11. Bleomycin concentration in patientsʹ plasma and tumors after electrochemotherapy : a study from InspECT GroupAleš Grošelj, Maša Omerzel, Mojca Kržan, Tina Kosjek, Krisztina Bottyán, Helena Plešnik, Črt Jamšek, Maja Čemažar, Erika Kis, Gregor Serša, 2021, original scientific article Keywords: electrochemotherapy, electroporation, bleomycin
Published in DiRROS: 10.10.2022; Views: 494; Downloads: 242
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12. Combination of pembrolizumab with electrochemotherapy in cutaneous metastases from melanoma : a comparative retrospective study from the InspECT and Slovenian Cancer RegistryLuca Giovanni Campana, Barbara Perić, Matteo Mascherini, Romina Spina, Christian Kunte, Erika Kis, Petra Rozsa, Pietro Quaglino, Maja Čemažar, Maša Omerzel, Gregor Serša, 2021, original scientific article Abstract: 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.
Keywords: electrochemotherapy, metastatic melanoma, skin metastases
Published in DiRROS: 10.10.2022; Views: 468; Downloads: 238
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13. Biological factors of the tumour response to electrochemotherapy : review of the evidence and a research roadmapGregor Serša, Katja Uršič Valentinuzzi, Maja Čemažar, Richard Heller, Maša Omerzel, Luca Giovanni Campana, 2021, review article Abstract: The beneficial effects of electrochemotherapy (ECT) for superficial tumours and, more recently, deepseated malignancies in terms of local control and quality of life are widely accepted. However, the variability in responses across histotypes needs to be explored. Currently, patient selection for ECT is based on clinical factors (tumour size, histotype, and exposure to previous oncological treatments), whereas there are no biomarkers to predict the response to treatment. In this field, two major areas of investigation can be identified, i.e., tumour cell characteristics and the tumour microenvironment (vasculature, extracellular matrix, and immune infiltrate). For each of these areas, we describe the current knowledge and discuss how to foster further investigation. This review aims to provide a summary of the currently used guiding clinical factors and delineates a research roadmap for future studies to identify putative biomarkers of response to ECT. These biomarkers may allow researchers to improve ECT practice by customising treatment parameters, manipulating the tumour and its microenvironment, and exploring novel therapeutic combinations.
Keywords: biological factors, biomarkers, electrochemotherapy, bleomycin, cisplatin
Published in DiRROS: 23.09.2022; Views: 526; Downloads: 161
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14. Electrochemotherapy in mucosal cancer of the head and neck : a systematic reviewPrimož Strojan, Aleš Grošelj, Gregor Serša, Christina Caroline Plaschke, Jan B. Vermorken, Sandra Nuyts, Remco De Bree, Avraham Eisbruch, William M. Mendenhall, Robert Smee, Alfio Ferlito, 2021, review article Abstract: Electrochemotherapy (ECT) is a local ablative treatment that is based on the reversible electroporation and intracellular accumulation of hydrophilic drug molecules, which greatly increases their cytotoxicity. In mucosal head and neck cancer (HNC), experience with ECT is limited due to the poor accessibility of tumors. In order to review the experience with ECT in mucosal HNC, we undertook a systematic review of the literature. In 22 articles, published between 1998 and 2020, 16 studies with 164 patients were described. Curative and palliative intent treatment were given to 36 (22%) and 128 patients (78%), respectively. The majority of tumors were squamous cell carcinomas (79.3%) and located in the oral cavity (62.8%). In the curative intent group, complete response after one ECT treatment was achieved in 80.5% of the patients, and in the palliative intent group, the objective (complete and partial) response rate was 73.1% (31.2% and 41.9%). No serious adverse events were reported during or soon after ECT and late effects were rare (19 events in 17 patients). The quality-of-life assessments did not show a significant deterioration at 12 months post-ECT. Provided these preliminary data are confirmed in randomized controlled trials, ECT may be an interesting treatment option in selected patients with HNC not amenable to standard local treatment.
