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

Comparing breast cancer characteristics and outcomes between black U.S.-born patients and black immigrant patients from individual Caribbean islands

e13633 Background: Caribbean-born black immigrants (CBI) represent 57% of all black immigrants in the US; they come mainly from Haiti, Jamaica, Dominican Republic (DR), and Cuba. Breast cancer (BC) is the leading cause of cancer deaths in women living in the Caribbean, however, our previous retrospective cohort of 1131 black women with BC shows that CBI have a better overall survival compared with US-born black (USB). The Caribbean has a majority of African ancestry; nonetheless, different ancestral populations differ in genetic composition, making the Caribbean a distinct population with several health disparities within it. Therefore, we stratified our study by each Caribbean country compared to USB patients with the objective of further studying the difference in BC outcomes between USB patients and CBI. Methods: We identified BC patients through a Safety Net and Private Hospital Tumor Registries. We selected the most populace sites: Haiti, Jamaica, Bahamas, Cuba and DR; and used data from 1,082 patients to estimate hazard rations (HRs) using Cox proportional hazards regression and Kaplan Meier analysis for overall survival; Chi Squared and independent sample t-test to verify associations in categorical variables. Results: The study has 250 Haitian, 89 Jamaican, 43 Bahamian, 38 Dominican, 38 Cuban and 624 USB women. Haitians underwent less surgery (HB 61.2% vs USB 72.9%; P = 0.001) and had less triple negative BC (18% vs USB 27.8%; P = 0.006). Bahamians were the youngest at diagnosis (50.5 years vs. USB 57.6 P < 0.001) and presented at more advanced stages (stage 3/4, 54.3% vs USB 35.3%; P = 0.02). Jamaicans and DR underwent more radiation therapy (43.8%, P = 0.002 and 44.7%, P = 0.028 vs. USB 28%). Jamaican women had a better overall survival compared to USB patients (median of 154.93 months, 95% CI: 114.1-195.5 vs 98.63 months, 95% CI: 76.4-120.8; Log-Rank Mantel Cox P = 0.034). Favorable factors for survival were: radiation therapy in Haitian and USB (aHR = 0.45, 95% 0.27-0.77; P = 0.004); and surgery in USB (aHR = 0.26 (0.19-0.36), p < 0.001), Bahamians (aHR = 0.05 (0.01-0.47), p = 0.008) and Jamaicans (aHR = 0.08 (0.03-0.24), p < 0.001). Conclusions: This study underlines the vast heterogeneity in the Caribbean population and demonstrates that Jamaican immigrants with BC have a higher overall survival compared to USB patients, proposing that genetic and other cancer related factors inherent to country of origin impact survival within Caribbean immigrants and highlighting the need for further studies in this immigrant sub-group

Abstract 3343: The Florida women’s cancer study: Breast cancer presentation among African American and Afro Caribbean women in south Florida, a 10-year cohort

Abstract Introduction: The Black population in the US constitutes about 4 million immigrants. Of this, 50% is from the Caribbean region. Jamaica is the largest contributing country, followed by Haiti and Trinidad and Tobago. Florida has the second largest Caribbean population in the USA. Breast cancer is the main cause of cancer death among females responsible for 14%-30% of cancer deaths in the Caribbean; this is up to two times higher than the USA. Little is known about the molecular subtypes of breast cancer and the demographics of Black Caribbean Immigrants. Objectives: Study the demographics of BC patients in the African diaspora, determine similarities and differences in cause, subtype and outcome of women with breast cancers in African American (AA) and Afro-Caribbean (AC) immigrants. Methods: Approved by the Ethics Committee of the University of Miami IRB. Patients treated for breast cancer between 2006 to 2016 were included. Abstracted data included sociodemographic factors, genetic testing results, and treatment histories. Results: A retrospective US-based cohort of 1369 women (self-identified as black), diagnosed with BC - the Florida Women’s Cancer Study (FLWCS), at Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital in Florida. This cohort contains data from 624 (46%) African-American (AA) women and 507 (37%) AC women diagnosed with breast cancer between 2006-2016. Ninety per cent (n=1232) of the cohort is of non-Hispanic ethnicity.FLWCS country distribution includes is composed of 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 (Antigua, St. Kitts and Nevis, Anguilla, Dominica, St. Lucia and Grenada) at 2.5%. ACwomen living in Miami were diagnosed at a younger age (53.7 years versus 54.9 years), than AA women.Twenty-eight percent of the AA women were premenopausal compared with 32% of the AC women. The AA women had a higher BMI, 32.1 vs 29.8 (p=0.0001), a lower proportion of HER2 positive breast cancer of 17.6% versus 23% (p=0.027), and more children 3.1 versus 2.8 (p=0.023), than the AC women. The rate of HER2 overexpression in the Caucasian population is12% while HER2 positivity was seen in 26.2% Jamaican women, 25.8% in Haitian women and 26.5% in Cuban women (p=0.043) respectively. Less than 5% of the cohort underwent genetic testing with less than 1% having a pathogenic germline mutation. Conclusion: African American (AA) and AC women have many similarities there are significant differences in terms of ancestral diversity, inherited genetic mutations, environmental exposures and access to medical care. Thus, it is imperative to gain an understanding of the causes of cancer in AC women in their own countries in order to better serve those immigrant populations once they reach the US. Citation Format: Priscila Barreto Coelho, Matthew Schlumbrecht, Danielle Cerbon, Carlos Parra, Judith Hurley, Sophia George. The Florida women’s cancer study: Breast cancer presentation among African American and Afro Caribbean women in south Florida, a 10-year cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3343

