Isolated Limb Infusion as First, Second, or Third or Later-Line Therapy for Metastatic In-Transit Melanoma.

BACKGROUND: Ten percent of patients with melanoma develop in-transit metastases (ITM). Isolated limb infusion (ILI) is a well-established therapy for unresectable ITM on the extremities, but the ideal sequencing/line of therapy of ILI has not been defined. This study evaluates ILI as first-line, second-line, or third or later-line therapy. METHODS: A retrospective review included all patients with unresectable ITM who underwent ILI from 2006-2023. RESULTS: A total of 130 patients were identified, 61% female, median age of 71 (31-89) years. Median follow-up was 37.5 months. ILI was first-line therapy in 80% (n = 104), second-line in 15% (n = 19), and third or later-line in 5.4% (n = 7). Overall response rate (ORR) and complete response (CR) rates for ILI as any line of therapy were 74% and 41%, respectively. ORR for ILI as first, second, or third or later-line therapy were 78%, 63%, and 57%, respectively. CR rates for ILI as first, second, or third or later-line therapy were 42%, 37%, and 43%, respectively. There were no significant differences in ORR, progression-free survival (PFS), overall survival, or disease-free survival between therapy lines. Median PFS for ILI as first, second, or third or later-line therapy were 6.9, 5.4, and 18 months, respectively. CONCLUSION: Patients responded well to ILI, whether or not they received previous therapies for unresectable ITM. First-line ILI appears to have a better ORR than later lines of ILI. Although sample size limited statistical significance, there was a 21% improvement in ORR when ILI was used as first-line vs third-line therapy, which is clinically meaningful. ILI is effective for unresectable melanoma ITM and can be used as salvage therapy.

Isolated limb infusion (ILI) is an excellent treatment option for patients with in-transit melanoma. In this study, patients responded notably well when ILI was used as first-line therapy, and also responded well when ILI was used as a salvage therapy.

Malignant Melanoma in the Groin Masquerading as a Vascular Tumour: A Rare Cytodiagnosis.

Malignant melanoma (MM) is an aggressive cutaneous neoplasm tending to metastasise anywhere within the body. It frequently metastasises to the draining lymph nodes. A distinct presentation of MM occurs when metastatic lesions appear in the regional lymph nodes, while the primary tumour remains clinically undetected. Fine needle aspiration cytology (FNAC) is highly sensitive, rapid, and cost-effective. The utility of the FNAC procedure is well established in the patient's diagnostic workup. However, the Indian data on the cytodiagnosis and cytomorphology of metastatic MM are very scarce. We submit a clinicopathological profile of a rare case in a 68-year-old male, where FNAC from an inguinal mass led to the diagnosis of metastatic MM, which mimicked clinically as a vascular tumour. The present case highlights MM's unusual clinical presentation and cytomorphological details through FNAC.

Comprehensive Literature Review on Melanoma of Unknown Primary Site Triggered by an Intriguing Case Report.

Melanoma is one of the most aggressive forms of skin cancer. While most melanomas have a discernible primary site, a small subset, approximately 3.2%, present as a metastatic disease without an identifiable primary origin, a condition known as melanoma of unknown primary (MUP). Unusual cases of primary melanoma have also been previously reported in the respiratory, gastrointestinal, and urogenital tracts. MUP typically is found in lymph nodes, subcutaneous sites, and visceral organs, with hypotheses about its origin including spontaneous primary tumor regression and ectopic melanocytes. MUP presents unique challenges in diagnosis and treatment due to the absence of a detectable primary tumor. Understanding its genetic and molecular features, epidemiology, prognostic factors, and treatment options is crucial for optimizing patient care and outcomes in this subset of melanoma patients. We conducted an extensive literature review triggered by a case report of a patient with suspected MUP. A 51-year-old woman was transferred from another hospital where an incision was performed for a suspected superinfected hematoma of the left thigh. Since the patient showed high leukocytosis and redness and swelling of the thigh, local debridement, drainage, and excisional biopsy of the tumor mass were performed in our unit in the emergency setting, and the tumor was taken for histopathology evaluation. Intraoperatively, the mass appeared nonspecific. The permanent histopathology report established a diagnosis of melanoma, with tumor proliferation also involving lymphoid tissue, and despite broad clinical and imagistic assessments, the primary melanoma could not be identified. Clinicians must be aware of the varied clinical manifestations of malignant melanoma, especially in cases of occult melanoma where the primary site is not evident.

