[Electrochemotherapy in metastatic melanoma]. / Elektrokemoterápia áttétes melanomában.

INTRODUCTION: In metastatic melanoma, despite the increased survival rates with new innovative therapies, therapeutic response is still quite heterogenous, not always durable. In the case of oligoprogression, several additional therapeutic modalities are available such as electrochemotherapy in the local treatment of cutaneous or subcutaneous metastases. OBJECTIVE: Analysis of our experiences with electrochemotherapy in patients with metastatic melanoma. METHOD AND RESULTS: 23 patients with metastatic melanoma (10 male and 13 female) were treated with electrochemotherapy, between 2016 and 2021 in our Institute. Median age was 74.5 years. The location of metastases varied. 13 of our patients (57%) had metastases on the lower limbs, in 5 cases (22%) metastases were located in the head and neck region, in 4 cases (17%) on the upper limbs, and one (4%) patient received electrochemotherapy for metastases located on the chest. Prior to electrochemotherapy, 7 patients (30%) received chemotherapy, 6 patients (26%) were treated with immunotherapy and 2 patients (9%) received targeted therapy, while electrochemotherapy was first-line treatment for 8 patients (35%). Complete remission was achieved in 12 cases (52%), and partial remission in 6 cases (26%). In 1 case (4%) stable disease was observed, and in 4 patients (35%) progression was detected. We continued the previous systemic therapy which was effective in other localizations after the electrochemotherapy in 8 patients (35%) and in the case of 4 patients (17%) no further systemic therapy was needed. Side effects were observed in 8 patients (35%), 1 had severity of G3. CONCLUSION: Electrochemotherapy in melanoma results in effective local tumor control, improved quality of life, and survival advantage in most of the patients, with tolerable side effects. Orv Hetil. 2023; 164(35): 1381-1386.

Therapeutic and Adverse Effect of Anti-PD1 Immunotherapy in Melanoma: A Retrospective, Single-Institute Study of 222 Patients.

BACKGROUND: The introduction of immuno- and targeted therapeutic modalities meant a breakthrough step in the therapy of melanoma. As a checkpoint inhibitor, the more effective and less toxic anti-PD1 therapy followed an anti-CTLA4 approach. METHODS: From our patient pool, 222 advanced melanoma cases were selected, where anti-PD1 (pembrolizumab, nivolumab) therapy was initiated between March 2015 and December 2020. During our retrospective analysis, the efficacy and safety of the therapy were assessed. RESULTS: The median follow-up was 16 months (interval: 0-64 months), and 150 patients (67.6%) received therapy in the first line, while second and third line therapy was performed among 72 patients (32.4%) for the median of 7.0 months (0-60). In 50 cases, BRAF mutations were detected. Ninety-six patients showed objective response (11.3% CR, 32.0% PR). The median PFS was 10.0 months (0-60), and the median OS was 23.0 months (0-64). Autoimmune side effects were found in 79 patients (35.5%); grade 3 occurred in 6.3% of the cases, while 1 patient died due to fulminant pneumonitis (0.25%). CONCLUSION: Although the range of immunotherapeutic options is getting wider, in the management of melanoma patients, anti-PD1 monotherapy remains an important, effective, and safe method. However, significant correlation was found between the immune-related side effects and therapeutic efficacy.

The Role of Stereotactic Radiotherapy in the Management of Melanoma, A Retrospective Single Institute Preliminary Study of 30 Patients.

Cutaneous melanoma is the third most common type of skin cancer in the world. The incidence of melanoma is increasing in most countries, however, mortality seems to be slowly decreasing. The treatment of advanced cutaneous melanoma changed radically since 2011. The new therapeutic modalities, such as immuno- and targeted therapies give a chance to successfully reach more prolonged progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma. Despite the great therapeutic benefit, most patients eventually develop resistance to these therapies, and the disease will progress. In some cases oligoprogression develops. In those cases local therapy, such as stereotactic radiotherapy can make it possible to continue the previously applied effective medical treatment for the benefit of patients. In our study of a total of 30 patients-20 of them received pre-treatment with systemic medical therapy-received stereotactic radiotherapy using various systems, in the National Institute of Oncology, Hungary, Budapest. We managed to prolong the systemic therapy for 12.5 months median period with the assistance of CyberKnife technique. Therapy related adverse events were mostly tolerable with only 3% of Grade 3 toxicity. We concluded that stereotactic radiotherapy and stereotactic radiosurgery, are safe, and effective therapeutic modalities for regional tumor control in cases of oligoprogression.

[BRAF-MEK inhibitor therapy in melanoma]. / BRAF-MEK gátló terápiával elért eredményeink 118, metasztatikus melanómában szenvedo betegnél az Országos Onkológiai Intézetben.

