Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Neoadjuvant cemiplimab and surgery for stage II-IV cutaneous squamous-cell carcinoma: follow-up and survival outcomes of a single-arm, multicentre, phase 2 study.

BACKGROUND: We previously reported rates of pathological complete responses (51% [95% CI 39-62] per independent central review, the primary endpoint) and major pathological responses (13% per independent central review, a secondary endpoint) to neoadjuvant cemiplimab (an anti-PD-1 inhibitor) among 79 patients with locoregionally advanced, resectable cutaneous squamous cell carcinoma. Here, we present follow-up data, including event-free, disease-free, and overall survival. METHODS: This single-arm, multicentre, phase 2 study included patients aged 18 years or older with resectable stage II-IV (M0) cutaneous squamous cell carcinoma and Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received up to four planned doses of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by curative-intent surgery. After surgery, per investigator discretion, patients received either adjuvant cemiplimab for up to 48 weeks, radiotherapy, or observation alone. Secondary endpoints included in this follow-up analysis are event-free survival, disease-free survival, and overall survival, all summarised using the Kaplan-Meier method. Activity and safety endpoints were analysed for all enrolled patients who received at least one dose of neoadjuvant cemiplimab. In this report, safety data are reported for all patients who received at least one dose of adjuvant cemiplimab. This trial is registered with ClinicalTrials.gov, NCT04154943, has completed enrolment and follow-up is ongoing. FINDINGS: Between March 20, 2020, and July 8, 2021, 79 patients were enrolled. Median age was 73 years (IQR 66-81), 67 (85%) patients were male, 12 (15%) were female, 69 (87%) were White, one was Asian (1%), one was other race (1%), and race was not reported for eight (10%). As of data cutoff (Dec 1, 2022), median follow-up was 18·7 months (IQR 15·6-22·1) for all 79 patients. Among 70 patients who had surgery, 65 (93%) had post-surgical management data: 32 (49%) of 65 were observed postoperatively, 16 (25%) received adjuvant cemiplimab, and 17 (26%) received adjuvant radiotherapy. 11 (14%) of 79 patients had event-free survival events, with an estimated 12-month event-free survival of 89% (95% CI 79-94) for all patients. None of 40 patients who had a pathological complete response and one (10%) of ten patients with major pathological response had recurrence. Six (9%) of 70 patients who completed surgery had a disease-free survival event, with an estimated 12-month disease-free survival of 92% (95% CI 82-97). Nine (11%) of 79 patients died, with an estimated 12-month overall survival for all patients of 92% (95% CI 83-96). Four (25%) of 16 patients who received adjuvant cemiplimab treatment had grade 3 adverse events, including one (6%) who had increased blood potassium, one (6%) who had traumatic limb amputation, and two who had serious adverse events (one [6%] cardiomyopathy and one [6%] hypophysitis). There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: For patients with resectable stage II-IV cutaneous squamous cell carcinoma, neoadjuvant cemiplimab followed by surgery might be a potential treatment option, addressing a substantial unmet need. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Opioid Prescribing Recommendations After Mohs Micrographic Surgery and Reconstruction: A Delphi Consensus.

BACKGROUND: Prescription opioids play a large role in the opioid epidemic. Even short-term prescriptions provided postoperatively can lead to dependence. OBJECTIVE: To provide opioid prescription recommendations after Mohs micrographic surgery (MMS) and reconstruction. METHODS: This was a multi-institutional Delphi consensus study consisting of a panel of members of the American College of Mohs Surgery from various practice settings. Participants were first asked to describe scenarios in which they prescribe opioids at various frequencies. These scenarios then underwent 2 Delphi ratings rounds that aimed to identify situations in which opioid prescriptions should, or should not, be routinely prescribed. Consensus was set at ≥80% agreement. Prescription recommendations were then distributed to the panelists for feedback and approval. RESULTS: Twenty-three Mohs surgeons participated in the study. There was no scenario in which consensus was met to routinely provide an opioid prescription. However, there were several scenarios in which consensus were met to not routinely prescribe an opioid. CONCLUSION: Opioids should not be routinely prescribed to every patient undergoing MMS. Prescription recommendations for opioids after MMS and reconstruction may decrease the exposure to these drugs and help combat the opioid epidemic.

