Evaluation of CD3 and CD8 T-Cell Immunohistochemistry for Prognostication and Prediction of Benefit From Adjuvant Chemotherapy in Early-Stage Colorectal Cancer Within the QUASAR Trial.

Autor:	Williams CJM; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., Gray R; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.; Deceased., Hills RK; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom., Shires M; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Zhang L; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Zhao Z; Roche Diagnostics Solutions, Imaging and Algorithms, Digital Pathology, Santa Clara, CA., Gardner T; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Sapanara N; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Xu XM; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Bai I; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Yan D; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Muranyi A; Roche Diagnostics Solutions, Research and Development, Oro Valley, AZ., Dance S; Roche Diagnostics Limited, Medical Affairs, Burgess Hill, West Sussex, United Kingdom., Aghaei F; Roche Diagnostics Solutions, Imaging and Algorithms, Digital Pathology, Santa Clara, CA., Hemmings G; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Hale M; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Kurkure U; Roche Diagnostics Solutions, Imaging and Algorithms, Digital Pathology, Santa Clara, CA., Guetter C; Roche Diagnostics Solutions, Imaging and Algorithms, Digital Pathology, Santa Clara, CA., Richman SD; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Hutchins G; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Seligmann JF; Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom., West NP; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom., Singh S; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Shanmugam K; Roche Diagnostics Solutions, Clinical Development and Medical Affairs, Oro Valley, AZ., Quirke P; Division of Pathology and Data Analytics, University of Leeds, Leeds, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Oct 10; Vol. 42 (29), pp. 3430-3442. Date of Electronic Publication: 2024 Jul 31.
DOI:	10.1200/JCO.23.02030
Abstrakt:	Purpose: High densities of tumor infiltrating CD3 and CD8 T-cells are associated with superior prognosis in colorectal cancer (CRC). Their value as predictors of benefit from adjuvant chemotherapy is uncertain. Patients and Methods: Tumor tissue from 868 patients in the QUASAR trial (adjuvant fluorouracil/folinic acid v observation in stage II/III CRC) was analyzed by CD3 and CD8 immunohistochemistry. Pathologists, assisted by artificial intelligence, calculated CD3 and CD8 cell densities (cells/mm 2 ) in the core tumor (CT) and invasive margin (IM). Participants were randomly partitioned into training and validation sets. The primary outcome was recurrence-free interval (RFI), 2-year RFI for assessment of biomarker-treatment interactions. Maximum-likelihood methods identified optimal high-risk/low-risk group cutpoints in the training set. Prognostic analyses were repeated in the validation set. Results: In the training set, the recurrence rate in the high-risk group was twice that in the low-risk group for all measures (CD3-CT: rate ratio [RR], 2.00, P = .0008; CD3-IM: 2.38, P < .00001; CD8-CT: 2.17, P = .0001; CD8-IM: 2.13, P = .0001). This was closely replicated in the validation set (RR, 1.96, 1.79, 1.72, 1.72, respectively). In multivariate analyses, prognostic effects were similar in colon and rectal cancers, and in stage II and III disease. Proportional reductions in recurrence with adjuvant chemotherapy were of similar magnitude in the high- and low-recurrence risk groups. Combining information from CD3-IM and CD3-CT (CD3 Score) generated high-, intermediate-, and low-risk groups with numbers needed to treat (NNTs) to prevent one disease recurrence being 11, 21, and 36, respectively. Conclusion: Recurrence rates in the high-risk CD3/CD8 groups are twice those in the low-risk groups. Proportional reductions with chemotherapy are similar, allowing NNTs derived in QUASAR to be updated using contemporary, nonrandomized data sets.
Databáze:	MEDLINE
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