Patient & Survivor Care

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

Disease progression is associated with worsening health-related quality of life (HRQOL) among patients with metastatic cancers, results of an observational study suggest.

The findings highlight the importance of patient-relevant outcomes when evaluating novel therapies for patients with metastatic cancers, according to Norbert Marschner, MD, of Praxis für interdisziplinäre onkologie und hämatologie in Freiburg, Germany, and colleagues. The researchers reported the findings in JAMA Network Open.

They used four nationwide German registries to evaluate the association of disease progression with HRQOL in patients receiving systemic therapy for metastatic colorectal, lung, pancreatic, or breast cancer.

The analysis included 2,314 adults with documented disease progression across 203 institutions in Germany. Data collection occurred during routine follow-up visits at participating centers during 2011-2018.

Various patient-reported outcome questionnaires were used to measure HRQOL and symptom severity among participants. For the present study, the team enrolled patients at the start of any systemic palliative treatment, defined as targeted therapy, chemotherapy, or endocrine therapy.

Mixed-model analyses of more than 8,000 questionnaires showed that the first disease progression was associated with significant deterioration in 37 of 45 HRQOL scales overall, 17 of which were considered clinically meaningful.

With respect to cancer type, significant worsening after the first progression occurred in 12 of 14 colorectal cancer HRQOL scales, 11 of 14 lung cancer scales, 10 of 10 pancreatic cancer scales, and 4 of 7 breast cancer scales.

The deterioration in global HRQOL associated with the first progression was of greatest magnitude in lung cancer (6.7 points; P < .001), followed by pancreatic cancer (5.4 points; P < .001), colorectal cancer (3.5 points; P = .002), and breast cancer (2.4 points; P = .001).

The researchers also found that 38 of 45 HRQOL scales showed a greater degree of worsening after the second disease progression than after the first. They observed significant worsening after the second disease progression in 32 of 45 HRQOL scales, and all 32 were considered clinically meaningful.

The researchers acknowledged that a key limitation of this study was the observational design. As a result, the study did not include specifications related to tumor assessment, such as frequency, timing, or criteria.

“We suggest that progression-related endpoints in metastatic breast, colorectal, lung, or pancreatic cancer should be considered when evaluating the benefit of novel treatments, in addition to survival, morbidity, and HRQOL outcomes,” the researchers concluded.

The registries used in this study are funded by iOMEDICO and industry sponsors. The authors disclosed relationships with iOMEDICO and several pharmaceutical companies.

SOURCE: Marschner N et al. JAMA Netw Open. 2020 Mar 10. doi: 10.1001/jamanetworkopen.2020.0643.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

For patients undergoing major oncologic surgery, the best definition of malnutrition used to assess postoperative risk varies by cancer type, results of a retrospective study suggest.

The current, one-size-fits-all approach to nutritional status leads to both undertreatment and overtreatment of malnutrition, as well as inaccurate estimations of postoperative risk, reported lead study author Nicholas P. McKenna, MD, of the Mayo Clinic in Rochester, Minn., and colleagues.

“Assessing nutritional status is important because it impacts preoperative planning, particularly with respect to the use of prehabilitation,” the investigators wrote. Their report is in the Journal of the American College of Surgeons. They noted that while prehabilitation has been shown to reduce postoperative risk among those who need it, identification of these patients is an area that needs improvement.

With this in mind, Dr. McKenna and colleagues analyzed 205,840 major oncologic operations, with data drawn from the American College of Surgeons National Surgical Quality Improvement (NSQIP) database.

The researchers evaluated patients’ nutritional status using three techniques: the NSQIP method, the European Society for Clinical Nutrition and Metabolism (ESPEN) definitions, and the World Health Organization body mass index (BMI) classification system.

Combining these three assessments led to seven hierarchical nutritional status categories:

• Severe malnutrition – BMI less than 18.5 kg/m² and greater than 10% weight loss
• ESPEN 1 – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• ESPEN 2 – BMI less than 18.5 kg/m²
• NSQIP – BMI greater than 20 kg/m² (if younger than 70 years) or 22 kg/m² (if 70 years or older) plus greater than 10% weight loss
• Mild malnutrition – BMI 18.5-20 kg/m² (if younger than 70 years) or less than 22 kg/m² (if 70 years or older)
• Obese – BMI at least 30 kg/m²
• No malnutrition.

The study’s primary outcomes were 30-day mortality and 30-day morbidity. The latter included a variety of complications, such as deep incisional surgical site infection, septic shock, and acute renal failure. Demographic and clinical factors were included in multivariate analyses.
 

Results

Most of the operations involved patients with colorectal cancer (74%), followed by pancreatic (10%), lung (9%), gastric (3%), esophageal (3%), and liver (2%) cancer.

Across all patients, 16% fell into one of five malnutrition categories: mild malnutrition (6%), NSQIP (6%), ESPEN 2 (2%), ESPEN 1 (1%), or severe malnutrition (0.6%). The remainder of patients were either obese (31%) or had normal nutritional status (54%).

Malnutrition was most common among patients with pancreatic cancer (28%) and least common among those with colorectal cancer (14%).

Aligning with previous research, this study showed that nutritional status was associated with postoperative risk. Mortality risk was highest among patients with severe malnutrition, and morbidity was most common in the severe and ESPEN 1 groups (P less than .0001 for both).

While the spectrum of classifications appeared accurate across the population, multivariable models for mortality and morbidity revealed an interaction between cancer type and malnutrition definition (P less than .0001 for both), which suggested the most accurate definition of malnutrition differed from one type of cancer to another.

Specifically, a classification of severe malnutrition was most predictive of mortality among patients with esophageal or colorectal cancer. ESPEN 1 was most predictive of mortality for patients with gastric or lung cancer, and NSQIP was most predictive for those with liver cancer.

For predicting morbidity, severe malnutrition was most accurate among patients with colorectal cancer, whereas ESPEN 1 was better suited for gastric and lung cancer.
 

Interpreting and applying the results

“The biggest takeaway is that the optimal definition of malnutrition varies by cancer type,” Dr. McKenna said in an interview.

He went on to explain that weight loss is a particularly important indicator of malnutrition for patients with esophageal or gastric cancer. “These are the cancers that more commonly undergo neoadjuvant chemotherapy,” he noted.

