Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.

BACKGROUND: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM). OBJECTIVES: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM. METHODS: This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS). RESULTS: In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02). CONCLUSIONS: Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.

A paradigm shift in understanding vulvovaginal melanoma as a distinct tumor type compared with cutaneous melanoma.

OBJECTIVE: Our goal was to compare molecular and immune profiles of vulvovaginal melanoma (VVM) with cutaneous melanoma (CM) and explore the significance of immune checkpoint inhibitor (ICI) agents on survival. METHODS: Samples from VVM and CM tumors underwent comprehensive molecular and immune profiling. Treatment and survival data were extracted from insurance claims data and OS was calculated from time of ICI treatment to last contact. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons. RESULTS: Molecular analysis was performed on 142 VVM and 3823 CM tumors. VVM demonstrated significantly (q < 0·01) less frequent BRAF and more frequent KIT, ATRX, and SF3B1 mutations. Alterations in pathways involving DNA damage and mRNA splicing were more common in VVM, while alterations in cell cycle and chromatin remodeling were less common. Immunogenicity of VVM was lower than CM, with an absence of high TMB (0% vs 46.9%) and lower PD-L1 positivity (18·0% vs 29·5%). Median immune checkpoint gene expression was lower in VVM, as were cell fractions for type I macrophages and CD8+ T-cells(q < 0·01). Myeloid dendritic cells were increased in VVM(q < 0·01). Median OS was shorter for VVM than for CM patients treated with ICIs (17·6 versus 37·9 months, HR:1·65 (95% CI 1·02-2·67) p = 0·04). CONCLUSIONS: VVM has a distinct molecular and immune profile compared to CM, which may contribute to the worse survival in VVM compared to CM patients treated with ICI therapy. Though ICIs have been a mainstay of treatment in recent years, our findings suggest that new therapeutic strategies are needed.

Influence of Anatomic Locations of T1b Melanomas and Patient Age on Outcomes.

BACKGROUND: There are no guidelines on when to more strongly recommend sentinel lymph node biopsy (SLNB) for T1b melanomas. OBJECTIVE: To examine whether anatomic locations of T1b melanomas and patient age influence metastases. METHODS: We conducted a retrospective study using data from two hospitals in Los Angeles County from January 2010 through January 2020. RESULTS: Out of 620 patients with primary melanomas, 566 melanomas were staged based on the American Joint Committee on Cancer 8th edition melanoma staging. Forty-one were T1b, of which 13 were located on the face/ear/scalp and 28 were located elsewhere. T1b melanomas located on the face/ear/scalp had an increased risk of lymph node or distant metastasis compared with other anatomic sites (31% vs 3.6%, P=0.028). For all melanomas, the risk of lymph node or distant metastasis decreased with age of 64 years or greater (P<0.001 and P=0.034). For T1b melanomas, the risk of distant metastasis increased with increasing age (P=0.047). LIMITATIONS: Data were from a single county.  Conclusion: T1b melanomas of the face/ear/scalp demonstrated a higher risk of lymph node or distant metastasis and may help guide the recommendation of SLNB, imaging, and surveillance. Younger patients may be more strongly considered for SLNB and older patients with T1b melanomas may warrant imaging.  J Drugs Dermatol. 2024;23(5):306-310. doi:10.36849/JDD.7667.

Disparities in nonmelanoma skin cancer in Hispanic/Latino patients based on Mohs micrographic surgery defect size: A multicenter retrospective study.

BACKGROUND: There is limited literature regarding potential disparities in nonmelanoma skin cancer for patients with skin of color. OBJECTIVE: Use the sizes of Mohs micrographic surgery defects to examine disparities in nonmelanoma skin cancer among Hispanic/Latino patients with a secondary aim to examine the effect of insurance type. METHODS: We conducted a multicenter retrospective study using data from 3 major institutions in Los Angeles County. A total of 3486 Mohs micrographic surgeries of basal cell, squamous cell, and basosquamous cell carcinomas were analyzed. RESULTS: Mohs micrographic surgery defect sizes were 17% larger among Hispanic/Latino patients compared with non-Hispanic White patients. More notably, when comparing defect sizes of squamous cell carcinomas to those of basal cell carcinomas, defects were 80% larger among Hispanic/Latino patients compared to non-Hispanic White patients who had 25% larger defect sizes. Compared to patients with Medicare, patients with health maintenance organization and Medicaid/health maintenance organization had 22% and 52% larger defect sizes, respectively, whereas patients with preferred provider organization, had 10% smaller defect sizes. LIMITATIONS: The data included were from a single county population. CONCLUSION: Disparities regarding nonmelanoma skin cancer exist between patients with skin of color and White patients. Patients and the medical community need to be cognizant that skin cancer can develop in patients regardless of their race and ethnicity.