Effectiveness of the Mohs and Close Technique in Increasing the Efficiency of a Mohs Micrographic Surgery.

Editor's note: JDD welcomes Letters to the Editor that discuss controversy surrounding a recently published article. Letters being considered for publication may be sent to the authors of the original article, who may be given the opportunity to reply. Letters will be published at the discretion of the Editors.

The Pharmacological Frontier in Pediatric Heart Failure Management: Innovations and Prospects.

Pediatric heart failure, encompassing a diverse range of conditions, imposes a significant burden despite its relatively low incidence. The contemporary landscape, with infants constituting a majority of admissions, underscores the need for specialized attention. This editorial delves into the evolving pharmacological interventions for pediatric heart failure, emphasizing the nuances of managing congenital heart defects, genetic factors, and diverse etiologies. The goal is to contribute knowledge that addresses the unique needs of children and explores innovations promising to redefine care standards. The narrative navigates through the current state of pediatric heart failure management, unique considerations, emerging pharmacological innovations, precision medicine, addressing underlying causes, combination therapies, clinical trials, and ethical considerations. Each section contributes to a comprehensive understanding of the evolving landscape and sets the stage for potential future directions in pediatric heart failure care.

Across Time: A Chronological Progression of Clinical Trials in India.

The journey of clinical research in India spans centuries, marked by significant milestones and advancements in scientific, ethical, and regulatory domains. From early trials conducted by pioneers like James Lind to modern standards shaped by landmark events such as the Nuremberg Code and the adoption of Good Clinical Practice guidelines, India's progression reflects a commitment to ethical conduct and patient welfare. The Indian Council of Medical Research (ICMR) has played a pivotal role in this evolution, establishing national research centers and ethical committees to oversee biomedical research. Regulatory frameworks, exemplified by Schedule Y of the Drugs and Cosmetics Act, have adapted over time to align with global standards, facilitating India's integration into the international clinical development landscape. Despite challenges and setbacks, including misconceptions surrounding regulatory reforms, India's clinical trial ecosystem continues to evolve, driven by a dedication to ethical research practices and excellence in healthcare.

A Growing Concern: The Prevalence of Self-Medication in Pediatric Healthcare in India.

Self-medication, the practice of using medications without a valid prescription based on self-diagnosed symptoms, has become a global phenomenon, with a significant presence in developing nations like India. This inclination often arises from the desire to reduce healthcare costs and save time, though it carries inherent risks, including serious adverse effects and the potential masking of chronic disease symptoms. In India, the prevalence of self-medication varies widely, with factors such as media-driven advertisements, positive attitudes, and financial constraints contributing to its adoption, especially among lower- and middle-income families. The pediatric population in India is witnessing a notable increase in self-medication practices, driven by a mix of affordability, convenience, and limited awareness among parents. The risks associated with self-medication in pediatric healthcare are diverse, posing threats to developing immune systems and metabolisms in children. Antibiotic misuse further exacerbates concerns about antibiotic resistance, a global health crisis. Understanding the root causes of self-medication, including restricted healthcare access and societal pressures, is crucial for developing effective interventions. To address this issue comprehensively, a multifaceted approach is essential, emphasizing the need for widespread educational initiatives targeting healthcare literacy. Concurrently, reinforcing regulatory measures to monitor over-the-counter medication sales and conducting public awareness campaigns can deter unauthorized dispensing and promote responsible healthcare practices. Collaborative efforts involving healthcare providers, government bodies, pharmaceutical companies, and educational institutions are imperative to champion policies prioritizing children's health. It is a collective responsibility to ensure access to proper healthcare as an inherent right for every child in India. Urgent action is necessary to address the rising prevalence of self-medication, securing the well-being of the younger generation and paving the way for a healthier and more resilient future.

Immunomodulators for Non-Melanoma Skin Cancers: Updated Perspectives.

