Mary Ann Moon

Participants in the Health, Aging, and Body Composition study who carried the apolipoprotein E–epsilon 4 allele had some degree of protection from the cognitive decline for which they are at high risk if they had behaviors that enhanced cognitive reserve or improved certain other psychosocial and health factors.

Allison R. Kaup, Ph.D., of Sierra Pacific Mental Illness Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center, and her associates analyzed data collected in the prospective Health ABC (Health, Aging, and Body Composition) study to identify factors that may promote cognitive resilience in carriers of the apolipoprotein E–epsilon 4 (APOE e4) allele. The study examined aging-related health in 3,075 older adults residing in Pittsburgh or Memphis in 1997-98. These study participants, aged 69-80 years at baseline, had repeated cognitive testing during 11 years of follow-up. A subset of 670 were APOE e4 carriers.

As expected, APOE e4 carriers showed greater cognitive decline over time than noncarriers; however, a subset of APOE e4 carriers showed high retention of cognitive status in comparison with demographically similar noncarriers. Among white carriers, the factors that strongly predicted cognitive resilience were, in order of importance, an absence of recent negative life events, higher literacy level, older age, higher education level, and more time spent reading. Among black carriers, the factors that most strongly predicted cognitive resilience were higher literacy level, higher education level, female sex, and absence of diabetes mellitus.

The reasons why some predictors differed by race aren’t yet understood. The investigators analyzed the two races separately because there are racial differences in the frequency of APOE e4 carriage (it occurs more frequently in blacks than in whites) and in its impact (its deleterious effects on cognition are weaker in blacks than in whites).

Their findings “raise the possibility that interventions targeting the modifiable factors among these predictors could help promote cognitive resilience in APOE e4 carriers,” Dr. Kaup and her associates said (JAMA Neurol. 2015;72:340-8). For example, promoting cognitive reserve would likely be protective across both races. In addition, whites would likely benefit most from stress reduction or stress management, while blacks would likely benefit most from prevention or close management of diabetes.

This study was supported by the National Institute on Aging, the National Institute on Nursing Research, the U.S. Department of Veterans Affairs, the San Francisco VA Medical Center, and the Sierra Pacific Mental Illness Research, Education, and Clinical Center. Dr. Kaup reported having no financial disclosures; her associates reported ties to Navidea Biopharmaceuticals, Novartis, Pfizer, Takeda, and Beeson.

Participants in the Health, Aging, and Body Composition study who carried the apolipoprotein E–epsilon 4 allele had some degree of protection from the cognitive decline for which they are at high risk if they had behaviors that enhanced cognitive reserve or improved certain other psychosocial and health factors.

Allison R. Kaup, Ph.D., of Sierra Pacific Mental Illness Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center, and her associates analyzed data collected in the prospective Health ABC (Health, Aging, and Body Composition) study to identify factors that may promote cognitive resilience in carriers of the apolipoprotein E–epsilon 4 (APOE e4) allele. The study examined aging-related health in 3,075 older adults residing in Pittsburgh or Memphis in 1997-98. These study participants, aged 69-80 years at baseline, had repeated cognitive testing during 11 years of follow-up. A subset of 670 were APOE e4 carriers.

As expected, APOE e4 carriers showed greater cognitive decline over time than noncarriers; however, a subset of APOE e4 carriers showed high retention of cognitive status in comparison with demographically similar noncarriers. Among white carriers, the factors that strongly predicted cognitive resilience were, in order of importance, an absence of recent negative life events, higher literacy level, older age, higher education level, and more time spent reading. Among black carriers, the factors that most strongly predicted cognitive resilience were higher literacy level, higher education level, female sex, and absence of diabetes mellitus.

The reasons why some predictors differed by race aren’t yet understood. The investigators analyzed the two races separately because there are racial differences in the frequency of APOE e4 carriage (it occurs more frequently in blacks than in whites) and in its impact (its deleterious effects on cognition are weaker in blacks than in whites).

Their findings “raise the possibility that interventions targeting the modifiable factors among these predictors could help promote cognitive resilience in APOE e4 carriers,” Dr. Kaup and her associates said (JAMA Neurol. 2015;72:340-8). For example, promoting cognitive reserve would likely be protective across both races. In addition, whites would likely benefit most from stress reduction or stress management, while blacks would likely benefit most from prevention or close management of diabetes.

This study was supported by the National Institute on Aging, the National Institute on Nursing Research, the U.S. Department of Veterans Affairs, the San Francisco VA Medical Center, and the Sierra Pacific Mental Illness Research, Education, and Clinical Center. Dr. Kaup reported having no financial disclosures; her associates reported ties to Navidea Biopharmaceuticals, Novartis, Pfizer, Takeda, and Beeson.

Participants in the Health, Aging, and Body Composition study who carried the apolipoprotein E–epsilon 4 allele had some degree of protection from the cognitive decline for which they are at high risk if they had behaviors that enhanced cognitive reserve or improved certain other psychosocial and health factors.

Allison R. Kaup, Ph.D., of Sierra Pacific Mental Illness Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center, and her associates analyzed data collected in the prospective Health ABC (Health, Aging, and Body Composition) study to identify factors that may promote cognitive resilience in carriers of the apolipoprotein E–epsilon 4 (APOE e4) allele. The study examined aging-related health in 3,075 older adults residing in Pittsburgh or Memphis in 1997-98. These study participants, aged 69-80 years at baseline, had repeated cognitive testing during 11 years of follow-up. A subset of 670 were APOE e4 carriers.

As expected, APOE e4 carriers showed greater cognitive decline over time than noncarriers; however, a subset of APOE e4 carriers showed high retention of cognitive status in comparison with demographically similar noncarriers. Among white carriers, the factors that strongly predicted cognitive resilience were, in order of importance, an absence of recent negative life events, higher literacy level, older age, higher education level, and more time spent reading. Among black carriers, the factors that most strongly predicted cognitive resilience were higher literacy level, higher education level, female sex, and absence of diabetes mellitus.

The reasons why some predictors differed by race aren’t yet understood. The investigators analyzed the two races separately because there are racial differences in the frequency of APOE e4 carriage (it occurs more frequently in blacks than in whites) and in its impact (its deleterious effects on cognition are weaker in blacks than in whites).

Their findings “raise the possibility that interventions targeting the modifiable factors among these predictors could help promote cognitive resilience in APOE e4 carriers,” Dr. Kaup and her associates said (JAMA Neurol. 2015;72:340-8). For example, promoting cognitive reserve would likely be protective across both races. In addition, whites would likely benefit most from stress reduction or stress management, while blacks would likely benefit most from prevention or close management of diabetes.

This study was supported by the National Institute on Aging, the National Institute on Nursing Research, the U.S. Department of Veterans Affairs, the San Francisco VA Medical Center, and the Sierra Pacific Mental Illness Research, Education, and Clinical Center. Dr. Kaup reported having no financial disclosures; her associates reported ties to Navidea Biopharmaceuticals, Novartis, Pfizer, Takeda, and Beeson.

Researchers have developed nomograms based on a variety of newly identified prognostic factors – tools that can enhance clinicians’ estimates of 2-year progression-free survival, 5-year overall survival, and pelvic recurrence for locally advanced cervical cancer, according to a report published online March 3 in Journal of Clinical Oncology.

