cancer Institute (NCI)
ID: NCT01688973
Locations: Hines VA Hospital, Illinois; VA New Jersey Health Care System, East Orange; Audie L. Murphy VA Hospital, San Antonio, Texas

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the U.S. and 2 in Canada will participate in this study.

Sponsor: Celgene
ID: NCT02223052
Location: VAMC Kansas City, Missouri

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.

Sponsor: National Cancer Institute
ID: NCT00942331
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Baltimore VAMC, Maryland; Columbia VA, Missouri; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; VA Western New York Health Care System, Buffalo; Dayton VAMC, Ohio

Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction

This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.

Sponsor: National Cancer Institute
ID: NCT00365157
Location: VA Hospital-Martinez, California

 

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Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting from those populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors more than 430 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 24, 2017; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for kidney cancer/renal cell carninoma. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma

This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least 1 line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients’ tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment that targets their tumor’s particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

ID: NCT02465060
Sponsor:
National Cancer Institute
Locations (contact): Naval Medical Center-San Diego, California (Preston S. Gable); VA Connecticut Healthcare System-West Haven Campus (Herta H. Chao); Durham VAMC, North Carolina (Michael J. Kelley); Walter Reed National Military Medical Center, Bethesda, Maryland (Jeremy G. Perkins)

Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer

This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.

ID: NCT00378703
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Jesse Brown VAMC, Chicago, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; VA New Jersey Health Care System East Orange; Dayton VAMC, Ohio; Michael E. DeBakey VAMC, Houston, Texas

Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery (S0931)

Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.

ID: NCT01120249
Sponsor: Southwest Oncology Group
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC Indianapolis, Indiana; VAMC Baltimore, Maryland; Minneapolis VeteransMedical Center, Minnesota; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; Wright-Patterson, Medical Center, Ohio; Michael E.DeBakey VAMC, Houston, Texas; Audie L. Murphy VA Hospital, San Antonio, Texas

Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer

This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.

ID: NCT01835158
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Minneapolis Veterans Medical Center, Minnesota; VAMC Columbia, Missouri; VA Western New York Health Care System, Buffalo

Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

Sponsor: National Cancer Institute
ID: NCT01198158
Locations: Jesse Brown VAMC, Chicago, Illinois; Walter Reed National Military Medical Center, Bethesda, Maryland; VA Western New York Health Care System, Buffalo

 

 

Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery

This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Sponsor: National Cancer Institute (NCI)
ID: NCT01688973
Locations: Hines VA Hospital, Illinois; VA New Jersey Health Care System, East Orange; Audie L. Murphy VA Hospital, San Antonio, Texas

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the U.S. and 2 in Canada will participate in this study.

Sponsor: Celgene
ID: NCT02223052
Location: VAMC Kansas City, Missouri

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.

Sponsor: National Cancer Institute
ID: NCT00942331
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Baltimore VAMC, Maryland; Columbia VA, Missouri; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; VA Western New York Health Care System, Buffalo; Dayton VAMC, Ohio

Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction

This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.

Sponsor: National Cancer Institute
ID: NCT00365157
Location: VA Hospital-Martinez, California

 

Click here to read the digital edition. 

Providing access to clinical trials for veteran and active-duty military patients can be a challenge, but a significant number of trials are now recruiting from those populations. Many trials explicitly recruit patients from the VA, the military, and IHS. The VA Office of Research and Development alone sponsors more than 430 research initiatives, and many more are sponsored by Walter Reed National Medical Center and other major defense and VA facilities. The clinical trials listed below are all open as of July 24, 2017; have at least 1 VA, DoD, or IHS location recruiting patients; and are focused on treatment for kidney cancer/renal cell carninoma. For additional information and full inclusion/exclusion criteria, please consult clinicaltrials.gov.

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma

This phase II trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least 1 line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients’ tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment that targets their tumor’s particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.

ID: NCT02465060
Sponsor:
National Cancer Institute
Locations (contact): Naval Medical Center-San Diego, California (Preston S. Gable); VA Connecticut Healthcare System-West Haven Campus (Herta H. Chao); Durham VAMC, North Carolina (Michael J. Kelley); Walter Reed National Military Medical Center, Bethesda, Maryland (Jeremy G. Perkins)

Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer

This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.

ID: NCT00378703
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Jesse Brown VAMC, Chicago, Illinois; Richard L. Roudebush VAMC, Indianapolis, Indiana; VA New Jersey Health Care System East Orange; Dayton VAMC, Ohio; Michael E. DeBakey VAMC, Houston, Texas

Everolimus in Treating Patients With Kidney Cancer Who Have Undergone Surgery (S0931)

Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. This phase III trial is studying everolimus to see how well it works in treating patients with kidney cancer who have undergone surgery.

ID: NCT01120249
Sponsor: Southwest Oncology Group
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Hines VA Hospital, Illinois; Richard L. Roudebush VAMC Indianapolis, Indiana; VAMC Baltimore, Maryland; Minneapolis VeteransMedical Center, Minnesota; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; Wright-Patterson, Medical Center, Ohio; Michael E.DeBakey VAMC, Houston, Texas; Audie L. Murphy VA Hospital, San Antonio, Texas

Cabozantinib-s-malate or Sunitinib Malate in Treating Patients With Previously Untreated Locally Advanced or Metastatic Kidney Cancer

This randomized phase II trial studies how well cabozantinib-s-malate works compared to sunitinib malate in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.

ID: NCT01835158
Sponsor: National Cancer Institute
Locations: VA San Diego Medical Center, California; Minneapolis Veterans Medical Center, Minnesota; VAMC Columbia, Missouri; VA Western New York Health Care System, Buffalo

Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy

This randomized phase III trial studies giving everolimus together with bevacizumab to see how well it works compared to everolimus alone in treating patients with advanced kidney cancer that progressed after first-line therapy. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can interfere with tumor growth by blocking the ability of tumor cells to grow and spread. Everolimus and bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with bevacizumab is better than everolimus alone in treating patients with advanced kidney cancer that has progressed after first-line therapy.

