Clinical significance of intra-thoracic and intra-abdominal sentinel lymph nodes detected on lymphoscintigraphy in truncal melanoma patients.

Background: Although most melanomas drain to the more common major lymph node basins (axilla, groin, neck), rarely they drain to deep SLN locations such as intra-abdominal and intra-thoracic (including intercostal and internal mammary) sites, which pose a higher surgical risk and complexity for procurement. Our study is aimed at determining the rate of positivity and likelihood of recurrence in these nodal sites to guide management decisions for patients with truncal melanomas which drain to these 'deep' SLN locations.

Methods: Retrospective data collected between May 2008 and May 2022 including all patients with truncal melanomas who underwent lymphoscintigraphy resulting in the identification of deep SLNs in intra-abdominal and intra-thoracic sites were included.

Single-cell spatial multiomics reveals tumor microenvironment vulnerabilities in cancer resistance to immunotherapy.

Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors.

The Effect of Neoadjuvant Systemic Therapy on Surgical Outcomes After Lymph Node Dissections for Stage III Melanoma; An Australian Cohort.

Background: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes.

Methods: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database.

Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma.

Background: Neoadjuvant dabrafenib plus trametinib has a high pathological response rate and impressive short-term survival in patients with resectable stage III melanoma. We report 5-year outcomes from the phase II NeoCombi trial.

Patients And Methods: NeoCombi (NCT01972347) was a single-arm, open-label, single-centre, phase II trial.

Prognostic Significance of Incipient Ulceration in Primary Cutaneous Melanoma.

Importance: Ulceration represents a key feature in cutaneous melanoma, contributing to staging according to the current American Joint Committee on Cancer (AJCC) system. However, cases with incipient ulceration do not quite fulfill the AJCC definition of ulceration and are consequently classified as nonulcerated, presenting interpretive difficulty for pathologists. The prognostic implication of incipient ulceration is uncertain.

Definitive treatment with PD-1 blockade and radiation therapy of unresected primary desmoplastic melanoma of the nose.

Two patients with primary desmoplastic melanoma of the nose were treated with definitive anti-PD-1 checkpoint inhibitor (anti-PD1) and radiation therapy. Both patients were technically resectable with partial rhinectomy but both declined for cosmetic reasons. The melanoma multidisciplinary team recommended that the patients receive PD1 blockade.

Effect of Histopathological Explanations for Dermoscopic Criteria on Learning Curves in Skin Cancer Training: a Randomized Controlled Trial.

Introduction: Case-based training improves novices pattern recognition and diagnostic accuracy in skin cancer diagnostics. However, it is unclear how pattern recognition is best taught in conjunction with the knowledge needed to justify a diagnosis.

Objectives: The aim of this study was to examine whether an explanation of the underlying histopathological reason for dermoscopic criteria improves skill acquisition and retention during case-based training in skin cancer diagnostics.

Practitioner characteristics, diagnostic accuracy metrics and discovering-individual with respect to 637 melanomas documented by 27 general practitioners on the Skin Cancer Audit Research Database.

Background And Objective: Knowledge of accuracy for melanoma diagnosis and melanoma discovering-individual in primary care is limited. We describe general practitioner (GP) characteristics and analyse defined diagnostic accuracy metrics for GPs in the current study comparing this with a previous study for GPs common to both, and we analyse the individual first discovering each melanoma as a lesion of concern.

Methods: The characteristics and diagnostic accuracy of 27 Australasian GPs documenting 637 melanomas on the Skin Cancer Audit Research Database (SCARD) in 2013 were described and analysed.

Improving Selection for Sentinel Lymph Node Biopsy Among Patients With Melanoma.

Importance: Refining eligibility guidelines may identify more appropriate patients to undergo useful medical procedures.

Objective: To improve cost-effectiveness in selecting patients with melanoma for sentinel lymph node biopsy (SLNB).

Design, Setting, And Participants: This hybrid prognostic study/decision analytical model was conducted among patients with melanoma who were eligible for SLNB at 2 melanoma centers from Australia and the US from 2000 to 2014.

Adjuvant radiotherapy after salvage surgery for melanoma recurrence in a node field following a previous lymph node dissection.

Background And Objectives: Adjuvant radiotherapy (RT) can be given to melanoma patients following salvage surgery for node field recurrence after a previous regional node dissection, but the value of this treatment strategy is poorly documented. This study evaluated long-term node field control and survival of patients treated in this way in an era before effective adjuvant systemic therapy became available.

Methods: Data for 76 patients treated between 1990 and 2011 were extracted from an institutional database.

Representativeness of initial skin biopsies showing pure desmoplastic melanoma: implications for management.

Desmoplastic melanoma (DM) is an uncommon subtype of melanoma with distinct clinicopathological features. It is classified into pure desmoplastic melanoma (PDM) when the proportion of desmoplastic melanoma is ≥90% of the dermally-invasive component, and mixed desmoplastic melanoma (MDM) when the proportion of desmoplastic melanoma is <90%. Studies have reported a lower sentinel lymph node biopsy (SLNB)-positivity rate in PDM compared to MDM and non-DM.

