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Povzetek: The combination of electrochemotherapy with immuno-modulatory treatments has already been explored and proven effective. However, the role of interferon alpha (IFN-alpha) adjuvant therapy of melanoma patients and implication on electrochemotherapy effectiveness has not been explored yet. Therefore, the aim of the study was to retrospectively evaluate the effectiveness and safety of electrochemotherapy after the previous adjuvant treatment with IFN-alpha in melanoma patients. Patients and methods. The study was a retrospective single-center observational analysis of the patients with advanced melanoma, treated with electrochemotherapy after previous IFN-alpha adjuvant therapy. Five patients, treated between January 2008 and December 2014, were included into the study, regardless of the time point of IFN-alpha adjuvant therapy. Results. Electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy proved to be a safe and effective treatment. Patients with one or two metastases responded completely. Among patients with multiple metastases, there was a variable response rate. In one patient all 23 metastases responded completely, in second patient more than 85% of all together 80 metastases responded completely and in third patient all 5 metastases had partial response. Taking into account all metastases from all patients together there was an 85% complete response rate. Conclusions. The study showed that electrochemotherapy of recurrent melanoma after the IFN-alpha adjuvant therapy is a safe and effective treatment modality, which results in a high complete response rate, not only in single metastasis, but also in multiple metastases. The high complete response rate might be due to an IFN-alpha immune-editing effect, however, further studies with a larger number of patients are needed to support this presumption.
Ključne besede: electrochemotherapy, IFN-alpha, melanoma
Objavljeno v DiRROS: 30.04.2024; Ogledov: 13; Prenosov: 3
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Ključne besede: melanoma therapy, bleomycin, electric stimulation therapy
Objavljeno v DiRROS: 15.01.2024; Ogledov: 166; Prenosov: 45
Celotno besedilo (418,42 KB)

Povzetek: Electrochemotherapy (ECT) is an effective locoregional therapy for cutaneous melanoma metastases and has been safely combined with immune checkpoint inhibitors in preliminary experiences. Since ECT is known to induce immunogenic cell death, its combination with immune checkpoint inhibitors might be beneficial. In this study, we aimed to investigate the effectiveness of ECT on cutaneous melanoma metastases in combination with pembrolizumab. We undertook a retrospective matched cohort analysis of stage IIIC%IV melanoma patients, included in the International Network for sharing practices of ECT (InspECT) and the Slovenian Cancer Registry. We compared the outcome of patients who received the following treatments: (a) pembrolizumab alone, (b) pembrolizumab plus ECT, and (c) ECT. The groups were matched for age, sex, performance status, and size of skin metastases. The local objective response rate (ORR) was higher in the pembrolizumab-ECT group than in the pembrolizumab group (78% and 39%, p < 0.001). The 1 year local progression-free survival (LPFS) rates were 86% and 51% (p < 0.001), and the 1 year systemic PFS rates were 64% and 39%, respectively (p = 0.034). The 1 year overall survival (OS) rates were 88% and 64%, respectively (p = 0.006). Our results suggest that skin-directed therapy with ECT improves superficial tumor control in melanoma patients treated with pembrolizumab. Interestingly, we observed longer PFS and OS in the pembrolizumab-ECT group than in the pembrolizumab group. These findings warrant prospective confirmation.
Ključne besede: electrochemotherapy, metastatic melanoma, skin metastases
Objavljeno v DiRROS: 10.10.2022; Ogledov: 472; Prenosov: 238
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Povzetek: Purpose: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.
Ključne besede: melanoma, malignant melanoma, immune-checkpoint inhibitors, molecular imaging biomarkers
Objavljeno v DiRROS: 07.09.2022; Ogledov: 520; Prenosov: 151
Celotno besedilo (9,65 MB)