COVID-19 Outcomes of Patients With Differentiated Thyroid Cancer: A Multicenter Los Angeles Cohort Study.

OBJECTIVE: Cancer may be a risk factor for worse outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infections. However, there is a significant variability across cancer types in the extent of disease burden and modalities of cancer treatment that may impact morbidity and mortality from coronavirus disease-19 (COVID-19). Therefore, we evaluated COVID-19 outcomes in patients with a differentiated thyroid cancer (DTC) history. METHODS: This is a retrospective cohort study of patients with a history of DTC and SARS-CoV2 infection from 2 academic Los Angeles healthcare systems. Demographic, thyroid cancer, and treatment data were analyzed for associations with COVID-19 outcomes. RESULTS: Of 21 patients with DTC and COVID-19, 8 (38.1%) were hospitalized and 2 (9.5%) died from COVID-19. Thyroid cancer initial disease burden and extent, treatment, or current response to therapy (eg, excellent vs incomplete) were not associated with COVID-19 severity in DTC patients. However, older age and the presence of a comorbidity other than DTC were significantly associated with COVID-19 hospitalization (P = .047 and P = .024, respectively). COVID-19-attributed hospitalization and mortality in DTC patients was lower than that previously reported in cancer patients, although similar to patients with nonthyroid malignancies in these centers. CONCLUSION: These data suggest that among patients with DTC, advanced age and comorbid conditions are significant contributors to the risk of hospitalization from SARS-CoV2 infection, rather than factors associated with thyroid cancer diagnosis, treatment, or disease burden. This multicenter report of clinical outcomes provides additional data to providers to inform DTC patients regarding their risk of COVID-19.

Prevalence and correlates of adherence to skin examination among adolescent and young adult survivors of melanoma from the Project Forward Study.

BACKGROUND: Melanoma is a common cancer among adolescents and young adults (AYAs), yet adherence to recommended surveillance and factors related to adherence are not well understood in this population. This study assessed the prevalence and correlates of physician-conducted skin examination (PSE) and skin self-examination (SSE) among AYA-aged long-term survivors of melanoma. PROCEDURES: Melanoma cases were identified from the Los Angeles County cancer registry and surveys were then completed by 128 respondents diagnosed between the ages 0 and 24, with stage 1 melanoma or higher, at least 5 years from diagnosis, and who were between the ages 18 and 39 at the time of survey. RESULTS: Eighty-two percent of AYA melanoma survivors reported SSE within the past 6 months, while 65% reported annual PSE. Greater health care self-efficacy was positively associated with adherence to PSE, SSE, and both types of skin examinations (P < .01). Higher socioeconomic status and having a regular source of primary health care were positively associated with annual PSE and adherence to both surveillance practices (P < .05 and P < .01, respectively). Hispanic ethnicity was negatively associated with annual PSE compared to non-Hispanics (P < .01), and greater depressive symptoms were negatively associated with adherence to both skin examinations (P < .05). CONCLUSIONS: High rates of SSE were observed, but PSE adherence was lower than optimal in this sample. Interventions to improve PSE are needed for at-risk AYA survivors of melanoma, and strategies that help melanoma survivors navigate the health care system and access primary care may facilitate greater adherence.

Clinicopathologic comparison of basal cell carcinoma among a diverse patient population in Los Angeles County.

Introduction: Basal cell carcinoma (BCC) is the most common malignancy in the United States. The majority of cases are identified in Non-Hispanic Whites (NHW) and are far less demonstrated in patients of colour (POC). However, the Hispanic population represents a large and growing proportion of the US population, and skin cancer diagnoses in Hispanics are rising. Thus, the goal of this study is to examine clinicopathologic differences between BCC in Hispanics versus NHW. Methods: A retrospective chart review of Hispanic and NHW patients with BCC at Los Angeles County + USC Medical Center from January 2018 to March 2020 was performed. In total, 101 BCC samples from the first 100 patients identified of Hispanic ancestry, as well as 50 BCC samples identified from the first 50 patients identifying as NHW, were included for analysis. Patient characteristics (age, sex, medical history, and ethnicity), as well as tumour characteristics (location, subtype, tumour depth, and perineural invasion), were collected. We used between subjects t-tests for continuous variables, and chi-square tests for categorical variables. Results: In total, 151 specimens were collected amongst 122 subjects (79 Hispanics and 43 NHW patients). Among NHW, the majority of patients (74.4%) were men, but among the Hispanic population, the majority (68.4%) were female (p < 0.001). Prior history of other skin cancer was more common among NHW (67.4%) than Hispanics (31.6%) (p=<0.001). The Hispanic population had a significantly higher proportion of head and neck tumours (p = 0.0004) but a lower proportion of extremity tumours (p = 0.001) compared to NHW. Pigmented BCC was significantly more common among Hispanic patients (p < 0.01). Finally, within the Hispanic group, there was a significant association between sex and histology (p = 0.004), with Hispanic men demonstrating more aggressive mix histology compared to Hispanic women. Discussion: Our study supports the notion that BCC disparities occur among POC compared to NHW. This includes variations in epidemiologic factors such as sex and past medical history, primary tumour location, and pathologic characteristics. Further research should be conducted to identify additional differences in skin cancer presentation in POC to reduce the gaps in skin cancer knowledge and care.

Innate and adaptive immune cell interaction drives inflammasome activation and hepatocyte apoptosis in murine liver injury from immune checkpoint inhibitors.

Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on these tolerogenic mechanisms, and their disruption with ICI use can trigger the unintended side effect of hepatotoxicity termed immune-mediated liver injury from ICIs (ILICI). Learning how to uncouple ILICI from ICI anti-tumor activity is of paramount clinical importance. We developed a murine model to recapitulate human ILICI using CTLA4+/- mice treated with either combined anti-CTLA4 + anti-PDL1 or IgG1 + IgG2. We tested two forms of antisense oligonucleotides to knockdown caspase-3 in a total liver (parenchymal and non-parenchymal cells) or in a hepatocyte-specific manner. We also employed imaging mass cytometry (IMC), a powerful multiplex modality for immunophenotyping and cell interaction analysis in our model. ICI-treated mice had significant evidence of liver injury. We detected cleaved caspase-3 (cC3), indicating apoptosis was occurring, as well as Nod-like receptor protein 3 (NLRP3) inflammasome activation, but no necroptosis. Total liver knockdown of caspase-3 worsened liver injury, and induced further inflammasome activation, and Gasdermin-D-mediated pyroptosis. Hepatocyte-specific knockdown of caspase-3 reduced liver injury and NLRP3 inflammasome activation. IMC-generated single-cell data for 77,692 cells was used to identify 22 unique phenotypic clusters. Spatial analysis revealed that cC3+ hepatocytes had significantly closer interactions with macrophages, Kupffer cells, and NLRP3hi myeloid cells than other cell types. We also observed zones of three-way interaction between cC3+ hepatocytes, CD8 + T-cells, and macrophages. Our work is the first to identify hepatocyte apoptosis and NLRP3 inflammasome activation as drivers of ILICI. Furthermore, we report that the interplay between adaptive and innate immune cells is critical to hepatocyte apoptosis and ILICI.

Ancestry and somatic profile predict acral melanoma origin and prognosis.

Acral melanoma, which is not ultraviolet (UV)-associated, is the most common type of melanoma in several low- and middle-income countries including Mexico. Latin American samples are significantly underrepresented in global cancer genomics studies, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures. To address this, here we characterise the genome and transcriptome of 128 acral melanoma tumours from 96 Mexican patients, a population notable because of its genetic admixture. Compared with other studies of melanoma, we found fewer frequent mutations in classical driver genes such as BRAF, NRAS or NF1. While most patients had predominantly Amerindian genetic ancestry, those with higher European ancestry had increased frequency of BRAF mutations and a lower number of structural variants. These BRAF-mutated tumours have a transcriptional profile similar to cutaneous non-volar melanocytes, suggesting that acral melanomas in these patients may arise from a distinct cell of origin compared to other tumours arising in these locations. KIT mutations were found in a subset of these tumours, and transcriptional profiling defined three expression clusters; these characteristics were associated with overall survival. We highlight novel low-frequency drivers, such as SPHKAP, which correlate with a distinct genomic profile and clinical characteristics. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.

