AVAHO

Clopidogrel appears to reduce the risk of colorectal cancer (CRC) as much as low-dose aspirin, based on a case-control study involving more than 15,000 cases.

Source: American Gastroenterological Association

Risk of CRC was reduced by 20%-30% when clopidogrel was given alone or in combination with aspirin, reported lead author Antonio Rodríguez-Miguel of Príncipe de Asturias University Hospital in Madrid and colleagues. This finding adds support to the hypothesis that low-dose aspirin is chemoprotective primarily because of its antiplatelet properties, they noted.

“The mechanism of action of low-dose aspirin to explain its protective effect is subject to debate,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Although aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and these drugs are known to prevent CRC through the inhibition of cyclooxygenase (COX)-2 in epithelial and stromal cells in the large bowel, at low doses (75-300 mg/d) aspirin has only transient effects on this isozyme, while permanently inactivating platelet COX-1 and suppressing thromboxane A₂ production. The apparent lack of dose-dependence of the chemoprotective effect of aspirin, as well as the potential role of locally activated platelets in upregulating COX-2 expression in adjacent nucleated cells of the intestinal mucosa, have led [to] the postulation that low-dose aspirin could exert its chemoprotective effect via its antiplatelet action.”

Although previous studies have explored the chemoprotective potential of other antiplatelet agents, such as clopidogrel, the resultant body of evidence remains small. In 2017, for example, Avi Leader, MD, and colleagues reported that the chemoprotective effect of dual-antiplatelet therapy (DAPT) with clopidogrel and aspirin was superior to aspirin monotherapy, based on an additional 8% risk reduction. The present study aimed to build on such findings with evaluation of a Mediterranean cohort, which could reduce confounding lifestyle factors, owing to a lower rate of cardiovascular morbidity than other populations.

The nested, case-control study involved 15,491 cases of CRC and 60,000 controls who were randomly selected and frequency matched by sex, age, and year of indexing. Data were drawn from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish medical record database with more than 7 million patients. Records of patients involved in the present study were screened for prescription of three antiplatelet agents: low-dose aspirin, clopidogrel, and triflusal. Additional categorization identified current users, recent users, past users, and nonusers. The effects of clopidogrel and aspirin were evaluated separately, as monotherapies, and together, as DAPT.

Demographically, the mean age of the entire study population was 68.6 years, with a slight male predominance (59%). Median follow-up was similar between cases and controls, at approximately 3 years, ranging from about 1.5 to 6 years. Cases showed higher rates of gout, alcohol abuse, acute digestive diseases, and peripheral artery disease, whereas controls were more likely to have histories involving stroke, acute myocardial infarction, chronic digestive diseases, and constipation.

Controls were more likely to be current aspirin users than patients diagnosed with CRC (12.8% vs. 12.2%), giving an associated adjusted odds ratio (AOR) of 0.83. Risk reduction became statistically apparent after 180 days of aspirin usage, with an AOR of 0.79, and more prominent in the 1- to 3-year range, with an AOR of 0.73. This chemoprotective effect faded rapidly with discontinuation.

Current clopidogrel usage led to a comparable level of risk reduction, with an AOR of 0.80. It wasn’t until a year of continuous clopidogrel monotherapy that risk reduction became statistically significant, with an AOR of 0.65, which dropped to 0.57 between years 1 and 3.

Turning to a matched comparison of aspirin or clopidogrel monotherapy versus DAPT, the investigators found similar rates of chemoprotection. Current aspirin usage of any duration offered an adjusted risk reduction of 17%, compared with 25% for clopidogrel, and 29% for DAPT. Beyond 1 year of continuous and current usage, the superiority of DAPT was called into question, as clopidogrel monotherapy offered the greatest risk reduction, at 37%, compared with 22% for aspirin, and 22% for DAPT. Risk analyses involving triflusal lacked statistical significance.

“The results of the present study are compatible with a chemoprotective effect of clopidogrel against CRC, equivalent in magnitude to the one observed for low-dose aspirin,” the investigators wrote. “This finding indirectly supports the hypothesis that the chemoprotective effect of low-dose aspirin is mediated mostly through the permanent inactivation of platelet COX-1.”

The investigators pointed out that the chemoprotective effects of antiplatelet therapy begin to appear early in treatment, independently from lifestyle factors, but risk reduction depends on current usage. Although short-term usage of either aspirin or clopidogrel was associated with an increased risk of CRC, the investigators suggested that this was more likely a perceived risk rather than an actual one. “In our view, this observation could be explained in part by a detection bias, owing to an increased risk of GI bleeding induced by antiplatelet agents that could lead to a greater number of colonoscopies, and, as a result, an early cancer diagnosis,” they wrote.

The study was funded by the Fundación Instituto Teófilo Hernando. Dr. García-Rodríguez disclosed a relationship with CEIFE, which has received funding from Bayer and AstraZeneca.

SOURCE: Rodríguez-Miguel et al. Clin Gastrenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.012.

Clopidogrel appears to reduce the risk of colorectal cancer (CRC) as much as low-dose aspirin, based on a case-control study involving more than 15,000 cases.

Source: American Gastroenterological Association

Risk of CRC was reduced by 20%-30% when clopidogrel was given alone or in combination with aspirin, reported lead author Antonio Rodríguez-Miguel of Príncipe de Asturias University Hospital in Madrid and colleagues. This finding adds support to the hypothesis that low-dose aspirin is chemoprotective primarily because of its antiplatelet properties, they noted.

“The mechanism of action of low-dose aspirin to explain its protective effect is subject to debate,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Although aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and these drugs are known to prevent CRC through the inhibition of cyclooxygenase (COX)-2 in epithelial and stromal cells in the large bowel, at low doses (75-300 mg/d) aspirin has only transient effects on this isozyme, while permanently inactivating platelet COX-1 and suppressing thromboxane A₂ production. The apparent lack of dose-dependence of the chemoprotective effect of aspirin, as well as the potential role of locally activated platelets in upregulating COX-2 expression in adjacent nucleated cells of the intestinal mucosa, have led [to] the postulation that low-dose aspirin could exert its chemoprotective effect via its antiplatelet action.”

Although previous studies have explored the chemoprotective potential of other antiplatelet agents, such as clopidogrel, the resultant body of evidence remains small. In 2017, for example, Avi Leader, MD, and colleagues reported that the chemoprotective effect of dual-antiplatelet therapy (DAPT) with clopidogrel and aspirin was superior to aspirin monotherapy, based on an additional 8% risk reduction. The present study aimed to build on such findings with evaluation of a Mediterranean cohort, which could reduce confounding lifestyle factors, owing to a lower rate of cardiovascular morbidity than other populations.

The nested, case-control study involved 15,491 cases of CRC and 60,000 controls who were randomly selected and frequency matched by sex, age, and year of indexing. Data were drawn from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish medical record database with more than 7 million patients. Records of patients involved in the present study were screened for prescription of three antiplatelet agents: low-dose aspirin, clopidogrel, and triflusal. Additional categorization identified current users, recent users, past users, and nonusers. The effects of clopidogrel and aspirin were evaluated separately, as monotherapies, and together, as DAPT.

Demographically, the mean age of the entire study population was 68.6 years, with a slight male predominance (59%). Median follow-up was similar between cases and controls, at approximately 3 years, ranging from about 1.5 to 6 years. Cases showed higher rates of gout, alcohol abuse, acute digestive diseases, and peripheral artery disease, whereas controls were more likely to have histories involving stroke, acute myocardial infarction, chronic digestive diseases, and constipation.

Controls were more likely to be current aspirin users than patients diagnosed with CRC (12.8% vs. 12.2%), giving an associated adjusted odds ratio (AOR) of 0.83. Risk reduction became statistically apparent after 180 days of aspirin usage, with an AOR of 0.79, and more prominent in the 1- to 3-year range, with an AOR of 0.73. This chemoprotective effect faded rapidly with discontinuation.

Current clopidogrel usage led to a comparable level of risk reduction, with an AOR of 0.80. It wasn’t until a year of continuous clopidogrel monotherapy that risk reduction became statistically significant, with an AOR of 0.65, which dropped to 0.57 between years 1 and 3.