Immunogenic cell death signatures from on-treatment tumor specimens predict immune checkpoint therapy response in metastatic melanoma.

Melanoma is a highly malignant form of skin cancer that typically originates from abnormal melanocytes. Despite significant advances in treating metastatic melanoma with immune checkpoint blockade (ICB) therapy, a substantial number of patients do not respond to this treatment and face risks of recurrence and metastasis. This study collected data from multiple datasets, including cohorts from Riaz et al., Gide et al., MGH, and Abril-Rodriguez et al., focusing on on-treatment samples during ICB therapy. We used the single-sample gene set enrichment analysis (ssGSEA) method to calculate immunogenic cell death scores (ICDS) and employed an elastic network algorithm to construct a model predicting ICB efficacy. By analyzing 18 ICD gene signatures, we identified 9 key ICD gene signatures that effectively predict ICB treatment response for on-treatment metastatic melanoma specimens. Results showed that patients with high ICD scores had significantly higher response rates to ICB therapy compared to those with low ICD scores. ROC analysis demonstrated that the AUC values for both the training and validation sets were around 0.8, indicating good predictive performance. Additionally, survival analysis revealed that patients with high ICD scores had longer progression-free survival (PFS). This study used an elastic network algorithm to identify 9 ICD gene signatures related to the immune response in metastatic melanoma. These gene features can not only predict the efficacy of ICB therapy but also provide references for clinical decision-making. The results indicate that ICD plays an important role in metastatic melanoma immunotherapy and that expressing ICD signatures can more accurately predict ICB treatment response and prognosis for on-treatment metastatic melanoma specimens, thus providing a basis for personalized treatment.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.

Despite advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors without an artificial extracellular scaffold. MBM SXOs were created by a novel protocol incorporating techniques for establishing glioma and cutaneous melanoma organoids. A BRAFV600K-mutant and BRAF-wildtype MBM sample were collected directly from the operating room. Organoids were cultured in an optimized culture medium without an artificial extracellular scaffold. Concurrently, matched patient-derived cell lines were created. Organoid growth was observed within 3-4 weeks, and MBM SXOs retained histological features of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, and strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF and MEK inhibitors. Further study using SXOs may improve the translational relevance of preclinical studies and enable the study of the metastatic melanoma tumor microenvironment.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

INTRODUCTION: Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. METHODS: A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. RESULTS: Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. CONCLUSIONS: GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Intrathecal anti-PD-1 treatment in metastatic melanoma patients with leptomeningeal disease (LMD): real-world data and evidence.

PURPOSE: Leptomeningeal disease (LMD) is a severe complication of melanoma with a very poor prognosis. Despite improved treatment strategies and prolonged survival, the incidence of LMD has increased over the past decade. This real-world study aims to evaluate the efficacy and safety of intrathecal anti-PD-1 treatment in melanoma patients with LMD. METHODS: Melanoma patients with LMD diagnosed by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology were treated with intrathecal infusions of nivolumab 20 mg once every 2 weeks (n = 5) or pembrolizumab 20 mg once every 3 weeks (n = 3), alongside systemic therapy. Patients received a median of 5.5 treatment cycles (range 2-9). Efficacy and safety analyses were performed on all treated patients. RESULTS: From June 2022 to February 2023, eight patients were treated, including four with cutaneous melanoma, two with acral melanoma, and two with primary leptomeningeal melanoma. All patients exhibited linear or small nodular enhancement of the leptomeninges on MRI. Four patients had concurrent parenchymal brain metastases. Tumor cells were identified in six patients by CSF cytology, and two patients underwent leptomeningeal biopsy for pathological diagnosis. According to the RANO-LM criteria, five patients responded to treatment with symptom improvement and reduction or disappearance of linear enhancement on MRI, while three patients developed progressive disease. With a median follow-up of 20.7 weeks (range 8.1-45.3 weeks), the median OS and median intracranial progression-free survival (IPFS) for intrathecal anti-PD-1 treatment were 21.1 and 16.1 weeks, respectively. All treatment-related adverse events were grade 1-2, including headache (grade 1, n = 1; grade 2, n = 2) and low back pain (grade 1, n = 1). CONCLUSIONS: In this real-world study, intrathecal anti-PD-1 treatment demonstrated potential clinical benefits and was well tolerated in metastatic melanoma patients with LMD.