The other major finding, Dr. McKenna said, offers some perspective on short-term versus long-term risk.

“Most people consider obesity a negative prognostic factor,” he said. “But in terms of operative risk, it’s kind of a neutral effect. It doesn’t really affect the short-term outcomes of an operation.”

Still, Dr. McKenna warned that a visual assessment of patient body condition is not enough to predict postoperative risk. Instead, he recommended accurate height and weight measurements during annual and preoperative exams. He also noted that more patients are at risk than clinicians may suspect.

“Even definitions that didn’t previously exist, such as mild malnutrition, had a somewhat negative effect within colorectal cancer and esophageal cancer,” Dr. McKenna said. “So these are patients who previously probably would be considered pretty healthy, but there is probably some room to improve their nutritional status.”

While the study revealed that different types of cancer should have unique tools for measuring nutritional status, development of these systems will require more research concerning prehabilitation outcomes, according to Dr. McKenna. In the meantime, he highlighted a point of action in the clinic.

“We think, overall, especially with the rise of neoadjuvant chemotherapy upfront, before surgery, that identifying patients at risk before they start neoadjuvant chemotherapy is going to be important,” he said. “They are the ones who really need to be targeted.”

There was no external funding for this study, and the investigators reported no conflicts of interest.
 

SOURCE: McKenna NP et al. J Am Coll Surg. 2020 Feb 26. doi: 10.1016/j.jamcollsurg.2019.12.034.

New research suggests the incidence of death from unintentional injury is higher among patients with cancer than among those in the general U.S. population.

The findings highlight the need for more initiatives to help recognize patients at risk of death from this category of injury, which is the third leading cause of death in the country, according to the study authors.

“The purpose of our study was to present a comprehensive analysis of death from unintentional injury among patients with cancer using a large population-based cohort,” wrote Kunyu Yang, MD, of Huazhong University of Science and Technology in China, and colleagues. Their report is in JAMA Network Open.

The retrospective study included 8,271,020 patients with cancer, 40,599 of whom died from unintentional injury. The researchers identified patients who received a new diagnosis of primary cancer between Jan. 1, 1973, and Dec. 31, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database.

The mean age of study participants was 63.0 years, and most were diagnosed in the 2000-2009 period (41.6%) or the 2010-2015 period (27.6%).

The SEER data was compared with mortality data representative of the general U.S. population obtained from the National Center for Health Statistics. Standardized mortality ratios and rates of death from unintentional injury were measured in both groups.

The rates of death from unintentional injury were 81.90 per 100,000 person-years in cancer patients and 51.21 per 100,000 person-years in the general population. The standardized mortality ratio was 1.60 (95% confidence interval, 1.58-1.61).

Factors associated with higher rates of death from unintentional injury among cancer patients included male sex (relative risk, 1.69; P less than .001), age greater than 80 years at diagnosis (RR, 2.91; P less than .001), and being unmarried (RR, 1.23; P less than .001).

“Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100,000 person-years), brain (175.04 per 100,000 person-years), larynx (148.78 per 100,000 person-years), and esophagus (144.98 per 100,000 person-years),” the researchers reported.

They acknowledged that a key limitation of this study was the potential role of reporting bias in death certificate analyses. As a result, death due to unintentional injury and death from suicide and homicide could have been misclassified.

“Cancer-related suicides, like all suicides, are preventable and should be viewed as cancer-related mortality. It is a silent killer with a peak incidence weeks after diagnosis – an undeniably hectic time for most patients and clinicians getting to know their patients,” said Daniel C. McFarland, DO, of Memorial Sloan Kettering Cancer Center in New York. He was not involved in this study.

“Suicide screening with appropriate systems in place to address suicidal thoughts and behavior is crucial for cancer patients throughout the trajectory of their care,” he added.

As with death from unintentional injury, higher rates of suicide have been reported among cancer patients in comparison to the general population (Nat Commun. 2019;10[1]:207).

No funding sources were reported for this study. The authors and Dr. McFarland disclosed no conflicts of interest.

SOURCE: Yang K et al. JAMA Netw Open. 2020 Feb 21. doi: 10.1001/jamanetworkopen.2019.21647.

New research suggests the incidence of death from unintentional injury is higher among patients with cancer than among those in the general U.S. population.

The findings highlight the need for more initiatives to help recognize patients at risk of death from this category of injury, which is the third leading cause of death in the country, according to the study authors.

“The purpose of our study was to present a comprehensive analysis of death from unintentional injury among patients with cancer using a large population-based cohort,” wrote Kunyu Yang, MD, of Huazhong University of Science and Technology in China, and colleagues. Their report is in JAMA Network Open.

The retrospective study included 8,271,020 patients with cancer, 40,599 of whom died from unintentional injury. The researchers identified patients who received a new diagnosis of primary cancer between Jan. 1, 1973, and Dec. 31, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database.

The mean age of study participants was 63.0 years, and most were diagnosed in the 2000-2009 period (41.6%) or the 2010-2015 period (27.6%).

The SEER data was compared with mortality data representative of the general U.S. population obtained from the National Center for Health Statistics. Standardized mortality ratios and rates of death from unintentional injury were measured in both groups.

The rates of death from unintentional injury were 81.90 per 100,000 person-years in cancer patients and 51.21 per 100,000 person-years in the general population. The standardized mortality ratio was 1.60 (95% confidence interval, 1.58-1.61).

Factors associated with higher rates of death from unintentional injury among cancer patients included male sex (relative risk, 1.69; P less than .001), age greater than 80 years at diagnosis (RR, 2.91; P less than .001), and being unmarried (RR, 1.23; P less than .001).

“Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100,000 person-years), brain (175.04 per 100,000 person-years), larynx (148.78 per 100,000 person-years), and esophagus (144.98 per 100,000 person-years),” the researchers reported.

They acknowledged that a key limitation of this study was the potential role of reporting bias in death certificate analyses. As a result, death due to unintentional injury and death from suicide and homicide could have been misclassified.

“Cancer-related suicides, like all suicides, are preventable and should be viewed as cancer-related mortality. It is a silent killer with a peak incidence weeks after diagnosis – an undeniably hectic time for most patients and clinicians getting to know their patients,” said Daniel C. McFarland, DO, of Memorial Sloan Kettering Cancer Center in New York. He was not involved in this study.

