Resection of metastases in patients with BRAF mutated metastatic colon cancer: results of a multicenter retrospective study
https://doi.org/10.18027/2224-5057-2021-11-3-5-14
Abstract
Introduction: local treatment of metastases is an integral part of colon cancer treatment. However, there is not enough data on the efficacy of surgical resection of metastases in patients with a BRAF gene mutation to recom‑mend this approach in routine practice. We initiated a retrospective multicenter study to assess the incidence of BRAF gene mutations in patients with metastatic colon cancer and to study the efficacy of metastasectomy in this group of patients.
Materials and methods: we selected all patients who underwent surgical resection of metastases in various sites from the database of patients with BRAF gene mutations created as a result of a multicenter retrospective study with participation of 7 clinics in the Russian Federation. All 57 patients with RAS gene mutations and 43 patients with wild‑type RAS and BRAF genes who also underwent surgical resection of metastases at any stage of treatment were selected from the register of the Chemotherapy Department No. 2 of the NMRC of Oncology named after N. N. Blokhin for comparative analysis. Disease‑free survival and overall survival were used as primary efficacy criteria.
Results: we found 26 patients with BRAF gene mutations who underwent surgical resection of metastases. When comparing disease‑free survival, the worst median was achieved in the group of patients with BRAF gene mutations: 7 months versus 14 months in patients with RAS gene mutations (HR 0.4, 94 % CI 0.23–0.7, P = 0.006); median disease‑free survival was not achieved in the wild‑type RAS and BRAF group (HR 0.2, 95 % CI 0.11–0.45, P <0.001).
The median overall survival in the BRAF gene mutation group was 26 months versus 38 months in the RAS gene mutations group (HR 0.8, 95 % CI 0.33–1.98, P = 0.6) and 49 months in the wtRAS/wtBRAF group (RR 0.46, 95 % CI 0.17–1.24, P = 0.1). Resection of recurrent tumors in patients with metastases in retroperitoneal lymph nodes was associated with extremely low disease‑free survival (2 months); at the same time, disease‑free survival was 7 months after resection of isolated metastases in the liver and 8 months for metastases in the peritoneum.
Conclusion: prognosis of patients with a BRAF gene mutation after surgical resection of metastases is worse than in patients with a different mutation phenotype. Nevertheless, literature data, as well as the results of our study, confirm the possibility of performing metastasectomy with careful selection of patients.
About the Authors
M. Yu. FedyaninRussian Federation
Mikhail Yu. Fedyanin, MD, PhD, DSc, Senior Researcher, Oncology Department of Drug Therapy (Chemotherapy) No.
2
Moscow
H. H.‑M. Elsnukaeva
Russian Federation
Heda H.‑M. Elsnukaeva, Postgraduate Student Breast Cancer Department of Drug Therapy (Chemotherapy) No. 2
Moscow
I. A. Demidova
Russian Federation
Irina A. Demidova, MD, PhD, Head of the Laboratory of Molecular Biology
Moscow
D. L. Stroyakovskii
Russian Federation
Daniil L. Stroyakovskii, MD, PhD, Head of the Chemotherapy Department
Moscow
Yu. A. Shelygin
Russian Federation
Yurii A. Shelygin, MD, PhD, DSc, Prof., Academician of the Russian Academy of Sciences, Scientific Director
Moscow
A. S. Tsukanov
Russian Federation
Aleksey S. Tsukanov, MD, PhD, DSc, Leading Researcher, Head of the Laboratory Genetics Department
Moscow
Yu. S. Sergeev
Russian Federation
Yurii S. Sergeev, MD, PhD, Oncologist at the Surgical Departmen
Moscow
A. A. Ponomarenko
Russian Federation
Aleksey A. Ponomarenko, MD, PhD, DSc, Leading Researcher of the 3th Surgical Department (Rectal Oncology)
Moscow
M. V. Panina
Russian Federation
Maria V. Panina, MD, PhD, Oncologist of the Department of Anticancer Chemotherapy
Moscow
V. P. Shubin
Russian Federation
Vitaliy P. Shubin, MD, PhD biol., Senior Researcher
Moscow
F. V. Moiseenko
Russian Federation
Fyodor V. Moiseenko, MD, PhD, DSc, Head of Chemotherapy Department
Saint Petersburg
E. Yu. Karpenko
Russian Federation
Elena Yu. Karpenko, Junior Researcher, Chemotherapy Department, Department of Tumor Drug Treatment
Moscow
L. V. Bolotina
Larisa V. Bolotina, MD, PhD, DSc, Head of the Chemotherapy Department
Moscow
A. V. Kudriavtseva
Anna V. Kudriavtseva, MD, PhD biol., Researcher, Department of Pathology
Moscow
M. L. Filipenko
Maksim L. Filipenko, MD, PhD biol., Chief Researcher, Head of the Pharmacogenomics Laboratory
Novosibirsk
M. E. Voskoboev
Mikhail E. Voskoboev
Novosibirsk
I. P. Oskorbin
Igor P. Oskorbin, MD, PhD biol., Junior Researcher, Pharmacogenomics Laboratory
Rostov‑on‑Don
L. Yu. Vladimirova
Lubov Yu. Vladimirova, MD, PhD, DSc, Professor, Head of the Department of Tumor Drug Treatment
Rostov‑on‑Don
O. I. Kit
Oleg I. Kit, MD, PhD, DSc, Professor, Honored Doctor of the Russian Federation, General Director
Rostov‑on‑Don
A. M. Stroganova
Anna M. Stroganova, MD, PhD, Head of the Molecular Biology Laboratory, Department of Morphological and Molecular
Genetic Diagnostics of Tumors, Research Institute of Clinical Oncology
Moscow
S. L. Dranko
Svetlana L. Dranko, Laboratory Geneticist, Molecular Biology Laboratory,
Moscow
A. I. Senderovich
Anastasiya I. Senderovich, MD, PhD, Laboratory Geneticist, Laboratory of Immunomorphology and Molecular Genetics
Moscow
A. A. Tryakin
Alexey A. Tryakin, MD, PhD, DSc, Chief Researcher, Oncology Department of Drug Therapy (Chemotherapy) No. 2
Moscow
S. A. Tjulandin
Sergei A. Tjulandin, MD, PhD, DSc, Prof., Head of the Oncology Department, of Drug Therapy (Chemotherapy) No. 2
Moscow
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Review
For citations:
Fedyanin M.Yu., Elsnukaeva H.H., Demidova I.A., Stroyakovskii D. ., Shelygin Yu.A., Tsukanov A.S., Sergeev Yu.S., Ponomarenko A.A., Panina M.V., Shubin V.P., Moiseenko F.V., Karpenko E.Yu., Bolotina L.V., Kudriavtseva A.V., Filipenko M.L., Voskoboev M.E., Oskorbin I.P., Vladimirova L.Yu., Kit O. ., Stroganova A.M., Dranko S. ., Senderovich A. ., Tryakin A.A., Tjulandin S. . Resection of metastases in patients with BRAF mutated metastatic colon cancer: results of a multicenter retrospective study. Malignant tumours. 2021;11(3):5-14. (In Russ.) https://doi.org/10.18027/2224-5057-2021-11-3-5-14