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.

Dosimetric predictors of acute haematological toxicity in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy

“…2,4,5 Furthermore, myelotoxicity has been identified as a significant poor prognostic factor in patients with T4 EC treated with CRT followed by curative resection. 6 Pelvic radiotherapy and chemotherapy are known to be myelosuppressive in patients with cervical and anal cancers, [7][8][9][10][11][12][13] and radiation oncologists have implemented efforts to mitigate the degree of haematological toxicity (HT) associated with these treatments. Given that the thorax contains approximately 35% of the functional BM, 14 irradiation of these thoracic structures could destroy radiosensitive BM stem cells and contribute to HT in patients with EC.…”

“…V x indicates the total organ volume percentage exceeding a radiation dose of x (Gy). Results: Greater thoracic vertebrae and rib irradiation doses, including mean vertebral dose (MVD), thoracic vertebrae V 5-30 (TVV ), mean rib dose and rib V [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , were associated with increased leukopenia (grade $ 3) risk. Additional BM sites (sternum, scapulae and clavicles) did not influence HT.…”

The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical Outcomes in Rectal Cancer

“…The use of 3DCRT compared to IMRT was associated with a lower WBC ratio and ANC cell count. When analyzing the dosimetric variables, coxal (ilium, ischium and pubis) bone marrow V45 and sacral bone marrow V45 were significantly correlated with a lower WBC and ANC ratio at nadir, respectively (45) but the sacrum is difficult to spare in a standard rectal field in which the mesorectum and presacrum require radiation coverage.…”

“…In some of the studies cited previously, IMRT has also been used to deliver a simultaneous integrated boost (SIB) for LARC (17, 19, 21, 27, 45-49). Target coverage including conformity and homogeneity indices and OAR sparing were superior with VMAT and IMRT compared to 3DCRT (17, 21).…”

Bone marrow tolerance during postoperative chemotherapy in colorectal carcinomas

“…There have been several studies evaluating the relationship between incidental pelvic bone marrow (PBM) irradiation and hematologic toxicity (HT) during CRT (6,7) in an attempt to create radiotherapy dose constraints to the PBM. Since nearly 40% of total human bone marrow (BM) (8) is in the PBM, sparing of the BM is thought to limit morbidity during the short period of CRT.…”