Adjuvant chemoradiation may improve survival over adjuvant chemotherapy in resected pancreatic cancer patients who are high risk for locoregional recurrence

Journal of Radiation Oncology - Tập 4 - Trang 271-276 - 2015
Aryavarta M. S. Kumar1, Gavin A. Falk2, Robert Pelley3, R. Matthew Walsh2, May Abdel-Wahab1
1Department of Radiation Oncology, Cleveland Clinic, Cleveland, USA
2Department of General Surgery, Cleveland Clinic, Cleveland, USA
3Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, USA

Tóm tắt

The objective of the study was to evaluate the benefit of adjuvant chemoradiation compared to adjuvant chemotherapy for resected pancreatic head cancer. Three hundred thirty-nine patients (2000–2012) had pancreatoduodenectomy for pancreatic cancer. Chemotherapy was gemcitabine or 5-fluorouracil (5-FU) and radiotherapy was 45–54 Gy. Locoregional recurrences (LRR) were operative bed or regional nodal failures. Logistical regression, Kaplan-Meier estimates, and log-rank tests were used for statistics. One hundred thirty patients had resection alone (A), 84 had adjuvant chemotherapy (B), and 129 had adjuvant chemoradiation (C). Median follow-up and median survival (MS) for all patients was 17.5 and 19.5 months, respectively. MS for groups A, B, and C were 13, 23, and 26 months, respectively. Groups B and C had R1 resection rates of 37 and 39 % (p = ns). LRR was 60, 63, and 38 % and distant failure was 64, 65, and 66 % for groups A, B, and C, respectively. Group C had significantly lower LRR compared to group B (p = 0.01); however, survival between groups B and C was not statistically different (p = 0.23). On univariate analysis, LRR (p = 0.0038), N-category (p < 0.0001), perineural invasion (PNI; p = 0.007), and R1 resection (p = 0.018) were significant predictors of survival. Multivariable analysis (MVA) showed that LRR (p = 0.004) and N-category (p = 0.01) were predictors of survival. On subgroup analysis, there was improved survival in group C vs B in patients with R1 resection, MS of 27 vs 16 months, respectively (p = 0.01), and in patients with lymph node ratio (LNR) ≤0.2 who had ≥8 LN dissected, MS of 32 vs 24 months (p = 0.04). Adjuvant chemoradiation significantly decreases LRR in resected pancreatic cancer patients compared to adjuvant chemotherapy. Significant predictors of survival on MVA were LRR and N-category. Additionally on subgroup analysis, chemoradiation improved survival over chemotherapy with a (1) positive surgical margin and/or (2) LNR ≤0.2 with ≥8 LNs dissected.

Tài liệu tham khảo

Hartwig W et al (2013) Improvement of surgical results for pancreatic cancer. Lancet Oncol 14:e476–e485. doi:10.1016/S1470-2045(1013)70172-70174 Hishinuma S et al (2006) Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg 10:511–518 Whittington R et al (1991) Adjuvant therapy of resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 21:1137–1143 Corsini MM et al (2008) Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975–2005). J Clin Oncol 26:3511–3516 Stocken DD et al (2005) Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer 92:1372–1381 O’Reilly EM (2013) Adjuvant therapy for pancreas adenocarcinoma. J Surg Oncol 107:78–85 Hattangadi JA et al (2009) Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma. Cancer 115:3640–3650 Winter JM et al (2013) Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to smad4 expression. Ann Surg 258:331–335 Moghanaki D et al (2011) Resection status, age and nodal involvement determine survival among patients receiving adjuvant chemoradiotherapy in pancreatic adenocarcinoma. JOP 12:438–444 Kim R et al (2010) A single institution review of adjuvant therapy outcomes for resectable pancreatic adenocarcinoma: outcome and prognostic indicators. J Gastrointest Surg 14:1159–1169 Herman JM et al (2008) Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol 26:3503–3510. doi:10.1200/JCO.2007.3515.8469 Butturini G et al (2008) Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials. Arch Surg (Chicago, Ill: 1960) 143:75–83, discussion 83 Kooby DA et al (2013) Impact of adjuvant radiotherapy on survival after pancreatic cancer resection: an appraisal of data from the national cancer data base. Annals Surg Oncol Gnerlich JL et al (2012) Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch Surg (Chicago, Ill: 1960) 147:753–760 Rau BM et al (2012) R1 resection in pancreatic cancer has significant impact on long-term outcome in standardized pathology modified for routine use. Surgery 152:S103–S111 Wentz SC et al (2012) Lymph node ratio and preoperative ca 19–9 levels predict overall survival and recurrence-free survival in patients with resected pancreatic adenocarcinoma. World J Gastrointest Oncol 4:207–215 Zhang Y et al (2012) Loco-recurrence after resection for ductal adenocarcinoma of the pancreas: predictors and implications for adjuvant chemoradiotherapy. J Cancer Res Clin Oncol 138:1063–1071 Asiyanbola B et al (2009) Determining pattern of recurrence following pancreaticoduodenectomy and adjuvant 5-flurouracil-based chemoradiation therapy: effect of number of metastatic lymph nodes and lymph node ratio. J Gastrointest Surg 13:752–759 Hall WA et al (2013) The influence of adjuvant radiotherapy dose on overall survival in patients with resected pancreatic adenocarcinoma. Cancer 119:2350–2357 Konstantinidis IT et al (2013) Pancreatic ductal adenocarcinoma: is there a survival difference for r1 resections versus locally advanced unresectable tumors? What is a “true” r0 resection? Ann Surg 257:731–736 Pawlik TM et al (2007) Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery 141:610–618