Surgical considerations for tumour-infiltrating lymphocyte therapy in melanoma: results from a randomized phase III trial.
Abstract Background: The aim of this study was to describe the impact of surgical resections on tumour-infiltrating lymphocyte (TIL) therapy, based on results from a randomized phase III trial comparing TIL therapy with standard ipilimumab in patients with metastatic melanoma (NCT02278887). Methods: Surgical details of all operations performed in the trial were collected. Location, total number, and size of resected metastases were assessed in relation to successful TIL investigational medicinal product (IMP) manufacture and response to TIL therapy. Results: A total of 93 operations were needed to treat 80 patients with TIL therapy. Surgical complications were detected in 17% of operations. These [...]
Diagnostic Potential of 68Ga-NeoB PET/CT with Estrogen Receptor- and Progesterone Receptor-Positive Breast Cancer Undergoing Staging or Restaging for Metastatic Disease.
Abstract Background: 18F-FDG PET/CT has low sensitivity for estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer. By contrast, gastrin-releasing peptide receptor is overexpressed in ER/PR-positive breast cancer. This study assessed the diagnostic potential of 68Ga-NeoB PET/CT in staging or restaging metastatic ER/PR-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: Patients with ER/PR-positive and HER2-negative breast cancer with clinical suspicion for metastatic disease undergoing staging or restaging were prospectively enrolled. All patients underwent 68Ga-NeoB PET/CT, in addition to standard 18F-FDG PET/CT. ER/PR-positive and HER2-negative status was confirmed in prior biopsy samples (primary or metastatic). Conventional imaging (18F-FDG PET/CT, bone scan, and [...]
ASO Visual Abstract: Cartilage Resection in the Surgical Management of Ear Melanoma.
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Do BRAF-targeted therapies have a role in the era of immunotherapy?
Abstract Over half of cutaneous melanomas have BRAF mutations, with this mutation being more prevalent in younger patients who often present with more aggressive disease. BRAF-targeted therapy and checkpoint inhibitor immunotherapy have led to marked improvements in outcomes for patients with BRAF-mutant melanoma. Despite these advances, novel combinatorial strategies are vital given that more than half of advanced melanoma patients will still die due to melanoma. Translational evidence has suggested potential immunostimulatory effects of BRAF-targeted therapies, yet their combination with immunotherapy has shown limited clinical success. The pathways that lead to acquired resistance to targeted therapy, which may confer [...]
Reflectance confocal microscopy terminology for nonmelanocytic skin lesions: A Delphi consensus of experts.
Abstract Background: There is lack of uniformity in reflectance confocal microscopy (RCM) terminology. Objective: To establish expert consensus on a standardized set of RCM terms that describe non-melanocytic lesions (NMLs). Methods: We invited RCM experts to participate in a Delphi-consensus study. Fifty-nine RCM descriptors were extracted from a previous systematic review on RCM terminology for describing NML. Of these, 35 items were presented as 4 groups of synonymous terms and 24 items as single, nonsynonymous terms. For the first round, an agreement threshold was set at >70%. Participants could also propose new terms. Terms with ≤70% agreement and newly proposed terms were [...]
Federated deep learning enables cancer subtyping by proteomics.
Abstract Artificial intelligence applications in biomedicine face major challenges from data privacy requirements. To address this issue for clinically annotated tissue proteomic data, we developed a Federated Deep Learning (FDL) approach (ProCanFDL), training local models on simulated sites containing data from a pan-cancer cohort (n=1,260) and 29 cohorts held behind private firewalls (n=6,265), representing 19,930 replicate data-independent acquisition mass spectrometry (DIA-MS) runs. Local parameter updates were aggregated to build the global model, achieving a 43% performance gain on the hold-out test set (n=625) in 14 cancer subtyping tasks compared to local models, and matching centralized model performance. The approach's [...]
The Value of Sentinel Node Biopsy in Patients With Higher-Risk (T3, T4) Primary Cutaneous Melanomas: Insights Provided by a Stage II Risk Calculator.
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Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of stage IIB/C melanoma in the randomized phase 3 CheckMate 76 K trial.
Abstract Background: In the phase 3 CheckMate 76 K trial, adjuvant nivolumab significantly improved recurrence-free survival and distant metastasis-free survival versus placebo in patients with resected stage IIB/C melanoma. We report patient-reported outcomes from CheckMate 76 K. Methods: Change from baseline to week 53 in health-related quality of life (HRQoL), as measured using the EORTC QLQ-C30 and EQ-5D-5L utility index and visual analog scale (VAS), was compared between treatment groups using linear mixed-effect models. Time to confirmed deterioration (TTCD) in HRQoL was assessed using Cox regression. Bother from side effects, as measured by the FACIT-GP5, was descriptively compared between treatment groups. [...]
Cartilage Resection in the Surgical Management of Ear Melanoma.
Abstract Background: Melanoma of the ear accounts for approximately 1% of cutaneous melanomas. Management recommendations are based on small retrospective series and case reports. Resection of melanoma of the ear requires a delicate balance between disease clearance, preservation of function, and aesthetics. The role of cartilage resection in the wide excision of melanoma of the ear remains unclear. We aimed to compare outcomes in patients having wide excision of ear melanoma who had cartilage resected with those who had a cartilage-sparing approach. Methods: Data were obtained from the Melanoma Institute Australia (MIA) prospectively maintained database. All patients diagnosed with invasive melanoma [...]
Clinical validation of droplet digital PCR assays in detecting BRAFV600-mutant circulating tumour DNA as a prognostic biomarker in patients with resected stage III melanoma receiving adjuvant therapy (COMBI-AD): a biomarker analysis from a double-blind, randomised phase 3 trial.
Abstract Background: Cell-free, circulating tumour DNA (ctDNA) is an established measure of minimal residual disease; however, it is not utilised in melanoma management. We investigated whether ctDNA measurements could predict survival outcomes during adjuvant targeted therapy or placebo treatment in stage III melanoma, thereby identifying patients at high risk and low risk of recurrence. Methods: Analytically validated mutation-specific droplet digital PCR assays were used to measure BRAFV600E or BRAFV600K ctDNA in patients aged 18 years or older who were enrolled in the COMBI-AD trial, which was a double-blind, randomised, phase 3 study of oral dabrafenib (150 mg twice daily) plus oral trametinib (2 [...]