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Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer

BACKGROUND: Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer. MET...

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Autores principales: Nilsson, Martin P., Johnsson, Anders, Scherman, Jonas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365937/
https://www.ncbi.nlm.nih.gov/pubmed/34399812
http://dx.doi.org/10.1186/s13014-021-01876-5
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author Nilsson, Martin P.
Johnsson, Anders
Scherman, Jonas
author_facet Nilsson, Martin P.
Johnsson, Anders
Scherman, Jonas
author_sort Nilsson, Martin P.
collection PubMed
description BACKGROUND: Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer. METHODS: Consecutive patients with locally advanced (T2 ≥ 4 cm—T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann–Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS). RESULTS: WBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia. CONCLUSIONS: Sarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose–response relationships. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01876-5.
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spelling pubmed-83659372021-08-17 Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer Nilsson, Martin P. Johnsson, Anders Scherman, Jonas Radiat Oncol Research BACKGROUND: Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer. METHODS: Consecutive patients with locally advanced (T2 ≥ 4 cm—T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann–Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS). RESULTS: WBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia. CONCLUSIONS: Sarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose–response relationships. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01876-5. BioMed Central 2021-08-16 /pmc/articles/PMC8365937/ /pubmed/34399812 http://dx.doi.org/10.1186/s13014-021-01876-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Nilsson, Martin P.
Johnsson, Anders
Scherman, Jonas
Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
title Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
title_full Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
title_fullStr Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
title_full_unstemmed Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
title_short Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
title_sort sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365937/
https://www.ncbi.nlm.nih.gov/pubmed/34399812
http://dx.doi.org/10.1186/s13014-021-01876-5
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