Race and Ethnicity Influence Survival Outcomes in Women of Caribbean Nativity With Epithelial Ovarian Cancer

Background: Caribbean immigrants represent one of the largest groups of minorities in the United States (US), yet are understudied. Racial and ethnic disparities among women with ovarian cancer have been reported, but not in immigrant populations. Our objective was to evaluate differences in the clinicopathologic features and survival outcomes of Caribbean-born (CB) immigrants with ovarian cancer, with special focus on the influence of race and ethnicity on these measures. Methods: A review of the institutional cancer registry was performed to identify women with known nativity treated for epithelial ovarian cancer between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were done using chi-square, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at p < 0.05. Results: 529 women were included in the analysis, 248 CB and 281 US-born (USB). CB women were more likely to have residual disease after debulking surgery (31.2 vs. 16.8%, p = 0.009) and be treated at a public facility (62.5 vs. 33.5%, p < 0.001). Black CB women less frequently received chemotherapy compared to White CB women (55.2 vs. 82.2%, p = 0.001). Among all CB women, Hispanic ethnicity was independently associated with improved survival when adjusting for other factors (HR 0.61 [95% CI 0.39–0.95], p = 0.03). White Hispanic CB women had a median overall survival (OS) of 59 months while Black, non-Hispanic CB women had a median OS of 24 months (log-rank p = 0.04). Conclusion: Among Caribbean-born women with ovarian cancer, Hispanic ethnicity is significantly associated with improved survival outcomes, regardless of race

Abstract B098: Intra-Caribbean Island differences drive breast cancer outcomes in US Caribbean-immigrant women compared to US-born Black women

Abstract Introduction The Caribbean accounts for half of all foreign-born blacks in the USA. The biggest contributors to this immigrant population come from Cuba, Dominican Republic (DR), Jamaica, Haiti and Trinidad and Tobago. Breast cancer (BC) is the most commonly diagnosed cancer in US Black women and the second cancer related cause of death. Breast cancer in the most common cause of death of native Caribbean women. In our previous work, we found that Caribbean immigrants with breast had a better overall survival than US born Blacks. The primary objective of this study was to investigate the etiology and outcomes within the most populace Caribbean born immigrants compared to US born Black women within our cohort. Methods Data were obtained from Jackson Memorial Health Systems and University of Miami Health System Tumor Registry. Data from 1,082 Black patients were used to estimate hazard rations (HRs) of women born in Haiti, Jamaica, Bahamas, Cuba, Dominican Republic or the US born (USB) using Cox proportional hazards regression analysis for overall survival. Clinicopathologic and treatment characteristics of women from each island were compared to USB using Chi Squared testing and independent sample t-test. Results The sub-cohort contained data from Haitian (250), Jamaican (89), Bahamian (43), Dominican (38), Cuban (38) and 624 USB women. Compared to USB (57.6 years), of all the sub-groups the Bahamians were the youngest (50.5 years, P <0.001) and presented at the highest advanced stage in the cohort (54.3% vs USB 35.3%; P=0.02). Cubans (26.5%), Jamaicans (26.2%), and Haitians (25.8%) had a higher prevalence of HER2+ breast cancer in contrast to USB (17.7%), Bahamians (18.9%) and Dominicans (18.9%). Surgery was a favorable factor for survival in USB (aHR=0.26 (0.19-0.36), p<0.001), Bahamians (aHR=0.05 (0.01-0.47), p=0.008) and Jamaicans (aHR=0.08 (0.03-0.24), p<0.001). Haitian were the only immigrant group with a significant favorable outcome from radiation therapy (aHR=0.45, 95% 0.27-0.77; P=0.004). Cubans and Dominicans had a significant favorable response to surgery (aHR=0.25 (0.04-1.58), p=0.14) and radiation (aHR=0.48 (0.05-4.19), p=0.51) but did not reach statistical significance due to small sample size. Conclusion This data demonstrates and highlights intra-island and ethnic differences linked to clinicopathologic features of breast cancer in Black women living in the US. Further studies are needed to identify biological factors impacting the etiology and outcomes breast cancer in the immigrant Caribbean population and US born Black. Citation Format: Danielle A Cerbon, Matthew Schlumbrecht, Camille Ragin, Priscila Barreto-Coelho, Judith Hurley, Sophia HL George. Intra-Caribbean Island differences drive breast cancer outcomes in US Caribbean-immigrant women compared to US-born Black women [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B098