Turning to a matched comparison of aspirin or clopidogrel monotherapy versus DAPT, the investigators found similar rates of chemoprotection. Current aspirin usage of any duration offered an adjusted risk reduction of 17%, compared with 25% for clopidogrel, and 29% for DAPT. Beyond 1 year of continuous and current usage, the superiority of DAPT was called into question, as clopidogrel monotherapy offered the greatest risk reduction, at 37%, compared with 22% for aspirin, and 22% for DAPT. Risk analyses involving triflusal lacked statistical significance.

“The results of the present study are compatible with a chemoprotective effect of clopidogrel against CRC, equivalent in magnitude to the one observed for low-dose aspirin,” the investigators wrote. “This finding indirectly supports the hypothesis that the chemoprotective effect of low-dose aspirin is mediated mostly through the permanent inactivation of platelet COX-1.”

The investigators pointed out that the chemoprotective effects of antiplatelet therapy begin to appear early in treatment, independently from lifestyle factors, but risk reduction depends on current usage. Although short-term usage of either aspirin or clopidogrel was associated with an increased risk of CRC, the investigators suggested that this was more likely a perceived risk rather than an actual one. “In our view, this observation could be explained in part by a detection bias, owing to an increased risk of GI bleeding induced by antiplatelet agents that could lead to a greater number of colonoscopies, and, as a result, an early cancer diagnosis,” they wrote.

The study was funded by the Fundación Instituto Teófilo Hernando. Dr. García-Rodríguez disclosed a relationship with CEIFE, which has received funding from Bayer and AstraZeneca.

SOURCE: Rodríguez-Miguel et al. Clin Gastrenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.012.

Clopidogrel appears to reduce the risk of colorectal cancer (CRC) as much as low-dose aspirin, based on a case-control study involving more than 15,000 cases.

Source: American Gastroenterological Association

Risk of CRC was reduced by 20%-30% when clopidogrel was given alone or in combination with aspirin, reported lead author Antonio Rodríguez-Miguel of Príncipe de Asturias University Hospital in Madrid and colleagues. This finding adds support to the hypothesis that low-dose aspirin is chemoprotective primarily because of its antiplatelet properties, they noted.

“The mechanism of action of low-dose aspirin to explain its protective effect is subject to debate,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Although aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and these drugs are known to prevent CRC through the inhibition of cyclooxygenase (COX)-2 in epithelial and stromal cells in the large bowel, at low doses (75-300 mg/d) aspirin has only transient effects on this isozyme, while permanently inactivating platelet COX-1 and suppressing thromboxane A₂ production. The apparent lack of dose-dependence of the chemoprotective effect of aspirin, as well as the potential role of locally activated platelets in upregulating COX-2 expression in adjacent nucleated cells of the intestinal mucosa, have led [to] the postulation that low-dose aspirin could exert its chemoprotective effect via its antiplatelet action.”

Although previous studies have explored the chemoprotective potential of other antiplatelet agents, such as clopidogrel, the resultant body of evidence remains small. In 2017, for example, Avi Leader, MD, and colleagues reported that the chemoprotective effect of dual-antiplatelet therapy (DAPT) with clopidogrel and aspirin was superior to aspirin monotherapy, based on an additional 8% risk reduction. The present study aimed to build on such findings with evaluation of a Mediterranean cohort, which could reduce confounding lifestyle factors, owing to a lower rate of cardiovascular morbidity than other populations.

The nested, case-control study involved 15,491 cases of CRC and 60,000 controls who were randomly selected and frequency matched by sex, age, and year of indexing. Data were drawn from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish medical record database with more than 7 million patients. Records of patients involved in the present study were screened for prescription of three antiplatelet agents: low-dose aspirin, clopidogrel, and triflusal. Additional categorization identified current users, recent users, past users, and nonusers. The effects of clopidogrel and aspirin were evaluated separately, as monotherapies, and together, as DAPT.

Demographically, the mean age of the entire study population was 68.6 years, with a slight male predominance (59%). Median follow-up was similar between cases and controls, at approximately 3 years, ranging from about 1.5 to 6 years. Cases showed higher rates of gout, alcohol abuse, acute digestive diseases, and peripheral artery disease, whereas controls were more likely to have histories involving stroke, acute myocardial infarction, chronic digestive diseases, and constipation.

Controls were more likely to be current aspirin users than patients diagnosed with CRC (12.8% vs. 12.2%), giving an associated adjusted odds ratio (AOR) of 0.83. Risk reduction became statistically apparent after 180 days of aspirin usage, with an AOR of 0.79, and more prominent in the 1- to 3-year range, with an AOR of 0.73. This chemoprotective effect faded rapidly with discontinuation.

Current clopidogrel usage led to a comparable level of risk reduction, with an AOR of 0.80. It wasn’t until a year of continuous clopidogrel monotherapy that risk reduction became statistically significant, with an AOR of 0.65, which dropped to 0.57 between years 1 and 3.

Turning to a matched comparison of aspirin or clopidogrel monotherapy versus DAPT, the investigators found similar rates of chemoprotection. Current aspirin usage of any duration offered an adjusted risk reduction of 17%, compared with 25% for clopidogrel, and 29% for DAPT. Beyond 1 year of continuous and current usage, the superiority of DAPT was called into question, as clopidogrel monotherapy offered the greatest risk reduction, at 37%, compared with 22% for aspirin, and 22% for DAPT. Risk analyses involving triflusal lacked statistical significance.

“The results of the present study are compatible with a chemoprotective effect of clopidogrel against CRC, equivalent in magnitude to the one observed for low-dose aspirin,” the investigators wrote. “This finding indirectly supports the hypothesis that the chemoprotective effect of low-dose aspirin is mediated mostly through the permanent inactivation of platelet COX-1.”

The investigators pointed out that the chemoprotective effects of antiplatelet therapy begin to appear early in treatment, independently from lifestyle factors, but risk reduction depends on current usage. Although short-term usage of either aspirin or clopidogrel was associated with an increased risk of CRC, the investigators suggested that this was more likely a perceived risk rather than an actual one. “In our view, this observation could be explained in part by a detection bias, owing to an increased risk of GI bleeding induced by antiplatelet agents that could lead to a greater number of colonoscopies, and, as a result, an early cancer diagnosis,” they wrote.

The study was funded by the Fundación Instituto Teófilo Hernando. Dr. García-Rodríguez disclosed a relationship with CEIFE, which has received funding from Bayer and AstraZeneca.

SOURCE: Rodríguez-Miguel et al. Clin Gastrenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.012.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Real-world outcome data from patients with advanced non–small cell lung cancer (NSCLC) treated with immunotherapy are robust enough to use for regulatory and payer decisions, suggests an analysis of six data sets and more than 13,000 patients.

“Study of routinely collected health care data is increasingly important for various stakeholders who are interested in better understanding particular patient populations, evaluating drug safety in the postmarketing setting, measuring health care use and clinical outcomes, performing comparative effectiveness research, and optimizing drug pricing models,” noted lead investigator Mark Stewart, PhD, Friends of Cancer Research, Washington, and coinvestigators. “However, before [real-world data] finds widespread use as an adjunct to – or in unique settings, an alternative for – [randomized clinical trials], the validity of readily extractable clinical outcomes measures – real-world endpoints – must be established.”

The investigators undertook a retrospective cohort study using administrative claims and electronic health records for patients with advanced NSCLC treated with inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) between January 2011 and October 2017 in real-world settings. They analyzed six data sets having 269 to 6,924 patients each (13,639 patients total).

Results reported in JCO Clinical Cancer Informatics showed that the real-world intermediate endpoints of time to treatment discontinuation and time to next treatment were moderately to highly correlated with real-world overall survival (Spearman’s rank correlation coefficient, 0.36 to 0.89, with most values 0.60 or higher).

In real-world settings, the 1-year rate of overall survival after starting immunotherapy ranged from 40% to 57%. Real-world data and trial data were similar with respect to median overall survival (8.6-13.5 months vs. 9.2-12.7 months).

The data sources used for the study have been extensively used for research and are curated on an ongoing basis to ensure the data are accurate and as complete as possible, Dr. Stewart and coinvestigators noted.

“These findings demonstrate that real-world endpoints are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision-making,” they maintained. “Differences observed likely reflect true differences between real-world and protocol-driven practices.

