Dynamic ctDNA Mutational Complexity in Patients with Melanoma Receiving Immunotherapy.

BACKGROUND: Circulating tumour DNA (ctDNA) analysis promises to improve the clinical care of people with cancer, address health inequities and guide translational research. This observational cohort study used ctDNA to follow 29 patients with advanced-stage cutaneous melanoma through multiple cycles of immunotherapy. METHOD: A melanoma-specific ctDNA next-generation sequencing (NGS) panel, droplet digital polymerase chain reaction (ddPCR) and mass spectrometry analysis were used to identify ctDNA mutations in longitudinal blood plasma samples from Aotearoa New Zealand (NZ) patients receiving immunotherapy for melanoma. These technologies were used in conjunction to identify the breadth and complexity of tumour genomic information that ctDNA analysis can reliably report. RESULTS: During the course of immunotherapy treatment, a high level of dynamic mutational complexity was identified in blood plasma, including multiple BRAF mutations in the same patient, clinically relevant BRAF mutations emerging through therapy and co-occurring sub-clonal BRAF and NRAS mutations. The technical validity of this ctDNA analysis was supported by high sample analysis-reanalysis concordance, as well as concordance between different ctDNA measurement technologies. In addition, we observed > 90% concordance in the detection of ctDNA when using cell-stabilising collection tubes followed by 7-day delayed processing, compared with standard EDTA blood collection protocols with rapid processing. We also found that the undetectability of ctDNA at a proportion of treatment cycles was associated with durable clinical benefit (DCB). CONCLUSION: We found that multiple ctDNA processing and analysis methods consistently identified complex longitudinal patterns of clinically relevant mutations, adding support for expanded clinical trials of this technology in a variety of oncology settings.

Virtual lesion clinic - Evaluation of a teledermatology triage system for referrals for suspected melanoma.

INTRODUCTION: The Virtual Lesion Clinic (VLC) of Waitemata District Health Board (WDHB) improves melanoma assessment and treatment using teledermatology. The VLC is reserved for pigmented lesions referred as suspected melanoma from primary care but indeterminate at the initial triage. OBJECTIVES: To assess the efficacy of the VLC diagnosis of melanoma. METHODS: A retrospective audit of suspected melanoma referrals (1 January 2012 to 31 December 2016) was conducted. Lesions were referred to the VLC if diagnostic uncertainty remained at the initial triage. VLC patients attended MoleMap imaging centres, a dermatologist reviewed history and images remotely and suggested a diagnosis and management plan. Post VLC provisional diagnosis of melanoma, all lesions subsequently excised were reviewed. A positive predictive value (PPV) was calculated using concordance between VLC diagnosis of melanoma and histopathological diagnosis of melanoma. Number needed to excise (NNE) for melanoma was derived, as well as an invasive to in-situ melanoma ratio (IM:MIS) and false negative rate (FNR). RESULTS: The VLC received 1874 referrals for 3546 lesions during the 5-year study period. Six hundred and seventy-nine lesions were recommended excision/biopsy or specialist face-to-face assessment, and 504 lesions were subsequently excised. The PPV was 62%, NNE 1.62 and IM:MIS 0.76 for lesions suspected to be melanoma at VLC assessment. The VLC had a melanoma-specific FNR of 7%. CONCLUSIONS: The VLC is effective in early diagnosis of melanoma with a high positive predictive value, low number needed to excise and low false negative rate amongst lesions referred as suspected melanoma.

WOUND Study: A Cost-Utility Analysis of Negative Pressure Wound Therapy After Split-Skin Grafting for Lower Limb Skin Cancer.

BACKGROUND: Skin cancer rates in New Zealand are estimated to be the highest in the world. Split-skin grafting is a common procedure after skin cancer excision in the lower limb. We sought to evaluate the cost-effectiveness of negative pressure wound therapy (NPWT) with same-day discharge in patients undergoing split-skin grafting of the lower limb for the treatment of skin cancer. MATERIALS AND METHODS: Using effectiveness and quality of life data from a blinded, randomized single-center trial, a decision analytic model was developed from the perspective of the New Zealand hospital health-care buyer. The patient population included adults aged >18 y undergoing elective removal of lower limb skin cancer who were deemed able to manage a portable negative pressure device at home. A deterministic cost-effectiveness model was constructed using cost and utility data from our single-center Wound outcomes in negative pressure dressing (WOUND) trial. Forty-nine patients were randomized to receive either a negative pressure dressing applied in theater with same-day discharge home or a traditional bolster dressing with 5 d of inpatient bed rest. Patients were followed up for 3 mo to assess the mean percentage of graft take and complications. Quality of life was assessed through a EuroQoL questionnaire at 5-7 d. Cost data were collected directly from hospital records for each patient. Probabilistic sensitivity analysis was used to characterize uncertainty. RESULTS: Compared with standard dressing, NPWT resulted in an average cost saving of $3903.28 per treatment and a disutility of 0.083. At a willingness-to-pay threshold of 25,000 New Zealand dollars, the incremental net benefit is $1828.27, indicating that NPWT is a cost-effective treatment option. The probability of NPWT being cost-effective was 73.15%. CONCLUSIONS: NPWT and same-day discharge in the appropriately selected patient is a cost-effective treatment compared with standard care.