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This article was originally published under a CC BY NC SA License, but has now been made available under a CC BY 4.0 License.
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BACKGROUND: Investigating tumour evolution and acquired chemotherapy resistance requires analysis of sequential tumour material. We describe the feasibility of obtaining research biopsies in women with relapsed ovarian high-grade serous carcinoma (HGSC). METHODS: Women with relapsed ovarian HGSC underwent either image-guided biopsy or intra-operative biopsy during secondary debulking, and samples were fixed in methanol-based fixative. Tagged-amplicon sequencing was performed on biopsy DNA. RESULTS: We screened 519 patients in order to enrol 220. Two hundred and two patients underwent successful biopsy, 118 of which were image-guided. There were 22 study-related adverse events (AE) in the image-guided biopsies, all grades 1 and 2; pain was the commonest AE. There were pre-specified significant AE in 3/118 biopsies (2.5%). 87% biopsies were fit-for-purpose for genomic analyses. Median DNA yield was 2.87 µg, and was higher in biopsies utilising 14 G or 16 G needles compared to 18 G. TP53 mutations were identified in 94.4% patients. CONCLUSIONS: Obtaining tumour biopsies for research in relapsed HGSC is safe and feasible. Adverse events are rare. The large majority of biopsies yield sufficient DNA for genomic analyses-we recommend use of larger gauge needles and methanol fixation for such biopsies, as DNA yields are higher but with no increase in AEs.
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Carcinoma/genética , Carcinoma/secundario , ADN de Neoplasias/análisis , Biopsia Guiada por Imagen , Neoplasias Hepáticas/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Peritoneales/patología , Adulto , Anciano , Anciano de 80 o más Años , Fosfatidilinositol 3-Quinasa Clase I , Análisis Mutacional de ADN , ADN de Neoplasias/aislamiento & purificación , Receptores ErbB/genética , Estudios de Factibilidad , Femenino , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/instrumentación , Hígado/patología , Neoplasias Hepáticas/secundario , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Epiplón/patología , Fosfohidrolasa PTEN/genética , Dolor/etiología , Neoplasias Peritoneales/secundario , Peritoneo/patología , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. PATIENTS AND METHODS: Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2-6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS). RESULTS: Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2-6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85-1.15; P = 0.93]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81-1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P < 0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value. CONCLUSIONS: Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia.
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Antineoplásicos/administración & dosificación , Carboplatino/administración & dosificación , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Área Bajo la Curva , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Quimioterapia de Inducción , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Pronóstico , Calidad de Vida , Resultado del TratamientoRESUMEN
A high incidence of central nervous system (CNS) metastases has been reported in patients with HER2-positive tumours receiving trastuzumab therapy for metastatic breast cancer. This study tested whether prophylactic cranial irradiation (PCI) could reduce the incidence of CNS metastases in this setting. This was a prospective, randomised phase III trial. Patients were randomised 1:1 to no PCI or PCI delivered at around 6 weeks after study entry. Cognitive function was assessed prospectively. In total, 51 patients were randomised over a 3 year period; 25 received PCI and 26 did not. The cumulative incidence of CNS metastases at 2 years was 32.4% (standard error = 9.8%) on the no PCI arm and 21.0% (standard error = 8.6%) on the PCI arm; the associated hazard ratio was 0.57 (95% confidence interval 0.18-1.74; P = 0.32). There was no evidence of cognitive dysfunction in PCI patients.