Prognostic Significance and Management of Sentinel Nodes in the Triangular Intermuscular Space of Patients with Melanoma.

Background: The clinical significance of sentinel nodes (SNs) in the triangular intermuscular space (TIS) of patients with melanoma is poorly understood. This study aimed to determine their incidence and positivity rate, and to report their management and patient outcomes.

Methods: This was a single-institution retrospective cohort study of patients with unilateral or bilateral TIS SNs on lymphoscintigraphy treated between 1992 and 2017.

Comparative Genomics Provides Etiologic and Biological Insight into Melanoma Subtypes.

Unlabelled: Melanoma is a cancer of melanocytes, with multiple subtypes based on body site location. Cutaneous melanoma is associated with skin exposed to ultraviolet radiation; uveal melanoma occurs in the eyes; mucosal melanoma occurs in internal mucous membranes; and acral melanoma occurs on the palms, soles, and nail beds. Here, we present the largest whole-genome sequencing study of melanoma to date, with 570 tumors profiled, as well as methylation and RNA sequencing for subsets of tumors.

Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting.

Background: The role of germline genetic factors in determining survival from cutaneous melanoma (CM) is not well understood.

Objective: To perform a genome-wide association study (GWAS) meta-analysis of melanoma-specific survival (MSS), and test whether a CM-susceptibility polygenic risk score (PRS) is associated with MSS.

Methods: We conducted two Cox proportional-hazard GWAS of MSS using data from the Melanoma Institute Australia, a high ultraviolet (UV) radiation setting (MIA; 5,762 patients with melanoma; 800 melanoma deaths) and UK Biobank (UKB: 5,220 patients with melanoma; 241 melanoma deaths), and combined them in a fixed-effects meta-analysis.

Clinicopathological Characteristics Predicting Further Recurrence and Survival Following Resection of In-Transit Melanoma Metastases.

Background: In-transit metastases (ITMs) affect approximately 4% of patients with cutaneous melanoma. This study sought to identify clinical and pathological characteristics that predict further recurrence and survival following resection of ITMs.

Patients And Methods: Patients (n = 573) who underwent surgical resection of their first presentation of ITM following previous surgical treatment of an American Joint Committee on Cancer (AJCC) stage I-II melanoma between 1969 and 2017 were identified from an institutional database.

Anchored Multiplex PCR Custom Melanoma Next Generation Sequencing Panel for Analysis of Circulating Tumor DNA.

Detection of melanoma mutations using circulating tumor DNA (ctDNA) is a potential alternative to using genomic DNA from invasive tissue biopsies. To date, mutations in the GC-rich promoter region, which is commonly mutated in melanoma, have been technically difficult to detect in ctDNA using next-generation sequencing (NGS) panels. In this study, we developed a custom melanoma NGS panel for detection of ctDNA, which encompasses the top 15 gene mutations in melanoma including the promoter.

Characteristics, treatment and outcomes of 589 melanoma patients documented by 27 general practitioners on the Skin Cancer Audit Research Database.

Background And Objective: General practitioners manage more melanomas than dermatologists or surgeons in Australia. Previously undescribed, the management and outcomes of melanoma patients treated by multiple Australasian general practitioners are examined.

Methods: The characteristics, management and outcomes of 589 melanoma patients, managed by 27 Australasian general practitioners and documented on the Skin Cancer Audit Research Database (SCARD), were analysed.

Effect of the time interval between melanoma diagnosis and sentinel node biopsy on the size of metastatic tumour deposits in node-positive patients.

Introduction: This study sought to assess whether the interval between diagnostic excision-biopsy of a primary melanoma and definitive wide excision with sentinel node biopsy (SNB) influenced the size of SN metastatic deposits, which might have implications for management and prognosis.

Methods: Data were collected for (i) a Dutch population-based cohort of patients treated between 2004 and 2014 who underwent SNB within 100 days of complete excision of their primary melanoma and who were SN-positive with known SN metastasis diameter (n = 1027) and (ii) a cohort from a large Australian melanoma treatment centre (n = 541) who presented in the same time period. The effects of SNB timing on the size of SN metastatic deposits were analysed.

BRAF mutation testing for patients diagnosed with stage III or stage IV melanoma: practical guidance for the Australian setting.

Targeted therapy (BRAF inhibitor plus MEK inhibitor) is now among the possible treatment options for patients with BRAF mutation-positive stage III or stage IV melanoma. This makes prompt BRAF mutation testing an important step in the management of patients diagnosed with stage III or IV melanoma; one that can help better ensure that the optimal choice of systemic treatment is initiated with minimal delay. This article offers guidance about when and how BRAF mutation testing should be conducted when patients are diagnosed with melanoma in Australia.