Jennifer Kelly Shepphird

After curative-intent surgery, patients with stage III colon cancer who received oxaliplatin plus capecitabine (XELOX) had improved disease-free survival and overall survival, compared with those who received fluorouracil/folinic acid (FU/FA), according to secondary analysis of the NO16968 study.

After a median 74-month follow-up, 320 of 944 patients in the XELOX group (34%) experienced relapse, developed a new colon cancer, or died, compared with 379 of 942 patients in the FU/FA group (40%), for a hazard ratio of 0.80 (95% confidence interval, 0.69-0.93; P = .004). After a median follow-up of 83 months, 242 (26%) in the XELOX group died, compared with 286 (30%) in the FU/FA group, for a HR of 0.83 (95% CI, 0.70-0.99; P = .04).

Disease-free survival (DFS) and overall survival (OS) rates were consistently higher for XELOX after 3-7 years of follow-up, and the differences between the treatments increased after the primary analysis. Survival rates for XELOX and FU/FA were 86% vs. 84%, respectively, in year 3; 80% vs. 78% in year 4; 77% vs. 74% in year 5; 76% vs. 71% in year 6; and 73% vs. 67% in year 7.

“Multiple incremental advances in the treatment and detection of recurrent colon cancer mean that a longer follow-up of 6 or 7 years may be required to assess survival benefit in modern adjuvant trials reliably,” wrote Dr. Hans-Joachim Schmoll of the department of oncology/hematology at Martin Luther University in Halle, Germany, and his colleagues (J Clin Oncol. 2015 Aug 31. doi: 10.1200/JCO.2014.60.9107).

The survival benefits observed in this trial are in line with those of the previous MOSAIC trial, which used a similar cumulative dose of oxaliplatin (1,040 mg/m² and 1,020 mg/m², respectively).

“Together, these trials show that oxaliplatin improves OS when added to a fluoropyrimidine as adjuvant therapy in patients with stage III colon cancer, and that the fluoropyrimidine may be delivered intravenously by infusion or orally for the same result,” the investigators observed.

The multinational, open-label, parallel, randomized phase III study included 1,886 patients who received XELOX or FU/FA from 2003 to 2004.

Subset analysis for patients older than 70 years showed an increased survival benefit for XELOX over FU/FA, but the effect size was smaller than in younger patients and the conclusions were not definitive because of the small subgroup sizes.

A biomarker analysis included 26% of the trial participants: 242 in the XELOX group and 256 in the FU/FA group. Patients in the XELOX group who had lower expression of dihydropyrimidine dehydrogenase had better outcomes (P less than 001). Patients in the FU/FA group showed no significant associations between tumor biomarkers and outcomes. The study was supported by F. Hoffmann-La Roche. Dr. Schmoll reported consulting or advisory roles with Genentech, Taiho Pharmaceutical, and Bayer Schering Pharma. Several of his coauthors reported ties to industry sources.

After curative-intent surgery, patients with stage III colon cancer who received oxaliplatin plus capecitabine (XELOX) had improved disease-free survival and overall survival, compared with those who received fluorouracil/folinic acid (FU/FA), according to secondary analysis of the NO16968 study.

After a median 74-month follow-up, 320 of 944 patients in the XELOX group (34%) experienced relapse, developed a new colon cancer, or died, compared with 379 of 942 patients in the FU/FA group (40%), for a hazard ratio of 0.80 (95% confidence interval, 0.69-0.93; P = .004). After a median follow-up of 83 months, 242 (26%) in the XELOX group died, compared with 286 (30%) in the FU/FA group, for a HR of 0.83 (95% CI, 0.70-0.99; P = .04).

Disease-free survival (DFS) and overall survival (OS) rates were consistently higher for XELOX after 3-7 years of follow-up, and the differences between the treatments increased after the primary analysis. Survival rates for XELOX and FU/FA were 86% vs. 84%, respectively, in year 3; 80% vs. 78% in year 4; 77% vs. 74% in year 5; 76% vs. 71% in year 6; and 73% vs. 67% in year 7.

“Multiple incremental advances in the treatment and detection of recurrent colon cancer mean that a longer follow-up of 6 or 7 years may be required to assess survival benefit in modern adjuvant trials reliably,” wrote Dr. Hans-Joachim Schmoll of the department of oncology/hematology at Martin Luther University in Halle, Germany, and his colleagues (J Clin Oncol. 2015 Aug 31. doi: 10.1200/JCO.2014.60.9107).

The survival benefits observed in this trial are in line with those of the previous MOSAIC trial, which used a similar cumulative dose of oxaliplatin (1,040 mg/m² and 1,020 mg/m², respectively).

“Together, these trials show that oxaliplatin improves OS when added to a fluoropyrimidine as adjuvant therapy in patients with stage III colon cancer, and that the fluoropyrimidine may be delivered intravenously by infusion or orally for the same result,” the investigators observed.

The multinational, open-label, parallel, randomized phase III study included 1,886 patients who received XELOX or FU/FA from 2003 to 2004.

Subset analysis for patients older than 70 years showed an increased survival benefit for XELOX over FU/FA, but the effect size was smaller than in younger patients and the conclusions were not definitive because of the small subgroup sizes.

A biomarker analysis included 26% of the trial participants: 242 in the XELOX group and 256 in the FU/FA group. Patients in the XELOX group who had lower expression of dihydropyrimidine dehydrogenase had better outcomes (P less than 001). Patients in the FU/FA group showed no significant associations between tumor biomarkers and outcomes. The study was supported by F. Hoffmann-La Roche. Dr. Schmoll reported consulting or advisory roles with Genentech, Taiho Pharmaceutical, and Bayer Schering Pharma. Several of his coauthors reported ties to industry sources.

After curative-intent surgery, patients with stage III colon cancer who received oxaliplatin plus capecitabine (XELOX) had improved disease-free survival and overall survival, compared with those who received fluorouracil/folinic acid (FU/FA), according to secondary analysis of the NO16968 study.

After a median 74-month follow-up, 320 of 944 patients in the XELOX group (34%) experienced relapse, developed a new colon cancer, or died, compared with 379 of 942 patients in the FU/FA group (40%), for a hazard ratio of 0.80 (95% confidence interval, 0.69-0.93; P = .004). After a median follow-up of 83 months, 242 (26%) in the XELOX group died, compared with 286 (30%) in the FU/FA group, for a HR of 0.83 (95% CI, 0.70-0.99; P = .04).