“Additional studies are needed to further support the use of [real-world evidence] and inform the development of regulatory guidance,” the investigators concluded. “Standardizing definitions for real-world endpoints and determining appropriate analytic methodologies for [real-world data] will be critical for broader adoption of real-world studies and will provide greater confidence in associated findings. As more refined and standardized approaches are developed that incorporate deep clinical and bioinformatics expertise, the greater the utility of [real-world data] will be for detecting even small, but important, differences in treatment effects.”

Dr. Stewart disclosed no conflicts of interest. The study was supported in part by the National Cancer Institute and the Patient Centered Outcomes Research Institute.

SOURCE: Stewart M et al. JCO Clin Cancer Inform. 2019 July 23. doi: 10.1200/CCI.18.00155.

Pediatric non-Hodgkin lymphomas should be added to the list of cancers associated with BRCA2 mutations, and survivors of childhood NHL should be considered for genetic counseling, investigators suggest.

Among 1,380 survivors of childhood lymphomas, those who were retrospectively found to be carriers of BRCA2 mutations had a fivefold higher risk for non-Hodgkin lymphoma than controls without cancer, reported Zhaoming Wang, PhD, and colleagues from St. Jude Children’s Research Hospital in Memphis.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non–Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” they wrote in JAMA Oncology.

The investigators had previously reported that BRCA2 was the third-most frequently mutated gene among 3006 survivors of childhood cancers, with the highest number of mutations seen in lymphoma survivors. In that study, 7 of 586 survivors of Hodgkin and non-Hodgkin lymphoma (1.2%) were found to carry BRCA2 mutations.

In the current study, the investigators performed germline whole-genome sequencing on samples from 815 survivors of childhood Hodgkin lymphoma and 748 survivors of non-Hodgkin lymphoma from the St. Jude Lifetime Cohort and Childhood Cancer Survivor studies and compared the data with those of controls without cancer from the Genome Aggregation Database.

They identified mutations in five Hodgkin lymphoma survivors (0.6%) and eight non-Hodgkin lymphoma survivors.

A comparison of cancer risk among lymphoma survivors and controls found that non-Hodgkin lymphoma survivors and BRCA2 carriers had an odds ratio for cancer of 5.0, compared with controls who were not BRCA2 carriers (P less than .001). Among Hodgkin lymphoma survivors the OR for carriers vs. controls was 2.1, but was not statistically significant.

Available family histories for seven of the eight non-Hodgkin lymphoma BRCA2 mutation carriers showed histories of BRCA2-linked cancers, including breast, prostate, and pancreas tumors and malignant melanoma.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies. Currently, it remains unclear whether surveillance for non–Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantages,” the investigators wrote.

“This study was funded by a grant to St Jude Children’s Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St Jude Children’s Research Hospital from the National Institutes of Health. The authors reported having no conflicts of interest.

SOURCE: Wang Z et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2203.

Pediatric non-Hodgkin lymphomas should be added to the list of cancers associated with BRCA2 mutations, and survivors of childhood NHL should be considered for genetic counseling, investigators suggest.

Among 1,380 survivors of childhood lymphomas, those who were retrospectively found to be carriers of BRCA2 mutations had a fivefold higher risk for non-Hodgkin lymphoma than controls without cancer, reported Zhaoming Wang, PhD, and colleagues from St. Jude Children’s Research Hospital in Memphis.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non–Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” they wrote in JAMA Oncology.

The investigators had previously reported that BRCA2 was the third-most frequently mutated gene among 3006 survivors of childhood cancers, with the highest number of mutations seen in lymphoma survivors. In that study, 7 of 586 survivors of Hodgkin and non-Hodgkin lymphoma (1.2%) were found to carry BRCA2 mutations.

In the current study, the investigators performed germline whole-genome sequencing on samples from 815 survivors of childhood Hodgkin lymphoma and 748 survivors of non-Hodgkin lymphoma from the St. Jude Lifetime Cohort and Childhood Cancer Survivor studies and compared the data with those of controls without cancer from the Genome Aggregation Database.

They identified mutations in five Hodgkin lymphoma survivors (0.6%) and eight non-Hodgkin lymphoma survivors.

A comparison of cancer risk among lymphoma survivors and controls found that non-Hodgkin lymphoma survivors and BRCA2 carriers had an odds ratio for cancer of 5.0, compared with controls who were not BRCA2 carriers (P less than .001). Among Hodgkin lymphoma survivors the OR for carriers vs. controls was 2.1, but was not statistically significant.

Available family histories for seven of the eight non-Hodgkin lymphoma BRCA2 mutation carriers showed histories of BRCA2-linked cancers, including breast, prostate, and pancreas tumors and malignant melanoma.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies. Currently, it remains unclear whether surveillance for non–Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantages,” the investigators wrote.

“This study was funded by a grant to St Jude Children’s Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St Jude Children’s Research Hospital from the National Institutes of Health. The authors reported having no conflicts of interest.

SOURCE: Wang Z et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2203.

Pediatric non-Hodgkin lymphomas should be added to the list of cancers associated with BRCA2 mutations, and survivors of childhood NHL should be considered for genetic counseling, investigators suggest.

Among 1,380 survivors of childhood lymphomas, those who were retrospectively found to be carriers of BRCA2 mutations had a fivefold higher risk for non-Hodgkin lymphoma than controls without cancer, reported Zhaoming Wang, PhD, and colleagues from St. Jude Children’s Research Hospital in Memphis.

“Genetic counseling and the option of BRCA2 genetic testing should be offered to survivors of pediatric or adolescent non–Hodgkin lymphoma, particularly those with a family history of BRCA2-associated cancers,” they wrote in JAMA Oncology.

The investigators had previously reported that BRCA2 was the third-most frequently mutated gene among 3006 survivors of childhood cancers, with the highest number of mutations seen in lymphoma survivors. In that study, 7 of 586 survivors of Hodgkin and non-Hodgkin lymphoma (1.2%) were found to carry BRCA2 mutations.

In the current study, the investigators performed germline whole-genome sequencing on samples from 815 survivors of childhood Hodgkin lymphoma and 748 survivors of non-Hodgkin lymphoma from the St. Jude Lifetime Cohort and Childhood Cancer Survivor studies and compared the data with those of controls without cancer from the Genome Aggregation Database.

They identified mutations in five Hodgkin lymphoma survivors (0.6%) and eight non-Hodgkin lymphoma survivors.

A comparison of cancer risk among lymphoma survivors and controls found that non-Hodgkin lymphoma survivors and BRCA2 carriers had an odds ratio for cancer of 5.0, compared with controls who were not BRCA2 carriers (P less than .001). Among Hodgkin lymphoma survivors the OR for carriers vs. controls was 2.1, but was not statistically significant.

Available family histories for seven of the eight non-Hodgkin lymphoma BRCA2 mutation carriers showed histories of BRCA2-linked cancers, including breast, prostate, and pancreas tumors and malignant melanoma.

“Survivors whose test results are positive for mutation should be offered surveillance for BRCA2-associated cancers, such as breast and ovarian, and counseled about cancer risk–reducing strategies. Currently, it remains unclear whether surveillance for non–Hodgkin lymphoma is associated with early detection of lymphomas or with other medical advantages,” the investigators wrote.

“This study was funded by a grant to St Jude Children’s Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St Jude Children’s Research Hospital from the National Institutes of Health. The authors reported having no conflicts of interest.

SOURCE: Wang Z et al. JAMA Oncology. 2019 Jul 25. doi: 10.1001/jamaoncol.2019.2203.

Mental health comorbidities increase the rates of opioid use and mortality among breast cancer survivors on endocrine therapy, based on a retrospective study of more than 10,000 patients in a Medicare-linked database.

Screen for mental health conditions in the early stages of cancer care and lean toward opioid alternatives for pain management, advised lead author Raj Desai, MS, of the University of Florida, Gainesville, and colleagues.

“The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood, despite the high prevalence of mental health comorbidities like depression and anxiety in breast cancer survivors, and the high rate of opioid use in those on AET [adjuvant endocrine therapy],” the investigators wrote in the Journal of Oncology Practice.

“Therefore, this study aimed to determine whether breast cancer survivors with varying levels of mental health comorbidities, such as depression and anxiety, are more likely to use opioids for AET-related pain,” they added.