Keywords: electrochemotherapy, head and neck cancer, mucosal cancer
Published in DiRROS: 23.09.2022; Views: 542; Downloads: 254
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15. Potentiation of electrochemotherapy effectiveness by immunostimulation with IL-12 gene electrotransfer in mice is dependent on tumor immune statusKatja Uršič Valentinuzzi, Špela Kos, Urška Kamenšek, Maja Čemažar, Simona Miceska, Boštjan Markelc, Simon Buček, Barbara Starešinič, Veronika Kloboves-Prevodnik, Richard Heller, Gregor Serša, 2021, original scientific article Abstract: Electrochemotherapy (ECT) exhibits high therapeutic effectiveness in the clinic, achieving up to 80% local tumor control but without a systemic (abscopal) effect. Therefore, we designed a combination therapy consisting of ECT via intratumoral application of bleomycin, oxaliplatin or cisplatin with peritumoral gene electrotransfer of a plasmid encoding interleukin-12 (p. t. IL-12 GET). Our hypothesis was that p. t. IL-12 GET potentiates the effect of ECT on local and systemic levels and that the potentiation varies depending on tumor immune status. Therefore, the combination therapy was tested in three immunologically different murine tumor models. In poorly immunogenic B16F10 melanoma, IL-12 potentiated the antitumor effect of ECT with biologically equivalent low doses of cisplatin, oxaliplatin or bleomycin. The most pronounced potentiation was observed after ECT using cisplatin, resulting in a complete response rate of 38% and an abscopal effect. Compared to B16F10 melanoma, better responsiveness to ECT was observed in more immunogenic 4%T1 mammary carcinoma and CT26 colorectal carcinoma. In both models, p. t. IL-12 GET did not significantly improve the therapeutic outcome of ECT using any of the chemotherapeutic drugs. Collectively, the effectiveness of the combination therapy depends on tumor immune status. ECT was more effective in more immunogenic tumors, but GET exhibited greater contribution in less immunogenic tumors. Thus, the selection of the therapy, namely, either ECT alone or combination therapy with p. t. IL-12, should be predominantly based on tumor immune status.
Keywords: electrochemotherapy, gene electrotransfer, interleukin-12
Published in DiRROS: 21.09.2022; Views: 570; Downloads: 197
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16. PARP inhibitor olaparib has a potential to increase the effectiveness of electrochemotherapy in BRCA1 mutated breast cancer in miceMaša Omerzel, Tanja Jesenko, Boštjan Markelc, Larisa Janžič, Maja Čemažar, Gregor Serša, 2021, original scientific article Abstract: Electrochemotherapy (ECT), a local therapy, has different effectiveness among tumor types. In breast can-cer, its effectiveness is low; therefore, combined therapies are needed. The aim of our study was to com-bine ECT with PARP inhibitor olaparib, which could inhibit the repair of bleomycin or cisplatin inducedDNA damage and potentiate the effectiveness of ECT. The effects of combined therapy were studied inBRCA1mutated (HCC1937) and non-mutated (HCC1143) triple negative breast cancer cell lines.Therapeutic effectiveness was studied in 2D and 3D cell cultures andin vivoon subcutaneousHCC1937 tumor model in mice. The underlying mechanism of combined therapy was determined withthe evaluation ofcH2AX foci. Combined therapy of ECT with bleomycin and olaparib potentiated theeffectiveness of ECT inBRCA1mutated HCC1937, but not in non-mutated HCC1143 cells. The combinedtherapy had a synergistic effect, which was due to the increased number of DNA double strand breaks.Addition of olaparib to ECT with bleomycinin vivoin HCC1937 tumor model had only minimal effect,indicating repetitive olaparib treatment would be needed. This study demonstrates that DNA repar inhibiting drugs, like olaparib, have the potential to increase the effectiveness of ECT with bleomycin.
Keywords: electrochemotherapy, breast cancer, olaparib, bleomycin
Published in DiRROS: 21.09.2022; Views: 516; Downloads: 181
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17. Neuroendocrine carcinoma of the larynx and pharynx : a clinical and histopathological studyPrimož Strojan, Robert Šifrer, Alfio Ferlito, Cvetka Grašič-Kuhar, Boštjan Lanišnik, Gaber Plavc, Nina Zidar, 2021, original scientific article Abstract: Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995%2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein%Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs % 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Keywords: electrochemotherapy, head and neck cancer, neuroendocrinic carcinoma
Published in DiRROS: 07.09.2022; Views: 486; Downloads: 221
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