Pancreatic ductal adenocarcinoma: tumour regression grading following neoadjuvant FOLFIRINOX and radiation.

AIMS: In the adjuvant setting, when compared to gemcitabine, patients with pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX (Folinic Acid, Fluorouracil, Irinotecan, and Oxaliplatin) show superior survival. In this study, we quantitatively assess the pathological tumour response to chemoradiation in pancreatectomy specimens and reassess guidelines for tumour regression grading. METHODS AND RESULTS: We evaluated 92 patients with borderline resectable/locally advanced PDAC following pancreatectomy and neoadjuvant treatment with FOLFIRINOX and radiation. Demographic data, CAP tumour regression grade (TRG) and overall survival (OS) were recorded. A quantitative analysis of residual tumour was performed on the slide with the highest tumour burden to derive a tumour-to-tumour bed ratio. On univariate analysis, only lymph node status (P = 0.043) and CAP TRG (P = 0.038) correlated with OS. Sixteen per cent of patients showed a complete pathological response. The optimal tumour-to-tumour bed ratio cut-point was 11.6%, and on a multivariate model was the only pathological parameter that correlated with OS (P = 0.016) (hazard ratio = 2.27). CONCLUSIONS: The high proportion of patients with PDAC showing complete and near-complete pathological responses supports the use of FOLFIRINOX and radiation in the neoadjuvant setting. Several traditional pathology parameters fail to predict OS in patients treated with chemoradiation, while a quantitative tumour-to-tumour bed ratio is a powerful predictor of OS. The data support a two-tiered approach to TRG based on tumour-to-tumour bed ratio, and quantitative analysis merits further consideration.

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.