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Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy
12. juli 2012 - Heidi RøndePurpose
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, D50,i, and the normalized dose-response gradient,
γ50,i.
Results
A highly significant dose-response relationship was found (P=.002).
For complete response (TRG1), the dose-response parameters were
D50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy),
γ50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2)
D50,TRG1&2 = 72.1 Gy (CI 65.3-94.0 Gy), γ50,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.
Ane L. Appelt, MSc; John Pløen, MD; Ivan R. Vogelius, PhD; Søren M. Bentzen, PhD, DSc; Anders Jakobsen, DMSc