Nomograms are graphic tools that allow rapid, simple calculation of a complex formula – in this case, survival odds and recurrence rates – based on the user’s input of relatively few data points. To develop the nomograms in this study, investigators first analyzed data from six multicenter Gynecologic Oncology Group clinical trials involving 2,042 patients with locally advanced cervical cancer. Most of these participants (65%) were treated with standard cisplatin-based chemoradiotherapy, and the remainder received either radiotherapy alone or a noncisplatin regimen, said Dr. Peter G. Rose of the Cleveland Clinic Foundation, and his associates.

They assessed numerous clinicopathologic and demographic factors to determine which ones were most useful for predicting survival and pelvic recurrence. Previous survival estimates for cervical cancer have been based primarily on disease stage, and, as expected, Dr. Rose and his colleagues found that disease stage, tumor size, pelvic node status, and performance status were significantly associated with progression-free and overall survival. But disease stage accounted for only 60% of the prognostic information in these study participants; the researchers discovered that tumor histology, patient race/ethnicity, tumor grade, and type of treatment also were significant predictors of survival.

They then used this information to devise the nomograms and to then validate their accuracy. The nomograms can now be used to more accurately estimate patient survival and disease recurrence, both in individual patients and in study populations, Dr. Rose and his associates said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/JCO.2014.57.7122]). One limitation of basing the nomograms on clinical trial participants is that such patients tend to have better performance status, to be more motivated to treat their cancer aggressively, and to be more compliant with treatment than is the general population of patients encountered in real-world clinical practice, the investigators added.

Researchers have developed nomograms based on a variety of newly identified prognostic factors – tools that can enhance clinicians’ estimates of 2-year progression-free survival, 5-year overall survival, and pelvic recurrence for locally advanced cervical cancer, according to a report published online March 3 in Journal of Clinical Oncology.

Nomograms are graphic tools that allow rapid, simple calculation of a complex formula – in this case, survival odds and recurrence rates – based on the user’s input of relatively few data points. To develop the nomograms in this study, investigators first analyzed data from six multicenter Gynecologic Oncology Group clinical trials involving 2,042 patients with locally advanced cervical cancer. Most of these participants (65%) were treated with standard cisplatin-based chemoradiotherapy, and the remainder received either radiotherapy alone or a noncisplatin regimen, said Dr. Peter G. Rose of the Cleveland Clinic Foundation, and his associates.

They assessed numerous clinicopathologic and demographic factors to determine which ones were most useful for predicting survival and pelvic recurrence. Previous survival estimates for cervical cancer have been based primarily on disease stage, and, as expected, Dr. Rose and his colleagues found that disease stage, tumor size, pelvic node status, and performance status were significantly associated with progression-free and overall survival. But disease stage accounted for only 60% of the prognostic information in these study participants; the researchers discovered that tumor histology, patient race/ethnicity, tumor grade, and type of treatment also were significant predictors of survival.

They then used this information to devise the nomograms and to then validate their accuracy. The nomograms can now be used to more accurately estimate patient survival and disease recurrence, both in individual patients and in study populations, Dr. Rose and his associates said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/JCO.2014.57.7122]). One limitation of basing the nomograms on clinical trial participants is that such patients tend to have better performance status, to be more motivated to treat their cancer aggressively, and to be more compliant with treatment than is the general population of patients encountered in real-world clinical practice, the investigators added.

Researchers have developed nomograms based on a variety of newly identified prognostic factors – tools that can enhance clinicians’ estimates of 2-year progression-free survival, 5-year overall survival, and pelvic recurrence for locally advanced cervical cancer, according to a report published online March 3 in Journal of Clinical Oncology.

Nomograms are graphic tools that allow rapid, simple calculation of a complex formula – in this case, survival odds and recurrence rates – based on the user’s input of relatively few data points. To develop the nomograms in this study, investigators first analyzed data from six multicenter Gynecologic Oncology Group clinical trials involving 2,042 patients with locally advanced cervical cancer. Most of these participants (65%) were treated with standard cisplatin-based chemoradiotherapy, and the remainder received either radiotherapy alone or a noncisplatin regimen, said Dr. Peter G. Rose of the Cleveland Clinic Foundation, and his associates.

They assessed numerous clinicopathologic and demographic factors to determine which ones were most useful for predicting survival and pelvic recurrence. Previous survival estimates for cervical cancer have been based primarily on disease stage, and, as expected, Dr. Rose and his colleagues found that disease stage, tumor size, pelvic node status, and performance status were significantly associated with progression-free and overall survival. But disease stage accounted for only 60% of the prognostic information in these study participants; the researchers discovered that tumor histology, patient race/ethnicity, tumor grade, and type of treatment also were significant predictors of survival.

They then used this information to devise the nomograms and to then validate their accuracy. The nomograms can now be used to more accurately estimate patient survival and disease recurrence, both in individual patients and in study populations, Dr. Rose and his associates said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/JCO.2014.57.7122]). One limitation of basing the nomograms on clinical trial participants is that such patients tend to have better performance status, to be more motivated to treat their cancer aggressively, and to be more compliant with treatment than is the general population of patients encountered in real-world clinical practice, the investigators added.

Maintenance therapy using sunitinib improved progression-free survival (PFS) among patients with extensive-stage small-cell lung cancer participating in a phase II clinical trial, investigators reported online March 3 in Journal of Clinical Oncology.

The proactive maintenance approach proved to be significantly less toxic than waiting for disease progression and then giving the same dose of sunitinib, which provides a strong rationale for investigating maintenance therapies in general for patients with extensive-stage small cell lung cancer (SCLC). In addition, since sunitinib inhibits multiple targets of interest in SCLC (including tyrosine kinase, vascular endothelial growth factor receptors, platelet-derived growth factor receptors, Flt-3, and Kit), the study findings also suggest that other multitarget inhibitors should be assessed as treatments for SCLC, said Dr. Neal E. Ready of Duke University Medical Center, Durham, N.C., and his associates.

In their study, 95 patients who had stable disease, partial response, or compete response to standard initial chemotherapy were randomly assigned in a double-blind fashion to receive either sunitinib or placebo as maintenance therapy until SCLC progressed. A total of 85 of these patients received at least one dose as assigned: 44 received sunitinib and 41 received placebo.

The main efficacy outcome – median PFS – was 3.7 months for sunitinib and 2.1 months for placebo, a significant difference. Three patients taking sunitinib achieved a complete response, compared with none taking placebo, the investigators said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/jco.2014.57.3105]).

In addition, 13 patients who were initially assigned to placebo showed disease progression and were permitted to cross over to sunitinib. Ten of them (77%) attained prolonged disease control, including three (23%) who achieved complete response. This demonstrates a major therapeutic benefit for a small subset of patients who have rapidly growing refractory SCLC, Dr. Ready and his associates said.

The most frequent adverse events were fatigue (19% of patients taking sunitinib and 10% of those taking placebo), decreased neutrophils (14% on sunitinib), decreased leukocytes (7% on sunitinib), and decreased platelets (7% on sunitinib). The most serious (grade 4) adverse events were one case each of GI hemorrhage, pancreatitis, hypocalcemia, and elevated lipase among patients taking sunitinib and hypernatremia in a patient taking placebo.

