Mary Ann Moon

The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence, according to in vitro analyses.

C. auris first attracted attention in 2009 because of its resistance to azoles and amphotericin B. Since then, it has been identified as the cause of life-threatening invasive infections worldwide, including hospital outbreaks across Asia and South America, wrote Leighann Sherry, PhD, a medical mycologist at the University of Glasgow, and her associates.

To determine whether the pathogen has the capacity to form biofilms, the investigators propagated several different strains in the laboratory and examined their development. In three separate trials, eight samples of each strain grew biofilms, which constitute “a key driver of candida pathogenicity.” In antifungal susceptibility tests, caspofungin was completely ineffective, an unexpected finding because the agent usually is highly effective against other candida species. Amphotericin B, liposomal amphotericin B, and fluconazole also were ineffective; micafungin and chlorhexidine were the most effective at clearing C. auris.

Biofilm formation “contributes not only to C. auris virulence but also to its [resistance] in hospital environments, increasing its ability to cause outbreaks,” Dr. Sherry and her associates said (Emerg. Infect. Dis. 2017 Feb;23[2]:328-31).

“Our findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone,” they noted, adding that “infection-prevention measures targeting C. auris biofilms in patients, on medical devices, and in the hospital environment will be required,” they noted.

The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence, according to in vitro analyses.

C. auris first attracted attention in 2009 because of its resistance to azoles and amphotericin B. Since then, it has been identified as the cause of life-threatening invasive infections worldwide, including hospital outbreaks across Asia and South America, wrote Leighann Sherry, PhD, a medical mycologist at the University of Glasgow, and her associates.

To determine whether the pathogen has the capacity to form biofilms, the investigators propagated several different strains in the laboratory and examined their development. In three separate trials, eight samples of each strain grew biofilms, which constitute “a key driver of candida pathogenicity.” In antifungal susceptibility tests, caspofungin was completely ineffective, an unexpected finding because the agent usually is highly effective against other candida species. Amphotericin B, liposomal amphotericin B, and fluconazole also were ineffective; micafungin and chlorhexidine were the most effective at clearing C. auris.

Biofilm formation “contributes not only to C. auris virulence but also to its [resistance] in hospital environments, increasing its ability to cause outbreaks,” Dr. Sherry and her associates said (Emerg. Infect. Dis. 2017 Feb;23[2]:328-31).

“Our findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone,” they noted, adding that “infection-prevention measures targeting C. auris biofilms in patients, on medical devices, and in the hospital environment will be required,” they noted.

The emerging multidrug-resistant yeast organism Candida auris forms biofilms that enhance both its resistance and its virulence, according to in vitro analyses.

C. auris first attracted attention in 2009 because of its resistance to azoles and amphotericin B. Since then, it has been identified as the cause of life-threatening invasive infections worldwide, including hospital outbreaks across Asia and South America, wrote Leighann Sherry, PhD, a medical mycologist at the University of Glasgow, and her associates.

To determine whether the pathogen has the capacity to form biofilms, the investigators propagated several different strains in the laboratory and examined their development. In three separate trials, eight samples of each strain grew biofilms, which constitute “a key driver of candida pathogenicity.” In antifungal susceptibility tests, caspofungin was completely ineffective, an unexpected finding because the agent usually is highly effective against other candida species. Amphotericin B, liposomal amphotericin B, and fluconazole also were ineffective; micafungin and chlorhexidine were the most effective at clearing C. auris.

Biofilm formation “contributes not only to C. auris virulence but also to its [resistance] in hospital environments, increasing its ability to cause outbreaks,” Dr. Sherry and her associates said (Emerg. Infect. Dis. 2017 Feb;23[2]:328-31).

“Our findings suggest it is improbable that the spread and prevalence of C. auris can be controlled with antifungal stewardship approaches alone,” they noted, adding that “infection-prevention measures targeting C. auris biofilms in patients, on medical devices, and in the hospital environment will be required,” they noted.

B-cell gene expression in the peripheral blood strongly correlates with the extent of gluten-induced damage to the intestinal mucosa in patients with celiac disease, according to a report in Cellular and Molecular Gastroenterology and Hepatology.

If this finding from a single-center cohort study is validated in other patient populations, the B-cell signature may become a useful, minimally invasive tool for diagnosing celiac disease. Eventually, if biomarkers are developed from the peripheral B-cell signature, a simple blood test could be used for monitoring changes in gut inflammation over time as well as treatment response, said Mitchell E. Garber, PhD, of Alvine Pharmaceuticals, San Carlos, Calif., and the department of chemistry at Stanford University, and his associates.

However, it would be “premature but intriguing” to speculate about using this discovery to devise new, B cell–centered treatments for celiac disease, they added.

Noting that an inflammatory, gluten-induced immune response in the gut can be reflected in the peripheral blood, the investigators assessed whether a 6-week gluten challenge would induce damage to the small intestine that would show up in B-cell gene expression detected in blood samples. They assigned 73 patients at a single medical center in Finland to follow their usual gluten-free diets but to ingest an additional 6 g (20 patients), 3 g (26 patients), or 1.5 g (27 patients) of wheat gluten with a meal once per day for the study period.

The study participants (median age, 59 years; range, 23-74 years) underwent small-bowel biopsies obtained from the descending duodenum at baseline and after the gluten challenge. Damage to the intestinal mucosa was assessed by measuring the ratio of the height of the intestinal villi to the depth of the proliferative crypts at the base of the villi (villi height to crypt depth, or Vh:Cd). In celiac disease, gluten blunts the projection of the villi and causes hypertrophy or elongation of the crypts, resulting in flattened mucosa and a Vh:Cd approaching zero.

The study participants showed a wide variation in mucosal damage from the gluten exposure, with some patients showing no change and relatively healthy mucosa, and others showing extensive change and nearly flattened mucosa. The mucosal damage did not differ by gluten dose.

The largest change in Vh:Cd occurred in three patients who transitioned from relatively healthy intestinal mucosa (Vh:Cd 3.1) at baseline to nearly flat mucosa (Vh:Cd 0.2) after gluten exposure.

Patients with undamaged gut mucosa showed a relative increase in B-cell gene expression during the study period, while those who had increasing damage showed a relative decrease in B-cell expression. “The peripheral B cell therefore tracked with oral tolerance across the full spectrum of intestinal damage, from no change to a nearly flat mucosa,” Dr. Garber and his associates said (Cell Molec Gastroenterol Hepatol. 2017. doi: 10.1016/j.jcmgh.2017.01.011).

