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

Background

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

Results

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

Author's Conclusions

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.

Clinical/Scientific Implications

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.