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Eur J Cancer. 2019 Sep;118:121-130. doi: 10.1016/j.ejca.2019.06.008. Epub 2019 Jul 19.

A validated prognostic classifier for V600EBRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study.

Author information

1
Unit of Oncology 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy. Electronic address: fotios.loupakis@iov.veneto.it.
2
Unit of Oncology 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.
3
Unit of Medical Oncology 2, Department of Translational Research and New Technologies in Medicine and Surgery, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
4
Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy.
5
Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Oncology and Hemato-oncology, Università Degli Studi di Milano, Milan, Italy.
6
Department of Oncology and Hemato-oncology, Università Degli Studi di Milano, Milan, Italy; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
7
Department of Oncology, University and General Hospital, Udine, Italy.
8
Department of Diagnostic Medicine and Public Health, Section of Pathology, Università di Modena e Reggio Emilia, Policlinico di Modena, Modena, Italy.
9
Medical Oncology, Campus Biomedico University, Rome, Italy.
10
Medical Oncology, University of Cagliari, University Hospital, Cagliari, Italy.
11
S.C.D.U. Medical Oncology, A.O. Ordine Mauriziano Hospital, Department of Oncology, University of Turin, Turin, Italy.
12
Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano (MI), Italy.
13
Medical Oncology Unit, Tor Vergata University, Rome, Italy.
14
Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Turin, Italy; Department of Oncology, University of Torino, Candiolo, Turin, Italy.
15
Department of Oncology, San Bortolo General Hospital, ULSS8 Berica - East District, Vicenza, Italy.
16
Medical Oncology, Careggi University Hospital, Firenze, Italy.
17
Medical Oncology, Policlinico Umberto I, Sapienza, Università Degli Studi di Roma, Rome, Italy.
18
Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium.
19
Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
20
Department of Medical Oncology, General Hospital, Prato, Italy.
21
Medical Oncology, Sesto San Giovanni Hospital, Sesto San Giovanni (MI), Italy.
22
Medical Oncology Unit, ASST of Cremona, Cremona Hospital, Cremona, Italy.
23
Experimental Abdomen Medical Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Napoli, Italy.
24
Medical Oncology Unit, Azienda ULSS 1, Belluno, Italy.
25
Unit of Oncology, Polyclinic GB Rossi, AOUI Verona, Italy.
26
Oncology Unit, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy; Unit of Oncology, Polyclinic GB Rossi, AOUI Verona, Italy.
27
Unit of Surgical Pathology, Department of Medicine, University of Padua, Padua, Italy.

Abstract

BACKGROUND:

Despite the well-known negative prognostic value of the V600EBRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined.

METHODS:

Two large retrospective series of V600EBRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated.

RESULTS:

A total of 395 V600EBRAF-mutated mCRCs were included in the exploratory set. Performance status, CA19.9, lactate dehydrogenase, neutrophil/lymphocyte ratio, grading and liver, lung and nodal involvement emerged as independent prognostic factors for overall survival (OS). Two different scoring systems were built: a 'complete' score (0-16) including all significant covariates and a 'simplified' score (0-9), based only on clinicopathological covariates, and excluding laboratory values. Adopting the complete score, proportions of patients with a low (0-4), intermediate (5-8) and high (9-16) score were 44.7%, 42.6% and 12.6%, respectively. The median OS was 29.6, 15.5 (hazard ratio [HR] for intermediate vs low risk: 2.16, 95% confidence interval [CI]: 1.44-3.22, p < .001) and 6.6 months (HR for high vs low risk: 4.72, 95% CI: 2.72-8.20, p < .001). Similar results were observed also after adjusting for the type of first-line treatment and adopting the simplified score. The simplified prognostic score derived from the exploratory set was then applied to the validation set for external confirmation.

CONCLUSIONS:

These scoring systems are based on easy-to-collect data and defined specific subgroups with relevant differences in their life expectancy. These tools could be useful in clinical practice, would allow better stratification of patients in clinical trials and may be adopted for proper adjustments in exploratory translational analyses.

KEYWORDS:

(V600E)BRAF; Colorectal cancer; Metastases; Prognostic markers; Scoring system

PMID:
31330487
DOI:
10.1016/j.ejca.2019.06.008

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