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.

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.

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.

Enhanced Neuroprotective Synergy of Atorvastatin and Magnesium L-Threonate in a Rat Model of Alzheimer's Disease Induced by Aluminum Chloride.

INTRODUCTION: Alzheimer's disease (AD) is a widespread neurodegenerative condition with complex causes and a significant global impact, particularly among the elderly. This brief introduction emphasizes AD's hallmark features and the urgent public health concern it poses, with numbers on the rise. It also highlights the potential of statins and magnesium L-threonate as a combined therapeutic approach to prevent AD and mitigate its underlying pathological features. The study's goal is to shed light on these promising interventions in a rat model induced by aluminum chloride (AlCl3). MATERIALS AND METHODS: A total of 30 aged female Wistar rats were divided into five groups (n=6/group). The vehicle control group received normal saline orally (p.o.).The model control group received AlCl3(4.2 mg/kg/day intraperitoneal (i.p.)). The standard-treated group received rivastigmine (1 mg/kg/day p.o.), and the atorvastatin-treated and atorvastatin with magnesium L-threonate-treated groups received atorvastatin (20 mg/kg/day p.o.) and atorvastatin (20 mg/kg/day) with magnesium L-threonate (604 mg/kg/day p.o.), respectively. Cognitive functions such as radial arm maze, elevated plus maze (EPM), passive shock avoidance test, and open-field test (OFT) were performed at weekly intervals up to 28 days. After completion of the study on the 29th day, all animals were sacrificed, and the brain was used for estimation of AchE enzyme activity, oxidative stress parameters, and histopathological analysis. RESULT: At the end of the fourth week, administration of atorvastatin and atorvastatin with magnesium L-threonate resulted in a decreased average time taken to reach the correct arm, reduced transfer latency (TL) in the EPM, shortened latency to reach the shock-free zone (SFZ), and an increase in rearing and counts by locomotion activity in the OFT. It also demonstrated improved anti-cholinesterase activity and suppressed oxidative stress, as indicated by a decrease in nitric oxide (NO) levels and an increase in superoxide dismutase (SOD) and catalase levels. Additionally, it led to reductions in brain changes observed in histopathological analysis. CONCLUSION: Atorvastatin with magnesium L-threonate provides a better beneficial protective effect against AD than atorvastatin alone. This combination can be a first choice for patients who are already taking atorvastatin in the early stages of AD.

Enduring Efficacy and Clinical Outcomes of Combined Palliative Chemotherapy With Gefitinib, Methotrexate, and Cyclophosphamide in Advanced Oral Cancer: A 3.5-Year Case Study of Carcinoma in the Buccal Mucosa and Hard Palate.

This case report outlines the diagnostic and treatment experience of a 50-year-old male diagnosed with moderately differentiated squamous cell carcinoma (SCC) in the right lower alveolus. It underscores the challenges of oral squamous cell carcinoma (OSCC) diagnosis and management, emphasizing the need for comprehensive multidisciplinary approaches. The patient's initial presentation with persistent mandibular pain highlighted the complexities of diagnosing oral and maxillofacial pathologies. A detailed clinical examination revealed unique ulceroproliferative growth, showcasing the importance of meticulous clinical assessment. Histopathological confirmation solidified the diagnosis. Treatment involved surgery, adjuvant radiotherapy, and concurrent chemotherapy. Post-chemotherapy, the patient responded positively, underlining treatment efficacy. Transitioning to oral chemotherapy demonstrated adaptability. Vigilant follow-up, exemplified by detecting non-healing ulcers and erosions, is crucial for early intervention. This case informs oral squamous cell carcinoma management. Integrated therapy's success underscores the value of combining surgery, chemotherapy, and radiotherapy. The patient's response to gefitinib, cyclophosphamide, and methotrexate suggests promise for targeted therapies. Patient-centered care, interdisciplinary collaboration, and adaptability are vital. This case report illustrates oral squamous cell carcinoma eradication through multidimensional treatment. The patient's journey highlights accurate diagnosis, adaptable therapy, and vigilant follow-up. It informs the field and fosters further research and innovation.

Antibiotic Utilization and Prophylaxis in Paediatric Cardiac Surgery: A Retrospective Observational Study at a Rural Tertiary Care Hospital in India.

