Endoscopic-Assisted Electrochemotherapy Versus Argon Plasma Coagulation in Non-Curable Esophageal Cancer – A Randomized Clinical Trial
Main Article Content
Abstract
Background: In this randomized clinical trial, we compared endoscopic-assisted electrochemotherapy (ECT) with argon plasma coagulation (APC) in patients suffering from esophageal cancer. We hypothesized that an initial, local tumor treatment could prevent or prolong the time to severe, obstructive dysphagia. Previous studies suggest that ablative therapies might have survival advantages compared with placing an esophageal stent. Methods: We aimed to include 50 patients with non-curable esophageal cancer. Patients were randomized to ECT or APC (1:1) as an upfront treatment and hereafter referred for standard treatment. The primary endpoint was the difference in time to interventional treatment demanding dysphagia. Secondary endpoints included side effects, symptom palliation, tumor response, and survival. Results: Ten patients were included (the study was prematurely terminated due to recruitment challenges), and the results are, therefore, mainly exploratory. Five patients received ECT, and four patients received APC. The median survival time among all patients was ten months. Two patients in the APC group and no patients in the ECT group had an esophageal stent placed during the follow-up period. One month after treatment, dysphagia relief was observed in five patients (two patients in the ECT group), and four patients had a partial response evaluated from CT imaging (three patients from the ECT group). No severe adverse events were registered in either group. Conclusion: ECT and ACP were administrated as initial therapy with few side effects, and none of the patients in the ECT group developed interventional treatment demanding dysphagia during their remaining lifetime. Future studies with ECT should focus on both symptom palliation, the need for re-intervention, and survival.
Article Details
How to Cite
EGELAND, Charlotte et al.
Endoscopic-Assisted Electrochemotherapy Versus Argon Plasma Coagulation in Non-Curable Esophageal Cancer – A Randomized Clinical Trial.
Medical Research Archives, [S.l.], v. 11, n. 9, sep. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4474>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i9.4474.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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5. Mariette C, Gronnier C, Duhamel A, Mabrut JY, Bail JP, Carrere N, et al. Self-expanding covered metallic stent as a bridge to surgery in esophageal cancer: impact on oncologic outcomes. J Am Coll Surg. 2015;220:287-296. doi:10.1016/j.jamcollsurg.2014.11.028.
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11. Gehl J, Sersa G, Matthiessen LW, Muir T, Soden D, Occhini A, et al. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol. 2018;57:874-882. doi:10.1080/0284186x.2018.1454602.
12. Clover AJP, de Terlizzi F, Bertino G, Curatolo P, Odili J, Campana LG, et al. Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019). Eur J Cancer. 2020;138:30-40. doi:10.1016/j.ejca.2020.06.020.
13. Gehl J. Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. Acta Physiol Scand. 2003;177:437-447. doi:10.1046/j.1365-201X.2003.01093.x.
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15. Egeland C, Baeksgaard L, Johannesen HH, Lofgren J, Plaschke CC, Svendsen LB, et al. Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study. Endosc Int Open. 2018;6:E727-E734. doi:10.1055/a-0590-4053.
16. Frandsen SK, Vissing M, Gehl J. A Comprehensive Review of Calcium Electroporation - A Novel Cancer Treatment Modality. Cancers. 2020;12. doi:10.3390/cancers12020290.
17. Egeland C, Baeksgaard L, Gehl J, Gögenur I, Achiam MP. Palliative Treatment of Esophageal Cancer Using Calcium Electroporation. Cancers. 2022;14. doi:10.3390/cancers14215283.
18. Falk Hansen H, Bourke M, Stigaard T, Clover J, Buckley M, O'Riordain M, et al. Electrochemotherapy for colorectal cancer using endoscopic electroporation: a phase 1 clinical study. Endosc Int Open. 2020;8:E124-E132. doi:10.1055/a-1027-6735.
19. Broholm M, Vogelsang R, Bulut M, Stigaard T, Falk H, Frandsen S, et al. Endoscopic Calcium Electroporation for Colorectal Cancer: a phase I study. Endosc Int Open. 2023;0. doi:10.1055/a-2033-9831.
20. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.
21. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. U.S. Department of Health and Human Services: Washington, DC, USA, 2017.
22. Mellow MH. Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction. Analysis of technical and functional efficacy. Arch Intern Med. 1985;145:1443-1446. doi:10.1001/archinte.145.8.1443.
23. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208.
24. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377-381. doi:10.1016/j.jbi.2008.08.010.
25. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191-2194. doi:10.1001/jama.2013.281053.
26. Frandsen SK, Gissel H, Hojman P, Tramm T, Eriksen J, Gehl J. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Res. 2012;72:1336-1341. doi:10.1158/0008-5472.can-11-3782.
27. Sabbagh C, Browet F, Diouf M, Cosse C, Brehant O, Bartoli E, et al. Is stenting as "a bridge to surgery" an oncologically safe strategy for the management of acute, left-sided, malignant, colonic obstruction? A comparative study with a propensity score analysis. Ann Surg. 2013;258:107-115. doi:10.1097/SLA.0b013e31827e30ce.
28. Yamashita S, Tanemura M, Sawada G, Moon J, Shimizu Y, Yamaguchi T, et al. Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer. Oncol Lett. 2018;15:400-406. doi:10.3892/ol.2017.7339.
29. Broholm M, Degett TH, Furbo S, Fiehn AK, Bulut M, Litman T, et al. Colonic Stent as Bridge to Surgery for Malignant Obstruction Induces Gene Expressional Changes Associated with a More Aggressive Tumor Phenotype. Ann Surg Oncol. 2021;28:8519-8531. doi:10.1245/s10434-021-10226-4.
30. Justesen TF, Orhan A, Raskov H, Nolsoe C, Gögenur I. Electroporation and Immunotherapy-Unleashing the Abscopal Effect. Cancers. 2022;14. doi:10.3390/cancers14122876.
31. Campana LG, Peric B, Mascherini M, Spina R, Kunte C, Kis E, et al. Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry. Cancers. 2021;13:4289. doi:10.3390/2072-6694/13/17/4289.
32. Heppt MV, Eigentler TK, Kähler KC, Herbst RA, Göppner D, Gambichler T, et al. Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis. Cancer Immunol Immunother. 2016;65:951-959. doi:10.1007/s00262-016-1856-z.
33. Theurich S, Rothschild SI, Hoffmann M, Fabri M, Sommer A, Garcia-Marquez M, et al. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma. Cancer Immunol Res. 2016;4:744-754. doi:10.1158/2326-6066.Cir-15-0156.
34. Hribernik A, Cemazar M, Sersa G, Bosnjak M, Snoj M. Effectiveness of electrochemotherapy after IFN-α adjuvant therapy of melanoma patients. Radiol Oncol. 2016;50:21-27. doi:10.1515/raon-2015-0048.
35. Mozzillo N, Simeone E, Benedetto L, Curvietto M, Giannarelli D, Gentilcore G, et al. Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy. Oncoimmunology. 2015;4:e1008842. doi:10.1080/2162402x.2015.1008842.
36. Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022;386:449-462. doi:10.1056/NEJMoa2111380.
37. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398:759-771. doi:10.1016/s0140-6736(21)01234-4.
38. Bastrup FA, Vissing M, Gehl J. Electrochemotherapy with intravenous bleomycin for patients with cutaneous malignancies, across tumour histology: a systematic review. Acta Oncol. 2022;61:1093-1104. doi:10.1080/0284186x.2022.2110385
2. Doğan Akagündüz D, Türker PF. Nutritional Support in Older Patients with Esophageal Cancer Undergoing Chemoradiotherapy. Nutr Cancer. 2022;74:3634-3639. doi:10.1080/01635581.2022.2096245.
3. Wilson CK, Frankowski SR, Steelman SC, Makhoul I. Risk Factors for Self-Expandable Metal Stent Complications in the Treatment of Esophageal Cancer: A Scoping Review. SN Compr Clin Med. 2020;2:1163-1173. doi:10.1007/s42399-020-00365-2.