The study involved 10,452 breast cancer survivors who first filled an AET prescription from 2006 to 2012 and had follow-up records available for at least 2 years. All patients had a diagnosis of incident, primary, hormone receptor–positive, stage I-III breast cancer. Data were drawn from the Surveillance, Epidemiology, and End Results–Medicare linked database. Records were evaluated for diagnoses of mental health conditions such as depression and anxiety, opioid use, and survival.

Analysis showed that the most common mental health conditions were depression and anxiety, diagnosed in 554 and 246 women, respectively. Patients with mental health comorbidities were compared with patients who did not have such problems, using both unmatched and matched cohorts. While unmatched comparison for opioid use was not statistically significant, matched comparison showed that survivors with mental health comorbidities were 33% more likely to use opioids than those without mental health comorbidities (95% confidence interval, 1.06-1.68). Similarly, greater adjusted probabilities of opioid use were reported in the mental health comorbidity cohort (72.5% vs. 66.9%; P = .01).

Concerning survival, unmatched comparison revealed a 44% higher risk of death among women with depression and a 32% increase associated with anxiety. Matched comparison showed an even higher increased risk of mortality among women with any mental health comorbidity (49%; P less than .05).

The investigators concluded that opioid use among breast cancer survivors with mental health comorbidities “remains a significant problem.”

“A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions,” the investigators wrote. “Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients, but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship.”

The investigators reported financial relationships with Merck.

SOURCE: Desai R et al. J Oncol Pract. 2019 Jul 19. doi: 10.1200/JOP.18.00781.

Mental health comorbidities increase the rates of opioid use and mortality among breast cancer survivors on endocrine therapy, based on a retrospective study of more than 10,000 patients in a Medicare-linked database.

Screen for mental health conditions in the early stages of cancer care and lean toward opioid alternatives for pain management, advised lead author Raj Desai, MS, of the University of Florida, Gainesville, and colleagues.

“The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood, despite the high prevalence of mental health comorbidities like depression and anxiety in breast cancer survivors, and the high rate of opioid use in those on AET [adjuvant endocrine therapy],” the investigators wrote in the Journal of Oncology Practice.

“Therefore, this study aimed to determine whether breast cancer survivors with varying levels of mental health comorbidities, such as depression and anxiety, are more likely to use opioids for AET-related pain,” they added.

The study involved 10,452 breast cancer survivors who first filled an AET prescription from 2006 to 2012 and had follow-up records available for at least 2 years. All patients had a diagnosis of incident, primary, hormone receptor–positive, stage I-III breast cancer. Data were drawn from the Surveillance, Epidemiology, and End Results–Medicare linked database. Records were evaluated for diagnoses of mental health conditions such as depression and anxiety, opioid use, and survival.

Analysis showed that the most common mental health conditions were depression and anxiety, diagnosed in 554 and 246 women, respectively. Patients with mental health comorbidities were compared with patients who did not have such problems, using both unmatched and matched cohorts. While unmatched comparison for opioid use was not statistically significant, matched comparison showed that survivors with mental health comorbidities were 33% more likely to use opioids than those without mental health comorbidities (95% confidence interval, 1.06-1.68). Similarly, greater adjusted probabilities of opioid use were reported in the mental health comorbidity cohort (72.5% vs. 66.9%; P = .01).

Concerning survival, unmatched comparison revealed a 44% higher risk of death among women with depression and a 32% increase associated with anxiety. Matched comparison showed an even higher increased risk of mortality among women with any mental health comorbidity (49%; P less than .05).

The investigators concluded that opioid use among breast cancer survivors with mental health comorbidities “remains a significant problem.”

“A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions,” the investigators wrote. “Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients, but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship.”

The investigators reported financial relationships with Merck.

SOURCE: Desai R et al. J Oncol Pract. 2019 Jul 19. doi: 10.1200/JOP.18.00781.

Mental health comorbidities increase the rates of opioid use and mortality among breast cancer survivors on endocrine therapy, based on a retrospective study of more than 10,000 patients in a Medicare-linked database.

Screen for mental health conditions in the early stages of cancer care and lean toward opioid alternatives for pain management, advised lead author Raj Desai, MS, of the University of Florida, Gainesville, and colleagues.

“The complex relationship among breast cancer, mental health problems, and the use of opioids is not well understood, despite the high prevalence of mental health comorbidities like depression and anxiety in breast cancer survivors, and the high rate of opioid use in those on AET [adjuvant endocrine therapy],” the investigators wrote in the Journal of Oncology Practice.

“Therefore, this study aimed to determine whether breast cancer survivors with varying levels of mental health comorbidities, such as depression and anxiety, are more likely to use opioids for AET-related pain,” they added.

The study involved 10,452 breast cancer survivors who first filled an AET prescription from 2006 to 2012 and had follow-up records available for at least 2 years. All patients had a diagnosis of incident, primary, hormone receptor–positive, stage I-III breast cancer. Data were drawn from the Surveillance, Epidemiology, and End Results–Medicare linked database. Records were evaluated for diagnoses of mental health conditions such as depression and anxiety, opioid use, and survival.

Analysis showed that the most common mental health conditions were depression and anxiety, diagnosed in 554 and 246 women, respectively. Patients with mental health comorbidities were compared with patients who did not have such problems, using both unmatched and matched cohorts. While unmatched comparison for opioid use was not statistically significant, matched comparison showed that survivors with mental health comorbidities were 33% more likely to use opioids than those without mental health comorbidities (95% confidence interval, 1.06-1.68). Similarly, greater adjusted probabilities of opioid use were reported in the mental health comorbidity cohort (72.5% vs. 66.9%; P = .01).

Concerning survival, unmatched comparison revealed a 44% higher risk of death among women with depression and a 32% increase associated with anxiety. Matched comparison showed an even higher increased risk of mortality among women with any mental health comorbidity (49%; P less than .05).

The investigators concluded that opioid use among breast cancer survivors with mental health comorbidities “remains a significant problem.”

“A need exists for collaborative care in the management of mental health comorbidities in women with breast cancer, which could improve symptoms, adherence to treatment, and recovery from these mental conditions,” the investigators wrote. “Mental health treatments also are recommended to be offered in primary care, which not only would be convenient for patients, but also would reduce the stigma associated with treatments for mental health comorbidities and improve the patient-provider relationship.”

The investigators reported financial relationships with Merck.

SOURCE: Desai R et al. J Oncol Pract. 2019 Jul 19. doi: 10.1200/JOP.18.00781.

The Food and Drug Administration requested on July 24 that Allergan pull six brands of textured breast implants and breast expanders from the U.S. market, an action the agency took because of new data that substantially increased the number of women who developed a rare cancer – anaplastic large-cell lymphoma – in association with receiving these textured breast devices.

gorodenkoff/iStock/Getty Images Plus

This is the first product recall the FDA has made to address the issue of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), a complication that first came to national attention with a 2011 FDA report that had tallied 60 identified BIA-ALCL cases worldwide. By the end of September 2018, the number of reported worldwide BIA-ALCL cases had jumped to 457 cases reported to the agency via medical device reporting. In July 2019, the FDA cited a total of 573 unique, global case reports for BIA-ALCL sent to the agency through July 6, including 33 episodes that led to death.

It was inclusion of these additional 116 cases since September 2018 and 24 additional deaths that led FDA researchers to conclude that “the risk of BIA-ALCL with Allergan BIOCELL textured implants is approximately six-times the risk of BIA-ALCL with textured implants from other manufacturers marketing in the U.S.,” according to a statement from the agency.

The FDA is not recommending that patients who received one of the six products covered by the recall have the material removed if symptoms have not appeared because of the potential risk from explantation.

The agency also stressed that its investigation of the risk posed by placement of other brands of textured breast implants is ongoing and that overall less than 5% of all breast implants performed in current U.S. practice involve the macrotextured implants of the type specified in the Allergan recall.

This U.S. recall follows similar actions taken in France (and the rest of the European Union), Canada, and Australia, and it contrasts with the agency’s prior decision in May 2019 not to start a recall or ban of textured implants following a advisory committee meeting that discussed BIA-ALCL.