Safety and efficacy of immune checkpoint inhibitor cancer therapy in patients with preexisting type 1 diabetes mellitus.

Introduction: Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM. Methods: This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class. Results: Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy. Discussion: These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.

Intraocular Spread of Ocular Surface Squamous Neoplasia Presenting as a Postoperative Anterior Chamber Opacity after Excisional Biopsy.

We describe a rare case of ocular surface squamous neoplasia (OSSN) with intraocular spread after excisional biopsy which presented as a postoperative anterior chamber (A/C) opacity, initially thought to be a hypopyon. A 60-year-old female with history of a right (OD) conjunctival mass involving the cornea, surgically excised and diagnosed as OSSN, presented 2 months postoperatively with an A/C opacity concerning for infection. The patient was prescribed prednisolone acetate and ofloxacin drops postoperatively; topical chemotherapy was not given. When the opacity did not respond to 3 weeks of topical treatment, they were referred to an ocular oncologist for management. Intraoperative records from biopsy were unavailable; use of cryotherapy is unknown. On presentation, the patient had reduced vision OD. On slit-lamp exam, a white plaque in the A/C was seen, obscuring the iris. Given concern for postoperative intraocular cancer spread and extent of disease, enucleation with extended conjunctival excision was done. Gross pathology revealed an A/C mass with a diffuse hazy membrane. Histopathology diagnosed moderately differentiated OSSN with extensive intraocular invasion; a full-thickness limbal defect was visualized. Disease was confined to the globe, without residual conjunctival malignancy. This case emphasizes the importance of taking surgical precaution when excising conjunctival lesions, especially large lesions which obscure ocular anatomy, to maintain scleral integrity and Bowman's layer with limbal lesions. Intraoperative cryotherapy and postoperative chemotherapy should also be employed. If a patient with history of ocular surface malignancy displays symptoms concerning postoperative infection, this case highlights the importance of considering invasive disease.

Prevalence and correlates of skin examination among ethnically diverse young adult survivors of childhood cancer.

BACKGROUND: Skin cancer is the most common secondary malignancy among young adult childhood cancer survivors (YA-CCS). Skin examination to detect skin cancer early (including melanoma as well as basal or squamous cell skin cancers), both physician-based (PSE) and self-skin exam (SSE), is recommended, particularly for radiotherapy-exposed YA-CCS who are at high risk of developing skin cancer. METHODS: Awareness and prevalence of skin examination and demographic, clinical, and healthcare correlates were examined in a population-based sample of YA-CCS with diverse cancer types excluding melanoma. Descriptive frequencies and logistic regression models were conducted using sample weights to correct for non-response bias with PSE, SSE and adherence to both as outcomes. RESULTS: The sample comprised 1064 participants with 53% Latino. Eight percent of participants were aware of the need for skin examination; 9% reported receipt of PSE within past 2 years; 35% reported regular SSE; and 6% were adherent to both. Among the radiotherapy-treated, 10% were aware of the need for skin examination, 10% reported recent PSE; 38% reported regular SSE; and 8% were adherent to both. Healthcare and clinical factors including healthcare self-efficacy, engagement in cancer-related follow-up care, greater treatment intensity and greater number of treatment-related late effects were positively associated with PSE and SSE. Latino YA-CCS were less likely to engage in PSE and SSE. CONCLUSION(S): Adherence to recommended screening for skin cancer was low in this at-risk population, notably for YA-CCS exposed to radiotherapy. The development of effective strategies to expand skin cancer screening is needed in this at-risk population.

Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases.

Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.

Social networks of oncology clinicians as a means for increasing survivorship clinic referral.