“The net increase in B-cell gene expression from baseline to 6 weeks in patients with little to no intestinal damage [suggests] that these individuals may have mounted a B-cell immune response to maintain mucosal homeostasis and circumvent inflammation,” they added.

Further study is needed to determine whether peripheral B cells are a marker that indicates tolerance to gluten but doesn’t play a functional role in the inflammatory process, or whether B cells may actually promote immune tolerance, the investigators said.

This study was funded by Alvine Pharmaceuticals, the American Recovery and Reinvestment Act, Tampere (Finland) University Hospital, the Academy of Finland Research Council for Health, and the U.S. National Institutes of Health. Dr. Garber reported ties to Alvine Pharmaceuticals, and his associates reported ties to ImmusanT, Celimmune, and ImmunogenX.

B-cell gene expression in the peripheral blood strongly correlates with the extent of gluten-induced damage to the intestinal mucosa in patients with celiac disease, according to a report in Cellular and Molecular Gastroenterology and Hepatology.

If this finding from a single-center cohort study is validated in other patient populations, the B-cell signature may become a useful, minimally invasive tool for diagnosing celiac disease. Eventually, if biomarkers are developed from the peripheral B-cell signature, a simple blood test could be used for monitoring changes in gut inflammation over time as well as treatment response, said Mitchell E. Garber, PhD, of Alvine Pharmaceuticals, San Carlos, Calif., and the department of chemistry at Stanford University, and his associates.

However, it would be “premature but intriguing” to speculate about using this discovery to devise new, B cell–centered treatments for celiac disease, they added.

Noting that an inflammatory, gluten-induced immune response in the gut can be reflected in the peripheral blood, the investigators assessed whether a 6-week gluten challenge would induce damage to the small intestine that would show up in B-cell gene expression detected in blood samples. They assigned 73 patients at a single medical center in Finland to follow their usual gluten-free diets but to ingest an additional 6 g (20 patients), 3 g (26 patients), or 1.5 g (27 patients) of wheat gluten with a meal once per day for the study period.

The study participants (median age, 59 years; range, 23-74 years) underwent small-bowel biopsies obtained from the descending duodenum at baseline and after the gluten challenge. Damage to the intestinal mucosa was assessed by measuring the ratio of the height of the intestinal villi to the depth of the proliferative crypts at the base of the villi (villi height to crypt depth, or Vh:Cd). In celiac disease, gluten blunts the projection of the villi and causes hypertrophy or elongation of the crypts, resulting in flattened mucosa and a Vh:Cd approaching zero.

The study participants showed a wide variation in mucosal damage from the gluten exposure, with some patients showing no change and relatively healthy mucosa, and others showing extensive change and nearly flattened mucosa. The mucosal damage did not differ by gluten dose.

The largest change in Vh:Cd occurred in three patients who transitioned from relatively healthy intestinal mucosa (Vh:Cd 3.1) at baseline to nearly flat mucosa (Vh:Cd 0.2) after gluten exposure.

Patients with undamaged gut mucosa showed a relative increase in B-cell gene expression during the study period, while those who had increasing damage showed a relative decrease in B-cell expression. “The peripheral B cell therefore tracked with oral tolerance across the full spectrum of intestinal damage, from no change to a nearly flat mucosa,” Dr. Garber and his associates said (Cell Molec Gastroenterol Hepatol. 2017. doi: 10.1016/j.jcmgh.2017.01.011).

“The net increase in B-cell gene expression from baseline to 6 weeks in patients with little to no intestinal damage [suggests] that these individuals may have mounted a B-cell immune response to maintain mucosal homeostasis and circumvent inflammation,” they added.

Further study is needed to determine whether peripheral B cells are a marker that indicates tolerance to gluten but doesn’t play a functional role in the inflammatory process, or whether B cells may actually promote immune tolerance, the investigators said.

This study was funded by Alvine Pharmaceuticals, the American Recovery and Reinvestment Act, Tampere (Finland) University Hospital, the Academy of Finland Research Council for Health, and the U.S. National Institutes of Health. Dr. Garber reported ties to Alvine Pharmaceuticals, and his associates reported ties to ImmusanT, Celimmune, and ImmunogenX.

B-cell gene expression in the peripheral blood strongly correlates with the extent of gluten-induced damage to the intestinal mucosa in patients with celiac disease, according to a report in Cellular and Molecular Gastroenterology and Hepatology.

If this finding from a single-center cohort study is validated in other patient populations, the B-cell signature may become a useful, minimally invasive tool for diagnosing celiac disease. Eventually, if biomarkers are developed from the peripheral B-cell signature, a simple blood test could be used for monitoring changes in gut inflammation over time as well as treatment response, said Mitchell E. Garber, PhD, of Alvine Pharmaceuticals, San Carlos, Calif., and the department of chemistry at Stanford University, and his associates.

However, it would be “premature but intriguing” to speculate about using this discovery to devise new, B cell–centered treatments for celiac disease, they added.

Noting that an inflammatory, gluten-induced immune response in the gut can be reflected in the peripheral blood, the investigators assessed whether a 6-week gluten challenge would induce damage to the small intestine that would show up in B-cell gene expression detected in blood samples. They assigned 73 patients at a single medical center in Finland to follow their usual gluten-free diets but to ingest an additional 6 g (20 patients), 3 g (26 patients), or 1.5 g (27 patients) of wheat gluten with a meal once per day for the study period.

The study participants (median age, 59 years; range, 23-74 years) underwent small-bowel biopsies obtained from the descending duodenum at baseline and after the gluten challenge. Damage to the intestinal mucosa was assessed by measuring the ratio of the height of the intestinal villi to the depth of the proliferative crypts at the base of the villi (villi height to crypt depth, or Vh:Cd). In celiac disease, gluten blunts the projection of the villi and causes hypertrophy or elongation of the crypts, resulting in flattened mucosa and a Vh:Cd approaching zero.

The study participants showed a wide variation in mucosal damage from the gluten exposure, with some patients showing no change and relatively healthy mucosa, and others showing extensive change and nearly flattened mucosa. The mucosal damage did not differ by gluten dose.

The largest change in Vh:Cd occurred in three patients who transitioned from relatively healthy intestinal mucosa (Vh:Cd 3.1) at baseline to nearly flat mucosa (Vh:Cd 0.2) after gluten exposure.