“Suicide screening with appropriate systems in place to address suicidal thoughts and behavior is crucial for cancer patients throughout the trajectory of their care,” he added.

As with death from unintentional injury, higher rates of suicide have been reported among cancer patients in comparison to the general population (Nat Commun. 2019;10[1]:207).

No funding sources were reported for this study. The authors and Dr. McFarland disclosed no conflicts of interest.

SOURCE: Yang K et al. JAMA Netw Open. 2020 Feb 21. doi: 10.1001/jamanetworkopen.2019.21647.

New research suggests the incidence of death from unintentional injury is higher among patients with cancer than among those in the general U.S. population.

The findings highlight the need for more initiatives to help recognize patients at risk of death from this category of injury, which is the third leading cause of death in the country, according to the study authors.

“The purpose of our study was to present a comprehensive analysis of death from unintentional injury among patients with cancer using a large population-based cohort,” wrote Kunyu Yang, MD, of Huazhong University of Science and Technology in China, and colleagues. Their report is in JAMA Network Open.

The retrospective study included 8,271,020 patients with cancer, 40,599 of whom died from unintentional injury. The researchers identified patients who received a new diagnosis of primary cancer between Jan. 1, 1973, and Dec. 31, 2015, from the Surveillance, Epidemiology, and End Results (SEER) database.

The mean age of study participants was 63.0 years, and most were diagnosed in the 2000-2009 period (41.6%) or the 2010-2015 period (27.6%).

The SEER data was compared with mortality data representative of the general U.S. population obtained from the National Center for Health Statistics. Standardized mortality ratios and rates of death from unintentional injury were measured in both groups.

The rates of death from unintentional injury were 81.90 per 100,000 person-years in cancer patients and 51.21 per 100,000 person-years in the general population. The standardized mortality ratio was 1.60 (95% confidence interval, 1.58-1.61).

Factors associated with higher rates of death from unintentional injury among cancer patients included male sex (relative risk, 1.69; P less than .001), age greater than 80 years at diagnosis (RR, 2.91; P less than .001), and being unmarried (RR, 1.23; P less than .001).

“Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100,000 person-years), brain (175.04 per 100,000 person-years), larynx (148.78 per 100,000 person-years), and esophagus (144.98 per 100,000 person-years),” the researchers reported.

They acknowledged that a key limitation of this study was the potential role of reporting bias in death certificate analyses. As a result, death due to unintentional injury and death from suicide and homicide could have been misclassified.

“Cancer-related suicides, like all suicides, are preventable and should be viewed as cancer-related mortality. It is a silent killer with a peak incidence weeks after diagnosis – an undeniably hectic time for most patients and clinicians getting to know their patients,” said Daniel C. McFarland, DO, of Memorial Sloan Kettering Cancer Center in New York. He was not involved in this study.

“Suicide screening with appropriate systems in place to address suicidal thoughts and behavior is crucial for cancer patients throughout the trajectory of their care,” he added.

As with death from unintentional injury, higher rates of suicide have been reported among cancer patients in comparison to the general population (Nat Commun. 2019;10[1]:207).

No funding sources were reported for this study. The authors and Dr. McFarland disclosed no conflicts of interest.

SOURCE: Yang K et al. JAMA Netw Open. 2020 Feb 21. doi: 10.1001/jamanetworkopen.2019.21647.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Cancer patients in states that opted to expand Medicaid insurance coverage under the Affordable Care Act saw a slightly better rate of early diagnosis, compared with patients in states that refused expansion, according to a new study. However, time to treatment was similar in states that opted for expansion and states that did not.

Samuel U. Takvorian, MD, of the University of Pennsylvania, Philadelphia, and colleagues reported these results in JAMA Network Open.

The researchers used the National Cancer Database to examine the changes in health insurance coverage and cancer health outcomes in nonelderly patients following implementation of the Affordable Care Act in January 2014. The investigators identified records for 925,543 patients who had new-onset breast (59%), colon (15%), or non–small cell lung (27%) cancer between 2011 and 2016. The patients’ mean age was 55 years (range, 40-64 years), 79% were women, 14% were black, and 6% were Hispanic.

The researchers looked at insurance status, cancer stage at diagnosis, and treatment initiation within 30 and 90 days of diagnosis. The cohort was equally divided between residents of Medicaid expansion states (48%) and nonexpansion states (52%).

Using a statistical technique that mimics a controlled experiment, the investigators found the percentage of uninsured patients decreased more in the expansion states (adjusted difference-in-differences, −0.7 percentage points; 95% confidence interval, −1.2 to −0.3; P = .001), compared with nonexpansion states. Expansion states also had a greater increase in early-stage cancer diagnoses (adjusted DID, 0.8; 95% CI 0.3-1.2; P = .001) and a greater decrease in advanced-stage cancer diagnoses (adjusted DID, −0.5; 95% CI, −0.9 to −0.2; P = .003).

Among the 848,329 patients who underwent cancer treatment within a year of diagnosis, the percentage initiating treatment within 30 days declined from 52.7% before to 48% after Medicaid expansion in states opting in (unadjusted DID, −4.7; percentage points, 95% CI; −5.1 to −4.5). States that did not expand their Medicaid programs, meanwhile, saw the share decline from 56.9% to 51.5% in the same time period (adjusted DID, −5.4; 95% CI, −5.6 to −5.1). There was no statistically significant difference in timely treatment associated with Medicaid expansion (adjusted DID, 0.6; 95% CI, −0.2 to 1.4; P = .14).

The researchers speculated that the lack of significant between-group differences in time to treatment, despite an improvement in early-stage diagnoses associated with Medicaid expansion, could reflect a cancer care system strained by a surge in insured patients, overall increases in cancer prevalence and complexity of care, a shortage of workers, or a mixture of factors.

In a related editorial, Sue Fu, MD, of Stanford (Calif.) University, and colleagues wrote that, while the findings of increased early diagnosis seen in the study are promising, the time to treatment results are “puzzling” and deserve further consideration.

Time to treatment is important in cancer, as longer times are associated with increased mortality, Dr. Fu and colleagues noted. Slowing times to cancer treatment is a systemic problem in the United States that has been documented since the mid-2000s. Paradoxically, expanded insurance coverage could contribute to increasing time to treatment even after timely diagnosis by adding administrative burdens leading to longer wait times. “Newly insured and underinsured individuals may be particularly vulnerable to this,” the editorialists wrote.

