Jennifer Kelly Shepphird

Among patients with early or advanced melanoma, elevated blood levels of C-reactive protein (CRP) predicted disease recurrence and poorer survival. In a subset of patients who had sequential blood draws, CRP levels indicated melanoma disease progression, according to a study published online March 16 in the Journal of Clinical Oncology.

CRP measurements for 1,144 patients demonstrated that elevated CRP was associated with increased overall risk of death (hazard ratio, 1.44/U increase of logarithmic CRP; 95% confidence interval, 1.30-1.59; P < .001), reported Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

“These data provide strong evidence that CRP is an independent prognostic biomarker in patients with melanoma, including those with early-stage disease as well as those with advanced-stage disease. A markedly elevated CRP level in particular seems to identify a subgroup of patients at high risk for disease recurrence and death,” they said (J. Clin. Onc. 2015 March 16 [doi: 10.1200/JCO.2014.58.0209]).

Investigators demonstrated a dose effect by dividing CRP levels into quintiles and showing patients in the highest quintile had significantly poorer overall survival than did those in the lowest quintile (HR, 4.14; 2.58-6.64), and significant trends across quintiles. Recursive partitioning indicated the best CRP cutoff value was 10.94 mg/L, close to the commonly used clinical cutoff of 10 mg/L. CRP levels greater than or equal to 10 mg/L predicted poorer survival and higher rates of recurrence.

For a subset of 115 patients, data from sequential blood draws showed a correlation between increasing CRP levels in an individual and disease progression. Changes in CRP levels were obtained at a median of 17.12 months apart, and increased levels were associated with poorer response to treatment (P < .001), progression of disease (P < .001), increase in cancer stage (P = .0065), and increase vs. no increase in number of metastases (P = .0013).

Dr. Fang and his associates suggest further studies on potential benefits of reducing inflammation and/or CRP on melanoma patients. Statins reduce CRP levels, but their effect on cancer prevention is unclear.

“Although there is as yet no defined role for clinical use of statins in cancer treatment, our data suggest that preclinical evaluation of statin therapy in melanoma models is reasonable to pursue,” they wrote.

Among patients with early or advanced melanoma, elevated blood levels of C-reactive protein (CRP) predicted disease recurrence and poorer survival. In a subset of patients who had sequential blood draws, CRP levels indicated melanoma disease progression, according to a study published online March 16 in the Journal of Clinical Oncology.

CRP measurements for 1,144 patients demonstrated that elevated CRP was associated with increased overall risk of death (hazard ratio, 1.44/U increase of logarithmic CRP; 95% confidence interval, 1.30-1.59; P < .001), reported Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

“These data provide strong evidence that CRP is an independent prognostic biomarker in patients with melanoma, including those with early-stage disease as well as those with advanced-stage disease. A markedly elevated CRP level in particular seems to identify a subgroup of patients at high risk for disease recurrence and death,” they said (J. Clin. Onc. 2015 March 16 [doi: 10.1200/JCO.2014.58.0209]).

Investigators demonstrated a dose effect by dividing CRP levels into quintiles and showing patients in the highest quintile had significantly poorer overall survival than did those in the lowest quintile (HR, 4.14; 2.58-6.64), and significant trends across quintiles. Recursive partitioning indicated the best CRP cutoff value was 10.94 mg/L, close to the commonly used clinical cutoff of 10 mg/L. CRP levels greater than or equal to 10 mg/L predicted poorer survival and higher rates of recurrence.

For a subset of 115 patients, data from sequential blood draws showed a correlation between increasing CRP levels in an individual and disease progression. Changes in CRP levels were obtained at a median of 17.12 months apart, and increased levels were associated with poorer response to treatment (P < .001), progression of disease (P < .001), increase in cancer stage (P = .0065), and increase vs. no increase in number of metastases (P = .0013).

Dr. Fang and his associates suggest further studies on potential benefits of reducing inflammation and/or CRP on melanoma patients. Statins reduce CRP levels, but their effect on cancer prevention is unclear.

“Although there is as yet no defined role for clinical use of statins in cancer treatment, our data suggest that preclinical evaluation of statin therapy in melanoma models is reasonable to pursue,” they wrote.

Among patients with early or advanced melanoma, elevated blood levels of C-reactive protein (CRP) predicted disease recurrence and poorer survival. In a subset of patients who had sequential blood draws, CRP levels indicated melanoma disease progression, according to a study published online March 16 in the Journal of Clinical Oncology.

CRP measurements for 1,144 patients demonstrated that elevated CRP was associated with increased overall risk of death (hazard ratio, 1.44/U increase of logarithmic CRP; 95% confidence interval, 1.30-1.59; P < .001), reported Dr. Shenying Fang of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

“These data provide strong evidence that CRP is an independent prognostic biomarker in patients with melanoma, including those with early-stage disease as well as those with advanced-stage disease. A markedly elevated CRP level in particular seems to identify a subgroup of patients at high risk for disease recurrence and death,” they said (J. Clin. Onc. 2015 March 16 [doi: 10.1200/JCO.2014.58.0209]).

Investigators demonstrated a dose effect by dividing CRP levels into quintiles and showing patients in the highest quintile had significantly poorer overall survival than did those in the lowest quintile (HR, 4.14; 2.58-6.64), and significant trends across quintiles. Recursive partitioning indicated the best CRP cutoff value was 10.94 mg/L, close to the commonly used clinical cutoff of 10 mg/L. CRP levels greater than or equal to 10 mg/L predicted poorer survival and higher rates of recurrence.

For a subset of 115 patients, data from sequential blood draws showed a correlation between increasing CRP levels in an individual and disease progression. Changes in CRP levels were obtained at a median of 17.12 months apart, and increased levels were associated with poorer response to treatment (P < .001), progression of disease (P < .001), increase in cancer stage (P = .0065), and increase vs. no increase in number of metastases (P = .0013).

Dr. Fang and his associates suggest further studies on potential benefits of reducing inflammation and/or CRP on melanoma patients. Statins reduce CRP levels, but their effect on cancer prevention is unclear.

“Although there is as yet no defined role for clinical use of statins in cancer treatment, our data suggest that preclinical evaluation of statin therapy in melanoma models is reasonable to pursue,” they wrote.

Patients with lung cancer who underwent surgery to remove solid tumors and who were treated with atrial natriuretic peptide (ANP) had significantly lower cancer recurrence than did untreated patients, according to a report published in the Proceedings of the National Academy of Sciences.

Investigators retrospectively evaluated patients with lung cancer who underwent surgical removal of tumors; 77 patients received perioperative treatment with ANP and 390 patients did not receive ANP treatment.

