Adjuvant chemoradiation for resected gallbladder cancer.

Abstract

319 Background: Gallbladder cancer (GBC) is the leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy in terms of overall survival of adjuvant chemoradiation (CR) after curative resection of GBC. Methods: We retrospectively analyzed the cohort of patients with curatively resected GBC diagnosed between January 1999 and April 2009, treated with adjuvant CR at the Instituto Nacional del Cáncer, Santiago de Chile. Treatment protocol considered external beam radiation therapy (RT) (45–54 Gy) to tumor bed and regional lymphnodes with concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-h continuous infusion on days 1-5 and 29-33). Data was obtained from medical records, mortality from death certificates. NCI CTC v 3.0 was used for toxicity grading, and 6th Edition of AJCC Cancer Staging Manual for staging. Survival was estimated by Kaplan- Meier curves. Results: 45 patients with curatively resected GBC received adjuvant CR. Mean age was 56 years (range 33-75), 38 patients were female. All patients had PS 0 or 1 at baseline. After diagnosis a second surgery was performed in 41 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 40 patients. For tumor and staging details see the Table. All patients received RT with a planned dose of 45 Gy in 25 fractions. 9 patients received a boost to the tumor bed up to 54 Gy. Three patients stopped RT early. 33 patients had concurrent 5-FU, 31 completed treatment as planned. Therapy was well tolerated, only 4 grade 3 toxicities were observed (1 neutropenia, 1 thrombocytopenia, 2 elevated alkaline phosphatase). No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Twenty two patients have died. Median survival was 26 months, with 3- and 5-year overall survival of 64% and 46% respectively. Conclusions: Adjuvant chemoradiation with 5-FU is well tolerated and might impact favorably on survival in patients with curatively resected GBC. [Table: see text] No significant financial relationships to disclose.

A systematic review of the effectiveness of adjuvant therapy for patients with gallbladder cancer

“…3 The second SR was composed of 10 PS with 816 patients; 4 and the third SR, analyzed 14 PS and 2405 patients. 15 The 24 observational studies consisted of 4 retrospective cohort studies, [16][17][18][19] with a total of 1772 patients; two PBCS (2867 patients), 20,21 and 18 retrospective PS (1130 patients). 2,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] In all this represents a total of 55 studies and 9887 patients with GBC treated with curative surgical intent.…”

“…However, it should be specified that those who received adjuvant CT were younger, had less comorbidities and often presented positive lymph nodes, than those who received surgery alone. 16 In another retrospective cohort, it was also found that adjuvant treatments were effective, in terms of higher OS in subjects with positive lymph node disease (HR: 2.759 [1.14, 6.66]) 18 (type 4 treatment and prognosis 2b studies). Moreover, in a large series of retrospective patients with stage T2-3 N0-1 M0, treated with R0 surgery and adjuvant protocols of CT and CRT; it was observed that patients with T3 or positive lymph node disease, treated with adjuvant CT had a slight OS advantage (0.25 years more, p = 0.009), since OS curves converged at 5 years of follow-up.…”

“…In a retrospective cohort study, the effect of CRT (5-FU + 45-54 Gy) was assessed following surgery with curative intent. An OS at 3 and 5 years was 57% and 51% respectively and a protective effect of CRT (HR: 2.759 [1.14, 6.66]) 18 was verified (type 4 treatment and 2b prognosis studies).…”

“…Information was obtained from a retrospective cohort study, 18 a PBCS 21 and 7 retrospective PS 25,26,30,[33][34][35][36] ; representing a total of 2006 patients treated with CRT.…”

“…Information was obtained from 3 SR, 3,4,15 2 retrospective cohort studies 16,18 and 5 retrospective PS, 20,23,26,34,35 representing a total of 7,171 patients treated with some adjuvant regimen.…”