We investigated the efficacy and safety of vemurafenib+cobimetinib (V+C) and dabrafenib+trametinib (D+T) based on real-life data. From 2015 and 2018 we have selected 118 BRAF-mutated metastatic melanoma patients, treated with V+C and D+T in our institute. We retrospectively analyzed the overall response rate (ORR), the progression-free survival (PFS), the overall survival (OS) and the adverse events of the therapies. The median follow-up time was 18 months (3-43) with V+C and 12 months (3-43) with D+T. The median PFS was 8 months in the V+C and 8.5 months in the D+T group. Median OS was 18 months in V+C group and 12 months with D+T. The ORR was revealed to be 82% in D+T group and 76% in V+C group. Each combination displayed a slightly different safety profile. In our retrospective analysis both BRAF-MEK inhibitor combination therapies showed favorable efficacy with a slightly different spectrum of toxicity profile.

[Stereotactic radiotherapy with CyberKnife and linear accelerator in the management of malignant melanoma]. / CyberKnife és lineáris gyorsító alapú sztereotaxiás sugárkezelés alkalmazása melanómában.

Stereotactic radiotherapy gains more and more importance in the management of malignant melanoma, owing to technical developments of recent years. This approach might be applied with success in solitary or oligometastatic cases, since the deliverable biological dose is far higher than that of conventional radiotherapy. Beyond chemotherapy of decreasing importance, there is a widening range of new targeted and immunotherapy agents, leading to longer survival times even in disseminated stages. This latter underlines that it is worth to treat metastatic lesions locally, making this strategy part of present clinical routine. The authors summarize relevant literature of strereotactic radiotherapy in malignant melanoma, and describe related concepts such as oligometastases, abscopal effect or the combination of radiosurgery with modern systemic therapies.

[COVID-19 and melanoma: a single center retrospective cohort study from Hungary]. / Covid-19 és a melanóma: egy év tapasztalatai az Országos Onkológiai Intézetben.

COVID-19 pandemic affected the diagnosis and management of many diseases, including the most vulnerable group of patients with cancer. In this retrospective survey we evaluated the course of disease of patients treated for melanoma, who got infected with COVID-19 virus between March 2020 and April 2021. 382 patients had been treated for advanced melanoma in our center in this time period. 24 of them had been infected with coronavirus. Six of them suffered in stage III melanoma, the remaining 18 patients had stage IV disease. 14, 5 and 4 of the infected patients had been administered with checkpoint inhibitor, targeted therapy and chemotherapy, respectively. Seven (29%) patients died in COVID-19 infection, in a median of 12 days. None of our patients who had been vaccinated at least one time, had severe symptoms. As a conclusion, the mortality of COVID-19 infection was significantly higher among our melanoma patients compared to the age-standardized mortality rate in Hungary.

Súlyos Covid-19-fertozés disszeminált melanómás betegnél, immunterápiát követoen.

The COVID-19 pandemic has created significant barriers to the treatment of cancer patients requiring regular hospitalisation, as coronavirus infection significantly increases the risk of serious and even fatal complications. In our case report, a middle-aged patient with advanced melanoma has developed immune-mediated pancreatitis after more than a year of pembrolizumab treatment. After changing the therapy, the patient was diagnosed with coronavirus infection, which led to nearly a month of hospitalisation and rehabilitation, thus suspending active oncotherapeutical treatment. Thanks to professional medical care, our patient successfully recovered from the severe COVID-19 pneumonia caused by the infection, even in the absence of a coronavirus vaccine. After recovery, he received two Pfizer- BioNTech vaccines in August and September 2021, and a follow-up CT scan showed almost complete remission. Given the patient's lack of complaints and the absence of tumours other than two residual pulmonary nodules, he was observed afterwards. Our patient was in a serious condition before the vaccines were introduced, but has recovered thanks to professional medical care.

[Large granular lymphocytic leukemia. A rare disease with personalized treatment options]. / Nagy, granulált citoplazmájú lymphocytás leukaemia. Ritka betegség, személyre szabott kezelési lehetoségekkel.

INTRODUCTION: Large granular lymphocyte leukemia is rare, mainly chronic disease. The most common complication is neutropenia, but other immune-mediated cytopenia may also occur. There are no unified treatment recommendations and initiation of treatment mainly depends on the severity of the symptoms. AIM: The aim of the authors was to analyze the main steps of the diagnosis and the necessity and outcome of treatment in their patients diagnosed with large granular lymphocyte leukaemia. METHOD: The authors retrospectively analyzed the data of 17 large granular lymphocyte leukemia patients. RESULTS: Of the 17 patients, 7 patients required treatment because of transfusion dependent anemia (4 patients) or neutropenia (3 patients). In 4 patients corticosteroid was given (supplemented with cyclosporine in one patients), while the other patients received anti-CD52 (one patient), low dose methotrexate (one patient) and combined chemotherapy (one patient). Five patients achieved partial response, and two patients died in sepsis. CONCLUSIONS: In this cohort only a smaller proportion of patients required therapy. Immunosuppression can be successful, but the effect in most cases was temporary. The most serious complication was sepsis, which is associated with a significant risk of mortality in cases with neutropenia.