Patients with undamaged gut mucosa showed a relative increase in B-cell gene expression during the study period, while those who had increasing damage showed a relative decrease in B-cell expression. “The peripheral B cell therefore tracked with oral tolerance across the full spectrum of intestinal damage, from no change to a nearly flat mucosa,” Dr. Garber and his associates said (Cell Molec Gastroenterol Hepatol. 2017. doi: 10.1016/j.jcmgh.2017.01.011).

“The net increase in B-cell gene expression from baseline to 6 weeks in patients with little to no intestinal damage [suggests] that these individuals may have mounted a B-cell immune response to maintain mucosal homeostasis and circumvent inflammation,” they added.

Further study is needed to determine whether peripheral B cells are a marker that indicates tolerance to gluten but doesn’t play a functional role in the inflammatory process, or whether B cells may actually promote immune tolerance, the investigators said.

This study was funded by Alvine Pharmaceuticals, the American Recovery and Reinvestment Act, Tampere (Finland) University Hospital, the Academy of Finland Research Council for Health, and the U.S. National Institutes of Health. Dr. Garber reported ties to Alvine Pharmaceuticals, and his associates reported ties to ImmusanT, Celimmune, and ImmunogenX.

Genetic mutations in blood samples may predict outcomes and guide treatment for patients of all ages who have myelodysplastic syndrome and are undergoing hematopoietic stem-cell transplantation, according to a report published online Feb. 8 in the New England Journal of Medicine.

Allogeneic hematopoietic stem-cell transplantation is the only potentially curative therapy currently available for myelodysplastic syndrome (MDS), but mortality due to relapse and to transplant-related complications is high. “Predicting which patients are most likely to benefit from transplantation is thus a central challenge,” and identifying patients most likely to relapse could help clinicians refine conditioning regimens and relapse-prevention strategies, said R. Coleman Lindsley, MD, PhD, of the division of hematological malignancies, Dana-Farber Cancer Institute, Boston, and his associates.

SilverV/thinkstockphotos

Genetic mutations in blood samples may predict outcomes and guide treatment for patients of all ages who have myelodysplastic syndrome and are undergoing hematopoietic stem-cell transplantation, according to a report published online Feb. 8 in the New England Journal of Medicine.

Allogeneic hematopoietic stem-cell transplantation is the only potentially curative therapy currently available for myelodysplastic syndrome (MDS), but mortality due to relapse and to transplant-related complications is high. “Predicting which patients are most likely to benefit from transplantation is thus a central challenge,” and identifying patients most likely to relapse could help clinicians refine conditioning regimens and relapse-prevention strategies, said R. Coleman Lindsley, MD, PhD, of the division of hematological malignancies, Dana-Farber Cancer Institute, Boston, and his associates.

SilverV/thinkstockphotos

Genetic mutations in blood samples may predict outcomes and guide treatment for patients of all ages who have myelodysplastic syndrome and are undergoing hematopoietic stem-cell transplantation, according to a report published online Feb. 8 in the New England Journal of Medicine.

Allogeneic hematopoietic stem-cell transplantation is the only potentially curative therapy currently available for myelodysplastic syndrome (MDS), but mortality due to relapse and to transplant-related complications is high. “Predicting which patients are most likely to benefit from transplantation is thus a central challenge,” and identifying patients most likely to relapse could help clinicians refine conditioning regimens and relapse-prevention strategies, said R. Coleman Lindsley, MD, PhD, of the division of hematological malignancies, Dana-Farber Cancer Institute, Boston, and his associates.

SilverV/thinkstockphotos

African Americans who have sickle cell trait show lower hemoglobin A_1c levels at any given concentration of fasting glucose than do those who don’t have sickle cell trait, according to a report published online Feb. 7 in JAMA.

This suggests that HbA_1c levels systematically underestimate glucose levels in black patients who carry the trait, who comprise approximately 10% of the African American population, said Mary E. Lacy, a doctoral candidate in the department of epidemiology, Brown University School of Public Health, Providence, R.I., and her associates.

The investigators examined a possible link between HbA_1c and sickle cell trait, which affects hemoglobin even though it doesn’t confer sickle cell disease, by analyzing data from two cohort studies involving African American adults. They focused on 4,620 participants who underwent serial HbA_1c and plasma glucose measurements during 5-25 years of follow-up. A total of 367 of them had sickle cell trait.

Analysis of 9,062 concurrent assessments of fasting glucose and HbA_1c plus 2,001 concurrent assessments of 2-hour postprandial glucose and HbA_1c showed mean HbA_1c was consistently significantly lower in people with sickle cell trait (mean level, 5.7%) than in those without the trait (mean level, 6%) despite similar glucose values.

“Our results suggest that currently accepted clinical measures of HbA_1c do not reflect recent past glycemia in the same way in African Americans with and without sickle cell trait,” Ms. Lacy and her associates said (JAMA 2017 Feb 7. doi: 10.1001/jama.2016.21035).

When used as a screen for prediabetes or diabetes, HbA_1c values “systematically underestimate long-term glucose levels,” which means a significant proportion of African American patients will miss the opportunity for treatment. In this study, “using standard clinical HbA_1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with sickle cell trait, compared to those without sickle cell trait,” the investigators noted.

“Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than [those of] white people, the cost of inaccurately assessing risk and treatment response is high,” they added.

The National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute on Minority Health Disparities, the Providence VA Medical Center, and the National Institute of Diabetes and Digestive and Kidney Diseases supported the study. Ms. Lacy and her associates reported having no relevant financial disclosures.

African Americans who have sickle cell trait show lower hemoglobin A_1c levels at any given concentration of fasting glucose than do those who don’t have sickle cell trait, according to a report published online Feb. 7 in JAMA.

This suggests that HbA_1c levels systematically underestimate glucose levels in black patients who carry the trait, who comprise approximately 10% of the African American population, said Mary E. Lacy, a doctoral candidate in the department of epidemiology, Brown University School of Public Health, Providence, R.I., and her associates.

The investigators examined a possible link between HbA_1c and sickle cell trait, which affects hemoglobin even though it doesn’t confer sickle cell disease, by analyzing data from two cohort studies involving African American adults. They focused on 4,620 participants who underwent serial HbA_1c and plasma glucose measurements during 5-25 years of follow-up. A total of 367 of them had sickle cell trait.

