title: Irradiation of FDG-PET-Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation.
abstract: OBJECTIVE
  Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT.
  
  
  METHODS
  The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM50 and IBM50, respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC.
  
  
  RESULTS
  Mean ± SD ANC nadir was 0.77 × 10(9)/L (±0.66 × 10(9)/L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM50 and IBM50 were all significantly associated with ANC nadir. However, model performance for ABM50 was not superior to that of the TBM and IBM50 models.
  
  
  CONCLUSIONS
  Irradiation of pelvic BM was associated with HT. However, FDG-PET-defined ABM models failed to improve model performance compared to the TBM model.
authors.affiliation: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: bsrose@lroc.harvard.edu.
authors.forename: Brent S
authors.initials: BS
authors.lastname: Rose
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Kyung-Wook
authors.initials: KW
authors.lastname: Jee
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Niemierko
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Murphy
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Blaszkowsky
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jill N
authors.initials: JN
authors.lastname: Allen
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Lee
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Yingbing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Drapek
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Hong
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Wo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000473:pathology / Q000628:therapy*; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000528:radiation effects*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009503:Neutropenia / Q000209:etiology; D010384:Pelvic Bones / Q000000981:diagnostic imaging / Q000528:radiation effects*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D016685:Mitomycin; D005472:Fluorouracil