The six products that Allergan agreed to recall from marketing at the FDA’s request are four textured breast implants (Natrelle Saline-Filled Breast Implants, Natrelle Silicone-Filled Breast Implants, Natrelle Inspira Silicone-Filled breast Implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants) and two tissue expanders used prior to a breast implant (Natrelle 133 Plus Tissue Expander and the Natrelle 133 Tissue Expander with Suture Tabs).

FDA officials said they are considering recommendations for changes to the labeling of breast implant products, including a possible boxed warning and beefed up patient information.

“The recall of these textured implants is a big deal in protecting women from the potential risks of developing, and dying from, this rare type of aggressive lymphoma,” Joshua Brody, MD, a medical oncologist and director of the lymphoma immunotherapy program at Mount Sinai Medical Center in New York said in a statement. “While case reports have suggested a potential link between some types of breast implants and this disease – anaplastic lymphoma – for over 20 years, it has taken time to gain sufficient evidence to suggest, and understand, the causality. Some types of implants induce inflammation, which can both increase the chance of developing cancer, and also help to ‘hide’ developing cancers from the immune system. By preventing further use of these implants, the FDA is helping women to protect themselves from the medically serious and emotionally exhausting effects of these risks.”

Dr. Brody reported having no relevant disclosures.

[email protected]

The Food and Drug Administration requested on July 24 that Allergan pull six brands of textured breast implants and breast expanders from the U.S. market, an action the agency took because of new data that substantially increased the number of women who developed a rare cancer – anaplastic large-cell lymphoma – in association with receiving these textured breast devices.

gorodenkoff/iStock/Getty Images Plus

This is the first product recall the FDA has made to address the issue of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), a complication that first came to national attention with a 2011 FDA report that had tallied 60 identified BIA-ALCL cases worldwide. By the end of September 2018, the number of reported worldwide BIA-ALCL cases had jumped to 457 cases reported to the agency via medical device reporting. In July 2019, the FDA cited a total of 573 unique, global case reports for BIA-ALCL sent to the agency through July 6, including 33 episodes that led to death.

It was inclusion of these additional 116 cases since September 2018 and 24 additional deaths that led FDA researchers to conclude that “the risk of BIA-ALCL with Allergan BIOCELL textured implants is approximately six-times the risk of BIA-ALCL with textured implants from other manufacturers marketing in the U.S.,” according to a statement from the agency.

The FDA is not recommending that patients who received one of the six products covered by the recall have the material removed if symptoms have not appeared because of the potential risk from explantation.

The agency also stressed that its investigation of the risk posed by placement of other brands of textured breast implants is ongoing and that overall less than 5% of all breast implants performed in current U.S. practice involve the macrotextured implants of the type specified in the Allergan recall.

This U.S. recall follows similar actions taken in France (and the rest of the European Union), Canada, and Australia, and it contrasts with the agency’s prior decision in May 2019 not to start a recall or ban of textured implants following a advisory committee meeting that discussed BIA-ALCL.

The six products that Allergan agreed to recall from marketing at the FDA’s request are four textured breast implants (Natrelle Saline-Filled Breast Implants, Natrelle Silicone-Filled Breast Implants, Natrelle Inspira Silicone-Filled breast Implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants) and two tissue expanders used prior to a breast implant (Natrelle 133 Plus Tissue Expander and the Natrelle 133 Tissue Expander with Suture Tabs).

FDA officials said they are considering recommendations for changes to the labeling of breast implant products, including a possible boxed warning and beefed up patient information.

“The recall of these textured implants is a big deal in protecting women from the potential risks of developing, and dying from, this rare type of aggressive lymphoma,” Joshua Brody, MD, a medical oncologist and director of the lymphoma immunotherapy program at Mount Sinai Medical Center in New York said in a statement. “While case reports have suggested a potential link between some types of breast implants and this disease – anaplastic lymphoma – for over 20 years, it has taken time to gain sufficient evidence to suggest, and understand, the causality. Some types of implants induce inflammation, which can both increase the chance of developing cancer, and also help to ‘hide’ developing cancers from the immune system. By preventing further use of these implants, the FDA is helping women to protect themselves from the medically serious and emotionally exhausting effects of these risks.”

Dr. Brody reported having no relevant disclosures.

[email protected]

The Food and Drug Administration requested on July 24 that Allergan pull six brands of textured breast implants and breast expanders from the U.S. market, an action the agency took because of new data that substantially increased the number of women who developed a rare cancer – anaplastic large-cell lymphoma – in association with receiving these textured breast devices.

gorodenkoff/iStock/Getty Images Plus

This is the first product recall the FDA has made to address the issue of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), a complication that first came to national attention with a 2011 FDA report that had tallied 60 identified BIA-ALCL cases worldwide. By the end of September 2018, the number of reported worldwide BIA-ALCL cases had jumped to 457 cases reported to the agency via medical device reporting. In July 2019, the FDA cited a total of 573 unique, global case reports for BIA-ALCL sent to the agency through July 6, including 33 episodes that led to death.

It was inclusion of these additional 116 cases since September 2018 and 24 additional deaths that led FDA researchers to conclude that “the risk of BIA-ALCL with Allergan BIOCELL textured implants is approximately six-times the risk of BIA-ALCL with textured implants from other manufacturers marketing in the U.S.,” according to a statement from the agency.

The FDA is not recommending that patients who received one of the six products covered by the recall have the material removed if symptoms have not appeared because of the potential risk from explantation.

The agency also stressed that its investigation of the risk posed by placement of other brands of textured breast implants is ongoing and that overall less than 5% of all breast implants performed in current U.S. practice involve the macrotextured implants of the type specified in the Allergan recall.

This U.S. recall follows similar actions taken in France (and the rest of the European Union), Canada, and Australia, and it contrasts with the agency’s prior decision in May 2019 not to start a recall or ban of textured implants following a advisory committee meeting that discussed BIA-ALCL.

The six products that Allergan agreed to recall from marketing at the FDA’s request are four textured breast implants (Natrelle Saline-Filled Breast Implants, Natrelle Silicone-Filled Breast Implants, Natrelle Inspira Silicone-Filled breast Implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants) and two tissue expanders used prior to a breast implant (Natrelle 133 Plus Tissue Expander and the Natrelle 133 Tissue Expander with Suture Tabs).

FDA officials said they are considering recommendations for changes to the labeling of breast implant products, including a possible boxed warning and beefed up patient information.

“The recall of these textured implants is a big deal in protecting women from the potential risks of developing, and dying from, this rare type of aggressive lymphoma,” Joshua Brody, MD, a medical oncologist and director of the lymphoma immunotherapy program at Mount Sinai Medical Center in New York said in a statement. “While case reports have suggested a potential link between some types of breast implants and this disease – anaplastic lymphoma – for over 20 years, it has taken time to gain sufficient evidence to suggest, and understand, the causality. Some types of implants induce inflammation, which can both increase the chance of developing cancer, and also help to ‘hide’ developing cancers from the immune system. By preventing further use of these implants, the FDA is helping women to protect themselves from the medically serious and emotionally exhausting effects of these risks.”

Dr. Brody reported having no relevant disclosures.

[email protected]

Natural disasters such as hurricanes cause delays in radiotherapy delivery for non–small cell lung cancer (NSCLC) that ultimately translate to poorer outcomes, suggests a retrospective cohort study.

“Radiotherapy is particularly vulnerable because it requires dependable electrical power and daily treatment,” lead investigator Leticia M. Nogueira, PhD, Surveillance and Health Services Research Program, American Cancer Society, and colleagues noted. “Disruptions are especially concerning for patients undergoing treatment for locally advanced ... NSCLC because treatment delays as little as 2 days negatively affect survival.”

The investigators used the National Cancer Database to identify patients receiving definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2014 who had at least 1 year of follow-up for vital status.

Each patient undergoing radiotherapy when a hurricane disaster was declared for their facility’s area was matched through propensity scoring with a patient treated during a declaration-free period having similar start month, sex, age, stage, nodal status, and income. Analyses compared 1,734 exposed patients with 1,734 unexposed patients.

Study results reported in JAMA showed that 101 hurricane disaster declarations were made during the study period, and they lasted from 1 day to 69 days. The radiation treatment duration was about 21 days (45%) longer for patients exposed to these declarations than for unexposed counterparts (66.9 vs. 46.2 days; P less than .001).

