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
Ultima Vez Modificado: 22 de septiembre del 2008

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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.

English
News
Gemcitabine Improves Overall Pancreatic Cancer Survival

Oct 9, 2013 - Adjuvant gemcitabine treatment after surgical removal of pancreatic cancer significantly improves both disease-free and overall survival compared with observation, according to a study published in the Oct. 9 issue of the Journal of the American Medical Association.



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