International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationMulti-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer
Introduction
Most patients with pancreatic adenocarcinoma (PC) present at an advanced stage of the disease, precluding long-term survival. In patients with localized disease, surgical resection still remains the only potentially curative therapy.
Both local and systemic relapses are common after radical surgical treatment 1, 2. Based on this pattern of failure, both systemic and local adjuvant therapy may have a positive impact on patients outcome. In the attempt to improve survival, the efficacy of adjuvant chemoradiation (CRT) and chemotherapy (CT) has been tested in several clinical trials.
A historical randomized trial conducted by the Gastro-Intestinal Tumor Study Group (GITSG) showed improved overall survival (OS) with the use of adjuvant CRT followed by adjuvant CT after definitive surgery 3, 4. These findings were supported by an analysis from Johns Hopkins Hospital comparing adjuvant CRT versus surgical resection alone (5). Patients receiving postoperative CRT showed improved median survival (20 vs 14 months) and 2-year survival (40% vs 31%; P=.003). In contrast, European trials did not confirm a statistically significant survival benefit with CRT (6). Moreover, some European studies suggested a detrimental effect on survival with CRT compared with chemotherapy or surgery alone 7, 8. The weaknesses of these trials complicate decision making about which patients should receive adjuvant CRT or chemotherapy alone (9).
Studies demonstrating a benefit in CRT have been criticized because of small sample size and patient-selection bias 10, 11. To address these limitations, a retrospective analysis of a large cohort of patients undergoing resection of PC in 9 different centers was performed. The purpose of the study is to evaluate whether adjuvant CRT improves survival in a large cohort of unselected patients.
Section snippets
Study design and participants
Clinical data (N=1120) from institutions in 9 different cities (Baltimore, Rochester, Montpellier, Madrid, Salzburg, Verona, Campobasso, Milan, and Rome) were pooled for this analysis on individual patient basis. Patients were treated between 1995 and 2008. The following variables were analyzed: age, sex, tumor location (head, body, tail), surgical procedure (duodenocephalopancreatectomy, distal, total), tumor grade (1-4), microscopic residual disease (no/yes), tumor diameter (mm), pathological
Results
Median follow-up time for all patients was 21.0 months and 21.5 months for survivors. Demographic data for patients are shown in Table 1. The mean age (± standard deviation [SD])for the entire cohort of patients was 62.7 ± 10.4 years. No differences between patients receiving or not receiving adjuvant chemoradiation were observed in terms of age (62.3 ± 10.6 years vs 63.5 ± 10.1 years; P=.090), tumor diameter (29.5 ± 14.1 mm vs 28.3 ± 12.2 mm; P=.287) and rate of R1 resection (26.8% vs 26.9%; P
Discussion
Adjuvant CRT was considered as a therapeutic option in patients with resected PC after publication of the GITSG trial (3). The results of that study showed an improved survival in the arm with postoperative CRT compared to the arm with surgery alone (median OS = 10.9 vs 21.0 months; P=.04) (3). In the GITSG trial, a relatively low dose (40 Gy) of RT was delivered using a split-course regimen. The positive results of this randomized study were subsequently confirmed after evaluation of another
Conclusions
In conclusion, our pooled analysis confirms the possibility of improving outcomes in patients with resected PC by use of adjuvant CRT. However, the prognosis of this disease remains very poor, justifying new trials based on innovative therapeutic strategies.
Acknowledgments
The authors sincerely thank Dr Cinzia Digesù for reviewing and editing the manuscript.
References (35)
- et al.
Patterns of recurrence after curative resection of pancreatic cancer based on autopsy findings
J Gastrointest Surg
(2006) - et al.
Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: A randomized controlled trial
Lancet
(2001) - et al.
The case for adjuvant chemoradiation for pancreatic cancer
Best Pract Res Clin Gastroenterol
(2006) - et al.
Interferon-based adjuvant chemoradiation therapy after pancreaticoduodenectomy for pancreatic adenocarcinoma
Am J Surg
(2003) - et al.
Adjuvant therapy in pancreatic cancer: Phase I trial of radiation dose escalation with concurrent full dose gemcitabine
Int J Radiat Oncol Biol Phys
(2004) - et al.
Intraoperative radiation therapy in resected pancreatic carcinoma: Long-term analysis
Int J Radiat Oncol Biol Phys
(2008) - et al.
Adjuvant radiotherapy in resectable pancreatic carcinoma
Eur J Surg Oncol
(2002) - et al.
A challenge to the therapeutic nihilism of ESPAC-1
Int J Radiat Oncol Biol Phys
(2005) - et al.
Continuing controversy over adjuvant therapy of pancreatic cancer
Lancet
(2001) - et al.
Is adjuvant 5-F U-based chemoradiotherapy for resectable pancreatic adenocarcinoma beneficial? A meta-analysis of an unanswered question
J Gastrointest Surg
(2006)
Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: Who really benefits?
J Am Coll Surg
Frequency with wich surgeons undertake pancreaticoduodenectomy determines length of stay, hospital charges, and in-hospital mortality
J Gastrointest Surg
Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704—a phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas
Int J Radiat Oncol Biol Phys
Analysis of paraaortic lymph node involvement in pancreatic carcinoma: A significant indication for surgery?
Cancer
Pancreatic cancer: Adjuvant combined radiation and chemotherapy following curative resection
Arch Surg
Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer
Cancer
Pancreaticoduodenectomy for pancreatic adenocarcinoma: Postoperative adjuvant chemoradiation improves survival—a prospective, single-institution experience
Ann Surg
Cited by (0)
A.G.M. and M.F share the first authorship.
M.F. is currently at the Department of Surgery, Università Politecnica delle Marche, Ancona, Italy.
Conflict of interest: none.