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Average cumulative relative dose of adjuvant chemotherapy is more important than average relative dose intensity for colorectal cancer survival, with implications for treating obese patients: The OCTOPUS consortium
Slawinski, C. Malcomson, Lee Barriuso, Jorge Guo, H. Harkin, A. Iveson, T. Glynne-Jones, R. Van de Velde, C
Slawinski, C.
Malcomson, Lee
Barriuso, Jorge
Guo, H.
Harkin, A.
Iveson, T.
Glynne-Jones, R.
Van de Velde, C
Citations
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Abstract
Background:After curative surgery for colorectal cancer (CRC), some studies indicatepoorer survival in obese patients. Adjuvant chemotherapy (ACT) for CRC is commonlycapped at a body surface area (BSA) 2.2m2, potentially reducing chemotherapyaverage cumulative relative dose (ACRD) and average relative dose intensity (ARDI) inobese patients.Methods:Individual participant-level data from MOSAIC, SCOT, PROCTORSCRIPT, andCHRONICLE (CRC-ACT) randomised-trials, with derivable BMI, BSA, and chemotherapydoses, were included from the OCTOPUS consortium. ARDI and ACRD were calculatedas percentages of actual to expected (full BSA-based) dose intensity (cumulativedose/treatment duration in weeks) or cumulative dose, respectively, averaged acrossthe drugs in the regimen. Two-stage random-effects meta-analyses of linear or Coxproportional hazards regression models were performed to explore BMI-ARDI/-ACRDand ARDI-/ACRD-survival relationships, respectively. The primary outcome was dis-ease-free survival (DFS), and secondary outcomes were overall (OS) and cancer-specific (CSS) survival, in addition to ARDI and ACRD. All models where adjusted for age, sex, performance status, t-stage and n-stage (in addition to BMI in the survivalmodels).Results:7269 patients were eligible. BMI 5kg/m2 increments were associated with a2.04% reduction in cycle 1 dose (95% CI:-2.45,-1.64; p ACRD 5% increments wereassociated with improved DFS (HR 0.953 (0.926, 0.980); p¼0.001), OS (HR0.931(0.908, 0.955); p<0.001) and CSS (HR 0.941(0.924, 0.959); p<0.001) survival.However, no significant relationship was demonstrated for ARDI (DFS HR 1.015 (0.967,1.065); p¼0.552; OS HR 1.035 (0.990, 1.081); p 0.134; CSS HR 1.022 (0.982, 1.064); p¼0.282), nor for sex-interactions for both ACRD and ARDI.Conclusions:ACRD is more important than ARDI in determining survival. Elevated BMIis associated with a reduced cycle 1 dose and a modest ACRD reduction. These in-direct effects through under-treatment might explain poorer survival in obese pa-tients, rather than direct effects of obesity resulting from, for example, tumour biology.
Description
Date
2021
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Slawinski C, Malcomson L, Barriuso J, Guo H, Harkin A, Iveson T, et al. O-4 Average cumulative relative dose of adjuvant chemotherapy is more important than average relative dose intensity for colorectal cancer survival, with implications for treating obese patients: The OCTOPUS consortium. Annals of Oncology. 2021 Jul;32:S218–9.