Clinical benefit with tebentafusp in a patient with GNAQ mutant metastatic blue nevus-associated melanoma.

Melanoma arising in association with a blue nevus (BN) is rare but has molecular similarities to uveal melanoma (UM), including GNAQ/11 mutations. Tebentafusp was recently approved for UM based on improved overall survival in a phase 3 study. We hypothesized that tebentafusp may be active in BN-associated melanoma.

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

To investigate how the sequence of checkpoint immunotherapy (CPI) and transarterial embolization (TAE) affects overall survival (OS) of patients with metastatic melanoma. This retrospective cohort study included 65 patients with metastatic melanoma who underwent both TAE and CPI between September 2011 and January 2022. Significantly higher OS was seen in patients who received CPI before and after embolization (22 months, 95% CI 14-NR,  < 0.

A phase II randomized trial of talimogene laherparepvec oncolytic immunotherapy with or without radiotherapy for patients with cutaneous metastases from solid tumors.

Background: Cutaneous metastases (CMs) are a manifestation of advanced cancer and can be treated with oncolytic immunotherapy. Laboratory studies suggest radiotherapy (RT) may facilitate response to immunotherapy. We hypothesized that oncolytic immunotherapy with talimogene lapherparepvec (T-VEC, an oncolytic immunotherapy that expresses granulocyte-macrophage colony stimulating factor) and RT would produce response in non-targeted metastases.

Diagnostic and Therapeutic Challenges of Rare Concurrent Intracranial Meningioma and Oligodendroglioma.

Introduction: Concurrent primary brain tumors are rare clinical entities, with a prevalence ranging from 0.1 to 0.5% of all diagnosed brain tumors.

Durable complete response in a patient with leptomeningeal melanoma after treatment with dabrafenib, trametinib, and nivolumab.

Leptomeningeal disease (LMD) is a devastating complication of melanoma with a dismal prognosis. We present the case of a young man with stage IV BRAF V600E mutant melanoma with lung, lymph node, and brain metastases initially treated with ipilimumab and nivolumab, who subsequently developed LMD. Upon change to BRAF/MEK targeted therapy with nivolumab, a durable complete response was achieved and remains ongoing, off treatment, 7 years from diagnosis.

Efficacy of axitinib in a US cohort of patients with programmed cell death protein 1-resistant mucosal melanoma.

Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and a low response rate to approved treatments. We retrospectively analyzed the clinical features, treatments, and outcomes of patients diagnosed with mucosal melanoma treated with axitinib ± anti-programmed cell death protein 1 (PD-1) therapy at a single US referral center between 2018 and 2021.

Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma.

Background: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

Patients And Methods: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+.

Early On-Treatment Assessment of T Cells, Cytokines, and Tumor DNA with Adaptively Dosed Nivolumab + Ipilimumab: Final Results from the Phase 2 ADAPT-IT Study.

Purpose: The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT;NCT03122522) investigated adaptive ipilimumab discontinuation in melanoma based on early radiographic assessment. Initial findings indicated similar effectiveness compared with conventional nivolumab-ipilimumab (nivo-ipi). Exploratory biomarker analyses and final clinical results are now reported.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved.

Clearance of plasma cell free DNA in metastatic uveal melanoma with radiographic response to immune checkpoint inhibitors.

Purpose: To report a case of metastatic uveal melanoma treated with immune checkpoint inhibition in which serial circulating tumor DNA (ctDNA) was assessed throughout treatment.

Observations: A 33-year-old man was diagnosed with metastatic uveal melanoma and initially had progression of disease following hepatic embolization and nivolumab/ipilimumab. At the time, plasma ctDNA and were measurable and repeat ctDNA showed increased variant allele frequency following further progression of disease on vorinostat.

Overall survival from tebentafusp versus nivolumab plus ipilimumab in first-line metastatic uveal melanoma: a propensity score-weighted analysis.

Background: Tebentafusp demonstrated a superior overall survival (OS) benefit [hazard ratio (HR) 0.51] compared to investigator's choice (82% pembrolizumab) in a randomized, phase III trial (IMCgp100-202; N = 378) in untreated metastatic uveal melanoma (mUM). The 1-year OS rates for tebentafusp and pembrolizumab were 73% and 59%, respectively.

The features and management of acquired resistance to PD1-based therapy in metastatic melanoma.

Background: Anti-PD-1 therapy (PD1) either alone or with anti-CTLA-4 (CTLA4), has high initial response rates, however 20% of patients (pts) with complete response (CR) and 30% with partial response (PR) within 12 months of treatment experience subsequent disease progression by 6 years. The nature and optimal management of this acquired resistance (AR) remains unknown.

