Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma

Vasudev, N.S.; Scelo, G.; Glennon, K.I.; Wilson, M.; Letourneau, L.; Eveleigh, R.; Nourbehesht, N.; Arseneault, M.; Paccard, A.; Egevad, L.; Viksna, J.; Celms, E.; Jackson, S.M.; Abedi-Ardekani, B.; Warren, A.Y.; Selby, P.J.; Trainor, S.; Kimuli, M.; Cartledge, J.; Soomro, N.; Adeyoju, A.; Patel, P.M.; Wozniak, M.B.; Holcatova, I.; Brisuda, A.; Janout, V.; Chanudet, E.; Zaridze, D.; Moukeria, A.; Shangina, O.; Foretova, L.; Navratilova, M.; Mates, D.; Jinga, V.; Bogdanovic, L.; Kovacevic, B.; Cambon-Thomsen, A.; Bourque, G.; Brazma, A.; Tost, J.; Brennan, P.; Lathrop, M.; Riazalhosseini, Y.; Banks, R.E.

Авторы: Vasudev Naveen S., Scelo Ghislaine, Glennon Kate I., Wilson Michelle, Letourneau Louis, Eveleigh Robert, Nourbehesht Nazanin, Arseneault Madeleine, Paccard Antoine, Egevad Lars, Viksna Juris, Celms Edgars, Jackson Sharon M., Abedi-Ardekani Behnoush, Warren Anne Y., Selby Peter J., Trainor Sebastian, Kimuli Michael, Cartledge Jon, Soomro Naeem, Adeyoju Adebanji, Patel Poulam M., Wozniak Magdalena B., Holcatova Ivana, Brisuda Antonin, Janout Vladimir, Chanudet Estelle, Zaridze David, Moukeria Anush, Shangina Oxana, Foretova Lenka, Navratilova Marie, Mates Dana, Jinga Viorel, Bogdanovic Ljiljana, Kovacevic Bozidar, Cambon-Thomsen Anne, Bourque Guillaume, Brazma Alvis, Tost Jörg, Brennan Paul, Lathrop Mark, Riazalhosseini Yasser, Banks Rosamonde E.
Журнал: Clinical Cancer Research
Том: 29
Номер: 7
Год издания: 2023
Издательство: American Association for Cancer Research
Местоположение издательства: United States
Первая страница: 1220
Последняя страница: 1231
DOI: 10.1158/1078-0432.ccr-22-1936
Аннотация: Purpose: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing.Experimental design: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework.Results: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy.Conclusions: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design.
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Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinomaстатья