Declining Clinical Utility of Tools for Predicting Sentinel Lymph Node Biopsy Status: A Single Institution Experience from 2000 to 2021.

Introduction: Clinicopathologic data-based sentinel lymph node (SLN) prediction models are used to select patients with melanoma for sentinel lymph node biopsy (SLNB). However, the temporal performance of these models is unknown. Therefore, we investigated whether the performance and clinical utility of the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center, and Friedman et al.

T-cell immunotherapy for melanoma.

This review explores T-cell immunotherapy for melanoma, highlighting immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1, anti-LAG-3), tumor-infiltrating lymphocytes (TILs), and emerging therapies that engineer T cells with specific receptors or T-cell receptors, such as CAR-T and TCR cells, and RNA vaccines. We discuss the history of T-cell immunotherapy, mechanisms of action, and future directions for improving patient outcomes.

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.

Immediate Lymphatic Reconstruction with Vascularized Omentum Lymph Node Transplant: Reducing the Risk of Both Painful Contracture and Lymphedema.

Patients undergoing extensive lymph node dissection and radiation are at high risk for not only lymphedema but also painful contracture. In a standard lymphadenectomy, immediate lymphatic reconstruction using a lymphovenous bypass is effective in reconstructing the lymphatic defect. However, a more aggressive nodal clearance leaves the patient with a large cavity and skeletonized neurovascular structures, often resulting in severe contracture, pain, cosmetic deformity, and venous stricture.

Clinical Utility of Melanoma Sentinel Lymph Node Biopsy Nomograms.

Background: For patients with melanoma, the decision to perform sentinel lymph node biopsy (SLNB) is based on the estimated risk of lymph node metastasis. We assessed 3 melanoma SLNB risk-prediction models' statistical performance and their ability to improve clinical decision making (clinical utility) on a cohort of melanoma SLNB cases.

Study Design: Melanoma patients undergoing SLNB at a single center from 2003 to 2021 were identified.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0.

Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival, and neoadjuvant strategies are an active area of investigation.

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.

Clinical Implications and Management of Non-BIA-ALCL Breast Implant Capsular Pathology.

The breast implant capsule is a dynamic structure that forms following the implantation of a device. Although normally benign, increased awareness of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) highlights that disease may arise from the capsule. BIA-ALCL presents as a late seroma or mass but explains few of the late seromas found in breast implant patients.

Fifty years of progress in surgical oncology: Melanoma.

This paper outlines the scientific and clinical advances in the treatment of melanoma over the past 50 years. Among the highlights of progress, the dominant themes include evidence-based reduction in the extent and morbidity of surgical procedures in patients with local or regional melanoma without compromising end results, and the introduction of effective systemic therapy, specifically targeted therapy matched to patients based on specific tumor mutations, and immune checkpoint blockade. Management of advanced disease has also changed dramatically, due to improved understanding of the genomic variability of the disease as well as continuing improvements in imaging.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery.

Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

Background: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes.

Methods: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.

Anatomic position determines oncogenic specificity in melanoma.

Oncogenic alterations to DNA are not transforming in all cellular contexts. This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes.

Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma.

Cancer immunotherapy can result in lasting tumor regression, but predictive biomarkers of treatment response remain ill-defined. Here, we performed single-cell proteomics, transcriptomics, and genomics on matched untreated and IL2 injected metastases from patients with melanoma. Lesions that completely regressed following intralesional IL2 harbored increased fractions and densities of nonproliferating CD8+ T cells lacking expression of PD-1, LAG-3, and TIM-3 (PD-1-LAG-3-TIM-3-).

Case Report: Response to Regional Melphalan Limb Infusion and Systemic PD1 Blockade in Recurrent Myxofibrosarcoma: A Report of 2 Cases.

Treatment options for patients with advanced sarcoma remain limited. Promising responses to checkpoint inhibition have been observed, but responses to single-agent PD-1 inhibition are rare. We report on two patients with multiply recurrent myxofibrosarcoma treated with the combination of regionally administered melphalan ( isolated limb infusion) and pembrolizumab.

Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade.

Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models.

Eradicating micrometastases with immune checkpoint blockade: Strike while the iron is hot.

Immune checkpoint blockade (ICB) is transforming treatment for many cancers. While ICB alone initially demonstrated efficacy in patients with metastatic melanoma, it has expanded to other types and to earlier-stage cancers. We describe ICB history, mechanisms underlying variation in response, and how ICB is being integrated into adjuvant and neoadjuvant treatment approaches.

Assessment of Frailty Can Guide Decision Making for Utilization of Sentinel Lymph Node Biopsy in Patients with Thick Melanoma.

Background: Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated.

Objective: We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma.

Methods: Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included.

Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors.

Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types.

Therapeutic Implications of Detecting MAPK-Activating Alterations in Cutaneous and Unknown Primary Melanomas.

Purpose: Cutaneous and unknown primary melanomas frequently harbor alterations that activate the MAPK pathway. Whether MAPK driver detection beyond BRAF V600 is clinically relevant in the checkpoint inhibitor era is unknown.

Experimental Design: Patients with melanoma were prospectively offered tumor sequencing of 341-468 genes.

Neoadjuvant Therapy for Melanoma: A U.S. Food and Drug Administration-Melanoma Research Alliance Public Workshop.

Tremendous progress has been made in treating patients with metastatic melanoma over the past decade. In that timeframe, the FDA has approved 12 novel treatments for patients with advanced unresectable melanoma, comprising both kinase-targeted therapies and immune checkpoint inhibitors (ICI), and five treatments for adjuvant (postoperative) use in patients with high-risk resectable stage III melanoma. It is not known whether outcomes can be further improved by administering kinase inhibitors or ICI in the neoadjuvant (presurgical) setting in patients with high-risk resectable melanomas.

Cost-Benefit Implication of Gene Expression Profiling and Adjuvant Therapy in Stage IIIA Melanoma.

Background: Indiscriminate use of adjuvant therapy in stage IIIA melanoma is controversial. We sought to model the clinical impact and cost of implementing a gene expression profile (GEP) test to guide adjuvant therapy.

Study Design: A Markov decision-analysis model was created to represent resected stage IIIA melanoma with 3 treatment options: observation (OBS), adjuvant pembrolizumab for all patients (ALL), and selective adjuvant therapy (SEL).

Sentinel Lymph Node Biopsy for T1b Melanoma: Balancing Prognostic Value and Cost.

Background: The purpose of this study is to report the additional prognostic information and cost associated with sentinel lymph node biopsy (SLNB) for patients with T1b melanoma.

Patients And Methods: An institutional database was queried for patients with T1b melanoma (0.8-1.

Regulatory T Cells Restrain Interleukin-2- and Blimp-1-Dependent Acquisition of Cytotoxic Function by CD4 T Cells.

In addition to helper and regulatory potential, CD4 T cells also acquire cytotoxic activity marked by granzyme B (GzmB) expression and the ability to promote rejection of established tumors. Here, we examined the molecular and cellular mechanisms underpinning the differentiation of cytotoxic CD4 T cells following immunotherapy. CD4 transfer into lymphodepleted animals or regulatory T (Treg) cell depletion promoted GzmB expression by tumor-infiltrating CD4, and this was prevented by interleukin-2 (IL-2) neutralization.