Sponsor: National Cancer Institute
ID: NCT01198158
Locations: Jesse Brown VAMC, Chicago, Illinois; Walter Reed National Military Medical Center, Bethesda, Maryland; VA Western New York Health Care System, Buffalo

 

 

Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot Be Removed by Surgery

This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Sponsor: National Cancer Institute (NCI)
ID: NCT01688973
Locations: Hines VA Hospital, Illinois; VA New Jersey Health Care System, East Orange; Audie L. Murphy VA Hospital, San Antonio, Texas

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

This study will enroll approximately 60 subjects in stage I and 60 subjects in stage II with hematologic or solid tumor malignancies, excluding gastrointestinal tumors and tumors that have originated or metastasized to the liver for which no standard treatment exists or have progressed or recurred following prior therapy. Subjects must not be eligible for therapy of higher curative potential where an alternative treatment has been shown to prolong survival in an analogous population. Approximately 23 sites in the U.S. and 2 in Canada will participate in this study.

Sponsor: Celgene
ID: NCT02223052
Location: VAMC Kansas City, Missouri

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

This randomized phase III trial studies gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride and cisplatin in treating patients with urinary tract cancer that has spread to other places in the body. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given with or without bevacizumab in treating patients with urinary tract cancer.

Sponsor: National Cancer Institute
ID: NCT00942331
Locations: Central Arkansas Veterans Healthcare System, Little Rock; Denver VAMC, Colorado; Baltimore VAMC, Maryland; Columbia VA, Missouri; VA New Jersey Health Care System, East Orange; VA New York Harbor Healthcare System-Brooklyn Campus; VA Western New York Health Care System, Buffalo; Dayton VAMC, Ohio

Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction

This phase I/II trial studies the side effects and best dose of eribulin mesylate and to see how well it works in treating patients with cancer of the urothelium that has spread to nearby tissue or to other places in the body and kidney dysfunction. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Chemotherapy drugs may have different effects in patients who have changes in their kidney function.

Sponsor: National Cancer Institute
ID: NCT00365157
Location: VA Hospital-Martinez, California

 

Click here to read the digital edition. 

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Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care (FULL)

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Depression Screening and Treatment: A Missed Opportunity in Lung Cancer Care
The integrated VA system is well positioned to be a leader in depression screening and treatment, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources.

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27

 

 

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

 

 

Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

 

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References

1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.

2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.

3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.

5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.

6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.

7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.

8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.

9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.

10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.

11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.

12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.

13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.

14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.

15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.

16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.

17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.

18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.

19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.

20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.

21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.

22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.

23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.

24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.

25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.

26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.

27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.

28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.

29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.

30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.

31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.

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Dr. Sullivan is an investigator, and Dr. Teo is a core investigator, both in the HSR&D Center to Improve Veteran Involvement in Care at VA Portland Health Care System in Oregon. Dr. Sullivan is an assistant professor in the Department of Medicine, in the Division of Pulmonary and Critical Care Medicine, and Dr. Teo is an assistant professor in the Department of Psychiatry and School of Public Health, both at Oregon Health & Science University in Portland.

Author and Disclosure Information

Dr. Sullivan is an investigator, and Dr. Teo is a core investigator, both in the HSR&D Center to Improve Veteran Involvement in Care at VA Portland Health Care System in Oregon. Dr. Sullivan is an assistant professor in the Department of Medicine, in the Division of Pulmonary and Critical Care Medicine, and Dr. Teo is an assistant professor in the Department of Psychiatry and School of Public Health, both at Oregon Health & Science University in Portland.

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The integrated VA system is well positioned to be a leader in depression screening and treatment, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources.
The integrated VA system is well positioned to be a leader in depression screening and treatment, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources.

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27

 

 

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

 

 

Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

 

Click here to read the digital edition. 

About Research in Context

In this article, the authors of recent scholarship have been asked to discuss the implications of their research on federal health care providers and specifically the veteran and active-duty service member patient populations. Because the article does not include new research and cannot be blinded, it has undergone an abbreviated peer review process. The original article can be found at Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

Although depression is common among patients with cancer, patients with lung cancer are at particularly high risk. The prevalence of major depressive disorder (MDD) among patients with cancer can be as high as 13%, whereas up to 44% of patients with lung cancer experience depression symptoms at some point following their cancer diagnosis.1-3 These estimates are consistently higher than those of other types of cancer, possibly related to the stigma of the disease and the associated morbidity and mortality that are its hallmarks.4-8 This potentially life-threatening cancer diagnosis often evokes psychological distress; however, additional stressors contribute to the development of depression, including the effects of chemotherapeutic agents, surgical procedures, radiotherapy, and the consequences of physical symptoms and paraneoplastic syndromes.

In addition to the crippling effects of comorbid depression on patients’ quality of life (QOL), severe and persistent depression among patients with cancer is associated with prolonged hospital stays, worse treatment adherence, physical distress and pain, and increased desire for hastened death.9-11 During treatment, depression can amplify physical symptoms and interfere with effective coping.12,13

Depression also is likely a significant factor for the risk of suicide, which is 4 times higher in patients with lung cancer than that of the general population.14 Most important, as our recent study demonstrated, depression that develops at cancer diagnosis or during cancer treatment may contribute to worse survival. This effect was strongest among patients with early stage disease, in other words, the patients who are most likely to achieve cure.3 This association with early stage disease also has been observed in a strictly veteran population from the northwest U.S.15

Another key finding of our study was the similar survival among patients who experienced a remission of their depression and those who were never depressed. This finding reinforces the importance of effective depression treatment, which has the potential to reduce depression-related mortality; however, depression treatment was not fully captured and could not be directly compared in our study. Unfortunately, comorbid depression often goes undiagnosed and untreated in cancer patients as they report unmet emotional needs and a desire for psychological support during and after completion of cancer treatment.16,17

Given the general lack of depression treatment that occurs in patients with cancer, the negative consequences of depression can be sustained well into survivorship—defined clinically as someone who is free of any sign of cancer for 5 years. Cancer survivors frequently report fatigue, mood disturbance, sleep disruption, pain, and cognitive limitations that significantly impact QOL and are associated with disability and increased health care use.18 These symptoms likely are intertwined with and contribute to the development and persistence of depression. The ramifications of untreated depression on long-term cancer survivor outcomes are not completely understood, as few high-quality studies of depression in cancer survivors exist. However, in a mixed group of patients with cancer, there was a 2-fold risk of mortality in survivors with depression symptoms when these patients were assessed from 1 to 10 years into survivorship.19 The impact of depression on cancer survivorship is an important aspect of cancer care that deserves significantly more attention from both a research and clinical perspective.

