Melanoma-specific expression of the tumor suppressor proteins p16 and PTEN is a favorable prognostic factor in established melanoma brain metastases

xlomafota13 shared this article with you from Inoreader Melanoma-specific expression of the tumor suppressor proteins p16 and PTEN is a favorable prognostic factor in established melanoma brain metastases Via Melanoma Research - Current Issue PTEN and p16 frequently undergo (epi)genetic aberrations in melanoma resulting in decreased, or absent, protein levels. We investigated the prognostic significance of these tumor suppressor genes in melanoma brain metastases (MBMs). Immunohistochemical analysis was performed on archived tissue sections from craniotomies. Expression of PTEN and p16 was semiquantitatively scored (0–3 scale) in melanoma cells, glia, TILs, and endothelial cells of tumor-associated vessels and was compared among the different brain tumor cell compartments. Overall survival (OS) analysis was performed according to PTEN and p16 prot ein expression in melanoma cells. 58 patients (median age 56, 37 male) underwent craniotomy for MBMs before February 2014. The OS of patients with decreased, or absent, protein expression (0, 1+) of PTEN and p16 in melanoma cells was significantly shorter compared to that of patients with high (2+, 3+) expression (median OS 2.40 vs. 10.75 months and 4.1 vs. 8.1 months, respectively; Gehan-Breslow-Wilcoxon test P = 0.026 and P = 0.037, respectively). PTEN and p16 protein expression were significantly lower in TILs compared to melanoma cells (Mann–Whitney test P = 0.023 and P  View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Treatment of in-transit melanoma metastases using intralesional PV-10

xlomafota13 shared this article with you from Inoreader Treatment of in-transit melanoma metastases using intralesional PV-10 Via Melanoma Research - Current Issue Melanoma in-transit metastases (ITMs) can sometimes be difficult to manage by surgical excision due to their number, size or location. Treatment by intralesional injection of PV-10, a 10% solution of rose bengal, has been reported to be a simple, safe and effective alternative, but more outcome data are required to confirm its value in the management of ITMs. Two hundred and twenty-six melanoma ITMs in 48 patients were treated with intralesional PV-10 supplied under a special-access scheme. By 8 weeks a complete response in all injected ITMs was achieved in 22 patients (46%) and a partial response in 19 patients (40%). Of 19 patients who had uninjected metastases, 3 (16%) had a response in these. The most common adverse event was transient localised pain in injected tumours. New ITMs developed in 25 patients within 8 weeks, and later in another 8 patients. Repeat injection cycles were given to 21 patients: 13 of these received repeat injection into partially responding or nonresponding tumours, 5 had new ITMs, as well as partially-responding lesions injected, and 3 received injection into new ITMs only. Twenty-two patients received subsequent systemic therapy. At 1 year 37 of the 48 patients were alive, 28 with melanoma, and at 2 years 27 were alive, and 19 with melanoma. Injection of PV-10 was simple and safe and resulted in tumour involution in most patients and sometimes in noninjected tumours. However, many patients developed new lesions; these were treated by further PV-10 injections or with alternative therapies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas

xlomafota13 shared this article with you from Inoreader A novel C-terminal Hsp90 inhibitor KU758 synergizes efficacy in combination with BRAF or MEK inhibitors and targets drug-resistant pathways in BRAF-mutant melanomas Via Melanoma Research - Current Issue Melanoma remains the most aggressive and fatal form of skin cancer, despite several FDA-approved targeted chemotherapies and immunotherapies for use in advanced disease. Of the 100 350 new patients diagnosed with melanoma in 2020 in the US, more than half will develop metastatic disease leading to a 5-year survival rate View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma

xlomafota13 shared this article with you from Inoreader Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma Via Melanoma Research - Current Issue No data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS ≥12, View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib

xlomafota13 shared this article with you from Inoreader Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib Via Melanoma Research - Current Issue The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initia lly managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients

xlomafota13 shared this article with you from Inoreader BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients Via Melanoma Research - Current Issue Although new compounds have improved the treatment landscape of metastatic melanoma, very limited data exist on the efficacy and safety of treating older patients with novel agents. Here, we provide results of BRAF (BRAFi) ± MEK (MEKi) inhibitor treatment in patients over 75 years (oldest-old patients) with metastatic melanoma. Between 2011 and 2020, 34 consecutive patients with metastatic melanoma over 75 years of age (range 75–89) were treated with BRAFi ± MEKi at the Comprehensive Cancer Center of Helsinki University Hospital. Data on clinical and histopathological features, toxicity, respo nse rate (RR), progression-free survival (PFS) and overall survival (OS) were collected. Patients were treated with BRAFi (n = 22) or BRAFi in combination with MEK inhibitor (MEKi) (n = 12). Grade 1–2 adverse events occurred in 68% of the patients, 32% had grade 3 adverse effects, dose reductions were made for 41% of patients and 29% terminated treatment due to toxicity. Overall, the RR was 62%. Complete responses were achieved in 27% of the patients, and 35% had partial responses. The median PFS was 8 months (range 0–57), and the median OS was 15 months (range 0–71). Tailored BRAFi ± MEKi treatment for older patients is feasible. Adverse effects occur frequently but are manageable by dose adjustment. The occurrence of toxicity of monotherapy was similar to that of combination therapy. The RR and median OS from our retrospective study are comparable with those reported in clinical trials and combination therapy produced somewhat more and longer-lasting respons es. Hence, it seems that older patients may benefit from BRAFi treatment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A case of hyperprolactinaemia in a patient with metastatic melanoma

xlomafota13 shared this article with you from Inoreader A case of hyperprolactinaemia in a patient with metastatic melanoma Via Melanoma Research - Current Issue Ectopic prolactin production from a malignancy is infrequently reported. We report here a 60-year-old gentleman who presented with hyperprolactinaemia (9100 mIU/L) causing expressible galactorrhoea, decreased libido and fatigue thought to be due to ectopic prolactin secretion from a metastatic melanoma. Upon initiation of pembrolizumab, the patient's symptoms resolved and he became normoprolactinaemic. This corresponded with a partial response on radiological imaging. Although the core biopsy of the metastatic melanoma did not exhibit immunostaining for prolactin, we believe that only a subset of the tumour cells possesses prolactin-secreting capacity. This case illustrates the need to consider ectopic prolactin production for a solid malignant tumour as a rare cause of hyperprolactinaemia in patients with a normal pituitary MRI, in the absence of other causes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.