Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study.

The incidence of melanoma has been increasing worldwide during recent decades. The objective of the study was to analyse the trends in incidence for in situ and invasive melanoma in the Spanish region of Catalonia during the period of 2008-2017. We designed a cross-sectional study with an age-period-cohort analysis of melanoma patient data from the Network of Melanoma Centres in Catalonia. Our database covered a population of over seven million and included a total of 8626 patients with incident melanoma. The main outcome measures were crude and age-standardised incidence rates to the European 2013 standard population. Joinpoint regression models were used to evaluate the population trends. We observed an increase in the age-standardised incidence rate (per 100,000 population) of all melanoma subtypes from 11.56 in 2008 to 13.78 in 2017 with an average annual percent change (AAPC) of 3.5%. This incidence increase was seen exclusively in the older population. Moreover, the stratified analysis showed a statistically significant increase in the age-standardised incidence rate for invasive (AAPC 2.1%) and in situ melanoma (AAPC 6.5%). In conclusion, the incidence of melanoma has continued to increase in the elderly population over recent decades, with a rapidly increasing trend of in situ melanomas and the lentigo maligna subtype.

Extranodal natural killer/T-cell lymphoma, nasal type: a Spanish multicentric retrospective survey.

BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive lymphoma with a very low incidence in western populations. OBJECTIVE: To review the clinicopathological features and outcome of a multicentre series of ENKTL in Spain. MATERIALS & METHODS: A multicentre retrospective study was performed based on cases of ENKTL, collected from 1995 to 2004, from 12 dermatology departments included in the Spanish Lymphoma Study Group. The clinical, histopathological, and evolutive features of all these cases were reviewed. RESULTS: Eighteen patients (three male, 15 female) with median age of 67 years were included in the study. The onset of lesions occurred in the nasal region in 11 patients and on the skin outside this region in the remaining cases. The observed lesions were clinically heterogeneous, corresponding to papules, plaques, and nodules, with or without ulceration. All patients except four received different polychemotherapy regimens, either alone (n = 11) or in combination with radiotherapy (n = 4). After a variable follow-up period (1-36 months), only two patients remained alive. One patient was recently diagnosed (four months ago) with ENKTL in the nasal region and the other presented with skin-limited disease. The median overall survival was 9.5 months. CONCLUSIONS: The results of this retrospective survey confirm that ENKTL is a rare subtype of lymphoma in the Spanish population. All patients showed an aggressive clinical course and poor prognosis, regardless of the initial clinical presentation. Prospective data on larger series of patients treated homogenously are needed to establish the best treatment modality.

Blockade of NFκB activity by Sunitinib increases cell death in Bortezomib-treated endometrial carcinoma cells.

Endometrial carcinoma is one of the most common malignancies in the female genital tract, usually treated by surgery and radiotherapy. Chemotherapy is used when endometrial carcinoma is associated with widespread metastasis or when the tumor recurs after radiation therapy. In the present study, we demonstrate that the tyrosine kinase receptor inhibitor Sunitinib reduces cell viability, proliferation, clonogenicity and induces apoptotic cell death in endometrial carcinoma cell lines, which is not due to its action through the most known targets like VEGFR, nor through EGFR as demonstrated in this work. Interestingly, Sunitinib reduces NFκB transcriptional activity either at basal level or activation by EGF or TNF-α. We observed that Sunitinib was able to inhibit the Bortezomib-induced NFκB transcriptional activity which correlates with a decrease of the phosphorylated levels of IKKα and ß, p65 and IκBα. We evaluated the nature of the interaction between Sunitinib and Bortezomib by the dose effect method and identified a synergistic effect (combination index < 1). Analogously, silencing of p65 expression by lentiviral-mediated short-hairpin RNA delivery in Bortezomib treated cells leads to a strongly increased sensitivity to Bortezomib apoptotic cell death. Altogether our results suggest that the combination of Sunitinib and Bortezomib could be considered a promising treatment for endometrial carcinoma after failure of surgery and radiation.

Biochemotherapy with low doses of subcutaneous interleukin-2 in patients with melanoma: results of a phase II trial.

INTRODUCTION: Metastatic melanoma has an ominous prognosis. Bio-chemotherapy regimens can increase the response rate but with a high degree of toxicity due, mainly, to the use of high-dose intravenous interleukin-2. OBJECTIVES: To test the feasibility and activity profile of a bio-chemotherapy regimen of low-dose subcutaneous interleukin-2. MATERIAL AND METHODS: Administration scheme: dacarbazine at 200 mg/m2/d on days 1-4, cisplatin at 20 mg/m2/d intravenous on days 1-4, vinblastine at 1.5 mg/m2/d on days 1-4, IL-2 at 4.5 MUI/m2/d subcutaneous on days 5-8, IFN-alpha at 5 MU subcutaneous on days 5-9, 11, 13, 15 of every 21-day cycle. RESULTS: Objective response was obtained in 11 patients (39.3%; 95%CI: 21-59) including 4 with complete response (14.3%; 95%CI: 4-33). With an extended follow-up of 49 months and 60 months, respectively, 2 patients continue with complete response. The main toxicities were haematological: grade 3-4 neutropenia in 8.2% of cycles, thrombocytopenia in 1.2% and anaemia in 3.2%. CONCLUSIONS: The regimen is safe and has a good activity profile. The presence of long-term survivors, despite the use of lower doses and subcutaneous IL-2, is encouraging.

Biochemotherapy with low doses of subcutaneous interleukin-2 in patients with melanoma: results of a phase II trial

Introduction. Metastatic melanoma has an ominous prognosis. Bio-chemotherapy regimens can increase the response rate but with a high degree of toxicity due, mainly, to the use of high-dose intravenous interleukin-2. Objectives. To test the feasibility and activity profile of a bio-chemotherapy regimen of low-dose subcutaneous interleukin-2. Material and methods. Administration scheme: dacarbazine at 200 mg/m²/d on days 1-4, cisplatin at 20 mg/m²/d intravenous on days 1-4, vinblastine at 1.5 mg/m²/d on days 1-4, IL-2 at 4.5 MUI/m²/d subcutaneous on days 5-8, IFN-alpha at 5 MU subcutaneous on days 5-9, 11, 13, 15 of every 21-day cycle. Results. Objective response was obtained in 11 patients (39.3%; 95%CI: 21-59) including 4 with complete response (14.3%; 95%CI: 4-33). With an extended follow-up of 49 months and 60 months, respectively, 2 patients continue with complete response. The main toxicities were haematological: grade 3-4 neutropenia in 8.2% of cycles, thrombocytopenia in 1.2% and anaemia in 3.2%. Conclusions. The regimen is safe and has a good activity profile. The presence of long-term survivors, despite the use of lower doses and subcutaneous IL-2, is encouraging