Pre-operative Radiation is Associated with Improved Survival Compared to Post-operative Radiation for Esophageal Cancer: A SEER Database Analysis

Proceedings of the 50th Annual ASTRO Meeting multiple (7-12) non-opposing, non-coplanar beams in the body frame with abdominal compression. Dose was prescribed to the 8090% isodose line covering the planning target volume [PTV= gross tumor volume (GTV) with 0.5 cm axial and 1 cm cranio-caudal margins]. Dose-limiting toxicity (DLT) was defined as Common Toxicity Criteria (CTC) grade $3 toxicity, attributed to the SBRT. The MTD was exceeded if 2/6 patients in a cohort experienced DLT. Dose escalation started at 36 Gy in 3 fractions (fxs) in 5-10 days with subsequent planned escalation of 2 Gy/fx/level. Results: Sixteen patients (7 Child’s A and 9 Child’s B) were enrolled between 3/05 and 8/07. Median GTV was 42.2 ml (range, 10.7-95.0 ml). Child’s A patients were successfully escalated to 48 Gy/3 fxs without DLT. Two of 6 patients in the Level Dose 2 (both Child’s B) developed grade 3 liver toxicity. The trial was amended for subsequent Child’s B patients to receive 40 Gy/5 fxs (800 cGy/fx, 1-2 fxs/week) and 4 patients were enrolled. At this dose level, 1 patient died of an unrelated co-morbid condition 4 months after SBRT. A second patient experienced declining of liver function to Child’s C and died 87 days post-SBRT from sepsis and liver failure. Both patients had CP scores $8. No other grade 3 or higher treatment related toxicities were encountered. Ten of 16 patients are alive without progression at a median follow-up post-SBRT of 14.5 months (range, 6.6-25.3 months). Clinical and/ or dosimetric factors found to be related to grade $3 liver toxicity or death within 6 months include higher CP score (p = 0.02) and GTV volume (p = 0.09, marginal). All 4 subjects with CP score $8 either had $3 toxicity or died within 6 months; they also had greater PTV, GTV, ratio PTV/uninvolved liver, mean liver dose, and dose to 1/3 uninvolved liver (all significant, p # 0.05). Five patients (3 Child’s B) have successfully bridged to OLT at the time of this analysis. Conclusion: Biologically potent doses of SBRT are well tolerated in patients with primary HCC and underlying Child’s A liver disease. Patients with CP scores $8 are at higher risk of severe toxicity unless they undergo OLT. Author Disclosure: H. Cardenes, None; T. Price, None; S. Perkins, None; M. Maluccio, None; P. Kwo, None; T. Breen, None; M. Henderson, None; K. Tudor, None; J. DeLuca, None; P. Johnstone, None.

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Pre-operative Radiation is Associated with Improved Survival Compared to Post-operative Radiation for Esophageal Cancer: A SEER Database Analysis

P. Sanghvi, J. Kalpathy-Cramer, J. Holland, J. Hunter, C. Thomas, S. Wang Oregon Health & Science University, Portland, OR Purpose/Objective(s): When locally advanced esophageal cancer is treated with multimodality therapy, the sequencing of surgery and chemoradiotherapy varies, with chemoradiotherapy given either pre-operatively or post-operatively. To date, there have been no randomized controlled trials directly comparing the sequencing of chemoradiotherapy with surgery. The specific aim of this study was to conduct a multivariate regression model from the NCI’s Surveillance, Epidemiology, and End Results (SEER) 17 database to compare historical survival rates for patients receiving pre-operative radiotherapy (PreRT) vs post-operative radiotherapy (PostRT) for esophageal cancer. Materials/Methods: Using the SEER 17 database, we collected all cases of non-metastatic resected esophageal cancer between 1988 and 2004. We examined trends over time in the number of patients receiving PreRT vs PostRT. We then performed a multivariate regression analysis using Cox proportional hazards (CPH) modeling to control for age, sex, T & N classification, histology, and tumor site. The primary endpoint was to compare overall survival (OS) between PreRT vs PostRT. Results: From 1988-2004, there were a total of 3759 patients who received a combination of surgery and radiotherapy. Overall, 2005 (53%) received PreRT and 1754 (47%) received PostRT. The proportion receiving pre-operative radiotherapy increased over time; during the era from 1988-1990, only 33% of patients received PreRT, but from 2002-2004, 62% received PreRT. In the unadjusted survival analysis, median OS for all patients was 18 months (95% CI 17-19). For those receiving PreRT, the median OS was 25 months (95% CI 23-26), while for those receiving PostRT, the median OS was 14 months (95% CI 14-15) (p \ 0.0001). In the CPH multivariate regression model, we found that male sex, higher T & N stage, and mid-esophageal tumor location were independent poor predictors of survival. Even after adjusting for these covariates, PreRT was associated with an improved hazard ratio of 0.85 (95% CI 0.75-0.96) compared to PostRT. Conclusions: In multivariate regression analysis of historical cases of esophageal cancer from the SEER database, we found that patients receiving PreRT had improved overall survival compared to those receiving PostRT. These findings are supportive of the current pattern of care using neoadjuvant chemoradiotherapy followed by surgical resection for locally advanced esophageal cancer. Author Disclosure: P. Sanghvi, None; J. Kalpathy-Cramer, None; J. Holland, None; J. Hunter, None; C. Thomas, None; S. Wang, None.

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A Randomized Phase II Study of Cisplatin/5-FU Concurrent Chemoradiotherapy for Esophageal Cancer: Short-term Infusion versus Protracted Infusion Chemotherapy (KROSG-0101, JROSG-021)

Y. Nishimura1, M. Mitsumori2, M. Hiraoka2, R. Koike1, K. Nakamatsu1, M. Kawamura3, Y. Negoro4, K. Fujiwara5, H. Sakurai6, N. Mitsuhashi7 1 Dept. of Radiation Oncology, Kinki University School of Medicine, Osaka, Japan, 2Kyoto University Graduate School of Medicine, Kyoto, Japan, 3Nara Social Insurance Hospital, Yamato-Koriyama, Japan, 4Fukui Red Cross Hospital, Fukui, Japan, 5 National Hospital Organization Kyoto Medical Center, Kyoto, Japan, 6Gunma University Graduate School of Medicine, Maebashi, Japan, 7Tokyo Women’s Medical University School of Medicine, Tokyo, Japan

Purpose/Objective(s): To obtain maximum radio-sensitization by chemotherapy (CT), daily administration of small dose CT may be better than short-term full dose CT. A randomized phase II study was conducted to compare the relative toxicity and efficacy of combining short-term infusion CT or protracted infusion CT with radiotherapy (RT) for esophageal cancer. Materials/Methods: Eligible patients were \75 years and PS 0-2, and had stages II-IVA (UICC 97) esophageal cancer excluding tumors with fistula. For arm A (short-term infusion), CDDP 70 mg/m2 days 1 and 29 and 5FU 700 mg/m2 days 1-5 and 29-33 were given concurrently with RT of 60 Gy/30 fr/7 weeks (1-week split). For arm B (protracted infusion), CDDP 7 mg/m2 days 1-5, 8-12,

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