Methods: Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined.

Most large structural variants in cancer genomes can be detected without long reads.

Short-read sequencing is the workhorse of cancer genomics yet is thought to miss many structural variants (SVs), particularly large chromosomal alterations. To characterize missing SVs in short-read whole genomes, we analyzed 'loose ends'-local violations of mass balance between adjacent DNA segments. In the landscape of loose ends across 1,330 high-purity cancer whole genomes, most large (>10-kb) clonal SVs were fully resolved by short reads in the 87% of the human genome where copy number could be reliably measured.

Phase Ib Trial of Phenformin in Patients with V600-mutated Melanoma Receiving Dabrafenib and Trametinib.

Purpose: Preclinical studies show that activation of AMP kinase by phenformin can augment the cytotoxic effect and RAF inhibitors in BRAF V600-mutated melanoma. We conducted a phase Ib dose-escalation trial of phenformin with standard dose dabrafenib/trametinib in patients with metastatic BRAF V600-mutated melanoma.

Experimental Design: We used a 3+3 dose-escalation design which explored phenformin doses between 50 and 200 mg twice daily.

Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.

Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.

Methods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level.

Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA).

Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients.

Prediction Model for Neurogenic Bladder Recovery One Year After Traumatic Spinal Cord Injury.

Introduction: Neurogenic bladder is a common complication after spinal cord injury (SCI) that carries substantial burdens on the inflicted individual. The objective of this study is to build a prediction model for neurogenic bladder recovery 1 year after traumatic SCI.

Methods: We queried the National Spinal Cord Injury Model Systems database for patients with traumatic SCI who had neurogenic bladder at the time of injury.

Early Detection of Avian Diseases Based on Thermography and Artificial Intelligence.

Non-invasive measures have a critical role in precision livestock and poultry farming as they can reduce animal stress and provide continuous monitoring. Animal activity can reflect physical and mental states as well as health conditions. If any problems are detected, an early warning will be provided for necessary actions.

Determinants of overall survival in patients with metastatic uveal melanoma.

Background: Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival.

Methods: A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti-CTLA-4 and anti-PD-1 therapies.

Tebentafusp in combination with durvalumab and/or tremelimumab in patients with metastatic cutaneous melanoma: a phase 1 study.

Background: Immune checkpoint inhibitors have significantly improved outcomes in first line cutaneous melanoma. However, there is a high unmet need for patients who progress on these therapies and combination therapies are being explored to improve outcomes. Tebentafusp is a first-in-class gp100×CD3 ImmTAC bispecific that demonstrated overall survival (OS) benefit (HR 0.

Bone morphogenetic proteins in spine surgery: a scientometric analysis to date.

Objective: Bone morphogenetic proteins (BMPs) are part of the transforming growth factor-beta superfamily and are involved in bone formation and repair. In spine surgery, recombinant human BMP (rhBMP) is used as an alternative to autografts for spinal fusions. This study aimed to evaluate bibliometric parameters and citations of the literature on BMPs to provide an overview of how the field has evolved.

Beyond the 5-year milestone: Long-term survivorship of melanoma patients treated off-trial with anti-PD-1.

Little is known about the long-term outcomes of anti-PD-1 treated patients with melanoma beyond 5 years, especially for patients treated off clinical trials. This retrospective cohort study includes patients with unresectable stage III/IV nonuveal melanoma treated with anti-PD-1 off-trial at Memorial Sloan Kettering Cancer Center between 2014 and 2017 who survived at least 5 years following their first anti-PD-1 dose (N = 139). We characterized overall survival (OS), melanoma-specific survival (MSS) estimates, treatment-free survival rates, and subsequent treatment courses.

Undifferentiated and Dedifferentiated Metastatic Melanomas Masquerading as Soft Tissue Sarcomas: Mutational Signature Analysis and Immunotherapy Response.

The distinction between undifferentiated melanoma (UM) or dedifferentiated melanoma (DM) from undifferentiated or unclassifiable sarcoma can be difficult and requires the careful correlation of clinical, pathologic, and genomic findings. In this study, we examined the utility of mutational signatures to identify patients with UM/DM with particular attention as to whether this distinction matters for treatment because the survival of patients with metastatic melanoma has dramatically improved with immunologic therapy, whereas durable responses are less frequent in sarcomas. We identified 19 cases of UM/DM that were initially reported as unclassified or undifferentiated malignant neoplasm or sarcoma and submitted for targeted next-generation sequencing analysis.