Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors

Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):306-312. doi: 10.1016/j.ijrobp.2016.10.010. Epub 2016 Oct 19.


Purpose: 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.

Methods and materials: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Multicenter Study

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Anus Neoplasms / blood
  • Anus Neoplasms / pathology
  • Anus Neoplasms / therapy*
  • Bone Marrow / radiation effects*
  • Capecitabine / administration & dosage
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy / adverse effects*
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Ilium / diagnostic imaging
  • Ilium / radiation effects
  • Leukopenia / etiology*
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Neutropenia / etiology
  • Pelvic Bones / diagnostic imaging
  • Pelvic Bones / radiation effects*
  • Radiotherapy Dosage
  • Radiotherapy, Conformal / adverse effects
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Retrospective Studies
  • Thrombocytopenia / etiology*
  • Time Factors


  • Antineoplastic Agents
  • Mitomycin
  • Capecitabine
  • Fluorouracil