Abscopal effect observed in visceral and osseous metastases after liver SBRT in combination with nivolumab and relatlimab for sinonasal mucosal melanoma—a case report

BackgroundPrimary sinonasal mucosal melanoma (SNMM) is a rare, aggressive histology usually diagnosed at advanced stages and associated with poor prognosis. Evidence regarding etiology, diagnosis, and treatment mainly derives from case reports, retrospective series, and national databases. In the treatment of metastatic melanoma, anti-CTLA-4 and anti-PD-1 checkpoint blockade increased 5-year overall survival from ~10% (prior to 2011) to ~50% (between 2011 and 2016). In March of 2022, the FDA approved the use of relatlimab, a novel anti-LAG3 immune checkpoint inhibitor, for the treatment of melanoma.Case presentationA 67-year-old woman with locally advanced SNMM underwent debulking surgery, adjuvant RT, and first-line immunotherapy (ImT) with nivolumab but developed local progression. The patient started a second course of ImT with nivolumab and ipilimumab, but this was discontinued after two cycles due to an immune-related adverse event (irAE, hepatitis with elevated liver enzymes). Interval imaging identified visceral and osseous metastases including multiple lesions in the liver and in the lumbar spine. She went on to receive a third course of ImT with nivolumab and the novel agent relatlimab with concurrent stereotactic body radiation therapy (SBRT) to the largest liver tumor only, delivered in five 10-Gy fractions using MRI guidance. A PET/CT performed 3 months after SBRT demonstrated complete metabolic response (CMR) of all disease sites including non-irradiated liver lesions and spinal metastatic sites. After two cycles of the third course of ImT, the patient developed severe immune-related keratoconjunctivitis and ImT was discontinued.ConclusionThis case report describes the first complete abscopal response (AR) in an SNMM histology and the first report of AR following liver SBRT with the use of relatlimab/nivolumab combination ImT for metastatic melanoma in the setting of both visceral and osseous lesions. This report suggests that the combination of SBRT with ImT potentiates the adaptive immune response and is a viable path for immune-mediated tumor rejection. The mechanisms behind this response are hypothesis-generating and remain an area of active research with exceedingly promising potential

Gene sequencing for pathogenic variants among adults with breast and ovarian cancer in the caribbean

Importance: Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population. Objective: To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations. Design, Setting, and Participants: This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020. Exposures: Breast and/or ovarian cancer diagnosis Main Outcomes and Measures: Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants. Results: Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P \u3c.001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P =.001). Conclusions and Relevance: In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.

Differences in breast cancer outcomes amongst Black United States-born and Caribbean-born immigrants

1088 Background: The Black population in the US constitutes of 4 million immigrants, with 50% from the Caribbean. It has been shown that breast cancer is responsible for 14%-30% of cancer deaths in the Caribbean; this is up to two times higher than the USA. Methods: Retrospective cohort of 1369 self-identified Black women with breast cancer. Data was obtained from Jackson Memorial Health Systems and University of Miami Health System Tumor Registry. Individual-level data from 1132 cases was used to estimate hazard rations (HRs) of women born in the Caribbean (CB) or in the USA (USB) using Cox proportional hazards regression analysis for overall survival. Median follow-up was 115 months (interquartile range, 91.9-138.1 months) per participant. Results: Data from 622 (54.9%) USB women and 507 (45%) CB women diagnosed with breast cancer between 2006-2017. 90% (n = 1232) of the cohort is of non-Hispanic ethnicity. Caribbean immigrants from Haiti (18.3%), Jamaica (6.5%), Bahamas (3.1%), Cuba and Dominica Republic (2.8% each), Trinidad and Tobago (1%) and other nationalities from the Organization of Eastern Caribbean States were included, mean age 55.7 [95% CI, 54.7-56.8]; USB mean age 57.6 [95% CI, 56.4-58.7] (P = 0.02). Compared to USB, CB had lower BMI at diagnosis 29.6 [95% CI, 28.9-30.3] versus 30.9 [95% CI, 30.1-31.7, P = 0.015]. Compared to CB patients, USB patients had more ER- [31.4% vs 39.1 %, P = 0.018] and triple negative breast cancers [19.6% vs 27.9%, P = 0.003]. Compared to USB patients, CB presented at more advanced stage, III and IV [44.2% vs 35.2%], p = 0.016. In spite of higher advanced stage at diagnoses, CB patients had a better breast cancer overall survival [HR = 0.75; 95%CI, 0.59-0.96; P = 0.024]. Black Hispanic patients had a better overall survival [HR = 0.51; 95%CI, 0.28-0.93; p = 0.028] compared to non-Hispanic Blacks. Compared to Hispanic Caribbean, non-Hispanic Caribbean had a worse overall survival [HR = 1.98; 95%CI, 1.00-3.94; P = 0.048]. The distribution of patients treated at the private cancer center and the safety net hospital were the same, differences in outcomes observed are due to intrinsic differences. Conclusions: This is the largest analysis to date of self-identified Black breast cancer patients in the context of nativity, race, ethnic identity and overall survival with clinico-pathologic characteristics. CB immigrants diagnosed with breast cancer have a better overall survival than US born Black patients. This finding suggests that within the African diaspora in the USA, additional factors beyond race contribute to the outcomes