Introduction Ilio-obturator lymphadenectomy (IOL) is used in the treatment of stage III melanoma. IOL can be performed using a conventional open approach, minimally invasive transperitoneal or extraperitoneal approach. IOL is traditionally combined with inguinal lymphadenectomy (IL). From 2010–2024, open IOL (O-IOL) was standard in our hospital. The first laparoscopic transperitoneal IOL (LT-IOL) for stage III melanoma we performed in our hospital, had a detrimental outcome. This prompted us to review our complications after O-IOL. The aim of this study is to assess surgical complication rates and safety of O-IOL when combined with IL.Methods This was a single-center retrospective case series on O-IOL with concurrent IL. Primary outcome measures were complication rates and severity, readmissions and surgical reinterventions. Secondary outcome measures were technique for surgical approach, unplanned visits and oncological outcome.Results Between 2010 and 2024, 11 patients underwent O-IOL combined with IL. One patient (9.1%) developed a surgical site infection after O-IOL, which was treated with antibiotics and outpatient wound debridement. No other complications were observed. All patients developed complications related to concurrent IL.Conclusions O-IOL using a Rutherford-Morrison incision for the retroperitoneal approach shows low complication rates in this case series. In our described case, combining LT-IOL with IL resulted in a disastrous outcome.
BACKGROUND:Although evidence suggests disparities in melanoma treatment, no comprehensive summary exists on whether insurance type, race/ethnicity, or socioeconomic status consistently influence systemic therapy receipt. Understanding these associations may inform strategies to reduce inequities. METHODS:We conducted a systematic review of United States (US) based studies assessing systemic therapy receipt by insurance, socioeconomic status, and race/ethnicity. Searches of PubMed, Embase, and Web of Science were performed through July 10, 2025. Evidence quality was evaluated using the Oxford Center for Evidence-Based Medicine. RESULTS:Of 6,604 records screened and 223 full-texts reviewed, 30 retrospective cohort studies were included, encompassing 1,212,437 melanoma patients (1975-2021). Twenty-five studies stratified by insurance, 24 by socioeconomic status, and 21 by race/ethnicity. Insurance-based disparities were reported in 88% of studies, socioeconomic status-based disparities were reported in 75% of studies, and race/ethnicity- based disparities were reported in 38% of studies. Although 67% of studies used the National Cancer Database, findings were inconsistent across studies. CONCLUSION:Insurance and socioeconomic status may be more consistent drivers of disparities in systemic therapy receipt for melanoma than race/ethnicity. However, variability in identifying disparities, even among studies using the same database, may complicate targeted interventions.
Poly (ADP-ribose) polymerase inhibitors (PARPi) have shown efficacy in treating cancers with homologous recombination deficiency (HRD), including subsets of melanoma. However, the potential synergy between PARPi and standard melanoma therapies remains understudied. Here, we report two cases of advanced metastatic melanoma refractory to standard-of-care treatment that demonstrated durable partial responses following the addition of PARPi in combination with immune checkpoint inhibitors (ICIs) and BRAF/MEK inhibitors. Both patients exhibited homologous recombination repair (HRR) pathway mutations and tolerated the combinatory regimens well, achieving progression-free survival of more than 11 months. Mechanistically, PARPi may enhance immunogenicity to ICI therapy via activation of the cyclic GMP-AMP synthase-stimulator of interferon (cGAS-STING) pathway and modulation of programmed death ligand 1 (PD-L1) expression. Preclinical studies also support synergism between PARPi and BRAF/MEK-targeted therapies. This report highlights the potential for PARPi to be integrated into advanced melanoma treatment, particularly in HRD tumors and in combination with ICI and targeted therapies. Although limited by the small sample size, our findings support the rationale for ongoing clinical trials evaluating PARPi-based combinations and underscore the need for further studies to clarify the optimal sequencing and combinations of therapy.
BACKGROUND:Vemurafenib (Zelboraf®, Roche), approved by the FDA in 2011 for unresectable and metastatic melanoma and Erdheim-Chester Disease, has been explored in trials for other BRAF-mutated cancers. Despite 12 years of clinical use, the risk-benefit profile for off-label indications remain unclear. RESEARCH DESIGN AND METHODS:This study systematically reviewed clinical trials utilizing vemurafenib in adult malignancies, with responses assessed using RECIST or similar criteria. On May 25, 2023, we searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. Screening and data extraction were performed in a masked, duplicate fashion, collecting data on trial characteristics, adverse events, progression-free survival, overall survival, and objective response rates. RESULTS:Vemurafenib was tested in 15 cancers beyond its FDA-approved indications. A 0% complete response rate was observed in colorectal cancer, non-small cell lung cancer, and papillary thyroid cancer. Adverse events were more frequent in non-melanoma cancers, with 5,205 grade 3-5 events reported, equating to two severe events for every three participants. Only metastatic melanoma consistently demonstrated efficacy, aligning with its FDA approval. CONCLUSIONS:Although vemurafenib showed efficacy in metastatic melanoma, off-label use resulted in limited benefit and increased adverse events. Unclear endpoints and underreported adverse events highlight the need for improved clinical trial design.
