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Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure
BACKGROUND: For locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Baishideng Publishing Group Inc
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896420/ https://www.ncbi.nlm.nih.gov/pubmed/33643528 http://dx.doi.org/10.4251/wjgo.v13.i2.119 |
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author | Tuta, Mojca Boc, Nina Brecelj, Erik Peternel, Monika Velenik, Vaneja |
author_facet | Tuta, Mojca Boc, Nina Brecelj, Erik Peternel, Monika Velenik, Vaneja |
author_sort | Tuta, Mojca |
collection | PubMed |
description | BACKGROUND: For locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery. AIM: To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure. METHODS: In a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis. RESULTS: Compared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05). CONCLUSION: Compared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score. |
format | Online Article Text |
id | pubmed-7896420 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-78964202021-02-25 Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure Tuta, Mojca Boc, Nina Brecelj, Erik Peternel, Monika Velenik, Vaneja World J Gastrointest Oncol Clinical and Translational Research BACKGROUND: For locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery. AIM: To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure. METHODS: In a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis. RESULTS: Compared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05). CONCLUSION: Compared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score. Baishideng Publishing Group Inc 2021-02-15 2021-02-15 /pmc/articles/PMC7896420/ /pubmed/33643528 http://dx.doi.org/10.4251/wjgo.v13.i2.119 Text en ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/ |
spellingShingle | Clinical and Translational Research Tuta, Mojca Boc, Nina Brecelj, Erik Peternel, Monika Velenik, Vaneja Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
title | Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
title_full | Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
title_fullStr | Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
title_full_unstemmed | Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
title_short | Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
title_sort | total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure |
topic | Clinical and Translational Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896420/ https://www.ncbi.nlm.nih.gov/pubmed/33643528 http://dx.doi.org/10.4251/wjgo.v13.i2.119 |
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