Adjuvant Chemoradiation Therapy after Surgical Resection for 1092 Cases of Pancreatic Adenocarcinoma: The Johns Hopkins Hospital - Mayo Clinic Collaborative Study of Pancreatic Cancer
Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 22, 2008
Presenter: C. C. Hsu
Presenter's Affiliation: Johns Hopkins Hospital, Baltimore, MD
Type of Session: Scientific
- Despite aggressive multimodality treatment, pancreatic cancer is associated with a high rate of mortality.
- Even the 15-20% of patients who present with resectable disease experience 5-year survivals of only 10-25%.
- Controversy exists regarding the use of adjuvant chemotherapy and radiation therapy in resected pancreatic cancer.
- Randomized GITSG and EORTC trials support the use of adjuvant chemoradiation, while the ESPAC-1 trial refutes its benefit.
Materials and Methods
- The purpose of this study is to examine the potential benefit of adjuvant chemoradation therapy in resectable pancreatic cancer and to determine which factors predict survival.
- This is a retrospective analysis of patients treated at Johns Hopkins Hospital and Mayo Clinic from 1985-2005.
- Two separate analyses were utilized to account for factors leading to treatment bias
- Propensity score was given using 16 variables and was used as a covariate in a Cox regression analysis
- 1:1 matched pair analysis was performed, with patients matched by institution, age, sex, T-stage, tumor grade, margin status, and nodal status
- Exclusion criteria included death within 60 days of surgery, unresectable disease, IORT, vaccine therapy, distal duodenal disease, or those receiving single modality adjuvant treatment
- 1092 patients were included in the analysis: 618 from Hopkins and 474 from Mayo
- Median follow-up 18.2 months
- Patients receiving adjuvant treatment were younger, had higher grade histology and greater incidence of positive surgical margins
- Median dose of radiation therapy was 50.4 Gy
- Several patients were treated with split course RT with similar results
- Overall survival improved with adjuvant therapy
- Median survival 21.1 (adjuvant chemoradiation) vs. 15.5 months (none)
- 2-year survival 44.7% (adjuvant chemoradiation) vs. 34.6% (none)
- 5-year survival 22.3% (adjuvant chemoradiation) vs. 16.1% (none)
- Cox regression by propensity score demonstrated that adjuvant therapy provides a relative risk for overall survival of 0.67 (p<0.001)
- On matched pair analysis, adjuvant therapy demonstrated an increased median survival of 21.9 months vs. 14.3 months
- The benefit was maintained across each risk stratification in both of these analyses
- Age < 70 yo, R0 resection, stage T1-2, lymph node negativity, and Grade 1/2 disease are the factors that predicted for improved survival
- These data suggest that adjuvant chemoradiation improves overall survival by approximately 35% in post-operative pancreas cancer patients.
- These results are consistent with the GITSG and EORTC randomized studies.
- Future trials are needed to address the sequencing of treatments and to investigate further aggressive therapies.
- The controversy involving adjuvant treatment for resectable pancreas cancer will continue.
- While some suggest that radiation has a role only in adjuvant treatment of patients with positive margins, these data show that a benefit exists with adjuvant concurrent chemoradiation, regardless of margin status. This is limited, however, by the lack of inclusion of patients treated with adjuvant chemotherapy alone in this study.
- The median survival of patients treated with chemoradiation in this study was 21.1 months, which compares favorably with the highly selected patients of the CONKO-1 trial (low post-operative CA 19-9 levels), where there was a median survival of 22.8 months in the gemcitabine arm and 20.2 months in the observation arm.