Concurrent Nab-paclitaxel and Radiotherapy: Novel Radiosensitization for Borderline Resectable or Unresectable Pancreatic Cancer.

PURPOSE: This study evaluates the toxicity and tumor response with concurrent nab-paclitaxel chemoradiotherapy (CRT) compared with standard (5-fluorouracil or gemcitabine) CRT. MATERIALS AND METHODS: Fifty patients with borderline resectable or unresectable pancreatic adenocarcinoma from 2014 to 2017 were divided into 2 groups: concurrent nab-paclitaxel (100 to 125 mg/m2 weekly) CRT (median: 2.1 Gy fraction size and 52.5 Gy total) or standard CRT (median: 1.8 Gy fraction size, 54.5 Gy total). The primary endpoint was toxicity, and secondary endpoints were local failure and conversion to resectability. Comparisons were made using rank-sum or Fisher exact test and multivariable competing risk regression for the cumulative incidence of local failure. RESULTS: There were 28 patients in the nab-paclitaxel CRT group and 22 in the standard CRT group; 88% had the unresectable disease. The median follow-up was 18 months. The median duration of chemotherapy before concurrent CRT was 1.9 and 2.3 months in the nab-paclitaxel and standard CRT groups (P=0.337), and radiotherapy dose was 52.5 Gy (range, 52.5 to 59.4 Gy) and 54.5 Gy (range, 45.0 to 59.4 Gy), respectively. There were no statistically significant grade ≥2 toxicities. The nab-paclitaxel CRT group experienced a nonstatistically significant lower incidence of local failure (hazard ratio=0.91, 95% confidence interval: 0.27-3.03, P=0.536). More patients in the nab-paclitaxel CRT group proceeded to surgery (9/28 compared with 3/22 in the standard CRT, P=0.186); of which 6 (25%) in the nab-paclitaxel CRT and 2 (10%) in the standard CRT groups were initially unresectable. CONCLUSIONS: Nab-paclitaxel CRT had similar toxicity compared with standard CRT in the treatment of borderline resectable or unresectable pancreatic cancer. Its use was associated with an arithmetically lower cumulative incidence of local failure and an arithmetically higher conversion to resectability, both of which were not statistically significant.

A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer.

PURPOSE: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of approximately 16 months. Novel methods to improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in pancreatic cancer and is FDA-approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced pancreatic carcinoma. METHODS: We performed a phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n = 3) or 125 mg/m2 (n = 6). There were no observed grade 3 gastrointestinal toxicities. One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%) and neutropenia (11%). No grade 4 toxicities were observed. Following chemoradiotherapy, four patients (borderline resectable, n = 2 and unresectable, n = 2) underwent surgical resection, all with negative margins and with significant treatment effect with limited tumor viability. CONCLUSIONS: The combination of fractionated radiation and weekly full dose nab-paclitaxel was safe and well-tolerated.

National Cancer Database Report on Pneumonectomy Versus Lung-Sparing Surgery for Malignant Pleural Mesothelioma.

INTRODUCTION: Controversy exists regarding the optimal surgical technique for malignant pleural mesothelioma (MPM). We evaluated national practice patterns and outcomes of MPM treated with extrapleural pneumonectomy (EPP) versus lung-sparing extended pleurectomy/decortication (P/D). METHODS: The National Cancer Database was queried for patients with newly diagnosed MPM undergoing EPP or P/D. Multivariable logistic regression ascertained clinical factors independently associated with P/D receipt. Kaplan-Meier analysis was used to evaluate overall survival (OS) between cohorts; multivariable Cox proportional hazards modeling was used to evaluate factors associated with OS. Survival was then evaluated between propensity-matched populations. RESULTS: Overall, 1307 patients (271 undergoing EPP [21%] and 1036 undergoing P/D [79%]) met the criteria. Patients receiving P/D were older (p = 0.028), whereas those undergoing EPP were more likely to live in a rural area (p = 0.044), live farther from the treating facility (p = 0.039), and receive treatment at an academic center (p = 0.050). There were no differences between cohorts in 30-day readmission or mortality (all p > 0.05). The median OS times in the EPP and P/D groups were 19 versus 16 months, respectively (p = 0.120); no differences were observed after propensity matching (p = 0.540). CONCLUSIONS: In this largest analysis of its kind to date, findings from this contemporary cohort demonstrate that P/D comprised most surgical procedures for MPM. Procedure type was influenced by sociodemographic and geographical factors, without observed differences in survival or postoperative mortality and readmission rates between techniques.