4. Kjaer DW, Nassar M, Jensen LS, Svendsen LB, Mortensen FV. A bridging stent to surgery in patients with esophageal and gastroesophageal junction cancer has a dramatic negative impact on patient survival: A retrospective cohort study through data acquired from a prospectively maintained national database. Dis Esophagus. 2017;30:1-7. doi:10.1111/dote.12474.
5. Mariette C, Gronnier C, Duhamel A, Mabrut JY, Bail JP, Carrere N, et al. Self-expanding covered metallic stent as a bridge to surgery in esophageal cancer: impact on oncologic outcomes. J Am Coll Surg. 2015;220:287-296. doi:10.1016/j.jamcollsurg.2014.11.028.
6. Akhtar K, Byrne JP, Bancewicz J, Attwood SE. Argon beam plasma coagulation in the management of cancers of the esophagus and stomach. Surg Endosc. 2000;14:1127-1130. doi:10.1007/s004640000266.
7. Sigounas DE, Krystallis C, Couper G, Paterson-Brown S, Tatsioni A, Plevris JN. Argon plasma coagulation compared with stent placement in the palliative treatment of inoperable oesophageal cancer. UEG J. 2017;5:21-31. doi:10.1177/2050640616650786.
8. Kofoed SC, Lundsgaard M, Ellemann AC, Svendsen LB. Low morbidity after palliation of obstructing gastro-oesophageal adenocarcinoma to restore swallowing function. Dan Med J. 2012;59:A4434.
9. Shenfine J, McNamee P, Steen N, Bond J, Griffin SM. A randomized controlled clinical trial of palliative therapies for patients with inoperable esophageal cancer. Am J Gastroenterol. 2009;104:1674-1685. doi:10.1038/ajg.2009.155.
10. Dallal HJ, Smith GD, Grieve DC, Ghosh S, Penman ID, Palmer KR. A randomized trial of thermal ablative therapy versus expandable metal stents in the palliative treatment of patients with esophageal carcinoma. Gastrointest Endosc. 2001;54:549-557. doi:10.1067/mge.2001.118947.
11. Gehl J, Sersa G, Matthiessen LW, Muir T, Soden D, Occhini A, et al. Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol. 2018;57:874-882. doi:10.1080/0284186x.2018.1454602.
12. Clover AJP, de Terlizzi F, Bertino G, Curatolo P, Odili J, Campana LG, et al. Electrochemotherapy in the treatment of cutaneous malignancy: Outcomes and subgroup analysis from the cumulative results from the pan-European International Network for Sharing Practice in Electrochemotherapy database for 2482 lesions in 987 patients (2008-2019). Eur J Cancer. 2020;138:30-40. doi:10.1016/j.ejca.2020.06.020.
13. Gehl J. Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. Acta Physiol Scand. 2003;177:437-447. doi:10.1046/j.1365-201X.2003.01093.x.
14. Gothelf A, Mir LM, Gehl J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev. 2003;29:371-387. doi:10.1016/s0305-7372(03)00073-2.
15. Egeland C, Baeksgaard L, Johannesen HH, Lofgren J, Plaschke CC, Svendsen LB, et al. Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study. Endosc Int Open. 2018;6:E727-E734. doi:10.1055/a-0590-4053.
16. Frandsen SK, Vissing M, Gehl J. A Comprehensive Review of Calcium Electroporation - A Novel Cancer Treatment Modality. Cancers. 2020;12. doi:10.3390/cancers12020290.
17. Egeland C, Baeksgaard L, Gehl J, Gögenur I, Achiam MP. Palliative Treatment of Esophageal Cancer Using Calcium Electroporation. Cancers. 2022;14. doi:10.3390/cancers14215283.
18. Falk Hansen H, Bourke M, Stigaard T, Clover J, Buckley M, O'Riordain M, et al. Electrochemotherapy for colorectal cancer using endoscopic electroporation: a phase 1 clinical study. Endosc Int Open. 2020;8:E124-E132. doi:10.1055/a-1027-6735.