Introduction Antimicrobial prophylaxis, involving short antibiotic courses preceding surgical procedures, is recommended to minimize postoperative infections. Paediatric cardiac surgeries are classified as clean procedures, though infection challenges persist due to illness severity and extended ICU stays. Antimicrobial prophylaxis varies, ranging from single doses to extended administration until catheters are removed. Typically lasting 24 to 48 hours, it has proven infection-reduction benefits. Despite these practices, uncertainties surround the optimal nature, timing, and duration of administration. This concern is amplified by escalating antimicrobial resistance driven by antibiotic overuse. Vulnerable paediatric populations bear heightened consequences of irrational antimicrobial use, contributing to global resistance trends. Yet, a defined optimal prophylaxis schedule for paediatric cardiac surgery is lacking. Importing adult guidelines may be inadequate due to paediatric research complexities and population diversity. Developing effective prophylaxis protocols is crucial for children undergoing cardiac surgery, given global antibiotic overuse and evolving drug resistance. Establishing an optimal prophylactic strategy remains a challenge, necessitating further research for evidence-based protocols to mitigate infections in this vulnerable patient cohort. Methods This study investigates antibiotic use in paediatric cardiac surgery. A retrospective analysis of 100 patients from a rural Indian hospital (2017-2018) assesses antibiotic patterns, including type, dose, duration, and adherence to prophylaxis protocols. Results In the studied cohort of paediatric cardiac surgery patients, complete compliance (100%) with antibiotic prophylaxis was observed. However, deviations were identified: 30% received antibiotics prematurely, and 30% did not align with institutional protocol criteria. Concerning antibiotic selection, 87% followed hospital policy with the recommended cefoperazone and sulbactam combination plus amikacin, while 9% received piperacillin/tazobactam + amikacin due to sepsis. Irregular use (22%) based on clinical records occurred. Furthermore, 4% received piperacillin/tazobactam + teicoplanin, with one instance of inappropriate higher antibiotic use. Regarding prophylaxis duration, only 27% adhered to the appropriate timeline, with 40% exceeding 48 hours, indicating extended use. Upon discharge, a notable proportion (45 patients) received antibiotic prescriptions. Among them, 73% were prescribed rationally, while 27% exhibited irrational antibiotic use. Conclusion The findings of this study shed a significant light on the issue of antibiotic misuse within the context of paediatric cardiac surgery. It underscores the pressing need for more stringent measures to regulate and address this concerning trend. The study underscores the pivotal importance of adhering rigorously to established protocols and guidelines for antibiotic prophylaxis. This adherence not only holds the potential to elevate the overall quality of patient care but also plays a critical role in combating the escalating challenge of antibiotic resistance. Through a concerted effort to optimize antibiotic usage, we can simultaneously enhance patient outcomes and contribute to the ongoing fight against the emergence of antibiotic-resistant strains, thus preserving the efficacy of these vital medications for future generations.

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.

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.

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.

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.).

CD137 agonist potentiates the abscopal efficacy of nanoparticle-based photothermal therapy for melanoma.

Despite the promise of immunotherapy such as the immune checkpoint inhibitors (ICIs) anti-PD-1 and anti-CTLA-4 for advanced melanoma, only 26%-52% of patients respond, and many experience grade III/IV immune-related adverse events. Motivated by the need for an effective therapy for patients non-responsive to clinically approved ICIs, we have developed a novel nanoimmunotherapy that combines locally administered Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) with systemically administered agonistic anti-CD137 monoclonal antibody therapy (aCD137). PBNP-PTT was administered at various thermal doses to melanoma cells in vitro, and was combined with aCD137 in vivo to test treatment effects on melanoma tumor progression, animal survival, immunological protection against tumor rechallenge, and hepatotoxicity. When administered at a melanoma-specific thermal dose, PBNP-PTT elicits immunogenic cell death (ICD) in melanoma cells and upregulates markers associated with antigen presentation and immune cell co-stimulation in vitro. Consequently, PBNP-PTT eliminates primary melanoma tumors in vivo, yielding long-term tumor-free survival. However, the antitumor immune effects generated by PBNP-PTT cannot eliminate secondary tumors, despite significantly slowing their growth. The addition of aCD137 enables significant abscopal efficacy and improvement of survival, functioning through activated dendritic cells and tumor-infiltrating CD8+ T cells, and generates CD4+ and CD8+ T cell memory that manifests in the rejection of tumor rechallenge, with no long-term hepatotoxicity. This study describes for the first time a novel and effective nanoimmunotherapy combination of PBNP-PTT with aCD137 mAb therapy for melanoma.

Cutaneous squamous cell carcinoma staging may influence management in users: A survey study.

PURPOSE: This study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease. MATERIALS AND METHODS: A survey regarding CSCC high-risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology. RESULTS: One hundred fifty-six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (>80%) as high-risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high-risk feature. Dermatologists were also more likely to utilize the Brigham and Women's Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post-operative radiation therapy, and increased follow-up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high-risk CSCC. CONCLUSION: This survey study highlights areas of consensus and differences regarding the definition of high-risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High-risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk-based management approach for CSCC.

The Merkel Cell Carcinoma Patient Registry: From Promise to Prototype to Patient.

The Merkel Cell Carcinoma (MCC) Patient Registry is a national multi-institutional collaborative effort that will prospectively follow and record outcomes and events in MCC patients. MCC is the prototypical rare tumor, and this Registry will trail blaze new methodologies that will enable multiple investigators to examine real world outcome data in real time. Deliverables from the Registry include precise patient stratification into risk categories, identification of best practices, real-world data for drug development programs, revelations about optimal sequence and combinations therapies, uncovering low incidence toxicities, and the generation of novel testable hypotheses. Importantly, the Registry offers a way forward in the yet-unsolved dilemma of drug development for rare tumors, since the Registry's design will allow the creation of highly defined patient-level data that can be used as a robust comparator for single arm phase I and II clinical trials. The MCC Task Force comprises members from academic medical centers, the drug industry, the National Institutes of Health, and the US Food and Drug Administration. Project Data Sphere, LLC provides a secure, open-access data sharing platform and comprehensive support to optimize research performance and ensure rigorous and timely results. The Registry is currently in development and is based on a REDCap database integrated into the host institution's electronic medical record. We plan to have the first patient accessioned on Project Data Sphere's data platform in the second quarter of 2022. Members of the MCC Registry Task Force represent a joint effort of research and clinical investigators from academia, industry and regulatory science to develop the first publicly held MCC registry on Project Data Sphere's open-access data platform. Our hope is that this shared repository will allow investigators to identify new approaches, improve treatment outcomes, shorten the time from discovery to implementation and, ultimately, improve patient lives.