title: Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer.
abstract: OBJECTIVE
  This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation.
  
  
  METHODS
  50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method.
  
  
  RESULTS
  Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V20was associated with lower WBC nadir. Increased LSBM-V40was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V40was found. Patients with LSBM-V40≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01).
  
  
  CONCLUSIONS
  Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium-high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V40was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V40could be used to limit HT.
authors.affiliation: Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy. pierfrancesco.franco@unito.it.
authors.forename: P
authors.initials: P
authors.lastname: Franco
authors.affiliation: Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ragona
authors.affiliation: Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Arcadipane
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mistrangelo
authors.affiliation: Department of Medical Sciences, Pathology Unit, University of Torino, Turin, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Cassoni
authors.affiliation: Department of Medical Imaging and Radiotherapy, Radiation Oncology, AOU Città della Salute e della Scienza, Turin, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Rondi
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morino
authors.affiliation: Oncological Centre for Gastrointestinal Neoplasm, Medical Oncology 1, AOU Città della Salute e della Scienza, Turin, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Racca
authors.affiliation: Department of Oncology, Radiation Oncology, University of Turin School of Medicine, Via Genova 3, 10126, Turin, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Ricardi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001005:Anus Neoplasms / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D016685:Mitomycin; D005472:Fluorouracil
keywords: Acute toxicity; Anal cancer; Concomitant radiochemotherapy; IMRT; Radiation; Radiotherapy; VMAT; Volumetric modulated arc-therapy