Mary Ann Moon

Rociletinib, a third-generation EGFR tyrosine kinase inhibitor that targets mutations causing treatment resistance, showed sustained activity against resistant non–small cell lung cancer (NSCLC) in a phase I clinical trial, according to a report published online April 30 in the New England Journal of Medicine.

The study, sponsored by Clovis Oncology, the maker of rociletinib, involved 130 patients enrolled over the course of 2 years at 10 medical centers in the United States, France, and Australia. All the study participants had received at least one first- or second-generation EGFR inhibitor (usually erlotinib), and their NSCLC tumors had mutated and developed resistance to the therapy. Half of these patients had three or more sites of metastasis, and 44% had brain involvement, said Dr. Lecia V. Sequist of the deparment of medicine, Massachusetts General Hospital, Boston, and her associates.

A total of 92 patients received therapeutic doses of rociletinib. After a median follow-up of 10 weeks, the response rate among the 46 whose cancer had known EGFR T790M mutations was 59%; 43 of these 46 patients achieved a partial response, a complete response, or disease stabilization. As expected, the response rate was lower, at 29%, among the 17 patients whose tumors were T790M negative, the investigators reported (New Engl. J. Med. 2015 April 30 [doi:10.1056/NEJMoa1413654]).

“Rociletinib did not cause the syndrome of rash, stomatitis, and paronychia that is associated with inhibition of nonmutant EGFR,” they wrote, and the most common grade 3 toxic effect was hyperglycemia. No hyperglycemic events led to discontinuation of treatment, and most were managed with a dose reduction plus use of an oral hypoglycemic agent, usually metformin. Both the hyperglycemia and the metformin may have contributed to gastrointestinal adverse events, which were generally mild.

The main limitation of this study is the small number of patients who have received rociletinib. Larger studies of the agent are now underway, Dr. Sequist and her associates said.

This study was funded by Clovis Oncology, maker of rociletinib, which also participated in study design and data collection and analysis. Dr. Sequist reported receiving personal fees from, and consulting for, Clovis Oncology, AstraZeneca, Boehringer Ingelheim, Novartis, Genentech, Merrimack, and Taiho, and her associates reported ties to numerous industry sources.

Rociletinib, a third-generation EGFR tyrosine kinase inhibitor that targets mutations causing treatment resistance, showed sustained activity against resistant non–small cell lung cancer (NSCLC) in a phase I clinical trial, according to a report published online April 30 in the New England Journal of Medicine.

The study, sponsored by Clovis Oncology, the maker of rociletinib, involved 130 patients enrolled over the course of 2 years at 10 medical centers in the United States, France, and Australia. All the study participants had received at least one first- or second-generation EGFR inhibitor (usually erlotinib), and their NSCLC tumors had mutated and developed resistance to the therapy. Half of these patients had three or more sites of metastasis, and 44% had brain involvement, said Dr. Lecia V. Sequist of the deparment of medicine, Massachusetts General Hospital, Boston, and her associates.

A total of 92 patients received therapeutic doses of rociletinib. After a median follow-up of 10 weeks, the response rate among the 46 whose cancer had known EGFR T790M mutations was 59%; 43 of these 46 patients achieved a partial response, a complete response, or disease stabilization. As expected, the response rate was lower, at 29%, among the 17 patients whose tumors were T790M negative, the investigators reported (New Engl. J. Med. 2015 April 30 [doi:10.1056/NEJMoa1413654]).

“Rociletinib did not cause the syndrome of rash, stomatitis, and paronychia that is associated with inhibition of nonmutant EGFR,” they wrote, and the most common grade 3 toxic effect was hyperglycemia. No hyperglycemic events led to discontinuation of treatment, and most were managed with a dose reduction plus use of an oral hypoglycemic agent, usually metformin. Both the hyperglycemia and the metformin may have contributed to gastrointestinal adverse events, which were generally mild.

The main limitation of this study is the small number of patients who have received rociletinib. Larger studies of the agent are now underway, Dr. Sequist and her associates said.

This study was funded by Clovis Oncology, maker of rociletinib, which also participated in study design and data collection and analysis. Dr. Sequist reported receiving personal fees from, and consulting for, Clovis Oncology, AstraZeneca, Boehringer Ingelheim, Novartis, Genentech, Merrimack, and Taiho, and her associates reported ties to numerous industry sources.

Rociletinib, a third-generation EGFR tyrosine kinase inhibitor that targets mutations causing treatment resistance, showed sustained activity against resistant non–small cell lung cancer (NSCLC) in a phase I clinical trial, according to a report published online April 30 in the New England Journal of Medicine.

The study, sponsored by Clovis Oncology, the maker of rociletinib, involved 130 patients enrolled over the course of 2 years at 10 medical centers in the United States, France, and Australia. All the study participants had received at least one first- or second-generation EGFR inhibitor (usually erlotinib), and their NSCLC tumors had mutated and developed resistance to the therapy. Half of these patients had three or more sites of metastasis, and 44% had brain involvement, said Dr. Lecia V. Sequist of the deparment of medicine, Massachusetts General Hospital, Boston, and her associates.

A total of 92 patients received therapeutic doses of rociletinib. After a median follow-up of 10 weeks, the response rate among the 46 whose cancer had known EGFR T790M mutations was 59%; 43 of these 46 patients achieved a partial response, a complete response, or disease stabilization. As expected, the response rate was lower, at 29%, among the 17 patients whose tumors were T790M negative, the investigators reported (New Engl. J. Med. 2015 April 30 [doi:10.1056/NEJMoa1413654]).

“Rociletinib did not cause the syndrome of rash, stomatitis, and paronychia that is associated with inhibition of nonmutant EGFR,” they wrote, and the most common grade 3 toxic effect was hyperglycemia. No hyperglycemic events led to discontinuation of treatment, and most were managed with a dose reduction plus use of an oral hypoglycemic agent, usually metformin. Both the hyperglycemia and the metformin may have contributed to gastrointestinal adverse events, which were generally mild.

The main limitation of this study is the small number of patients who have received rociletinib. Larger studies of the agent are now underway, Dr. Sequist and her associates said.

This study was funded by Clovis Oncology, maker of rociletinib, which also participated in study design and data collection and analysis. Dr. Sequist reported receiving personal fees from, and consulting for, Clovis Oncology, AstraZeneca, Boehringer Ingelheim, Novartis, Genentech, Merrimack, and Taiho, and her associates reported ties to numerous industry sources.

A new agent targeting tumors that develop resistance to EGFR tyrosine kinase inhibitors proved to be “highly active” in a phase I clinical trial involving 253 patients with advanced, resistant NSCLC, according to a report published online April 30 in the New England Journal of Medicine.

