RESUMO
BACKGROUND: Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, party related to a possible radiotherapy resistance leading to local-regional recurrences (LRR). The objective of the present study was to identify predictive molecular biomarkers of LRR of BC. PATIENTS AND METHODS: Genetic profile of 146 BC patients' tumours included in the ProfiLER clinical trial (NC01774409) between 2013 and 2016 were analysed using next-generation-sequencing and comparative-genomic-hybridization tests. Patients and tumour characteristics were retrospectively collected and analysed for association with genomic rearrangements (mutations, amplification, deletions). Only gene alterations observed in >3% of the tumours were selected. RESULTS: A total of 193 genomic rearrangements were identified, and 16 were observed in >3% of tumours. One was statistically correlated to the risk of local relapse. A median loco-regional progression-free survival (LRPFS) of 23.6 years was reported for PIK3CA mutation carriers (n = 31, 21.2%) versus 9.9 years for PIK3CA wild-type patients (HR 0.27, 95% CI 0.12-0.65, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor on LRR using multivariate analysis (HR 0.29, 95% CI 0.09-0.99, P = 0.047). All other mutations, amplifications or deletions were not found associated with LRPFS. CONCLUSION: PIK3CA mutation was associated with a lower risk of local relapse in this population of BCs. This is consistent with recent studies suggesting PIK3CA to be part of biological pathways impacting the radiosensitivity.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Rearranjo Gênico , Recidiva Local de Neoplasia/genética , Tolerância a Radiação/genética , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/radioterapia , Carcinoma Lobular/secundário , Classe I de Fosfatidilinositol 3-Quinases/genética , Terapia Combinada , Feminino , Seguimentos , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Mutação , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIM: SOS/VOD is a relevant clinical syndrome that usually appears early after hematopoietic stem cell transplantation. The purpose of this article was to report a case series of SOS/VOD in non-susceptible patients and draw physicians' attention to the plausible relationship between liver injury and oxaliplatin-based chemotherapy, preceding autologous transplantation. METHODS: In this study, we report a case series of SOS/VOD in 4 lymphoma patients following autologous transplantation. The data were collected between July 2013 and November 2015 by analyzing patient's characteristics and outcomes. RESULTS: We noticed 4 severe cases of SOS with unusual presentations in patients who did exhibit few classical risk factors. These patients received R-DHAO before transplantation. CONCLUSIONS: Physicians need to be aware that oxaliplatin-based regimen could contribute to SOS/VOD complications in hematological patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Linfoma/terapia , Oxaliplatina/administração & dosagem , Idoso , Terapia Combinada , Feminino , Hepatopatia Veno-Oclusiva/diagnóstico , Humanos , Linfoma/complicações , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Transplante AutólogoRESUMO
Carcinomatous meningitis complicates 5 to 10% of cancers, essentially with breast cancers, lung cancers and melanomas. The incidence probably increased because of therapeutic advances in oncology. Treatment is based on external beam radiotherapy, systemic treatment, intrathecal chemotherapy and supportive care. The aim of this work was to review data on external radiation therapy and carcinomatous meningitis. There are few evidences on the subject, but it is a major topic of interest. A whole brain radiation therapy is indicated in case of brain metastases or clinical encephalitis. Focal radiation therapy is recommended on symptomatic, bulky or obstructive sites. The dose depends on performance status (20 to 40 Gy in five to 20 fractions), volume to treat and available techniques (classic fractionation or hypofractionation via stereotactic radiosurgery). The objective of radiation therapy is to improve quality of life. Association with systemic therapy improves overall survival. Administration of sequential intrathecal chemotherapy may also improve overall survival, but induces more toxicity. The use of new radiotherapy techniques and development of radiosensitizing molecules in patients with good performance status could improve survival in this frequent complication of cancer.