Triple combination of vemurafenib, cobimetinib, and atezolizumab in real clinical practice in the Russian Federation: results of the A1 cohort of the ISABELLA study.

Background: Among several treatment options for BRAF-mutant metastatic melanoma, a combination of BRAF inhibitor, MEK inhibitor, and anti-PDL1 antibody seems to be a new emergent approach recently registered in the Russian Federation. It is still not clear which patient population benefits more from this simultaneous use of three drugs instead of its sequencing. Aim: This study aimed to evaluate patients' characteristics treated in real practice in 14 Russian regions by triple combination and to analyze their outcomes depending on biomarkers (PD-L1 expression). Methods: This was a part (cohort A1) of a prospective non-interventional study of clinical outcomes and biomarkers in patients with skin melanoma. Patients were included in cohort A1 if combination treatment with vemurafenib (vem) + cobimetinib (cobi) + atezolizumab (atezo) was initiated no earlier than 12 weeks (84 days) prior to written informed consent to participate in this study. The index event was the initiation of therapy with all three drugs vem + cobi + atezo (i.e., triple combination). The primary efficacy endpoint of the study was the 24-month overall survival (OS), defined as the time from the index date to the date of death from any cause. If the patient did not experience an event, the OS will be censored at the date of the last contact. Objective response rate (ORR), duration of response (DoR), and progression-free survival (PFS) in the Intention to treat (ITT) population, in biomarker positive population, and in population with brain metastases were also evaluated. Quality of life questionnaires were pre-planned by protocol if it was a part of routine practice. Adverse events were also collected. Results: Between March 2021 and May 2023, 59 patients were enrolled in 19 centers from 14 regions of Russia. Thirty-one of 59 (52.4%) patients had central nervous system metastases, and 18 of 31 (58.4%) were symptomatic. Forty of 59 patients (68%) received the triple combination as the first-line treatment. The median follow-up period was 16.83 [95% confidence interval (CI) 13.8-19.8] months. The mean duration of therapy with this regimen was 9.95 months (95% CI 7.48-13.8). ORR was 55.1%; progression as the best outcome was seen in 16.3%. The median DoR was 12.95 months (95% CI 11.0-14.8 months), with a median of 20.3 months (95% CI 9.1-31.5 months) when triple therapy was administered in the first-line treatment. In patients with brain metastases (N = 31), ORR was 45.1%; the median DoR was 12.95 (95% CI 11.0-14.8 months). The median PFS in the entire population was 13.6 months (95% CI 8.6-18.6); the 24-month PFS was 22%. The estimated median OS in the entire population was 15.8 months (95% CI NA); 24-month OS was 45% (95% CI 0.32-0.64). In multivariate Cox regression model, biomarkers of interest [lactate dehydrogenase, Programmed cell death ligand-1 (PD-L1)] did not have statistically significant impact on PFS, OS, or DoR probably due to high data missing rate. No unexpected adverse events were reported. Grades 3-4 AEs were seen in 23 of 59 patients (38%) with most common were skin and liver toxicity. Conclusion: Triple combination of atezolizumab, vemurafenib, and cobimetinib had proven its efficacy and tolerability in real settings. No impact of potential predictive biomarkers was seen (NCT05402059).

Is primary breast melanoma a true pathological entity? The argument against it.