Special Considerations for Veterans

There is a higher prevalence of mental health diagnoses in veterans than that in the general population, and depressive disorders are the most common.20-22 According to the VA National Registry for Depression, 11% of veterans aged ≥ 65 years have a diagnosis of MDD, a rate more than twice that in the general population of a similar age.23 However, the actual rate of depression among veterans may be even higher, as studies suggest depression is underdiagnosed in the veteran population.24 In addition to depression, veterans experience other disabling psychological illnesses, such as posttraumatic stress disorder (PTSD) related to deployment and combat duty or combat-related injuries, such as traumatic brain injuries. The negative consequences of PTSD on cancer outcomes are largely unexplored, but PTSD can contribute to increased health care utilization and costs.25,26 A similar psychological construct, cancer-related posttraumatic stress (PTS), which develops as a result of a cancer diagnosis or treatment, is associated with missed medical appointments and procedures, which could impact survival.27

 

 

Depression Screening and Treatment

Given the negative consequences of comorbid mental illness, professional oncology societies have started developing guidelines regarding the assessments and care of patients with cancer who are experiencing symptoms of depression and/or anxiety.11,28,29 Among these, the American Society of Clinical Oncology (ASCO) has adapted the Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer.28 Per ASCO, the target audience for these guidelines is health care providers (eg, medical, surgical, and radiation oncologists; psychiatrists; psychologists; primary care providers; nurses; and others involved in the delivery of care for adults with cancer) as well as patients with cancer and their family members and caregivers.28 These guidelines address the optimum screening, assessment, and psychosocial-supportive care interventions for adults with cancer who are identified as experiencing symptoms of depression. Among the most imperative recommendations are periodic assessments across the trajectory of cancer care, including after cure, as well as employing institutional and community resources for depression treatment.

In clinical practice in a VA setting, implementing these guidelines might involve various interventions. First, it is vital for providers to conduct depression screening during periodic health care encounters. Given the high prevalence of depression in patients with lung cancer, we suggest using the 9-item Patient Health Questionnaire (PHQ-9) as an initial screening tool.30 Unlike the abridged 2-item PHQ-2 commonly used in the VA, the PHQ-9 provides an assessment of the full range of depressive symptoms. An elevated PHQ-9 score (≥ 10) is consistent with a major depressive episode and should trigger next steps.30

Once clinically significant depression is identified, initiation of treatment should occur next. The VA is well suited to assist and support non-mental health clinicians—particularly primary care—in treatment initiation and monitoring. This model of partnership is frequently called collaborative care, or integrated care, and it is well positioned to help patients with lung cancer with concomitant depression. In the VA, this model of care is called primary care-mental healthintegration (PC-MHI). One PC-MHI resource is called TIDES (Translating Initiatives for Depression into Effective Solutions), and when a patient is referred, a mental health nurse care manager helps to track the patients’ antidepressant adherence and treatment response while reporting results to primary care clinicians, who are generally responsible for initiating and continuing the antidepressant prescription. For patients preferring nonpharmacologic approaches or for whom an antidepressant may be contraindicated, PC-MHI can provide other assistance. For example, psychologists working in PC-MHI are equipped to provide a brief course of cognitive behavioral therapy sessions, another first-line, evidence-based treatment for clinical depression.

Clinician follow-up to ensure patient adherence, response, and satisfaction, and to adjust treatment as needed is essential. Besides ongoing coordination with PC-MHI services, including mental health clinicians as part of multidisciplinary cancer clinics could offer substantial added value to patients’ comprehensive cancer care. Indeed, the initiation of multicomponent depression care has been shown to improve QOL and role functioning in patients with cancer.31 Besides the established benefits on QOL, patients with lung cancer who achieve depression symptom remission also may enjoy a significant survival benefit over patients whose depression symptoms remain untreated during lung cancer treatment as our study suggests.3

Conclusion

Depression is a common comorbid disease among patients with lung cancer with important negative implications for QOL and survival. When it occurs after a cancer diagnosis, depression is expected to impact all phases of a patient’s life through treatment and survivorshi —ultimately affecting long-term survival. Veterans may be at particularly high risk given the increased prevalence of mental illness, including depression and PTSD in this group compared with that of the general population. Early detection and prompt treatment can promote depression remission, prevent relapse, and reduce the eventual emotional and financial burden of the disease. This approach may ultimately diminish the prevalence and persistence of depression symptoms and decrease the associated negative effects of this disease on patients with lung cancer.

The importance of integrated systems of depression treatment for patients with cancer as part of comprehensive cancer care cannot be overstated. Development and implementation of these systems should be a priority of lung cancer clinicians and treatment centers. The integrated system within the VA is well positioned to be a leader in this area, and VA clinicians who care for patients with lung cancer are encouraged to take advantage of available mental health resources. Additional research is urgently needed to explore optimal implementation of depression screening and subsequent treatment delivery to improve cancer patient outcomes in VA and non-VA health care settings.

 

 

Overall, there is minimal evidence that depression treatment can improve lung cancer survival; however, the lack of high-quality studies is a considerable limitation. Given the significant impact of depression on survival among patients with lung cancer, additional funding and resources are urgently needed to combat this debilitating comorbid disease.

Acknowledgments
This project was supported in part by the National Cancer Institute of the National Institutes of Health under award K07CA190706 to Dr. Sullivan, a Career Development Award from the Veterans Health Administration Health Service Research and Development (CDA 14-428) to Dr. Teo and the HSR&D Center to Improve Veteran Involvement in Care (CIVIC) (CIN 13-404) at the VA Portland Health Care System.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The VA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The opinions expressed herein are those of the authors and do not necessarily reflect those of
Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies.

 

Click here to read the digital edition. 

References

1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.

2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.

3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.

5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.

6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.

7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.

8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.

9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.

10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.

11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.

12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.

13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.

14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.

15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.

16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.

17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.

18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.

19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.

20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.

21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.

22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.

23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.