ANP-treated patients had significantly greater 2-year relapse-free survival (RFS) after surgery than did those who did not receive ANP (91% vs. 75%, P = .018). Analysis of propensity-matched patients also showed significantly greater 2-year RFS in the ANP group (91% vs. 67%, P = .0013), reported Dr. Takashi Nojiri of Osaka (Japan) University Graduate School of Medicine, and his associates.

“We demonstrated that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients, suggesting that ANP could potentially be used to prevent cancer recurrence after surgery,” wrote Dr. Nojiri and colleagues (Proc. Natl. Acad. Sci. USA 2015 March 16 [doi:10.1073/pnas.1417273112]).

Atrial natriuretic peptide is a vasodilating hormone from the human heart and acts as a diuretic; previous studies have shown that administration during the perioperative period reduces inflammatory responses and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery.

Patients with lung cancer who underwent surgery to remove solid tumors and who were treated with atrial natriuretic peptide (ANP) had significantly lower cancer recurrence than did untreated patients, according to a report published in the Proceedings of the National Academy of Sciences.

Investigators retrospectively evaluated patients with lung cancer who underwent surgical removal of tumors; 77 patients received perioperative treatment with ANP and 390 patients did not receive ANP treatment.

ANP-treated patients had significantly greater 2-year relapse-free survival (RFS) after surgery than did those who did not receive ANP (91% vs. 75%, P = .018). Analysis of propensity-matched patients also showed significantly greater 2-year RFS in the ANP group (91% vs. 67%, P = .0013), reported Dr. Takashi Nojiri of Osaka (Japan) University Graduate School of Medicine, and his associates.

“We demonstrated that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients, suggesting that ANP could potentially be used to prevent cancer recurrence after surgery,” wrote Dr. Nojiri and colleagues (Proc. Natl. Acad. Sci. USA 2015 March 16 [doi:10.1073/pnas.1417273112]).

Atrial natriuretic peptide is a vasodilating hormone from the human heart and acts as a diuretic; previous studies have shown that administration during the perioperative period reduces inflammatory responses and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery.

Patients with lung cancer who underwent surgery to remove solid tumors and who were treated with atrial natriuretic peptide (ANP) had significantly lower cancer recurrence than did untreated patients, according to a report published in the Proceedings of the National Academy of Sciences.

Investigators retrospectively evaluated patients with lung cancer who underwent surgical removal of tumors; 77 patients received perioperative treatment with ANP and 390 patients did not receive ANP treatment.

ANP-treated patients had significantly greater 2-year relapse-free survival (RFS) after surgery than did those who did not receive ANP (91% vs. 75%, P = .018). Analysis of propensity-matched patients also showed significantly greater 2-year RFS in the ANP group (91% vs. 67%, P = .0013), reported Dr. Takashi Nojiri of Osaka (Japan) University Graduate School of Medicine, and his associates.

“We demonstrated that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients, suggesting that ANP could potentially be used to prevent cancer recurrence after surgery,” wrote Dr. Nojiri and colleagues (Proc. Natl. Acad. Sci. USA 2015 March 16 [doi:10.1073/pnas.1417273112]).

Atrial natriuretic peptide is a vasodilating hormone from the human heart and acts as a diuretic; previous studies have shown that administration during the perioperative period reduces inflammatory responses and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery.

Outcomes among 411 pediatric patients with acute lymphoblastic leukemia after hematopoietic stem-cell transplantation were similar from well-matched sibling and nonrelative donors, according to a study published online March 9 in the Journal of Clinical Oncology.

After a median follow up of 4.2 years, investigators found no significant differences in 4-year event-free survival, overall survival, or relapse incidence between 306 patients with transplantations from unrelated donors and 105 with sibling donors. However, nonrelapse mortality rates from matched unrelated donors (MUDs) was 0.10 ± 0.02 vs. 0.03 ± 0.02 from matched sibling donors (MSDs), Dr. Christina Peters, professor of pediatrics at St. Anna Children’s Hospital, Vienna, Austria, and associates reported.

Patients who received MSD-HSCT had significantly faster engraftment than did those who received MUD-HSCT (median time to neutrophil engraftment 17 days vs. 22 days, and 30-day cumulative incidence of 75% vs. 44%, respectively).

“Despite excellent outcomes of MUD-HSCT, our data indicate that MSD BM (bone marrow) transplantation remains superior, which is possibly a result of fewer severe infections. We speculate that this is influenced by the short and limited GVHD prophylaxis in this setting,” the investigators wrote (J. Clin. Oncol. 2015 March 9 [doi: 10.1200/JCO.2014.58.9747]).

Patients in the MUD-HSCT group had superior event-free and overall survival compared to previous studies of children with high-risk ALL, results which may have been influenced by the use of high-resolution HLA typing and the requirement that donors have 9/10 or 10/10 HLA matches. Over 70% of patients who lacked MSDs were matched with MUDs, and no outcome differences were observed in patients who received transplantations from 9/10 or 10/10 matches. Patients older than 2 years and in the absence of contraindications had conditioning by total-body irradiation (TBI) and etoposide.

“Our data demonstrate excellent EFS and OS, and low incidence of relapse in children with high-risk ALL after treatment with TBI and etoposide before allogeneic HSCT from HLA-matched siblings or well-matched unrelated donors. This large, prospective, multicenter trial suggest that MUD-HSCT could be a standard of care for patients with ALL who have a high risk of relapse and who lack MSDs,” the investigators concluded.

Outcomes among 411 pediatric patients with acute lymphoblastic leukemia after hematopoietic stem-cell transplantation were similar from well-matched sibling and nonrelative donors, according to a study published online March 9 in the Journal of Clinical Oncology.

After a median follow up of 4.2 years, investigators found no significant differences in 4-year event-free survival, overall survival, or relapse incidence between 306 patients with transplantations from unrelated donors and 105 with sibling donors. However, nonrelapse mortality rates from matched unrelated donors (MUDs) was 0.10 ± 0.02 vs. 0.03 ± 0.02 from matched sibling donors (MSDs), Dr. Christina Peters, professor of pediatrics at St. Anna Children’s Hospital, Vienna, Austria, and associates reported.

Patients who received MSD-HSCT had significantly faster engraftment than did those who received MUD-HSCT (median time to neutrophil engraftment 17 days vs. 22 days, and 30-day cumulative incidence of 75% vs. 44%, respectively).

“Despite excellent outcomes of MUD-HSCT, our data indicate that MSD BM (bone marrow) transplantation remains superior, which is possibly a result of fewer severe infections. We speculate that this is influenced by the short and limited GVHD prophylaxis in this setting,” the investigators wrote (J. Clin. Oncol. 2015 March 9 [doi: 10.1200/JCO.2014.58.9747]).