Over a median follow-up of 15 months, exposed patients were more likely to die (adjusted hazard ratio, 1.19; P = .001). Moreover, risk generally rose with the duration of the declaration, peaking for patients exposed to those lasting 27 days (adjusted relative risk, 1.27).

“Because data on other potentially explanatory factors are lacking, the relative contribution of treatment delay to the observed association cannot be quantified. However, treatment delay is one of the few hurricane-related disruptions that can be prevented,” Dr. Nogueira and colleagues maintain.

“Because no recommended correction for radiotherapy delays exists ... strategies for identifying patients, arranging for transferring treatment, and eliminating patient out-of-network insurance charges should be considered in disaster mitigation planning,” they recommend.

Dr. Nogueira disclosed no relevant conflicts of interest. The investigators conducted the study as part of the in-tramural research program at the American Cancer Society or contributed their time.

SOURCE: Nogueira LM et al. JAMA. 2019 Jul 16;322(3):269-71.

Natural disasters such as hurricanes cause delays in radiotherapy delivery for non–small cell lung cancer (NSCLC) that ultimately translate to poorer outcomes, suggests a retrospective cohort study.

“Radiotherapy is particularly vulnerable because it requires dependable electrical power and daily treatment,” lead investigator Leticia M. Nogueira, PhD, Surveillance and Health Services Research Program, American Cancer Society, and colleagues noted. “Disruptions are especially concerning for patients undergoing treatment for locally advanced ... NSCLC because treatment delays as little as 2 days negatively affect survival.”

The investigators used the National Cancer Database to identify patients receiving definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2014 who had at least 1 year of follow-up for vital status.

Each patient undergoing radiotherapy when a hurricane disaster was declared for their facility’s area was matched through propensity scoring with a patient treated during a declaration-free period having similar start month, sex, age, stage, nodal status, and income. Analyses compared 1,734 exposed patients with 1,734 unexposed patients.

Study results reported in JAMA showed that 101 hurricane disaster declarations were made during the study period, and they lasted from 1 day to 69 days. The radiation treatment duration was about 21 days (45%) longer for patients exposed to these declarations than for unexposed counterparts (66.9 vs. 46.2 days; P less than .001).

Over a median follow-up of 15 months, exposed patients were more likely to die (adjusted hazard ratio, 1.19; P = .001). Moreover, risk generally rose with the duration of the declaration, peaking for patients exposed to those lasting 27 days (adjusted relative risk, 1.27).

“Because data on other potentially explanatory factors are lacking, the relative contribution of treatment delay to the observed association cannot be quantified. However, treatment delay is one of the few hurricane-related disruptions that can be prevented,” Dr. Nogueira and colleagues maintain.

“Because no recommended correction for radiotherapy delays exists ... strategies for identifying patients, arranging for transferring treatment, and eliminating patient out-of-network insurance charges should be considered in disaster mitigation planning,” they recommend.

Dr. Nogueira disclosed no relevant conflicts of interest. The investigators conducted the study as part of the in-tramural research program at the American Cancer Society or contributed their time.

SOURCE: Nogueira LM et al. JAMA. 2019 Jul 16;322(3):269-71.

Natural disasters such as hurricanes cause delays in radiotherapy delivery for non–small cell lung cancer (NSCLC) that ultimately translate to poorer outcomes, suggests a retrospective cohort study.

“Radiotherapy is particularly vulnerable because it requires dependable electrical power and daily treatment,” lead investigator Leticia M. Nogueira, PhD, Surveillance and Health Services Research Program, American Cancer Society, and colleagues noted. “Disruptions are especially concerning for patients undergoing treatment for locally advanced ... NSCLC because treatment delays as little as 2 days negatively affect survival.”

The investigators used the National Cancer Database to identify patients receiving definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2014 who had at least 1 year of follow-up for vital status.

Each patient undergoing radiotherapy when a hurricane disaster was declared for their facility’s area was matched through propensity scoring with a patient treated during a declaration-free period having similar start month, sex, age, stage, nodal status, and income. Analyses compared 1,734 exposed patients with 1,734 unexposed patients.

Study results reported in JAMA showed that 101 hurricane disaster declarations were made during the study period, and they lasted from 1 day to 69 days. The radiation treatment duration was about 21 days (45%) longer for patients exposed to these declarations than for unexposed counterparts (66.9 vs. 46.2 days; P less than .001).

Over a median follow-up of 15 months, exposed patients were more likely to die (adjusted hazard ratio, 1.19; P = .001). Moreover, risk generally rose with the duration of the declaration, peaking for patients exposed to those lasting 27 days (adjusted relative risk, 1.27).

“Because data on other potentially explanatory factors are lacking, the relative contribution of treatment delay to the observed association cannot be quantified. However, treatment delay is one of the few hurricane-related disruptions that can be prevented,” Dr. Nogueira and colleagues maintain.

“Because no recommended correction for radiotherapy delays exists ... strategies for identifying patients, arranging for transferring treatment, and eliminating patient out-of-network insurance charges should be considered in disaster mitigation planning,” they recommend.

Dr. Nogueira disclosed no relevant conflicts of interest. The investigators conducted the study as part of the in-tramural research program at the American Cancer Society or contributed their time.

SOURCE: Nogueira LM et al. JAMA. 2019 Jul 16;322(3):269-71.

The strategy of simultaneously inhibiting proliferation and reactivating apoptosis can eradicate chronic lymphocytic leukemia (CLL) in a large share of patients, suggest results from the phase 2 CLARITY trial.

©Ed Uthman/Flickr

“Both ibrutinib and venetoclax are active in CLL with improved survival; however, as monotherapies, both currently are given until disease progression,” wrote Peter Hillmen, MBChB, PhD, St. James’s University Hospital, Leeds, England, and his colleagues.

In the single-arm, open-label trial, the investigators treated 53 patients with relapsed or refractory CLL with combination ibrutinib (Imbruvica), a small-molecule inhibitor of Bruton’s tyrosine kinase, and venetoclax (Venclexta), a small molecule inhibitor of the anti-apoptotic protein Bcl-2. The primary endpoint was MRD negativity, defined as presence of fewer than one CLL cell in 10,000 leukocytes, after 12 months of combination therapy.

Results reported in the Journal of Clinical Oncology showed that the combination was highly active, with 53% of patients achieving MRD negativity in the blood and 36% achieving MRD negativity in the marrow.

Most patients, 89%, had a treatment response, and slightly more than half, 51%, achieved a complete remission. With a median 21.1-month follow-up, only a single patient experienced progression and all were still alive.

Adverse effects were generally manageable. Grade 3-4 adverse events of special interest included 34 cases of neutropenia and 1 case of biochemical tumor lysis syndrome that was managed by delaying venetoclax.

“We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects,” the investigators wrote. “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission.”


Whether the combination leads to permanent disease eradication in certain patients is still unclear, the investigators added.

The trial was supported by Bloodwise under the Trials Acceleration Programme, by the National Institute for Health Research Leeds Clinical Research Facility, and by an unrestricted educational grant from Janssen-Cilag and AbbVie. Ibrutinib was provided free of charge by Janssen-Cilag, and venetoclax was provided free of charge by AbbVie. Dr. Hillman reported financial relationships with Janssen, AbbVie, Roche, Pharmacyclics, and Gilead Sciences.

SOURCE: Hillmen P et al. J Clin Oncol. 2019 Jul 11. doi: 10.1200/JCO.19.00894.

The strategy of simultaneously inhibiting proliferation and reactivating apoptosis can eradicate chronic lymphocytic leukemia (CLL) in a large share of patients, suggest results from the phase 2 CLARITY trial.

©Ed Uthman/Flickr

“Both ibrutinib and venetoclax are active in CLL with improved survival; however, as monotherapies, both currently are given until disease progression,” wrote Peter Hillmen, MBChB, PhD, St. James’s University Hospital, Leeds, England, and his colleagues.

In the single-arm, open-label trial, the investigators treated 53 patients with relapsed or refractory CLL with combination ibrutinib (Imbruvica), a small-molecule inhibitor of Bruton’s tyrosine kinase, and venetoclax (Venclexta), a small molecule inhibitor of the anti-apoptotic protein Bcl-2. The primary endpoint was MRD negativity, defined as presence of fewer than one CLL cell in 10,000 leukocytes, after 12 months of combination therapy.