Analysis of 9,062 concurrent assessments of fasting glucose and HbA_1c plus 2,001 concurrent assessments of 2-hour postprandial glucose and HbA_1c showed mean HbA_1c was consistently significantly lower in people with sickle cell trait (mean level, 5.7%) than in those without the trait (mean level, 6%) despite similar glucose values.

“Our results suggest that currently accepted clinical measures of HbA_1c do not reflect recent past glycemia in the same way in African Americans with and without sickle cell trait,” Ms. Lacy and her associates said (JAMA 2017 Feb 7. doi: 10.1001/jama.2016.21035).

When used as a screen for prediabetes or diabetes, HbA_1c values “systematically underestimate long-term glucose levels,” which means a significant proportion of African American patients will miss the opportunity for treatment. In this study, “using standard clinical HbA_1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with sickle cell trait, compared to those without sickle cell trait,” the investigators noted.

“Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than [those of] white people, the cost of inaccurately assessing risk and treatment response is high,” they added.

The National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute on Minority Health Disparities, the Providence VA Medical Center, and the National Institute of Diabetes and Digestive and Kidney Diseases supported the study. Ms. Lacy and her associates reported having no relevant financial disclosures.

African Americans who have sickle cell trait show lower hemoglobin A_1c levels at any given concentration of fasting glucose than do those who don’t have sickle cell trait, according to a report published online Feb. 7 in JAMA.

This suggests that HbA_1c levels systematically underestimate glucose levels in black patients who carry the trait, who comprise approximately 10% of the African American population, said Mary E. Lacy, a doctoral candidate in the department of epidemiology, Brown University School of Public Health, Providence, R.I., and her associates.

The investigators examined a possible link between HbA_1c and sickle cell trait, which affects hemoglobin even though it doesn’t confer sickle cell disease, by analyzing data from two cohort studies involving African American adults. They focused on 4,620 participants who underwent serial HbA_1c and plasma glucose measurements during 5-25 years of follow-up. A total of 367 of them had sickle cell trait.

Analysis of 9,062 concurrent assessments of fasting glucose and HbA_1c plus 2,001 concurrent assessments of 2-hour postprandial glucose and HbA_1c showed mean HbA_1c was consistently significantly lower in people with sickle cell trait (mean level, 5.7%) than in those without the trait (mean level, 6%) despite similar glucose values.

“Our results suggest that currently accepted clinical measures of HbA_1c do not reflect recent past glycemia in the same way in African Americans with and without sickle cell trait,” Ms. Lacy and her associates said (JAMA 2017 Feb 7. doi: 10.1001/jama.2016.21035).

When used as a screen for prediabetes or diabetes, HbA_1c values “systematically underestimate long-term glucose levels,” which means a significant proportion of African American patients will miss the opportunity for treatment. In this study, “using standard clinical HbA_1c criteria to identify prediabetes and diabetes resulted in identifying 40% fewer cases of prediabetes and 48% fewer cases of diabetes among participants with sickle cell trait, compared to those without sickle cell trait,” the investigators noted.

“Because black people typically have a higher prevalence of diabetes and experience a number of diabetic complications at higher rates than [those of] white people, the cost of inaccurately assessing risk and treatment response is high,” they added.

The National Heart, Lung, and Blood Institute, the National Institute on Aging, the National Institute on Minority Health Disparities, the Providence VA Medical Center, and the National Institute of Diabetes and Digestive and Kidney Diseases supported the study. Ms. Lacy and her associates reported having no relevant financial disclosures.

Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.

In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.

The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.

Among the strongest recommendations based on the highest-quality evidence:

• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.

• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.

• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.

• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.

Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.

Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.

In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.

The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.

Among the strongest recommendations based on the highest-quality evidence:

• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.

• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.

• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.

• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.

Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.

Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.

In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.

The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.

Among the strongest recommendations based on the highest-quality evidence:

• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.

• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.

• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.

• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.

Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.

Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more), according to a report in the Journal of Clinical Oncology.

Endometrial cancer is the malignancy most strongly associated with obesity, but to date few studies have examined the effect of intentional weight loss on risk. Researchers analyzed data from the prospective Women’s Health Initiative to assess this relationship in a large, ethnically diverse population of postmenopausal women with detailed records on potentially confounding factors such as body mass index, smoking status, physical activity level, hormone therapy use, parity, age at menarche, age at first birth, and family history.

They focused on 36,793 women who participated in the WHI and who reported whether they had maintained a stable weight, lost 5% or more of their total weight, or gained 5% or more of their total weight during the first 3 years after enrollment. During a mean of 11.4 years of follow-up, 566 of these women developed endometrial cancer, said Juhua Luo, PhD, of the department of epidemiology and biostatistics, Indiana University School of Public Health, Bloomington, and her associates.

Women who lost weight intentionally showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71). This association was most pronounced among obese women: Those who lost at least 5% of their body weight intentionally showed a dramatic reduction in endometrial cancer risk (HR, 0.44). In contrast, unintentional weight loss was not associated with a lower risk of endometrial cancer. And women who gained 10 pounds or more during the first 3 years of the study showed a significantly higher risk of endometrial cancer, the investigators said (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.70.5822).

In a sensitivity analysis, women who intentionally lost weight and achieved a normal BMI showed the same risk of endometrial cancer as that of those who had maintained a stable BMI throughout the study.

Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more), according to a report in the Journal of Clinical Oncology.

Endometrial cancer is the malignancy most strongly associated with obesity, but to date few studies have examined the effect of intentional weight loss on risk. Researchers analyzed data from the prospective Women’s Health Initiative to assess this relationship in a large, ethnically diverse population of postmenopausal women with detailed records on potentially confounding factors such as body mass index, smoking status, physical activity level, hormone therapy use, parity, age at menarche, age at first birth, and family history.

They focused on 36,793 women who participated in the WHI and who reported whether they had maintained a stable weight, lost 5% or more of their total weight, or gained 5% or more of their total weight during the first 3 years after enrollment. During a mean of 11.4 years of follow-up, 566 of these women developed endometrial cancer, said Juhua Luo, PhD, of the department of epidemiology and biostatistics, Indiana University School of Public Health, Bloomington, and her associates.

Women who lost weight intentionally showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71). This association was most pronounced among obese women: Those who lost at least 5% of their body weight intentionally showed a dramatic reduction in endometrial cancer risk (HR, 0.44). In contrast, unintentional weight loss was not associated with a lower risk of endometrial cancer. And women who gained 10 pounds or more during the first 3 years of the study showed a significantly higher risk of endometrial cancer, the investigators said (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.70.5822).