Background: Previous studies have reported cases of primary melanoma of the breast parenchyma (PMBP), but the pathogenesis of this disease remains poorly understood. We review the presentation and outcomes of reported cases and provide detailed pathological analysis of four additional cases. Furthermore, we discuss potential theories regarding the pathogenesis of this clinical presentation. Results: We identified 29 published studies (n = 95 patients) and report four new cases (n = 99). Ninety-one (92 %) patients were female, with a median age of 50 years. Previous skin melanomas were reported by 56 % of patients, with the trunk being the most common location (32.7 %) followed by the upper extremities (20 %). The most common tumor location reported (n = 73) was the right (49 %) upper outer quadrant (56 %). The median time from skin melanoma diagnosis to the presence of a breast mass was 65 months (1-192). Nodal status at presentation was reported in n = 67 (68 %) patients. Of these, positive nodal metastases were seen in 40.3 %, while distant metastatic disease at presentation was reported in 30 % of patients. Surgery was performed in 66 %, being partial mastectomy (PM) the most common procedure in 82 %. Adjuvant therapy was described in 38 patients. The reported (n = 12) median survival was 11.5 (1-70) months. Conclusion: Melanomas identified in the breast parenchyma are likely the result of nodal or hematogenous spread from previously known or unknown melanomas, and should not be considered as PMBP. Management should be multidisciplinary, including surgical excision aimed at obtaining negative margins with lymphadenectomy of clinically positive nodes and neoadjuvant/adjuvant immunotherapy.

Metastatic melanoma: an unexpected cause of acute liver failure.

Acute liver failure secondary to metastatic melanoma is exceedingly rare with the literature limited to case reports. The disease itself presents with vague symptoms making diagnosis difficult without a high clinical suspicion. Further to this, the prognosis of acute liver failure secondary to metastatic melanoma is dismal. We present the case of a 59-year-old male with a distant history of previously excised cutaneous melanoma who presented to our institution with abdominal pain and liver enzyme derangement suggestive of acute hepatitis. Due to progressive derangement in liver function and cross-sectional imaging suggestive of an infiltrative cause, a left axillary lymph node was biopsied which demonstrated metastatic melanoma. The patient subsequently deteriorated into acute liver failure and despite acute treatment of his underlying metastatic melanoma died 17 days post initial presentation. This case highlights an uncommon cause of acute liver failure as well as the poor prognosis associated with acute liver failure secondary to metastatic melanoma.

A Combined Proteomic and Transcriptomic Signature Is Predictive of Response to Anti-PD-1 Treatment: A Retrospective Study in Metastatic Melanoma Patients.

Resistance biomarkers are needed to identify patients with advanced melanoma obtaining a response to ICI treatment and developing resistance later. We searched a combination of molecular signatures of response to ICIs in patients with metastatic melanoma. In a retrospective study on patients with metastatic melanoma treated with an anti-PD-1 agent carried out at Istituto Nazionale Tumori-IRCCS-Fondazione "G. Pascale", Naples, Italy. We integrated a whole proteome profiling of metastatic tissue with targeted transcriptomics. To assess the prognosis of patients according to groups of low and high risk, we used PFS and OS as outcomes. To identify the proteins and mRNAs gene signatures associated with the patient's response groups, the discriminant analysis for sparse data performed via partial least squares procedure was performed. Tissue samples from 22 patients were analyzed. A combined protein and gene signature associated with poorer response to ICI immunotherapy in terms of PFS and OS was identified. The PFS and OS Kaplan-Meier curves were significantly better for patients with high expression of the protein signature compared to patients with low expression of the protein signature and who were high-risk (Protein: HR = 0.023, 95% CI: 0.003-0.213; p < 0.0001. Gene: HR = 0.053, 95% CI: 0.011-0.260; p < 0.0001). The Kaplan-Meier curves showed that patients with low-risk gene signatures had better PFS (HR = 0 0.221, 95% CI: 0.071-0.68; p = 0.007) and OS (HR = 0.186, 95% CI: 0.05-0.695; p = 0.005). The proteomic and transcriptomic combined analysis was significantly associated with the outcomes of the anti-PD-1 treatment with a better predictive value compared to a single signature. All the patients with low expression of protein and gene signatures had progression within 6 months of treatment (median PFS = 3 months, 95% CI: 2-3), with a significant difference vs. the low-risk group (median PFS = not reached; p < 0.0001), and significantly poorer survival (OS = 9 months, 95% CI: 5-9) compared to patients with high expression of protein and gene signatures (median OS = not reached; p < 0.0001). We propose a combined proteomic and transcriptomic signature, including genes involved in pro-tumorigenic pathways, thereby identifying patients with reduced probability of response to immunotherapy with ICIs for metastatic melanoma.