Disease-free survival (DFS) and overall survival (OS) rates were consistently higher for XELOX after 3-7 years of follow-up, and the differences between the treatments increased after the primary analysis. Survival rates for XELOX and FU/FA were 86% vs. 84%, respectively, in year 3; 80% vs. 78% in year 4; 77% vs. 74% in year 5; 76% vs. 71% in year 6; and 73% vs. 67% in year 7.

“Multiple incremental advances in the treatment and detection of recurrent colon cancer mean that a longer follow-up of 6 or 7 years may be required to assess survival benefit in modern adjuvant trials reliably,” wrote Dr. Hans-Joachim Schmoll of the department of oncology/hematology at Martin Luther University in Halle, Germany, and his colleagues (J Clin Oncol. 2015 Aug 31. doi: 10.1200/JCO.2014.60.9107).

The survival benefits observed in this trial are in line with those of the previous MOSAIC trial, which used a similar cumulative dose of oxaliplatin (1,040 mg/m² and 1,020 mg/m², respectively).

“Together, these trials show that oxaliplatin improves OS when added to a fluoropyrimidine as adjuvant therapy in patients with stage III colon cancer, and that the fluoropyrimidine may be delivered intravenously by infusion or orally for the same result,” the investigators observed.

The multinational, open-label, parallel, randomized phase III study included 1,886 patients who received XELOX or FU/FA from 2003 to 2004.

Subset analysis for patients older than 70 years showed an increased survival benefit for XELOX over FU/FA, but the effect size was smaller than in younger patients and the conclusions were not definitive because of the small subgroup sizes.

A biomarker analysis included 26% of the trial participants: 242 in the XELOX group and 256 in the FU/FA group. Patients in the XELOX group who had lower expression of dihydropyrimidine dehydrogenase had better outcomes (P less than 001). Patients in the FU/FA group showed no significant associations between tumor biomarkers and outcomes. The study was supported by F. Hoffmann-La Roche. Dr. Schmoll reported consulting or advisory roles with Genentech, Taiho Pharmaceutical, and Bayer Schering Pharma. Several of his coauthors reported ties to industry sources.

Regorafenib carries high incremental cost and delivers small incremental benefit, providing low value for patients with metastatic colorectal cancer, researchers reported online Aug. 24 in the Journal of Clinical Oncology.

Compared with best supportive care, use of regorafenib resulted in a gain of 6 weeks of life, which dropped to 2 quality-adjusted weeks of life (0.04 quality-adjusted life years [QALYs]) in light of its significant toxicity profile. With the cost of treatment estimated between $32,000 and $43,000, depending on the dose, the incremental cost-effectiveness ratio (ICER) was $730,000-$980,000 per QALY, Dr. Daniel Goldstein and his associates reported (J Clin Oncol. 2015 Aug 24. doi: 10.1200/JCO.2014.61.9569).

“With increasing deductibles and copays, our patients are now bearing a significant burden of the cost of drugs,” wrote Dr. Goldstein of the department of hematology and medical oncology at Emory University, Atlanta, and his colleagues. There is a need, they wrote, for new strategies “in patient selection for clinical trials, guideline development, and payer coverage determination that address clinical value in addition to statistically significant clinical benefit.”

The CORRECT (Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy) trial indicated an overall survival benefit of 1.4 months for regorafenib, compared with placebo, in patients with colorectal cancer who progressed after standard regimens. Adverse events of grade 3 or 4 occurred in 54% of the regorafenib arm, compared with 14% in the placebo arm.

The analysis based on the CORRECT data indicated a low likelihood that regorafenib would be considered cost effective at a willingness to pay threshold less than $600,000 per QALY. Regorafenib exceeds typical accepted values for cost-effectiveness.

Model parameters that most influenced ICER were regorafenib cost, probability of stopping treatment due to an adverse event, and baseline utility value. The ICER remained greater than $550,000 per QALY across a broad range of each of these variables.

Given the increasing amount of out-of-pocket costs for patients, the investigators recommend “a careful discussion between physicians and patients regarding the additional benefit and potential total drug cost before starting regorafenib.”

The study was supported by internal funds and by a grant from the National Institutes of Health. Dr. Goldstein reported having no disclosures. Three of his coauthors reported ties to industry.

Regorafenib carries high incremental cost and delivers small incremental benefit, providing low value for patients with metastatic colorectal cancer, researchers reported online Aug. 24 in the Journal of Clinical Oncology.

Compared with best supportive care, use of regorafenib resulted in a gain of 6 weeks of life, which dropped to 2 quality-adjusted weeks of life (0.04 quality-adjusted life years [QALYs]) in light of its significant toxicity profile. With the cost of treatment estimated between $32,000 and $43,000, depending on the dose, the incremental cost-effectiveness ratio (ICER) was $730,000-$980,000 per QALY, Dr. Daniel Goldstein and his associates reported (J Clin Oncol. 2015 Aug 24. doi: 10.1200/JCO.2014.61.9569).

“With increasing deductibles and copays, our patients are now bearing a significant burden of the cost of drugs,” wrote Dr. Goldstein of the department of hematology and medical oncology at Emory University, Atlanta, and his colleagues. There is a need, they wrote, for new strategies “in patient selection for clinical trials, guideline development, and payer coverage determination that address clinical value in addition to statistically significant clinical benefit.”

The CORRECT (Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy) trial indicated an overall survival benefit of 1.4 months for regorafenib, compared with placebo, in patients with colorectal cancer who progressed after standard regimens. Adverse events of grade 3 or 4 occurred in 54% of the regorafenib arm, compared with 14% in the placebo arm.

The analysis based on the CORRECT data indicated a low likelihood that regorafenib would be considered cost effective at a willingness to pay threshold less than $600,000 per QALY. Regorafenib exceeds typical accepted values for cost-effectiveness.

Model parameters that most influenced ICER were regorafenib cost, probability of stopping treatment due to an adverse event, and baseline utility value. The ICER remained greater than $550,000 per QALY across a broad range of each of these variables.

