OBJECTIVE: With the promising results of immunotherapy in patients with stage III melanoma, the role of adjuvant radiotherapy after resection and complete lymph-node dissection must be reassessed. We evaluate the outcomes and safety of adjuvant radiotherapy and immunotherapy compared to immunotherapy only in patients with resected stage III melanoma.
METHODS: This retrospective and single institution study included patients treated for a stage III melanoma with complete lymph-node dissection and adjuvant immunotherapy from January 2019 to December 2022. The radiotherapy associated with immunotherapy group was defined by completion of immunotherapy and adjuvant radiotherapy in the lymph-node dissection area. The primary endpoint was disease-free survival. The secondary endpoints were locoregional progression, incidence of adverse events grade 3 or above and disease-free survival rate in patients with high risk of locoregional recurrence.
RESULTS: Thirty-three patients were included. Among them, twelve received adjuvant lymph-node field radiotherapy. The median duration of follow-up was 17months (range: 8-45months). Patients receiving radiotherapy and immunotherapy had a significantly higher disease stage and more frequent extracapsular extension. At 12months, the disease-free survival rate was 66.7% for the patients receiving immunotherapy alone (95% CI: 42.5-82.5%) and 83.3% for those receiving radiotherapy and immunotherapy (95% CI: 48.2-95.6%; P=0.131). The locoregional progression rate was 24% in patients receiving immunotherapy and 8% in patients receiving immunotherapy and radiotherapy (P=0.379). After adjuvant treatment, 6% of patients developed grade 3 or above immunotherapy-related events and none developed grade 3 or above radiation-related adverse events.
CONCLUSIONS: In patients with stage III melanoma, adjuvant lymph-node field radiotherapy combined with immunotherapy seems to be associated with longer disease-free survival, with acceptable tolerance. However, these results need to be confirmed by long-term and prospective studies.

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BACKGROUND: Primary laryngeal mucosal melanoma is a rare tumour with a poor prognosis. Its often difficult diagnosis should rule out laryngeal metastatic localization of cutaneous melanoma.
METHODS: We report a case of primary laryngeal mucosal melanoma diagnosed in a 65-year-old man, treated 6 years previously with radio-chemotherapy and surgery for squamous cell carcinoma of the right lateral oropharyngeal region. The definitive diagnosis of primary laryngeal mucosal melanoma was made on the resection specimen, whereas the initial biopsy of the epilaryngeal mass discovered during the patient\'s surveillance had concluded that it was a laryngeal recurrence of the known squamous cell carcinoma.
CONCLUSIONS: Through this case, we propose to remind the main characteristics and the diagnostic pitfalls of these tumours.

In some tumoral subtypes chromosomal translocations lead to an oncogenic chimeric protein acting as a tumorigenesis driver event. The main fusion model combines the promoter swapping of an inactivated tumor suppressor gene and a functional kinase that evades its regulatory system. The range of described fusions keeps growing in the 2023 WHO classification of melanocytic tumours. It is not limited to the group of Spitz tumours as previously but now extends to blue tumours and dermal tumours with a melanocytic phenotype. Molecular pathology helps detect these anomalies using clinical and morphological features. This analysis is essential as this strongly conditions the adapted local treatment of such tumours who are often overtreated.

We report a case of primary melanoma of a female urethra diagnosed at a non-metastatic stage in a 48-year-old patient with a history of breast carcinoma treated with radiotherapy and hormone therapy. The patient was consulting for dysuria, hematuria, and perineal pain. The clinical examination found a prolapsed and black mass, developed at the expense of the urethra and located at the anterosuperior part of the vulva. The mass biopsy revealed a proliferation of fusiform and globular cells loaded with black pigment expressing the anti-HMB 45 and PS 100 antibodies. The extension assessment showed an absence of secondary localization. The patient underwent total cystourethrectomy without inguinal lymphadenectomy. There was no recurrence observed on day 100 following the surgery.

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OBJECTIVE: Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery.
METHODS: From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3.
RESULTS: The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05).
CONCLUSIONS: A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.

Despite the efficacy of targeted therapies in melanoma, the management of adverse events with BRAFi and MEKi (inhibitors) is one of the limits of these treatments. Close monitoring is required to ensure efficacy and patient safety. In this case study, we report a patient treated for metastatic melanoma with an unusual and innovative combination of dabrafenib (BRAFi) and cobimetinib (MEKi), to manage pyrexia, and lead to complete remission for 19 months. This is the first case ever reported of metastatic melanoma treated with this off-label combination and characterized by the use of therapeutic drug monitoring.

Melanoma is the most aggressive skin cancer, and surgery is the standard of care for localised disease. However, a risk of local and distant relapse exists despite tumour removal, particularly with thick or ulcerated tumours or lymph node involvement. Immunotherapy with immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L-1 or CTLA-4 demonstrated improved relapse-free survival and distant metastasis-free survival against placebo after surgery for stage-III and high-risk stage-II melanoma. In unresectable localised and metastatic tumours, the double immunotherapy with ICIs (anti-PD-1+ anti-CTLA-4) allows for long-term survival in more than 50% of the patients. Novel immunotherapies (anti-LAG-3 ICI, adoptive cell therapy, intra-tumoural immunotherapy, cancer vaccines) and new combinations are in development to overcome resistance and improve patients\' survival. Therapeutic decisions for each patient should be discussed in a specialised multidisciplinary team.

In oncology, genome-wide testing is a major element in facilitating the implementation of precision medicine. However, current recommendations do not always specify the indication and utility of these tests according to the type of cancer. A national consensus approach based on a modified Delphi methodology was set up to provide expert opinion on the use of genome-wide testing in clinical practice in France. Four groups of experts - 4 each representing the following topics of interest - were defined: non-small cell lung cancer (NSCLC), breast cancer, melanoma, and cancer of unknown primary (CUP). In each group, assertions were formulated by a lead expert (8, 5, 7 and 6, respectively) and rated by five panellists involved in the management of these cancers, on a scale from 1 (strongly disagree) to 9 (strongly agree). Consensus was reached when 75% of the scores were above 7. In case of disagreement, the panellists were asked to justify their rate. In total, 24 statements reached consensus after two to four rounds of rating, depending on the group. While the experts advocated the routine use of genome-wide testing in the diagnostic management of NSCLC and CUP, they did not recommend the systematisation of these tests for breast cancer and melanoma. Nevertheless, access to innovation in France could soon remove certain barriers and allow greater standardisation of broad molecular screening in oncology.