Trial reportCancer reports (Hoboken, N.J.)2026
Association of HRD Score With Efficacy of Neoadjuvant Short-Course Radiotherapy Plus Sequential Chemoimmunotherapy in pMMR Locally Advanced Rectal Cancer.
Trial report in Cancer reports (Hoboken, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05515796 (Clinical Application of Efficacy Prediction Model Based on Epigenetics Multi-omics Sequencing in Neoadjuvant Immunotherapy of Gastrointestinal Tumors), which is not on this map. Not yet cited in PubMed.
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The trial behind it
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Clinical Application of Efficacy Prediction Model Based on Epigenetics Multi-omics Sequencing in Neoadjuvant Immunotherapy of Gastrointestinal Tumors
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16 authors.
Funding
Abstract
backgroundHomologous recombination deficiency (HRD) has been reported to be associated with increased sensitivity to platinum-based treatment and radiotherapy in some solid tumors.
aimThis study investigated the correlation between HRD score and treatment response to neoadjuvant short-course radiotherapy combined with sequential chemotherapy and tislelizumab in mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC). METHODS AND
resultsThirty-two pMMR LARC patients from clinical trial NCT05515796 were enrolled. Pretreatment biopsy samples were analyzed for HRD scores and tumor immune microenvironment (TIME) gene expression profiles. Using receiver operating characteristic (ROC) analysis, patients were stratified into low (0-8), intermediate (9-37), and high (> 37) HRD score groups to compare pathological complete response (pCR) rates. Abundance of immune cells and immune-related pathways were assessed with MCPcounter and single sample gene set enrichment analysis (ssGSEA) respectively and compared among the three HRD score groups. The entire cohort demonstrated pCR rate of 40.62% (13/32) with a median HRD score of 9 (range: 0-70). ROC analysis showed that HRD score as a continuous variable did not reach statistical significance in distinguishing pCR patients from non-pCR patients, nor did TMB and HR mutation. However, the proportion of categorized HRD score was significantly different between pCR and non-pCR groups (low, intermediate, high HRD score: 61.54%, 23.08%, 15.38% vs. 31.58%, 68.42%, 0%, p = 0.017). High-HRD tumors exhibited the highest CD8+ T-cell abundance followed by low-HRD and intermediate-HRD groups.
conclusionHRD score may be associated with efficacy of neoadjuvant radioimmunotherapy in pMMR LARC patients, potentially mediated through enhanced CD8+ T-cell recruitment. These findings support precision patient selection, though mechanistic validation is required.
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