Real-World Cardiotoxicity in Metastatic Melanoma Patients Treated with Encorafenib and Binimetinib.

Modern therapies targeting the BRAF gene mutation in advanced melanoma have significantly improved patient outcomes but pose cardiovascular risks. This retrospective study in Eastern Denmark (2019-2022) assessed 108 melanoma patients treated with encorafenib and binimetinib. Patients were monitored for heart function using multigated acquisition (MUGA) scans. The study defined major cardiotoxicity as a decline in left ventricular ejection fraction (LVEF) by more than 10 percentage points to below 50%, and minor cardiotoxicity as a decrease in LVEF by more than 15 points but remaining above 50%. Results showed that 19 patients (18%) developed minor cardiotoxicity and were asymptomatic, while 7 (6%) experienced major cardiotoxicity, with two requiring intervention. Notably, no significant declines in LVEF were observed after six months of treatment. The study concluded that significant cardiotoxicity occurred in 6% of cases, mostly asymptomatic and reversible, and suggests that monitoring LVEF could potentially be reduced after 6-9 months if no early signs of cardiotoxicity are detected. This provides valuable insights into the cardiac safety of these treatments in real-world settings.

Prognostic Role of Clinicopathological Characteristics and Serum Markers in Metastatic Melanoma Patients Treated with BRAF and MEK Inhibitors.

Prognostic studies can provide important information about disease biology and improve the use of biomarkers to optimize treatment decisions. METHODS: A total of 199 patients with advanced melanoma treated with BRAF + MEK inhibitors were included in our single-center retrospective study. We analyzed the risk of progression and death using multivariate Cox proportional hazard models. The predictive effect of prognostic factors on progression-free survival (PFS) was evaluated in ROC analysis. RESULTS: We found that primary tumor localization, Clark level, pT category, baseline M stage and baseline serum S100B are independent and significant prognostic factors for PFS. The discriminative power of the combination of these factors was excellent for predicting 18 month PFS (AUC 0.822 [95% CI 0.727; 0.916], p < 0.001). Primary tumor localization on the extremities, Clark level V, baseline M1c stage or M1d stage, and elevated baseline serum S100B and LDH levels were independently and significantly associated with unfavorable overall survival (OS). CONCLUSION: Baseline M stage and serum S100B appear to be independent prognostic factors for both PFS and OS in melanoma patients treated with BRAF + MEK inhibitors. We newly identified significant and independent prognostic effects of primary tumor localization and Clark level on survival that warrant further investigation.

Immunotherapy and transarterial embolization in patients with metastatic melanoma: a retrospective cohort study.

Aim: To investigate how the sequence of checkpoint immunotherapy (CPI) and transarterial embolization (TAE) affects overall survival (OS) of patients with metastatic melanoma.Materials & methods: This retrospective cohort study included 65 patients with metastatic melanoma who underwent both TAE and CPI between September 2011 and January 2022.Results: Significantly higher OS was seen in patients who received CPI before and after embolization (22 months, 95% CI 14-NR, p < 0.001) compared with only before embolization (4.5 months 95% CI, 14-NR). ≤3 hepatic metastasis (p < 0.01), more TAE procedures (p < 0.001) and CPI sequence (before and after embolization) (p < 0.001) were independent predictors of survival.Conclusion: Metastatic melanoma patients who underwent TAE have longer survival when CPI was sequenced both before and after embolization.

This study looked at how the order of two treatments, called checkpoint immunotherapy (CPI) and transarterial embolization (TAE), affects how long people with metastatic melanoma live. Sixty-five patients who had both treatments between September 2011 and January 2022 took part in the study. Patients with fewer than three liver metastases, cancer in just one part of the liver, and who had more TAE treatments tended to live longer. Patients who got CPI both before and after TAE lived longer compared with those who only got CPI before TAE.

A Complete Response in a Metastatic Melanoma Patient After a Single Dose of Dual Checkpoint Inhibitors Blockade Could Be Predictable: A Case Report.