Most patients who initially respond to EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib develop resistance and show disease progression within 2 years, because the tumors develop additional EGFR mutations, particularly T790M resistance mutations. Preliminary studies suggested that a new oral agent, AZD9291, would target T790M-mediated resistance. In a phase I trial to assess its safety and efficacy, 127 study participants had known EGFR T790M mutations, and the remainder had other or unknown mutations, said Dr. Pasi A. Janne of the Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Institute, Boston, and his associates.

The study – designed and funded by AstraZeneca, which also collected and analyzed the data in conjunction with the scientific authors – was conducted at 33 sites in Japan, South Korea, Taiwan, France, Spain, Germany, Australia, the United Kingdom, and the United States. Of the 239 patients who could be evaluated for a response, 123 (51%) showed a partial or complete response. In the subset of patients with known EGFR T790M mutations, the objective response rate was even higher, at 61%.

In contrast, the objective response rate was 21% in the subset of 61 patients who did not have known EGFR T790M mutations, the investigators said (N. Engl. J. Med. 2015 April 30 [doi:10.1056/NEJMoa1411817]). Median progression-free survival was estimated to be 9.6 months in patients with EGFR T790M-positive tumors, although many are still alive and the final survival data have yet to be calculated. In contrast, progression-free survival was 2.8 months in patients with EGFR T790M-negative tumors.

No dose-limiting toxic effects occurred and therefore the maximal efficacy dose with an acceptable level of adverse events cannot be established yet. The most common adverse events were diarrhea (47% of patients), rash (40%), nausea (22%), and decreased appetite (21%). Serious events that were considered to be possibly treatment-related occurred in 6% of patients, and included one fatal case of pneumonia and six cases of pneumonitis-like events that resolved when the drug was discontinued.

These findings demonstrate that “a structurally distinct EGFR inhibitor, one that is selective for the mutated form of EGFR, can be clinically effective and has a side-effect profile that is not dose limiting in the majority of patients in whom T790M-mediated drug resistance has developed,” Dr. Janne and his associates said.

Astra Zeneca is the maker of AZD9291. Dr. Janne reported ties to AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Merrimack, Clovis Oncology, Roche, and Gatekeeper, as well as several patents related to genetically targeted cancer treatments; his associates reported ties to numerous industry sources.

A new agent targeting tumors that develop resistance to EGFR tyrosine kinase inhibitors proved to be “highly active” in a phase I clinical trial involving 253 patients with advanced, resistant NSCLC, according to a report published online April 30 in the New England Journal of Medicine.

Most patients who initially respond to EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib develop resistance and show disease progression within 2 years, because the tumors develop additional EGFR mutations, particularly T790M resistance mutations. Preliminary studies suggested that a new oral agent, AZD9291, would target T790M-mediated resistance. In a phase I trial to assess its safety and efficacy, 127 study participants had known EGFR T790M mutations, and the remainder had other or unknown mutations, said Dr. Pasi A. Janne of the Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Institute, Boston, and his associates.

The study – designed and funded by AstraZeneca, which also collected and analyzed the data in conjunction with the scientific authors – was conducted at 33 sites in Japan, South Korea, Taiwan, France, Spain, Germany, Australia, the United Kingdom, and the United States. Of the 239 patients who could be evaluated for a response, 123 (51%) showed a partial or complete response. In the subset of patients with known EGFR T790M mutations, the objective response rate was even higher, at 61%.

In contrast, the objective response rate was 21% in the subset of 61 patients who did not have known EGFR T790M mutations, the investigators said (N. Engl. J. Med. 2015 April 30 [doi:10.1056/NEJMoa1411817]). Median progression-free survival was estimated to be 9.6 months in patients with EGFR T790M-positive tumors, although many are still alive and the final survival data have yet to be calculated. In contrast, progression-free survival was 2.8 months in patients with EGFR T790M-negative tumors.

No dose-limiting toxic effects occurred and therefore the maximal efficacy dose with an acceptable level of adverse events cannot be established yet. The most common adverse events were diarrhea (47% of patients), rash (40%), nausea (22%), and decreased appetite (21%). Serious events that were considered to be possibly treatment-related occurred in 6% of patients, and included one fatal case of pneumonia and six cases of pneumonitis-like events that resolved when the drug was discontinued.

These findings demonstrate that “a structurally distinct EGFR inhibitor, one that is selective for the mutated form of EGFR, can be clinically effective and has a side-effect profile that is not dose limiting in the majority of patients in whom T790M-mediated drug resistance has developed,” Dr. Janne and his associates said.

Astra Zeneca is the maker of AZD9291. Dr. Janne reported ties to AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Merrimack, Clovis Oncology, Roche, and Gatekeeper, as well as several patents related to genetically targeted cancer treatments; his associates reported ties to numerous industry sources.

A new agent targeting tumors that develop resistance to EGFR tyrosine kinase inhibitors proved to be “highly active” in a phase I clinical trial involving 253 patients with advanced, resistant NSCLC, according to a report published online April 30 in the New England Journal of Medicine.

Most patients who initially respond to EGFR tyrosine kinase inhibitors such as gefitinib, erlotinib, and afatinib develop resistance and show disease progression within 2 years, because the tumors develop additional EGFR mutations, particularly T790M resistance mutations. Preliminary studies suggested that a new oral agent, AZD9291, would target T790M-mediated resistance. In a phase I trial to assess its safety and efficacy, 127 study participants had known EGFR T790M mutations, and the remainder had other or unknown mutations, said Dr. Pasi A. Janne of the Lowe Center for Thoracic Oncology and the Belfer Institute for Applied Cancer Science, Dana-Farber Institute, Boston, and his associates.

The study – designed and funded by AstraZeneca, which also collected and analyzed the data in conjunction with the scientific authors – was conducted at 33 sites in Japan, South Korea, Taiwan, France, Spain, Germany, Australia, the United Kingdom, and the United States. Of the 239 patients who could be evaluated for a response, 123 (51%) showed a partial or complete response. In the subset of patients with known EGFR T790M mutations, the objective response rate was even higher, at 61%.

In contrast, the objective response rate was 21% in the subset of 61 patients who did not have known EGFR T790M mutations, the investigators said (N. Engl. J. Med. 2015 April 30 [doi:10.1056/NEJMoa1411817]). Median progression-free survival was estimated to be 9.6 months in patients with EGFR T790M-positive tumors, although many are still alive and the final survival data have yet to be calculated. In contrast, progression-free survival was 2.8 months in patients with EGFR T790M-negative tumors.

No dose-limiting toxic effects occurred and therefore the maximal efficacy dose with an acceptable level of adverse events cannot be established yet. The most common adverse events were diarrhea (47% of patients), rash (40%), nausea (22%), and decreased appetite (21%). Serious events that were considered to be possibly treatment-related occurred in 6% of patients, and included one fatal case of pneumonia and six cases of pneumonitis-like events that resolved when the drug was discontinued.

These findings demonstrate that “a structurally distinct EGFR inhibitor, one that is selective for the mutated form of EGFR, can be clinically effective and has a side-effect profile that is not dose limiting in the majority of patients in whom T790M-mediated drug resistance has developed,” Dr. Janne and his associates said.

