Survival Outcomes of Salvage Metastasectomy After Failure of Modern-Era Systemic Therapy for Melanoma
Li AT, Vakharia K, Lo SN, Varey AHR, Carlino MS, Saw RPM, Shannon KF, Howle JR, Pennington TE, Stretch JR, Nieweg OE, Spillane AJ, Long GV, Menzies AM, Scolyer RA, Thompson JF, Ch'ng S. Ann Surg Oncol. (Epub 4 Aug 2021)
Histological regression in melanoma: impact on sentinel lymph node status and survival.
Abstract Regression in melanoma is an immunological phenomenon that results in partial or complete replacement of the tumor with variably vascular fibrous tissue, often accompanied by pigment-laden macrophages and chronic inflammation. In some cases, tumor-infiltrating lymphocytes (TILs) may represent the earliest phase of this process. The prognostic significance of regression has long been a matter of debate, with inconsistent findings reported in the literature to date. This study sought to determine whether regression in primary cutaneous melanomas predicted sentinel lymph node (SLN) status and survival outcomes in a large cohort of patients managed at a single centre. Clinical and [...]
Melanoma In Situ: A Critical Review and Re-Evaluation of Current Excision Margin Recommendations.
Abstract Most international clinical guidelines recommend 5-10 mm clinical margins for excision of melanoma in situ (MIS). While the evidence supporting this is weak, these guidelines are generally consistent. However, as a result of the high incidence of subclinical extension of MIS, especially of the lentigo maligna (LM) subtype, wider margins will often be needed to achieve complete histologic clearance. In this review, we assessed all available contemporary evidence on clearance margins for MIS. No randomized trials were identified and the 31 non-randomized studies were largely retrospective reviews of single-surgeon or single-institution experiences using Mohs micrographic surgery (MMS) for [...]
A multicentre study of naevus-associated melanoma vs. de novo melanoma, tumour thickness and body site differences.
Abstract Background: Whether melanoma in histological contiguity with a naevus [naevus-associated melanoma (NAM)] is distinctly different from melanoma arising de novo remains unclear. Objectives: To determine whether the characteristics of de novo melanoma differ from NAM and are not due to naevus obliteration in thicker tumours. Methods: We conducted a multicentre retrospective study of de novo melanoma and NAM in seven referral centres in Europe, Australia and the USA between 2006 and 2015. Results: In a total of 9474 localized melanomas, de novo melanoma was associated with thicker tumours and body site differences compared with NAM. In the subset of T1 melanomas (n = [...]
Clinical and Molecular Heterogeneity in Patients with Innate Resistance to Anti-PD-1 +/- Anti-CTLA-4 Immunotherapy in Metastatic Melanoma Reveals Distinct Therapeutic Targets.
Abstract While immune checkpoint inhibitors targeting the CTLA-4 and PD-1 receptors have significantly improved outcomes of many patients with metastatic melanoma, there remains a group of patients who demonstrate no benefit. In this study, we sought to characterise patients who do not respond to anti-PD-1-based therapies based on their clinical, genetic and immune profiles. Forty patients with metastatic melanoma who did not respond to anti-PD-1 +/− anti-CTLA-4 treatment were identified. Targeted RNA sequencing (n = 37) was performed on pretreatment formalin-fixed paraffin-embedded (FFPE) melanoma specimens. Patients clustered into two groups based on the expression profiles of 26 differentially expressed genes: [...]
Re-defining the role of surgery in the management of patients with oligometastatic stage IV melanoma in the era of effective systemic therapies.
Abstract Although previously the mainstay of treatment, the role of surgery in the management of patients with oligometastatic stage IV melanoma has changed with the advent of effective systemic therapies (most notably immunotherapy). Contemporary treatment options for patients with asymptomatic solitary or oligo-metastases include upfront surgery followed by adjuvant immunotherapy or upfront immunotherapy with salvage surgery as required. For suspected solitary or oligo-metastases, surgery serves both diagnostic and therapeutic purposes. Advances in radiological technology allow metastases to be detected earlier and surgery to be less morbid. Surgical morbidities are generally more tolerable than serious immune-related adverse effects, but surgery [...]
PDCD1 Polymorphisms May Predict Response to Anti-PD-1 Blockade in Patients With Metastatic Melanoma.
Abstract A significant number of patients (pts) with metastatic melanoma do not respond to anti-programmed cell death 1 (PD1) therapies. Identifying predictive biomarkers therefore remains an urgent need. We retrospectively analyzed plasma DNA of pts with advanced melanoma treated with PD-1 antibodies, nivolumab or pembrolizumab, for five PD-1 genotype single nucleotide polymorphisms (SNPs): PD1.1 (rs36084323, G>A), PD1.3 (rs11568821, G>A), PD1.5 (rs2227981, C>T) PD1.6 (rs10204225, G>A) and PD1.9 (rs2227982, C>T). Clinico-pathological and treatment parameters were collected, and presence of SNPs correlated with response, progression free survival (PFS) and overall survival (OS). 115 patients were identified with a median follow up [...]
Neoadjuvant Immunotherapy in Melanoma – The New Frontier
Abstract Neoadjuvant immunotherapy is gathering pace, particularly in melanoma. A recent study of pembrolizumab and HDI not only further supports the safety and activity of neoadjuvant anti-PD-1 based immunotherapy but also highlights neoadjuvant therapy as a solid platform for drug development that is likely to become a standard-of-care in the near future. Read Full Paper
Neoadjuvant immunotherapy in melanoma – the new frontier
Abstract Neoadjuvant immunotherapy is gathering pace, particularly in melanoma. A recent study of pembrolizumab and HDI not only further supports the safety and activity of neoadjuvant anti-PD-1 based immunotherapy but also highlights neoadjuvant therapy as a solid platform for drug development that is likely to become a standard-of-care in the near future. Read Full Paper