Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAF-mutant resectable melanoma: the randomized phase 2 NeoTrio trial.

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 BRAF-mutant melanoma.

Leg Lymphoedema After Inguinal and Ilio-Inguinal Lymphadenectomy for Melanoma: Results from a Prospective, Randomised Trial.

Background: The Evaluation of Groin Lymphadenectomy Extent for Melanoma (EAGLE FM) study sought to address the question of whether to perform inguinal (IL) or ilio-inguinal lymphadenectomy (I-IL) for patients with inguinal nodal metastatic melanoma who have no clinical or imaging evidence of pelvic disease. Primary outcome measure was disease-free survival at 5 years, and secondary endpoints included lymphoedema.

Methods: EAGLE FM was designed to recruit 634 patients but closed with 88 patients randomised because of slow recruitment and changes in melanoma management.

Follow-up assessment of sleep-related symptoms in patients after treatment for cancer: responses to continuous positive airway pressure treatment for co-morbid obstructive sleep apnoea.

Purpose: To assess changes in sleep-related symptoms in patients with breast cancer, endometrial cancer and melanoma previously examined for sleep-related symptoms and the presence of PSG (polysomnography)-determined OSA, ≥ 3 years post-treatment; and to evaluate how CPAP treatment affects sleep-related symptoms in patients previously diagnosed with OSA.

Methods: Patients initially recruited from breast cancer, endometrial cancer, and melanoma follow-up clinics at Westmead Hospital (Sydney, Australia) participated in this questionnaire-based study. Demographic and change in cancer status data were collected at follow-up.

Does preoperative imaging for scalp non-melanocytic skin cancer accurately predict invasion of the cranial vault? A systematic review and meta-analysis.

Purpose: This study aimed to determine the diagnostic accuracy of CT and MRI in the preoperative detection of bone involvement for non-melanoma skin cancers (NMSCs) located on the scalp. This study further aimed to evaluate the predictive value of these imaging modalities in determining the need for craniectomy and to identify gaps in the existing literature.

Methods: Electronic searches of the MEDLINE, Embase, Cochrane and Google Scholar databases were performed for English language studies of any type.

Has the advent of modern adjuvant systemic therapy for melanoma rendered sentinel node biopsy unnecessary?

The prognostic value of sentinel node biopsy (SNB) is well established and SNB was therefore adopted as a requirement for pathological staging of melanomas>1 mm thick in the American Joint Committee on Cancer (AJCC) 8th edition. Consequently, a negative SNB status became an eligibility criterion for clinical trials of adjuvant systemic therapy in resected stage IIB/C melanoma. However, since the Keynote 716 trial demonstrated an improvement in relapse-free survival (RFS) in patients with Stage IIB/C melanoma, all of whom had SNB staging, some have argued that SNB is no longer required for patients with T3 and T4 primary melanomas.

Immunotherapy in advanced cutaneous squamous cell carcinoma: Sydney west cancer network experience.

Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common malignancy in the Caucasian population. A minority of cases are inoperable at presentation, recur or develop metastatic disease with a historical 5-year overall survival of ~10%. Treatment options in this setting are generally palliative.

Screening for obstructive sleep apnoea in post-treatment cancer patients.

Background And Aims: For cancer patients, comorbid obstructive sleep apnea (OSA) poses additional risk to their surgical/anaesthetic outcomes, quality of life, and survival. However, OSA screening is not well-established in oncology settings. We tested two screening tools (STOP-Bang questionnaire [SBQ] and the at-home monitoring device, ApneaLink™Air), for predicting polysomnography (PSG) confirmed OSA in post-treatment cancer patients.

Metastatic papillary thyroid cancer to cerebellum with incidental medullary microcarcinoma.

Thyroid cancer is the most common endocrine cancer, with papillary thyroid carcinoma (PTC) accounting for the majority of these cases. Cerebellar metastasis is rarely the presenting feature and confers poor prognosis. Genetic mutations in this setting are most commonly , in contrast to in the majority of PTC.

Cancer sleep symptom-related phenotypic clustering differs across three cancer specific patient cohorts.

Specific sleep disorders have been linked to disease progression in different cancers. We hypothesised sleep symptom clusters would differ between cancer types. The aim of this study was to compare sleep symptom clusters in post-treatment melanoma, breast and endometrial cancer patients.

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.

Merkel cell carcinoma in situ: A systematic review of prognosis and management.

