Sistema de Salut de Catalunya
Institut Català de la Salut
[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
Vall d'Hebron Barcelona Hospital Campus
2024-05-22T07:21:27Z
2024-05-22T07:21:27Z
2024-07-01
Neoadjuvant therapy; Prognosis; Rectal cancer
Teràpia neoadjuvant; Pronòstic; Càncer de recte
Terapia neoadyuvante; Pronóstico; Cáncer de recto
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.
This study was supported by The Swedish Cancer Society, grant number 190382PJ01H.
Article
Published version
English
Recte - Càncer - Recaiguda; Recte - Càncer - Quimioteràpia; Recte - Càncer - Radioteràpia; Anomalies cromosòmiques; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal Neoplasms; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy; DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales::neoplasias del recto; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante; ENFERMEDADES::neoplasias::procesos neoplásicos::recurrencia neoplásica local
Wiley
International Journal of Cancer;155(1)
https://doi.org/10.1002/ijc.34880
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