24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.

25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.

26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.

27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.

28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.

29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.

30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.

31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.

References

1. Derogatis LR, Morrow GR, Fetting J, et al. The prevalence of psychiatric disorders among cancer patients. JAMA. 1983;249(6):751-757.

2. Walker J, Holm Hansen C, Martin P, et al. Prevalence of depression in adults with cancer: a systematic review. Ann Oncol. 2013;24(4):895-900.

3. Sullivan DR, Forsberg CW, Ganzini L, et al. Longitudinal changes in depression symptoms and survival among patients with lung cancer: a national cohort assessment. J Clin Oncol. 2016;34(33):3984-3991.

4. Linden W, Vodermaier A, Mackenzie R, Greig D. Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age. J Affect Disord. 2012;141(2-3):343-351.

5. Massie MJ. Prevalence of depression in patients with cancer. J Natl Cancer Inst Monogr. 2004;(32):57-71.

6. Brown Johnson CG, Brodsky JL, Cataldo JK. Lung cancer stigma, anxiety, depression, and quality of life. J Psychosoc Oncol. 2014;32(1):59-73.

7. Cataldo JK, Jahan TM, Pongquan VL. Lung cancer stigma, depression, and quality of life among ever and never smokers. Eur J Oncol Nurs. 2012;16(3):264-269.

8. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2010. https://seer.cancer.gov/archive/csr/1975_2010/. Revised February 21, 2014. Accessed July 12, 2017.

9. Li M, Boquiren V, Lo C, et al. Depression and anxiety in supportive oncology. In: Davis M, Feyer P, Ortner P, Zimmermann C, eds. Supportive Oncology. 1st ed. Philadelphia, PA: Elsevier; 2011:528-540.

10. Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/or pain. Psychooncology. 2010;19(7):734-741.

11. Lazenby M, Ercolano E, Grant M, Holland JC, Jacobsen PB, McCorkle R. Supporting Commission on Cancer-mandated psychosocial distress screening with implementation strategies. J Oncol Pract. 2015;11(3):e413-e420.

12. Mystakidou K, Tsilika E, Parpa E, Katsouda E, Galanos A, Vlahos L. Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs. 2006;29(5):400-405.

13. Passik SD, Dugan W, McDonald MV, Rosenfeld B, Theobald DE, Edgerton S. Oncologists’ recognition of depression in their patients with cancer. J Clin Oncol. 1998;16(4):1594-1600.

14. Rahuma M, Kamel M, Nasar A, et al. Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population based analysis. Am J Respir Crit Care Med. 2017;195:A6730.

15. Sullivan DR, Ganzini L, Duckart JP, et al. Treatment receipt and outcomes among lung cancer patients with depression. Clin Oncol (R Coll Radiol). 2014;26(1):25-31.

16. Merckaert I, Libert Y, Messin S, Milani M, Slachmuylder JL, Razavi D. Cancer patients’ desire for psychological support: prevalence and implications for screening patients psychological needs. Psychooncology. 2010;19(2):141-149.

17. Harrison JD, Young JM, Price MA, Butow PN, Solomon MJ. What are the unmet supportive care needs of people with cancer? A systematic review. Support Care Cancer. 2009;17(8):1117-1128.

18. Wu HS, Harden JK. Symptom burden and quality of life in survivorship: a review of the literature. Cancer Nurs. 2015;38(1):E29-E54.

19. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013;7(3):484-492.

20. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351(1):13-22.

21. Fortney JC, Curran GM, Hunt JB, et al. Prevalence of probable mental disorders and help-seeking behaviors among veteran and non-veteran community college students. Gen Hosp Psychiatry. 2016;38:99-104.

22. Pickett T, Rothman D, Crawford EF, Brancu M, Fairbank JA, Kudler HS. Mental health among military personnel and veterans. N C Med J. 2015;76(5):299-306.

23. U.S. Department of Veterans Affairs, Veterans Health Administration. One in ten older vets is depressed. https://www.va.gov/health/NewsFeatures/20110624a.asp. Updated April 17, 2015. Accessed July 12, 2017.

24. Fontana A, Rosenheck R. Treatment-seeking veterans of Iraq and Afghanistan: comparison with veterans of previous wars. J Nerv Ment Dis. 2008;196(7):513-521.

25. Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry. 2000;61(suppl 5):4-12; discussion, 13-14.

26. Kartha A, Brower V, Saitz R, Samet JH, Keane TM, Liebschutz J. The impact of trauma exposure and post-traumatic stress disorder on healthcare utilization among primary care patients. Med Care. 2008;46(4):388-393.

27. National Cancer Institute. Cancer-related post-traumatic stress (PDQ®)–Patient version. https://www.cancer.gov/about-cancer/coping/survivorship/new-normal/ptsd-pdq. Updated July 7, 2015. Accessed July 12, 2017.

28. Andersen BL, DeRubeis RJ, Berman BS, et al; American Society of Clinical Oncology. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32(15):1605-1619.

29. Howell D, Keller-Olaman S, Oliver TK, et al. A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue. Curr Oncol. 2013;20(3):e233-e246.

30. Kroenke K, Wu J, Bair MJ, Krebs EE, Damush TM, Tu W. Reciprocal relationship between pain and depression: a 12-month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.

31. Walker J, Hansen CH, Martin P, et al; SMaRT (Symptom Management Research Trials) Oncology-3 Team. Integrated collaborative care for major depression comorbid with a poor prognosis cancer (SMaRT oncology-3): a multicentre randomised controlled trial in patients with lung cancer. Lancet Oncol. 2014;15(10):1168-1176.

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New MS criteria may create more false positives

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The revised McDonald criteria for multiple sclerosis (MS) has led to more diagnoses in patients with clinically isolated syndrome (CIS), but a new study of the criteria has suggested that they may lead to a number of false positive MS diagnoses among patients with a less severe disease state.

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“In our data, specificity of the 2017 criteria was significantly lower than for the 2010 criteria,” Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, and her colleagues wrote in JAMA Neurology. “Earlier data showed that the previous McDonald criteria lead to a higher number of MS diagnoses in patients who will not have a second attack.”