Astra Zeneca is the maker of AZD9291. Dr. Janne reported ties to AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Merrimack, Clovis Oncology, Roche, and Gatekeeper, as well as several patents related to genetically targeted cancer treatments; his associates reported ties to numerous industry sources.

People who survive Hodgkin’s lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease for at least 40 years – the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

Until now, follow-up studies of such patients “rarely exceeded 20-25 years,” before most survivors reached the age at which cardiovascular disease (CVD) becomes commonplace in the general population. To compare CVD rates between survivors and the general population at later ages, investigators examined the medical records of 2,524 individuals who survived 5 years or more after being treated for Hodgkin’s lymphoma as adolescents or young adults at five Dutch medical centers between 1965 and 1995.

A total of 81% of the cohort had received mediastinal radiotherapy and 31% had received anthracycline-containing chemotherapy. After 5-47 years of follow-up, 797 of these patients experienced 1,713 cardiovascular events. The most frequently occurring events included 401 coronary heart disease events (such as myocardial infarction and angina pectoris), 374 valvular heart disease events, and 140 heart failure events (such as cardiomyopathy and congestive heart failure), Frederika A. van Nimwegen of the department of epidemiology, the Netherlands Cancer Institute, Amsterdam, and her colleagues wrote in JAMA Internal Medicine on April 27 (doi:10.1001/jamainternmed.2015.1180).

Compared with the general population, Hodgkin’s survivors had a 3.2-fold higher standardized incidence ratio (SIR) of developing coronary heart disease and a 6.8-fold higher SIR of developing heart failure, corresponding to 70 excess cases of coronary heart disease and 58 excess cases of heart failure per 10,000 person-years.

These risks were significantly higher for survivors than for the general population at all ages, but patients who had been diagnosed and treated before the age of 25 years were at particularly elevated risk: they carried a 4.6- to 7.5-fold higher risk of coronary heart disease and a 10.9- to 40.5-fold higher risk of heart failure. At 40 years after Hodgkin’s diagnosis and treatment, the cumulative incidence of any type of CVD was 50%, the investigators wrote. Both survivors of Hodgkin’s lymphoma and their physicians should be aware that these patients remain at substantially increased cardiovascular risk throughout their lives, Ms. Van Nimwegen and her colleagues wrote.

This study was supported by the Dutch Cancer Society. Ms. van Nimwegen and her colleagues reported having no financial disclosures.

People who survive Hodgkin’s lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease for at least 40 years – the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

Until now, follow-up studies of such patients “rarely exceeded 20-25 years,” before most survivors reached the age at which cardiovascular disease (CVD) becomes commonplace in the general population. To compare CVD rates between survivors and the general population at later ages, investigators examined the medical records of 2,524 individuals who survived 5 years or more after being treated for Hodgkin’s lymphoma as adolescents or young adults at five Dutch medical centers between 1965 and 1995.

A total of 81% of the cohort had received mediastinal radiotherapy and 31% had received anthracycline-containing chemotherapy. After 5-47 years of follow-up, 797 of these patients experienced 1,713 cardiovascular events. The most frequently occurring events included 401 coronary heart disease events (such as myocardial infarction and angina pectoris), 374 valvular heart disease events, and 140 heart failure events (such as cardiomyopathy and congestive heart failure), Frederika A. van Nimwegen of the department of epidemiology, the Netherlands Cancer Institute, Amsterdam, and her colleagues wrote in JAMA Internal Medicine on April 27 (doi:10.1001/jamainternmed.2015.1180).

Compared with the general population, Hodgkin’s survivors had a 3.2-fold higher standardized incidence ratio (SIR) of developing coronary heart disease and a 6.8-fold higher SIR of developing heart failure, corresponding to 70 excess cases of coronary heart disease and 58 excess cases of heart failure per 10,000 person-years.

These risks were significantly higher for survivors than for the general population at all ages, but patients who had been diagnosed and treated before the age of 25 years were at particularly elevated risk: they carried a 4.6- to 7.5-fold higher risk of coronary heart disease and a 10.9- to 40.5-fold higher risk of heart failure. At 40 years after Hodgkin’s diagnosis and treatment, the cumulative incidence of any type of CVD was 50%, the investigators wrote. Both survivors of Hodgkin’s lymphoma and their physicians should be aware that these patients remain at substantially increased cardiovascular risk throughout their lives, Ms. Van Nimwegen and her colleagues wrote.

This study was supported by the Dutch Cancer Society. Ms. van Nimwegen and her colleagues reported having no financial disclosures.

People who survive Hodgkin’s lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease for at least 40 years – the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

Until now, follow-up studies of such patients “rarely exceeded 20-25 years,” before most survivors reached the age at which cardiovascular disease (CVD) becomes commonplace in the general population. To compare CVD rates between survivors and the general population at later ages, investigators examined the medical records of 2,524 individuals who survived 5 years or more after being treated for Hodgkin’s lymphoma as adolescents or young adults at five Dutch medical centers between 1965 and 1995.

A total of 81% of the cohort had received mediastinal radiotherapy and 31% had received anthracycline-containing chemotherapy. After 5-47 years of follow-up, 797 of these patients experienced 1,713 cardiovascular events. The most frequently occurring events included 401 coronary heart disease events (such as myocardial infarction and angina pectoris), 374 valvular heart disease events, and 140 heart failure events (such as cardiomyopathy and congestive heart failure), Frederika A. van Nimwegen of the department of epidemiology, the Netherlands Cancer Institute, Amsterdam, and her colleagues wrote in JAMA Internal Medicine on April 27 (doi:10.1001/jamainternmed.2015.1180).

Compared with the general population, Hodgkin’s survivors had a 3.2-fold higher standardized incidence ratio (SIR) of developing coronary heart disease and a 6.8-fold higher SIR of developing heart failure, corresponding to 70 excess cases of coronary heart disease and 58 excess cases of heart failure per 10,000 person-years.

These risks were significantly higher for survivors than for the general population at all ages, but patients who had been diagnosed and treated before the age of 25 years were at particularly elevated risk: they carried a 4.6- to 7.5-fold higher risk of coronary heart disease and a 10.9- to 40.5-fold higher risk of heart failure. At 40 years after Hodgkin’s diagnosis and treatment, the cumulative incidence of any type of CVD was 50%, the investigators wrote. Both survivors of Hodgkin’s lymphoma and their physicians should be aware that these patients remain at substantially increased cardiovascular risk throughout their lives, Ms. Van Nimwegen and her colleagues wrote.

This study was supported by the Dutch Cancer Society. Ms. van Nimwegen and her colleagues reported having no financial disclosures.

Most U.S. physicians who made political contributions during the 2013-2014 congressional election cycle donated to Democrats, continuing the trend away from Republicans that was first noted among medical professionals between 1991 and 2012, according to a report published April 27 in JAMA Internal Medicine.

