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J Natl Cancer Inst. 2017 Dec 1;109(12). doi: 10.1093/jnci/djx095.

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

Author information

1
Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.
2
German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
German Cancer Consortium (DKTK), partner site: Frankfurt/Mainz, Heidelberg, Germany.
4
Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany.
5
Department of Radiation Therapy, University of Erlangen-Nürnberg, Nürnberg, Germany.
6
Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany.
7
Department of Radiation Oncology and Radiotherapy, DiaCura and Klinikum Coburg, Coburg, Germany.
8
Institute of Pathology.
9
Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
10
Department of Hematology/Oncology and Gastroenterology, Kliniken Maria Hilf GmbH Mönchengladbach, Mönchengladbach, Germany.
11
Department of Radiation Oncology, Kliniken Maria Hilf GmbH Mönchengladbach, Mönchengladbach, Germany.
12
Department of General and Visceral Surgery, University of Oldenburg, Oldenburg, Germany.
13
Institute of Pathology, University of Leipzig, Leipzig, Germany.

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.

PMID:
29206996
DOI:
10.1093/jnci/djx095
[Indexed for MEDLINE]

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