Dr. van der Vuurst de Vries and her colleagues analyzed data from 229 patients with a CIS who underwent an MRI of the spinal cord to assess for dissemination in space (DIS); of these, 180 patients were scored for both DIS and dissemination in time (DIT) and had a “baseline MRI scan that included T1 images after gadolinium administration or scans that did not show any T2 hyperintense lesions.” Some patients also underwent a baseline lumbar puncture if clinically required.



Patients were assessed using both the 2010 and 2017 McDonald criteria for MS, and results were measured using sensitivity, specificity, positive predictive and negative predictive values, and accuracy at 1-year, 3-year, and 5-year follow-up. “The most important addition is that the new criteria allow MS diagnosis when the MRI scan meets criteria for DIS and unique oligoclonal bands (OCB) are present in [cerebrospinal fluid], even in absence of DIT on the MRI scan,” the researchers wrote. “The other major difference is that not only asymptomatic but also symptomatic lesions can be used to demonstrate DIS and DIT on MRI. Furthermore, cortical lesions can be used to demonstrate dissemination in space.”

The researchers found that 124 patients met 2010 DIS criteria (54%) and that 74 patients (60%) went on to develop clinically definite MS, while 149 patients (65%) met 2017 DIS criteria, and 89 patients (60%) went on to clinically definite MS. There were 46 patients (26%) who met 2010 DIT criteria, and 33 of those patients (72%) were diagnosed with clinically definite MS; 126 patients (70%) met 2017 DIT criteria, and 76 of those patients (60%) had clinically definite MS. The sensitivity for the 2010 criteria was 36% (95% confidence interval, 27%-47%)versus 68% for the 2017 criteria (95% CI, 57%-77%; P less than .001). However, specificity for the 2017 criteria was lower (61%; 95% CI, 50%-71%) when compared with the 2010 criteria (85%; 95% CI, 76%-92%; P less than .001). Researchers found more baseline MS diagnoses with the 2017 criteria than with the 2010 criteria, but they noted that 14 of 22 patients (64%) under the 2010 criteria and 26 of 48 patients (54%) under the 2017 criteria with MS had a second attack within 5 years.

The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.

SOURCE: van der Vuurst de Vries RM, et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.

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The revised McDonald criteria for multiple sclerosis (MS) has led to more diagnoses in patients with clinically isolated syndrome (CIS), but a new study of the criteria has suggested that they may lead to a number of false positive MS diagnoses among patients with a less severe disease state.

solitude72/iStockphoto


“In our data, specificity of the 2017 criteria was significantly lower than for the 2010 criteria,” Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, and her colleagues wrote in JAMA Neurology. “Earlier data showed that the previous McDonald criteria lead to a higher number of MS diagnoses in patients who will not have a second attack.”

Dr. van der Vuurst de Vries and her colleagues analyzed data from 229 patients with a CIS who underwent an MRI of the spinal cord to assess for dissemination in space (DIS); of these, 180 patients were scored for both DIS and dissemination in time (DIT) and had a “baseline MRI scan that included T1 images after gadolinium administration or scans that did not show any T2 hyperintense lesions.” Some patients also underwent a baseline lumbar puncture if clinically required.



Patients were assessed using both the 2010 and 2017 McDonald criteria for MS, and results were measured using sensitivity, specificity, positive predictive and negative predictive values, and accuracy at 1-year, 3-year, and 5-year follow-up. “The most important addition is that the new criteria allow MS diagnosis when the MRI scan meets criteria for DIS and unique oligoclonal bands (OCB) are present in [cerebrospinal fluid], even in absence of DIT on the MRI scan,” the researchers wrote. “The other major difference is that not only asymptomatic but also symptomatic lesions can be used to demonstrate DIS and DIT on MRI. Furthermore, cortical lesions can be used to demonstrate dissemination in space.”

The researchers found that 124 patients met 2010 DIS criteria (54%) and that 74 patients (60%) went on to develop clinically definite MS, while 149 patients (65%) met 2017 DIS criteria, and 89 patients (60%) went on to clinically definite MS. There were 46 patients (26%) who met 2010 DIT criteria, and 33 of those patients (72%) were diagnosed with clinically definite MS; 126 patients (70%) met 2017 DIT criteria, and 76 of those patients (60%) had clinically definite MS. The sensitivity for the 2010 criteria was 36% (95% confidence interval, 27%-47%)versus 68% for the 2017 criteria (95% CI, 57%-77%; P less than .001). However, specificity for the 2017 criteria was lower (61%; 95% CI, 50%-71%) when compared with the 2010 criteria (85%; 95% CI, 76%-92%; P less than .001). Researchers found more baseline MS diagnoses with the 2017 criteria than with the 2010 criteria, but they noted that 14 of 22 patients (64%) under the 2010 criteria and 26 of 48 patients (54%) under the 2017 criteria with MS had a second attack within 5 years.

The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.

SOURCE: van der Vuurst de Vries RM, et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.

 

The revised McDonald criteria for multiple sclerosis (MS) has led to more diagnoses in patients with clinically isolated syndrome (CIS), but a new study of the criteria has suggested that they may lead to a number of false positive MS diagnoses among patients with a less severe disease state.

solitude72/iStockphoto


“In our data, specificity of the 2017 criteria was significantly lower than for the 2010 criteria,” Roos M. van der Vuurst de Vries, MD, from the department of neurology at Erasmus Medical Center in Rotterdam, the Netherlands, and her colleagues wrote in JAMA Neurology. “Earlier data showed that the previous McDonald criteria lead to a higher number of MS diagnoses in patients who will not have a second attack.”

Dr. van der Vuurst de Vries and her colleagues analyzed data from 229 patients with a CIS who underwent an MRI of the spinal cord to assess for dissemination in space (DIS); of these, 180 patients were scored for both DIS and dissemination in time (DIT) and had a “baseline MRI scan that included T1 images after gadolinium administration or scans that did not show any T2 hyperintense lesions.” Some patients also underwent a baseline lumbar puncture if clinically required.