In an analysis of physicians’ federal political contributions, 55% of contributors donated to Democrats and 45% to Republicans during the most recent congressional election cycle. In contrast, general public support resulted in the “Republican surge” in which conservatives gained nine Senate seats and increased their majority in the House, said Adam Bonica, Ph.D., of the department of political science, Stanford (Calif.) University, and his associates.

© BrianAJackson/Thinkstock

The current report shows that the shift away from predominantly Republican and toward predominantly Democratic support, which began in the 1990s, still persists for physicians.

“Given the increasing numbers of women physicians and salaried physicians, who typically ally with the Democrats, in contrast to surgeons, who typically ally with the Republicans, our findings suggest that the medical profession will be challenged to achieve consensus on health policy issues. The profession is unlikely to speak with one voice on questions such as the provision of health insurance or controlling the costs of medical care,” the investigators wrote (JAMA Intern. Med. 2015 April 27 [doi:10.1001/jamainternmed.2015.1332]).

However, this polarization among physicians “may spur both political parties to work harder to maintain and increase physicians’ support. Thus, the political divisions among physicians may have the unintended effect of enhancing the political standing of the medical profession,” they added.

Most U.S. physicians who made political contributions during the 2013-2014 congressional election cycle donated to Democrats, continuing the trend away from Republicans that was first noted among medical professionals between 1991 and 2012, according to a report published April 27 in JAMA Internal Medicine.

In an analysis of physicians’ federal political contributions, 55% of contributors donated to Democrats and 45% to Republicans during the most recent congressional election cycle. In contrast, general public support resulted in the “Republican surge” in which conservatives gained nine Senate seats and increased their majority in the House, said Adam Bonica, Ph.D., of the department of political science, Stanford (Calif.) University, and his associates.

© BrianAJackson/Thinkstock

The current report shows that the shift away from predominantly Republican and toward predominantly Democratic support, which began in the 1990s, still persists for physicians.

“Given the increasing numbers of women physicians and salaried physicians, who typically ally with the Democrats, in contrast to surgeons, who typically ally with the Republicans, our findings suggest that the medical profession will be challenged to achieve consensus on health policy issues. The profession is unlikely to speak with one voice on questions such as the provision of health insurance or controlling the costs of medical care,” the investigators wrote (JAMA Intern. Med. 2015 April 27 [doi:10.1001/jamainternmed.2015.1332]).

However, this polarization among physicians “may spur both political parties to work harder to maintain and increase physicians’ support. Thus, the political divisions among physicians may have the unintended effect of enhancing the political standing of the medical profession,” they added.

Most U.S. physicians who made political contributions during the 2013-2014 congressional election cycle donated to Democrats, continuing the trend away from Republicans that was first noted among medical professionals between 1991 and 2012, according to a report published April 27 in JAMA Internal Medicine.

In an analysis of physicians’ federal political contributions, 55% of contributors donated to Democrats and 45% to Republicans during the most recent congressional election cycle. In contrast, general public support resulted in the “Republican surge” in which conservatives gained nine Senate seats and increased their majority in the House, said Adam Bonica, Ph.D., of the department of political science, Stanford (Calif.) University, and his associates.

© BrianAJackson/Thinkstock

The current report shows that the shift away from predominantly Republican and toward predominantly Democratic support, which began in the 1990s, still persists for physicians.

“Given the increasing numbers of women physicians and salaried physicians, who typically ally with the Democrats, in contrast to surgeons, who typically ally with the Republicans, our findings suggest that the medical profession will be challenged to achieve consensus on health policy issues. The profession is unlikely to speak with one voice on questions such as the provision of health insurance or controlling the costs of medical care,” the investigators wrote (JAMA Intern. Med. 2015 April 27 [doi:10.1001/jamainternmed.2015.1332]).

However, this polarization among physicians “may spur both political parties to work harder to maintain and increase physicians’ support. Thus, the political divisions among physicians may have the unintended effect of enhancing the political standing of the medical profession,” they added.

People who survive Hodgkin’s lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease for at least 40 years – the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

Until now, follow-up studies of such patients “rarely exceeded 20-25 years,” before most survivors reached the age at which cardiovascular disease (CVD) becomes commonplace in the general population. To compare CVD rates between survivors and the general population at later ages, investigators examined the medical records of 2,524 individuals who survived 5 years or more after being treated for Hodgkin’s lymphoma as adolescents or young adults at five Dutch medical centers between 1965 and 1995.

A total of 81% of the cohort had received mediastinal radiotherapy and 31% had received anthracycline-containing chemotherapy. After 5-47 years of follow-up, 797 of these patients experienced 1,713 cardiovascular events. The most frequently occurring events included 401 coronary heart disease events (such as myocardial infarction and angina pectoris), 374 valvular heart disease events, and 140 heart failure events (such as cardiomyopathy and congestive heart failure), Frederika A. van Nimwegen of the department of epidemiology, the Netherlands Cancer Institute, Amsterdam, and her colleagues wrote in JAMA Internal Medicine on April 27 (doi:10.1001/jamainternmed.2015.1180).

Compared with the general population, Hodgkin’s survivors had a 3.2-fold higher standardized incidence ratio (SIR) of developing coronary heart disease and a 6.8-fold higher SIR of developing heart failure, corresponding to 70 excess cases of coronary heart disease and 58 excess cases of heart failure per 10,000 person-years.

These risks were significantly higher for survivors than for the general population at all ages, but patients who had been diagnosed and treated before the age of 25 years were at particularly elevated risk: they carried a 4.6- to 7.5-fold higher risk of coronary heart disease and a 10.9- to 40.5-fold higher risk of heart failure. At 40 years after Hodgkin’s diagnosis and treatment, the cumulative incidence of any type of CVD was 50%, the investigators wrote. Both survivors of Hodgkin’s lymphoma and their physicians should be aware that these patients remain at substantially increased cardiovascular risk throughout their lives, Ms. Van Nimwegen and her colleagues wrote.

This study was supported by the Dutch Cancer Society. Ms. van Nimwegen and her colleagues reported having no financial disclosures.

People who survive Hodgkin’s lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease for at least 40 years – the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

Until now, follow-up studies of such patients “rarely exceeded 20-25 years,” before most survivors reached the age at which cardiovascular disease (CVD) becomes commonplace in the general population. To compare CVD rates between survivors and the general population at later ages, investigators examined the medical records of 2,524 individuals who survived 5 years or more after being treated for Hodgkin’s lymphoma as adolescents or young adults at five Dutch medical centers between 1965 and 1995.