Patients in the MUD-HSCT group had superior event-free and overall survival compared to previous studies of children with high-risk ALL, results which may have been influenced by the use of high-resolution HLA typing and the requirement that donors have 9/10 or 10/10 HLA matches. Over 70% of patients who lacked MSDs were matched with MUDs, and no outcome differences were observed in patients who received transplantations from 9/10 or 10/10 matches. Patients older than 2 years and in the absence of contraindications had conditioning by total-body irradiation (TBI) and etoposide.

“Our data demonstrate excellent EFS and OS, and low incidence of relapse in children with high-risk ALL after treatment with TBI and etoposide before allogeneic HSCT from HLA-matched siblings or well-matched unrelated donors. This large, prospective, multicenter trial suggest that MUD-HSCT could be a standard of care for patients with ALL who have a high risk of relapse and who lack MSDs,” the investigators concluded.

Outcomes among 411 pediatric patients with acute lymphoblastic leukemia after hematopoietic stem-cell transplantation were similar from well-matched sibling and nonrelative donors, according to a study published online March 9 in the Journal of Clinical Oncology.

After a median follow up of 4.2 years, investigators found no significant differences in 4-year event-free survival, overall survival, or relapse incidence between 306 patients with transplantations from unrelated donors and 105 with sibling donors. However, nonrelapse mortality rates from matched unrelated donors (MUDs) was 0.10 ± 0.02 vs. 0.03 ± 0.02 from matched sibling donors (MSDs), Dr. Christina Peters, professor of pediatrics at St. Anna Children’s Hospital, Vienna, Austria, and associates reported.

Patients who received MSD-HSCT had significantly faster engraftment than did those who received MUD-HSCT (median time to neutrophil engraftment 17 days vs. 22 days, and 30-day cumulative incidence of 75% vs. 44%, respectively).

“Despite excellent outcomes of MUD-HSCT, our data indicate that MSD BM (bone marrow) transplantation remains superior, which is possibly a result of fewer severe infections. We speculate that this is influenced by the short and limited GVHD prophylaxis in this setting,” the investigators wrote (J. Clin. Oncol. 2015 March 9 [doi: 10.1200/JCO.2014.58.9747]).

Patients in the MUD-HSCT group had superior event-free and overall survival compared to previous studies of children with high-risk ALL, results which may have been influenced by the use of high-resolution HLA typing and the requirement that donors have 9/10 or 10/10 HLA matches. Over 70% of patients who lacked MSDs were matched with MUDs, and no outcome differences were observed in patients who received transplantations from 9/10 or 10/10 matches. Patients older than 2 years and in the absence of contraindications had conditioning by total-body irradiation (TBI) and etoposide.

“Our data demonstrate excellent EFS and OS, and low incidence of relapse in children with high-risk ALL after treatment with TBI and etoposide before allogeneic HSCT from HLA-matched siblings or well-matched unrelated donors. This large, prospective, multicenter trial suggest that MUD-HSCT could be a standard of care for patients with ALL who have a high risk of relapse and who lack MSDs,” the investigators concluded.

A large, population-based Swedish study found that patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance had better overall survival than patients without prior knowledge, according to a report published online March 5 in JAMA Oncology.

Despite having a higher prevalence of comorbidities, those with prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) had significantly higher median survival than patients without prior knowledge (hazard ratio, 0.86; 95% confidence interval 0.77-0.96; P < .01), Ms. Elin Edda Sigurdardottir of the University of Iceland, Reykjavik, and her associates report.

“We speculate that the reason for the prolonged survival observed in our study most likely reflects the fact that MGUS patients are evaluated more often for signs of MM [multiple myeloma] progression and may be diagnosed and started on antimyeloma therapy at an earlier stage. This argues for early treatment approaches in MM and raises the question of whether systematic screening for MGUS should be initiated,” they said (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.23]).

Virtually all cases of MM are preceded by MGUS, characterized by detectable serum M protein and the absence of end-organ damage. Most MGUS cases go undiagnosed, and only a fraction progress to malignant disease, with absolute risk of progression 0.5%-1% per year. Studies show MGUS is present in 2%-3% of adults aged 50 years and older and about 5% of adults aged 70 years and older.

The population-based study analyzed Swedish national health registry data from 1976 to 2005 and included 14,798 MM patients, 394 (2.7%) of whom had previously been diagnosed with MGUS. MGUS was typically detected as part of a medical work-up for another cause, and patients with prior MGUS knowledge had significantly more comorbidities, including autoimmune diseases, infections, ischemic heart disease, heart failure, cerebrovascular diseases, and renal diseases (P < .001 for all comparisons).

Among the subset of patients with prior knowledge of MGUS, the median M-protein concentration at diagnosis was 1.2 g/dL. Surprisingly, those with M-protein concentrations less than 0.5 g/dL had poorer survival than did those with greater M-protein concentrations (HR, 1.86; 95% CI, 1.13-3.04; P = .01). The authors speculate this may be due to current guidelines that suggest less frequent monitoring of individuals with lower M-protein concentrations.

“Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of MM and lead to better MM survival,” Ms. Sigurdardottir and her associates wrote.

A large, population-based Swedish study found that patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance had better overall survival than patients without prior knowledge, according to a report published online March 5 in JAMA Oncology.

Despite having a higher prevalence of comorbidities, those with prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) had significantly higher median survival than patients without prior knowledge (hazard ratio, 0.86; 95% confidence interval 0.77-0.96; P < .01), Ms. Elin Edda Sigurdardottir of the University of Iceland, Reykjavik, and her associates report.

“We speculate that the reason for the prolonged survival observed in our study most likely reflects the fact that MGUS patients are evaluated more often for signs of MM [multiple myeloma] progression and may be diagnosed and started on antimyeloma therapy at an earlier stage. This argues for early treatment approaches in MM and raises the question of whether systematic screening for MGUS should be initiated,” they said (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.23]).

Virtually all cases of MM are preceded by MGUS, characterized by detectable serum M protein and the absence of end-organ damage. Most MGUS cases go undiagnosed, and only a fraction progress to malignant disease, with absolute risk of progression 0.5%-1% per year. Studies show MGUS is present in 2%-3% of adults aged 50 years and older and about 5% of adults aged 70 years and older.

The population-based study analyzed Swedish national health registry data from 1976 to 2005 and included 14,798 MM patients, 394 (2.7%) of whom had previously been diagnosed with MGUS. MGUS was typically detected as part of a medical work-up for another cause, and patients with prior MGUS knowledge had significantly more comorbidities, including autoimmune diseases, infections, ischemic heart disease, heart failure, cerebrovascular diseases, and renal diseases (P < .001 for all comparisons).