Given the increasing amount of out-of-pocket costs for patients, the investigators recommend “a careful discussion between physicians and patients regarding the additional benefit and potential total drug cost before starting regorafenib.”

The study was supported by internal funds and by a grant from the National Institutes of Health. Dr. Goldstein reported having no disclosures. Three of his coauthors reported ties to industry.

Regorafenib carries high incremental cost and delivers small incremental benefit, providing low value for patients with metastatic colorectal cancer, researchers reported online Aug. 24 in the Journal of Clinical Oncology.

Compared with best supportive care, use of regorafenib resulted in a gain of 6 weeks of life, which dropped to 2 quality-adjusted weeks of life (0.04 quality-adjusted life years [QALYs]) in light of its significant toxicity profile. With the cost of treatment estimated between $32,000 and $43,000, depending on the dose, the incremental cost-effectiveness ratio (ICER) was $730,000-$980,000 per QALY, Dr. Daniel Goldstein and his associates reported (J Clin Oncol. 2015 Aug 24. doi: 10.1200/JCO.2014.61.9569).

“With increasing deductibles and copays, our patients are now bearing a significant burden of the cost of drugs,” wrote Dr. Goldstein of the department of hematology and medical oncology at Emory University, Atlanta, and his colleagues. There is a need, they wrote, for new strategies “in patient selection for clinical trials, guideline development, and payer coverage determination that address clinical value in addition to statistically significant clinical benefit.”

The CORRECT (Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy) trial indicated an overall survival benefit of 1.4 months for regorafenib, compared with placebo, in patients with colorectal cancer who progressed after standard regimens. Adverse events of grade 3 or 4 occurred in 54% of the regorafenib arm, compared with 14% in the placebo arm.

The analysis based on the CORRECT data indicated a low likelihood that regorafenib would be considered cost effective at a willingness to pay threshold less than $600,000 per QALY. Regorafenib exceeds typical accepted values for cost-effectiveness.

Model parameters that most influenced ICER were regorafenib cost, probability of stopping treatment due to an adverse event, and baseline utility value. The ICER remained greater than $550,000 per QALY across a broad range of each of these variables.

Given the increasing amount of out-of-pocket costs for patients, the investigators recommend “a careful discussion between physicians and patients regarding the additional benefit and potential total drug cost before starting regorafenib.”

The study was supported by internal funds and by a grant from the National Institutes of Health. Dr. Goldstein reported having no disclosures. Three of his coauthors reported ties to industry.

Patients with human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) who had human papillomavirus type 16 (HPV16) detected in oral rinses both at diagnosis and at any time after treatment were more likely to have OPC recurrence, according to a report published online in JAMA Oncology.

Detection of HPV16 DNA was frequent among patients at diagnosis (67 of 124 patients), but rare posttreatment (6 of 124 patients). Persistent HPV16 detection (at and after diagnosis) was associated with greater risk of disease recurrence (hazard ratio, 29.7) and death (HR, 23.5).

National Cancer Institute

Approximately 10%-25% of patients with HPV-OPC experience progression after treatment, and surgical salvage is the most favorable treatment in these cases. However, surgery is not feasible for the significant proportion of HPV-OPC cases that have already spread to distant sites at the time of diagnosis.

“There is a need for clinically relevant biomarkers of disease recurrence to facilitate timely initiation of aggressive diagnostic investigation and subsequent salvage treatment to potentially improve outcomes for the growing population of HPV-OPC survivors,” wrote Dr. Eleni M. Rettig of the department of otolaryngology–head and neck surgery, Johns Hopkins University, Baltimore, and her colleagues (JAMA Oncol. 2015 July 30 [doi:10.1001/jamaoncol.2015.2524]).

“Detection of recurrent local or locoregional disease prior to distant spread is particularly desirable given the favorable response of HPV-OPC to surgical salvage,” the study authors observed.

The multisite, prospective cohort study evaluated 124 patients with HPV-related oropharyngeal carcinoma who had at least one posttreatment oral rinse sample. Most patients with HPV16 DNA detected at diagnosis had none detected after treatment (62 of 67 patients). Contrary to persistent HPV16 DNA detection, HPV16 detected at diagnosis was not significantly associated with disease-free or overall survival.

Based on the six patients who had posttreatment detection of HPV16 DNA in oral rinses, the sensitivity and specificity of predicting recurrence at 9-12 months were 43% and 100%, respectively. Considering only local disease recurrence, the sensitivity and specificity were 100% and 100%, respectively.

The median time from the first posttreatment detection of HPV16 DNA to recurrence was 7.0 months. That “clinically meaningful lead time” is important in evaluating HPV16 DNA detection in oral rinses as “a valuable tool for long-term posttreatment surveillance of HPV-OPC for local recurrence,” the investigators concluded.

Dr. Rettig reported having no disclosures. Several coauthors reported ties to industry sources.

Patients with human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) who had human papillomavirus type 16 (HPV16) detected in oral rinses both at diagnosis and at any time after treatment were more likely to have OPC recurrence, according to a report published online in JAMA Oncology.

Detection of HPV16 DNA was frequent among patients at diagnosis (67 of 124 patients), but rare posttreatment (6 of 124 patients). Persistent HPV16 detection (at and after diagnosis) was associated with greater risk of disease recurrence (hazard ratio, 29.7) and death (HR, 23.5).

National Cancer Institute

Approximately 10%-25% of patients with HPV-OPC experience progression after treatment, and surgical salvage is the most favorable treatment in these cases. However, surgery is not feasible for the significant proportion of HPV-OPC cases that have already spread to distant sites at the time of diagnosis.

“There is a need for clinically relevant biomarkers of disease recurrence to facilitate timely initiation of aggressive diagnostic investigation and subsequent salvage treatment to potentially improve outcomes for the growing population of HPV-OPC survivors,” wrote Dr. Eleni M. Rettig of the department of otolaryngology–head and neck surgery, Johns Hopkins University, Baltimore, and her colleagues (JAMA Oncol. 2015 July 30 [doi:10.1001/jamaoncol.2015.2524]).

“Detection of recurrent local or locoregional disease prior to distant spread is particularly desirable given the favorable response of HPV-OPC to surgical salvage,” the study authors observed.

