Adjuvant Therapy for Resected Gallbladder Cancer: Analysis of the National Cancer Data Base.

Background: Management of resected gallbladder cancer relies on single-arm trials and retrospective observations. Our objective was to evaluate adjuvant therapy in a nationwide data set using causal inference methods to address sources of bias. Methods: We studied patients with T2-3 or node-positive, nonmetastatic gallbladder cancer, resected with grossly negative margins and reported to the National Cancer Data Base between 2004 and 2011. We defined adjuvant therapy as any chemotherapy within 90 days of surgery, and upfront concurrent chemoradiation as radiation within 14 days of first chemotherapy. After adjusting for missing data and guarantee-time bias, and using propensity score analysis to minimize indication bias, we compared overall survival of patients receiving adjuvant therapies with untreated case subjects. Results: Adjuvant chemotherapy was administered to 28.8% of 4775 patients, and upfront chemoradiation to 13.5%. Treatment was less frequent among patients who were older, patients with comorbidities, and among white Hispanic women. T3 or node-positive disease, microscopically positive margins, or extended resection increased the likelihood of adjuvant therapy. Overall survival at three years was 39.9% (95% confidence interval [CI] = 38.4% to 41.4%) and was unaffected by adjuvant therapy after adjusting for multiple confounders (hazard ratio = 1.01, 95% CI = 0.92 to 1.10). Patients with T3 or node-positive tumors treated with upfront adjuvant chemoradiation had a modest early survival advantage (absolute difference at two years = 6.8%, 95% CI = 1.1% to 12.6%), but survival curves converged after five years of follow-up. Conclusions: The curative potential of current adjuvant therapy in gallbladder cancer is questionable, justifying placebo-controlled investigation of novel chemotherapy combinations or alternative approaches. Chemoradiation may provide a short-term benefit in locally advanced tumors.

Risk Factors for Early Death After Rituximab-Based Immunochemotherapy in Older Patients With Diffuse Large B-Cell Lymphoma.

BACKGROUND: Older patients with diffuse large B-cell lymphoma (DLBCL) are at risk of severe chemotherapy-related morbidity and mortality. Our objective was to quantify the risk and identify factors associated with death during the first cycle of immunochemotherapy in this population. PATIENTS AND METHODS: Using Medicare claims linked to the population-based SEER registry (SEER-Medicare), we studied patients with DLBCL aged 65 years and older who received immunochemotherapy containing rituximab, cyclophosphamide, and vincristine, in combination with doxorubicin, mitoxantrone, or etoposide in 2003-2012. Risk factors for death and hospitalization within the first 30 days of treatment were studied in multivariable logistic regression models. RESULTS: We identified 5,530 patients with a median age of 76 years, of whom 94% received doxorubicin-containing immunochemotherapy. Granulocyte colony-stimulating factor (G-CSF) was administered to 66% of patients during the first treatment cycle. Cumulative incidence of death at day 30 was 2.2%. The risk was significantly higher in patients aged 75 years and older and those who had B symptoms, chronic kidney disease, poor functional status, use of walking aids or wheelchairs, and prior hospitalization or upper endoscopy. The group with 0 to 1 risk factors (56% of patients) had a very low (0.6%) risk of early death, whereas the group with 4 or more risk factors (6% of patients) had a risk of 8.3%. Receipt of G-CSF was associated with a lower probability of early death in the high-risk group. The incidence of hospitalization within the first 30 days was 23.5%, peaking at day 8 of the cycle. CONCLUSIONS: Among older patients with DLBCL who receive contemporary immunochemotherapy, 1 in 45 die during the first month of treatment, and 1 in 4 are hospitalized. Factors identifiable from administrative/electronic records can stratify this risk and could be incorporated into decision support tools. Prophylactic G-CSF is not administered to more than one-third of patients, indicating an opportunity for improved preventive interventions.

Optimizing initial chemotherapy for metastatic pancreatic cancer.

The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

Clinical Trial Accrual Targeting Genomic Alterations After Next-Generation Sequencing at a Non-National Cancer Institute-Designated Cancer Program.

PURPOSE: Successful clinical trial accrual targeting uncommon genomic alterations will require broad national participation from both National Cancer Institute (NCI)-designated comprehensive cancer centers and community cancer programs. This report describes the initial experience with clinical trial accrual after next-generation sequencing (NGS) from three affiliated non-NCI-designated cancer programs. MATERIALS AND METHODS: Clinical trial participation was reviewed after enrollment of the first 200 patients undergoing comprehensive genomic profiling by NGS as part of an institutional intuitional review board-approved protocol at three affiliated hospitals in Rhode Island and was compared with published experience from NCI-designated cancer centers. RESULTS: Patient characteristics included a median age of 64 years, a median of two lines of prior therapy, and a predominance of GI carcinomas (58%). One hundred sixty-four of 200 patients (82%) had adequate tumor for NGS, 95% had genomic alterations identified, and 100% had variants of unknown significance. Fifteen of 164 patients (9.2%) enrolled in genotype-directed clinical trials, and three patients (1.8%) received commercially available targeted agents off clinical trials. The reasons for nonreceipt of NGS-directed therapy were no locally available matching trial (48.6%), ineligibility (33.6%) because of comorbidities or interim clinical deterioration, physician's choice of a different therapy (6.8%), or stable disease (11%). CONCLUSION: This experience demonstrates that a program enrolling patients in specific targeted agent clinical trials after NGS can be implemented successfully outside of the NCI-designated cancer program network, with comparable accrual rates. This is important because targetable genes have rare mutation rates and clinical trial accrual after NGS is low.