Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

Abstract

Background and purpose: To identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer.

Materials and methods: We analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models.

Results: Nadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p=0.04), and patients ⩾59 years of age had a lower hemoglobin ratio trend during PRT (p=0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p=0.03), and women had lower hemoglobin cell count trend compared to men (p=0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p=0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p=0.03) and sacral BM V45 (p=0.03) were associated with a lower WBC and ANC ratio at nadir, respectively.

Conclusions: HT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered.

Keywords: Acute radiation toxicity; Clinical predictors; Dose constraint; Rectal cancer.

Conflict of interest statement

Conflict of interest notification

The authors of this manuscript have no actual or potential conflicts of interest to disclose.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig. 1

Pelvic bone marrow subsites (A), and a comparison of dose distribution of intensity modulated radiation therapy rectal cancer treatment (B) versus three-dimensional conformal radiation therapy rectal cancer treatment (C). These snapshots were captured using our in-house software (Computational Environment for Radiotherapy Research).

Fig. 2

Cell count ratio trend (mean and 95% confidence interval plotted): (A) weekly cell count ratio for all cell types; (B) treatment type versus weekly WBC count ratio; (C) age versus weekly hemoglobin count ratio during pelvic radiotherapy.