The multisite, prospective cohort study evaluated 124 patients with HPV-related oropharyngeal carcinoma who had at least one posttreatment oral rinse sample. Most patients with HPV16 DNA detected at diagnosis had none detected after treatment (62 of 67 patients). Contrary to persistent HPV16 DNA detection, HPV16 detected at diagnosis was not significantly associated with disease-free or overall survival.

Based on the six patients who had posttreatment detection of HPV16 DNA in oral rinses, the sensitivity and specificity of predicting recurrence at 9-12 months were 43% and 100%, respectively. Considering only local disease recurrence, the sensitivity and specificity were 100% and 100%, respectively.

The median time from the first posttreatment detection of HPV16 DNA to recurrence was 7.0 months. That “clinically meaningful lead time” is important in evaluating HPV16 DNA detection in oral rinses as “a valuable tool for long-term posttreatment surveillance of HPV-OPC for local recurrence,” the investigators concluded.

Dr. Rettig reported having no disclosures. Several coauthors reported ties to industry sources.

Patients with human papillomavirus–related oropharyngeal carcinoma (HPV-OPC) who had human papillomavirus type 16 (HPV16) detected in oral rinses both at diagnosis and at any time after treatment were more likely to have OPC recurrence, according to a report published online in JAMA Oncology.

Detection of HPV16 DNA was frequent among patients at diagnosis (67 of 124 patients), but rare posttreatment (6 of 124 patients). Persistent HPV16 detection (at and after diagnosis) was associated with greater risk of disease recurrence (hazard ratio, 29.7) and death (HR, 23.5).

National Cancer Institute

Approximately 10%-25% of patients with HPV-OPC experience progression after treatment, and surgical salvage is the most favorable treatment in these cases. However, surgery is not feasible for the significant proportion of HPV-OPC cases that have already spread to distant sites at the time of diagnosis.

“There is a need for clinically relevant biomarkers of disease recurrence to facilitate timely initiation of aggressive diagnostic investigation and subsequent salvage treatment to potentially improve outcomes for the growing population of HPV-OPC survivors,” wrote Dr. Eleni M. Rettig of the department of otolaryngology–head and neck surgery, Johns Hopkins University, Baltimore, and her colleagues (JAMA Oncol. 2015 July 30 [doi:10.1001/jamaoncol.2015.2524]).

“Detection of recurrent local or locoregional disease prior to distant spread is particularly desirable given the favorable response of HPV-OPC to surgical salvage,” the study authors observed.

The multisite, prospective cohort study evaluated 124 patients with HPV-related oropharyngeal carcinoma who had at least one posttreatment oral rinse sample. Most patients with HPV16 DNA detected at diagnosis had none detected after treatment (62 of 67 patients). Contrary to persistent HPV16 DNA detection, HPV16 detected at diagnosis was not significantly associated with disease-free or overall survival.

Based on the six patients who had posttreatment detection of HPV16 DNA in oral rinses, the sensitivity and specificity of predicting recurrence at 9-12 months were 43% and 100%, respectively. Considering only local disease recurrence, the sensitivity and specificity were 100% and 100%, respectively.

The median time from the first posttreatment detection of HPV16 DNA to recurrence was 7.0 months. That “clinically meaningful lead time” is important in evaluating HPV16 DNA detection in oral rinses as “a valuable tool for long-term posttreatment surveillance of HPV-OPC for local recurrence,” the investigators concluded.

Dr. Rettig reported having no disclosures. Several coauthors reported ties to industry sources.

For patients with esophageal cancer, salvage surgery after definitive chemoradiotherapy had similar mortality and morbidity rates, and similar survival outcomes, to the combination of neoadjuvant chemoradiation and planned surgery, according to a study published online in the Journal of Clinical Oncology.

Definitive chemoradiotherapy (dCRT) is an alternative to highly invasive surgical resection, which carries a significant rate of morbidity and mortality; however, recent data indicate that 50% of patients with complete response to dCRT experience tumor recurrence.

“Our study demonstrated a similar survival and recurrence pattern for the SALV [salvage surgery after definitive chemoradiotherapy] and NCRS [neoadjuvant chemoradiation and planned surgery] groups, potentially validating an approach of dCRT with reserved SALV for persistent or recurrent disease. Importantly, there were no differences in oncologic safety of surgery, including extent of nodal dissection, between the SALV and NCRS groups,” wrote Dr. Sheraz Markar, a clinical research fellow from Imperial College, London, and colleagues (Journ. Clin. Onc. 2015 July 20 [doi:10.1200/JCO.2014.59.9092]).

The retrospective study compared 308 patients with esophageal cancer who underwent SALV with 540 patients who received NCRS at European centers from 2000 to 2010. After a median follow up of 54 months, the SALV and NCRS groups had similar rates of 3-year overall survival (43.3% vs. 40.1% ) and disease-free survival (39.2% vs. 32.8%). The two groups also had similar rates tumor recurrence: overall (46.8% vs. 47.9%), locoregional (18.8% vs. 15.9%), distant (24.3% vs. 28.1%) and mixed (13.0% vs. 13.5%).

The SALV and NCRS groups had similar rates of in-hospital mortality (8.4% vs. 9.3%) and morbidity (63.6% vs. 58.9%), but SALV patients had significantly more complications from anastomotic leak (17.2% vs. 10.7%) and surgical site infection (18.5% vs. 12.2%).

Subset analysis of the SALV group showed that patients who received a total radiation dose ≥ 55 Gy (compared with SALV patients who received a lower dose) had significantly increased in-hospital mortality (27.8% vs. 4.3%; P < .001), overall morbidity (75.9% vs. 61%; P = .039), anastomotic leak (27.8% vs. 15%; P = .023), surgical site infection (29.6% vs. 16.1%; P = .02), and pulmonary complications (55.6% vs. 40.2%; P = .038).

“Currently, there is no evidence in terms of locoregional control or survival benefit to support a high total radiation dose (> 50 Gy) in patients receiving dCRT,” according to the researchers, who noted that the findings suggest, “an upper threshold of 50 Gy should be used in these patients to optimize the benefits of dCRT without compromising the safety of SALV, if required.”