Background: Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine tumour. While dermally invasive MCC is known to have a five-year survival of only 30-40%, the prognosis and management of MCC in situ (MCCis) is not widely reported.

Objective: We present a systematic review to elucidate the prognosis and management of MCCis.

Irregular Sleep/Wake Patterns Are Associated With Reduced Quality of Life in Post-treatment Cancer Patients: A Study Across Three Cancer Cohorts.

Cancer patients often describe poor sleep quality and sleep disruption as contributors to poor quality of life (QoL). In a cross-sectional study of post-treatment breast, endometrial, and melanoma cancer patients, we used actigraphy to quantify sleep regularity using the sleep regularity index (SRI), and examined relationships with reported sleep symptoms and QoL. Participants were recruited post-primary treatment (35 diagnosed with breast cancer, 24 endometrial cancer, and 29 melanoma) and wore an actigraphy device for up to 2 weeks and SRI was calculated.

Survival Outcomes of Salvage Metastasectomy After Failure of Modern-Era Systemic Therapy for Melanoma.

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.

Immunotherapy in advanced Merkel cell carcinoma: Sydney west cancer network experience.

Introduction: Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with no survival benefit demonstrated using palliative cytotoxic chemotherapy in the setting of metastatic MCC. Recently, immune checkpoint inhibitors (anti-PD-L1/PD1) have been approved in this setting after durable clinical response was demonstrated in several clinical trials. In this series, we present a multicentre real-world experience in using anti-PD-L1/PD1 in advanced MCC.

Outcomes of patients with metastatic cutaneous squamous cell carcinoma to the axilla: a multicentre cohort study.

Background: Metastatic cutaneous squamous cell carcinoma to the axilla is uncommon, with limited data to guide management. We sought to assess the outcomes of patients with this condition after surgery and radiotherapy.

Methods: A retrospective cohort study of patients treated at two Australian hospitals from 1994 through 2016 was performed.

Design and Testing of a Custom Melanoma Next Generation Sequencing Panel for Analysis of Circulating Tumor DNA.

Detection of melanoma-associated mutations using circulating tumor DNA (ctDNA) from plasma is a potential alternative to using genomic DNA from invasive tissue biopsies. In this study, we developed a custom melanoma next-generation sequencing (NGS) panel which includes 123 amplicons in 30 genes covering driver and targetable mutations and alterations associated with treatment resistance. Analysis of a cohort of 74 stage III and IV treatment-naïve melanoma patients revealed that sensitivity of ctDNA detection was influenced by the amount of circulating-free DNA (cfDNA) input and stage of melanoma.

The changing paradigm of managing Merkel cell carcinoma in Australia: An expert commentary.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine tumor of the skin with an estimated disease-associated mortality of 15-33%. Australia has a higher incidence of MCC compared to the rest of the world, thought to be due to a higher ultraviolet index. The Australian MCC population is distinct from the MCC population of the Northern hemisphere, characterized by a predominantly viral negative etiology with high tumor mutational burden.

Sentinel lymph node biopsy in clinically node-negative Merkel cell carcinoma: the Westmead Hospital experience.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with a propensity to metastasize to regional lymph nodes. Sentinel lymph node biopsy (SLNB) in patients with clinically node-negative MCC has been utilized to identify patients with subclinical nodal metastases. This study aims to review the accuracy of SLNB in MCC and to evaluate the impact of SLNB on management.

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

Background: The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.

Updated evidence-based clinical practice guidelines for the diagnosis and management of melanoma: definitive excision margins for primary cutaneous melanoma.

Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.

PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors.

To examine the relationship between immune activity, PD-L1 expression, and tumor cell signaling, in metastatic melanomas prior to and during treatment with targeted MAPK inhibitors. Thirty-eight tumors from 17 patients treated with BRAF inhibitor ( = 12) or combination BRAF/MEK inhibitors ( = 5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pretreatment (PRE, = 17), early during treatment (EDT, = 8), and progression (PROG, = 13) biopsies.

Dynamic Changes in PD-L1 Expression and Immune Infiltrates Early During Treatment Predict Response to PD-1 Blockade in Melanoma.

Disruption of PD-L1/cytotoxic T-cell PD-1 signaling by immune checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD-1 therapies in patients with melanoma, particularly early during treatment, and correlate them with treatment response. Forty-six tumor biopsies from 23 patients with unresectable AJCC stage III/IV melanoma receiving pembrolizumab/nivolumab were analyzed.