dc.contributor
Institut Català de la Salut
dc.contributor
[Hammarström K, Nunes L, Mathot L, Lundin E] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. [Mezheyeuski A] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Korsavidou Hult N] Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Hammarström, Klara
dc.contributor.author
Nunes, Luis
dc.contributor.author
Mathot, Lucy
dc.contributor.author
Lundin, Emma
dc.contributor.author
Korsavidou Hult, Nafsika Dimitra
dc.contributor.author
Mezheyeuski, Artur
dc.date.accessioned
2025-10-25T05:39:22Z
dc.date.available
2025-10-25T05:39:22Z
dc.date.issued
2024-05-22T07:21:27Z
dc.date.issued
2024-05-22T07:21:27Z
dc.date.issued
2024-07-01
dc.identifier
Hammarström K, Nunes L, Mathot L, Mezheyeuski A, Lundin E, Korsavidou Hult N, et al. Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer. Int J Cancer. 2024 Jul 1;155(1):40–53.
dc.identifier
https://hdl.handle.net/11351/11484
dc.identifier
10.1002/ijc.34880
dc.identifier
001166000400001
dc.identifier.uri
http://hdl.handle.net/11351/11484
dc.description.abstract
Neoadjuvant therapy; Prognosis; Rectal cancer
dc.description.abstract
Teràpia neoadjuvant; Pronòstic; Càncer de recte
dc.description.abstract
Terapia neoadyuvante; Pronóstico; Cáncer de recto
dc.description.abstract
Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.
dc.description.abstract
This study was supported by The Swedish Cancer Society, grant number 190382PJ01H.
dc.format
application/pdf
dc.relation
International Journal of Cancer;155(1)
dc.relation
https://doi.org/10.1002/ijc.34880
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Recte - Càncer - Recaiguda
dc.subject
Recte - Càncer - Quimioteràpia
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Recte - Càncer - Radioteràpia
dc.subject
Anomalies cromosòmiques
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal Neoplasms
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy
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DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales::neoplasias del recto
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TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante
dc.subject
ENFERMEDADES::neoplasias::procesos neoplásicos::recurrencia neoplásica local
dc.title
Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