Patients who underwent SALV at high-volume centers had significantly lower rates of in-hospital mortality (6.3% vs. 16.2%; P = .009) and overall morbidity (58.8% vs. 80.9%; P = .001) compared with procedures done at low-volume centers.

Compared with recurrent disease, patients with persistent disease after dCRT had poorer long-term prognoses, suggesting a more aggressive tumor biology. Early identification of CRT-resistant tumors to allow early surgical treatment is an important area for future investigation, the investigators said.

For patients with esophageal cancer, salvage surgery after definitive chemoradiotherapy had similar mortality and morbidity rates, and similar survival outcomes, to the combination of neoadjuvant chemoradiation and planned surgery, according to a study published online in the Journal of Clinical Oncology.

Definitive chemoradiotherapy (dCRT) is an alternative to highly invasive surgical resection, which carries a significant rate of morbidity and mortality; however, recent data indicate that 50% of patients with complete response to dCRT experience tumor recurrence.

“Our study demonstrated a similar survival and recurrence pattern for the SALV [salvage surgery after definitive chemoradiotherapy] and NCRS [neoadjuvant chemoradiation and planned surgery] groups, potentially validating an approach of dCRT with reserved SALV for persistent or recurrent disease. Importantly, there were no differences in oncologic safety of surgery, including extent of nodal dissection, between the SALV and NCRS groups,” wrote Dr. Sheraz Markar, a clinical research fellow from Imperial College, London, and colleagues (Journ. Clin. Onc. 2015 July 20 [doi:10.1200/JCO.2014.59.9092]).

The retrospective study compared 308 patients with esophageal cancer who underwent SALV with 540 patients who received NCRS at European centers from 2000 to 2010. After a median follow up of 54 months, the SALV and NCRS groups had similar rates of 3-year overall survival (43.3% vs. 40.1% ) and disease-free survival (39.2% vs. 32.8%). The two groups also had similar rates tumor recurrence: overall (46.8% vs. 47.9%), locoregional (18.8% vs. 15.9%), distant (24.3% vs. 28.1%) and mixed (13.0% vs. 13.5%).

The SALV and NCRS groups had similar rates of in-hospital mortality (8.4% vs. 9.3%) and morbidity (63.6% vs. 58.9%), but SALV patients had significantly more complications from anastomotic leak (17.2% vs. 10.7%) and surgical site infection (18.5% vs. 12.2%).

Subset analysis of the SALV group showed that patients who received a total radiation dose ≥ 55 Gy (compared with SALV patients who received a lower dose) had significantly increased in-hospital mortality (27.8% vs. 4.3%; P < .001), overall morbidity (75.9% vs. 61%; P = .039), anastomotic leak (27.8% vs. 15%; P = .023), surgical site infection (29.6% vs. 16.1%; P = .02), and pulmonary complications (55.6% vs. 40.2%; P = .038).

“Currently, there is no evidence in terms of locoregional control or survival benefit to support a high total radiation dose (> 50 Gy) in patients receiving dCRT,” according to the researchers, who noted that the findings suggest, “an upper threshold of 50 Gy should be used in these patients to optimize the benefits of dCRT without compromising the safety of SALV, if required.”

Patients who underwent SALV at high-volume centers had significantly lower rates of in-hospital mortality (6.3% vs. 16.2%; P = .009) and overall morbidity (58.8% vs. 80.9%; P = .001) compared with procedures done at low-volume centers.

Compared with recurrent disease, patients with persistent disease after dCRT had poorer long-term prognoses, suggesting a more aggressive tumor biology. Early identification of CRT-resistant tumors to allow early surgical treatment is an important area for future investigation, the investigators said.

For patients with esophageal cancer, salvage surgery after definitive chemoradiotherapy had similar mortality and morbidity rates, and similar survival outcomes, to the combination of neoadjuvant chemoradiation and planned surgery, according to a study published online in the Journal of Clinical Oncology.

Definitive chemoradiotherapy (dCRT) is an alternative to highly invasive surgical resection, which carries a significant rate of morbidity and mortality; however, recent data indicate that 50% of patients with complete response to dCRT experience tumor recurrence.

“Our study demonstrated a similar survival and recurrence pattern for the SALV [salvage surgery after definitive chemoradiotherapy] and NCRS [neoadjuvant chemoradiation and planned surgery] groups, potentially validating an approach of dCRT with reserved SALV for persistent or recurrent disease. Importantly, there were no differences in oncologic safety of surgery, including extent of nodal dissection, between the SALV and NCRS groups,” wrote Dr. Sheraz Markar, a clinical research fellow from Imperial College, London, and colleagues (Journ. Clin. Onc. 2015 July 20 [doi:10.1200/JCO.2014.59.9092]).

The retrospective study compared 308 patients with esophageal cancer who underwent SALV with 540 patients who received NCRS at European centers from 2000 to 2010. After a median follow up of 54 months, the SALV and NCRS groups had similar rates of 3-year overall survival (43.3% vs. 40.1% ) and disease-free survival (39.2% vs. 32.8%). The two groups also had similar rates tumor recurrence: overall (46.8% vs. 47.9%), locoregional (18.8% vs. 15.9%), distant (24.3% vs. 28.1%) and mixed (13.0% vs. 13.5%).

The SALV and NCRS groups had similar rates of in-hospital mortality (8.4% vs. 9.3%) and morbidity (63.6% vs. 58.9%), but SALV patients had significantly more complications from anastomotic leak (17.2% vs. 10.7%) and surgical site infection (18.5% vs. 12.2%).

Subset analysis of the SALV group showed that patients who received a total radiation dose ≥ 55 Gy (compared with SALV patients who received a lower dose) had significantly increased in-hospital mortality (27.8% vs. 4.3%; P < .001), overall morbidity (75.9% vs. 61%; P = .039), anastomotic leak (27.8% vs. 15%; P = .023), surgical site infection (29.6% vs. 16.1%; P = .02), and pulmonary complications (55.6% vs. 40.2%; P = .038).

“Currently, there is no evidence in terms of locoregional control or survival benefit to support a high total radiation dose (> 50 Gy) in patients receiving dCRT,” according to the researchers, who noted that the findings suggest, “an upper threshold of 50 Gy should be used in these patients to optimize the benefits of dCRT without compromising the safety of SALV, if required.”