Dr. Takvorian and colleagues noted as weaknesses of their study its observational design, a limited range of ages and cancers included, and an inability to adjust for state-level effects.

This study was funded by the National Cancer Institute and the Agency for Health Research and Quality. The authors of the study and the editorial disclosed no relevant conflicts of interest.

SOURCES: Takvorian SU et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921653; Fu S et al. JAMA Netw Open. 2020 Feb 5;3(2):e1921690.

Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.

The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.

Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.

“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.

To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.

Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).

Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.

However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).

Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.

Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).

Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m²). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.

Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.

“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”

In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).

They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.

The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”

The authors reported having no disclosures.

[email protected]

SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.

Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.

The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.

Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.

“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.

To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.

Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).

Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.

However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).

Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.

Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).

Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m²). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.

Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.

“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”

In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).

They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.

The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”

The authors reported having no disclosures.

[email protected]

SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.

Obesity during adolescence is associated with increased midlife cancer risk, according to findings from a large population-based cohort of Israeli teens examined between 1967 and 2010.

The association, which was stronger in individuals in the later period of the cohort than in those in the earlier years, suggests that the burden of obesity-related cancers might increase over time, given the increasing prevalence of adolescent obesity, wrote Ariel Furer, MD, of Israel Defense Forces Medical Corps, Ramat Gan, and colleagues. Their report is in The Lancet.

Obesity is a known causal factor for several types of cancer, but most studies have looked at middle-age or older individuals and had relatively short follow-up, and period effects are rarely assessed, the investigators said, noting that “the attributable burden of obesity-related cancer was previously calculated with an unverified assumption that the association remained unchanged over time.

“In contrast to this paucity of knowledge, the prevalence of youth obesity – particularly severe obesity – has increased worldwide, which parallels the rise in youth cancer incidence,” they wrote.

To address this paucity of data, the researchers reviewed medical and sociodemographic data for adolescents who were assessed at age 17 years for medical eligibility for mandatory military service, and linked that information with data from the National Cancer Registry to create a unified file. The primary study outcome was any cancer diagnosis between Jan. 1, 1967, and Dec. 31, 2012, and a secondary endpoint was all-cause mortality through Dec. 31, 2017, among those who developed cancer.

Among nearly 2.3 million participating adolescents who were evaluated for associations between body mass index at age 17 years and later cancer incidence, 1,370,020 were men with more than 29.5 million person-years of follow-up, and 928,110 were women with more than 18 million person-years of follow-up. The numbers of incident cancer cases in the men and women were 26,353 and 29,488, and the mean ages at diagnosis were 43.2 and 40.0 years, respectively, the investigators reported (Lancet. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X).

Adolescent obesity in men was significantly associated with midlife cancer incidence (hazard ratio, 1.26), but in women, no association was seen due to the previously reported inverse associations between obesity and cervical and breast cancers, they said.

However, when those cancers were excluded for women, the adjusted hazard ratio was similar to that for men (HR, 1.27).

Cancer incidence in both men and women increased gradually across BMI percentiles, and for both sexes, overweight BMI was associated with an increased cancer risk after 10 years of follow-up (HR, 1.14 for men, 1.22 for women after exclusion of cervical and breast cancer). Therefore, in some cases the increased cancer risk in those who were overweight as teens was evident before age 30 years, the authors noted.

Further, BMI was positively associated with greater mortality risk. For men, 5-year survival rates were 75.2% in those with adolescent BMI in the 5th-49th percentile, compared with 72.2% in those with BMI in the obesity range (95th percentile or greater), and the corresponding rates in women were 89.3% and 83.1% (HR, 1.33 and 1.89, respectively).

Of note, the investigators identified a period effect. That is, after stratification by enrollment period/cancer recording period (1967-1981/1982-1996 vs. 1982-1996/1997-2011), a stronger association was noted in individuals who entered the study during the later period, compared with those who entered in the early period (HR, 1.36 vs. 1.13; adjusted HR, 1.11 vs. 1.07 per 5 kg/m²). Possible mechanisms for this finding include environmental and nutritional factors, increased use of medical services, and changes in early cancer screening techniques, but further study is needed to verify the trend and “refine the exact nature of carcinogenic elements, compared with earlier periods,” they said.

Also of note, some cancers that were not associated with BMI in the early period, including stomach cancer, non-Hodgkin lymphoma, thyroid cancer, and colorectal and oral cavity cancers, became significantly associated with BMI in the late period.

“The projected population attributable risk percentage, using 2017 prevalence data of high BMI, was 5.1% for any cancer in men and 5.7% for cancers other than breast and cervical in women,” the researchers wrote, noting that this “is probably an underestimation, given the accentuation of the BMI-cancer association and the rapid increase in adolescent obesity prevalence within the past decade in Israel and worldwide.”

In an accompanying editorial, the journal editors noted that the findings by Dr. Furer and colleagues highlight the need to tackle obesity early in life and the need for obesity prevention strategies to reduce cancer incidence and mortality for those cancers that can be prevented by lifestyle modifications. They added, however, that care would be needed to avoid stigmatizing those with obesity, as obesity itself is a “multifactorial condition driven by social injustice and health inequalities” that most often affect those who are least able to implement lifestyle change (Lancet. 2020 Feb 3. doi: 10.106/S2213-8587(20)30031-0).

They also emphasized that the links between obesity and cancer, like those between obesity and other diseases such as diabetes, underscore the fact that noncommunicable diseases do not exist in isolation, and that tackling them requires bold action, a consolidated approach, and elimination of the environmental and social factors driving the epidemic.

The study was limited by a number of factors, including the lack of data on lifestyle factors, underrepresentation of some ethnicities, and lack of data on BMI and medical comorbidities at the time of cancer diagnosis. However, strengths of the study include the systematic data collection, narrow range of age at study entry, strict control of coexisting conditions, and high statistical power, which strengthen the generalizability of the results, the investigators said, concluding, therefore, that “[c]urrent trends of rising BMI among adolescents could constitute an important intervention target for cancer prevention.”

The authors reported having no disclosures.

