[PMID]: | 29206996 |
[Au] Autor: | Fokas E; Ströbel 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; Rödel C; German Rectal Cancer Study Group |
[Ad] Endereço: | Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany. |
[Ti] Título: | Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer. |
[So] Source: | J Natl Cancer Inst;109(12), 2017 Dec 01. |
[Is] ISSN: | 1460-2105 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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. |
[Mh] Termos MeSH primário: |
Carcinoma/secundário Carcinoma/terapia Recidiva Local de Neoplasia Neoplasias Retais/patologia Neoplasias Retais/terapia
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[Mh] Termos MeSH secundário: |
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Quimiorradioterapia Adjuvante Intervalo Livre de Doença Feminino Fluoruracila/administração & dosagem Seguimentos Seres Humanos Masculino Margens de Excisão Gradação de Tumores Recidiva Local de Neoplasia/patologia Neoplasia Residual Compostos Organoplatínicos/administração & dosagem Período Pré-Operatório
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[Pt] Tipo de publicação: | CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL |
[Nm] Nome de substância:
| 0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin); U3P01618RT (Fluorouracil) |
[Em] Mês de entrada: | 1712 |
[Cu] Atualização por classe: | 180308 |
[Lr] Data última revisão:
| 180308 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171206 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1093/jnci/djx095 |
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