Academic Journal
Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer
| Τίτλος: | Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer |
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| Συγγραφείς: | Klara Hammarström, Luís Nunes, Lucy Mathot, Artur Mezheyeuski, Emma Lundin, Nafsika Korsavidou Hult, Israa Imam, Emerik Osterlund, Tobias Sjöblom, Bengt Glimelius |
| Συνεισφορές: | 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 |
| Πηγή: | Scientia Scientia. Dipòsit d'Informació Digital del Departament de Salut instname |
| Στοιχεία εκδότη: | Wiley, 2024. |
| Έτος έκδοσης: | 2024 |
| Θεματικοί όροι: | Male, Adult, 0301 basic medicine, complete remission, Nerve Tissue Proteins, chemoradiotherapy, Recte - Càncer - Quimioteràpia, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales::neoplasias del recto, 0302 clinical medicine, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante, Biomarkers, Tumor, Humans, Rectal cancer, targeted sequencing, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimiorradioterapia, radiotherapy, Aged, Smad4 Protein, Aged, 80 and over, Cancer och onkologi, FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemoradiotherapy, Rectal Neoplasms, DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms::Rectal Neoplasms, Nuclear Proteins, Chemoradiotherapy, Middle Aged, Recte - Càncer - Radioteràpia, Neoadjuvant Therapy, Cytoskeletal Proteins, Anomalies cromosòmiques, Treatment Outcome, Cancer and Oncology, PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation, ENFERMEDADES::neoplasias::procesos neoplásicos::recurrencia neoplásica local, Mutation, response pre-diction, Recte - Càncer - Recaiguda, Female, prognosis, Neoplasm Recurrence, Local |
| Περιγραφή: | 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. |
| Τύπος εγγράφου: | Article |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | English |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.34880 |
| Σύνδεσμος πρόσβασης: | https://pubmed.ncbi.nlm.nih.gov/38376070 https://hdl.handle.net/11351/11484 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-493842 https://publications.scilifelab.se/publication/60d83cc8c444462f8cfce90048ed5781 |
| Rights: | CC BY |
| Αριθμός Καταχώρησης: | edsair.doi.dedup.....c7d2f1d6ee6750118f1acf5b47468080 |
| Βάση Δεδομένων: | OpenAIRE |
| ISSN: | 10970215 00207136 |
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| DOI: | 10.1002/ijc.34880 |