19. Broholm M, Vogelsang R, Bulut M, Stigaard T, Falk H, Frandsen S, et al. Endoscopic Calcium Electroporation for Colorectal Cancer: a phase I study. Endosc Int Open. 2023;0. doi:10.1055/a-2033-9831.
20. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655.
21. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. U.S. Department of Health and Human Services: Washington, DC, USA, 2017.
22. Mellow MH. Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction. Analysis of technical and functional efficacy. Arch Intern Med. 1985;145:1443-1446. doi:10.1001/archinte.145.8.1443.
23. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208.
24. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377-381. doi:10.1016/j.jbi.2008.08.010.
25. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191-2194. doi:10.1001/jama.2013.281053.
26. Frandsen SK, Gissel H, Hojman P, Tramm T, Eriksen J, Gehl J. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Res. 2012;72:1336-1341. doi:10.1158/0008-5472.can-11-3782.
27. Sabbagh C, Browet F, Diouf M, Cosse C, Brehant O, Bartoli E, et al. Is stenting as "a bridge to surgery" an oncologically safe strategy for the management of acute, left-sided, malignant, colonic obstruction? A comparative study with a propensity score analysis. Ann Surg. 2013;258:107-115. doi:10.1097/SLA.0b013e31827e30ce.
28. Yamashita S, Tanemura M, Sawada G, Moon J, Shimizu Y, Yamaguchi T, et al. Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer. Oncol Lett. 2018;15:400-406. doi:10.3892/ol.2017.7339.
29. Broholm M, Degett TH, Furbo S, Fiehn AK, Bulut M, Litman T, et al. Colonic Stent as Bridge to Surgery for Malignant Obstruction Induces Gene Expressional Changes Associated with a More Aggressive Tumor Phenotype. Ann Surg Oncol. 2021;28:8519-8531. doi:10.1245/s10434-021-10226-4.
30. Justesen TF, Orhan A, Raskov H, Nolsoe C, Gögenur I. Electroporation and Immunotherapy-Unleashing the Abscopal Effect. Cancers. 2022;14. doi:10.3390/cancers14122876.
31. Campana LG, Peric B, Mascherini M, Spina R, Kunte C, Kis E, et al. Combination of Pembrolizumab with Electrochemotherapy in Cutaneous Metastases from Melanoma: A Comparative Retrospective Study from the InspECT and Slovenian Cancer Registry. Cancers. 2021;13:4289. doi:10.3390/2072-6694/13/17/4289.
32. Heppt MV, Eigentler TK, Kähler KC, Herbst RA, Göppner D, Gambichler T, et al. Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis. Cancer Immunol Immunother. 2016;65:951-959. doi:10.1007/s00262-016-1856-z.
33. Theurich S, Rothschild SI, Hoffmann M, Fabri M, Sommer A, Garcia-Marquez M, et al. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma. Cancer Immunol Res. 2016;4:744-754. doi:10.1158/2326-6066.Cir-15-0156.
34. Hribernik A, Cemazar M, Sersa G, Bosnjak M, Snoj M. Effectiveness of electrochemotherapy after IFN-α adjuvant therapy of melanoma patients. Radiol Oncol. 2016;50:21-27. doi:10.1515/raon-2015-0048.
35. Mozzillo N, Simeone E, Benedetto L, Curvietto M, Giannarelli D, Gentilcore G, et al. Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy. Oncoimmunology. 2015;4:e1008842. doi:10.1080/2162402x.2015.1008842.
36. Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med. 2022;386:449-462. doi:10.1056/NEJMoa2111380.
37. Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021;398:759-771. doi:10.1016/s0140-6736(21)01234-4.
38. Bastrup FA, Vissing M, Gehl J. Electrochemotherapy with intravenous bleomycin for patients with cutaneous malignancies, across tumour histology: a systematic review. Acta Oncol. 2022;61:1093-1104. doi:10.1080/0284186x.2022.2110385