Among the subset of patients with prior knowledge of MGUS, the median M-protein concentration at diagnosis was 1.2 g/dL. Surprisingly, those with M-protein concentrations less than 0.5 g/dL had poorer survival than did those with greater M-protein concentrations (HR, 1.86; 95% CI, 1.13-3.04; P = .01). The authors speculate this may be due to current guidelines that suggest less frequent monitoring of individuals with lower M-protein concentrations.

“Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of MM and lead to better MM survival,” Ms. Sigurdardottir and her associates wrote.

A large, population-based Swedish study found that patients with multiple myeloma who had prior knowledge of monoclonal gammopathy of undetermined significance had better overall survival than patients without prior knowledge, according to a report published online March 5 in JAMA Oncology.

Despite having a higher prevalence of comorbidities, those with prior knowledge of monoclonal gammopathy of undetermined significance (MGUS) had significantly higher median survival than patients without prior knowledge (hazard ratio, 0.86; 95% confidence interval 0.77-0.96; P < .01), Ms. Elin Edda Sigurdardottir of the University of Iceland, Reykjavik, and her associates report.

“We speculate that the reason for the prolonged survival observed in our study most likely reflects the fact that MGUS patients are evaluated more often for signs of MM [multiple myeloma] progression and may be diagnosed and started on antimyeloma therapy at an earlier stage. This argues for early treatment approaches in MM and raises the question of whether systematic screening for MGUS should be initiated,” they said (JAMA Oncol. 2015 March 5 [doi:10.1001/jamaoncol.2015.23]).

Virtually all cases of MM are preceded by MGUS, characterized by detectable serum M protein and the absence of end-organ damage. Most MGUS cases go undiagnosed, and only a fraction progress to malignant disease, with absolute risk of progression 0.5%-1% per year. Studies show MGUS is present in 2%-3% of adults aged 50 years and older and about 5% of adults aged 70 years and older.

The population-based study analyzed Swedish national health registry data from 1976 to 2005 and included 14,798 MM patients, 394 (2.7%) of whom had previously been diagnosed with MGUS. MGUS was typically detected as part of a medical work-up for another cause, and patients with prior MGUS knowledge had significantly more comorbidities, including autoimmune diseases, infections, ischemic heart disease, heart failure, cerebrovascular diseases, and renal diseases (P < .001 for all comparisons).

Among the subset of patients with prior knowledge of MGUS, the median M-protein concentration at diagnosis was 1.2 g/dL. Surprisingly, those with M-protein concentrations less than 0.5 g/dL had poorer survival than did those with greater M-protein concentrations (HR, 1.86; 95% CI, 1.13-3.04; P = .01). The authors speculate this may be due to current guidelines that suggest less frequent monitoring of individuals with lower M-protein concentrations.

“Our findings raise the question whether screening for MGUS in the general population could translate into earlier detection and treatment of MM and lead to better MM survival,” Ms. Sigurdardottir and her associates wrote.

Surgical performance data gathered within the American College of Surgeons, National Surgical Quality Improvement Program (ACS NSQIP) from the period of 2006-2013 indicate improved performance by most participating hospitals over time. In the categories of mortality, morbidity, and surgical site infections (SSI), the ratio of observed to expected surgery-related adverse events declined over time, showing that with increasing years of participation in ACS NSQIP, hospitals saw cumulative reductions in observed/expected ratios.

Dr. Clifford Y. Ko, coauthor of the report, an ACS Fellow and professor of surgery at David Geffen School of Medicine, University of California Los Angeles, spoke in an interview about the results, which were published in Annals of Surgery.

“An important finding from our study is that hospitals get better when they participate in ACS NSQIP, and the longer they are in the program, the better they get. It means that if hospitals commit to going on the journey of quality improvement, the longer they are on that journey, the better they get, the more experience they get in quality improvement, and the more their outcomes improve.

“Another important point that became evident from the analysis was that the biggest area for improvement is in the rate of complications, more so than mortality. The mortality rate is already low, and the number of preventable deaths is low. There are many more preventable complications than preventable deaths. The data show that risk-adjusted complications decrease over time because many opportunities lie in decreasing rates of infection, blood clot, pneumonia, urinary tract infection, and others. Whatever rate the hospital starts in ACS NSQIP, there is more opportunity to realize improvements in the number of complications than in mortality.”

The researchers used clinical data collected from 2006 to 2013 from 515 hospitals participating in ACS NSQIP.

Hospitals participating in the program receive semiannual reports that benchmark performance compared to other similar institutions. But the performance benchmarks are continuously updated to reflect current practices across groups of similar institutions, so individual hospitals cannot gauge whether their performance improves over time relative to fixed standard.

“The aim of the study was to determine if over several years hospitals who participated in ACS NSQIP got better. Benchmarking data provides feedback, but does not indicate whether over time hospitals improve. Our analysis looked at hospital performance longitudinally to evaluate if they got better from year to year,” said Dr. Ko.

To make meaningful comparisons of surgical outcomes, expected outcomes were calculated based on risk adjustments to compensate for differences in patient characteristics and the risk profile of procedures performed. Dr. Ko explained, “Large, tertiary institutions that care for very sick patients, or very complex cases, are expected to have worse outcomes than hospitals that perform more common procedures with lower expected event rates. In this analysis, the results of interest are the trends in observed/expected (O/E) event rates, which adjust for these risks.”

For all hospitals, 62%, 70%, and 65% had negative slopes for mortality, morbidity, and any SSI, respectively. The O/E ratios for mortality, morbidity, and SSI declined with each year of participation in the program, and the slope of the decline was steepest for morbidity and SSI. SSI is the most common complication and largely mirrors morbidity. For hospitals in the program at least 3 years, annual reductions in mortality, morbidity, and SSI were estimated to be 0.8%, 3.1%, and 2.6%, respectively.

One of the hallmarks of ACS NSQIP is the accuracy of the data, which come directly from medical records. In a large study comparing clinical with billing (or administrative) data, Dr. Ko and colleagues found the accuracy of billing data to be low.

“In a 2-year study we merged clinical and administrative data from over 100,000 patients and found the agreement to be poor. Billing data had a detection rate for SSI of 25% and a false-positive rate of 70%,” he said.

“In developing programs to improve patient care, we want to base our work on the most accurate data possible. Our analysis shows that hospitals committed to using ACS NSQIP improve over time.”

The authors reported having no financial disclosures.

Surgical performance data gathered within the American College of Surgeons, National Surgical Quality Improvement Program (ACS NSQIP) from the period of 2006-2013 indicate improved performance by most participating hospitals over time. In the categories of mortality, morbidity, and surgical site infections (SSI), the ratio of observed to expected surgery-related adverse events declined over time, showing that with increasing years of participation in ACS NSQIP, hospitals saw cumulative reductions in observed/expected ratios.

Dr. Clifford Y. Ko, coauthor of the report, an ACS Fellow and professor of surgery at David Geffen School of Medicine, University of California Los Angeles, spoke in an interview about the results, which were published in Annals of Surgery.