[email protected]

SOURCE: Furer A et al. Lancet Diabetes Endocrinol. 2020 Feb 3. doi: 10.1016/S2213-8587(20)30019-X.

The Food and Drug Administration has issued a public health alert warning consumers to avoid the use of dietary supplements that contain cesium chloride or any other cesium salt because of significant safety risks.

Cesium salts are sometimes advertised as an alternative treatment for cancer, the FDA said in the announcement, but these salts have never proved to be safe or effective at treating cancer or any other disease. Clinical case reports and nonclinical trials have shown that cesium salts are associated with a variety of adverse events, including cardiac arrhythmias, hypokalemia, seizures, syncope, and death.

The FDA warned health care providers that cesium salts presented a significant safety risk in compounding drugs in July 2018.

Health care providers should not recommend dietary supplements containing cesium salts to their patients, the FDA said, and if a patient experiences an adverse event while taking a supplement containing cesium salt, the event should be reported to the agency.

While there are few dietary supplements on the market that contain cesium salt, consumers should be aware of the risks and avoid these products. The FDA noted that “if claims sound too good to be true, they probably are.”

[email protected]

The Food and Drug Administration has issued a public health alert warning consumers to avoid the use of dietary supplements that contain cesium chloride or any other cesium salt because of significant safety risks.

Cesium salts are sometimes advertised as an alternative treatment for cancer, the FDA said in the announcement, but these salts have never proved to be safe or effective at treating cancer or any other disease. Clinical case reports and nonclinical trials have shown that cesium salts are associated with a variety of adverse events, including cardiac arrhythmias, hypokalemia, seizures, syncope, and death.

The FDA warned health care providers that cesium salts presented a significant safety risk in compounding drugs in July 2018.

Health care providers should not recommend dietary supplements containing cesium salts to their patients, the FDA said, and if a patient experiences an adverse event while taking a supplement containing cesium salt, the event should be reported to the agency.

While there are few dietary supplements on the market that contain cesium salt, consumers should be aware of the risks and avoid these products. The FDA noted that “if claims sound too good to be true, they probably are.”

[email protected]

The Food and Drug Administration has issued a public health alert warning consumers to avoid the use of dietary supplements that contain cesium chloride or any other cesium salt because of significant safety risks.

Cesium salts are sometimes advertised as an alternative treatment for cancer, the FDA said in the announcement, but these salts have never proved to be safe or effective at treating cancer or any other disease. Clinical case reports and nonclinical trials have shown that cesium salts are associated with a variety of adverse events, including cardiac arrhythmias, hypokalemia, seizures, syncope, and death.

The FDA warned health care providers that cesium salts presented a significant safety risk in compounding drugs in July 2018.

Health care providers should not recommend dietary supplements containing cesium salts to their patients, the FDA said, and if a patient experiences an adverse event while taking a supplement containing cesium salt, the event should be reported to the agency.

While there are few dietary supplements on the market that contain cesium salt, consumers should be aware of the risks and avoid these products. The FDA noted that “if claims sound too good to be true, they probably are.”

[email protected]

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

Adding cannabinoids to opioids does not appear to improve control of cancer-related pain in adults with late-stage disease, authors of a systematic review and meta-analysis contend.

Among 1,442 participants in five randomized controlled trials of cannabinoids compared with placebo, there was no significant difference in the primary outcome of pain intensity scores, reported Elaine G. Boland, MD, PhD, of Hull University Teaching Hospitals NHS Trust in Cottingham, England, and colleagues.

“For a medication to be useful, there needs to be a net overall benefit, with the positive effects (analgesia) outweighing adverse effects. None of the included phase III studies show benefit of cannabinoids,” they wrote. Their report is in BMJ Supportive & Palliative Care.

According to NORML, the National Organization for the Reform of Marijuana Laws, 33 U.S. states currently have legalized medical use of marijuana or cannabinoids, and Dr. Boland and coauthors report that medical marijuana is legal in some 40 nations worldwide.

Survey data and a randomized sample of urine tests from a cancer center in Washington State, were marijuana is legal, show that cannabis or cannabinoid use is common among cancer patients. Despite its widespread use, good quality evidence of the efficacy of cannabis for control of cancer pain is sparse, the investigators said.-

They designed a systematic review and meta-analysis to identify randomized controlled trials with a low risk for bias, eventually settling on five with a total of 1,442 patients. Four of the studies evaluated nabiximols (Sativex), an oromucosal formulation of delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD), and one tested THC:CBD or THC abstract vs. placebo.

To bolster confidence in their results, the investigators contacted the authors of the included studies to obtain additional findings and information about each study’s design.

They found that in the pooled data there was no significant difference between cannabinoids and placebo for the difference in average pain on a Numeric Rating Scale (NRS). The mean difference was –0.21 (P = .14) and did not reach significance when the analysis was restricted to phase 3 trials (mean difference –.02, P = .80).

For the secondary outcomes of adverse events and dropouts, they found that cannabinoids were associated with significantly higher risk for somnolence (odds ratio [OR] 2.69, P less than .001) and dizziness (OR 1.58, P = .05), and that dropouts due to adverse events were more frequent in the cannabinoid arms.

The investigators acknowledged that the study was limited by its reliance on the NRS pain score “as this simple instrument does not capture the complexity of pain especially when it has been [a] long-standing problem,” and by the possibility that vagaries in the use of the oromucosal spray might affect the absorption and efficacy of the cannabinoids.

The authors did not report a funding source. No conflicts of interest were reported.

SOURCE: Boland EG et al. BMJ Supportive & Palliative Care 2020 Jan 20. doi: 10.1136/bmjspcare-2019-002032.

A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.

Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.

Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.

“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.

“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
 

Baseline characteristics and treatment

Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.

Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.

Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.

The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).

GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
 

Outcomes

Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).

Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).

Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
 

Potential drivers of outcome

Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.

Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”

The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”

“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”

Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.

“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”

Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.

This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.

[email protected]

SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
 

A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.

Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.

Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.

“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.

“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
 

Baseline characteristics and treatment

Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.

Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.

Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.

The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).

GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
 

Outcomes

Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).

Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).

Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
 

Potential drivers of outcome

Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.

Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”

The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”

“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”

Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.

“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”

Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.

This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.

[email protected]

SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
 

A cancer center has seen improved outcomes of allogeneic transplant in recent years, despite increases in patient age and comorbidities.

