Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: Survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels

Citation
Ra. Abrams et al., Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: Survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels, INT J RAD O, 44(5), 1999, pp. 1039-1046
Citations number
31
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN journal
03603016 → ACNP
Volume
44
Issue
5
Year of publication
1999
Pages
1039 - 1046
Database
ISI
SICI code
0360-3016(19990715)44:5<1039:IATFPA>2.0.ZU;2-O
Abstract
Purpose: Primary endpoints were 1. To determine if, in the context of posto perative adjuvant therapy of pancreatic and nonpancreatic periampullary ade nocarcinoma, continuous infusion (C.I.) 5-fluorouracil (5-FU) and leucovori n (Lv), combined with continuous-course external-beam radiotherapy (EBRT) t o liver (23.4-27.0 Gy), regional lymph nodes (50.4-54.0 Gy) and tumor bed ( 50.4-57.6 Gy), followed by 4 months of C.I. 5-FU/Lv,without EBRT could be g iven with acceptable toxicity. 2. To determine an estimate of disease-free and overall survival (DFS, OS) with this treatment in this context. Seconda ry endpoints were 1. To observe the effects of therapy at two different dos e levels of irradiation, and 2. To observe for correlations among DFS, OS a nd CA 19-9 levels during therapy. Methods: Patients received C.I. 5-FU 200 mg/m(2) and Lv 5 mg/m2 Monday thro ugh Friday during EBRT, and 4 cycles of the same chemotherapy without EBRT were planned for each 2 weeks of 4, beginning 1 month following the complet ion of EBRT. Therapy was to begin within 10 weeks of surgery and patients w ere monitored for disease recurrence, toxicity, and CA 19-9 levels before t he start of EBRT/5-FU/Lv, before each cycle of C.I. 5-FU/Lv, and periodical ly after the completion of therapy. There were two EBRT dosage groups: Low EBRT, 23.4 Gy to the whole liver, 50.4 Gy to regional nodes and 50.4 Gy to the tumor bed; High EBRT, 27.0 Gy to the whole liver, 54.0 Gy to regional n odes, and 57.6 Gy to the tumor bed. Results: 29 patients were enrolled and treated (23 with pancreatic cancer, and 6 with nonpancreatic periampullary cancer). Of these, 18 had tumor size s greater than or equal to 3 cm and 23 had at least one histologically invo lved lymph node; 6 had histologically positive resection margins. Mean time to start of EBRT/5-FU/Lv was 53 a 2 days following surgery. The first 18 p atients were in the Low EBRT Group and the last 11 in the High EBRT Group. Toxicity was moderate and manageable, including a possible case of late rad iation hepatitis. Median DFS was 8.3 months (pancreatic cancer patients 8.5 months) and OS was 14.1 months (pancreatic cancer patients 15.9 months). A mong patients with pancreatic cancer, results were similar for the Low and High EBRT Groups (DFS: 8.3 vs. 8.6 months; OS: 14.4 vs. 16.9 months, respec tively). With a mean follow up of 2.6 a 0.3 years for the surviving patient s and a minimal follow-up of 2.5 years, 27 of 29 pts have relapsed and 25 p ts have died. A rise in CA 19-9 levels preceded clinical relapse by 9.1 a 1 .5 months. Time to first relapse by site showed inverse correlation with do se of radiotherapy to that site: peritoneal (5 a 1 month), hepatic (7 a 0.9 months), regional nodes/tumor bed (9.6 a 1.8 months). Mean postresection C A 19-9 level was 63.3 a 16.2 U/ml. Postresection CA 19-9 values did not cor relate with survival, margin status, or with the identification of metastat ic carcinoma in resected lymph nodes. However, among patients with histolog ically involved nodes in the resected specimen, postresection CA 19-9 value s did correlate with the number of positive nodes identified (p = 0.05). Conclusions: Although toxicity was acceptable, survival results were not im proved over those seen with standard adjuvant treatment. Most patients rela psed before the planned chemotherapy cycles mere completed, or within 100 d ays thereof, suggesting disease resistance to C.I. 5-FU/Lv as used in this study. Although this regimen is not recommended for further study, the dose s of EBRT utilized may be suitable for evaluation with other chemotherapy c ombinations. Postoperative CA 19-9 levels did not correlate with survival, but did correlate with the number of histologically involved lymph nodes fo und in the resected specimen among node-positive patients. Moreover, rising CA 19-9 levels anticipated ultimate clinical failure by 9 months. (C) 1999 Elsevier Science Inc.