In a sensitivity analysis, women who intentionally lost weight and achieved a normal BMI showed the same risk of endometrial cancer as that of those who had maintained a stable BMI throughout the study.

Among postmenopausal women, intentional weight loss protects against endometrial cancer, even if that loss is modest (5% or more), according to a report in the Journal of Clinical Oncology.

Endometrial cancer is the malignancy most strongly associated with obesity, but to date few studies have examined the effect of intentional weight loss on risk. Researchers analyzed data from the prospective Women’s Health Initiative to assess this relationship in a large, ethnically diverse population of postmenopausal women with detailed records on potentially confounding factors such as body mass index, smoking status, physical activity level, hormone therapy use, parity, age at menarche, age at first birth, and family history.

They focused on 36,793 women who participated in the WHI and who reported whether they had maintained a stable weight, lost 5% or more of their total weight, or gained 5% or more of their total weight during the first 3 years after enrollment. During a mean of 11.4 years of follow-up, 566 of these women developed endometrial cancer, said Juhua Luo, PhD, of the department of epidemiology and biostatistics, Indiana University School of Public Health, Bloomington, and her associates.

Women who lost weight intentionally showed a significantly lower risk of endometrial cancer than did those who had stable weight (HR, 0.71). This association was most pronounced among obese women: Those who lost at least 5% of their body weight intentionally showed a dramatic reduction in endometrial cancer risk (HR, 0.44). In contrast, unintentional weight loss was not associated with a lower risk of endometrial cancer. And women who gained 10 pounds or more during the first 3 years of the study showed a significantly higher risk of endometrial cancer, the investigators said (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.70.5822).

In a sensitivity analysis, women who intentionally lost weight and achieved a normal BMI showed the same risk of endometrial cancer as that of those who had maintained a stable BMI throughout the study.

A smaller, centrifugal-flow left ventricular assist device that lies entirely within the pericardial space was found noninferior to the HeartMate II axial-flow device in patients with advanced heart failure who weren’t eligible for heart transplant, according to a report published online Feb. 2 in the New England Journal of Medicine.

The two LVADs were compared in ENDURANCE (A Clinical Trial to Evaluate the HeartWare Ventricular Assist System), a prospective, randomized trial in 445 patients who were treated at 48 U.S. sites and followed for 2 years. The study participants had an LV ejection fraction of 25% or less and high prevalences of abnormal renal function and dependence on intravenous inotropic support, said Joseph G. Rogers, MD, of Duke University, Durham, N.C., and his associates.

The study participants were randomly assigned to receive the HeartWare, an investigational centrifugal-flow LVAD (297 patients) or the standard axial-flow HeartMate II LVAD (148 patients). In the intention-to-treat analysis, the primary endpoint – a composite of survival free from disabling stroke and no removal of the device for malfunction or failure – was 55.4% with the new device and 59.1% in the control group. The results were similar in the per-protocol and the as-treated analyses, demonstrating that the new device was noninferior but not superior to the axial-flow LVAD, the investigators said (N Engl J Med. 2017 Feb 2. doi: 10.1056/NEJMoa1602954).

There were significantly more cases of device malfunction or failure requiring urgent surgery in the control group than in the centrifugal-flow group (16.2% vs 8.8%), but significantly more cases of stroke (29.7% vs 12.1%), sepsis, and right heart failure. Rates of major bleeding, cardiac arrhythmia, renal dysfunction, and infection were similar between the two study groups. Overall survival* also was not significantly different (60.2% with the new LVAD and 67.6% in the control group).

Both study groups showed significant and comparable improvement after LVAD implantation. Functional status improved to New York Heart Association class I or II in roughly 80% of patients. Mean 6-minute walk distance improved from 100.2 to 199.4 meters with the new device and from 91.9 to 190.1 meters in the control group, a change that was noted within 3 months of surgery and persisted through the end of follow-up. Similarly, mean scores on the Kansas City Cardiomyopathy Questionnaire improved by 25.8 points and 25.3 points, respectively, and mean scores on the European Quality of Life 5 Dimensions scale improved by 22.5 points and 25.5 points, respectively.

This trial was sponsored by HeartWare, which was also involved in data management and analysis. Dr. Rogers reported having no relevant financial disclosures; his associates reported ties to HeartWare (Medtronic), Thoratec (St. Jude Medical), Novartis, and GE HealthCare.

*Correction 2/2/17: An earlier version of this article misidentified survival rates as mortality rates.

A smaller, centrifugal-flow left ventricular assist device that lies entirely within the pericardial space was found noninferior to the HeartMate II axial-flow device in patients with advanced heart failure who weren’t eligible for heart transplant, according to a report published online Feb. 2 in the New England Journal of Medicine.

The two LVADs were compared in ENDURANCE (A Clinical Trial to Evaluate the HeartWare Ventricular Assist System), a prospective, randomized trial in 445 patients who were treated at 48 U.S. sites and followed for 2 years. The study participants had an LV ejection fraction of 25% or less and high prevalences of abnormal renal function and dependence on intravenous inotropic support, said Joseph G. Rogers, MD, of Duke University, Durham, N.C., and his associates.

The study participants were randomly assigned to receive the HeartWare, an investigational centrifugal-flow LVAD (297 patients) or the standard axial-flow HeartMate II LVAD (148 patients). In the intention-to-treat analysis, the primary endpoint – a composite of survival free from disabling stroke and no removal of the device for malfunction or failure – was 55.4% with the new device and 59.1% in the control group. The results were similar in the per-protocol and the as-treated analyses, demonstrating that the new device was noninferior but not superior to the axial-flow LVAD, the investigators said (N Engl J Med. 2017 Feb 2. doi: 10.1056/NEJMoa1602954).

There were significantly more cases of device malfunction or failure requiring urgent surgery in the control group than in the centrifugal-flow group (16.2% vs 8.8%), but significantly more cases of stroke (29.7% vs 12.1%), sepsis, and right heart failure. Rates of major bleeding, cardiac arrhythmia, renal dysfunction, and infection were similar between the two study groups. Overall survival* also was not significantly different (60.2% with the new LVAD and 67.6% in the control group).