Researchers compared patients who received allogeneic hematopoietic cell transplants (allo-HCTs) during two periods, 2003-2007 and 2013-2017.

Patients treated in the 2013-2017 period were older and had more HCT-specific comorbidities at baseline, but they had lower rates of mortality, relapse, and graft-versus-host disease (GVHD) post transplant. George B. McDonald, MD, an emeritus member at Fred Hutchinson Cancer Research Center in Seattle, and coauthors described these findings in Annals of Internal Medicine.

“The primary question being addressed by this study was whether the striking improvement in survival … from the 1990s to the early 2000s, that we and other transplant centers have reported, had reached a plateau or whether further improvements in survival were being seen,” Dr. McDonald said in an interview.

“We knew that older and sicker patients were now coming for transplant, compared to 10 years ago. Our transplant protocols have backed away from the highest doses of chemotherapy and irradiation used to prepare patients for transplant, toward less toxic therapies, including reduced-intensity conditioning,” he added. “Our investigators have sought to prevent and more effectively treat the myriad of complications of allogeneic transplant, based on research done at the Fred Hutchinson Cancer Research Center and at transplant centers throughout the world.”
 

Baseline characteristics and treatment

Dr. McDonald and his colleagues analyzed data on patients who received allo-HCTs at Seattle Cancer Care Alliance. There were 1,148 patients treated in the 2003-2007 period and 1,131 patients treated in the 2013-2017 period.

Indications for allo-HCT were similar between the time periods. Patients were diagnosed with aplastic anemia, acute and chronic leukemias, Hodgkin and non-Hodgkin lymphomas, myelodysplastic syndromes, and multiple myeloma.

Patients in the 2013-2017 group were older and had more HCT-specific comorbidities than did the patients in the 2003-2007 group. The median age was 50.0 years (range, 0.1-80.9 years) and 47.2 years (range, 0.4-78.9 years), respectively. The median score on the augmented HCT-specific comorbidity index was 4.0 and 3.0, respectively.

The 2013-2017 group was more likely to have intermediate-risk disease (73% vs. 54%) but less likely to have high-risk disease (14% vs. 31%). The 2013-2017 group was less likely to receive high-dose myeloablative conditioning (15% vs. 67%) but more likely to have an unrelated donor (70% vs. 59%) or receive a cord blood transplant (13% vs. 4%).

GVHD prophylaxis differed between the time periods, with patients in the 2013-2017 group being more likely to receive sirolimus, posttransplant cyclophosphamide, and abatacept.
 

Outcomes

Overall, outcomes were superior in the 2013-2017 group. The rate of nonrelapse mortality at day 200 was higher in the 2003-2007 group than in the 2013-2017 group – 16% and 11%, respectively (adjusted hazard ratio, 0.66; P = .008).

Relapse or progression was more common in the 2003-2007 group – 348 patients vs. 244 patients (aHR, 0.76; P = .011). More patients died from relapse in the 2003-2007 group – 307 patients vs. 186 patients (aHR, 0.69; P = .002). More patients died from any cause in the 2003-2007 group – 653 patients vs. 418 patients (aHR, 0.66; P less than .001). The rate of grade 2-4 acute GVHD was higher in the 2003-2007 group – 71% vs. 69% (aHR, 0.80) – and so was the rate of chronic GVHD – 44% vs. 29% (aHR, 0.40). The risk of developing gram-negative bacteremia was lower in the 2013-2017 group (aHR, 0.42), as was the risk of invasive mold infection (aHR, 0.55).

Patients in the 2013-2017 group had a higher risk of cytomegalovirus (CMV) infection (aHR = 1.15), but they were less likely to have high levels of CMV viremia (aHR, 0.78 for greater than 250 IU/mL; aHR, 0.46 for greater than 1,000 IU/mL). Having higher levels of CMV viremia was associated with an increased risk of non-relapse mortality.
 

Potential drivers of outcome

Dr. McDonald said this study’s design makes it difficult to determine the causes of improved outcomes in the 2013-2017 period. However, the researchers do have theories about which practice changes may have contributed to better allo-HCT outcomes.

Dr. McDonald said the decrease in GVHD over time was “likely owing to the introduction of newer preventive strategies and immune-suppressive drugs.”

The decrease in nonrelapse mortality may have been driven, in part, by a reduction in fatal infections. Dr. McDonald said these infections were less frequent in the 2013-2017 period because of “molecular methods of diagnosis (especially for herpesviruses) and newer treatments (especially for fungal infections).”

“Another reason for a lower frequency of serious infection was a change in practice for treating graft-versus-host disease,” Dr. McDonald added. “Based on a randomized trial comparing lower- versus higher-dose prednisone for less-severe GVHD … both initial doses of prednisone and total prednisone exposure were reduced.”

Another factor that may have improved allo-HCT outcomes is the center’s change in approach to conditioning therapy over time.

“The gradual shift from very-high-dose conditioning therapy to less-intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years,” Dr. McDonald said. “We were able to identify patients who were at especially high risk for mortality during a screening process before transplant ... thus allowing patients at highest risk to receive less intense conditioning therapy.”

Dr. McDonald added that this study’s results are encouraging, particularly the reduction in nonrelapse mortality. However, there is still room for improvement when it comes to relapse and progression.

This research was funded by the National Institutes of Health, the American Cancer Society, and the Patient-Centered Outcomes Research Institute. Dr. McDonald reported relationships with Sangamo Therapeutics, Soligenix Therapeutics, and Lucent Medical Systems. His coauthors disclosed relationships with a range of companies.

[email protected]

SOURCE: McDonald GB et al. Ann Intern Med. 2020 Jan 20. doi: 10.7326/M19-2936.
 

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

Declines in death rates for lung cancer and melanoma have gained momentum in recent years, fueling a record drop in cancer mortality, the American Cancer Society says.

Lung cancer death rates, which were falling by 3% in men and 2% in women annually in 2008 through 2013, dropped by 5% in men and nearly 4% per year in women annually from 2013 to 2017, according to the society’s 2020 statistical report.

Those accelerating reductions in death rates helped fuel the biggest-ever single year decline in overall cancer mortality, of 2.2%, from 2016 to 2017, their report shows.

