Adjuvant Chemoradiation for Adenocarcinoma of the Pancreas: The Johns Hopkins Experience

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Ultima Vez Modificado: 8 de noviembre del 2006

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Presenter: M.J. Schwartz
Presenter's Affiliation: Johns Hopkins University School of Medicine, Baltimore, MD
Type of Session: Scientific

Background

  • At time of initial presentation, 15% to 20% of patients will have resectable pancreatic cancers.
  • The 5-year survival for patients after curative surgical resection is reported between 20% and 25%.
  • The use of adjuvant chemoradiotherapy following surgery is controversial.
  • Three randomized clinical trials have had conflicting results regarding the benefits of adjuvant chemoradiotherapy.
  • American physicians tend to utilize adjuvant chemoradiotherapy in this disease, while their European counterparts often omit such therapy.
  • This study was undertaken to examine the effect of adjuvant chemoradiation therapy after pancreaticoduodenectomy (Whipple resection) at a single, high volume center.

Materials and Methods

  • Between 8/30/93 and 2/28/05, all patients at Johns Hopkins University who underwent a Whipple procedure for pancreatic cancer were identified and reviewed.
  • 902 patients underwent surgery, and 408 of these had adjuvant therapy.
  • 190 of the patients who received adjuvant therapy were not treated with chemoradiation at Johns Hopkins.
  • Of the 218 patients who received therapy at Johns Hopkins, 63 received an experimental vaccine based therapy and were excluded from analysis.
  • 155 patients received chemoradiation therapy.
  • Chemoradiation consisted of 5-FU based therapy with concurrent radiation.
  • Radiation was delivered to a median dose of 50 Gy.
  • Chemoradiation was followed with maintenance 5-FU for 3-6 cycles.
  • Median follow-up was 5.8 years.

Results

  • Tumor-related factors (size, nodal status, etc) were not significantly different between the patients who received adjuvant therapy and those who did not.
  • Patients who did not receive adjuvant therapy were more likely to be older (median age 68 vs 63, p<0.001) and to have suffered post-operative complications (40% vs 26%, p=0.002).
  • Patients who received adjuvant therapy had a
    • median time-to-progression of 12 months
    • local failure rate of 22%
    • median survival of 21 months
    • 2-year overall survival of 45%
    • 5-year overall survival of 25%
  • Patients who did not receive adjuvant therapy had worse median survival (16 months vs 21 months, worse 2-year overall survival (36% vs 45%), and worse 5-year overall survival (16% vs 25%) than the patients who received adjuvant therapy.
  • On multivariate analysis, poor differentiation and positive margin status predicted for worse survival.
  • Even after controlling for age, margin status, nodal status, tumor size and post-operative complications, the use of adjuvant therapy still predicted for improved overall survival.

Author's Conclusions

  • These results compare favorably with results seen from previous randomized trials, despite the fact that the patients treated at Johns Hopkins had more advanced disease and higher positive margin rates.
  • Adjuvant 5-FU-based chemoradiation is associated with improved survival compared to observation alone.
  • Survival data from this series are consistent with previously reported studies of patients treated with adjuvant chemoradiation, and lend support to its continued use after definitive surgery.

Clinical/Scientific Implications

The authors present an interesting analysis of a single institution's experience in treating pancreatic cancer. Pancreatic cancer is a very difficult disease to treat and cure. Previous research has shown that patients have improved outcomes when treated at centers that perform a high volume of Whipple procedures. The surgeons at Johns Hopkins are quite experienced in this procedure, and the good results seen in this study may certainly in part be a reflection of the quality of surgery that the patients received. When this disease is studied in a multi-institutional setting, there may be a number of patients who receive suboptimal surgery, which could potentially diminish any benefit of adjuvant chemoradiation in such trials. The authors' conclusions regarding this disease at their institution are appropriate, and further research should continue to consider adjuvant chemoradiotherapy with 5-FU as the current standard of care.

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