RESUMO
BACKGROUND: Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors. METHODS: Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated. RESULTS: 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176). CONCLUSIONS: Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.
Assuntos
Sobreviventes de Câncer , Carcinoma Epitelial do Ovário , Citocromo P-450 CYP3A , Neoplasias Ovarianas , Doenças do Sistema Nervoso Periférico , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/genética , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Idoso , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Sobreviventes de Câncer/estatística & dados numéricos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP2C8/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Adulto , Estudos de Coortes , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Translational research in radiation oncology is undergoing intense development. An increasingly rapid transfer is taking place from the laboratory to the patients, both in the selection of patients who can benefit from radiotherapy and in the development of innovative irradiation strategies or the development of combinations with drugs. Accelerating the passage of discoveries from the laboratory to the clinic represents the ideal of any translational research program but requires taking into account the multiple obstacles that can slow this progress. The ambition of the RadioTransNet network, a project to structure preclinical research in radiation oncology in France, is precisely to promote scientific and clinical interactions at the interface of radiotherapy and radiobiology, in its preclinical positioning, in order to identify priorities for strategic research dedicated to innovation in radiotherapy. The multidisciplinary radiotherapy teams with experts in biology, medicine, medical physics, mathematics and engineering sciences are able to meet these new challenges which will allow these advances to be made available to patients as quickly as possible.