Results reported in the Journal of Clinical Oncology showed that the combination was highly active, with 53% of patients achieving MRD negativity in the blood and 36% achieving MRD negativity in the marrow.

Most patients, 89%, had a treatment response, and slightly more than half, 51%, achieved a complete remission. With a median 21.1-month follow-up, only a single patient experienced progression and all were still alive.

Adverse effects were generally manageable. Grade 3-4 adverse events of special interest included 34 cases of neutropenia and 1 case of biochemical tumor lysis syndrome that was managed by delaying venetoclax.

“We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects,” the investigators wrote. “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission.”


Whether the combination leads to permanent disease eradication in certain patients is still unclear, the investigators added.

The trial was supported by Bloodwise under the Trials Acceleration Programme, by the National Institute for Health Research Leeds Clinical Research Facility, and by an unrestricted educational grant from Janssen-Cilag and AbbVie. Ibrutinib was provided free of charge by Janssen-Cilag, and venetoclax was provided free of charge by AbbVie. Dr. Hillman reported financial relationships with Janssen, AbbVie, Roche, Pharmacyclics, and Gilead Sciences.

SOURCE: Hillmen P et al. J Clin Oncol. 2019 Jul 11. doi: 10.1200/JCO.19.00894.

The strategy of simultaneously inhibiting proliferation and reactivating apoptosis can eradicate chronic lymphocytic leukemia (CLL) in a large share of patients, suggest results from the phase 2 CLARITY trial.

©Ed Uthman/Flickr

“Both ibrutinib and venetoclax are active in CLL with improved survival; however, as monotherapies, both currently are given until disease progression,” wrote Peter Hillmen, MBChB, PhD, St. James’s University Hospital, Leeds, England, and his colleagues.

In the single-arm, open-label trial, the investigators treated 53 patients with relapsed or refractory CLL with combination ibrutinib (Imbruvica), a small-molecule inhibitor of Bruton’s tyrosine kinase, and venetoclax (Venclexta), a small molecule inhibitor of the anti-apoptotic protein Bcl-2. The primary endpoint was MRD negativity, defined as presence of fewer than one CLL cell in 10,000 leukocytes, after 12 months of combination therapy.

Results reported in the Journal of Clinical Oncology showed that the combination was highly active, with 53% of patients achieving MRD negativity in the blood and 36% achieving MRD negativity in the marrow.

Most patients, 89%, had a treatment response, and slightly more than half, 51%, achieved a complete remission. With a median 21.1-month follow-up, only a single patient experienced progression and all were still alive.

Adverse effects were generally manageable. Grade 3-4 adverse events of special interest included 34 cases of neutropenia and 1 case of biochemical tumor lysis syndrome that was managed by delaying venetoclax.

“We have demonstrated promising efficacy that indicates potent synergy between ibrutinib and venetoclax for inducing MRD-negative responses with manageable adverse effects,” the investigators wrote. “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission.”


Whether the combination leads to permanent disease eradication in certain patients is still unclear, the investigators added.

The trial was supported by Bloodwise under the Trials Acceleration Programme, by the National Institute for Health Research Leeds Clinical Research Facility, and by an unrestricted educational grant from Janssen-Cilag and AbbVie. Ibrutinib was provided free of charge by Janssen-Cilag, and venetoclax was provided free of charge by AbbVie. Dr. Hillman reported financial relationships with Janssen, AbbVie, Roche, Pharmacyclics, and Gilead Sciences.

SOURCE: Hillmen P et al. J Clin Oncol. 2019 Jul 11. doi: 10.1200/JCO.19.00894.

Colorectal cancer (CRC) incidence continues to rise in younger adults, with no signs of plateauing, according to investigators who recently conducted an analysis of a large US cancer registry.

Adults aged 50 years and younger accounted for about 12% of colorectal cancer diagnoses in 2015, up from 10% in 2004, and significantly more of those younger patients had advanced disease at diagnosis as compared to older adults, according to the analysis of the National Cancer Database (NCDB) by Boone Goodgame, MD, of the University of Texas at Austin, and colleagues.

“These results may provide support for adjusting CRC screening guidelines to identify patients before the age of 50 years,” said Dr. Goodgame and study coauthors in Cancer.

Only 5.8% of colorectal cancer cases were diagnosed in individuals younger than 45 years, suggesting that age may be an “appropriate target” for the screening age, the authors said in their report, alluding to the 2018 qualified recommendation from the American Cancer Society to begin screening at age 45.

However, a member of the U.S. Preventive Services Task Force – which continues to recommend screening of asymptomatic adults starting at 50 years – said in an editorial that it remains “unknown” whether the harms of screening for sporadic cases of colorectal cancer in younger individuals would outweigh the benefits.

The study by Dr. Goodgame and colleagues included a total of 1,185,763 colorectal cancer cases in the NCDB during 2004-2015, of which 89% were diagnosed at the age of 50 or older, and 11% were diagnosed in younger individuals.

The proportion of colorectal cancer cases diagnosed in people aged 50 years and younger increased from 10.0% to 12.2% during the study period (P less than .0001), with comparable increases for both rectal and colon primary tumors, according to the the journal article.

Younger patients were more likely to have stage III and stage IV disease than older patients were, according to the investigators. Stage III disease was reported for 28.1% and 23.1% of younger individuals and those over 50 years, respectively, while stage IV disease was reported for 23.5% and 16.9% (P less than .0001 for both comparisons).

Race and sex differences were seen in proportions of patients younger than 50 years with colorectal cancer, further analysis of the NCDB data showed.

Among men, only non-Hispanic whites had a significant increase in colorectal cancer diagnoses under the age of 50 years over the study period, while in women, significant increases were seen in Hispanic and non-Hispanic whites, according to the report.

It’s unclear exactly what’s behind the increase in colorectal cancer diagnosis, the authors acknowledged in their report, citing a host of potentially explanatory factors, such as access to health care, lifestyle factors such as obesity, or increased antibiotic use.

Some say the increase could simply be from the more liberal use of colonoscopy, resulting in a lead time bias, the authors noted.

“However, a change in the lead-time bias should also increase the proportion of earlier stage disease in younger adults, and we did not see this in our study,” they said in the report. “Therefore, increasing colonoscopy use does not appear to be a sufficient explanation for this association.”

In any case, more studies are needed to better determine the risks, benefits, and costs of screening individuals younger than 50 years for colorectal cancer, they concluded, saying that their data should be included in an “ongoing discussion” of screening guidelines.

Dr. Goodgame and coauthors made no conflict of interest disclosures related to the study, which was supported by the National Cancer Institute and the Cancer Prevention and Research Institute of Texas.

SOURCE: Virostko J et al. Cancer. 2019 Jul 22. doi: 10.1002/cncr.32347.

Colorectal cancer (CRC) incidence continues to rise in younger adults, with no signs of plateauing, according to investigators who recently conducted an analysis of a large US cancer registry.

Adults aged 50 years and younger accounted for about 12% of colorectal cancer diagnoses in 2015, up from 10% in 2004, and significantly more of those younger patients had advanced disease at diagnosis as compared to older adults, according to the analysis of the National Cancer Database (NCDB) by Boone Goodgame, MD, of the University of Texas at Austin, and colleagues.

“These results may provide support for adjusting CRC screening guidelines to identify patients before the age of 50 years,” said Dr. Goodgame and study coauthors in Cancer.

Only 5.8% of colorectal cancer cases were diagnosed in individuals younger than 45 years, suggesting that age may be an “appropriate target” for the screening age, the authors said in their report, alluding to the 2018 qualified recommendation from the American Cancer Society to begin screening at age 45.

However, a member of the U.S. Preventive Services Task Force – which continues to recommend screening of asymptomatic adults starting at 50 years – said in an editorial that it remains “unknown” whether the harms of screening for sporadic cases of colorectal cancer in younger individuals would outweigh the benefits.

The study by Dr. Goodgame and colleagues included a total of 1,185,763 colorectal cancer cases in the NCDB during 2004-2015, of which 89% were diagnosed at the age of 50 or older, and 11% were diagnosed in younger individuals.