Patients who underwent SALV at high-volume centers had significantly lower rates of in-hospital mortality (6.3% vs. 16.2%; P = .009) and overall morbidity (58.8% vs. 80.9%; P = .001) compared with procedures done at low-volume centers.

Compared with recurrent disease, patients with persistent disease after dCRT had poorer long-term prognoses, suggesting a more aggressive tumor biology. Early identification of CRT-resistant tumors to allow early surgical treatment is an important area for future investigation, the investigators said.

Patients diagnosed with colorectal cancer at a younger age are more likely to have hereditary cancer syndromes, according to a study published online in the Journal of Clinical Oncology.

About one-third of patients who were diagnosed with colorectal cancer (CRC) at age 35 years or younger had a hereditary cancer syndrome, which is much higher than the 2%-5% rate seen in the general CRC population.

“Our results support a referral to genetic counseling for hereditary cancer syndromes for all patients diagnosed with CRC at 35 years or younger, regardless of family history of CRC, even when patients have normal MSI [microsatellite instability] and IHC [immunohistochemistry] tumor study results,” wrote Maureen Mork and colleagues from the University of Texas MD Anderson Cancer, Houston (J. Clin. Oncol. 2015 July 20).

Many of the patients with hereditary syndromes had no family history of CRC, and they represented both de novo mutations and incomplete penetrance. Among 67 patients in the hereditary group, about 23 were diagnosed with Lynch syndrome (LS), 22 with mutation-negative LS, and 20 presented with a familial adenomatous polyposis (FAP) phenotype.

Patients without a hereditary syndrome had more frequent left-sided colon tumors, metastatic disease, and poor differentiation, compared with the hereditary group. Differences in disease stage at diagnosis may have resulted from increased surveillance among those with family history of disease.

Revised Bethesda guidelines recommend testing patients for LS, but the authors support broader evaluation because the hereditary syndromes observed in the study were not limited to LS. Adolescent and young adult patients with CRC may benefit from having “comprehensive hereditary CRC genetic testing panels, especially in the absence of a clinical phenotype or with normal MSI and IHC tumor studies,” they wrote.

Patients diagnosed with colorectal cancer at a younger age are more likely to have hereditary cancer syndromes, according to a study published online in the Journal of Clinical Oncology.

About one-third of patients who were diagnosed with colorectal cancer (CRC) at age 35 years or younger had a hereditary cancer syndrome, which is much higher than the 2%-5% rate seen in the general CRC population.

“Our results support a referral to genetic counseling for hereditary cancer syndromes for all patients diagnosed with CRC at 35 years or younger, regardless of family history of CRC, even when patients have normal MSI [microsatellite instability] and IHC [immunohistochemistry] tumor study results,” wrote Maureen Mork and colleagues from the University of Texas MD Anderson Cancer, Houston (J. Clin. Oncol. 2015 July 20).

Many of the patients with hereditary syndromes had no family history of CRC, and they represented both de novo mutations and incomplete penetrance. Among 67 patients in the hereditary group, about 23 were diagnosed with Lynch syndrome (LS), 22 with mutation-negative LS, and 20 presented with a familial adenomatous polyposis (FAP) phenotype.

Patients without a hereditary syndrome had more frequent left-sided colon tumors, metastatic disease, and poor differentiation, compared with the hereditary group. Differences in disease stage at diagnosis may have resulted from increased surveillance among those with family history of disease.

Revised Bethesda guidelines recommend testing patients for LS, but the authors support broader evaluation because the hereditary syndromes observed in the study were not limited to LS. Adolescent and young adult patients with CRC may benefit from having “comprehensive hereditary CRC genetic testing panels, especially in the absence of a clinical phenotype or with normal MSI and IHC tumor studies,” they wrote.

Patients diagnosed with colorectal cancer at a younger age are more likely to have hereditary cancer syndromes, according to a study published online in the Journal of Clinical Oncology.

About one-third of patients who were diagnosed with colorectal cancer (CRC) at age 35 years or younger had a hereditary cancer syndrome, which is much higher than the 2%-5% rate seen in the general CRC population.

“Our results support a referral to genetic counseling for hereditary cancer syndromes for all patients diagnosed with CRC at 35 years or younger, regardless of family history of CRC, even when patients have normal MSI [microsatellite instability] and IHC [immunohistochemistry] tumor study results,” wrote Maureen Mork and colleagues from the University of Texas MD Anderson Cancer, Houston (J. Clin. Oncol. 2015 July 20).

Many of the patients with hereditary syndromes had no family history of CRC, and they represented both de novo mutations and incomplete penetrance. Among 67 patients in the hereditary group, about 23 were diagnosed with Lynch syndrome (LS), 22 with mutation-negative LS, and 20 presented with a familial adenomatous polyposis (FAP) phenotype.

Patients without a hereditary syndrome had more frequent left-sided colon tumors, metastatic disease, and poor differentiation, compared with the hereditary group. Differences in disease stage at diagnosis may have resulted from increased surveillance among those with family history of disease.

Revised Bethesda guidelines recommend testing patients for LS, but the authors support broader evaluation because the hereditary syndromes observed in the study were not limited to LS. Adolescent and young adult patients with CRC may benefit from having “comprehensive hereditary CRC genetic testing panels, especially in the absence of a clinical phenotype or with normal MSI and IHC tumor studies,” they wrote.

In patients with multiple myeloma refractory to lenalidomide, pomalidomide administered in a lower-dose, continuous schedule resulted in overall and event-free survival similar to that of intermittent dosing, which is approved by the Food and Drug Administration, according to a report published in Blood.

Both regimens led to rapid activation of innate and adaptive immunity and benefitted expected survival in the heavily pretreated patient population. The cohort given intermittent dosing had a mean 54% reduction in measurable disease, compared with 28% for the cohort given continuous dosing (P = .02); both cohorts had similar event-free survival (4.3 vs. 5.3 months) and overall survival (21.7 vs. 17.7 months).

“In our study, although the 21/28-day schedule led to a greater reduction in measurable disease (although the differences in overall response rate did not reach statistical significance), it also led to a greater incidence of grade 3/4 treatment-related adverse events. Taken together, in our view, these data do not suggest a clear advantage for either regimen based on clinical parameters alone,” wrote Dr. Kartik Sehgal of Yale University, New Haven, Conn., and his colleagues (Blood 2015 June 25 [doi:10.1001/jamaoncol.2015.2010]).