Maintenance therapy using sunitinib improved progression-free survival (PFS) among patients with extensive-stage small-cell lung cancer participating in a phase II clinical trial, investigators reported online March 3 in Journal of Clinical Oncology.

The proactive maintenance approach proved to be significantly less toxic than waiting for disease progression and then giving the same dose of sunitinib, which provides a strong rationale for investigating maintenance therapies in general for patients with extensive-stage small cell lung cancer (SCLC). In addition, since sunitinib inhibits multiple targets of interest in SCLC (including tyrosine kinase, vascular endothelial growth factor receptors, platelet-derived growth factor receptors, Flt-3, and Kit), the study findings also suggest that other multitarget inhibitors should be assessed as treatments for SCLC, said Dr. Neal E. Ready of Duke University Medical Center, Durham, N.C., and his associates.

In their study, 95 patients who had stable disease, partial response, or compete response to standard initial chemotherapy were randomly assigned in a double-blind fashion to receive either sunitinib or placebo as maintenance therapy until SCLC progressed. A total of 85 of these patients received at least one dose as assigned: 44 received sunitinib and 41 received placebo.

The main efficacy outcome – median PFS – was 3.7 months for sunitinib and 2.1 months for placebo, a significant difference. Three patients taking sunitinib achieved a complete response, compared with none taking placebo, the investigators said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/jco.2014.57.3105]).

In addition, 13 patients who were initially assigned to placebo showed disease progression and were permitted to cross over to sunitinib. Ten of them (77%) attained prolonged disease control, including three (23%) who achieved complete response. This demonstrates a major therapeutic benefit for a small subset of patients who have rapidly growing refractory SCLC, Dr. Ready and his associates said.

The most frequent adverse events were fatigue (19% of patients taking sunitinib and 10% of those taking placebo), decreased neutrophils (14% on sunitinib), decreased leukocytes (7% on sunitinib), and decreased platelets (7% on sunitinib). The most serious (grade 4) adverse events were one case each of GI hemorrhage, pancreatitis, hypocalcemia, and elevated lipase among patients taking sunitinib and hypernatremia in a patient taking placebo.

Maintenance therapy using sunitinib improved progression-free survival (PFS) among patients with extensive-stage small-cell lung cancer participating in a phase II clinical trial, investigators reported online March 3 in Journal of Clinical Oncology.

The proactive maintenance approach proved to be significantly less toxic than waiting for disease progression and then giving the same dose of sunitinib, which provides a strong rationale for investigating maintenance therapies in general for patients with extensive-stage small cell lung cancer (SCLC). In addition, since sunitinib inhibits multiple targets of interest in SCLC (including tyrosine kinase, vascular endothelial growth factor receptors, platelet-derived growth factor receptors, Flt-3, and Kit), the study findings also suggest that other multitarget inhibitors should be assessed as treatments for SCLC, said Dr. Neal E. Ready of Duke University Medical Center, Durham, N.C., and his associates.

In their study, 95 patients who had stable disease, partial response, or compete response to standard initial chemotherapy were randomly assigned in a double-blind fashion to receive either sunitinib or placebo as maintenance therapy until SCLC progressed. A total of 85 of these patients received at least one dose as assigned: 44 received sunitinib and 41 received placebo.

The main efficacy outcome – median PFS – was 3.7 months for sunitinib and 2.1 months for placebo, a significant difference. Three patients taking sunitinib achieved a complete response, compared with none taking placebo, the investigators said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/jco.2014.57.3105]).

In addition, 13 patients who were initially assigned to placebo showed disease progression and were permitted to cross over to sunitinib. Ten of them (77%) attained prolonged disease control, including three (23%) who achieved complete response. This demonstrates a major therapeutic benefit for a small subset of patients who have rapidly growing refractory SCLC, Dr. Ready and his associates said.

The most frequent adverse events were fatigue (19% of patients taking sunitinib and 10% of those taking placebo), decreased neutrophils (14% on sunitinib), decreased leukocytes (7% on sunitinib), and decreased platelets (7% on sunitinib). The most serious (grade 4) adverse events were one case each of GI hemorrhage, pancreatitis, hypocalcemia, and elevated lipase among patients taking sunitinib and hypernatremia in a patient taking placebo.

Paclitaxel plus carboplatin was noninferior to paclitaxel plus cisplatin in extending overall survival in incurable metastatic or recurrent cervical cancer in a multicenter open-label randomized phase III clinical trial published online March 3 in Journal of Clinical Oncology.

Given that carboplatin induces less toxicity than does cisplatin, doesn’t require 24-hour hospitalization when administered, and doesn’t require monitored hydration to prevent nephrotoxicity as cisplatin does, the paclitaxel-plus-carboplatin therapy should be a standard treatment option for this patient population, said Dr. Ryo Kitagawa of NTT Medical Center, Tokyo, and associates.

Worldwide, cisplatin plus paclitaxel is considered the standard cytotoxic treatment for metastatic or recurrent cervical cancer. Carboplatin has been reported to be less effective in three studies, but the two agents have never been compared against each other in a phase III trial. Dr. Kitagawa and her associates performed such a comparison study in 253 women whose disease was not amenable to curative surgery or radiotherapy. These patients were randomly assigned to receive either paclitaxel plus carboplatin (126 patients) or standard paclitaxel plus cisplatin (127 patients) and were followed for a median of 18 months.

The carboplatin regimen, with a median overall survival of 17.5 months, proved to be noninferior to the cisplatin regimen, which had a median OS of 18.3 months. The carboplatin regimen also was either noninferior or superior to the cisplatin regimen for the secondary outcomes of progression-free survival (6.2 months vs. 6.9 months), complete response rate (7.1% vs. 3.9%), and complete or partial response rate (62.6% vs. 58.8%), the investigators said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/JCO.2014.58.4391]).

The percentages of patients who completed the treatment protocol were nearly the same in both study groups (72% and 71%), and the patients who discontinued treatment because of adverse effects also was similar (9.5% and 11.8%). Quality of life was judged to be significantly better with the carboplatin regimen because the percentage of nonhospitalization time was much greater (61.9% vs 46.4%). The carboplatin regimen also induced markedly less grade 4 neutropenia, grade 3-4 febrile neutropenia, creatinine elevation, and nausea/vomiting, but thrombocytopenia and reversible neuropathy tended to be more frequent with carboplatin than with cisplatin.

Paclitaxel plus carboplatin was noninferior to paclitaxel plus cisplatin in extending overall survival in incurable metastatic or recurrent cervical cancer in a multicenter open-label randomized phase III clinical trial published online March 3 in Journal of Clinical Oncology.

Given that carboplatin induces less toxicity than does cisplatin, doesn’t require 24-hour hospitalization when administered, and doesn’t require monitored hydration to prevent nephrotoxicity as cisplatin does, the paclitaxel-plus-carboplatin therapy should be a standard treatment option for this patient population, said Dr. Ryo Kitagawa of NTT Medical Center, Tokyo, and associates.