Both study groups showed significant and comparable improvement after LVAD implantation. Functional status improved to New York Heart Association class I or II in roughly 80% of patients. Mean 6-minute walk distance improved from 100.2 to 199.4 meters with the new device and from 91.9 to 190.1 meters in the control group, a change that was noted within 3 months of surgery and persisted through the end of follow-up. Similarly, mean scores on the Kansas City Cardiomyopathy Questionnaire improved by 25.8 points and 25.3 points, respectively, and mean scores on the European Quality of Life 5 Dimensions scale improved by 22.5 points and 25.5 points, respectively.

This trial was sponsored by HeartWare, which was also involved in data management and analysis. Dr. Rogers reported having no relevant financial disclosures; his associates reported ties to HeartWare (Medtronic), Thoratec (St. Jude Medical), Novartis, and GE HealthCare.

*Correction 2/2/17: An earlier version of this article misidentified survival rates as mortality rates.

A smaller, centrifugal-flow left ventricular assist device that lies entirely within the pericardial space was found noninferior to the HeartMate II axial-flow device in patients with advanced heart failure who weren’t eligible for heart transplant, according to a report published online Feb. 2 in the New England Journal of Medicine.

The two LVADs were compared in ENDURANCE (A Clinical Trial to Evaluate the HeartWare Ventricular Assist System), a prospective, randomized trial in 445 patients who were treated at 48 U.S. sites and followed for 2 years. The study participants had an LV ejection fraction of 25% or less and high prevalences of abnormal renal function and dependence on intravenous inotropic support, said Joseph G. Rogers, MD, of Duke University, Durham, N.C., and his associates.

The study participants were randomly assigned to receive the HeartWare, an investigational centrifugal-flow LVAD (297 patients) or the standard axial-flow HeartMate II LVAD (148 patients). In the intention-to-treat analysis, the primary endpoint – a composite of survival free from disabling stroke and no removal of the device for malfunction or failure – was 55.4% with the new device and 59.1% in the control group. The results were similar in the per-protocol and the as-treated analyses, demonstrating that the new device was noninferior but not superior to the axial-flow LVAD, the investigators said (N Engl J Med. 2017 Feb 2. doi: 10.1056/NEJMoa1602954).

There were significantly more cases of device malfunction or failure requiring urgent surgery in the control group than in the centrifugal-flow group (16.2% vs 8.8%), but significantly more cases of stroke (29.7% vs 12.1%), sepsis, and right heart failure. Rates of major bleeding, cardiac arrhythmia, renal dysfunction, and infection were similar between the two study groups. Overall survival* also was not significantly different (60.2% with the new LVAD and 67.6% in the control group).

Both study groups showed significant and comparable improvement after LVAD implantation. Functional status improved to New York Heart Association class I or II in roughly 80% of patients. Mean 6-minute walk distance improved from 100.2 to 199.4 meters with the new device and from 91.9 to 190.1 meters in the control group, a change that was noted within 3 months of surgery and persisted through the end of follow-up. Similarly, mean scores on the Kansas City Cardiomyopathy Questionnaire improved by 25.8 points and 25.3 points, respectively, and mean scores on the European Quality of Life 5 Dimensions scale improved by 22.5 points and 25.5 points, respectively.

This trial was sponsored by HeartWare, which was also involved in data management and analysis. Dr. Rogers reported having no relevant financial disclosures; his associates reported ties to HeartWare (Medtronic), Thoratec (St. Jude Medical), Novartis, and GE HealthCare.

*Correction 2/2/17: An earlier version of this article misidentified survival rates as mortality rates.

Adding antiandrogen treatment to salvage radiotherapy markedly improves long-term survival and disease-specific mortality, reduces the rate of distant metastases, and decreases the incidence of further recurrences in men who have an initial biochemical recurrence of prostate cancer, according to a report in the New England Journal of Medicine.

These are the long-term findings of a prospective multicenter trial begun in 1998, which compared standard radiotherapy plus daily oral bicalutamide against radiotherapy plus placebo. The survival benefit became evident only during the second decade after treatment, said William U. Shipley, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates.

During the course of this study, bicalutamide was superseded by injectable GnRH agonists as the add-on antiandrogen treatment of choice, “but the hypothesis tested in this trial remains very relevant,” they noted. “Our trial presents proof of principle that the addition of hormone-based therapy to salvage radiation therapy is associated with significant and clinically important lower rates of prostate-cancer metastases and death.”

The study involved 760 men (median age, 65 years) who had undergone radical prostatectomy with lymphadenectomy for T2 or T3 prostate cancer without nodal involvement. A median of 2 years after surgery, all of them showed rising PSA levels (biochemical recurrence) but no metastases. They were randomly assigned in a double-blind fashion to receive salvage radiotherapy plus a 2-year course of bicalutamide (384 patients) or matching placebo (376 patients) and were followed for a median of 13 years.

The primary endpoint – the rate of overall survival at 12 years – was 76.3% in the bicalutamide group and 71.3% in the placebo group, for a hazard ratio of 0.77. An estimated 20 patients would need to be treated with bicalutamide to avoid one death over a 12-year period, the investigators said (N Engl J Med. 2017 Feb 2 [doi: 10.1056/NEJMoa1607529]).

The rates of prostate cancer–specific death were 5.8% and 13.4%, respectively (HR, 0.49). The cumulative incidences of distant metastases were 14.5% vs. 23.0% (HR, 0.63), and those of biochemical recurrence were 44.0% vs. 67.9% (HR, 0.48). Post hoc subgroup analyses showed that the survival benefit was greatest among men who had the most aggressive cancers, such as those with the highest PSA levels, the highest Gleason scores, and positive rather than negative surgical margins.

Compared with placebo, bicalutamide did not exacerbate early or late bladder, bowel, hematologic, or hepatic effects of radiotherapy, and it was not associated with any increase in cardiac death, Dr. Shipley and his associates said.

The National Cancer Institute and AstraZeneca supported the trial. Dr. Shipley reported previously holding stock in PFS Genomics; his associates reported ties to numerous industry sources.

Adding antiandrogen treatment to salvage radiotherapy markedly improves long-term survival and disease-specific mortality, reduces the rate of distant metastases, and decreases the incidence of further recurrences in men who have an initial biochemical recurrence of prostate cancer, according to a report in the New England Journal of Medicine.

These are the long-term findings of a prospective multicenter trial begun in 1998, which compared standard radiotherapy plus daily oral bicalutamide against radiotherapy plus placebo. The survival benefit became evident only during the second decade after treatment, said William U. Shipley, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates.

