Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities.

Importance: Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date. Objective: To assess PD-L1 expression in treatment-naive and treated BCCs. Design, Setting, and Participants: This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016. Exposures: Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs. Main Outcomes and Measures: Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities. Results: Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P = .003) and TILs (47% vs 18%, P = .008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P = .007). Conclusions and Relevance: Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.

Estimation of individual cumulative ultraviolet exposure using a geographically-adjusted, openly-accessible tool.

BACKGROUND: Estimates of an individual's cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist. The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual's self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability. METHODS: A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case-control design. Reliability was assessed in a separate convenience sample. RESULTS: 1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 - 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n = 149) and controls (n = 298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p = 0.003) and (2) less engagement in UV protective behaviors (p < 0.01). In a multivariate analysis of age-matched data, individuals with CUES in the lowest quartile were less likely to develop skin cancer compared to those in the highest quartile. In reliability testing among 19 volunteers, the 2-week intra-class correlation coefficient for CUES was 0.94. We have provided the programming code for this tool as well as the tool itself via open access. CONCLUSIONS: CUES is a useable and comprehensive tool to better estimate lifetime ultraviolet exposure, so that individuals with higher levels of exposure may be identified for counseling on photo-protective measures.

Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to smoothened inhibitors.

IMPORTANCE: Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. OBSERVATIONS: A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. CONCLUSIONS AND RELEVANCE: We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

Two different scenarios of squamous cell carcinoma within advanced Basal cell carcinomas: cases illustrating the importance of serial biopsy during vismodegib usage.

IMPORTANCE: Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. OBSERVATIONS: The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. CONCLUSIONS AND RELEVANCE: These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

A pilot study examining food insecurity and HIV risk behaviors among individuals recently released from prison.

Annually 700,000 individuals are released from U.S. prison, many at risk for food insecurity and HIV. The association between food insecurity and HIV risk behaviors has been established but not in this population. To investigate this association, we recruited 110 recently released prisoners to participate in a survey. Ninety-one percent of our sample was food insecure; 37% did not eat for an entire day in the past month. Those who did not eat for an entire day were more likely to report using alcohol, heroin, or cocaine before sex or exchanging sex for money compared to those who had at least a meal each day. From this pilot study, released prisoners appear to be at risk for food insecurity, and not eating for an entire day is associated with certain HIV risk behaviors. HIV prevention efforts should include longitudinal studies on the relationship between food insecurity and HIV risk behaviors among recently released prisoners.