According to the investigators, the decline in melanoma death rates escalated to 6.9% per year among 20- to 49-year-olds over 2013-2017, compared with a decline of just 2.9% per year during 2006-2010. Likewise, the melanoma death rate decline was 7.2% annually for the more recent time period, compared with just 1.3% annually in the earlier time period. The finding was even more remarkable for those 65 years of age and older, according to investigators, since the declines in melanoma death rates reached 6.2% annually, compared with a 0.9% annual increase in the years before immunotherapy.

Smoking cessation has been the main driver of progress in cutting lung cancer death rates, according to the report, while in melanoma, death rates have dropped after the introduction of immune checkpoint inhibitors and targeted therapies.

By contrast, reductions in death rates have slowed for colorectal cancers and female breast cancers, and have stabilized for prostate cancer, Ms. Siegel and coauthors stated, adding that racial and geographic disparities persist in preventable cancers, including those of the lung and cervix.

“Increased investment in both the equitable application of existing cancer control interventions and basic and clinical research to further advance treatment options would undoubtedly accelerate progress against cancer,” said the investigators. The report appears in CA: A Cancer Journal for Clinicians.

While the decline in lung cancer death rates is good news, the disease remains a major killer, responsible for more deaths than breast, colorectal, and ovarian cancer combined, said Jacques P. Fontaine, MD, a thoracic surgeon at Moffitt Cancer Center in Tampa, Fla.

“Five-year survival rates are still around the 18%-20% range, which is much lower than breast and prostate cancer,” Dr. Fontaine said in an interview. “Nonetheless, we’ve made a little dent in that, and we’re improving.”

Two other factors that have helped spur that improvement, according to Dr. Fontaine, are the reduced incidence of squamous cell carcinomas, which are linked to smoking, and the increased use of lung cancer screening with low-dose computed tomography.

Squamous cell carcinomas tend to be a central rather than peripheral, which makes the tumors harder to resect: “Surgery is sometimes not an option, and even to this day in 2020, the single most effective treatment for lung cancer remains surgical resection,” said Dr. Fontaine.

Likewise, centrally located tumors may preclude giving high-dose radiation and may result in more “collateral damage” to healthy tissue, he added.

Landmark studies show that low-dose CT scans reduce lung cancer deaths by 20% or more; however, screening can have false-positive results that lead to unnecessary biopsies and other harms, suggesting that the procedures should be done in centers of excellence that provide high-quality, responsible screening for early lung cancer, Dr. Fontaine said.

While the drop in melanoma death rates is encouraging and, not surprising in light of new cutting-edge therapies, an ongoing unmet treatment need still exists, according to Vishal Anil Patel, MD, director of cutaneous oncology at the George Washington Cancer Center in Washington.

“We still have a lot to learn, and a way to go, because we’ve really just made the first breakthrough,” Dr. Patel said in an interview.

SOURCE: Siegel RL et al. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

A Food and Drug Administration advisory committee voted 27-0 on Jan. 14 against recommending agency approval of oxycodegol, a new type of opioid molecule designed to slow passage of the drug through the blood-brain barrier and hence cause less of a “high” and potentially blunt the drug’s abuse potential.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

But the panel, which includes members from both the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, unanimously shared the opinion that the data submitted by the drug developer, Nektar, failed to clearly demonstrate the drug’s safety and efficacy.

“There was a lot of ambiguity [in the data] about safety and efficacy, and this is too important an issue to have so much ambiguity,” summed up Ronald S. Litman, DO, professor of anesthesiology and critical care at the University of Pennsylvania in Philadelphia and chair of the combined committee.

“The subliminal message” that would surround oxycodegol if it received FDA approval would be that it is a “safer” opioid, “and that would make it a blockbuster drug, and for that to happen you need data that [prove] the benefits outweigh risks, but we didn’t see those data. It was all speculation, and we can’t approve a potential blockbuster opioid in the middle of a public health opioid crisis based on speculation,” commented Steve B. Meisel, PharmD, system director of medication safety for Fairview Health Services in Minneapolis and a committee member.

According to Nektar, oxycodegol is a new molecular entity that combines a morphinan pharmacophore, oxycodol, with a six-unit chain of polyethylene glycol, a design that slows movement of the drug into the brain by about an hour after an oral dose when compared with oxycodone. It works as a full mu opioid receptor agonist that inhibits the nociceptive pathways while it reduces reinforcing or euphoric effects and other negative CNS-mediated side effects because of its slowed entry into the central nervous system.

But, as became apparent during the course of the day’s presentations and questions, while the clinical evidence in general supported this mechanism, the data were flawed by many limitations and caveats. FDA staffers critiqued the company’s data set for a variety of issues, including testing dosages that were “arbitrary and flawed,” evidence for “high oral abuse potential” in one study, including “a high rate of euphoria” of 17% even at the recommended dosage level (and a higher euphoria incidence at a higher dosage), limited information on additional pain medications that enrolled patients had used both before enrollment and during the study, and possible enrollment bias. Many panel members also raised concerns that included the efficacy data coming from a single randomized study, incomplete data on possible hepatic toxicity, no data to address potential abuse via injection or inhalation, a very modest demonstrated increment in pain relief, and abuse potential studies that relied on a single dose of the drug.

On the other hand, many committee members, and others in the pain field, applauded the general concept behind oxycodegol and urged the developer to run additional studies and collect more data for a future FDA application.

There has been “a lot of controversy” about oxycodegol, often centered on the question “why do we need another opioid,” commented Steven P. Cohen, MD, professor of anesthesiology, neurology, and pain medicine and chief of pain medicine at Johns Hopkins Health in Baltimore. “Having another opioid on the market with a different pain indication and possibly lower abuse potential” would be welcome and “almost certainly would not result in more prescriptions or abuse,” said Dr. Cohen, who was not a committee member but addressed in an interview the need for new and effective pain medications that offer an alternative to conventional opioids. “Patients who might otherwise be prescribed a different opioid might receive oxycodegol instead,” he suggested. But first, the developing company will need to collect a lot more clinical data than it has reported so far.

[email protected]

A Food and Drug Administration advisory committee voted 27-0 on Jan. 14 against recommending agency approval of oxycodegol, a new type of opioid molecule designed to slow passage of the drug through the blood-brain barrier and hence cause less of a “high” and potentially blunt the drug’s abuse potential.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

But the panel, which includes members from both the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, unanimously shared the opinion that the data submitted by the drug developer, Nektar, failed to clearly demonstrate the drug’s safety and efficacy.