Worldwide, cisplatin plus paclitaxel is considered the standard cytotoxic treatment for metastatic or recurrent cervical cancer. Carboplatin has been reported to be less effective in three studies, but the two agents have never been compared against each other in a phase III trial. Dr. Kitagawa and her associates performed such a comparison study in 253 women whose disease was not amenable to curative surgery or radiotherapy. These patients were randomly assigned to receive either paclitaxel plus carboplatin (126 patients) or standard paclitaxel plus cisplatin (127 patients) and were followed for a median of 18 months.

The carboplatin regimen, with a median overall survival of 17.5 months, proved to be noninferior to the cisplatin regimen, which had a median OS of 18.3 months. The carboplatin regimen also was either noninferior or superior to the cisplatin regimen for the secondary outcomes of progression-free survival (6.2 months vs. 6.9 months), complete response rate (7.1% vs. 3.9%), and complete or partial response rate (62.6% vs. 58.8%), the investigators said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/JCO.2014.58.4391]).

The percentages of patients who completed the treatment protocol were nearly the same in both study groups (72% and 71%), and the patients who discontinued treatment because of adverse effects also was similar (9.5% and 11.8%). Quality of life was judged to be significantly better with the carboplatin regimen because the percentage of nonhospitalization time was much greater (61.9% vs 46.4%). The carboplatin regimen also induced markedly less grade 4 neutropenia, grade 3-4 febrile neutropenia, creatinine elevation, and nausea/vomiting, but thrombocytopenia and reversible neuropathy tended to be more frequent with carboplatin than with cisplatin.

Paclitaxel plus carboplatin was noninferior to paclitaxel plus cisplatin in extending overall survival in incurable metastatic or recurrent cervical cancer in a multicenter open-label randomized phase III clinical trial published online March 3 in Journal of Clinical Oncology.

Given that carboplatin induces less toxicity than does cisplatin, doesn’t require 24-hour hospitalization when administered, and doesn’t require monitored hydration to prevent nephrotoxicity as cisplatin does, the paclitaxel-plus-carboplatin therapy should be a standard treatment option for this patient population, said Dr. Ryo Kitagawa of NTT Medical Center, Tokyo, and associates.

Worldwide, cisplatin plus paclitaxel is considered the standard cytotoxic treatment for metastatic or recurrent cervical cancer. Carboplatin has been reported to be less effective in three studies, but the two agents have never been compared against each other in a phase III trial. Dr. Kitagawa and her associates performed such a comparison study in 253 women whose disease was not amenable to curative surgery or radiotherapy. These patients were randomly assigned to receive either paclitaxel plus carboplatin (126 patients) or standard paclitaxel plus cisplatin (127 patients) and were followed for a median of 18 months.

The carboplatin regimen, with a median overall survival of 17.5 months, proved to be noninferior to the cisplatin regimen, which had a median OS of 18.3 months. The carboplatin regimen also was either noninferior or superior to the cisplatin regimen for the secondary outcomes of progression-free survival (6.2 months vs. 6.9 months), complete response rate (7.1% vs. 3.9%), and complete or partial response rate (62.6% vs. 58.8%), the investigators said (J. Clin. Oncol. 2015 March 3 [doi:10.1200/JCO.2014.58.4391]).

The percentages of patients who completed the treatment protocol were nearly the same in both study groups (72% and 71%), and the patients who discontinued treatment because of adverse effects also was similar (9.5% and 11.8%). Quality of life was judged to be significantly better with the carboplatin regimen because the percentage of nonhospitalization time was much greater (61.9% vs 46.4%). The carboplatin regimen also induced markedly less grade 4 neutropenia, grade 3-4 febrile neutropenia, creatinine elevation, and nausea/vomiting, but thrombocytopenia and reversible neuropathy tended to be more frequent with carboplatin than with cisplatin.

Light to moderate coffee drinking – less than 5 cups per day – is associated with decreased coronary artery calcium, and thus decreased risk of cardiovascular disease, according to an analysis of a large cohort published online March 2 in Heart.

Coffee consumption’s effect on cardiovascular health has been controversial, even though the bulk of the substantial evidence collected to date suggests that it is cardioprotective. To clarify the association between coffee drinking and CVD, researchers performed a cross-sectional analysis of data from a large cohort study of asymptomatic young and middle-age South Korean adults attending a comprehensive health screening during a 3-year period. Members of the cohort (mean age 41 years) completed a detailed food-frequency questionnaire and underwent cardiac CT to measure coronary artery calcium, a marker of subclinical coronary atherosclerosis that predicts future heart disease, said Dr. Yuni Choi of Sungkyunkwan University, Seoul, South Korea, and her associates.

s-photo/iStockphoto.com

For this analysis, results for 25,138 participants who had no clinical evidence of CVD were assessed. The large sample size allowed for the data to be adjusted to account for numerous confounding factors such as medication use, personal and family medical history, physical activity level, alcohol consumption, smoking status, and sociodemographic factors.

Coffee consumption correlated with coronary artery calcium in a U-shaped pattern: Adults who drank up to 3 cups of coffee per day (light intake) had a decreased prevalence of subclinical coronary athersclerosis, those who drank 3-4 cups per day (moderate intake) had the lowest prevalence, and those who drank 5 or more cups per day had an increased prevalence, compared with people who didn’t drink coffee. Coronary artery calcium ratios that compared coffee drinkers with nondrinkers were 0.86 at less than 1 cup per day, 0.82 at 1-2 cups per day, 0.78 at 3-4 cups per day, and 1.77 at 5 or more cups per day. The association between coffee intake and coronary artery calcium scores remained consistent across all subgroup analyses and in sensitivity analyses, the investigators said (Heart 2015 March 2 [doi:10.1136/heartjnl-2014-306663]).

The cross-sectional design of this study means that it can establish only an association, not causality, between coffee intake and CVD risk. “Further research is needed to confirm our findings and establish the biological basis of coffee’s potential preventive effects on coronary artery disease,” Dr. Choi and her associates wrote.

But the evidence already is strong enough that for the first time this year, dietary guidelines will likely state that moderate coffee consumption appears to be cardioprotective and “can be incorporated into a healthy dietary pattern.” Coffee drinkers need only minimize the sugars and fats they add to their coffee, in the form of sweeteners and creamers, to benefit from the beverage, the 2015 Dietary Guidelines Advisory Committee recommended in a report submitted for review to the secretaries of the U.S. Department of Health & Human Services and the U.S. Department of Agriculture in February.

Light to moderate coffee drinking – less than 5 cups per day – is associated with decreased coronary artery calcium, and thus decreased risk of cardiovascular disease, according to an analysis of a large cohort published online March 2 in Heart.

Coffee consumption’s effect on cardiovascular health has been controversial, even though the bulk of the substantial evidence collected to date suggests that it is cardioprotective. To clarify the association between coffee drinking and CVD, researchers performed a cross-sectional analysis of data from a large cohort study of asymptomatic young and middle-age South Korean adults attending a comprehensive health screening during a 3-year period. Members of the cohort (mean age 41 years) completed a detailed food-frequency questionnaire and underwent cardiac CT to measure coronary artery calcium, a marker of subclinical coronary atherosclerosis that predicts future heart disease, said Dr. Yuni Choi of Sungkyunkwan University, Seoul, South Korea, and her associates.

s-photo/iStockphoto.com

For this analysis, results for 25,138 participants who had no clinical evidence of CVD were assessed. The large sample size allowed for the data to be adjusted to account for numerous confounding factors such as medication use, personal and family medical history, physical activity level, alcohol consumption, smoking status, and sociodemographic factors.

