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

Abstract

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% vsmore » 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.« less

Authors:
;  [1];  [2]; ;  [1]; ;  [3]
  1. Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States)
  2. Department of Radiation Oncology, The Ohio State University, Columbus, Ohio (United States)
  3. Department of Radiation Oncology, Stanford University, Stanford, California (United States)
Publication Date:
OSTI Identifier:
22645768
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 97; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BLOOD COUNT; BONE MARROW; CHEMOTHERAPY; FLUORINE COMPOUNDS; GY RANGE 10-100; METRICS; MULTIVARIATE ANALYSIS; NEOPLASMS; NEUTROPHILS; PATIENTS; RADIATION DOSES; RADIATION HAZARDS; RADIOTHERAPY; TOXICITY

Citation Formats

Lee, Andrew Y., Golden, Daniel W., Bazan, Jose G., Kopec, Malgorzata, Pelizzari, Charles A., Aggarwal, Sonya, Chang, Daniel T., and Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu. Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors. United States: N. p., 2017. Web. doi:10.1016/J.IJROBP.2016.10.010.
Lee, Andrew Y., Golden, Daniel W., Bazan, Jose G., Kopec, Malgorzata, Pelizzari, Charles A., Aggarwal, Sonya, Chang, Daniel T., & Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu. Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors. United States. doi:10.1016/J.IJROBP.2016.10.010.
Lee, Andrew Y., Golden, Daniel W., Bazan, Jose G., Kopec, Malgorzata, Pelizzari, Charles A., Aggarwal, Sonya, Chang, Daniel T., and Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu. Wed . "Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors". United States. doi:10.1016/J.IJROBP.2016.10.010.
@article{osti_22645768,
title = {Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors},
author = {Lee, Andrew Y. and Golden, Daniel W. and Bazan, Jose G. and Kopec, Malgorzata and Pelizzari, Charles A. and Aggarwal, Sonya and Chang, Daniel T. and Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu},
abstractNote = {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.},
doi = {10.1016/J.IJROBP.2016.10.010},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 97,
place = {United States},
year = {2017},
month = {2}
}