During the course of this study, bicalutamide was superseded by injectable GnRH agonists as the add-on antiandrogen treatment of choice, “but the hypothesis tested in this trial remains very relevant,” they noted. “Our trial presents proof of principle that the addition of hormone-based therapy to salvage radiation therapy is associated with significant and clinically important lower rates of prostate-cancer metastases and death.”

The study involved 760 men (median age, 65 years) who had undergone radical prostatectomy with lymphadenectomy for T2 or T3 prostate cancer without nodal involvement. A median of 2 years after surgery, all of them showed rising PSA levels (biochemical recurrence) but no metastases. They were randomly assigned in a double-blind fashion to receive salvage radiotherapy plus a 2-year course of bicalutamide (384 patients) or matching placebo (376 patients) and were followed for a median of 13 years.

The primary endpoint – the rate of overall survival at 12 years – was 76.3% in the bicalutamide group and 71.3% in the placebo group, for a hazard ratio of 0.77. An estimated 20 patients would need to be treated with bicalutamide to avoid one death over a 12-year period, the investigators said (N Engl J Med. 2017 Feb 2 [doi: 10.1056/NEJMoa1607529]).

The rates of prostate cancer–specific death were 5.8% and 13.4%, respectively (HR, 0.49). The cumulative incidences of distant metastases were 14.5% vs. 23.0% (HR, 0.63), and those of biochemical recurrence were 44.0% vs. 67.9% (HR, 0.48). Post hoc subgroup analyses showed that the survival benefit was greatest among men who had the most aggressive cancers, such as those with the highest PSA levels, the highest Gleason scores, and positive rather than negative surgical margins.

Compared with placebo, bicalutamide did not exacerbate early or late bladder, bowel, hematologic, or hepatic effects of radiotherapy, and it was not associated with any increase in cardiac death, Dr. Shipley and his associates said.

The National Cancer Institute and AstraZeneca supported the trial. Dr. Shipley reported previously holding stock in PFS Genomics; his associates reported ties to numerous industry sources.

Adding antiandrogen treatment to salvage radiotherapy markedly improves long-term survival and disease-specific mortality, reduces the rate of distant metastases, and decreases the incidence of further recurrences in men who have an initial biochemical recurrence of prostate cancer, according to a report in the New England Journal of Medicine.

These are the long-term findings of a prospective multicenter trial begun in 1998, which compared standard radiotherapy plus daily oral bicalutamide against radiotherapy plus placebo. The survival benefit became evident only during the second decade after treatment, said William U. Shipley, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates.

During the course of this study, bicalutamide was superseded by injectable GnRH agonists as the add-on antiandrogen treatment of choice, “but the hypothesis tested in this trial remains very relevant,” they noted. “Our trial presents proof of principle that the addition of hormone-based therapy to salvage radiation therapy is associated with significant and clinically important lower rates of prostate-cancer metastases and death.”

The study involved 760 men (median age, 65 years) who had undergone radical prostatectomy with lymphadenectomy for T2 or T3 prostate cancer without nodal involvement. A median of 2 years after surgery, all of them showed rising PSA levels (biochemical recurrence) but no metastases. They were randomly assigned in a double-blind fashion to receive salvage radiotherapy plus a 2-year course of bicalutamide (384 patients) or matching placebo (376 patients) and were followed for a median of 13 years.

The primary endpoint – the rate of overall survival at 12 years – was 76.3% in the bicalutamide group and 71.3% in the placebo group, for a hazard ratio of 0.77. An estimated 20 patients would need to be treated with bicalutamide to avoid one death over a 12-year period, the investigators said (N Engl J Med. 2017 Feb 2 [doi: 10.1056/NEJMoa1607529]).

The rates of prostate cancer–specific death were 5.8% and 13.4%, respectively (HR, 0.49). The cumulative incidences of distant metastases were 14.5% vs. 23.0% (HR, 0.63), and those of biochemical recurrence were 44.0% vs. 67.9% (HR, 0.48). Post hoc subgroup analyses showed that the survival benefit was greatest among men who had the most aggressive cancers, such as those with the highest PSA levels, the highest Gleason scores, and positive rather than negative surgical margins.

Compared with placebo, bicalutamide did not exacerbate early or late bladder, bowel, hematologic, or hepatic effects of radiotherapy, and it was not associated with any increase in cardiac death, Dr. Shipley and his associates said.

The National Cancer Institute and AstraZeneca supported the trial. Dr. Shipley reported previously holding stock in PFS Genomics; his associates reported ties to numerous industry sources.

A 12-week course of daily oral peficitinib improved the severity of refractory rheumatoid arthritis in a manufacturer-sponsored phase II trial of the investigational drug, which inhibits all of the intracellular signaling molecules in the Janus kinase family.

The randomized, double-blind dose-finding study was performed at 41 sites in six countries and involved 289 adults with long-standing moderate to severe rheumatoid arthritis (RA) who had not responded to or who were intolerant of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The participants were permitted to take nonsteroidal anti-inflammatory drugs, hydroxychloroquine, chloroquine, sulfasalazine, and/or oral corticosteroids (10 mg or less of prednisone or equivalent) as needed throughout the trial, but not methotrexate, gold, penicillamine, leflunomide, azathioprine, minocycline, and cyclophosphamide. The patients also were allowed to have previously taken a biologic and were not required to have had an inadequate response or intolerance to a previous biologic, said Mark C. Genovese, MD, of the division of immunology and rheumatology at Stanford University, Palo Alto, Calif., and his associates.

A 12-week course of daily oral peficitinib improved the severity of refractory rheumatoid arthritis in a manufacturer-sponsored phase II trial of the investigational drug, which inhibits all of the intracellular signaling molecules in the Janus kinase family.

The randomized, double-blind dose-finding study was performed at 41 sites in six countries and involved 289 adults with long-standing moderate to severe rheumatoid arthritis (RA) who had not responded to or who were intolerant of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The participants were permitted to take nonsteroidal anti-inflammatory drugs, hydroxychloroquine, chloroquine, sulfasalazine, and/or oral corticosteroids (10 mg or less of prednisone or equivalent) as needed throughout the trial, but not methotrexate, gold, penicillamine, leflunomide, azathioprine, minocycline, and cyclophosphamide. The patients also were allowed to have previously taken a biologic and were not required to have had an inadequate response or intolerance to a previous biologic, said Mark C. Genovese, MD, of the division of immunology and rheumatology at Stanford University, Palo Alto, Calif., and his associates.

A 12-week course of daily oral peficitinib improved the severity of refractory rheumatoid arthritis in a manufacturer-sponsored phase II trial of the investigational drug, which inhibits all of the intracellular signaling molecules in the Janus kinase family.

The randomized, double-blind dose-finding study was performed at 41 sites in six countries and involved 289 adults with long-standing moderate to severe rheumatoid arthritis (RA) who had not responded to or who were intolerant of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The participants were permitted to take nonsteroidal anti-inflammatory drugs, hydroxychloroquine, chloroquine, sulfasalazine, and/or oral corticosteroids (10 mg or less of prednisone or equivalent) as needed throughout the trial, but not methotrexate, gold, penicillamine, leflunomide, azathioprine, minocycline, and cyclophosphamide. The patients also were allowed to have previously taken a biologic and were not required to have had an inadequate response or intolerance to a previous biologic, said Mark C. Genovese, MD, of the division of immunology and rheumatology at Stanford University, Palo Alto, Calif., and his associates.

The Residual Cancer Burden (RCB), a standardized measure of residual disease in pathologic resection specimens following neoadjuvant chemotherapy, was found to be prognostic of long-term survival across all three phenotypic subtypes when it was applied to five breast cancer cohorts totaling 1,158 patients from a single institution, investigators report in the Journal of Clinical Oncology.

If the findings of this retrospective cohort analysis are validated in other cohorts, it would indicate that assessing patients’ RCB index could add “meaningful information to pretreatement clinical and pathologic information and posttreatment yp stage [American Joint Commission on Cancer stage],” said W. Fraser Symmans, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.

Residual disease is categorized into four groups: an index of zero (RCB-0) reflects a complete pathologic response to neoadjuvant treatment, RCB-I indicates minimal residual disease, RCB-II indicates moderate residual disease, and RCB-III indicates extensive residual disease. The investigators reviewed pathology specimens to determine the RCB index in a cohort of 219 patients followed for 13 years, a cohort of 262 patients followed for 9 years, a cohort of 342 patients followed for 7 years, a cohort of 132 patients followed for more than 16 years, and a cohort of 203 patients followed for 7 years.

They found that the RCB index predicted the risk of relapse or death across all five cohorts, regardless of other clinical and pathologic variables such as tumor stage or grade, patient age, and type of surgery (J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2015.63.1010).

RCB also was predictive regardless of whether patients had triple-negative disease, HR-positive/HER2-negative disease, HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide alone, or HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide plus trastuzumab.

In two especially high-risk groups of patients – those with triple-negative breast cancer and those with HER2-positive breast cancer – RCB was the only or the most important predictor of survival. Approximately half of the patients with triple-negative disease had an index of RCB-0 or RCB-I and a good prognosis, while those with an RCB-II or RCB-III index had poor survival, Dr. Symmans and his associates said.

The Residual Cancer Burden (RCB), a standardized measure of residual disease in pathologic resection specimens following neoadjuvant chemotherapy, was found to be prognostic of long-term survival across all three phenotypic subtypes when it was applied to five breast cancer cohorts totaling 1,158 patients from a single institution, investigators report in the Journal of Clinical Oncology.

If the findings of this retrospective cohort analysis are validated in other cohorts, it would indicate that assessing patients’ RCB index could add “meaningful information to pretreatement clinical and pathologic information and posttreatment yp stage [American Joint Commission on Cancer stage],” said W. Fraser Symmans, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.

Residual disease is categorized into four groups: an index of zero (RCB-0) reflects a complete pathologic response to neoadjuvant treatment, RCB-I indicates minimal residual disease, RCB-II indicates moderate residual disease, and RCB-III indicates extensive residual disease. The investigators reviewed pathology specimens to determine the RCB index in a cohort of 219 patients followed for 13 years, a cohort of 262 patients followed for 9 years, a cohort of 342 patients followed for 7 years, a cohort of 132 patients followed for more than 16 years, and a cohort of 203 patients followed for 7 years.

They found that the RCB index predicted the risk of relapse or death across all five cohorts, regardless of other clinical and pathologic variables such as tumor stage or grade, patient age, and type of surgery (J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2015.63.1010).

RCB also was predictive regardless of whether patients had triple-negative disease, HR-positive/HER2-negative disease, HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide alone, or HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide plus trastuzumab.

In two especially high-risk groups of patients – those with triple-negative breast cancer and those with HER2-positive breast cancer – RCB was the only or the most important predictor of survival. Approximately half of the patients with triple-negative disease had an index of RCB-0 or RCB-I and a good prognosis, while those with an RCB-II or RCB-III index had poor survival, Dr. Symmans and his associates said.

The Residual Cancer Burden (RCB), a standardized measure of residual disease in pathologic resection specimens following neoadjuvant chemotherapy, was found to be prognostic of long-term survival across all three phenotypic subtypes when it was applied to five breast cancer cohorts totaling 1,158 patients from a single institution, investigators report in the Journal of Clinical Oncology.

If the findings of this retrospective cohort analysis are validated in other cohorts, it would indicate that assessing patients’ RCB index could add “meaningful information to pretreatement clinical and pathologic information and posttreatment yp stage [American Joint Commission on Cancer stage],” said W. Fraser Symmans, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.

Residual disease is categorized into four groups: an index of zero (RCB-0) reflects a complete pathologic response to neoadjuvant treatment, RCB-I indicates minimal residual disease, RCB-II indicates moderate residual disease, and RCB-III indicates extensive residual disease. The investigators reviewed pathology specimens to determine the RCB index in a cohort of 219 patients followed for 13 years, a cohort of 262 patients followed for 9 years, a cohort of 342 patients followed for 7 years, a cohort of 132 patients followed for more than 16 years, and a cohort of 203 patients followed for 7 years.

They found that the RCB index predicted the risk of relapse or death across all five cohorts, regardless of other clinical and pathologic variables such as tumor stage or grade, patient age, and type of surgery (J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2015.63.1010).

RCB also was predictive regardless of whether patients had triple-negative disease, HR-positive/HER2-negative disease, HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide alone, or HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide plus trastuzumab.

In two especially high-risk groups of patients – those with triple-negative breast cancer and those with HER2-positive breast cancer – RCB was the only or the most important predictor of survival. Approximately half of the patients with triple-negative disease had an index of RCB-0 or RCB-I and a good prognosis, while those with an RCB-II or RCB-III index had poor survival, Dr. Symmans and his associates said.