“An important finding from our study is that hospitals get better when they participate in ACS NSQIP, and the longer they are in the program, the better they get. It means that if hospitals commit to going on the journey of quality improvement, the longer they are on that journey, the better they get, the more experience they get in quality improvement, and the more their outcomes improve.

“Another important point that became evident from the analysis was that the biggest area for improvement is in the rate of complications, more so than mortality. The mortality rate is already low, and the number of preventable deaths is low. There are many more preventable complications than preventable deaths. The data show that risk-adjusted complications decrease over time because many opportunities lie in decreasing rates of infection, blood clot, pneumonia, urinary tract infection, and others. Whatever rate the hospital starts in ACS NSQIP, there is more opportunity to realize improvements in the number of complications than in mortality.”

The researchers used clinical data collected from 2006 to 2013 from 515 hospitals participating in ACS NSQIP.

Hospitals participating in the program receive semiannual reports that benchmark performance compared to other similar institutions. But the performance benchmarks are continuously updated to reflect current practices across groups of similar institutions, so individual hospitals cannot gauge whether their performance improves over time relative to fixed standard.

“The aim of the study was to determine if over several years hospitals who participated in ACS NSQIP got better. Benchmarking data provides feedback, but does not indicate whether over time hospitals improve. Our analysis looked at hospital performance longitudinally to evaluate if they got better from year to year,” said Dr. Ko.

To make meaningful comparisons of surgical outcomes, expected outcomes were calculated based on risk adjustments to compensate for differences in patient characteristics and the risk profile of procedures performed. Dr. Ko explained, “Large, tertiary institutions that care for very sick patients, or very complex cases, are expected to have worse outcomes than hospitals that perform more common procedures with lower expected event rates. In this analysis, the results of interest are the trends in observed/expected (O/E) event rates, which adjust for these risks.”

For all hospitals, 62%, 70%, and 65% had negative slopes for mortality, morbidity, and any SSI, respectively. The O/E ratios for mortality, morbidity, and SSI declined with each year of participation in the program, and the slope of the decline was steepest for morbidity and SSI. SSI is the most common complication and largely mirrors morbidity. For hospitals in the program at least 3 years, annual reductions in mortality, morbidity, and SSI were estimated to be 0.8%, 3.1%, and 2.6%, respectively.

One of the hallmarks of ACS NSQIP is the accuracy of the data, which come directly from medical records. In a large study comparing clinical with billing (or administrative) data, Dr. Ko and colleagues found the accuracy of billing data to be low.

“In a 2-year study we merged clinical and administrative data from over 100,000 patients and found the agreement to be poor. Billing data had a detection rate for SSI of 25% and a false-positive rate of 70%,” he said.

“In developing programs to improve patient care, we want to base our work on the most accurate data possible. Our analysis shows that hospitals committed to using ACS NSQIP improve over time.”

The authors reported having no financial disclosures.

Surgical performance data gathered within the American College of Surgeons, National Surgical Quality Improvement Program (ACS NSQIP) from the period of 2006-2013 indicate improved performance by most participating hospitals over time. In the categories of mortality, morbidity, and surgical site infections (SSI), the ratio of observed to expected surgery-related adverse events declined over time, showing that with increasing years of participation in ACS NSQIP, hospitals saw cumulative reductions in observed/expected ratios.

Dr. Clifford Y. Ko, coauthor of the report, an ACS Fellow and professor of surgery at David Geffen School of Medicine, University of California Los Angeles, spoke in an interview about the results, which were published in Annals of Surgery.

“An important finding from our study is that hospitals get better when they participate in ACS NSQIP, and the longer they are in the program, the better they get. It means that if hospitals commit to going on the journey of quality improvement, the longer they are on that journey, the better they get, the more experience they get in quality improvement, and the more their outcomes improve.

“Another important point that became evident from the analysis was that the biggest area for improvement is in the rate of complications, more so than mortality. The mortality rate is already low, and the number of preventable deaths is low. There are many more preventable complications than preventable deaths. The data show that risk-adjusted complications decrease over time because many opportunities lie in decreasing rates of infection, blood clot, pneumonia, urinary tract infection, and others. Whatever rate the hospital starts in ACS NSQIP, there is more opportunity to realize improvements in the number of complications than in mortality.”

The researchers used clinical data collected from 2006 to 2013 from 515 hospitals participating in ACS NSQIP.

Hospitals participating in the program receive semiannual reports that benchmark performance compared to other similar institutions. But the performance benchmarks are continuously updated to reflect current practices across groups of similar institutions, so individual hospitals cannot gauge whether their performance improves over time relative to fixed standard.

“The aim of the study was to determine if over several years hospitals who participated in ACS NSQIP got better. Benchmarking data provides feedback, but does not indicate whether over time hospitals improve. Our analysis looked at hospital performance longitudinally to evaluate if they got better from year to year,” said Dr. Ko.

To make meaningful comparisons of surgical outcomes, expected outcomes were calculated based on risk adjustments to compensate for differences in patient characteristics and the risk profile of procedures performed. Dr. Ko explained, “Large, tertiary institutions that care for very sick patients, or very complex cases, are expected to have worse outcomes than hospitals that perform more common procedures with lower expected event rates. In this analysis, the results of interest are the trends in observed/expected (O/E) event rates, which adjust for these risks.”

For all hospitals, 62%, 70%, and 65% had negative slopes for mortality, morbidity, and any SSI, respectively. The O/E ratios for mortality, morbidity, and SSI declined with each year of participation in the program, and the slope of the decline was steepest for morbidity and SSI. SSI is the most common complication and largely mirrors morbidity. For hospitals in the program at least 3 years, annual reductions in mortality, morbidity, and SSI were estimated to be 0.8%, 3.1%, and 2.6%, respectively.

One of the hallmarks of ACS NSQIP is the accuracy of the data, which come directly from medical records. In a large study comparing clinical with billing (or administrative) data, Dr. Ko and colleagues found the accuracy of billing data to be low.

“In a 2-year study we merged clinical and administrative data from over 100,000 patients and found the agreement to be poor. Billing data had a detection rate for SSI of 25% and a false-positive rate of 70%,” he said.

“In developing programs to improve patient care, we want to base our work on the most accurate data possible. Our analysis shows that hospitals committed to using ACS NSQIP improve over time.”

The authors reported having no financial disclosures.

Patients with advanced melanoma who were treated with immunotherapy responded better if they harbored mutations in the NRAS gene, according to a study published March 3 in Cancer Immunology Research.

Out of 229 cases retrospectively analyzed, 26% had mutations in NRAS^G12/G13/Q61, 23% had BRAF^V600, and 51% were wild type for NRAS and BRAF. Patients received first-line therapy with high-dose IL-2 (25%), ipilimumab (62%), or anti-PD-1/PD-L1 (12%), investigators reported (Cancer Immunol. Res. 2015 March 3).