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

There are few studies that directly investigate disparities in outcome within the African diaspora in the US. We investigated the association between nativity of Black women diagnosed with breast cancer (Caribbean or USA place of birth) and ethnicity, age at diagnosis, treatment, tumor characteristics and outcome. The data were obtained from the University of Miami Health System, and Jackson Health System. Individual-level data from 1132 cases was used to estimate hazard rations (HRs) of women born in the Caribbean (Caribbean Blacks, CB) or in the USA (US Black, USB) using Cox proportional hazards regression analysis for overall survival. The cohort contains data from 624 (54.9%) USB women and 507 (45%) CB women diagnosed with breast cancer between 2006 and 2017. Compared to CB patients, USB patients had more Estrogen Receptor negative (31.4% vs. 39.1%, P = 0.018) and triple negative breast cancers (19.6% vs. 27.9%, P = 0.003). CB women presented at more advanced stages III/IV (44.2% vs. 35.2%; P = 0.016). CB patients showed a better overall survival (hazard ratio, HR = 0.75; 95% CI 0.59-0.96; P = 0.024). Overall Black Hispanic patients had a better overall survival (HR = 0.51; 95% CI 0.28-0.93; P = 0.028) compared to non-Hispanic Black patients. In conclusion the study found that CB immigrants diagnosed with breast cancer have an improved overall survival when compared with USB patients. This finding suggests that within the African diaspora in the USA, additional factors beyond race contribute to worse outcomes in African Americans

The Genetic Paradigm of Hereditary Breast and Ovarian Cancer (HBOC) in the Afro-Caribbean Population

Differences in tumor biology and genetic predisposition have been suggested as factors influencing overall survival and increased mortality in Black breast and ovarian cancer patients. Therefore, it is key to evaluate genetic susceptibilities in Afro-Caribbean patients because the black population in the US is not homogeneous. Identifying a high incidence of hereditary breast and ovarian cancer (HBOC) in Afro-Caribbean countries can lead to understanding the pattern of inherited traits in US-Caribbean immigrants and their subsequent generations. The paucity of projects studying the genetic landscape in these populations makes it difficult to design studies aimed at optimizing screening and prophylaxis strategies, which in turn, improve survival and mortality rates. This scoping review identifies and categorizes current research on the genetic paradigm of HBOC in the Afro-Caribbean population. We performed an evaluation of the evidence and generated a summary of findings according to preferred reporting items for systematic review and meta-analysis (PRISMA) Extension for Scoping Reviews guidelines. We included articles that assessed the incidence and prevalence of pathologic germline mutations and experience/barriers for genetic testing in Afro-Caribbean Countries and US-Caribbean patients. Our results highlight countries where genetic landscapes remain severely understudied and support recommending multigene testing in Caribbean-born patients. They highlight a need for further research on the genetic paradigm of HBOC in the Afro-Caribbean population to improve genetic testing/counseling and the subsequent adoption of early detection and risk reduction strategies

Post-Mastectomy Implant Complications in the Hispanic Breast Cancer Patient Population

BACKGROUND/AIMThe purpose was to analyze the impact of post-mastectomy radiation therapy (PMRT) on implant-based breast reconstruction (IBR) in self-identified Hispanic patients compared to non-Hispanic counterparts.PATIENTS AND METHODSWe retrospectively reviewed patients who underwent IBR between January 1, 2017 and December 31, 2019 at a single hospital system. Patients were cisgender women, assigned female at birth, 18 years or older, and underwent mastectomy with immediate IBR +/- PMRT. We compared characteristics between Hispanic and non-Hispanic patients, assessing capsular contracture and implant loss rates. Multivariable analysis was performed to identify factors associated with complications.RESULTSA total of 317 patients underwent mastectomy and reconstruction. Of these patients, 302 underwent a total of 467 mastectomies with IBR, and these 467 procedures were included in the analysis of complications. Complications occurred in 175 breasts (37.5%), regardless of PMRT. Seventy-two of the 302 patients (24%) received PMRT to one breast. The overall rates of capsular contracture, implant loss, and overall complications did not vary significantly between Hispanic and non-Hispanic patients (p=0.866, 0.974, and 0.761, respectively). When comparing only irradiated patients, there was a trend towards increased implant loss and overall complication rates in Hispanic versus non-Hispanic patients (p=0.107 and 0.113, respectively). Following PMRT the rate of any complication was 71% in Hispanic women and 53% in non-Hispanic women.CONCLUSIONOur study illuminates a trend towards higher complication rates after PMRT in Hispanic versus non-Hispanic patients. Further studies are needed to understand why Hispanic patients may have more side effects from radiation therapy