Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

Patient experiences with tobacco use during substance use disorder treatment and early recovery: a mixed method analysis of phone interview responses.

Tobacco use and related mortality remain disproportionately high among individuals with substance use disorders (SUDs). Though engagement in tobacco cessation interventions is associated with improved long-term recovery, many individuals in SUD treatment do not participate. The goal of the present study was to better understand patient views regarding tobacco use/cessation during residential SUD treatment, in order to decrease barriers for this vulnerable population. This study utilized a cross-sectional design and mixed methods analysis. Following discharge from residential SUD treatment, individuals who reported any use of tobacco were invited to participate in a brief phone interview. Forty-one of the 60 who were reached (68%) agreed to participate. Responses were quantified for analysis when appropriate, and descriptive statistics were calculated for quantitative data. Thematic analysis was used to analyze qualitative responses. Most respondents (83%) reported that tobacco cessation was an important goal and were open to tobacco cessation treatment. The vast majority (85%) did not think tobacco use interfered with their recovery from other SUDs. Respondents noted the socially-reinforcing nature of tobacco use in treatment, and indicated a desire for increased access to cessation services. Results suggest increased patient education and changes to treatment center tobacco policies may assist individuals recovering from SUD with tobacco cessation.

Secondary hemophagocytic lymphohistiocytosis due to Heartland virus.

An older man from the mid-Southeastern USA presented with acute onset of fever, fatigue, and non-bloody diarrhoea. There was high suspicion for tick-borne illness given exposure history, clinical presentation and laboratory abnormalities. Despite prompt treatment with doxycycline, the patient clinically worsened. He was diagnosed with secondary hemophagocytic lymphohistiocytosis (HLH) due to Heartland virus (HRTV). This is the second documented case of secondary HLH due to HRTV, and the first in a relatively immunocompetent patient. Furthermore, though HRTV has been primarily concentrated in the Central USA, our case provides evidence of further geographic expansion of HRTV, mirroring the increased range of the Lone Star tick. Clinicians should consider HRTV when a patient with a clinical presentation consistent with tick-borne illness fails to respond to doxycycline. Furthermore, healthcare providers should be aware of the geographic expansion of HRTV and the potential of HRTV to lead to secondary HLH.

Anti-MuSK-Positive Myasthenic Crisis in a 7-Year-Old Female.

A seven-year-old African American female with anti-MuSK-positive Juvenile Myasthenia Gravis collapsed while at school from progressively worsening weakness and dyspnea. On initial emergency department presentation, she required 15 liters per minute of supplemental oxygen to maintain oxygen saturation above 92%. Initial pulmonary function tests and venous blood gas led to the decision to place her on noninvasive positive pressure ventilation (NPPV) with BiPAP in the emergency department. Due to worsening hypercarbia, she later required mechanical intubation in the PICU and underwent IVIG therapy followed by plasmapheresis in order to achieve a stable discharge from the hospital. A respiratory virus panel PCR was positive for influenza A, influenza B, and rhinovirus, likely precipitating the respiratory failure and myasthenic crisis in this seven-year-old patient. Given the rarity of this condition, this case report is to provide further education to the clinician managing severe, prepubertal Juvenile Myasthenia Gravis and myasthenic crisis.