Non-melanoma skin cancers (NMSCs) are the most common cancers worldwide and may be associated with significant morbidity and mortality, especially in immunosuppressed populations. Successful management of NMSC must take primary, secondary and tertiary prevention strategies into consideration. In response to an improved understanding of the pathophysiology of NMSC and associated risk factors, multiple systemic and topical immunomodulatory drugs have been developed and integrated into clinical practice. Many of these drugs are efficacious in the prevention and treatment of precursor lesions (actinic keratoses; AKs), low-risk NMSC, and advanced disease. The identification of patients at high risk for the development of NMSC is critical in reducing disease morbidity. Understanding the various treatment options available and their comparative effectiveness is paramount for developing a personalized treatment regimen for such patients. This review article provides an updated overview of the various topical and systemic immunomodulatory drugs available for the prevention and treatment of NMSC, and the published data supporting their use in clinical practice.

Advances in Topical Treatments of Cutaneous Malignancies.

Surgical excision has been the preferred treatment for cutaneous malignancies, but can be affected by various considerations. Noninvasive, self-administered topical treatments represent an alternative option. The aim of this review was to evaluate and summarize evidence-based recommendations for topical treatments of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (CSCC), in situ melanoma (MIS), and extramammary Paget's disease (EMPD). Studies were reviewed on PubMed. Included studies were summarized, assessed for biases, and assigned a level of evidence to develop treatment recommendations. For the treatment of superficial BCC, complete clearance rates ranged from 90 to 93% for 5% 5-fluorouracil (5-FU) and 71 to 76% for imiquimod (IMQ). For the treatment of nodular BCC, clearance rates for photodynamic therapy (PDT) were 91% at 3 months, with a sustained lesion clearance response rate of 76% after 5 years of follow-up. Clearance rates were 53 to 76% with IMQ. For squamous cell carcinoma in situ, clearance rates ranged from 52 to 98% for PDT, 67 to 92% for 5-FU, and 75 to 93% for IMQ. For MIS, clearance rates ranged from 53 to 92% for IMQ. For EMPD, 54% of 110 patients in cohort studies and case series had a clinical complete response with IMQ. While surgical intervention remains the standard of care for skin cancer, non-invasive, self-administered topical treatments are highly desirable alternative options. Ultimately, the patient and provider should find a treatment modality that aligns with the patient's expectations and maintenance of quality of life.

Risk factors of sepsis and prevalence of multidrug-resistant organisms in pediatric cardiac surgery in tertiary care teaching rural hospital in India: A retrospective observational study.

Background and aims: Cardiac surgery and cardiopulmonary bypass result in an immunoparalyzed state in children making them susceptible to sepsis and other hospital-acquired infections. Therefore, identification of the risk factors of sepsis would lead to appropriate management. The current study seeks to evaluate the prevalence of sepsis and risk factors linked to sepsis in pediatric cardiac surgical patients and the subsequent prevalence of multidrug-resistant organisms. Methods: A retrospective, single-center observational study was conducted including 100 pediatric patients admitted to the pediatric intensive care unit (ICU) after cardiac surgery between January 2017 and February 2018. All patient data were obtained from the medical record department of the hospital. Patient case report form comprised demography, surgery details, preoperative and postoperative hematological reports, and clinical details. After collecting the data, chi-square test and logistic regression analysis were used to determine the risk factors linked to sepsis. Results: The prevalence of sepsis in our population was 27% and the mortality rate due to sepsis was 1%. The only statistically significant risk factor for sepsis we discovered in this analysis was prolonged ICU stay for more than 5 days. A total of eight patients had blood cultures positive for bacterial infection. The alarming finding was that all eight were infected with multidrug-resistant organisms, demanding the last line of antibacterials. Conclusion: Our study indicates that special clinical care is required when ICU stay is prolonged to lower the risk of sepsis. These new and upcoming infections not only promote high mortality and morbidity rates but also contribute to increased cost of care due to the use of newer broad-spectrum antibiotics and longer hospital stay. The high prevalence of multidrug-resistant organisms is unacceptable in the current scenario and hospital infection and prevention control play a crucial role in minimizing such infections.