Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).
Abstract Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to [...]
The emerging role of the lung microbiome and its importance in non-small cell lung cancer diagnosis and treatment
Abstract Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile. However, in recent years, it has become clear that the lower airways are home to a dynamic bacterial population sustained by the migration and elimination [...]
The emerging role of the lung microbiome and its importance in non-small cell lung cancer diagnosis and treatment.
Abstract Over the last 10 years, with the development of culture-free bacterial identification techniques, understanding of how the microbiome influences diseases has increased exponentially and has highlighted potential opportunities for its use as a diagnostic biomarker and interventional target in many diseases including malignancy. Initial research focused on the faecal microbiome since it contains the densest bacterial populations and many other mucosal sites, such as the lungs, were until recently thought to be sterile. However, in recent years, it has become clear that the lower airways are home to a dynamic bacterial population sustained by the migration and elimination [...]
Successful treatment of eruptive keratoacanthomas with actitretin for patients on checkpoint inhibitor immunotherapy.
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Competing risks analysis with missing cause-of-failure-penalized likelihood estimation of cause-specific Cox models
Abstract Competing risks models are attractive tools to analyze time-to-event data where several causes of an event are competing. However, a complexity may arise when, for instance, some subjects experience the event of interest but the causes are not known. Assuming that unknown causes of events are missing at random, we developed a novel constrained maximum penalized likelihood method for fitting semi-parametric cause-specific Cox regression models. Here, penalty functions were used to smooth the baseline hazards. An appealing feature of this approach is that all the relevant estimands in competing risks models are estimated including cause-specific hazard ratios, cause-specific [...]
Competing risks analysis with missing cause-of-failure-penalized likelihood estimation of cause-specific Cox models.
Abstract Competing risks models are attractive tools to analyze time-to-event data where several causes of an event are competing. However, a complexity may arise when, for instance, some subjects experience the event of interest but the causes are not known. Assuming that unknown causes of events are missing at random, we developed a novel constrained maximum penalized likelihood method for fitting semi-parametric cause-specific Cox regression models. Here, penalty functions were used to smooth the baseline hazards. An appealing feature of this approach is that all the relevant estimands in competing risks models are estimated including cause-specific hazard ratios, cause-specific [...]
Pathology: the next chapter
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Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance
Abstract We concurrently examine the whole genome, transcriptome, methylome, and immune cell infiltrates in baseline tumors from 77 patients with advanced cutaneous melanoma treated with anti-PD-1 with or without anti-CTLA-4. We show that high tumor mutation burden (TMB), neoantigen load, expression of IFNγ-related genes, programmed death ligand expression, low PSMB8 methylation (therefore high expression), and T cells in the tumor microenvironment are associated with response to immunotherapy. No specific mutation correlates with therapy response. A multivariable model combining the TMB and IFNγ-related gene expression robustly predicts response (89% sensitivity, 53% specificity, area under the curve [AUC], 0.84); tumors with [...]
Dermoscopic features and screening strategies for the detection of small-diameter melanomas.
Abstract Background: Around 70% of cutaneous malignant melanomas (MMs) develop de novo, and small-diameter or 'tiny' lesions are expected to represent the earliest manifestation of most MMs. Aim: To describe the clinical, histopathological and dermoscopic features of tiny MMs, and to investigate the impact of imaging tools, including total body photography (TBP) and sequential digital dermoscopy imaging (SDDI) in their detection. Methods: Consecutive MMs diagnosed over 2 years in a referral centre were retrospectively included. Tiny MMs were defined as MMs with a diameter of ≤ 5 mm on dermoscopy. Dermoscopic features and the performance of four imaging methods were evaluated. Results: Of [...]
Assessing the Potential for Patient-led Surveillance After Treatment of Localized Melanoma (MEL-SELF): A Pilot Randomized Clinical Trial
Abstract Importance: Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma. Objective: To determine whether patient-led surveillance in patients with prior localized primary cutaneous melanoma is as safe, feasible, and acceptable as clinician-led surveillance. Design, setting, and participants: This was a pilot for a randomized clinical trial at 2 specialist-led clinics in metropolitan Sydney, Australia, and a primary care skin cancer clinic managed by general practitioners in metropolitan Newcastle, Australia. The participants were 100 patients who had been treated for localized melanoma, owned a smartphone, had a partner to assist with skin self-examination (SSE), and had [...]