Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer

Fokas E, Stroebel P, Fietkau R, Ghadimi M, Liersch T, Grabenbauer GG, Hartmann A, Kaufmann M, Sauer R, Graeven U, Hoffmanns H, Raab HR, Hothorn T, Wittekind C, Roedel C (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Journal of the National Cancer Institute Oxford University Press

Book Volume: 109

Journal Issue: 12

DOI: 10.1093/jnci/djx095

Abstract

Background: We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial. Methods: TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided. Results: With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4. Conclusions: Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.

Authors with CRIS profile

Rainer Fietkau Lehrstuhl für Strahlentherapie Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Universitätsklinikum Göttingen DE Germany (DE) DiaCura - Praxis für Radiologische Diagnostik, Strahlentherapie und Radioonkologie DE Germany (DE) University of Zurich / Universität Zürich (UZH) CH Switzerland (CH) Kliniken Maria Hilf GmbH DE Germany (DE) Carl von Ossietzky Universität Oldenburg DE Germany (DE) Universität Leipzig DE Germany (DE)

How to cite

APA:

Fokas, E., Stroebel, P., Fietkau, R., Ghadimi, M., Liersch, T., Grabenbauer, G.G.,... Roedel, C. (2017). Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer. Journal of the National Cancer Institute, 109(12). https://doi.org/10.1093/jnci/djx095

MLA:

Fokas, Emmanouil, et al. "Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer." Journal of the National Cancer Institute 109.12 (2017).

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