The proportion of colorectal cancer cases diagnosed in people aged 50 years and younger increased from 10.0% to 12.2% during the study period (P less than .0001), with comparable increases for both rectal and colon primary tumors, according to the the journal article.

Younger patients were more likely to have stage III and stage IV disease than older patients were, according to the investigators. Stage III disease was reported for 28.1% and 23.1% of younger individuals and those over 50 years, respectively, while stage IV disease was reported for 23.5% and 16.9% (P less than .0001 for both comparisons).

Race and sex differences were seen in proportions of patients younger than 50 years with colorectal cancer, further analysis of the NCDB data showed.

Among men, only non-Hispanic whites had a significant increase in colorectal cancer diagnoses under the age of 50 years over the study period, while in women, significant increases were seen in Hispanic and non-Hispanic whites, according to the report.

It’s unclear exactly what’s behind the increase in colorectal cancer diagnosis, the authors acknowledged in their report, citing a host of potentially explanatory factors, such as access to health care, lifestyle factors such as obesity, or increased antibiotic use.

Some say the increase could simply be from the more liberal use of colonoscopy, resulting in a lead time bias, the authors noted.

“However, a change in the lead-time bias should also increase the proportion of earlier stage disease in younger adults, and we did not see this in our study,” they said in the report. “Therefore, increasing colonoscopy use does not appear to be a sufficient explanation for this association.”

In any case, more studies are needed to better determine the risks, benefits, and costs of screening individuals younger than 50 years for colorectal cancer, they concluded, saying that their data should be included in an “ongoing discussion” of screening guidelines.

Dr. Goodgame and coauthors made no conflict of interest disclosures related to the study, which was supported by the National Cancer Institute and the Cancer Prevention and Research Institute of Texas.

SOURCE: Virostko J et al. Cancer. 2019 Jul 22. doi: 10.1002/cncr.32347.

Colorectal cancer (CRC) incidence continues to rise in younger adults, with no signs of plateauing, according to investigators who recently conducted an analysis of a large US cancer registry.

Adults aged 50 years and younger accounted for about 12% of colorectal cancer diagnoses in 2015, up from 10% in 2004, and significantly more of those younger patients had advanced disease at diagnosis as compared to older adults, according to the analysis of the National Cancer Database (NCDB) by Boone Goodgame, MD, of the University of Texas at Austin, and colleagues.

“These results may provide support for adjusting CRC screening guidelines to identify patients before the age of 50 years,” said Dr. Goodgame and study coauthors in Cancer.

Only 5.8% of colorectal cancer cases were diagnosed in individuals younger than 45 years, suggesting that age may be an “appropriate target” for the screening age, the authors said in their report, alluding to the 2018 qualified recommendation from the American Cancer Society to begin screening at age 45.

However, a member of the U.S. Preventive Services Task Force – which continues to recommend screening of asymptomatic adults starting at 50 years – said in an editorial that it remains “unknown” whether the harms of screening for sporadic cases of colorectal cancer in younger individuals would outweigh the benefits.

The study by Dr. Goodgame and colleagues included a total of 1,185,763 colorectal cancer cases in the NCDB during 2004-2015, of which 89% were diagnosed at the age of 50 or older, and 11% were diagnosed in younger individuals.

The proportion of colorectal cancer cases diagnosed in people aged 50 years and younger increased from 10.0% to 12.2% during the study period (P less than .0001), with comparable increases for both rectal and colon primary tumors, according to the the journal article.

Younger patients were more likely to have stage III and stage IV disease than older patients were, according to the investigators. Stage III disease was reported for 28.1% and 23.1% of younger individuals and those over 50 years, respectively, while stage IV disease was reported for 23.5% and 16.9% (P less than .0001 for both comparisons).

Race and sex differences were seen in proportions of patients younger than 50 years with colorectal cancer, further analysis of the NCDB data showed.

Among men, only non-Hispanic whites had a significant increase in colorectal cancer diagnoses under the age of 50 years over the study period, while in women, significant increases were seen in Hispanic and non-Hispanic whites, according to the report.

It’s unclear exactly what’s behind the increase in colorectal cancer diagnosis, the authors acknowledged in their report, citing a host of potentially explanatory factors, such as access to health care, lifestyle factors such as obesity, or increased antibiotic use.

Some say the increase could simply be from the more liberal use of colonoscopy, resulting in a lead time bias, the authors noted.

“However, a change in the lead-time bias should also increase the proportion of earlier stage disease in younger adults, and we did not see this in our study,” they said in the report. “Therefore, increasing colonoscopy use does not appear to be a sufficient explanation for this association.”

In any case, more studies are needed to better determine the risks, benefits, and costs of screening individuals younger than 50 years for colorectal cancer, they concluded, saying that their data should be included in an “ongoing discussion” of screening guidelines.

Dr. Goodgame and coauthors made no conflict of interest disclosures related to the study, which was supported by the National Cancer Institute and the Cancer Prevention and Research Institute of Texas.

SOURCE: Virostko J et al. Cancer. 2019 Jul 22. doi: 10.1002/cncr.32347.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

Researchers say they have identified potential prognostic markers and targets for treatment in patients with non–small cell lung cancer (NSCLC) and brain metastases (BM).

There was “substantial” concordance in driver mutations, such as EGFR and KRAS, between BM and primary tumor samples but greater genomic instability in BM samples, reported Hong-Sheng Wang, PhD, of Sun Yat-Sen University in Guangzhou, China, and colleagues.

PI3K signaling was significantly associated with an increased risk of BM, and CDKs and PIK3CA were “potential druggable mutations,” they reported in Cancer.

The researchers conducted a retrospective study of 61 Chinese patients with NSCLC and BM. The patients had adenocarcinoma (n = 50), squamous cell carcinoma (n = 3), and mixed subtypes (n = 8). Less than half of patients (n = 28) had stage IV disease at diagnosis, 36 had metachronous disease, and 25 had synchronous disease. All patients had undergone surgery, 33 had received chemoradiation, 26 had received no systemic treatment, and 5 had been treated with tyrosine kinase inhibitors.

The researchers performed next-generation sequencing on primary tumors and matched BM samples from the 61 patients, targeting 416 cancer-relevant genes.

Results showed high concordance between the primary and BM samples with regard to major driver mutations – 92% for EGFR, 82% for KRAS, and 83% for TP53 mutations.

For nearly half of patients (48%), all mutations found in primary tumor samples were also found in BM samples. In fact, 18% of patients had the same mutational profiles in lung and brain lesions.

Conversely, 30% of patients had more brain-specific mutations, 13% had more lung-specific mutations, 28% had mixed profiles, and 11% had completely unique mutational profiles in lung and brain lesions.

Compared with primary tumor samples, BM samples had a significantly higher frequency of copy number variations (P = .0002); alterations in CDKN2A/2B, CCND1, CDK4, and RB1 (P = .0019); and alterations in PIK3CA, PTEN, STK11, RICTOR, and NF2 (P = .0037).

Patients with activated PI3K signaling in their primary tumors had significantly shorter BM-free survival. The hazard ratio (adjusted for baseline clinicopathologic parameters) was 8.49 (P = .0005).

There was no significant difference in BM-free survival between EGFR-/KRAS-mutated patients and patients with wild-type EGFR/KRAS (P = .29). However, there was a trend toward shorter BM-free survival in patients with TP53 mutations (P = .15).

There was a trend toward shorter BM-free intervals in patients with an activated WNT pathway via CTNNB1 mutations (P = .22) or APC and AXIN2 mutations (P = .015). However, the researchers said these findings should be treated with caution due to a small sample size.

The National Natural Science Foundation of China and the Natural Science Foundation of Guangdong Province supported the research. The researchers disclosed relationships with Geneseeq Technology Inc. in Toronto and Nanjing Geneseeq Technology Inc.

SOURCE: Wang H et al. Cancer. 2019 Jul 9. doi: 10.1002/cncr.32372.

There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.

In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.

For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).

Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.

When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.

About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).

In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)

“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.

“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”

Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.

SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.

There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.

In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.

For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).

Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.

When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.

About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).

In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)

“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.

“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”

Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.

SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.

There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.

In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.

For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).

Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.

When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.

About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).

In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)

“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.

“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”

Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.

SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.