Objectives. The role of endocrine therapy (ET) in high grade serous ovarian carcinoma (HGSOC) is poorly defined due to the lack of phase III data and significant heterogeneity of clinical trials performed. In this study, we sought to identify predictive factors of endocrine sensitivity in HGSOC. Methods. HGSOC patients who received at least four weeks of ET for relapsed disease following one line of chemotherapy at the Edinburgh Cancer Centre were identified. Exclusion criteria were use of endocrine therapy as maintenance therapy or of unknown duration. Duration of therapy and best CA125 response as per modified GCIG criteria were recorded. Oestrogen receptor (ER) histoscore, treatment free interval, prior lines of chemotherapy, and type of ET were evaluated as predictive factors. Results. Of 431 patients identified, 269 were eligible (77.0 % letrozole, 18.6% tamoxifen, 2.2% megesterol acetate, 2.2% other). The median duration of therapy was 126 days (range 28-1427 days). 32.7% remained on ET for ≥180 days and 14.1% for ≥365 days. The CA125 response and clinical benefit rates (response or stable disease) were 8.1% and 40.1% respectively. ER histoscore >200 (P=0.0016) and a treatment free interval of ≥180 days (P<0.0001) were independent predictive factors upon multivariable analysis. Conclusions. ET should be considered as a viable strategy to defer subsequent chemotherapy for relapsed HGSOC. Patients with an ER histoscore >200 and a treatment free interval of ≥180 days are most likely to derive benefit. 7 2.5 Statistical analysis Duration of therapy according to ER histoscore, TFI, prior lines of chemotherapy, best CA125 response and type of ET was evaluated using the Kaplan-Meier method and Cox regression models for univariable and multivariable analyses. Comparisons of CA125 ORR and CBR1 between groups were assessed using Chi-squared and Fisher's exact tests as appropriate. Statistical analyses were performed using R version 3.3.3. 3. RESULTS 431 patients received at least one line of ET. 162 patients were excluded (figure 1). 269 received ET as treatment for relapsed disease. 143(53.2%) were confirmed as HGSOC through contemporary pathology review conducted through other research studies, and 118(43.9%) and 8(3.0%) had a historical diagnosis of grade 3 and grade 2 serous carcinomas, respectively. The median age of diagnosis was 65 years (range 28-91 years). 3.1 First endocrine therapy for relapse Of 269 patients, 209 (77.7%), 55 (20.4%) and five (1.9%) patients received one, two and three lines of ET, respectively. 207 (77.0%), 50 (18.6%) and six (2.2%) patients received letrozole, tamoxifen and megesterol acetate, respectively. 156 (58.0%) patients received ET after one prior line of chemotherapy, 87 (32.3%) after two lines, and 26 (9.7%) after three or more lines. 229 (85.1%) and 36 (13.4%) patients last received chemotherapy in the platinum sensitive and platinum resistant setting, respectively. ER histoscores were available in 225 (83.6%) patients. The range of ER scores are illustrated in table 1. The ma...
BackgroundHereditary breast and ovary cancer syndrome affects both genders but little is known about the uptake of genetic services by men. The objective of this study is to characterise the male population counselled through a multidisciplinary breast/ovarian program.MethodsDescriptive analysis of male patients counselled from January 2000 to December 2015. Data in this analysis include new cancer diagnoses during prospective follow up.ResultsFrom 4,320 families registered, 362 male patients were identified: 236 (65.2%) from hereditary cancer families (HCF) and 126 (34.8%) from non-HCF. In HCF, 121 patients (51.3%) were mutation carriers (MC): BRCA2 – 102 (84.3%), BRCA1 – 16 (13.2%), CHEK2 – 1 (0.8%) and TP53 – 2 (1.7%). Non-HCF included 126 patients: 85 (67.5%) belonged to families without pathogenic mutations or with variants of unknown clinical significance; 22 (17.5%) refused testing after counselling and 19 (15.0%) did not meet criteria for testing. Both HCF and non-HCF included patients with previous cancer diagnoses: HCF- Breast Cancer (BC) - 18; prostate cancer (PC) - 13; melanoma - 1; others - 7) and non-HCF (BC - 77; PC - 20; gastric cancer (GC) - 1; melanoma - 8; bladder cancer - 1; others - 22). From the 121 MC identified (including the TP53 and CHEK2 carriers), 97 patients (80.2%) adhered to prospective surveillance. With a median follow-up of 36.9 months, 17 cancers were diagnosed in 14 patients, PC being the most frequently diagnosed neoplasia (5 cases). Eleven patients (78.6%) are alive and three patients died of advanced cancer (2 with GC, 1 with disseminated adenocarcinoma).ConclusionWe observed a high adherence to counselling, genetic testing and active surveillance by men belonging to hereditary BC families. Male carriers of pathogenic DNA variants are at risk for several cancers and should be included in prospective follow-up studies.
Our multicenter retrospective analysis included 499 patients treated with anti-PD-1 agents (nivolumab or pembrolizumab) between 2017 and 2019. 208 patients were aged <65 years, 218 patients were aged 65-79 years, and 73 patients were aged 80-100 years. We analysed the efficacy and toxicity of anti-PD-1 therapy at the age of 80-100 years compared to the age of 65-79 years and to <65 years. Baseline parameters, response rate (overall response rate -ORR), best response, progression-free survival (PFS), melanoma-specific survival (MSS) and immunerelated adverse events were analysed. The KaplaneMeier method was used to estimate PFS and MSS, Cox regression, t test, and chi-square test were used for statistical analysis.Results: Baseline parameters were comparable. There was no statistically significant difference between the groups aged <65 years, aged 65-79 years and aged 80-100 years of MSS (p¼0.2781), PFS (p¼0.5373), the number of responses to treatment (p¼0.155) and the occurrence of irAE (p¼ 0.821). In the multivariate analysis, the presence of brain metastases, elevated LDH levels, and the occurrence of at least one irAE had a statistically significant impact on OS and PFS. The age, gender, BRAF mutation, primary lesion location, type of anti-PD-1 therapy had no statistically significant effect on MSS and PFS in the multivariate analysis. Toxicity for all groups was similar. Immune related adverse events in grade 3 or 4 were reported in 5%, 5.5% and 4% of patients in the groups aged <65 years, aged 65-79 years and aged 80-100 years, respectively.Conclusions: Anti PD-1 therapy in octogenarian and nonagenarian metastatic melanoma patients has similar efficacy and toxicity compared to patients aged <65 years and 65-79 years. The patient's age cannot be the reason for disqualification from anti-PD-1 treatment.Legal entity responsible for the study: Bo_ zena Cybulska-Stopa.
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