title: Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors.
abstract: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity.
  
  
  
  Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs.
  
  
  
  Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1).
  
  
  
  Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total "marrow reserve" can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Lee
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Golden
authors.affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, Ohio.
authors.forename: Jose G
authors.initials: JG
authors.lastname: Bazan
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kopec
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Pelizzari
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Sonya
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Chang
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois. Electronic address: sliauw@radonc.uchicago.edu.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Liauw
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001005:Anus Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D001853:Bone Marrow / Q000528:radiation effects*; D000069287:Capecitabine / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007085:Ilium / Q000000981:diagnostic imaging / Q000528:radiation effects; D007970:Leukopenia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009503:Neutropenia / Q000209:etiology; D010384:Pelvic Bones / Q000000981:diagnostic imaging / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000209:etiology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D000069287:Capecitabine; D005472:Fluorouracil