Adjuvant radiotherapy after salvage surgery for melanoma recurrence in a node field following a previous lymph node dissection.
Abstract 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. Baseline patient characteristics, treatment details and oncological outcomes were analysed. Results: Adjuvant RT with conventional fractionation (median dose 48 Gy in 20 [...]
Genomic profiling of metastatic basal cell carcinoma reveals candidate drivers of disease and therapeutic targets.
Abstract Basal cell carcinomas (BCCs) are human beings’ most common malignant tumors. Most are easily managed by surgery or topical therapies, and metastasis is rare. Although BCCs can become locally advanced, metastatic BCCs are very uncommon and may be biologically distinct. We assessed the clinicopathologic characteristics of 17 patients with metastatic BCC and pursued whole-exome sequencing of tumor and germline DNA from 8 patients. Genomic profiling revealed aberrant activation of Hedgehog signaling and alterations in GLI transcriptional regulators and Notch and Hippo signaling. Matched local recurrences of primary BCCs and metastases from 3 patients provided evidence of a clonal [...]
Prognostic Significance and Management of Sentinel Nodes in the Triangular Intermuscular Space of Patients with Melanoma.
Abstract 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. Recurrence-free survival was analyzed. Results Lymphoscintigraphy identified TIS SNs in 266 patients. They were bilateral in 17 patients. Of the 2296 patients with a melanoma on the upper back, 259 (11%) had TIS SNs. Procurement of [...]
Recursive Partitioning to Determine Order of Significance of Regional Metastasis Characteristics in Head and Neck Cutaneous Squamous Cell Carcinoma.
Abstract Background: The order of significance of clinicopathologic characteristics for the prognosis of patients with regional metastases from head and neck cutaneous squamous cell carcinoma (HNcSCC) is not well characterized. This study aimed to understand the impact of the known characteristics, including the presence of immunosuppression, number of deposits, largest deposit size, location and laterality of deposits, and presence of extranodal extension (ENE) on overall survival (OS) and disease-specific survival (DSS). Methods: A retrospective study of 366 patients treated with curative intent for HNcSCC with regional metastatic disease was undertaken using recursive partitioning analysis (RPA). Results: Using RPA modeling, the study determined [...]
Comparative genomics provides etiological and biological insights into melanoma subtypes
Abstract Background: Metastasectomy for selected patients with melanoma was associated with improved survival in the era before effective systemic therapy. Emerging evidence shows that these benefits persist even in this era of BRAF-targeted therapy and immune checkpoint inhibitor immunotherapy. This study aimed to evaluate the outcomes of salvage metastasectomy after failure of systemic therapy. Methods: Stage 3 or 4 melanoma patients with extracranial disease progression after at least 4 weeks of systemic treatment between 2009 and 2020 were identified and categorized as resected to no evidence of disease (NED), non-progressive residual disease (NPRD), or progressive residual disease (PRD). Systemic [...]
Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting.
Abstract 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. Significant (P < 5 × 10-8) [...]
Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome.
Abstract The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae-dominated microbiomes [...]
Survival outcomes of perineural spread in head and neck cutaneous squamous cell carcinoma.
Abstract Aim: To present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS). Method: Retrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high-volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco-regional failure and survival data were obtained. Results: Forty-five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43-90). Median follow-up was 16.1 months [...]
Outcomes after definitive treatment for head and neck angiosarcoma.
Abstract Introduction: Head and neck angiosarcoma (HN-AS) is a rare and aggressive, representing <1% of all head and neck malignancies. It is characterized by a high rate of local recurrence and poor 5-year survival (10-54%). Australian data in this rare disease is lacking. We aim review the clinical outcomes of HN-AS from two high volume head and neck cancer units in Australia. Methods: Retrospective chart review. Results: A total 26 patients were identified, consist of predominantly male patients (81%) with a mean age of 77 year old. Most of the HN-AS arises from the scalp (62%). The 5-year overall survival (OS) and [...]