Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer.

PURPOSE: We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes. MATERIALS AND METHODS: We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival. RESULTS: All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS. CONCLUSIONS: We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.

Long-term outcomes and toxicities of a large cohort of anal cancer patients treated with dose-painted IMRT per RTOG 0529.

PURPOSE: To describe the outcomes and toxicities of the largest cohort to date of patients with anal squamous cell carcinoma uniformly treated with concurrent chemoradiation using dose-painted intensity modulated radiation therapy (DP-IMRT) according to RTOG 0529. METHODS AND MATERIALS: We identified 99 eligible patients with anal cancer who were treated at our institution with definitive chemoradiation using DP-IMRT between 2005 and 2015 per RTOG 0529 dosing guidelines. Primary study endpoints included event-free survival (defined as recurrence, colostomy, or death) and overall survival. Secondary endpoints were treatment duration and acute and late toxicity. RESULTS: At a median follow-up of 49 months (range, 2-114 months), 92% of patients had a clinical complete response. Fifteen percent underwent colostomy, including 4 pretreatment colostomies, 6 planned abdominoperineal resections (APRs), 4 salvage APRs, and 1 APR for treatment-related complications. Thirteen patients developed local recurrence, of whom 6 developed synchronous metastatic disease. The 4-year overall survival was 85.8%, and 4-year event-free survival was 75.5%. Median treatment duration was 43 days (range, 10-68 days). The overall rate of non-hematologic grade 3+ acute and grade 2+ late toxicities was 20% and 15%, respectively. CONCLUSIONS: Long-term outcomes and tolerability were excellent In the largest cohort to date of patients with anal cancer who received DP-IMRT prescribed per RTOG 0529.

Irradiation of anatomically defined pelvic subsites and acute hematologic toxicity in anal cancer patients undergoing chemoradiation.

PURPOSE: Chemoradiation for the treatment of anal cancer is known to cause significant hematologic toxicity (HT). We sought to investigate if radiation dose to specific pelvic subsites is associated with increased HT risk. METHODS AND MATERIALS: Forty-five patients with nonmetastatic anal cancer who received definitive chemoradiation with intensity modulated radiation therapy and concurrent mitomycin-C and 5-fluorouracil were studied. Total pelvic bone marrow (TBM) was divided into 3 subsites: lumbosacral bone marrow (LSBM), including the entire sacrum and L5 vertebral body; iliac bone marrow (IBM) extending from the iliac crests to the superior border of the femoral head; and lower pelvic bone marrow, including the pubic bones, ischia, acetabula, and proximal femurs. The primary endpoint was absolute neutrophil count (ANC) nadir during or within 2 weeks of treatment completion. Generalized linear modeling was used to analyze the correlation between the equivalent uniform dose (with an "a" value of 0.5) to the individual pelvic subsites and the various hematologic endpoints. Age, body mass index, sex, baseline blood counts, and immunosuppression were analyzed as potential covariates. RESULTS: Mean ± standard deviation ANC nadir was 0.77 × 109/L (±0.66 × 109/L). Grades 3+ and 4+ neutropenia occurred in 71.1% and 44.4% of patients, respectively. In addition to radiation dose to pelvic bone marrow, baseline ANC was the only significant predictor of hematologic toxicity on multivariable analysis and was included in all models. The equivalent uniform doses of TBM, LSBM, and IBM were each significantly associated with neutropenia. The model performance of TBM (adjusted R2 = 0.226) was similar to both LSBM (adjusted R2 = 0.206) and IBM (adjusted R2 = 0.249). CONCLUSIONS: Radiation doses to TBM, LSBM, and IBM were individually associated with HT, suggesting that sparing just a portion of pelvic bone marrow is insufficient to decrease rates of clinically significant bone marrow suppression.