title: Predictors of acute toxicities during definitive chemoradiation using intensity-modulated radiotherapy for anal squamous cell carcinoma.
abstract: OBJECTIVE
  To identify clinical and dosimetric factors associated with acute hematologic and gastrointestinal (GI) toxicities during definitive therapy using intensity-modulated radiotherapy (IMRT) for anal squamous cell carcinoma (ASCC).
  
  
  METHODS
  We retrospectively analyzed 108 ASCC patients treated with IMRT. Clinical information included age, gender, stage, concurrent chemotherapy, mitomycin (MMC) chemotherapy and weekly hematologic and GI toxicity during IMRT. From contours of the bony pelvis and bowel, dose-volume parameters were extracted. Logistic regression models were used to test associations between toxicities and clinical or dosimetric predictors.
  
  
  RESULTS
  The median age was 59 years, 81 patients were women and 84 patients received concurrent MMC and 5-fluorouracil (5FU). On multivariate analysis (MVA), the model most predictive of Grade 2 + anemia included the maximum bony pelvis dose (Dmax), female gender, and T stage [p = 0.035, cross validation area under the curve (cvAUC) = 0.66]. The strongest model of Grade 2 + leukopenia included V10 (percentage of pelvic bone volume receiving ≥ 10 Gy) and number of MMC cycles (p = 0.276, cvAUC = 0.57). The model including MMC cycle number and T stage correlated best with Grade 2 + neutropenia (p = 0.306, cvAUC = 0.57). The model predictive of combined Grade 2 + hematologic toxicity (HT) included V10 and T stage (p = 0.016, cvAUC = 0.66). A model including VA45 (absolute bowel volume receiving ≥ 45 Gy) and MOH5 (mean dose to hottest 5% of bowel volume) best predicted diarrhea (p = 0.517, cvAUC = 0.56).
  
  
  CONCLUSIONS
  Dosimetric constraints to the pelvic bones should be integrated into IMRT planning to reduce toxicity, potentially reducing treatment interruptions and improving disease outcomes in ASCC. Specifically, our results indicate that Dmax should be confined to ≤ 57 Gy to minimize anemia and that V10 should be restricted to ≤ 87% to reduce incidence of all HT.
authors.affiliation: a Department of Radiation Oncology , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Diana A R
authors.initials: DA
authors.lastname: Julie
authors.affiliation: b Department of Medical Physics , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Oh
authors.affiliation: b Department of Medical Physics , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Aditya P
authors.initials: AP
authors.lastname: Apte
authors.affiliation: b Department of Medical Physics , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
authors.affiliation: a Department of Radiation Oncology , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Ashlyn
authors.initials: A
authors.lastname: Tom
authors.affiliation: a Department of Radiation Oncology , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Wu
authors.affiliation: a Department of Radiation Oncology , Memorial Sloan-Kettering Cancer Center , New York, New York , USA.
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Goodman
mesh_terms: D000740:Anemia / Q000139:chemically induced / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D019540:Area Under Curve; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000209:etiology; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil