Background The treatment of advanced periocular basal cell carcinomas becomes a challenge as surgery may involve highly mutilating procedures. Vismodegib is the first selective hedgehog inhibitor approved for the treatment of locally advanced tumors or metastatic disease. Objective Analyze the results of treatment with vismodegib for advanced periocular basal cell carcinomas in a real-life setting of a reference center between 2014 and 2020. Methods Retrospective longitudinal study. The patient's demographic profile, comorbidities, tumor characteristics, and treatment outcomes were analyzed. Results A total of 13 patients were included. Median follow-up and treatment duration were 15.9 and 10.5 months, respectively. Objective clinical response rate was 76.9%: 30.8% had a complete response and 46.2% a partial response. The median duration of response was 13 months. Progressive disease was observed in 38.5% of cases, with a median of 19 months after the beginning of treatment. Eighty-four percent of the patients had at least one adverse event, and 61.54% needed to interrupt treatment temporarily or permanently to increase tolerability. Study limitations Being a retrospective study in a real-life setting, the evaluation of objective clinical response was subjective to physician appreciation. Conclusion Vismodegib is a safe and effective treatment for locally advanced basal cell carcinoma. To prevent recurrences, the drug should be used continually when tolerated. The role of neoadjuvant vismodegib before surgery is being investigated and might add an important step in searching for a definitive treatment for these cases.

PURPOSERecent studies questioned the role of BRCA2 as a prognostic factor. Although differences between clinicopathological characteristics of BRCA1-breast cancer (BC) and BRCA2-BC have been described, long-term follow-up data related to prognosis and survival is lacking. We report the analysis of our cohort of BRCA1/2-BC patients (pts) included in our multidisciplinary program. This cohort includes BRCA2-BC c.156_157insAlu carriers, which was previously described as a Portuguese founder mutation. PATIENTS AND METHODS All pts underwent comprehensive BRCA1/2 testing. Data was obtained from all BRCA1/2 pts included in prospective follow up from January 2000 to June 2019, with BC as first cancer diagnosis. Follow-up started after genetic testing. RESULTSFrom 5504 cases (4021 index, 1483 family relatives) that consented on BRCA1/2 testing, 613 BRCA1/2 were cancer pts, of which 478 (78%) had BC as their first cancer diagnosis. These were mostly BRCA2 (n=321, 67.2% vs BRCA1 n=156, 32.6%) females (95.2%), and 129 (40%) of all BRCA2 cases were 156_157insAlu. Three pts had double pathogenic mutations (BRCA1+CHEK2, BRCA2+CHEK2 and BRCA1+BRCA2). Median follow-up was 4.3 yrs (0-17.8).Median age at testing was 50.3 (21-84) yrs and median age at BC diagnosis was significantly higher for BRCA2-BC (45.9 (21-80) vs 42.7 yrs (28-65), p<0.02) than for BRCA1-BC. Compared to BRCA1 pts, BRCA2 pts had higher prevalence of tumors <1cm at diagnosis (10.6% vs 5.8%, p=0.057), hormone receptor positive status (60.4% vs 28.8%, p<0.0001), and lower prevalence of TN phenotype (9.3% vs 48.7%, p<0.0001). BRCA2-BC was associated with longer median time to relapse (TTR) (63.6m, 95% CI 43.1-84.2, vs 23.3m, 95% CI 18.6-28.5, p<0.05), even if relapse rates were similar (9.9% vs 9.6%) and, for a median follow up of 4.3 yrs, no statistically significant difference for survival was observed (7.2 yrs (95% CI 4.1-10.3) vs 5.9 yrs (95% CI 3.8-7.9) for BRCA2-BC and BRCA1-BC respectively).Uptake of preventive surgeries (bilateral or contralateral mastectomy*, adnexectomy, or both) was similar between both groups (BRCA2 17.8%, 27.1% and 11.5% vs BRCA1 18.6%, 26.9% and 10.9%, respectively). Subsequent cancers occurred in 169 pts (35.4%), and were mostly BC (BRCA2 69.1% vs BRCA1 58.7%). Having subsequent cancer was associated with BRCA2 status (72.8% vs 27.2%, p<0.04), not undergoing risk-reducting mastectomy (91.7% vs 8.3%, p<0.0001) and not undergoing risk-reducting mastectomy with bilateral anexectomy (95.3% vs 4.7%, p=0.001). Regarding subsequent cancers, 116 cases were detected during prospective follow-up, 89 in 66 BRCA2-BC and [CB1] 27 cancers in 27 BRCA1-BC. CONCLUSIONIn our population, there is a higher prevalence of BRCA2-BC than BRCA1-BC, not completely explained by the founder effect of c.156_157insAlu. For the described follow up, TTR was longer for BRCA2-BC pts but survival was not different between the two groups, even though BRCA2 status was associated with more subsequent cancer diagnoses. As expected, preventive surgeries were inversely associated with second cancers. Data on prognosis and survival needs to be confirmed with longer follow up. *- includes pts previously treated with conservative surgery Citation Format: Catarina Bexiga, Priscila Nejo, Inês Oliveira, Paula Rodrigues, Patrícia Pereira, Sofia Fragoso, Alexandra Mayer, Joana Parreira, Sidónia Santos, Pedro Louro, Ana Luís, Sandra Bento, Isália Miguel, Cecília Moura, Ana Clara, Fátima Vaz. When BRCA2-breast cancer is more prevalent than BRCA1-breast cancer: Prospective follow-up data from a multidisciplinary program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-17.