A total of 81% of the cohort had received mediastinal radiotherapy and 31% had received anthracycline-containing chemotherapy. After 5-47 years of follow-up, 797 of these patients experienced 1,713 cardiovascular events. The most frequently occurring events included 401 coronary heart disease events (such as myocardial infarction and angina pectoris), 374 valvular heart disease events, and 140 heart failure events (such as cardiomyopathy and congestive heart failure), Frederika A. van Nimwegen of the department of epidemiology, the Netherlands Cancer Institute, Amsterdam, and her colleagues wrote in JAMA Internal Medicine on April 27 (doi:10.1001/jamainternmed.2015.1180).

Compared with the general population, Hodgkin’s survivors had a 3.2-fold higher standardized incidence ratio (SIR) of developing coronary heart disease and a 6.8-fold higher SIR of developing heart failure, corresponding to 70 excess cases of coronary heart disease and 58 excess cases of heart failure per 10,000 person-years.

These risks were significantly higher for survivors than for the general population at all ages, but patients who had been diagnosed and treated before the age of 25 years were at particularly elevated risk: they carried a 4.6- to 7.5-fold higher risk of coronary heart disease and a 10.9- to 40.5-fold higher risk of heart failure. At 40 years after Hodgkin’s diagnosis and treatment, the cumulative incidence of any type of CVD was 50%, the investigators wrote. Both survivors of Hodgkin’s lymphoma and their physicians should be aware that these patients remain at substantially increased cardiovascular risk throughout their lives, Ms. Van Nimwegen and her colleagues wrote.

This study was supported by the Dutch Cancer Society. Ms. van Nimwegen and her colleagues reported having no financial disclosures.

People who survive Hodgkin’s lymphoma in adolescence or young adulthood remain at very high risk for cardiovascular disease for at least 40 years – the longest period for which they have been followed, according to the results of a retrospective cohort study of more than 2,500 patients.

Until now, follow-up studies of such patients “rarely exceeded 20-25 years,” before most survivors reached the age at which cardiovascular disease (CVD) becomes commonplace in the general population. To compare CVD rates between survivors and the general population at later ages, investigators examined the medical records of 2,524 individuals who survived 5 years or more after being treated for Hodgkin’s lymphoma as adolescents or young adults at five Dutch medical centers between 1965 and 1995.

A total of 81% of the cohort had received mediastinal radiotherapy and 31% had received anthracycline-containing chemotherapy. After 5-47 years of follow-up, 797 of these patients experienced 1,713 cardiovascular events. The most frequently occurring events included 401 coronary heart disease events (such as myocardial infarction and angina pectoris), 374 valvular heart disease events, and 140 heart failure events (such as cardiomyopathy and congestive heart failure), Frederika A. van Nimwegen of the department of epidemiology, the Netherlands Cancer Institute, Amsterdam, and her colleagues wrote in JAMA Internal Medicine on April 27 (doi:10.1001/jamainternmed.2015.1180).

Compared with the general population, Hodgkin’s survivors had a 3.2-fold higher standardized incidence ratio (SIR) of developing coronary heart disease and a 6.8-fold higher SIR of developing heart failure, corresponding to 70 excess cases of coronary heart disease and 58 excess cases of heart failure per 10,000 person-years.

These risks were significantly higher for survivors than for the general population at all ages, but patients who had been diagnosed and treated before the age of 25 years were at particularly elevated risk: they carried a 4.6- to 7.5-fold higher risk of coronary heart disease and a 10.9- to 40.5-fold higher risk of heart failure. At 40 years after Hodgkin’s diagnosis and treatment, the cumulative incidence of any type of CVD was 50%, the investigators wrote. Both survivors of Hodgkin’s lymphoma and their physicians should be aware that these patients remain at substantially increased cardiovascular risk throughout their lives, Ms. Van Nimwegen and her colleagues wrote.

This study was supported by the Dutch Cancer Society. Ms. van Nimwegen and her colleagues reported having no financial disclosures.

Here are 5 articles in the May issue of Clinician Reviews (accreditation valid until January 1, 2016):

1. Clindamycin, TMP-SMX Are Equally Effective for Skin Infections
To take the posttest, go to: http://bit.ly/1cVxR85

VITALS
Key clinical point: Clindamycin and TMP-SMX had similar efficacy and adverse-effect profiles for treating uncomplicated skin infections, including both abscesses and cellulitis.
Major finding: At 7-10 days after therapy completion, the rates of cure in the evaluable population were 89.5% with clindamycin and 88.2% with TMP-SMX.
Data source: A prospective, multicenter, randomized, double-blind clinical trial involving 524 adults and children followed for 1 month after treatment.
Disclosures: This trial was supported by the National Institutes of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences (NCT00730028). Dr Miller reported receiving consulting fees from Cubist, Durata, and Pfizer; his associates reported ties to Cubist, Pfizer, EMMES, Theravance, AstraZeneca, Trius, Merck, and Cerexa.

2. Hormone Therapy 10 Years Postmenopause Increases Risks
To take the posttest, go to: http://bit.ly/1OBYcUe

VITALS
Key clinical point: Hormone therapy in postmenopausal women increases stroke risk.
Major finding: Stroke increased by 24%, venous thromboembolism by 92%, and pulmonary embolism by 81% in postmenopausal women receiving hormone therapy.
Data source: A review and meta-analysis of 19 randomized controlled trials involving 40,140 postmenopausal women who received orally administered hormone therapy, placebo, or no treatment for prevention of cardiovascular disease.
Disclosures: One study was funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-La Roche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.

3. "Perfect storm" of Depression, Stress Raises Risk for MI, Death
To take the posttest, go to: http://bit.ly/1yM2HtF

VITALS
Key clinical point: Concurrent depression and stress in coronary heart disease patients may increase early risk for MI and death. 
Major finding: CHD patients with high depressive symptoms and high stress at baseline had an increased risk for MI and death early during follow-up (adjusted HR, 1.48).
Data source: A prospective cohort study of 4,487 adults.
Disclosures: The National Institute of Neurological Disorders and Stroke and the National Heart, Lung, and Blood Institute supported the study. Dr Alcántara reported having no disclosures; two other authors received salary support from Amgen for research, and one served as a consultant for DiaDexus.

4. Type 2 Diabetes Lower in Familial Hypercholesterolemia
To take the posttest, go to: http://bit.ly/1bplTDc

VITALS
Key clinical point: The prevalence of type 2 diabetes appears to be significantly lower in patients with familial hypercholesterolemia than in their unaffected relatives.
Major finding: The prevalence of type 2 diabetes was 1.75% in 25,137 patients with familial hypercholesterolemia, compared with 2.93% in 38,183 of their unaffected relatives.
Data source: An observational cross-sectional analysis of data for 63,320 people in the Dutch national registry of familial hypercholesterolemia.
Disclosures: The study sponsor was not specified; the familial hypercholesterolemia registry is subsidized by the Dutch government. Dr Besseling reported having no financial disclosures; his associates reported ties to Aegerion, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Eli Lilly, Genzyme, JSiS, MSD, Novartis, Pfizer, Regeneron, Roche, and Sanofi.

