Lumbar-sacral bone marrow dose modeling for acute hematological toxicity in anal cancer patients treated with concurrent chemo-radiation.
The aim of the study was to model acute hematologic toxicity (HT) and dose to pelvic osseous structures in anal cancer patients treated with definitive chemo-radiation (CT-RT). A total of 53 patients receiving CT-RT were analyzed. Pelvic bone marrow and corresponding subsites were contoured: ilium, lower pelvis and lumbosacral spine (LSBM). Dose-volume histograms points and mean doses were collected. Logistic regression was performed to correlate dosimetric parameters and ≥G3 HT as endpoint. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Logistic regression showed a significant correlation between LSBM-mean dose and ≥G3 leukopenia (β coefficient 0.122; p = 0.030; 95% CI 0.012-0.233). According to NTCP modeling, the predicted HT probability had the following parameters: TD50: 37.5 Gy, γ50: 1.15, m: 0.347. For node positive patients, TD50: 35.2 Gy, γ50: 2.27, m: 0.176 were found. Node positive patients had significantly higher PBM-V15(Mean 81.1 vs. 86.7%; p = 0.04), -V20(Mean 72.7 vs. 79.9%; p = 0.01) and V30(Mean 50.2 vs. 57.3%; p = 0.03). Patients with a mean LSBM dose >32 Gy had a 1.81 (95% CI 0.81-4.0) relative risk to develop ≥G3 leukopenia. For node positive patients, those risks were 2.67 (95% CI 0.71-10). LKB modeling seems to suggest that LSBM-mean dose should be kept below 32 Gy to minimize ≥G3 HT in anal cancer patients treated with IMRT and concurrent chemotherapy. The contribution of LSBM dose in the development of HT above 25 Gy seems steeper in node positive patients.
Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy. pierfrancesco.franco@unito.it.
Pierfrancesco
http://orcid.org/0000-0003-2276-0687
P
Franco
Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy.
Riccardo
R
Ragona
Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy.
Francesca
F
Arcadipane
Department of Surgical Sciences, University of Turin, Turin, Italy.
Massimiliano
M
Mistrangelo
Department of Medical Sciences, University of Turin, Turin, Italy.
Paola
P
Cassoni
Department of Oncology, Radiation Oncology, AOU Città della Salute e della Scienza, Turin, Italy.
Nadia
N
Rondi
Department of Surgical Sciences, University of Turin, Turin, Italy.
Mario
M
Morino
Oncological Centre for Gastrointestinal Neoplasm, Medical Oncology 1, AOU Città della Salute e della Scienza, Turin, Italy.
Patrizia
P
Racca
Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy.
Umberto
U
Ricardi
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D059248:Chemoradiotherapy / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000139:chemically induced / Q000209:etiology*; D006801:Humans; D008161:Lumbosacral Region / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D008954:Models, Biological; D011832:Radiation Injuries / Q000209:etiology*; D011874:Radiometry / Q000379:methods; D012189:Retrospective Studies
D016685:Mitomycin; D005472:Fluorouracil
Acute hematologic toxicity; Anal cancer; Concomitant radiochemotherapy; IMRT; VMAT; Volumetric modulated arc therapy