“There was a lot of ambiguity [in the data] about safety and efficacy, and this is too important an issue to have so much ambiguity,” summed up Ronald S. Litman, DO, professor of anesthesiology and critical care at the University of Pennsylvania in Philadelphia and chair of the combined committee.

“The subliminal message” that would surround oxycodegol if it received FDA approval would be that it is a “safer” opioid, “and that would make it a blockbuster drug, and for that to happen you need data that [prove] the benefits outweigh risks, but we didn’t see those data. It was all speculation, and we can’t approve a potential blockbuster opioid in the middle of a public health opioid crisis based on speculation,” commented Steve B. Meisel, PharmD, system director of medication safety for Fairview Health Services in Minneapolis and a committee member.

According to Nektar, oxycodegol is a new molecular entity that combines a morphinan pharmacophore, oxycodol, with a six-unit chain of polyethylene glycol, a design that slows movement of the drug into the brain by about an hour after an oral dose when compared with oxycodone. It works as a full mu opioid receptor agonist that inhibits the nociceptive pathways while it reduces reinforcing or euphoric effects and other negative CNS-mediated side effects because of its slowed entry into the central nervous system.

But, as became apparent during the course of the day’s presentations and questions, while the clinical evidence in general supported this mechanism, the data were flawed by many limitations and caveats. FDA staffers critiqued the company’s data set for a variety of issues, including testing dosages that were “arbitrary and flawed,” evidence for “high oral abuse potential” in one study, including “a high rate of euphoria” of 17% even at the recommended dosage level (and a higher euphoria incidence at a higher dosage), limited information on additional pain medications that enrolled patients had used both before enrollment and during the study, and possible enrollment bias. Many panel members also raised concerns that included the efficacy data coming from a single randomized study, incomplete data on possible hepatic toxicity, no data to address potential abuse via injection or inhalation, a very modest demonstrated increment in pain relief, and abuse potential studies that relied on a single dose of the drug.

On the other hand, many committee members, and others in the pain field, applauded the general concept behind oxycodegol and urged the developer to run additional studies and collect more data for a future FDA application.

There has been “a lot of controversy” about oxycodegol, often centered on the question “why do we need another opioid,” commented Steven P. Cohen, MD, professor of anesthesiology, neurology, and pain medicine and chief of pain medicine at Johns Hopkins Health in Baltimore. “Having another opioid on the market with a different pain indication and possibly lower abuse potential” would be welcome and “almost certainly would not result in more prescriptions or abuse,” said Dr. Cohen, who was not a committee member but addressed in an interview the need for new and effective pain medications that offer an alternative to conventional opioids. “Patients who might otherwise be prescribed a different opioid might receive oxycodegol instead,” he suggested. But first, the developing company will need to collect a lot more clinical data than it has reported so far.

[email protected]

A Food and Drug Administration advisory committee voted 27-0 on Jan. 14 against recommending agency approval of oxycodegol, a new type of opioid molecule designed to slow passage of the drug through the blood-brain barrier and hence cause less of a “high” and potentially blunt the drug’s abuse potential.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

But the panel, which includes members from both the Anesthetic and Analgesic Drug Products Advisory Committee and the Drug Safety and Risk Management Advisory Committee, unanimously shared the opinion that the data submitted by the drug developer, Nektar, failed to clearly demonstrate the drug’s safety and efficacy.

“There was a lot of ambiguity [in the data] about safety and efficacy, and this is too important an issue to have so much ambiguity,” summed up Ronald S. Litman, DO, professor of anesthesiology and critical care at the University of Pennsylvania in Philadelphia and chair of the combined committee.

“The subliminal message” that would surround oxycodegol if it received FDA approval would be that it is a “safer” opioid, “and that would make it a blockbuster drug, and for that to happen you need data that [prove] the benefits outweigh risks, but we didn’t see those data. It was all speculation, and we can’t approve a potential blockbuster opioid in the middle of a public health opioid crisis based on speculation,” commented Steve B. Meisel, PharmD, system director of medication safety for Fairview Health Services in Minneapolis and a committee member.

According to Nektar, oxycodegol is a new molecular entity that combines a morphinan pharmacophore, oxycodol, with a six-unit chain of polyethylene glycol, a design that slows movement of the drug into the brain by about an hour after an oral dose when compared with oxycodone. It works as a full mu opioid receptor agonist that inhibits the nociceptive pathways while it reduces reinforcing or euphoric effects and other negative CNS-mediated side effects because of its slowed entry into the central nervous system.

But, as became apparent during the course of the day’s presentations and questions, while the clinical evidence in general supported this mechanism, the data were flawed by many limitations and caveats. FDA staffers critiqued the company’s data set for a variety of issues, including testing dosages that were “arbitrary and flawed,” evidence for “high oral abuse potential” in one study, including “a high rate of euphoria” of 17% even at the recommended dosage level (and a higher euphoria incidence at a higher dosage), limited information on additional pain medications that enrolled patients had used both before enrollment and during the study, and possible enrollment bias. Many panel members also raised concerns that included the efficacy data coming from a single randomized study, incomplete data on possible hepatic toxicity, no data to address potential abuse via injection or inhalation, a very modest demonstrated increment in pain relief, and abuse potential studies that relied on a single dose of the drug.

On the other hand, many committee members, and others in the pain field, applauded the general concept behind oxycodegol and urged the developer to run additional studies and collect more data for a future FDA application.

There has been “a lot of controversy” about oxycodegol, often centered on the question “why do we need another opioid,” commented Steven P. Cohen, MD, professor of anesthesiology, neurology, and pain medicine and chief of pain medicine at Johns Hopkins Health in Baltimore. “Having another opioid on the market with a different pain indication and possibly lower abuse potential” would be welcome and “almost certainly would not result in more prescriptions or abuse,” said Dr. Cohen, who was not a committee member but addressed in an interview the need for new and effective pain medications that offer an alternative to conventional opioids. “Patients who might otherwise be prescribed a different opioid might receive oxycodegol instead,” he suggested. But first, the developing company will need to collect a lot more clinical data than it has reported so far.

[email protected]