Coffee consumption correlated with coronary artery calcium in a U-shaped pattern: Adults who drank up to 3 cups of coffee per day (light intake) had a decreased prevalence of subclinical coronary athersclerosis, those who drank 3-4 cups per day (moderate intake) had the lowest prevalence, and those who drank 5 or more cups per day had an increased prevalence, compared with people who didn’t drink coffee. Coronary artery calcium ratios that compared coffee drinkers with nondrinkers were 0.86 at less than 1 cup per day, 0.82 at 1-2 cups per day, 0.78 at 3-4 cups per day, and 1.77 at 5 or more cups per day. The association between coffee intake and coronary artery calcium scores remained consistent across all subgroup analyses and in sensitivity analyses, the investigators said (Heart 2015 March 2 [doi:10.1136/heartjnl-2014-306663]).

The cross-sectional design of this study means that it can establish only an association, not causality, between coffee intake and CVD risk. “Further research is needed to confirm our findings and establish the biological basis of coffee’s potential preventive effects on coronary artery disease,” Dr. Choi and her associates wrote.

But the evidence already is strong enough that for the first time this year, dietary guidelines will likely state that moderate coffee consumption appears to be cardioprotective and “can be incorporated into a healthy dietary pattern.” Coffee drinkers need only minimize the sugars and fats they add to their coffee, in the form of sweeteners and creamers, to benefit from the beverage, the 2015 Dietary Guidelines Advisory Committee recommended in a report submitted for review to the secretaries of the U.S. Department of Health & Human Services and the U.S. Department of Agriculture in February.

Light to moderate coffee drinking – less than 5 cups per day – is associated with decreased coronary artery calcium, and thus decreased risk of cardiovascular disease, according to an analysis of a large cohort published online March 2 in Heart.

Coffee consumption’s effect on cardiovascular health has been controversial, even though the bulk of the substantial evidence collected to date suggests that it is cardioprotective. To clarify the association between coffee drinking and CVD, researchers performed a cross-sectional analysis of data from a large cohort study of asymptomatic young and middle-age South Korean adults attending a comprehensive health screening during a 3-year period. Members of the cohort (mean age 41 years) completed a detailed food-frequency questionnaire and underwent cardiac CT to measure coronary artery calcium, a marker of subclinical coronary atherosclerosis that predicts future heart disease, said Dr. Yuni Choi of Sungkyunkwan University, Seoul, South Korea, and her associates.

s-photo/iStockphoto.com

For this analysis, results for 25,138 participants who had no clinical evidence of CVD were assessed. The large sample size allowed for the data to be adjusted to account for numerous confounding factors such as medication use, personal and family medical history, physical activity level, alcohol consumption, smoking status, and sociodemographic factors.

Coffee consumption correlated with coronary artery calcium in a U-shaped pattern: Adults who drank up to 3 cups of coffee per day (light intake) had a decreased prevalence of subclinical coronary athersclerosis, those who drank 3-4 cups per day (moderate intake) had the lowest prevalence, and those who drank 5 or more cups per day had an increased prevalence, compared with people who didn’t drink coffee. Coronary artery calcium ratios that compared coffee drinkers with nondrinkers were 0.86 at less than 1 cup per day, 0.82 at 1-2 cups per day, 0.78 at 3-4 cups per day, and 1.77 at 5 or more cups per day. The association between coffee intake and coronary artery calcium scores remained consistent across all subgroup analyses and in sensitivity analyses, the investigators said (Heart 2015 March 2 [doi:10.1136/heartjnl-2014-306663]).

The cross-sectional design of this study means that it can establish only an association, not causality, between coffee intake and CVD risk. “Further research is needed to confirm our findings and establish the biological basis of coffee’s potential preventive effects on coronary artery disease,” Dr. Choi and her associates wrote.

But the evidence already is strong enough that for the first time this year, dietary guidelines will likely state that moderate coffee consumption appears to be cardioprotective and “can be incorporated into a healthy dietary pattern.” Coffee drinkers need only minimize the sugars and fats they add to their coffee, in the form of sweeteners and creamers, to benefit from the beverage, the 2015 Dietary Guidelines Advisory Committee recommended in a report submitted for review to the secretaries of the U.S. Department of Health & Human Services and the U.S. Department of Agriculture in February.

Alternating-air and low-air-loss mattresses and overlays have little data to support their use for preventing or treating pressure ulcers, the Clinical Guidelines Committee of the American College of Physicians has concluded.

Many U.S. acute-care hospitals, home caregivers, and long-term nursing facilities use alternating-air and low-air-loss mattresses and overlays, even though the evidence in favor of using these surfaces is sparse and of poor quality, the guideline writers said.

The devices have not been show to actually reduce pressure ulcers. The harms have been poorly reported but could be significant. “Using these support systems is expensive and adds unnecessary burden on the health care system. Based on a review of the current evidence, lower-cost support surfaces should be the preferred approach to care,” Dr. Amir Qaseem, of the ACP, Philadelphia, and his associates wrote.

The committee performed an extensive review of the literature on pressure ulcers and compiled two Clinical Practice Guidelines – one concerning prevention (Ann. Intern. Med. 2015;162 [doi:10.7326/M14-1567]) and the other concerning treatment (Ann. Intern. Med. 2015;162 [doi:10.7326/M14-1568]) – in part because “a growing industry” has developed in recent years and aggressively pitches a wide array of products for this patient population. The guidelines present the available evidence on the comparative effectiveness of tools and strategies but state repeatedly that evidence regarding pressure ulcers is sparse and of poor quality.

The prevention guideline strongly recommends that clinicians choose advanced static mattresses or advanced static overlays rather than standard hospital mattresses for at-risk patients. Static mattresses and advanced static overlays provide a constant level of inflation or support and evenly distribute body weight. These products are among the few actually shown to reduce the incidence of pressure ulcers. They are also preferable to alternating-air mattresses and overlays, which change the distribution of pressure by inflating or deflating cells within the devices, and to low-air-loss mattresses and overlays, which use flowing air to regulate heat and humidity and adjust pressure.

Evidence is similarly poor or lacking concerning the use of other support surfaces such as heel supports or boots and a variety of wheelchair cushions. Also lacking evidence are other preventive interventions that extend beyond “usual care,” such as different types of repositioning schemes, a variety of leg elevations, various nutritional supplements, and a wide variety of skin care strategies and topical treatments.

The prevention guideline advises patient assessments to identify those at risk of developing pressure ulcers. However, there is not enough evidence to demonstrate that any one of the many risk assessment tools for this purpose is superior to the others, nor that any of these tools is superior to simple clinical judgment. Risk factors for pressure ulcers include older age; black race or Hispanic ethnicity; low body weight; cognitive impairment; physical impairments; and comorbid conditions that may affect soft-tissue integrity and healing, such as urinary or fecal incontinence, diabetes, edema, impaired microcirculation, hypoalbuminemia, and malnutrition, Dr. Qaseem and his associates wrote (Ann. Intern. Med. 2015 March 2 [doi:10.7326/M14-1567]).