5. Mongersen Induces 55%-65% Remission Rates in Crohn’s
To take the posttest, go to: http://bit.ly/1DctonL

VITALS
Key clinical point: Mongersen, an oral SMAD7 antisense oligonucleotide, induced remission rates as high as 55%-65% in a small 2-week phase II clinical trial.
Major finding: Rates of remission were 65% in the 43 participants who received 160 mg of mongersen, 55% in the 40 who received 40 mg, 12% in the 41 who received 10 mg, and 10% in the 42 who received placebo.
Data source: A randomized, placebo-controlled, double-blind phase II clinical trial involving 166 adults at 17 medical centers in Italy and Germany.
Disclosures: This study was sponsored by Giuliani, acting under contract to Nogra Pharma. Dr Monteleone reported ties to Giuliani, Novo Nordisk, Teva, Sirtris, Lycera, Sofar, and Zambon, and holds a patent related to the use of SMAD7 antisense oligonucleotides in Crohn’s disease. His associates reported financial ties to numerous industry sources.

Here are 5 articles in the May issue of Clinician Reviews (accreditation valid until January 1, 2016):

1. Clindamycin, TMP-SMX Are Equally Effective for Skin Infections
To take the posttest, go to: http://bit.ly/1cVxR85

VITALS
Key clinical point: Clindamycin and TMP-SMX had similar efficacy and adverse-effect profiles for treating uncomplicated skin infections, including both abscesses and cellulitis.
Major finding: At 7-10 days after therapy completion, the rates of cure in the evaluable population were 89.5% with clindamycin and 88.2% with TMP-SMX.
Data source: A prospective, multicenter, randomized, double-blind clinical trial involving 524 adults and children followed for 1 month after treatment.
Disclosures: This trial was supported by the National Institutes of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences (NCT00730028). Dr Miller reported receiving consulting fees from Cubist, Durata, and Pfizer; his associates reported ties to Cubist, Pfizer, EMMES, Theravance, AstraZeneca, Trius, Merck, and Cerexa.

2. Hormone Therapy 10 Years Postmenopause Increases Risks
To take the posttest, go to: http://bit.ly/1OBYcUe

VITALS
Key clinical point: Hormone therapy in postmenopausal women increases stroke risk.
Major finding: Stroke increased by 24%, venous thromboembolism by 92%, and pulmonary embolism by 81% in postmenopausal women receiving hormone therapy.
Data source: A review and meta-analysis of 19 randomized controlled trials involving 40,140 postmenopausal women who received orally administered hormone therapy, placebo, or no treatment for prevention of cardiovascular disease.
Disclosures: One study was funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-La Roche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.

3. "Perfect storm" of Depression, Stress Raises Risk for MI, Death
To take the posttest, go to: http://bit.ly/1yM2HtF

VITALS
Key clinical point: Concurrent depression and stress in coronary heart disease patients may increase early risk for MI and death. 
Major finding: CHD patients with high depressive symptoms and high stress at baseline had an increased risk for MI and death early during follow-up (adjusted HR, 1.48).
Data source: A prospective cohort study of 4,487 adults.
Disclosures: The National Institute of Neurological Disorders and Stroke and the National Heart, Lung, and Blood Institute supported the study. Dr Alcántara reported having no disclosures; two other authors received salary support from Amgen for research, and one served as a consultant for DiaDexus.

4. Type 2 Diabetes Lower in Familial Hypercholesterolemia
To take the posttest, go to: http://bit.ly/1bplTDc

VITALS
Key clinical point: The prevalence of type 2 diabetes appears to be significantly lower in patients with familial hypercholesterolemia than in their unaffected relatives.
Major finding: The prevalence of type 2 diabetes was 1.75% in 25,137 patients with familial hypercholesterolemia, compared with 2.93% in 38,183 of their unaffected relatives.
Data source: An observational cross-sectional analysis of data for 63,320 people in the Dutch national registry of familial hypercholesterolemia.
Disclosures: The study sponsor was not specified; the familial hypercholesterolemia registry is subsidized by the Dutch government. Dr Besseling reported having no financial disclosures; his associates reported ties to Aegerion, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Eli Lilly, Genzyme, JSiS, MSD, Novartis, Pfizer, Regeneron, Roche, and Sanofi.

5. Mongersen Induces 55%-65% Remission Rates in Crohn’s
To take the posttest, go to: http://bit.ly/1DctonL

VITALS
Key clinical point: Mongersen, an oral SMAD7 antisense oligonucleotide, induced remission rates as high as 55%-65% in a small 2-week phase II clinical trial.
Major finding: Rates of remission were 65% in the 43 participants who received 160 mg of mongersen, 55% in the 40 who received 40 mg, 12% in the 41 who received 10 mg, and 10% in the 42 who received placebo.
Data source: A randomized, placebo-controlled, double-blind phase II clinical trial involving 166 adults at 17 medical centers in Italy and Germany.
Disclosures: This study was sponsored by Giuliani, acting under contract to Nogra Pharma. Dr Monteleone reported ties to Giuliani, Novo Nordisk, Teva, Sirtris, Lycera, Sofar, and Zambon, and holds a patent related to the use of SMAD7 antisense oligonucleotides in Crohn’s disease. His associates reported financial ties to numerous industry sources.

Here are 5 articles in the May issue of Clinician Reviews (accreditation valid until January 1, 2016):

1. Clindamycin, TMP-SMX Are Equally Effective for Skin Infections
To take the posttest, go to: http://bit.ly/1cVxR85

VITALS
Key clinical point: Clindamycin and TMP-SMX had similar efficacy and adverse-effect profiles for treating uncomplicated skin infections, including both abscesses and cellulitis.
Major finding: At 7-10 days after therapy completion, the rates of cure in the evaluable population were 89.5% with clindamycin and 88.2% with TMP-SMX.
Data source: A prospective, multicenter, randomized, double-blind clinical trial involving 524 adults and children followed for 1 month after treatment.
Disclosures: This trial was supported by the National Institutes of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences (NCT00730028). Dr Miller reported receiving consulting fees from Cubist, Durata, and Pfizer; his associates reported ties to Cubist, Pfizer, EMMES, Theravance, AstraZeneca, Trius, Merck, and Cerexa.

2. Hormone Therapy 10 Years Postmenopause Increases Risks
To take the posttest, go to: http://bit.ly/1OBYcUe

VITALS
Key clinical point: Hormone therapy in postmenopausal women increases stroke risk.
Major finding: Stroke increased by 24%, venous thromboembolism by 92%, and pulmonary embolism by 81% in postmenopausal women receiving hormone therapy.
Data source: A review and meta-analysis of 19 randomized controlled trials involving 40,140 postmenopausal women who received orally administered hormone therapy, placebo, or no treatment for prevention of cardiovascular disease.
Disclosures: One study was funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-La Roche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.

