Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

A. L. Appelt, J. Ploen, I. R. Vogelius, S. M. Bentzen, A. Jakobsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D-50,D-TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), gamma(50,TRG1) = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D-50,D-TRG1&2 = 72.1 Gy (CI 65.3-94.0 Gy), gamma(50,TRG1&2) = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered. (C) 2013 Elsevier Inc.
Original languageEnglish
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume85
Issue number1
Pages (from-to)74-80
Number of pages7
ISSN0360-3016
DOIs
Publication statusPublished - 2013

Keywords

  • PHASE-III TRIAL TUMOR-REGRESSION NEOADJUVANT CHEMORADIOTHERAPY CHEMOTHERAPY RADIOTHERAPY CARCINOMA ESCALATION
  • Radiotherapy Dosage
  • Rectal Neoplasms/pathology
  • Humans
  • Middle Aged
  • Brachytherapy/methods
  • Logistic Models
  • Male
  • Tumor Burden
  • Uracil/administration & dosage
  • Patient Selection
  • Remission Induction/methods
  • Chemoradiotherapy/methods
  • Tegafur/administration & dosage
  • Models, Biological
  • Preoperative Care/methods
  • Adult
  • Female
  • Watchful Waiting
  • Aged
  • Neoplasm Staging
  • Dose-Response Relationship, Radiation
  • Adenocarcinoma/pathology

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