Transforming Clinical Trials in Skin Cancer Research: Exploring the Potential of Flexible and Innovative Designs.
Abstract Over the past 2 decades, innovations in trial design have significantly advanced the field of clinical research. Methodological developments, such as adaptive designs, basket trials, umbrella trials, and platform trials, along with technological advancements such as virtual studies have proven effective in tackling complex research questions and managing resource constraints. These approaches enable prospectively planned modifications to trial designs and facilitate addressing multiple research questions within a single infrastructure, with technological advancements such as virtual studies enhancing accessibility, efficiency, and patient engagement. These designs can also integrate biomarker information or risk-prediction scores to enhance the efficacy of future [...]
Characterizing Chronic Cutaneous Immune-Related Adverse Events Following Immune Checkpoint Inhibitors.
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Association of inherited genetic variants with multiple primary melanoma.
Abstract Background: Recent genome-wide association studies (GWAS) have identified new susceptibility loci for melanoma, but their associations with multiple primary melanoma (MPM) are unclear. Methods: We investigated the associations of 69 single nucleotide polymorphisms (SNPs) in 39 GWAS-identified loci with odds of MPM relative to single primary melanoma (SPM) in the international, population-based Genes, Environment, and Melanoma (GEM) study. Per-minor allele odds ratios (ORs) and 95% confidence intervals (CIs) for individuals with MPM 'cases' (n=1,205) relative to SPM 'controls' (n=2,458) were estimated using multivariable logistic regression, and polygenic risk scores (PRS) were calculated and weighted based on a 2020 GWAS meta-analysis [...]
Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced BRAF-V600E/K mutated melanoma (EBIN): an international randomized phase II study.
Abstract Background: Current first-line treatment for patients with metastatic melanoma with BRAFV600E or BRAFV600K mutations includes immunotherapy with immune checkpoint inhibitors and targeted therapy; however, the optimal sequencing of these treatments is unclear. We aimed to investigate the use of a targeted-therapy induction regimen before treatment with immune checkpoint inhibitors. Methods: This open-label, randomised, controlled, phase 2 trial (EBIN) was conducted at 37 centres in eight European countries. Eligible patients were 18 years or older and had previously untreated, unresectable, stage III or IV melanoma with BRAFV600E or BRAFV600K mutations and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly [...]
Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study.
Abstract Background: Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. Methods: This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results: Among 110 pts, median age [...]
FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.
Abstract Background: Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS). Methods: Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid [...]
Single-Cell Multi-Omics: Insights into Therapeutic Innovations to Advance Treatment in Cancer.
Abstract Advances in single-cell multi-omics technologies have deepened our understanding of cancer biology by integrating genomic, transcriptomic, epigenomic, and proteomic data at single-cell resolution. These single-cell multi-omics technologies provide unprecedented insights into tumour heterogeneity, tumour microenvironment, and mechanisms of therapeutic resistance, enabling the development of precision medicine strategies. The emerging field of single-cell multi-omics in genomic medicine has improved patient outcomes. However, most clinical applications still depend on bulk genomic approaches, which fail to directly capture the genomic variations driving cellular heterogeneity. In this review, we explore the common single-cell multi-omics platforms and discuss key analytical steps for data [...]
Incarcerated lateral inguinal hernia following ilioinguinal lymph node dissection: an unusual case.
Abstract Penile squamous cell carcinoma (SCC) spreads predictably from primary tumour to inguinal lymph nodes then pelvic nodes and finally, to distant sites. Inguinal dissection involves resection of all femoral and inguinal nodes and is part of the recommended management. Femoral hernias are a commonly reported consequence of these extensive dissections. This case describes an unusual hernia which developed lateral to the femoral vessels. A 68 year old man presented with penile SCC of the distal glans penis and underwent bilateral ilioinguinal node dissections for nodal recurrence. On post operative day 1, the patient developed abdominal distention and obstipation. [...]
Timing of nivolumab with neoadjuvant carboplatin and paclitaxel for early triple-negative breast cancer (BCT1902/IBCSG 61-20; Neo-N): a non-comparative, open-label, randomised, phase 2 trial.
Abstract Background: The optimal scheduling of PD-1 inhibitors with neoadjuvant chemotherapy in patients with early triple-negative breast cancer is unknown. We aimed to investigate the activity of two differing schedules of neoadjuvant nivolumab initiation with 12 weeks of carboplatin and paclitaxel for this patient population. Methods: Neo-N is an investigator-initiated, non-comparative, open-label, randomised, phase 2 trial conducted at 12 hospitals in Australia, one in New Zealand, and one in Italy. Participants had to be aged 18 years or older; have an Eastern Cooperative Oncology Group performance status of 0-1, clinical stage I (cT1cN0) or II (cT1cN1, cT2cN0-1, or cT3cN0), oestrogen receptor [...]