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Journal of Clinical Oncology, Vol 25, No 30 (October 20), 2007: pp. 4861 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.13.0054
Radiotherapy for Locally Advanced Pancreatic CancerDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI
Department of Internal Medicine, University of Michigan, Ann Arbor, MI To the Editor: We read Isacoff et al's article1 with mixed response. While we congratulate the authors and the Southwest Oncology Group for the successful conduct of this phase II trial, we strongly disagree with its underlying premise that radiation therapy must compromise systemic therapy for pancreatic cancer. In fact, radiotherapy can be delivered safely with concurrent full-dose systemic therapy in patients with unresectable pancreatic cancer if appropriate techniques are used. Over the past decade, our group at the University of Michigan (Ann Arbor, MI) has completed a series of trials examining the combinations of radiotherapy with full-dose gemcitabine,2 gemcitabine/cisplatinum,3 and gemcitabine/oxaliplatin.4 The key to the success of this approach has been the abandonment of prophylactic irradiation of regional lymph nodes necessitating use of large radiation fields. We have recently demonstrated that this approach does not result in an excess of failures within these nodes.5 The authors' downplay of the importance of local control in this disease is unfortunate. Local progression of disease results in pain, gastric outlet and duodenal obstruction, and upper gastrointestinal ulceration and bleeding. Indeed, in one of the few studies that addressed this issue, radiotherapy alone was shown to offer palliation in up to 50% of patients, leading to decreased pain and analgesic consumption.6 Improved local control not only provides a palliative benefit, but may also impact on survival. The Gastrointestinal Tumor Study Group has conducted a prospective phase III trial7 comparing streptozotocin, mitomycin, and fluorouracil chemotherapy alone with streptozotocin, mitomycin, and fluorouracil plus external-beam radiotherapy. They reported a significant benefit in median survival (9.7 v 7.4 months) in favor of the combined modality arm. In our patients,5 we found local failure to be strongly associated with survival. Analyzed as a time-dependant covariate, local failure was predictive of early mortality with a hazard ratio of 2.15 (P = .007). Furthermore, local control remained an independent predictor of survival in a multivariate analysis that included distant failure as a covariate (P = .0023). We would like to draw the attention of the readers to the often unappreciated low local control rates in unresectable pancreatic cancer. We have examined this issue in a recent report by having a single abdominal radiologist systematically review all pre- and post-treatment computed tomography scans. Even in our patients treated with full-dose gemcitabine and modern day three-dimensional radiotherapy, the 1- and 2- year freedom from local progression rates were 64% and 38%, respectively.5 Given that persistence of disease after chemoradiotherapy in locally advanced pancreatic cancer is nearly universal, this should not be surprising. Many reasons account for this under-reporting of local failure, including lack of attention after metastatic disease is discovered. In summary, local progression of disease is a common problem in patients with advanced, nonmetastatic pancreatic cancer. Radiotherapy has an important role in the management of this disease and can be integrated safely with intensive systemic regimens. Rather than pit one treatment modality against another, we need to collaborate to use all therapies to improve the outcome for this terrible disease. As has been clearly demonstrated in the case of breast cancer, as more effective systemic therapy is introduced, the contribution of local control to survival will become increasingly more evident. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Isacoff WH, Bendetti JK, Barstis JJ, et al: Phase II trial of infusional fluorouracil, leucovorin, mitomycin, and dipyridamole in locally advanced unresectable pancreatic adenocarcinoma: SWOG S9700. J Clin Oncol 25:1665-1669, 2007 2. McGinn CJ, Zalupski MM, Shureiqi I, et al: Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 19:4202-4208, 2001 3. Muler JH, McGinn CJ, Normolle D, et al: Phase I trial using a time-to-event continual reassessment strategy for dose escalation of cisplatin combined with gemcitabine and radiation therapy in pancreatic cancer. J Clin Oncol 22:238-243, 2004 4. Desai S, et al: A phase I study of oxaliplatin, full-dose gemcitabine and concurrent radiation therapy in patients with pancreatic cancer. J Clin Oncol 24:204s, 2006 (abstr 4107) 5. Murphy JD, Adusumilli S, Griffith KA, et al: Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys 68:801-808, 2007[Medline] 6. Haslam JB, Cavanaugh PJ, Stroup SL: Radiation therapy in the treatment of irresectable adenocarcinoma of the pancreas. Cancer 32:1341-1345, 1973[CrossRef][Medline] 7. Treatment of locally unresectable carcinoma of the pancreas: Comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone: Gastrointestinal Tumor Study Group. J Natl Cancer Inst 80:751-755, 1988
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Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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