Clinical Investigation
Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

https://doi.org/10.1016/j.ijrobp.2014.07.024Get rights and content

Purpose

To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma.

Methods and Materials

A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT.

Results

Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014)

Conclusion

This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

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.

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  • 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.

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