3. "Perfect storm" of Depression, Stress Raises Risk for MI, Death
To take the posttest, go to: http://bit.ly/1yM2HtF

VITALS
Key clinical point: Concurrent depression and stress in coronary heart disease patients may increase early risk for MI and death. 
Major finding: CHD patients with high depressive symptoms and high stress at baseline had an increased risk for MI and death early during follow-up (adjusted HR, 1.48).
Data source: A prospective cohort study of 4,487 adults.
Disclosures: The National Institute of Neurological Disorders and Stroke and the National Heart, Lung, and Blood Institute supported the study. Dr Alcántara reported having no disclosures; two other authors received salary support from Amgen for research, and one served as a consultant for DiaDexus.

4. Type 2 Diabetes Lower in Familial Hypercholesterolemia
To take the posttest, go to: http://bit.ly/1bplTDc

VITALS
Key clinical point: The prevalence of type 2 diabetes appears to be significantly lower in patients with familial hypercholesterolemia than in their unaffected relatives.
Major finding: The prevalence of type 2 diabetes was 1.75% in 25,137 patients with familial hypercholesterolemia, compared with 2.93% in 38,183 of their unaffected relatives.
Data source: An observational cross-sectional analysis of data for 63,320 people in the Dutch national registry of familial hypercholesterolemia.
Disclosures: The study sponsor was not specified; the familial hypercholesterolemia registry is subsidized by the Dutch government. Dr Besseling reported having no financial disclosures; his associates reported ties to Aegerion, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Eli Lilly, Genzyme, JSiS, MSD, Novartis, Pfizer, Regeneron, Roche, and Sanofi.

5. Mongersen Induces 55%-65% Remission Rates in Crohn’s
To take the posttest, go to: http://bit.ly/1DctonL

VITALS
Key clinical point: Mongersen, an oral SMAD7 antisense oligonucleotide, induced remission rates as high as 55%-65% in a small 2-week phase II clinical trial.
Major finding: Rates of remission were 65% in the 43 participants who received 160 mg of mongersen, 55% in the 40 who received 40 mg, 12% in the 41 who received 10 mg, and 10% in the 42 who received placebo.
Data source: A randomized, placebo-controlled, double-blind phase II clinical trial involving 166 adults at 17 medical centers in Italy and Germany.
Disclosures: This study was sponsored by Giuliani, acting under contract to Nogra Pharma. Dr Monteleone reported ties to Giuliani, Novo Nordisk, Teva, Sirtris, Lycera, Sofar, and Zambon, and holds a patent related to the use of SMAD7 antisense oligonucleotides in Crohn’s disease. His associates reported financial ties to numerous industry sources.

Neither pentoxifylline nor prednisolone reduced 28-day mortality, 90-day mortality, or 1-year mortality among adults with alcoholic hepatitis in a multicenter clinical trial comparing the two agents, according to a report published online April 23 in the New England Journal of Medicine.

Pentoxifylline and glucocorticoids are the only drugs endorsed for this indication in treatment guidelines from the American Association for the Study of Liver Disease and the European Association for the Study of the Liver. However, the evidence in support of both has been conflicting, and their use remains controversial. The Steroids or Pentoxifylline for Alcoholic Hepatitis (SOPAH) study was a randomized, double-blind trial comparing the two drugs against each other and against placebo in 1,103 patients enrolled during a 3-year period at 65 hospitals across the United Kingdom, said Dr. Mark R. Thursz of Imperial College, London, and his associates.

The primary endpoint of the study, mortality at the conclusion of the 28-day course of treatment, was 14% in the group taking prednisolone plus placebo, 19% in those taking pentoxifylline plus placebo, 13% in those taking both prednisolone plus pentoxifylline, and 17% in those taking two placebos – all nonsignificant differences. In addition, neither active drug affected mortality or the need for liver transplantation at 90 days or at 1 year, the investigators reported (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1412278]).

Cumulative mortality at 1 year was “alarming” but nearly identical between the groups who received the two active agents and the groups who did not: 56% with pentoxifylline and 57% without it; 57% with prednisolone and 56% without it.

Infection accounted for 24% of all deaths, but the number of infections among patients receiving prednisolone was no higher than that for the other patient groups, Dr. Thursz and his associates added.

Neither pentoxifylline nor prednisolone reduced 28-day mortality, 90-day mortality, or 1-year mortality among adults with alcoholic hepatitis in a multicenter clinical trial comparing the two agents, according to a report published online April 23 in the New England Journal of Medicine.

Pentoxifylline and glucocorticoids are the only drugs endorsed for this indication in treatment guidelines from the American Association for the Study of Liver Disease and the European Association for the Study of the Liver. However, the evidence in support of both has been conflicting, and their use remains controversial. The Steroids or Pentoxifylline for Alcoholic Hepatitis (SOPAH) study was a randomized, double-blind trial comparing the two drugs against each other and against placebo in 1,103 patients enrolled during a 3-year period at 65 hospitals across the United Kingdom, said Dr. Mark R. Thursz of Imperial College, London, and his associates.

The primary endpoint of the study, mortality at the conclusion of the 28-day course of treatment, was 14% in the group taking prednisolone plus placebo, 19% in those taking pentoxifylline plus placebo, 13% in those taking both prednisolone plus pentoxifylline, and 17% in those taking two placebos – all nonsignificant differences. In addition, neither active drug affected mortality or the need for liver transplantation at 90 days or at 1 year, the investigators reported (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1412278]).

Cumulative mortality at 1 year was “alarming” but nearly identical between the groups who received the two active agents and the groups who did not: 56% with pentoxifylline and 57% without it; 57% with prednisolone and 56% without it.

Infection accounted for 24% of all deaths, but the number of infections among patients receiving prednisolone was no higher than that for the other patient groups, Dr. Thursz and his associates added.

Neither pentoxifylline nor prednisolone reduced 28-day mortality, 90-day mortality, or 1-year mortality among adults with alcoholic hepatitis in a multicenter clinical trial comparing the two agents, according to a report published online April 23 in the New England Journal of Medicine.

Pentoxifylline and glucocorticoids are the only drugs endorsed for this indication in treatment guidelines from the American Association for the Study of Liver Disease and the European Association for the Study of the Liver. However, the evidence in support of both has been conflicting, and their use remains controversial. The Steroids or Pentoxifylline for Alcoholic Hepatitis (SOPAH) study was a randomized, double-blind trial comparing the two drugs against each other and against placebo in 1,103 patients enrolled during a 3-year period at 65 hospitals across the United Kingdom, said Dr. Mark R. Thursz of Imperial College, London, and his associates.

The primary endpoint of the study, mortality at the conclusion of the 28-day course of treatment, was 14% in the group taking prednisolone plus placebo, 19% in those taking pentoxifylline plus placebo, 13% in those taking both prednisolone plus pentoxifylline, and 17% in those taking two placebos – all nonsignificant differences. In addition, neither active drug affected mortality or the need for liver transplantation at 90 days or at 1 year, the investigators reported (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1412278]).