©benjaminalbiach/ThinkStock

Complete or partial responses were found in 32% of patients with NRAS-mutant melanomas, compared with 20% of those without NRAS mutations (P = .07). Clinical benefit (defined as complete response, partial response, or stable disease for 24 weeks or longer) was observed in 50% of the NRAS mutant group vs. 30% of the non–mutant NRAS group (P < .01), reported Dr. Douglas B. Johnson of Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and associates.

Although the numbers for individual agents were small, the NRAS-mutant benefit was most pronounced for immune checkpoint inhibitors, especially anti-PD-1/PD-L1 therapy, where clinical benefit was observed in 8 of 11 NRAS-mutant patients vs. 13 of 37 patients with wild-type NRAS.

“This finding could have implications for molecular testing and treatment decision making, and it provides early insights into the complex relationship between tumor genetics and the immune response,” Dr. Johnson and associates wrote.

Patients with NRAS-mutant melanoma account for 15%-20% of all melanomas, and the mutation is associated with a poorer prognosis. The authors speculate that elevated PD-1 expression may be a factor in inferior prognosis of NRAS-mutant phenotypes as well as the observed improved response to anti-PD-1.

“We studied a small group of patients, but the results were quite suggestive. Our findings need to be confirmed in a prospective study. This study highlights the need to find predictive markers that can help us understand which patients will respond to therapy. Our study will hopefully lead to understanding the biological mechanisms that explain why NRAS mutations predict response,” Dr. Johnson and his associates said.

Patients with advanced melanoma who were treated with immunotherapy responded better if they harbored mutations in the NRAS gene, according to a study published March 3 in Cancer Immunology Research.

Out of 229 cases retrospectively analyzed, 26% had mutations in NRAS^G12/G13/Q61, 23% had BRAF^V600, and 51% were wild type for NRAS and BRAF. Patients received first-line therapy with high-dose IL-2 (25%), ipilimumab (62%), or anti-PD-1/PD-L1 (12%), investigators reported (Cancer Immunol. Res. 2015 March 3).

©benjaminalbiach/ThinkStock

Complete or partial responses were found in 32% of patients with NRAS-mutant melanomas, compared with 20% of those without NRAS mutations (P = .07). Clinical benefit (defined as complete response, partial response, or stable disease for 24 weeks or longer) was observed in 50% of the NRAS mutant group vs. 30% of the non–mutant NRAS group (P < .01), reported Dr. Douglas B. Johnson of Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and associates.

Although the numbers for individual agents were small, the NRAS-mutant benefit was most pronounced for immune checkpoint inhibitors, especially anti-PD-1/PD-L1 therapy, where clinical benefit was observed in 8 of 11 NRAS-mutant patients vs. 13 of 37 patients with wild-type NRAS.

“This finding could have implications for molecular testing and treatment decision making, and it provides early insights into the complex relationship between tumor genetics and the immune response,” Dr. Johnson and associates wrote.

Patients with NRAS-mutant melanoma account for 15%-20% of all melanomas, and the mutation is associated with a poorer prognosis. The authors speculate that elevated PD-1 expression may be a factor in inferior prognosis of NRAS-mutant phenotypes as well as the observed improved response to anti-PD-1.

“We studied a small group of patients, but the results were quite suggestive. Our findings need to be confirmed in a prospective study. This study highlights the need to find predictive markers that can help us understand which patients will respond to therapy. Our study will hopefully lead to understanding the biological mechanisms that explain why NRAS mutations predict response,” Dr. Johnson and his associates said.

Patients with advanced melanoma who were treated with immunotherapy responded better if they harbored mutations in the NRAS gene, according to a study published March 3 in Cancer Immunology Research.

Out of 229 cases retrospectively analyzed, 26% had mutations in NRAS^G12/G13/Q61, 23% had BRAF^V600, and 51% were wild type for NRAS and BRAF. Patients received first-line therapy with high-dose IL-2 (25%), ipilimumab (62%), or anti-PD-1/PD-L1 (12%), investigators reported (Cancer Immunol. Res. 2015 March 3).

©benjaminalbiach/ThinkStock

Complete or partial responses were found in 32% of patients with NRAS-mutant melanomas, compared with 20% of those without NRAS mutations (P = .07). Clinical benefit (defined as complete response, partial response, or stable disease for 24 weeks or longer) was observed in 50% of the NRAS mutant group vs. 30% of the non–mutant NRAS group (P < .01), reported Dr. Douglas B. Johnson of Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tenn., and associates.

Although the numbers for individual agents were small, the NRAS-mutant benefit was most pronounced for immune checkpoint inhibitors, especially anti-PD-1/PD-L1 therapy, where clinical benefit was observed in 8 of 11 NRAS-mutant patients vs. 13 of 37 patients with wild-type NRAS.

“This finding could have implications for molecular testing and treatment decision making, and it provides early insights into the complex relationship between tumor genetics and the immune response,” Dr. Johnson and associates wrote.

Patients with NRAS-mutant melanoma account for 15%-20% of all melanomas, and the mutation is associated with a poorer prognosis. The authors speculate that elevated PD-1 expression may be a factor in inferior prognosis of NRAS-mutant phenotypes as well as the observed improved response to anti-PD-1.

“We studied a small group of patients, but the results were quite suggestive. Our findings need to be confirmed in a prospective study. This study highlights the need to find predictive markers that can help us understand which patients will respond to therapy. Our study will hopefully lead to understanding the biological mechanisms that explain why NRAS mutations predict response,” Dr. Johnson and his associates said.

The type of epidermal growth factor receptor (EGFR) mutation, L858R or exon 19 deletion, detected in either tissue or circulating free DNA, was significantly associated with outcomes in a study of patients with advanced NSCLC, a study has shown.

The findings were published online Feb. 26 in JAMA Oncology.

The results suggest the potential of liquid biopsies or circulating free (cfDNA) as a substitute for tumor biopsy to detect EGFR mutations.

“The amount of tumor tissue obtained by biopsy is often insufficient, especially in advanced NSCLC, raising the question of whether cfDNA may be used as a surrogate liquid biopsy for the noninvasive assessment of EGFR mutations,” wrote Dr. Niki Karachaliou and associates (JAMA Oncol. 2015 Feb. 26 [doi:10.1001/jamaoncol.2014.257]).

From 173 patients with oncogenic EGFR mutations (identified by tumor biopsy) enrolled in the EURTAC trial, 97 blood samples were suitable for analysis to detect EGFR mutations in cfDNA, and 76 (78%) EGFR mutations were detected from the blood samples. The investigators developed a novel peptide nucleic acid-mediated PCR assay with 78% sensitivity and 100% specificity, an improvement from sensitivity rates for other methods reported to be below 65%.