Patients were assessed using both the 2010 and 2017 McDonald criteria for MS, and results were measured using sensitivity, specificity, positive predictive and negative predictive values, and accuracy at 1-year, 3-year, and 5-year follow-up. “The most important addition is that the new criteria allow MS diagnosis when the MRI scan meets criteria for DIS and unique oligoclonal bands (OCB) are present in [cerebrospinal fluid], even in absence of DIT on the MRI scan,” the researchers wrote. “The other major difference is that not only asymptomatic but also symptomatic lesions can be used to demonstrate DIS and DIT on MRI. Furthermore, cortical lesions can be used to demonstrate dissemination in space.”

The researchers found that 124 patients met 2010 DIS criteria (54%) and that 74 patients (60%) went on to develop clinically definite MS, while 149 patients (65%) met 2017 DIS criteria, and 89 patients (60%) went on to clinically definite MS. There were 46 patients (26%) who met 2010 DIT criteria, and 33 of those patients (72%) were diagnosed with clinically definite MS; 126 patients (70%) met 2017 DIT criteria, and 76 of those patients (60%) had clinically definite MS. The sensitivity for the 2010 criteria was 36% (95% confidence interval, 27%-47%)versus 68% for the 2017 criteria (95% CI, 57%-77%; P less than .001). However, specificity for the 2017 criteria was lower (61%; 95% CI, 50%-71%) when compared with the 2010 criteria (85%; 95% CI, 76%-92%; P less than .001). Researchers found more baseline MS diagnoses with the 2017 criteria than with the 2010 criteria, but they noted that 14 of 22 patients (64%) under the 2010 criteria and 26 of 48 patients (54%) under the 2017 criteria with MS had a second attack within 5 years.

The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.

SOURCE: van der Vuurst de Vries RM, et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.

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Key clinical point: The 2017 McDonald criteria for MS may diagnose more patients with a clinically isolated syndrome, but a lower specificity may also capture more patients who do not have a second CIS event.

Major finding: The sensitivity for the 2017 criteria was greater at 68%, compared with 36% in the 2010 criteria; however, specificity was significantly lower in the 2017 criteria at 61%, compared with 85% in the 2010 criteria.

Data source: An original study of 229 patients from the Netherlands with CIS who underwent an MRI scan within 3 months of symptoms.

Disclosures: The study was supported by the Dutch Multiple Sclerosis Research Foundation. One or more authors received compensation from Teva, Merck, Roche, Sanofi Genzyme, Biogen, and Novartis in the form of honoraria, for advisory board membership, as travel grants, or for participation in trials.

Source: van der Vuurst de Vries RM et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2160.

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Treatment of relapsing progressive MS may reduce disability progression

Results begin to answer questions about inflammation in progressive MS
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Superimposed relapses were associated with a significantly reduced risk of disability progression in a longitudinal, prospective cohort study of 1,419 multiple sclerosis patients (MS) of the progressive-onset type.

HUNG KUO CHUN/Thinkstock
“Progressive-onset MS with and without superimposed relapse is associated with a reduced time to irreversible disability milestones; however, there is limited research to date identifying factors that contribute to this disability accrual,” wrote Jordana Hughes, MD, of the University of Melbourne, and her colleagues.

To determine the role of inflammatory relapses on disability in the progressive-relapsing phenotype of progressive-onset MS, the researchers collected data from MSBase, an international, observational cohort of MS patients, from January 1995 to February 2017. The study population included 1,419 adults with MS (553 in the relapse subgroup, 866 in a nonrelapse subgroup) from 83 centers in 28 countries; the median prospective follow-up period was 5 years. The patients included in the analysis had adult-onset disease, at least three clinic visits with Expanded Disability Status Scale (EDSS) score recorded, and a time frame of more than 3 months between the second and last visit.

Overall, patients with relapses had significantly less risk of disability progression after adjusting for confounding variables (adjusted hazard ratio, 0.83; 95% confidence interval, 0.74-0.94; P = .003). Disease progression was defined as worsening of the EDSS score.

In addition, the researchers examined the data in a stratified model and found a 4% relative decrease in the hazard of confirmed disability progression events for each 10% increment of follow-up time for receiving disease-modifying therapy (DMT). However, DMT did not reduce disease progression risk in progressive-onset MS patients without relapse.

“This suggests that relapses in progressive-onset MS, as a clinical correlate of episodic inflammatory activity, represent a positive prognostic marker and provide an opportunity to improve disease outcomes through prevention of relapse-related disability accrual,” the researchers wrote.

Interferon-beta was the most common DMT, given to 73% of the relapse patients and 56% of the nonrelapse patients, followed by glatiramer acetate (20% and 13%, respectively), and fingolimod (12% and 16%, respectively).

The study’s main limitation was the use of the EDSS as a measure of disability, as well as the absence of quantifiable disability change to confirm relapse, the researchers noted. However, “these findings provide further evidence for a progressive-onset MS phenotype with acute episodic inflammatory changes, thereby identifying patients who may respond to existing immunotherapies.”

The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies including Merck, Novartis, Sanofi. Genzyme, and Biogen.

SOURCE: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.

Body

 

This study is important because it addresses an area of controversy in management of patients with a progressive multiple sclerosis (MS) phenotype. The role of superimposed relapses in patients with progressive MS has long been debated, with some studies reporting no impact on long-term disability accrual and other reporting a negative impact of relapses. Treatment of progressive MS remains controversial as well, with only one therapy approved by the Food and Drug Administration for any form of progressive MS. There is considerable ongoing debate about whether MS disease-modifying therapies (MSDMT) are effective in progressive forms of MS, and whether clinical or MRI evidence of active inflammation predicts a better chance of response.

Dr. Jonathan L. Carter
The article by Hughes et al. attempted to answer some of these questions through the use of the MSBase database, which is a multicenter, multinational, observational cohort study that provides a large patient population for study using standardized methodologies. The study included almost 1,500 patients with either primary progressive MS (PPMS) or progressive relapsing MS (PRMS) who had at least three visits with disability status (EDSS) recorded, with at least 3 months between the second and last visit. Median prospective follow-up in this cohort was 5 years, which is important given the generally slow rate of progression in this patient population. Patients with PRMS were younger and less disabled at baseline than were those with PPMS, and the cumulative hazard of confirmed disability progression was slightly lower (hazard ratio, 0.86; 95% CI, 0.78-0.96; P = .005). Multivariate analysis showed a slightly lower disability progression risk in patients with PRMS who were on MSDMT for longer periods of time, but this was not seen in PPMS patients. Male sex and higher EDSS score at baseline were poorer prognostic factors in both groups.

