Domingo, E. et al. (2024) Prognostic and predictive value of Immunoscore in stage III colorectal cancer: pooled analysis of 2,608 cases from the SCOT and IDEA-HORG studies. Journal of Clinical Oncology, (doi: 10.1200/JCO.23.01648) (PMID:38484206) (Early Online Publication)
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Abstract
Purpose Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 v 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials. Methods Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing. Predefined cutoffs (IS-Low and IS-High) were used to classify cases into two groups for analysis of disease-free survival (3-year DFS) and multivariable-adjusted hazard ratios (mvHRs) by Cox regression. Results IS was determined in 2,608 (99.5%) eligible cases, with 877 (33.7%) samples classified as IS-Low. IS-Low tumors were more commonly high-risk (T4 and/or N2; 52.9% IS-Low v 42.2% IS-High; P < .001) and in younger patients (P = .024). Patients with IS-Low tumors had significantly shorter DFS in the CAPOX, FOLFOX, and combined cohorts (mvHR, 1.52 [95% CI, 1.28 to 1.82]; mvHR, 1.58 [95% CI, 1.22 to 2.04]; and mvHR, 1.55 [95% CI, 1.34 to 1.79], respectively; P < .001 all comparisons), regardless of sex, BMI, clinical risk group, tumor location, treatment duration, or chemotherapy regimen. IS prognostic value was greater in younger (≤65 years) than older (>65 years) patients in the CAPOX cohort (mvHR, 1.92 [95% CI, 1.50 to 2.46] v 1.28 [95% CI, 1.01 to 1.63], PINTERACTION = .026), and in DNA mismatch repair proficient than deficient mismatch repair disease (mvHR, 1.68 [95% CI, 1.41 to 2.00] v 0.67 [95% CI, 0.30 to 1.49], PINTERACTION = .03), although these exploratory analyses were uncorrected for multiple testing. Adding IS to a model containing all clinical variables significantly improved prediction of DFS (likelihood ratio test, P < .001) regardless of MMR status. Conclusion IS is prognostic in stage III CRC treated with FOLFOX or CAPOX, including within clinically relevant tumor subgroups. Possible variation in IS prognostic value by age and MMR status, and prediction of benefit from extended adjuvant therapy merit validation.
| Item Type: | Articles |
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| Additional Information: | Supported by the Medical Research Council (transferred to NETSCC— Efficacy and Mechanism Evaluation; Grant Ref: G0601705), NIHR Health Technology Assessment (Grant Ref: 14/140/84), Cancer Research UK Core CTU Glasgow Funding (Funding Ref: C6716/A9894), Cancer Research UK funding to the Cancer Research UK Glasgow Centre (Grant Ref: A25142) and the Swedish Cancer Society. The TransSCOT sample collection was funded by a Cancer Research UK Clinical Trials Awards and Advisory Committee—Sample Collection (Grant Ref: C6716/A13941). The IDEA-HORG trial was funded by the HORG foundation. This biomarker study was funded by an award to the TransSCOT and HORG consortia from HalioDx/Veracyte, the Oxford NIHR Comprehensive Biomedical Research Centre (BRC) and CRUK award A25142 to the CRUK Glasgow Centre. VHK acknowledges funding by the Promedica Foundation (F-87701-41-01). DNC is funded by a Cancer Research UK (CRUK) Advanced Clinician Scientist Fellowship (C26642/A27963). |
| Status: | Early Online Publication |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Edwards, Professor Joanne and Easton, Dr Alistair and Kelly, Mrs Caroline and Domingo, Dr Enric and Sansom, Professor Owen and Harkin, Mrs Andrea and Hay, Miss Jennifer |
| Authors: | Domingo, E., Kelly, C., Hay, J., Sansom, O., Maka, N., Oien, K., Iveson, T., Saunders, M., Kerr, R., Tomlinson, I., Edwards, J., Harkin, A., Nowak, M., Koelzer, V., Easton, A., Boukovinas, I., Moustou, E., Messaritakis, I., Chondrozoumaki, M., Karagianni, M., Pagès, F., Arnoux, F., Lautard, C., Lovera, Y., Boquet, I., Catteau, A., Galon, J., TransSCOT Consortium, , Souglakos, I., and Church, D. N. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Clinical Oncology |
| Publisher: | American Society of Clinical Oncology |
| ISSN: | 0732-183X |
| ISSN (Online): | 1527-7755 |
| Published Online: | 14 March 2024 |
| Copyright Holders: | Copyright: © 2024 American Society of Clinical Oncology |
| First Published: | First published in Journal of Clinical Oncology 2024 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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