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.

PURPOSE Previous studies referred to uptake of preventive surgeries (PS) in BRCA1/2 healthy carriers in ages older than recommended (35yrs). Since our population has a higher prevalence of BRCA2 mutations (usually associated with an older age at Breast Cancer diagnosis) we proposed to study ages and type of preventive surgeries uptaken by BRCA1/2 women included in prospective follow up. PATIENTS AND METHODS Review of all healthy (without a previous cancer diagnosis) BRCA1/2 carriers included in our program from January 2000 to June 2019. Follow-up started after genetic testing. Men were excluded from this analysis. RESULTS A total of 5504 cases (4021 index, 1483 relatives) consented for BRCA1/2 testing. We identified 238 healthy BRCA1/2 carriers (BRCA2:158 (66.4%) vs BRCA1 80 (33.6%). Median age at genetic diagnosis was 38.9 yrs (16-78). With a median follow up of 4yrs, bilateral adnexectomy (BA) was the most frequent PS observed (45 BRCA2 and 28 BRCA1 cases) with 15/45 % and 6/28% undergoing BA and bilateral mastectomy (BM) simultaneously. Bilateral mastectomy was uptaken by 14% BRCA2 women and 10% BRCA1 women. Median ages for PS were: BRCA2-AB: 47,4 (28-71), BRCA1-AB: 46.7 (37-59); BRCA2-BM: 36.6 (31-52) and BRCA1-BM:42.5 (30-55). Isolated BM was observed in 7 BRCA2 cases and 2 BRCA1 cases. Most of women submitted to BA, also underwent total hysterectomy (HT): 65% for BRCA2 and 61% BRCA1. Most cases (88% non-adherent) adhere to radiological surveillance, 111/238 with annual breast S MRI and mammography. All pts submitted to BM are prescribed at least one breast MRI to check for remaining breast tissue. CONCLUSION Our data reveal that even if, in general, BRCA1/2 women uptake preventive surgeries at a later age that recommended, we observed a strong adherence to radiological (most with breast MRI) surveillance. BA is the PS most frequently observed but, surprisingly for healthy women, most cases also underwent TH. BRCA2 healthy women uptaken bilateral mastectomy at an earlier age than BRCA1 women. It´s possible that BRCA1 women, when deciding for BM also decided for BA. Citation Format: Priscila Nejo, Catarina Bexiga, S. Fragoso, A Mayer, S Santos, P Louro, A Luis, C Moura, Ana Clara, Fatima Vaz. Uptake of preventive surgeries in a prospective cohort of BRCA1/2 healthy women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-36.