(P096) Preoperative Radiation Dose Escalation for Rectal Cancer Improves Tumor Downstaging Without Significant Increase in Toxicity: A Matched-Pair Analysis

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OncologyOncology Vol 28 No 1S
Volume 28
Issue 1S

We sought to explore a potential dose-response relationship with tumor downstaging after neoadjuvant chemoradiation therapy for rectal cancer. To this end, we conducted a case-control analysis of 152 patients treated preoperatively, with and without a concomitant boost.

David Weksberg, C.V. Patel, K.V. Kattepogu, Jonathan D. Grant, I.J. Park, Cathy Eng, Marc E. Delclos, Barry Feig, Chris H. Crane, J.M. Skibber, Prajnan Das, Miguel A. Rodriguez-Bigas, Bruce D. Minsky, Sunil Krishnan, George Chang; UT MD Anderson Cancer Center

PURPOSE: With large studies demonstrating improved sphincter preservation and local control following neoadjuvant chemoradiation therapy (NCRT) for rectal cancer, this approach has been established as standard in locally advanced or node-positive disease. While a tantalizing minority of patients enjoys pathologic complete response (pCR) at the time of surgery, ~50% of lesions fail to be downstaged by treatment. We sought to explore a potential dose-response relationship with tumor downstaging after NCRT. To this end, we conducted a case-control analysis of 152 patients treated preoperatively, with and without a concomitant boost.

METHODS: From 1995–2003, 76 patients were enrolled on an institutional review board (IRB)-approved phase II protocol examining the feasibility of adding a concomitant boost to NCRT. Patients received venous infusion 5-fluorouracil (5-FU) and 52.5 Gy in 5 weeks-42.5 Gy at 1.8 Gy per fraction daily, plus a concomitant boost of 1.5 Gy per day in the final week of treatment. Using a case-control approach, 76 additional patients were identified who received low-dose NCRT (5-FU plus 45 Gy in 1.8-Gy fractions), matching for type of surgery performed, tumor stage (T-stage), and clinical nodal metastases (N-stage). For all 152 patients, chart review was undertaken with respect to clinicopathologic parameters and treatment outcomes. Radiation toxicity and surgical complications were assessed in a subset of 63 pairs with complete toxicity data available. McNemar’s chi-square test and Kaplan-Meier analyses were used as appropriate.

RESULTS: The high-dose (HD) and low-dose (LD) cohorts were well matched; in addition to the selection criteria, there were no significant differences in gender (HD 64.5% male vs LD 65.8% male) or age (HD 57.1 yr vs LD 55.9 yr). For a subset of patients, information regarding circumferential involvement (50% of patients) and tumor length was available (65% of patients); there were no significant differences in these criteria. A statistically significant difference in distance from the anal verge was noted (HD 4.7 cm vs LD 5.7 cm; P < .03).

The rate of tumor downstaging was substantially improved in the HD cohort, with 76% of patients found to have reduction in T-stage vs 51% in the LD arm (P < .01). However, the rates of pCR did not differ significantly (HD 17.1% vs LD 15.8%). Toxicity data reveal that T-downstaging did not appear to come at a cost of substantially increased toxicity. While ~90% of patients experienced some radiation toxicity, the incidence of grade 3 or higher toxicities was low (HD 9% vs LD 3%), as was the rate of wound complication (HD 8% vs LD 7%), with no statistically significant differences between the cohorts.

CONCLUSIONS: Our results suggest that dose escalation in NCRT is feasible without significant increase in radiation toxicity or surgical complication. While pCR rates did not differ between HD and LD NCRT groups, the increased T-downstaging seen in the HD arm supports a dose-response relationship with tumor downstaging and suggests further exploration of dose escalation as a tool to improve sphincter preservation rates in appropriately selected patients.

Articles in this issue

(P113) Age and Marital Status Are Associated With Choice of Mastectomy in Patients Eligible for Breast Conservation Therapy
(P112) Single-Institution Experience With Intrabeam IORT for Treatment of Early-Stage Breast Cancer
(P110) Breast Cancer Before Age 40: Current Patterns in Clinical Presentation and Local Management
(P111) Accelerated Partial-Breast Irradiation With Multicatheter High-Dose-Rate Brachytherapy: Feasibility and Results in a Private Practice Cohort
(P115) Breast Cancer Laterality Does Not Influence Overall Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality
(P117) Anatomical Variations and Radiation Technique for Breast Cancer
(P116) Bilateral Immediate DIEP Reconstruction and Postmastectomy Radiotherapy: Experience at a Tertiary Care Institution
(P118) Metadherin Overexpression Is Associated With Improved Locoregional Control After Mastectomy
(P119) Effect of Economic Environment on Use of Postlumpectomy Radiation Therapy for Stage I Breast Cancer
(P120) Immediate Versus Delayed Reconstruction After Mastectomy in the United States Medicare Breast Cancer Patient
(P121) Trend in Age and Racial Disparities in the Receipt of Postlumpectomy Radiation Therapy for Stage I Breast Cancer: 2004–2009
(P122) Streamlining Referring Physicians Orders With ‘Reflex Testing’ Significantly Decreases Time to Resolution for Abnormal Screening Mammograms
(P123) National Trends in the Local Management of Early-Stage Paget Disease of the Breast
(P124) Effect of Inhomogeneity on Cardiac and Lung Dose in Partial-Breast Irradiation Using HDR Brachytherapy
(P125) Breast Cancer Outcomes With Anthracycline-Based Chemotherapy for Residual Disease Burden After Full-Dose Neoadjuvant Chemotherapy and Surgery Followed by Radiation Treatment
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