Predicting sentinel node positivity in patients with primary cutaneous melanoma: an international multicentre study validating and refining the MIA risk calculator
Background: The Melanoma Institute Australia (MIA) sentinel node (SN) metastasis risk-prediction online calculator[Lo2020] is now widely used around the world. The tool comprises eight models that variously use between three and six input parameters. However, the full (six-parameter) model has only been validated in the US population, the model with missing mitoses was validated for the Dutch and Swedish populations. Furthermore, some confidence intervals (CIs) of the tool are large due to uncommon input parameter values. This study further validated the tool in other populations and improved the precision of the risk estimates. Methods: Validation data were pooled from the Danish [...]
DP03 Melanoma detection in whole-slide images using a convolutional neural network for objective prognostic biomarker generation
Abstract The current melanoma staging system is predictive of 74% of the variance in survival, with prognostic biomarkers subject to high levels of interobserver and intraobserver variation. Melanoma morphology appears to be of greater significance than in other solid tumours, with Breslow thickness remaining the strongest prognostic indicator. The application of convolutional neural networks (CNNs) to whole-slide images (WSIs) may reveal new insights into tumour morphology and therefore patient prognosis. This work outlines the development and evaluation of a CNN for invasive cutaneous melanoma detection in WSIs, to enable the creation of objective prognostic biomarkers based on the tissue [...]
Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAFV600-mutant resectable melanoma: the randomized phase 2 NeoTrio trial.
Abstract Immune checkpoint inhibitors and BRAF-targeted therapy each improve survival in melanoma. Immune changes early during targeted therapy suggest the mechanisms of each drug class could work synergistically. In the non-comparative, randomized, phase 2 NeoTrio trial, we investigated whether targeted therapy could boost the proportion of patients achieving long-term recurrence-free survival with neoadjuvant immunotherapy in resectable stage III BRAFV600-mutant melanoma. Sixty patients (42% females) were randomized to pembrolizumab alone (n = 20), sequential therapy (dabrafenib plus trametinib followed by pembrolizumab; n = 20) or concurrent (triple) therapy (n = 20), followed by surgery and adjuvant therapy. The primary outcome [...]
Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09)
Abstract Background: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. Methods: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. Results: The trial ceased prematurely due to slow recruitment and [...]
Mohs micrographic surgery for the treatment of invasive melanoma: A systematic review with meta-analyses
Abstract Background: The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking. Objectives: This systematic review aimed to analyse clinical outcomes for patients with invasive melanomas treated with Mohs rather than wide local excision (WLE). Methods: Embase, MEDLINE and Cochrane databases (to 30 August 2023) were searched for studies using Mohs to treat invasive melanoma. Outcomes of interest were local recurrence and death from melanoma. Results: Thirty-five articles involving 41,499 patients with invasive melanoma treated with Mohs were identified. Sixteen studies compared Mohs with WLE and 19 were Mohs-only, non-comparative studies. Patients treated with Mohs [...]
Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma.
Abstract Background: In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy. Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received adjuvant treatment. The primary end point was event-free survival. Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% [...]
Use of early circulating tumour DNA dynamics in patients with stage III melanoma receiving neoadjuvant combination immunotherapy.
Abstract Background: Neoadjuvant therapy in resectable stage III cutaneous melanoma improves relapse-free survival compared to adjuvant therapy alone and is now a standard of care.While pathological response can help predict recurrence risk and the need for further treatment, more biomarkers are required. We investigated circulating tumour DNA (ctDNA) as a predictive biomarker for recurrence in stage IIIB/C melanoma patients following neoadjuvant immunotherapy and surgery. Methods: We retrospectively analysed plasma samples collected at baseline and six weeks post-surgery from 30 patients enrolled in the OpACIN-neo and PRADO clinical trials, who received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before [...]
Impact of an Online Risk Calculator for Sentinel Node Positivity on Management of Patients with T1 and T2 Melanomas
Abstract Background: Predicting which patients with American Joint Committee on Cancer (AJCC) T1-T2 melanomas will have a positive sentinel lymph node (SLN) is challenging. Melanoma Institute Australia (MIA) developed an internationally validated SLN metastatic risk calculator. This study evaluated the nomogram's impact on T1-T2 melanoma patient management at MIA. Methods: SLN biopsy (SLNB) rates were compared for the pre- and post-nomogram periods of 1 July 2018-30 June 2019 and 1 August 2020-31 July 2021, respectively. Results: Overall, 850 patients were identified (pre-nomogram, 383; post-nomogram, 467). SLNB was performed in 29.0% of patients in the pre-nomogram group and 34.5% in the post-nomogram group [...]
The Effect of Neoadjuvant Systemic Therapy on Surgical Outcomes After Lymph Node Dissections for Stage III Melanoma; An Australian Cohort
Abstract 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. Results: The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of [...]