This study has several important strengths and limitations. The large sample size allowed statistical power to detect relatively small differences in disability progression risk between progressive MS subtypes. The better prognosis in progressive patients with superimposed relapses contradicts some earlier studies that suggested a worse prognosis or no difference in prognosis between progressive patients with and without relapses. This study also supports a role for MSDMT in progressive MS patients, at least those with clinical evidence of relapses, and possibly MRI evidence of inflammatory disease activity (although this was not specifically addressed in the current study). Limitations of the study include the observational nature of the database, variable periods of follow-up, lack of objective verification of recorded relapses either with EDSS scores or MRI confirmation, and lack of an untreated control group. Therefore, no conclusions can be drawn as to whether MSDMT exposure had a favorable impact on the whole cohort of progressive patients versus no treatment.

Jonathan L. Carter, MD , is an MS specialist at the Mayo Clinic in Scottsdale, Ariz. He had no relevant disclosures to report.

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Body

 

This study is important because it addresses an area of controversy in management of patients with a progressive multiple sclerosis (MS) phenotype. The role of superimposed relapses in patients with progressive MS has long been debated, with some studies reporting no impact on long-term disability accrual and other reporting a negative impact of relapses. Treatment of progressive MS remains controversial as well, with only one therapy approved by the Food and Drug Administration for any form of progressive MS. There is considerable ongoing debate about whether MS disease-modifying therapies (MSDMT) are effective in progressive forms of MS, and whether clinical or MRI evidence of active inflammation predicts a better chance of response.

Dr. Jonathan L. Carter
The article by Hughes et al. attempted to answer some of these questions through the use of the MSBase database, which is a multicenter, multinational, observational cohort study that provides a large patient population for study using standardized methodologies. The study included almost 1,500 patients with either primary progressive MS (PPMS) or progressive relapsing MS (PRMS) who had at least three visits with disability status (EDSS) recorded, with at least 3 months between the second and last visit. Median prospective follow-up in this cohort was 5 years, which is important given the generally slow rate of progression in this patient population. Patients with PRMS were younger and less disabled at baseline than were those with PPMS, and the cumulative hazard of confirmed disability progression was slightly lower (hazard ratio, 0.86; 95% CI, 0.78-0.96; P = .005). Multivariate analysis showed a slightly lower disability progression risk in patients with PRMS who were on MSDMT for longer periods of time, but this was not seen in PPMS patients. Male sex and higher EDSS score at baseline were poorer prognostic factors in both groups.

This study has several important strengths and limitations. The large sample size allowed statistical power to detect relatively small differences in disability progression risk between progressive MS subtypes. The better prognosis in progressive patients with superimposed relapses contradicts some earlier studies that suggested a worse prognosis or no difference in prognosis between progressive patients with and without relapses. This study also supports a role for MSDMT in progressive MS patients, at least those with clinical evidence of relapses, and possibly MRI evidence of inflammatory disease activity (although this was not specifically addressed in the current study). Limitations of the study include the observational nature of the database, variable periods of follow-up, lack of objective verification of recorded relapses either with EDSS scores or MRI confirmation, and lack of an untreated control group. Therefore, no conclusions can be drawn as to whether MSDMT exposure had a favorable impact on the whole cohort of progressive patients versus no treatment.

Jonathan L. Carter, MD , is an MS specialist at the Mayo Clinic in Scottsdale, Ariz. He had no relevant disclosures to report.

Body

 

This study is important because it addresses an area of controversy in management of patients with a progressive multiple sclerosis (MS) phenotype. The role of superimposed relapses in patients with progressive MS has long been debated, with some studies reporting no impact on long-term disability accrual and other reporting a negative impact of relapses. Treatment of progressive MS remains controversial as well, with only one therapy approved by the Food and Drug Administration for any form of progressive MS. There is considerable ongoing debate about whether MS disease-modifying therapies (MSDMT) are effective in progressive forms of MS, and whether clinical or MRI evidence of active inflammation predicts a better chance of response.

Dr. Jonathan L. Carter
The article by Hughes et al. attempted to answer some of these questions through the use of the MSBase database, which is a multicenter, multinational, observational cohort study that provides a large patient population for study using standardized methodologies. The study included almost 1,500 patients with either primary progressive MS (PPMS) or progressive relapsing MS (PRMS) who had at least three visits with disability status (EDSS) recorded, with at least 3 months between the second and last visit. Median prospective follow-up in this cohort was 5 years, which is important given the generally slow rate of progression in this patient population. Patients with PRMS were younger and less disabled at baseline than were those with PPMS, and the cumulative hazard of confirmed disability progression was slightly lower (hazard ratio, 0.86; 95% CI, 0.78-0.96; P = .005). Multivariate analysis showed a slightly lower disability progression risk in patients with PRMS who were on MSDMT for longer periods of time, but this was not seen in PPMS patients. Male sex and higher EDSS score at baseline were poorer prognostic factors in both groups.

This study has several important strengths and limitations. The large sample size allowed statistical power to detect relatively small differences in disability progression risk between progressive MS subtypes. The better prognosis in progressive patients with superimposed relapses contradicts some earlier studies that suggested a worse prognosis or no difference in prognosis between progressive patients with and without relapses. This study also supports a role for MSDMT in progressive MS patients, at least those with clinical evidence of relapses, and possibly MRI evidence of inflammatory disease activity (although this was not specifically addressed in the current study). Limitations of the study include the observational nature of the database, variable periods of follow-up, lack of objective verification of recorded relapses either with EDSS scores or MRI confirmation, and lack of an untreated control group. Therefore, no conclusions can be drawn as to whether MSDMT exposure had a favorable impact on the whole cohort of progressive patients versus no treatment.

Jonathan L. Carter, MD , is an MS specialist at the Mayo Clinic in Scottsdale, Ariz. He had no relevant disclosures to report.

Title
Results begin to answer questions about inflammation in progressive MS
Results begin to answer questions about inflammation in progressive MS

 

Superimposed relapses were associated with a significantly reduced risk of disability progression in a longitudinal, prospective cohort study of 1,419 multiple sclerosis patients (MS) of the progressive-onset type.