Cumulative mortality at 1 year was “alarming” but nearly identical between the groups who received the two active agents and the groups who did not: 56% with pentoxifylline and 57% without it; 57% with prednisolone and 56% without it.

Infection accounted for 24% of all deaths, but the number of infections among patients receiving prednisolone was no higher than that for the other patient groups, Dr. Thursz and his associates added.

For patients with early-stage Hodgkin’s lymphoma, forgoing radiotherapy after three cycles of chemotherapy when PET scans show negative findings – known as a PET-directed or response-adapted approach – was not found to be noninferior to routine consolidation radiotherapy in extending progression-free survival, according to a report published online April 23 in the New England Journal of Medicine.

The PET-directed technique is intended to spare the estimated 9 out of 10 patients who are cured by the chemotherapy from having to receive unnecessary radiotherapy, which carries late toxic effects such as secondary cancers and premature cardiovascular disease. To determine whether this approach caused an unacceptable increase in the relapse rate, researchers performed a randomized, controlled, phase III noninferiority trial in 602 previously untreated patients aged 16-75 years (median age, 34 years) who had stage IA or IIA Hodgkin’s lymphoma with no mediastinal bulk and no night sweats, unexplained fever, or weight loss, reported Dr. John Radford of the Institute of Cancer Sciences, University of Manchester (England), and his associates.

The study participants, enrolled and treated at 94 medical centers across the United Kingdom, had three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine therapy and then underwent PET scanning. The 420 who had negative findings on PET then were randomly assigned to receive either 30 Gy of involved-field radiotherapy (209 patients) or no further treatment (211 patients).

After a median of 62 months of follow-up, both groups had excellent outcomes. Three-year progression-free survival was 94.6% with radiotherapy and 90.8% without it; overall survival was 97.1% with radiotherapy and 99.0% without it. However, the modest advantage conveyed by radiotherapy in the 3-year progression-free survival rate – 3.8 percentage points in the intention-to-treat analysis and 6.3 percentage points in the per-protocol analysis – was enough to negate a finding of noninferiority for forgoing radiotherapy, the investigators wrote (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1408648]).

It is important to note that this marginal survival advantage “is bought at the expense of exposing all patients to radiation, most of whom will not benefit and some of whom will be harmed,” Dr. Radford and his associates wrote.

This report addressed medium-term outcomes. Continued follow-up in this ongoing study will determine whether the response-adapted approach leads to fewer second cancers, less cardiovascular disease, and superior survival in the long term, they added.

For patients with early-stage Hodgkin’s lymphoma, forgoing radiotherapy after three cycles of chemotherapy when PET scans show negative findings – known as a PET-directed or response-adapted approach – was not found to be noninferior to routine consolidation radiotherapy in extending progression-free survival, according to a report published online April 23 in the New England Journal of Medicine.

The PET-directed technique is intended to spare the estimated 9 out of 10 patients who are cured by the chemotherapy from having to receive unnecessary radiotherapy, which carries late toxic effects such as secondary cancers and premature cardiovascular disease. To determine whether this approach caused an unacceptable increase in the relapse rate, researchers performed a randomized, controlled, phase III noninferiority trial in 602 previously untreated patients aged 16-75 years (median age, 34 years) who had stage IA or IIA Hodgkin’s lymphoma with no mediastinal bulk and no night sweats, unexplained fever, or weight loss, reported Dr. John Radford of the Institute of Cancer Sciences, University of Manchester (England), and his associates.

The study participants, enrolled and treated at 94 medical centers across the United Kingdom, had three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine therapy and then underwent PET scanning. The 420 who had negative findings on PET then were randomly assigned to receive either 30 Gy of involved-field radiotherapy (209 patients) or no further treatment (211 patients).

After a median of 62 months of follow-up, both groups had excellent outcomes. Three-year progression-free survival was 94.6% with radiotherapy and 90.8% without it; overall survival was 97.1% with radiotherapy and 99.0% without it. However, the modest advantage conveyed by radiotherapy in the 3-year progression-free survival rate – 3.8 percentage points in the intention-to-treat analysis and 6.3 percentage points in the per-protocol analysis – was enough to negate a finding of noninferiority for forgoing radiotherapy, the investigators wrote (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1408648]).

It is important to note that this marginal survival advantage “is bought at the expense of exposing all patients to radiation, most of whom will not benefit and some of whom will be harmed,” Dr. Radford and his associates wrote.

This report addressed medium-term outcomes. Continued follow-up in this ongoing study will determine whether the response-adapted approach leads to fewer second cancers, less cardiovascular disease, and superior survival in the long term, they added.

For patients with early-stage Hodgkin’s lymphoma, forgoing radiotherapy after three cycles of chemotherapy when PET scans show negative findings – known as a PET-directed or response-adapted approach – was not found to be noninferior to routine consolidation radiotherapy in extending progression-free survival, according to a report published online April 23 in the New England Journal of Medicine.

The PET-directed technique is intended to spare the estimated 9 out of 10 patients who are cured by the chemotherapy from having to receive unnecessary radiotherapy, which carries late toxic effects such as secondary cancers and premature cardiovascular disease. To determine whether this approach caused an unacceptable increase in the relapse rate, researchers performed a randomized, controlled, phase III noninferiority trial in 602 previously untreated patients aged 16-75 years (median age, 34 years) who had stage IA or IIA Hodgkin’s lymphoma with no mediastinal bulk and no night sweats, unexplained fever, or weight loss, reported Dr. John Radford of the Institute of Cancer Sciences, University of Manchester (England), and his associates.

The study participants, enrolled and treated at 94 medical centers across the United Kingdom, had three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine therapy and then underwent PET scanning. The 420 who had negative findings on PET then were randomly assigned to receive either 30 Gy of involved-field radiotherapy (209 patients) or no further treatment (211 patients).

After a median of 62 months of follow-up, both groups had excellent outcomes. Three-year progression-free survival was 94.6% with radiotherapy and 90.8% without it; overall survival was 97.1% with radiotherapy and 99.0% without it. However, the modest advantage conveyed by radiotherapy in the 3-year progression-free survival rate – 3.8 percentage points in the intention-to-treat analysis and 6.3 percentage points in the per-protocol analysis – was enough to negate a finding of noninferiority for forgoing radiotherapy, the investigators wrote (N. Engl. J. Med. 2015 April 23 [doi:10.1056/NEJMoa1408648]).

It is important to note that this marginal survival advantage “is bought at the expense of exposing all patients to radiation, most of whom will not benefit and some of whom will be harmed,” Dr. Radford and his associates wrote.

This report addressed medium-term outcomes. Continued follow-up in this ongoing study will determine whether the response-adapted approach leads to fewer second cancers, less cardiovascular disease, and superior survival in the long term, they added.