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Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm

Approximately one-third of all newly diagnosed colorectal cancer (CRC) is composed of rectal cancer, with the incidence rising in younger patients. The principal neoadjuvant treatments consist of neoadjuvant short-course radiotherapy and long-course chemoradiation. Locally advanced rectal cancer (LA...

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Autores principales: Ryan, Éanna J., Creavin, Ben, Sheahan, Kieran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456909/
https://www.ncbi.nlm.nih.gov/pubmed/32923389
http://dx.doi.org/10.3389/fonc.2020.01369
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author Ryan, Éanna J.
Creavin, Ben
Sheahan, Kieran
author_facet Ryan, Éanna J.
Creavin, Ben
Sheahan, Kieran
author_sort Ryan, Éanna J.
collection PubMed
description Approximately one-third of all newly diagnosed colorectal cancer (CRC) is composed of rectal cancer, with the incidence rising in younger patients. The principal neoadjuvant treatments consist of neoadjuvant short-course radiotherapy and long-course chemoradiation. Locally advanced rectal cancer (LARC) is particularly challenging to manage given the anatomical constrictions of the pelvis and the risk for local recurrence. In appropriately treated patients, 5- and 10-year overall survival is estimated at 60 and 50%, respectively. The prognosis for LARC has improved in recent years with more access to screening, advances in surgical techniques, and perioperative care. Furthermore, the refinement of the multidisciplinary team with combined-modality management strategies has improved outcomes. These advancements have been augmented by significant improvements in the understanding of the underlying tumor biology. However, there are many instances where patient outcomes do not match those for their tumor stage and accurate prognostic information for individual patients can be difficult to estimate owing to the heterogeneous nature of LARC. Many new combinations of chemotherapy with radiotherapy, including total neoadjuvant therapy with targeted therapies that aim to diminish toxicity and increase survival, are being evaluated in clinical trials. Despite these advances, local recurrence and distant metastasis remain an issue, with one-third of LARC patients dying within 5 years of initial treatment. Although much of the new pathological, molecular genetics, and immunological biomarkers allow refinement in the classification and prognostication of CRC, the relative importance of each of these factors with regards to the development and progression of LARC remains incompletely understood. These factors are often insufficiently validated and seldom consider the individual characteristics of the host, the tumor and its location, the local available expertise, or the probable location of recurrence. Appreciating the mechanisms behind these differences will allow for a more comprehensive, personalized approach and more informed treatment options, leading to ultimately superior outcomes. This review aims to first outline the current multidisciplinary context in which LARC care should be delivered and then discuss how some key prognosticators, including novel histopathological, molecular genetics, and immunological biomarkers, might fit into the wider context of personalized LARC management in the coming years.
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spelling pubmed-74569092020-09-11 Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm Ryan, Éanna J. Creavin, Ben Sheahan, Kieran Front Oncol Oncology Approximately one-third of all newly diagnosed colorectal cancer (CRC) is composed of rectal cancer, with the incidence rising in younger patients. The principal neoadjuvant treatments consist of neoadjuvant short-course radiotherapy and long-course chemoradiation. Locally advanced rectal cancer (LARC) is particularly challenging to manage given the anatomical constrictions of the pelvis and the risk for local recurrence. In appropriately treated patients, 5- and 10-year overall survival is estimated at 60 and 50%, respectively. The prognosis for LARC has improved in recent years with more access to screening, advances in surgical techniques, and perioperative care. Furthermore, the refinement of the multidisciplinary team with combined-modality management strategies has improved outcomes. These advancements have been augmented by significant improvements in the understanding of the underlying tumor biology. However, there are many instances where patient outcomes do not match those for their tumor stage and accurate prognostic information for individual patients can be difficult to estimate owing to the heterogeneous nature of LARC. Many new combinations of chemotherapy with radiotherapy, including total neoadjuvant therapy with targeted therapies that aim to diminish toxicity and increase survival, are being evaluated in clinical trials. Despite these advances, local recurrence and distant metastasis remain an issue, with one-third of LARC patients dying within 5 years of initial treatment. Although much of the new pathological, molecular genetics, and immunological biomarkers allow refinement in the classification and prognostication of CRC, the relative importance of each of these factors with regards to the development and progression of LARC remains incompletely understood. These factors are often insufficiently validated and seldom consider the individual characteristics of the host, the tumor and its location, the local available expertise, or the probable location of recurrence. Appreciating the mechanisms behind these differences will allow for a more comprehensive, personalized approach and more informed treatment options, leading to ultimately superior outcomes. This review aims to first outline the current multidisciplinary context in which LARC care should be delivered and then discuss how some key prognosticators, including novel histopathological, molecular genetics, and immunological biomarkers, might fit into the wider context of personalized LARC management in the coming years. Frontiers Media S.A. 2020-08-14 /pmc/articles/PMC7456909/ /pubmed/32923389 http://dx.doi.org/10.3389/fonc.2020.01369 Text en Copyright © 2020 Ryan, Creavin and Sheahan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Ryan, Éanna J.
Creavin, Ben
Sheahan, Kieran
Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm
title Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm
title_full Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm
title_fullStr Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm
title_full_unstemmed Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm
title_short Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm
title_sort delivery of personalized care for locally advanced rectal cancer: incorporating pathological, molecular genetic, and immunological biomarkers into the multimodal paradigm
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456909/
https://www.ncbi.nlm.nih.gov/pubmed/32923389
http://dx.doi.org/10.3389/fonc.2020.01369
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