Cellular bases of hypofractionated radiotherapy protocols for lung cancer
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Anais da Academia Brasileira de Ciências (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652022000600601 |
Resumo: | Abstract The extreme demand on health systems due to the COVID-19 pandemic has led to reconsider hypofractionation. Although the best clinical efficacy of these schemes is being demonstrated, the biological bases have not been established. Thus, after validating basic clinical parameters, through complementary in vitro models, we characterized the cellular and molecular mechanisms of hypofractionation protocols. Cell cultures of human lung cancer cell line A549 were irradiated with 0, 2, 4, 8, 12, 16 and 20 Gy. The clastogenic, cytotoxic, proliferative and clonogenic capacities and bystander effect were evaluated. In addition, we assessed survival and toxicity in a retrospective study of 49 patients with lung cancer. Our findings showed that the greater efficacy of ablative regimens should not only be attributed to events of direct cell death induced by genotoxic damage, but also to a lower cell repopulation and the indirect action of clastogenic factors secreted. These treatments were optimal in terms of 1- and 2-year overall survival (74 and 65%, respectively), and progression-free survival at 1 and 2 years (71 and 61%, respectively). The greater efficacy of high doses per fraction could be attributed to a multifactorial mechanism that goes beyond the 4Rs of conventional radiotherapy. |
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Cellular bases of hypofractionated radiotherapy protocols for lung cancerradiotherapy dose hypofractionation4RsLinear-Quadratic Modelcytotoxic effectstereotactic body radiotherapyAbstract The extreme demand on health systems due to the COVID-19 pandemic has led to reconsider hypofractionation. Although the best clinical efficacy of these schemes is being demonstrated, the biological bases have not been established. Thus, after validating basic clinical parameters, through complementary in vitro models, we characterized the cellular and molecular mechanisms of hypofractionation protocols. Cell cultures of human lung cancer cell line A549 were irradiated with 0, 2, 4, 8, 12, 16 and 20 Gy. The clastogenic, cytotoxic, proliferative and clonogenic capacities and bystander effect were evaluated. In addition, we assessed survival and toxicity in a retrospective study of 49 patients with lung cancer. Our findings showed that the greater efficacy of ablative regimens should not only be attributed to events of direct cell death induced by genotoxic damage, but also to a lower cell repopulation and the indirect action of clastogenic factors secreted. These treatments were optimal in terms of 1- and 2-year overall survival (74 and 65%, respectively), and progression-free survival at 1 and 2 years (71 and 61%, respectively). The greater efficacy of high doses per fraction could be attributed to a multifactorial mechanism that goes beyond the 4Rs of conventional radiotherapy.Academia Brasileira de Ciências2022-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652022000600601Anais da Academia Brasileira de Ciências v.94 n.4 2022reponame:Anais da Academia Brasileira de Ciências (Online)instname:Academia Brasileira de Ciências (ABC)instacron:ABC10.1590/0001-3765202220210056info:eu-repo/semantics/openAccessOCOLOTOBICHE,ELIANA EVELINABANEGAS,YULIANA CATALINAFERRARIS,GUSTAVOMARTÍNEZ,MARCELOGÜERCI,ALBA MABELeng2022-07-19T00:00:00Zoai:scielo:S0001-37652022000600601Revistahttp://www.scielo.br/aabchttps://old.scielo.br/oai/scielo-oai.php||aabc@abc.org.br1678-26900001-3765opendoar:2022-07-19T00:00Anais da Academia Brasileira de Ciências (Online) - Academia Brasileira de Ciências (ABC)false |
dc.title.none.fl_str_mv |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
title |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
spellingShingle |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer OCOLOTOBICHE,ELIANA EVELINA radiotherapy dose hypofractionation 4Rs Linear-Quadratic Model cytotoxic effect stereotactic body radiotherapy |
title_short |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
title_full |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
title_fullStr |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
title_full_unstemmed |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
title_sort |
Cellular bases of hypofractionated radiotherapy protocols for lung cancer |
author |
OCOLOTOBICHE,ELIANA EVELINA |
author_facet |
OCOLOTOBICHE,ELIANA EVELINA BANEGAS,YULIANA CATALINA FERRARIS,GUSTAVO MARTÍNEZ,MARCELO GÜERCI,ALBA MABEL |
author_role |
author |
author2 |
BANEGAS,YULIANA CATALINA FERRARIS,GUSTAVO MARTÍNEZ,MARCELO GÜERCI,ALBA MABEL |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
OCOLOTOBICHE,ELIANA EVELINA BANEGAS,YULIANA CATALINA FERRARIS,GUSTAVO MARTÍNEZ,MARCELO GÜERCI,ALBA MABEL |
dc.subject.por.fl_str_mv |
radiotherapy dose hypofractionation 4Rs Linear-Quadratic Model cytotoxic effect stereotactic body radiotherapy |
topic |
radiotherapy dose hypofractionation 4Rs Linear-Quadratic Model cytotoxic effect stereotactic body radiotherapy |
description |
Abstract The extreme demand on health systems due to the COVID-19 pandemic has led to reconsider hypofractionation. Although the best clinical efficacy of these schemes is being demonstrated, the biological bases have not been established. Thus, after validating basic clinical parameters, through complementary in vitro models, we characterized the cellular and molecular mechanisms of hypofractionation protocols. Cell cultures of human lung cancer cell line A549 were irradiated with 0, 2, 4, 8, 12, 16 and 20 Gy. The clastogenic, cytotoxic, proliferative and clonogenic capacities and bystander effect were evaluated. In addition, we assessed survival and toxicity in a retrospective study of 49 patients with lung cancer. Our findings showed that the greater efficacy of ablative regimens should not only be attributed to events of direct cell death induced by genotoxic damage, but also to a lower cell repopulation and the indirect action of clastogenic factors secreted. These treatments were optimal in terms of 1- and 2-year overall survival (74 and 65%, respectively), and progression-free survival at 1 and 2 years (71 and 61%, respectively). The greater efficacy of high doses per fraction could be attributed to a multifactorial mechanism that goes beyond the 4Rs of conventional radiotherapy. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652022000600601 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0001-37652022000600601 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/0001-3765202220210056 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Academia Brasileira de Ciências |
publisher.none.fl_str_mv |
Academia Brasileira de Ciências |
dc.source.none.fl_str_mv |
Anais da Academia Brasileira de Ciências v.94 n.4 2022 reponame:Anais da Academia Brasileira de Ciências (Online) instname:Academia Brasileira de Ciências (ABC) instacron:ABC |
instname_str |
Academia Brasileira de Ciências (ABC) |
instacron_str |
ABC |
institution |
ABC |
reponame_str |
Anais da Academia Brasileira de Ciências (Online) |
collection |
Anais da Academia Brasileira de Ciências (Online) |
repository.name.fl_str_mv |
Anais da Academia Brasileira de Ciências (Online) - Academia Brasileira de Ciências (ABC) |
repository.mail.fl_str_mv |
||aabc@abc.org.br |
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1754302872468586496 |