Overall, the median OS for the 173 patients enrolled in the EURTAC study was 22.9 months (95% CI, 17.0-30.9) for those in the erlotinib arm vs. 22.1 months (16.5-28.4) for the chemotherapy arm. As in previous study findings, OS for patients with the exon 19 deletion detected in tissue were significantly longer than for those with L858R mutations (25.0 months [18.9-30.9] vs 17.7 [13.5-23.5]; P = .001). In the subset of 97 samples that underwent cfDNA analysis, the OS for those with exon 19 deletions was 30.0 months (19.3-37.7) vs. 13.7 months (7.1-17.7) for L858R mutations (P < .001). Among the 40 samples in the erlotinib arm with EGFR mutations detected in cfDNA, the median OS for exon 19 deletions was 34.4 months (22.9-not reached) vs 13.7 months (2.6-21.9) for L858R mutations (P = .001).

Patients with L858R mutations detected in both tissue and cfDNA had significantly shorter median OS than did those with L858R detected in tissue only (13.7 vs 27.7 months; HR, 2.22; P = .03), reported Dr. Karachaliou of Quiron-Dexeus University Hospital, Barcelona.

For patients in the erlotinib arm, progression-free survival was longer for those with exon 19 deletions than L858R mutations, detected both in tissue and cfDNA. No significant difference in PFS was seen in the chemotherapy arm based on EGFR mutation type.

“The shorter OS – both for all patients and for those receiving erlotinib therapy – observed in the present study among patients with L858R mutations in tissue or cfDNA reinforces this concept of the existence of more than one clinical phenotype of EGFR-mutant NSCLC and suggests that in future analyses, outcomes of patients with exon 19 deletions and those with L858R mutations should not be pooled,” Dr. Karachaliou wrote.

Citing the favorable comparison between their assay and previous methods, the authors concluded that “cfDNA may be a promising method for screening for EGFR mutations in clinical studies, minimizing the need for invasive tumor biopsies.”

The type of epidermal growth factor receptor (EGFR) mutation, L858R or exon 19 deletion, detected in either tissue or circulating free DNA, was significantly associated with outcomes in a study of patients with advanced NSCLC, a study has shown.

The findings were published online Feb. 26 in JAMA Oncology.

The results suggest the potential of liquid biopsies or circulating free (cfDNA) as a substitute for tumor biopsy to detect EGFR mutations.

“The amount of tumor tissue obtained by biopsy is often insufficient, especially in advanced NSCLC, raising the question of whether cfDNA may be used as a surrogate liquid biopsy for the noninvasive assessment of EGFR mutations,” wrote Dr. Niki Karachaliou and associates (JAMA Oncol. 2015 Feb. 26 [doi:10.1001/jamaoncol.2014.257]).

From 173 patients with oncogenic EGFR mutations (identified by tumor biopsy) enrolled in the EURTAC trial, 97 blood samples were suitable for analysis to detect EGFR mutations in cfDNA, and 76 (78%) EGFR mutations were detected from the blood samples. The investigators developed a novel peptide nucleic acid-mediated PCR assay with 78% sensitivity and 100% specificity, an improvement from sensitivity rates for other methods reported to be below 65%.

Overall, the median OS for the 173 patients enrolled in the EURTAC study was 22.9 months (95% CI, 17.0-30.9) for those in the erlotinib arm vs. 22.1 months (16.5-28.4) for the chemotherapy arm. As in previous study findings, OS for patients with the exon 19 deletion detected in tissue were significantly longer than for those with L858R mutations (25.0 months [18.9-30.9] vs 17.7 [13.5-23.5]; P = .001). In the subset of 97 samples that underwent cfDNA analysis, the OS for those with exon 19 deletions was 30.0 months (19.3-37.7) vs. 13.7 months (7.1-17.7) for L858R mutations (P < .001). Among the 40 samples in the erlotinib arm with EGFR mutations detected in cfDNA, the median OS for exon 19 deletions was 34.4 months (22.9-not reached) vs 13.7 months (2.6-21.9) for L858R mutations (P = .001).

Patients with L858R mutations detected in both tissue and cfDNA had significantly shorter median OS than did those with L858R detected in tissue only (13.7 vs 27.7 months; HR, 2.22; P = .03), reported Dr. Karachaliou of Quiron-Dexeus University Hospital, Barcelona.

For patients in the erlotinib arm, progression-free survival was longer for those with exon 19 deletions than L858R mutations, detected both in tissue and cfDNA. No significant difference in PFS was seen in the chemotherapy arm based on EGFR mutation type.

“The shorter OS – both for all patients and for those receiving erlotinib therapy – observed in the present study among patients with L858R mutations in tissue or cfDNA reinforces this concept of the existence of more than one clinical phenotype of EGFR-mutant NSCLC and suggests that in future analyses, outcomes of patients with exon 19 deletions and those with L858R mutations should not be pooled,” Dr. Karachaliou wrote.

Citing the favorable comparison between their assay and previous methods, the authors concluded that “cfDNA may be a promising method for screening for EGFR mutations in clinical studies, minimizing the need for invasive tumor biopsies.”

The type of epidermal growth factor receptor (EGFR) mutation, L858R or exon 19 deletion, detected in either tissue or circulating free DNA, was significantly associated with outcomes in a study of patients with advanced NSCLC, a study has shown.

The findings were published online Feb. 26 in JAMA Oncology.

The results suggest the potential of liquid biopsies or circulating free (cfDNA) as a substitute for tumor biopsy to detect EGFR mutations.

“The amount of tumor tissue obtained by biopsy is often insufficient, especially in advanced NSCLC, raising the question of whether cfDNA may be used as a surrogate liquid biopsy for the noninvasive assessment of EGFR mutations,” wrote Dr. Niki Karachaliou and associates (JAMA Oncol. 2015 Feb. 26 [doi:10.1001/jamaoncol.2014.257]).

From 173 patients with oncogenic EGFR mutations (identified by tumor biopsy) enrolled in the EURTAC trial, 97 blood samples were suitable for analysis to detect EGFR mutations in cfDNA, and 76 (78%) EGFR mutations were detected from the blood samples. The investigators developed a novel peptide nucleic acid-mediated PCR assay with 78% sensitivity and 100% specificity, an improvement from sensitivity rates for other methods reported to be below 65%.