The prospective phase II trial randomized 39 patients, who had received at least two (median four) prior therapies including lenalidomide, to receive pomalidomide in continuous (2 mg/day for 28/28 days) or intermittent (4 mg/day for 21/28 days) dosing schedules. All patients received dexamethasone at 40 mg weekly, starting with cycle two.

The most common adverse effect was myelosuppression, and the pattern of specific toxicities was similar in the two groups. Patients in the intermittent dosing cohort experienced more grade 3/4 adverse effects than the continuous dosing cohort (90% vs. 58%; P = .03).

Both pomalidomide and lenalidomide share the same cellular target (cereblon), and pharmacodynamic studies of the two pomalidomide regimens sought to clarify the mechanism of pomalidomide activity in lenalidomide-refractory multiple myeloma. The data suggest that pomalidomide affects the tumor microenvironment and immune cells. These effects may be amplified by blockade of immune checkpoints, the authors noted.

“Optimizing the immune effects of pomalidomide/lenalidomide on the tumor microenvironment with combination therapies may enhance their therapeutic potential in MM [multiple myeloma] and other cancers,” the authors wrote.

In patients with multiple myeloma refractory to lenalidomide, pomalidomide administered in a lower-dose, continuous schedule resulted in overall and event-free survival similar to that of intermittent dosing, which is approved by the Food and Drug Administration, according to a report published in Blood.

Both regimens led to rapid activation of innate and adaptive immunity and benefitted expected survival in the heavily pretreated patient population. The cohort given intermittent dosing had a mean 54% reduction in measurable disease, compared with 28% for the cohort given continuous dosing (P = .02); both cohorts had similar event-free survival (4.3 vs. 5.3 months) and overall survival (21.7 vs. 17.7 months).

“In our study, although the 21/28-day schedule led to a greater reduction in measurable disease (although the differences in overall response rate did not reach statistical significance), it also led to a greater incidence of grade 3/4 treatment-related adverse events. Taken together, in our view, these data do not suggest a clear advantage for either regimen based on clinical parameters alone,” wrote Dr. Kartik Sehgal of Yale University, New Haven, Conn., and his colleagues (Blood 2015 June 25 [doi:10.1001/jamaoncol.2015.2010]).

The prospective phase II trial randomized 39 patients, who had received at least two (median four) prior therapies including lenalidomide, to receive pomalidomide in continuous (2 mg/day for 28/28 days) or intermittent (4 mg/day for 21/28 days) dosing schedules. All patients received dexamethasone at 40 mg weekly, starting with cycle two.

The most common adverse effect was myelosuppression, and the pattern of specific toxicities was similar in the two groups. Patients in the intermittent dosing cohort experienced more grade 3/4 adverse effects than the continuous dosing cohort (90% vs. 58%; P = .03).

Both pomalidomide and lenalidomide share the same cellular target (cereblon), and pharmacodynamic studies of the two pomalidomide regimens sought to clarify the mechanism of pomalidomide activity in lenalidomide-refractory multiple myeloma. The data suggest that pomalidomide affects the tumor microenvironment and immune cells. These effects may be amplified by blockade of immune checkpoints, the authors noted.

“Optimizing the immune effects of pomalidomide/lenalidomide on the tumor microenvironment with combination therapies may enhance their therapeutic potential in MM [multiple myeloma] and other cancers,” the authors wrote.

In patients with multiple myeloma refractory to lenalidomide, pomalidomide administered in a lower-dose, continuous schedule resulted in overall and event-free survival similar to that of intermittent dosing, which is approved by the Food and Drug Administration, according to a report published in Blood.

Both regimens led to rapid activation of innate and adaptive immunity and benefitted expected survival in the heavily pretreated patient population. The cohort given intermittent dosing had a mean 54% reduction in measurable disease, compared with 28% for the cohort given continuous dosing (P = .02); both cohorts had similar event-free survival (4.3 vs. 5.3 months) and overall survival (21.7 vs. 17.7 months).

“In our study, although the 21/28-day schedule led to a greater reduction in measurable disease (although the differences in overall response rate did not reach statistical significance), it also led to a greater incidence of grade 3/4 treatment-related adverse events. Taken together, in our view, these data do not suggest a clear advantage for either regimen based on clinical parameters alone,” wrote Dr. Kartik Sehgal of Yale University, New Haven, Conn., and his colleagues (Blood 2015 June 25 [doi:10.1001/jamaoncol.2015.2010]).

The prospective phase II trial randomized 39 patients, who had received at least two (median four) prior therapies including lenalidomide, to receive pomalidomide in continuous (2 mg/day for 28/28 days) or intermittent (4 mg/day for 21/28 days) dosing schedules. All patients received dexamethasone at 40 mg weekly, starting with cycle two.

The most common adverse effect was myelosuppression, and the pattern of specific toxicities was similar in the two groups. Patients in the intermittent dosing cohort experienced more grade 3/4 adverse effects than the continuous dosing cohort (90% vs. 58%; P = .03).

Both pomalidomide and lenalidomide share the same cellular target (cereblon), and pharmacodynamic studies of the two pomalidomide regimens sought to clarify the mechanism of pomalidomide activity in lenalidomide-refractory multiple myeloma. The data suggest that pomalidomide affects the tumor microenvironment and immune cells. These effects may be amplified by blockade of immune checkpoints, the authors noted.

“Optimizing the immune effects of pomalidomide/lenalidomide on the tumor microenvironment with combination therapies may enhance their therapeutic potential in MM [multiple myeloma] and other cancers,” the authors wrote.

In patients presenting with cutaneous melanoma, use of molecular data can help determine whether there is a high likelihood of nodal metastasis that warrants sentinel lymph node biopsy, according to a report published online in the Journal of Clinical Oncology.

A large number of sentinel lymph node (SLN) biopsies could be avoided if nodal metastasis in patients with primary cutaneous melanoma were better identified at the time of diagnosis, according to Dr. Alexander Meves of the department of dermatology at the Mayo Clinic in Rochester, Minn., and colleagues.

