PURPOSE: We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer. PATIENTS AND METHODS: We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy. RESULTS: Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95). CONCLUSION: The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.
PURPOSE: We developed quantitative gene expression assays to assess recurrence risk and benefits from chemotherapy in patients with stage II colon cancer. PATIENTS AND METHODS: We sought validation by using RNA extracted from fixed paraffin-embedded primary colon tumor blocks from 1,436 patients with stage II colon cancer in the QUASAR (Quick and Simple and Reliable) study of adjuvant fluoropyrimidine chemotherapy versus surgery alone. A recurrence score (RS) and a treatment score (TS) were calculated from gene expression levels of 13 cancer-related genes (n = 7 recurrence genes and n = 6 treatment benefit genes) and from five reference genes with prespecified algorithms. Cox proportional hazards regression models and log-rank methods were used to analyze the relationship between the RS and risk of recurrence in patients treated with surgery alone and between TS and benefits of chemotherapy. RESULTS: Risk of recurrence was significantly associated with RS (hazard ratio [HR] per interquartile range, 1.38; 95% CI, 1.11 to 1.74; P = .004). Recurrence risks at 3 years were 12%, 18%, and 22% for predefined low, intermediate, and high recurrence risk groups, respectively. T stage (HR, 1.94; P < .001) and mismatch repair (MMR) status (HR, 0.31; P < .001) were the strongest histopathologic prognostic factors. The continuous RS was associated with risk of recurrence (P = .006) beyond these and other covariates. There was no trend for increased benefit from chemotherapy at higher TS (P = .95). CONCLUSION: The continuous 12-gene RS has been validated in a prospective study for assessment of recurrence risk in patients with stage II colon cancer after surgery and provides prognostic value that complements T stage and MMR. The TS was not predictive of chemotherapy benefit.
Authors: Marlies S Reimers; Charla C Engels; Peter J K Kuppen; Cornelis J H van de Velde; Gerrit J Liefers Journal: Nat Rev Clin Oncol Date: 2014-06-24 Impact factor: 66.675
Authors: P García-Alfonso; J García-Foncillas; R Salazar; P Pérez-Segura; R García-Carbonero; E Musulén-Palet; M Cuatrecasas; S Landolfi; S Ramón Y Cajal; S Navarro Journal: Clin Transl Oncol Date: 2014-11-06 Impact factor: 3.405
Authors: Felipe De Sousa E Melo; Xin Wang; Marnix Jansen; Evelyn Fessler; Anne Trinh; Laura P M H de Rooij; Joan H de Jong; Onno J de Boer; Ronald van Leersum; Maarten F Bijlsma; Hans Rodermond; Maartje van der Heijden; Carel J M van Noesel; Jurriaan B Tuynman; Evelien Dekker; Florian Markowetz; Jan Paul Medema; Louis Vermeulen Journal: Nat Med Date: 2013-04-14 Impact factor: 53.440
Authors: Alan P Venook; Donna Niedzwiecki; Margarita Lopatin; Xing Ye; Mark Lee; Paula N Friedman; Wendy Frankel; Kim Clark-Langone; Carl Millward; Steven Shak; Richard M Goldberg; Najjia N Mahmoud; Robert S Warren; Richard L Schilsky; Monica M Bertagnolli Journal: J Clin Oncol Date: 2013-03-25 Impact factor: 44.544