Overall, the median OS for the 173 patients enrolled in the EURTAC study was 22.9 months (95% CI, 17.0-30.9) for those in the erlotinib arm vs. 22.1 months (16.5-28.4) for the chemotherapy arm. As in previous study findings, OS for patients with the exon 19 deletion detected in tissue were significantly longer than for those with L858R mutations (25.0 months [18.9-30.9] vs 17.7 [13.5-23.5]; P = .001). In the subset of 97 samples that underwent cfDNA analysis, the OS for those with exon 19 deletions was 30.0 months (19.3-37.7) vs. 13.7 months (7.1-17.7) for L858R mutations (P < .001). Among the 40 samples in the erlotinib arm with EGFR mutations detected in cfDNA, the median OS for exon 19 deletions was 34.4 months (22.9-not reached) vs 13.7 months (2.6-21.9) for L858R mutations (P = .001).

Patients with L858R mutations detected in both tissue and cfDNA had significantly shorter median OS than did those with L858R detected in tissue only (13.7 vs 27.7 months; HR, 2.22; P = .03), reported Dr. Karachaliou of Quiron-Dexeus University Hospital, Barcelona.

For patients in the erlotinib arm, progression-free survival was longer for those with exon 19 deletions than L858R mutations, detected both in tissue and cfDNA. No significant difference in PFS was seen in the chemotherapy arm based on EGFR mutation type.

“The shorter OS – both for all patients and for those receiving erlotinib therapy – observed in the present study among patients with L858R mutations in tissue or cfDNA reinforces this concept of the existence of more than one clinical phenotype of EGFR-mutant NSCLC and suggests that in future analyses, outcomes of patients with exon 19 deletions and those with L858R mutations should not be pooled,” Dr. Karachaliou wrote.

Citing the favorable comparison between their assay and previous methods, the authors concluded that “cfDNA may be a promising method for screening for EGFR mutations in clinical studies, minimizing the need for invasive tumor biopsies.”

A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.

Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).

Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.

This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).

“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.

Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.

A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.

Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).

Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.

This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).

“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.

Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.

A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.

Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).

Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.

This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).

“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.

Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.

Addition of the vascular-targeted bevacizumab to gemcitabine-docetaxel in patients with chemotherapy-naive metastatic uterine leiomyosarcoma did not improve progression-free survival, overall survival, overall response rate, or response duration, according to a report published online Feb. 23 in the Journal of Clinical Oncology.

The phase III trial found similar outcomes between the 54 patients who took gemcitabine-docetaxel plus placebo and the 53 women who took gemcitabine-docetaxel plus bevacizumab. Progression-free survival was 6.2 months (95% CI, 2.9 to 9.9) vs. 4.2 months (3.1 to 8.4) for gemcitabine-docetaxel plus placebo vs. gemcitabine-docetaxel plus bevacizumab, respectively; the proportion of patients progression free after 12 months was 26.4% vs. 25%, respectively; and the proportion of patients alive after 12 months was 74.7% and 71%, respectively. Safety profiles were similar for the two groups, reported Dr. Martee L. Hensley and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.3781]).

Notable in this study was that docetaxel was used at a lower dose, 75 mg/m², than in previous phase II studies of docetaxel-gemcitabine fixed-dose combinations that used docetaxel at 100 mg/m². These results show similar overall response rates and response durations for the docetaxel-gemcitabine plus placebo arm and suggest that the lower dose will likely yield similar outcomes with less toxicity.

Few chemotherapy agents have shown activity against metastatic uterine leiomyosarcoma (mLMS). “The failure of bevacizumab to improve any clinical outcome in uLMS raises the question of whether there is any role for antivascular-directed therapy in this disease. Phase II single-agent studies of vascular-targeted agents have mostly yielded negative results,” wrote Dr. Hensley of Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, and associates.

Addition of the vascular-targeted bevacizumab to gemcitabine-docetaxel in patients with chemotherapy-naive metastatic uterine leiomyosarcoma did not improve progression-free survival, overall survival, overall response rate, or response duration, according to a report published online Feb. 23 in the Journal of Clinical Oncology.

The phase III trial found similar outcomes between the 54 patients who took gemcitabine-docetaxel plus placebo and the 53 women who took gemcitabine-docetaxel plus bevacizumab. Progression-free survival was 6.2 months (95% CI, 2.9 to 9.9) vs. 4.2 months (3.1 to 8.4) for gemcitabine-docetaxel plus placebo vs. gemcitabine-docetaxel plus bevacizumab, respectively; the proportion of patients progression free after 12 months was 26.4% vs. 25%, respectively; and the proportion of patients alive after 12 months was 74.7% and 71%, respectively. Safety profiles were similar for the two groups, reported Dr. Martee L. Hensley and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.3781]).

Notable in this study was that docetaxel was used at a lower dose, 75 mg/m², than in previous phase II studies of docetaxel-gemcitabine fixed-dose combinations that used docetaxel at 100 mg/m². These results show similar overall response rates and response durations for the docetaxel-gemcitabine plus placebo arm and suggest that the lower dose will likely yield similar outcomes with less toxicity.

Few chemotherapy agents have shown activity against metastatic uterine leiomyosarcoma (mLMS). “The failure of bevacizumab to improve any clinical outcome in uLMS raises the question of whether there is any role for antivascular-directed therapy in this disease. Phase II single-agent studies of vascular-targeted agents have mostly yielded negative results,” wrote Dr. Hensley of Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, and associates.

Addition of the vascular-targeted bevacizumab to gemcitabine-docetaxel in patients with chemotherapy-naive metastatic uterine leiomyosarcoma did not improve progression-free survival, overall survival, overall response rate, or response duration, according to a report published online Feb. 23 in the Journal of Clinical Oncology.

The phase III trial found similar outcomes between the 54 patients who took gemcitabine-docetaxel plus placebo and the 53 women who took gemcitabine-docetaxel plus bevacizumab. Progression-free survival was 6.2 months (95% CI, 2.9 to 9.9) vs. 4.2 months (3.1 to 8.4) for gemcitabine-docetaxel plus placebo vs. gemcitabine-docetaxel plus bevacizumab, respectively; the proportion of patients progression free after 12 months was 26.4% vs. 25%, respectively; and the proportion of patients alive after 12 months was 74.7% and 71%, respectively. Safety profiles were similar for the two groups, reported Dr. Martee L. Hensley and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.3781]).

Notable in this study was that docetaxel was used at a lower dose, 75 mg/m², than in previous phase II studies of docetaxel-gemcitabine fixed-dose combinations that used docetaxel at 100 mg/m². These results show similar overall response rates and response durations for the docetaxel-gemcitabine plus placebo arm and suggest that the lower dose will likely yield similar outcomes with less toxicity.

Few chemotherapy agents have shown activity against metastatic uterine leiomyosarcoma (mLMS). “The failure of bevacizumab to improve any clinical outcome in uLMS raises the question of whether there is any role for antivascular-directed therapy in this disease. Phase II single-agent studies of vascular-targeted agents have mostly yielded negative results,” wrote Dr. Hensley of Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, and associates.