Cutaneous malignant melanoma is one of the most aggressive forms of skin cancer and thus, a high mortality has been reported over decades. The prognosis for melanoma varies widely based on several factors, including the stage at which it is diagnosed, the location and thickness of the tumor, the patient's age and overall health, and specific genetic factors associated with melanoma. Therapeutic options include checkpoint inhibitors, regardless of V-Raf Murine Sarcoma Viral Oncogene Homolog B status (BRAF), and targeted therapy (anti-BRAF) in the adjuvant or metastatic setting. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but predicting which patients will benefit from these therapies remains challenging. Biomarkers like leukocytes, neutrophils, eosinophils, basophils, platelets, and other peripheral blood biomarkers have been investigated for their potential to predict responses to ICIs. Tumor mutational burden (TMB), circulating tumor DNA (ctDNA), and soluble PD-L1 (sPD-L1) have emerged as potential biomarkers for predicting responses to ICIs. Elevated baseline levels of ctDNA and elevated sPD-L1 levels have been associated with worse prognosis in melanoma patients. High TMB is often associated with better responses to ICIs in melanoma. Here we present a case from our department, of a 57-year-old patient, diagnosed in 2019 with stage IV - pT4cNx cM1 (lymph nodes metastases) and suspicion of lung metastases, BRAF wild-type right hallux malignant melanoma. Due to impressive results, first-line treatment with ICIs nivolumab and ipilimumab was the preferred treatment of choice, which showed a favorable response, with regression of oncological disease after the first cycle, and achieving complete response afterward. Unfortunately, the treatment was discontinued due to severe hepatic and pancreatic toxicity, but the favorable response to immunotherapy has been maintained for four years and is ongoing. Identifying predictive biomarkers is important to achieve the best response for the patient, with minimal adverse events, especially if long-term clinical benefit can be reached.

Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.

Symptomatic aseptic sinusitis induced by immune checkpoint inhibitors for metastatic melanoma treatment.

Immune-mediated sinusitis is poorly described and may easily go undiagnosed. We conducted a retrospective, multicenter, national study focusing on symptomatic immune-mediated sinusitis in patients receiving immune checkpoint inhibitors (ICIs) for melanoma treatment. Twelve patients were included (50% women, median age 58 years). Overall, the paraclinical assessment, the inefficacy of antibiotic/antihistaminic treatment, the improvement of symptoms on immunosuppressants and/or after ICI discontinuation, and the presence of multiple concomitant immune-related adverse-events, suggested a noninfectious etiology. Recognizing this toxicity is imperative for limitation of diagnostic wandering and appropriate treatment. However, additional epidemiological studies are needed to assess its prevalence as a potential immune-related adverse-event, and its prognostic value in patients treated with ICIs.

Immunotherapy is a type of cancer treatment that enhances the immune system's natural ability to target cancer cells. This immune response can sometimes become overstimulated or misdirected, causing side effects, known as immune-related adverse-events (IrAEs). IrAEs involving the nasal sinuses are rarely reported and often overlooked by medical oncologists. Herein, we report a series of twelve patients presenting a symptomatic sinusitis, occurring during immunotherapy for advanced melanoma. Our study shows that sinusitis, is an often-overlooked IrAE, that can become invalidating for patients, and even impair immunotherapy continuation. Therefore, recognizing this toxicity is crucial for appropriate patient care.

Primary Dermal Melanoma: A Rare Subtype of Melanoma and Clinical Mimicker of Basal Cell Carcinoma.

Primary dermal melanoma (PDM) is a rare variant of melanoma. We present the case of a 76-year-old female diagnosed with PDM following initial suspicion of basal cell carcinoma, prompting extensive workup to exclude metastasis. This case demonstrates the diagnostic challenges and need for rigorous evaluation in suspected PDM cases. Current literature lacks definitive diagnostic markers for PDM, and we highlight the ongoing need for research and collaborative efforts between dermatology and oncology.

The Role of Surgery for Stage IV Melanoma.

Historically, stage IV melanoma carried a dismal prognosis and surgical resection was the only potential treatment offering long-term survival or palliation of symptomatic disease. With modern systemic therapies that can provide durable disease control for many patients with metastatic disease, we are actively redefining the role of surgery in metastatic melanoma. Contemporary treatment strategies can employ surgical resection in the upfront setting followed by adjuvant therapy, or used in tailored approach following systemic therapy. The combination of surgical resection and modern therapies has been associated with good long-term survival.