The treatment guideline for patients who already have pressure ulcers similarly notes that the lack of evidence for advanced support surfaces such as alternating-air and low-air-loss mattresses and overlays. It similarly recommends advanced static mattresses or overlays for these patients.

The treatment guideline recommends protein or amino acid supplements as well as hydrocolloid or foam dressings to reduce wound size, and electrical stimulation to accelerate wound healing. The evidence for these recommendations is “weak” and of low- to moderate-quality, Dr. Qaseem and his associates said (Ann. Intern. Med. 2015 March 2 [doi:10.7326/M14-1568]).

The evidence for the safety and efficacy of hyperbaric oxygen therapy, even though it is often used to treat pressure ulcers in hospitals, is similarly inconclusive. Also lacking good-quality evidence are the use of alternating-air chair cushions, three-dimensional polyester overlays, zinc supplements, L-carnosine supplements, wound dressings other than the ones already discussed, debriding enzymes, topical phenytoin, maggot therapy, biological agents other than platelet-derived growth factor, or hydrotherapy in which wounds are cleaned using a whirlpool or pulsed lavage.

Alternating-air and low-air-loss mattresses and overlays have little data to support their use for preventing or treating pressure ulcers, the Clinical Guidelines Committee of the American College of Physicians has concluded.

Many U.S. acute-care hospitals, home caregivers, and long-term nursing facilities use alternating-air and low-air-loss mattresses and overlays, even though the evidence in favor of using these surfaces is sparse and of poor quality, the guideline writers said.

The devices have not been show to actually reduce pressure ulcers. The harms have been poorly reported but could be significant. “Using these support systems is expensive and adds unnecessary burden on the health care system. Based on a review of the current evidence, lower-cost support surfaces should be the preferred approach to care,” Dr. Amir Qaseem, of the ACP, Philadelphia, and his associates wrote.

The committee performed an extensive review of the literature on pressure ulcers and compiled two Clinical Practice Guidelines – one concerning prevention (Ann. Intern. Med. 2015;162 [doi:10.7326/M14-1567]) and the other concerning treatment (Ann. Intern. Med. 2015;162 [doi:10.7326/M14-1568]) – in part because “a growing industry” has developed in recent years and aggressively pitches a wide array of products for this patient population. The guidelines present the available evidence on the comparative effectiveness of tools and strategies but state repeatedly that evidence regarding pressure ulcers is sparse and of poor quality.

The prevention guideline strongly recommends that clinicians choose advanced static mattresses or advanced static overlays rather than standard hospital mattresses for at-risk patients. Static mattresses and advanced static overlays provide a constant level of inflation or support and evenly distribute body weight. These products are among the few actually shown to reduce the incidence of pressure ulcers. They are also preferable to alternating-air mattresses and overlays, which change the distribution of pressure by inflating or deflating cells within the devices, and to low-air-loss mattresses and overlays, which use flowing air to regulate heat and humidity and adjust pressure.

Evidence is similarly poor or lacking concerning the use of other support surfaces such as heel supports or boots and a variety of wheelchair cushions. Also lacking evidence are other preventive interventions that extend beyond “usual care,” such as different types of repositioning schemes, a variety of leg elevations, various nutritional supplements, and a wide variety of skin care strategies and topical treatments.

The prevention guideline advises patient assessments to identify those at risk of developing pressure ulcers. However, there is not enough evidence to demonstrate that any one of the many risk assessment tools for this purpose is superior to the others, nor that any of these tools is superior to simple clinical judgment. Risk factors for pressure ulcers include older age; black race or Hispanic ethnicity; low body weight; cognitive impairment; physical impairments; and comorbid conditions that may affect soft-tissue integrity and healing, such as urinary or fecal incontinence, diabetes, edema, impaired microcirculation, hypoalbuminemia, and malnutrition, Dr. Qaseem and his associates wrote (Ann. Intern. Med. 2015 March 2 [doi:10.7326/M14-1567]).

The treatment guideline for patients who already have pressure ulcers similarly notes that the lack of evidence for advanced support surfaces such as alternating-air and low-air-loss mattresses and overlays. It similarly recommends advanced static mattresses or overlays for these patients.

The treatment guideline recommends protein or amino acid supplements as well as hydrocolloid or foam dressings to reduce wound size, and electrical stimulation to accelerate wound healing. The evidence for these recommendations is “weak” and of low- to moderate-quality, Dr. Qaseem and his associates said (Ann. Intern. Med. 2015 March 2 [doi:10.7326/M14-1568]).

The evidence for the safety and efficacy of hyperbaric oxygen therapy, even though it is often used to treat pressure ulcers in hospitals, is similarly inconclusive. Also lacking good-quality evidence are the use of alternating-air chair cushions, three-dimensional polyester overlays, zinc supplements, L-carnosine supplements, wound dressings other than the ones already discussed, debriding enzymes, topical phenytoin, maggot therapy, biological agents other than platelet-derived growth factor, or hydrotherapy in which wounds are cleaned using a whirlpool or pulsed lavage.

Alternating-air and low-air-loss mattresses and overlays have little data to support their use for preventing or treating pressure ulcers, the Clinical Guidelines Committee of the American College of Physicians has concluded.

Many U.S. acute-care hospitals, home caregivers, and long-term nursing facilities use alternating-air and low-air-loss mattresses and overlays, even though the evidence in favor of using these surfaces is sparse and of poor quality, the guideline writers said.

The devices have not been show to actually reduce pressure ulcers. The harms have been poorly reported but could be significant. “Using these support systems is expensive and adds unnecessary burden on the health care system. Based on a review of the current evidence, lower-cost support surfaces should be the preferred approach to care,” Dr. Amir Qaseem, of the ACP, Philadelphia, and his associates wrote.

The committee performed an extensive review of the literature on pressure ulcers and compiled two Clinical Practice Guidelines – one concerning prevention (Ann. Intern. Med. 2015;162 [doi:10.7326/M14-1567]) and the other concerning treatment (Ann. Intern. Med. 2015;162 [doi:10.7326/M14-1568]) – in part because “a growing industry” has developed in recent years and aggressively pitches a wide array of products for this patient population. The guidelines present the available evidence on the comparative effectiveness of tools and strategies but state repeatedly that evidence regarding pressure ulcers is sparse and of poor quality.

The prevention guideline strongly recommends that clinicians choose advanced static mattresses or advanced static overlays rather than standard hospital mattresses for at-risk patients. Static mattresses and advanced static overlays provide a constant level of inflation or support and evenly distribute body weight. These products are among the few actually shown to reduce the incidence of pressure ulcers. They are also preferable to alternating-air mattresses and overlays, which change the distribution of pressure by inflating or deflating cells within the devices, and to low-air-loss mattresses and overlays, which use flowing air to regulate heat and humidity and adjust pressure.

Evidence is similarly poor or lacking concerning the use of other support surfaces such as heel supports or boots and a variety of wheelchair cushions. Also lacking evidence are other preventive interventions that extend beyond “usual care,” such as different types of repositioning schemes, a variety of leg elevations, various nutritional supplements, and a wide variety of skin care strategies and topical treatments.