“In this study, we found that molecular data in combination with Breslow depth, tumor ulceration, and patient age were useful for discriminating between primary cutaneous melanomas that had or had not metastasized to SLN,” they wrote (J. Clin. Oncol. 2015 July 6 [doi:10.1200/JCO.2014.60.7002]).

Based on samples from 160 patients that included benign nevi and primary skin melanomas with and without SLN metastasis, investigators identified genes differentially expressed between metastatic and nonmetastatic pigmented skin lesions, and found a cluster of genes associated with integrin cell adhesion. Of particular interest, the integrin cell adhesion receptor, beta-3 integrin (ITGB3), was upregulated in regionally metastatic melanoma.

Information from a cohort of 360 patients, including 74 (20.6%) with biopsy-confirmed nodal metastasis, was used to derive prediction models for SLN metastasis based on clinicopathologic factors alone and in combination with molecular data. Younger age, tumor ulceration, and greater Breslow depth contributed to the clinicopathologic model. The combined model added expression data from four genes: ITGB3, cellular tumor antigen p53 (TP53), laminin B1 chain (LAMB1), and tissue-type plasminogen activator (PLAT; protein name, t-PA). Area under the receiver operating characteristic (ROC) curve for the combined clinicopathologic plus molecular model was 0.89, compared with 0.78 for the clinicopathologic model alone (P < .001). Performance of the models on the validation cohort (n = 146) was similar, with the area under the ROC curve at 0.93. Using a 10% cutoff, the false-positive rate was 22% and the false-negative rate was 0%.

Expression data combined with clinicopathologic features can be used to calculate the predicted probability of SLN positivity at the time of primary diagnosis, which has “the potential to improve patient care by avoiding unnecessary SLN procedures,” the authors wrote.

In patients presenting with cutaneous melanoma, use of molecular data can help determine whether there is a high likelihood of nodal metastasis that warrants sentinel lymph node biopsy, according to a report published online in the Journal of Clinical Oncology.

A large number of sentinel lymph node (SLN) biopsies could be avoided if nodal metastasis in patients with primary cutaneous melanoma were better identified at the time of diagnosis, according to Dr. Alexander Meves of the department of dermatology at the Mayo Clinic in Rochester, Minn., and colleagues.

“In this study, we found that molecular data in combination with Breslow depth, tumor ulceration, and patient age were useful for discriminating between primary cutaneous melanomas that had or had not metastasized to SLN,” they wrote (J. Clin. Oncol. 2015 July 6 [doi:10.1200/JCO.2014.60.7002]).

Based on samples from 160 patients that included benign nevi and primary skin melanomas with and without SLN metastasis, investigators identified genes differentially expressed between metastatic and nonmetastatic pigmented skin lesions, and found a cluster of genes associated with integrin cell adhesion. Of particular interest, the integrin cell adhesion receptor, beta-3 integrin (ITGB3), was upregulated in regionally metastatic melanoma.

Information from a cohort of 360 patients, including 74 (20.6%) with biopsy-confirmed nodal metastasis, was used to derive prediction models for SLN metastasis based on clinicopathologic factors alone and in combination with molecular data. Younger age, tumor ulceration, and greater Breslow depth contributed to the clinicopathologic model. The combined model added expression data from four genes: ITGB3, cellular tumor antigen p53 (TP53), laminin B1 chain (LAMB1), and tissue-type plasminogen activator (PLAT; protein name, t-PA). Area under the receiver operating characteristic (ROC) curve for the combined clinicopathologic plus molecular model was 0.89, compared with 0.78 for the clinicopathologic model alone (P < .001). Performance of the models on the validation cohort (n = 146) was similar, with the area under the ROC curve at 0.93. Using a 10% cutoff, the false-positive rate was 22% and the false-negative rate was 0%.

Expression data combined with clinicopathologic features can be used to calculate the predicted probability of SLN positivity at the time of primary diagnosis, which has “the potential to improve patient care by avoiding unnecessary SLN procedures,” the authors wrote.

In patients presenting with cutaneous melanoma, use of molecular data can help determine whether there is a high likelihood of nodal metastasis that warrants sentinel lymph node biopsy, according to a report published online in the Journal of Clinical Oncology.

A large number of sentinel lymph node (SLN) biopsies could be avoided if nodal metastasis in patients with primary cutaneous melanoma were better identified at the time of diagnosis, according to Dr. Alexander Meves of the department of dermatology at the Mayo Clinic in Rochester, Minn., and colleagues.

“In this study, we found that molecular data in combination with Breslow depth, tumor ulceration, and patient age were useful for discriminating between primary cutaneous melanomas that had or had not metastasized to SLN,” they wrote (J. Clin. Oncol. 2015 July 6 [doi:10.1200/JCO.2014.60.7002]).

Based on samples from 160 patients that included benign nevi and primary skin melanomas with and without SLN metastasis, investigators identified genes differentially expressed between metastatic and nonmetastatic pigmented skin lesions, and found a cluster of genes associated with integrin cell adhesion. Of particular interest, the integrin cell adhesion receptor, beta-3 integrin (ITGB3), was upregulated in regionally metastatic melanoma.

Information from a cohort of 360 patients, including 74 (20.6%) with biopsy-confirmed nodal metastasis, was used to derive prediction models for SLN metastasis based on clinicopathologic factors alone and in combination with molecular data. Younger age, tumor ulceration, and greater Breslow depth contributed to the clinicopathologic model. The combined model added expression data from four genes: ITGB3, cellular tumor antigen p53 (TP53), laminin B1 chain (LAMB1), and tissue-type plasminogen activator (PLAT; protein name, t-PA). Area under the receiver operating characteristic (ROC) curve for the combined clinicopathologic plus molecular model was 0.89, compared with 0.78 for the clinicopathologic model alone (P < .001). Performance of the models on the validation cohort (n = 146) was similar, with the area under the ROC curve at 0.93. Using a 10% cutoff, the false-positive rate was 22% and the false-negative rate was 0%.

Expression data combined with clinicopathologic features can be used to calculate the predicted probability of SLN positivity at the time of primary diagnosis, which has “the potential to improve patient care by avoiding unnecessary SLN procedures,” the authors wrote.