دورية أكاديمية
Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures.
| العنوان: | Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures. |
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| المؤلفون: | Mahmood U; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom., Blake A; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom., Rathee S; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom., Samuel L; School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom., Murray G; School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom., Sebag-Montefiore D; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Gollins S; North Wales Cancer Treatment Centre, Besti Cadwaladr University Health Board, Bodelwyddan, United Kingdom.; Lingen Davies Cancer Centre, Shrewsbury and Telford Hospital NHS Trust, Shrewsbury, United Kingdom., West NP; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Begum R; Cancer Research & University College London Clinical Trial Unit, London, United Kingdom., Bach SP; Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, United Kingdom., Richman SD; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Quirke P; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Redmond KL; The Patrick G Johnston Centre for Cancer Research, Queens University Belfast, Belfast, United Kingdom., Salto-Tellez M; The Patrick G Johnston Centre for Cancer Research, Queens University Belfast, Belfast, United Kingdom., Koelzer VH; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Department of Oncology and Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Leedham SJ; Wellcome Trust Centre for Human genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Tomlinson I; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom., Dunne PD; The Patrick G Johnston Centre for Cancer Research, Queens University Belfast, Belfast, United Kingdom., Buffa FM; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom.; Department of Computing Sciences, Bocconi University, and Bocconi Institute for Data Science and Analytics (BIDSA), Milano, Italy., Maughan TS; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom.; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom., Domingo E; Department of Oncology, Medical Science Division, University of Oxford, Oxford, United Kingdom.; Cancer Research UK Scotland Centre, Edinburgh, United Kingdom. |
| مؤلفون مشاركون: | S:CORT consortium |
| المصدر: | Cancer research communications [Cancer Res Commun] 2024 Jul 01; Vol. 4 (7), pp. 1765-1776. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]- |
| مواضيع طبية MeSH: | Rectal Neoplasms*/pathology , Rectal Neoplasms*/genetics , Rectal Neoplasms*/therapy , Rectal Neoplasms*/radiotherapy , Rectal Neoplasms*/mortality , Neoadjuvant Therapy* , Transcriptome*, Humans ; Male ; Female ; Middle Aged ; Aged ; Capecitabine/therapeutic use ; Capecitabine/administration & dosage ; Fluorouracil/therapeutic use ; Fluorouracil/administration & dosage ; Fluorouracil/pharmacology ; Gene Expression Profiling ; Oxaliplatin/therapeutic use ; Oxaliplatin/administration & dosage ; Oxaliplatin/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Gene Expression Regulation, Neoplastic/drug effects |
| مستخلص: | Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826). Exploratory analyses were done with transcriptomic signatures for the endpoint of pathologic complete response (pCR), considering treatment regimen or CMS subtype. Relevant findings were tested for overall survival and recurrence-free survival. Immune and stromal signatures were strongly associated with pCR and lack of pCR, respectively, in RT and capecitabine (Cap)/5-fluorouracil (5FU)-treated patients (N = 387), in which the radiosensitivity signature (RSS) showed the strongest association. Upon addition of oxaliplatin (Ox; N = 123), stromal signatures switched direction and showed higher chances to achieve pCR than without Ox (p for interaction 0.02). Among Cap/5FU patients, most signatures performed similarly across CMS subtypes, except cytotoxic lymphocytes that were associated with pCR in CMS1 and CMS4 cases compared with other CMS subtypes (p for interaction 0.04). The only variables associated with survival were pCR and RSS. Although the frequency of pCR across different chemoradiation regimens is relatively similar, our data suggest that response rates may differ depending on the biological landscape of rectal cancer. Response to neoadjuvant RT in stroma-rich tumors may potentially be improved by the addition of Ox. RSS in preoperative biopsies provides predictive information for response specifically to neoadjuvant RT with 5FU. Significance: Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer. (©2024 The Authors; Published by the American Association for Cancer Research.) |
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| المشرفين على المادة: | 6804DJ8Z9U (Capecitabine) U3P01618RT (Fluorouracil) 04ZR38536J (Oxaliplatin) |
| تواريخ الأحداث: | Date Created: 20240718 Date Completed: 20240718 Latest Revision: 20240720 |
| رمز التحديث: | 20240720 |
| مُعرف محوري في PubMed: | PMC11257085 |
| DOI: | 10.1158/2767-9764.CRC-23-0502 |
| PMID: | 39023969 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2767-9764 |
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| DOI: | 10.1158/2767-9764.CRC-23-0502 |