The prevention guideline advises patient assessments to identify those at risk of developing pressure ulcers. However, there is not enough evidence to demonstrate that any one of the many risk assessment tools for this purpose is superior to the others, nor that any of these tools is superior to simple clinical judgment. Risk factors for pressure ulcers include older age; black race or Hispanic ethnicity; low body weight; cognitive impairment; physical impairments; and comorbid conditions that may affect soft-tissue integrity and healing, such as urinary or fecal incontinence, diabetes, edema, impaired microcirculation, hypoalbuminemia, and malnutrition, Dr. Qaseem and his associates wrote (Ann. Intern. Med. 2015 March 2 [doi:10.7326/M14-1567]).

The treatment guideline for patients who already have pressure ulcers similarly notes that the lack of evidence for advanced support surfaces such as alternating-air and low-air-loss mattresses and overlays. It similarly recommends advanced static mattresses or overlays for these patients.

The treatment guideline recommends protein or amino acid supplements as well as hydrocolloid or foam dressings to reduce wound size, and electrical stimulation to accelerate wound healing. The evidence for these recommendations is “weak” and of low- to moderate-quality, Dr. Qaseem and his associates said (Ann. Intern. Med. 2015 March 2 [doi:10.7326/M14-1568]).

The evidence for the safety and efficacy of hyperbaric oxygen therapy, even though it is often used to treat pressure ulcers in hospitals, is similarly inconclusive. Also lacking good-quality evidence are the use of alternating-air chair cushions, three-dimensional polyester overlays, zinc supplements, L-carnosine supplements, wound dressings other than the ones already discussed, debriding enzymes, topical phenytoin, maggot therapy, biological agents other than platelet-derived growth factor, or hydrotherapy in which wounds are cleaned using a whirlpool or pulsed lavage.

An inherited genetic mutation in the CEP72 gene appears to predispose carriers to develop peripheral neuropathy when they are treated with vincristine, according to a report published online Feb. 24 in JAMA.

The genetic variation, a single nucleotide polymorphism (SNP) in the T allele at rs924607 in the promoter region of the CEP72 gene, was identified in a genome-wide association study that analyzed DNA samples from 321 children with acute lymphoblastic leukemia who received standard vincristine therapy while participating in two prospective clinical trials. Carriers had both a higher incidence and a greater severity of vincristine-induced peripheral neuropathy than noncarriers. Moreover, the risk of neuropathy increased in a linear fashion as the number of copies of the risk allele increased, said Barthelemy Diouf, Pharm.D., Ph.D., of the hematological malignancies program in the department of pharmaceutical sciences, St. Jude’s Children’s Research Hospital, Memphis, and his associates.

Vincristine is one of the most frequently used and effective agents for treating leukemias, lymphomas, brain tumors, and solid tumors in both children and adults. If the findings of this preliminary study are replicated in future research, they “may provide a basis for safer dosing of this widely prescribed anticancer agent,” the investigators noted.

Vincristine-induced peripheral neuropathy is characterized by pain as well as sensory and motor dysfunction that causes extensive morbidity, including impaired manual dexterity, impaired balance and deep-tendon reflexes, and altered gait. At present there is no way to identify which patients will develop this toxicity and no strategy for mitigating it.

The disorder occurs at different rates in various races and is known to develop less frequently in African-Americans than in members of other racial groups.

To explore whether there might be a genetic basis for this discrepancy and to identify possible polymorphisms associated with the disorder, Dr. Diouf and his associates performed a genome-wide association study using germline DNA samples collected from children participating in two clinical trials. One cohort involved children with newly diagnosed ALL who were enrolled in 1994-1998 (222 patients); the other cohort involved children with relapsed ALL who were enrolled in 2007-2010 (99 patients). All the study participants were followed for toxic effects through 2011. Vincristine-induced peripheral neuropathy developed in 28.8% of the first cohort and 22.2% of the second.

The researchers found 5,051 typed SNPs and 10,195 imputed SNPs that occurred with some frequency in both study groups, but only rs924607 on the CEP72 gene on chromosome 5 was significantly related to the development of vincristine-induced peripheral neuropathy. In the first cohort, 20 of 32 patients (62%) with the TT genotype had at least one episode of the disorder, as did 8 of 18 patients (44%) in the second cohort. Fewer patients with the CC or CT genotypes (21%) did so, indicating a dose-response relationship between the number of copies of the risk allele and the likelihood of developing vincristine-induced neuropathy.

In this analysis of the data, the alleic odds ratios for the development of neuropathy among rs924607 carriers were 2.43 in the first cohort and 4.1 in the second, the investigators reported (JAMA 2015 Feb. 24 [doi:10.1001/jama.2015.0894]).

Another analysis showed that the cumulative incidence of all neuropathy episodes differed significantly by CEP72 genotype in both study cohorts. Similarly, the cumulative incidence of severe neuropathy episodes also was significantly higher in patients homozygous for the CEP72 risk allele. Approximately 55% of patients with the TT genotype developed grade 2-4 neuropathy, compared with only 20% of those with the CC or CT genotype.

In addition, the median time to the first episode of neuropathy was significantly shorter in carriers than in noncarriers of the CEP72 polymorphism. The average time was 225 days in patients with the TT genotype, compared with 307 days in those with the CT or CC genotype. The grade (severity) of neuropathy also correlated with the number of copies of the risk allele patients carried: It was nearly three times higher in patients with the TT genotype and 1.5 times higher in those with the CT or CC genotypes than in noncarriers.

African-American patients were less likely to carry the CEP72 polymorphism than were other racial groups, which is consistent with their lower incidence of vincristine-induced neuropathy, Dr. Diouf and his associates said.

If these findings are verified in other patient populations, it could lead to a new approach for identifying patients who are susceptible to vincristine-induced neuropathy. As important, the data also suggest that the leukemia cells of patients who are homozygous for the CEP72 risk allele are more sensitive to vincristine than are the leukemia cells of other patients. If that is confirmed, “it may be possible to treat these patients with a lower dose of vincristine to decrease the risk or severity of neuropathy without compromising the antileukemic effects of” the drug, they added.

An inherited genetic mutation in the CEP72 gene appears to predispose carriers to develop peripheral neuropathy when they are treated with vincristine, according to a report published online Feb. 24 in JAMA.

The genetic variation, a single nucleotide polymorphism (SNP) in the T allele at rs924607 in the promoter region of the CEP72 gene, was identified in a genome-wide association study that analyzed DNA samples from 321 children with acute lymphoblastic leukemia who received standard vincristine therapy while participating in two prospective clinical trials. Carriers had both a higher incidence and a greater severity of vincristine-induced peripheral neuropathy than noncarriers. Moreover, the risk of neuropathy increased in a linear fashion as the number of copies of the risk allele increased, said Barthelemy Diouf, Pharm.D., Ph.D., of the hematological malignancies program in the department of pharmaceutical sciences, St. Jude’s Children’s Research Hospital, Memphis, and his associates.

Vincristine is one of the most frequently used and effective agents for treating leukemias, lymphomas, brain tumors, and solid tumors in both children and adults. If the findings of this preliminary study are replicated in future research, they “may provide a basis for safer dosing of this widely prescribed anticancer agent,” the investigators noted.

Vincristine-induced peripheral neuropathy is characterized by pain as well as sensory and motor dysfunction that causes extensive morbidity, including impaired manual dexterity, impaired balance and deep-tendon reflexes, and altered gait. At present there is no way to identify which patients will develop this toxicity and no strategy for mitigating it.