Background: Specialized cancer survivorship clinics are recommended for addressing treatment-related health concerns of long-term survivors, but their relative newness in medical oncology necessitates strategies to expand services and clinic referrals. This study used social network analysis to identify personal and/or network factors associated with referral of patients to a survivorship clinic. Methods: We conducted a cross-sectional social network survey of clinical personnel at a National Cancer Institute-designated comprehensive cancer center. Participants identified colleagues with whom they consult for advice (advice network) and/or discuss patient care (discussion network). Exponential random graph models and logistic regression were used to identify key opinion leaders in the network and factors associated with referral of patients to the center's survivorship clinic. Results: Here we show that of the respondents (n = 69), 78.0% report being aware of the survivorship clinic, yet only 30.4% had ever referred patients to it. Individuals tend to associate with others in the same occupational role (homophily). In the discussion network, holding an influential network position (betweenness centrality) is associated with patient referral to the survivorship clinic. In the advice network, several social workers are identified as opinion leaders. Conclusions: This study shows that there is strong homophily in both networks, potentially inhibiting information sharing between groups. In designing an inclusive network intervention, persons occupying influential network positions and opinion leaders (e.g., social workers in this case) are well-positioned to promote survivorship clinic referrals.

Factors Associated With Hospitalization Among Breast Cancer Patients With COVID-19: A Diverse Multi-Center Los Angeles Cohort Study.

BACKGROUND: The SARS-CoV-2 virus has infected and killed millions of people worldwide. Breast cancer is the most prevalent cancer in women and few studies have investigated the outcomes of patients with a history of breast cancer and COVID-19. We report the clinical outcomes of patients with invasive breast cancer who tested positive for SARS-CoV-2, including hospitalization and death, and evaluate demographic and cancer-related factors associated with these outcomes. PATIENTS: Patients with a history of invasive breast cancer and positive SARS-CoV-2 test from January 1 to December 31, 2020 at two large, academic Los Angeles health systems were included. METHODS: Retrospective chart review of the electronic medical record was performed. Data for demographic and cancer-related factors were manually abstracted. Relationships between outcomes and clinical variables were evaluated using Fisher's exact test and linear regression analysis. RESULTS: Among a total of 132 patients, 40 (30.3%) were hospitalized, while 11 (8.3%) required intensive care support, and 8 patients (6.1%) died. Older age and presence of one or more additional comorbidities were associated with hospitalization and death (P = .010, P = .003, P = .034, P < .001). Hispanic/Latinx ethnicity was associated with hospitalization (P = .047). Cancer treatment was not associated with hospitalization or death. CONCLUSION: In our diverse, multi-center, breast cancer cohort, Hispanic/Latinx ethnicity, older age and presence of other comorbidities were associated with worse outcomes from COVID-19. Breast cancer treatment, including surgery, radiation, systemic therapy, and endocrine therapy, was not associated with hospitalization in our cohort. Further studies are needed to explore the relationship between breast cancer and COVID-19 outcomes.

Transcriptional Profiling of Malignant Melanoma Reveals Novel and Potentially Targetable Gene Fusions.

Invasive melanoma is the deadliest type of skin cancer, with 101,110 expected cases to be diagnosed in 2021. Recurrent BRAF and NRAS mutations are well documented in melanoma. Biologic implications of gene fusions and the efficacy of therapeutically targeting them remains unknown. Retrospective review of patient samples that underwent next-generation sequencing of the exons of 592 cancer-relevant genes and whole transcriptome sequencing for the detection of gene fusion events and gene expression profiling. Expression of PDL1 and ERK1/2 was assessed by immunohistochemistry (IHC). There were 33 (2.6%) cases with oncogenic fusions (14 novel), involving BRAF, RAF1, PRKCA, TERT, AXL, and FGFR3. MAPK pathway-associated genes were over-expressed in BRAF and RAF1 fusion-positive tumors in absence of other driver alterations. Increased expression in tumors with PRKCA and TERT fusions was concurrent with MAPK pathway alterations. For a subset of samples with available tissue, increased phosphorylation of ERK1/2 was observed in BRAF, RAF1, and PRKCA fusion-positive tumors. Oncogenic gene fusions are associated with transcriptional activation of the MAPK pathway, suggesting they could be therapeutic targets with available inhibitors. Additional analyses to fully characterize the oncogenic effects of these fusions may support biomarker driven clinical trials.