HUNG KUO CHUN/Thinkstock
“Progressive-onset MS with and without superimposed relapse is associated with a reduced time to irreversible disability milestones; however, there is limited research to date identifying factors that contribute to this disability accrual,” wrote Jordana Hughes, MD, of the University of Melbourne, and her colleagues.

To determine the role of inflammatory relapses on disability in the progressive-relapsing phenotype of progressive-onset MS, the researchers collected data from MSBase, an international, observational cohort of MS patients, from January 1995 to February 2017. The study population included 1,419 adults with MS (553 in the relapse subgroup, 866 in a nonrelapse subgroup) from 83 centers in 28 countries; the median prospective follow-up period was 5 years. The patients included in the analysis had adult-onset disease, at least three clinic visits with Expanded Disability Status Scale (EDSS) score recorded, and a time frame of more than 3 months between the second and last visit.

Overall, patients with relapses had significantly less risk of disability progression after adjusting for confounding variables (adjusted hazard ratio, 0.83; 95% confidence interval, 0.74-0.94; P = .003). Disease progression was defined as worsening of the EDSS score.

In addition, the researchers examined the data in a stratified model and found a 4% relative decrease in the hazard of confirmed disability progression events for each 10% increment of follow-up time for receiving disease-modifying therapy (DMT). However, DMT did not reduce disease progression risk in progressive-onset MS patients without relapse.

“This suggests that relapses in progressive-onset MS, as a clinical correlate of episodic inflammatory activity, represent a positive prognostic marker and provide an opportunity to improve disease outcomes through prevention of relapse-related disability accrual,” the researchers wrote.

Interferon-beta was the most common DMT, given to 73% of the relapse patients and 56% of the nonrelapse patients, followed by glatiramer acetate (20% and 13%, respectively), and fingolimod (12% and 16%, respectively).

The study’s main limitation was the use of the EDSS as a measure of disability, as well as the absence of quantifiable disability change to confirm relapse, the researchers noted. However, “these findings provide further evidence for a progressive-onset MS phenotype with acute episodic inflammatory changes, thereby identifying patients who may respond to existing immunotherapies.”

The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies including Merck, Novartis, Sanofi. Genzyme, and Biogen.

SOURCE: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.

 

Superimposed relapses were associated with a significantly reduced risk of disability progression in a longitudinal, prospective cohort study of 1,419 multiple sclerosis patients (MS) of the progressive-onset type.

HUNG KUO CHUN/Thinkstock
“Progressive-onset MS with and without superimposed relapse is associated with a reduced time to irreversible disability milestones; however, there is limited research to date identifying factors that contribute to this disability accrual,” wrote Jordana Hughes, MD, of the University of Melbourne, and her colleagues.

To determine the role of inflammatory relapses on disability in the progressive-relapsing phenotype of progressive-onset MS, the researchers collected data from MSBase, an international, observational cohort of MS patients, from January 1995 to February 2017. The study population included 1,419 adults with MS (553 in the relapse subgroup, 866 in a nonrelapse subgroup) from 83 centers in 28 countries; the median prospective follow-up period was 5 years. The patients included in the analysis had adult-onset disease, at least three clinic visits with Expanded Disability Status Scale (EDSS) score recorded, and a time frame of more than 3 months between the second and last visit.

Overall, patients with relapses had significantly less risk of disability progression after adjusting for confounding variables (adjusted hazard ratio, 0.83; 95% confidence interval, 0.74-0.94; P = .003). Disease progression was defined as worsening of the EDSS score.

In addition, the researchers examined the data in a stratified model and found a 4% relative decrease in the hazard of confirmed disability progression events for each 10% increment of follow-up time for receiving disease-modifying therapy (DMT). However, DMT did not reduce disease progression risk in progressive-onset MS patients without relapse.

“This suggests that relapses in progressive-onset MS, as a clinical correlate of episodic inflammatory activity, represent a positive prognostic marker and provide an opportunity to improve disease outcomes through prevention of relapse-related disability accrual,” the researchers wrote.

Interferon-beta was the most common DMT, given to 73% of the relapse patients and 56% of the nonrelapse patients, followed by glatiramer acetate (20% and 13%, respectively), and fingolimod (12% and 16%, respectively).

The study’s main limitation was the use of the EDSS as a measure of disability, as well as the absence of quantifiable disability change to confirm relapse, the researchers noted. However, “these findings provide further evidence for a progressive-onset MS phenotype with acute episodic inflammatory changes, thereby identifying patients who may respond to existing immunotherapies.”

The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies including Merck, Novartis, Sanofi. Genzyme, and Biogen.

SOURCE: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.

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Key clinical point: Disease-modifying therapy was significantly associated with less disability progression in multiple sclerosis patients with superimposed relapses, compared with those without relapses.

Major finding: Progressive-onset multiple sclerosis patients with superimposed relapses were significantly less likely to have confirmed disability progression (adjusted hazard ratio, 0.83).

Study details: The data came from a longitudinal, prospective cohort study of 1,419 adults with progressive-onset multiple sclerosis.

Disclosures: The study was supported by grants from the National Health and Medical Research Council of Australia and the MSBase Foundation, a nonprofit organization that itself receives support from multiple companies, including Merck, Novartis, and Sanofi. Dr. Hughes had no financial conflicts to disclose, but most coauthors disclosed relationships with multiple companies, including Merck, Novartis, Sanofi, Genzyme, and Biogen.

Source: Hughes J et al. JAMA Neurol. 2018 Aug 6. doi: 10.1001/jamaneurol.2018.2109.

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Insurance is a matter of life or death for lymphoma patients

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Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

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A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.

“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.

The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

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Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

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A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.

“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.

The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.

Thinkstock

A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).

“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.

“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.

The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.

To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.

They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.

Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.

However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).

Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.

The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).

“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.

The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

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Key clinical point: Insurance status is significantly associated with survival disparities in patients with follicular lymphoma.

Major finding: The risk for death among patients under age 65 with no insurance, Medicaid, or Medicare was nearly twice that of similar patients with private health insurance.

Study details: Review of data on 43,648 patients with follicular lymphoma in the National Cancer Database.

Disclosures: The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.

Source: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.

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