The disorder occurs at different rates in various races and is known to develop less frequently in African-Americans than in members of other racial groups.

To explore whether there might be a genetic basis for this discrepancy and to identify possible polymorphisms associated with the disorder, Dr. Diouf and his associates performed a genome-wide association study using germline DNA samples collected from children participating in two clinical trials. One cohort involved children with newly diagnosed ALL who were enrolled in 1994-1998 (222 patients); the other cohort involved children with relapsed ALL who were enrolled in 2007-2010 (99 patients). All the study participants were followed for toxic effects through 2011. Vincristine-induced peripheral neuropathy developed in 28.8% of the first cohort and 22.2% of the second.

The researchers found 5,051 typed SNPs and 10,195 imputed SNPs that occurred with some frequency in both study groups, but only rs924607 on the CEP72 gene on chromosome 5 was significantly related to the development of vincristine-induced peripheral neuropathy. In the first cohort, 20 of 32 patients (62%) with the TT genotype had at least one episode of the disorder, as did 8 of 18 patients (44%) in the second cohort. Fewer patients with the CC or CT genotypes (21%) did so, indicating a dose-response relationship between the number of copies of the risk allele and the likelihood of developing vincristine-induced neuropathy.

In this analysis of the data, the alleic odds ratios for the development of neuropathy among rs924607 carriers were 2.43 in the first cohort and 4.1 in the second, the investigators reported (JAMA 2015 Feb. 24 [doi:10.1001/jama.2015.0894]).

Another analysis showed that the cumulative incidence of all neuropathy episodes differed significantly by CEP72 genotype in both study cohorts. Similarly, the cumulative incidence of severe neuropathy episodes also was significantly higher in patients homozygous for the CEP72 risk allele. Approximately 55% of patients with the TT genotype developed grade 2-4 neuropathy, compared with only 20% of those with the CC or CT genotype.

In addition, the median time to the first episode of neuropathy was significantly shorter in carriers than in noncarriers of the CEP72 polymorphism. The average time was 225 days in patients with the TT genotype, compared with 307 days in those with the CT or CC genotype. The grade (severity) of neuropathy also correlated with the number of copies of the risk allele patients carried: It was nearly three times higher in patients with the TT genotype and 1.5 times higher in those with the CT or CC genotypes than in noncarriers.

African-American patients were less likely to carry the CEP72 polymorphism than were other racial groups, which is consistent with their lower incidence of vincristine-induced neuropathy, Dr. Diouf and his associates said.

If these findings are verified in other patient populations, it could lead to a new approach for identifying patients who are susceptible to vincristine-induced neuropathy. As important, the data also suggest that the leukemia cells of patients who are homozygous for the CEP72 risk allele are more sensitive to vincristine than are the leukemia cells of other patients. If that is confirmed, “it may be possible to treat these patients with a lower dose of vincristine to decrease the risk or severity of neuropathy without compromising the antileukemic effects of” the drug, they added.

An inherited genetic mutation in the CEP72 gene appears to predispose carriers to develop peripheral neuropathy when they are treated with vincristine, according to a report published online Feb. 24 in JAMA.

The genetic variation, a single nucleotide polymorphism (SNP) in the T allele at rs924607 in the promoter region of the CEP72 gene, was identified in a genome-wide association study that analyzed DNA samples from 321 children with acute lymphoblastic leukemia who received standard vincristine therapy while participating in two prospective clinical trials. Carriers had both a higher incidence and a greater severity of vincristine-induced peripheral neuropathy than noncarriers. Moreover, the risk of neuropathy increased in a linear fashion as the number of copies of the risk allele increased, said Barthelemy Diouf, Pharm.D., Ph.D., of the hematological malignancies program in the department of pharmaceutical sciences, St. Jude’s Children’s Research Hospital, Memphis, and his associates.

Vincristine is one of the most frequently used and effective agents for treating leukemias, lymphomas, brain tumors, and solid tumors in both children and adults. If the findings of this preliminary study are replicated in future research, they “may provide a basis for safer dosing of this widely prescribed anticancer agent,” the investigators noted.

Vincristine-induced peripheral neuropathy is characterized by pain as well as sensory and motor dysfunction that causes extensive morbidity, including impaired manual dexterity, impaired balance and deep-tendon reflexes, and altered gait. At present there is no way to identify which patients will develop this toxicity and no strategy for mitigating it.

The disorder occurs at different rates in various races and is known to develop less frequently in African-Americans than in members of other racial groups.

To explore whether there might be a genetic basis for this discrepancy and to identify possible polymorphisms associated with the disorder, Dr. Diouf and his associates performed a genome-wide association study using germline DNA samples collected from children participating in two clinical trials. One cohort involved children with newly diagnosed ALL who were enrolled in 1994-1998 (222 patients); the other cohort involved children with relapsed ALL who were enrolled in 2007-2010 (99 patients). All the study participants were followed for toxic effects through 2011. Vincristine-induced peripheral neuropathy developed in 28.8% of the first cohort and 22.2% of the second.

The researchers found 5,051 typed SNPs and 10,195 imputed SNPs that occurred with some frequency in both study groups, but only rs924607 on the CEP72 gene on chromosome 5 was significantly related to the development of vincristine-induced peripheral neuropathy. In the first cohort, 20 of 32 patients (62%) with the TT genotype had at least one episode of the disorder, as did 8 of 18 patients (44%) in the second cohort. Fewer patients with the CC or CT genotypes (21%) did so, indicating a dose-response relationship between the number of copies of the risk allele and the likelihood of developing vincristine-induced neuropathy.

In this analysis of the data, the alleic odds ratios for the development of neuropathy among rs924607 carriers were 2.43 in the first cohort and 4.1 in the second, the investigators reported (JAMA 2015 Feb. 24 [doi:10.1001/jama.2015.0894]).

Another analysis showed that the cumulative incidence of all neuropathy episodes differed significantly by CEP72 genotype in both study cohorts. Similarly, the cumulative incidence of severe neuropathy episodes also was significantly higher in patients homozygous for the CEP72 risk allele. Approximately 55% of patients with the TT genotype developed grade 2-4 neuropathy, compared with only 20% of those with the CC or CT genotype.

In addition, the median time to the first episode of neuropathy was significantly shorter in carriers than in noncarriers of the CEP72 polymorphism. The average time was 225 days in patients with the TT genotype, compared with 307 days in those with the CT or CC genotype. The grade (severity) of neuropathy also correlated with the number of copies of the risk allele patients carried: It was nearly three times higher in patients with the TT genotype and 1.5 times higher in those with the CT or CC genotypes than in noncarriers.

African-American patients were less likely to carry the CEP72 polymorphism than were other racial groups, which is consistent with their lower incidence of vincristine-induced neuropathy, Dr. Diouf and his associates said.

If these findings are verified in other patient populations, it could lead to a new approach for identifying patients who are susceptible to vincristine-induced neuropathy. As important, the data also suggest that the leukemia cells of patients who are homozygous for the CEP72 risk allele are more sensitive to vincristine than are the leukemia cells of other patients. If that is confirmed, “it may be possible to treat these patients with a lower dose of vincristine to decrease the risk or severity of neuropathy without compromising the antileukemic effects of” the drug, they added.