Endoscopic electrochemotherapy for esophageal cancer: a phase I clinical study

Charlotte Egeland, Lene Baeksgaard, Helle Hjorth Johannesen, Johan Löfgren, Christina Caroline Plaschke, Lars Bo Svendsen, Julie Gehl, Michael Patrick Achiam, Charlotte Egeland, Lene Baeksgaard, Helle Hjorth Johannesen, Johan Löfgren, Christina Caroline Plaschke, Lars Bo Svendsen, Julie Gehl, Michael Patrick Achiam

Abstract

Background and study aims: Esophageal cancer is on the rise in the western world and the disease has a poor 5-year survival prognosis below 20 %. Electrochemotherapy is a treatment where a chemotherapeutic drug is combined with locally applied electrical pulses, in order to increase the drug's cytotoxicity in malignant cells. This study presents the first results with electrochemotherapy treatment in esophageal cancer.

Patients and methods: In this first-in-human trial, six patients with advanced esophageal cancer were treated with electrochemotherapy using intravenous bleomycin. All side effects and adverse events (AEs) were registered and the patients were later evaluated with gastroscopy and 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).

Results: Treatment were well tolerated, main AEs being nausea, vomiting, oral thrush, pneumonia, retrosternal pain, fever, and hoarseness. No serious complications were observed. Five patients had a visual tumor response confirmed by gastroscopy. In two cases, these findings were confirmed with 18F-FDG PET/MRI as it revealed a reduction of total tumor mass.

Conclusion: Electrochemotherapy in patients with advanced esophageal cancer was conducted without major safety concerns. This study paves the way for larger studies, which may further elucidate response rates for and side effects of this new treatment.

Conflict of interest statement

Competing interests None

Figures

Fig. 1
Fig. 1
EndoVE (source: Cork Cancer Research Centre). Images of the device used in the trial- EndoVE ® . The electrode is attached to an endoscope. Tumor tissue is captured in place within the chamber (1 × 1 × 1.5 cm) of the device by a vacuum; this brings the tumor in contact with the two parallel electrodes which deliver pulses in 100 µs intervals. The procedure is repeated until the whole tumor area is covered.
Fig. 2
Fig. 2
Endoscopic treatment response. Individual endoscopic treatment response. The image at the top shows the tumor before treatment, the images in the middle show the tumors after four weeks and the lowest line shows the tumor after eight weeks. Earlier ulcerated tissue is replaced with necrotic tissue with a fibrin layer and the tumors are found less exophytic. Not all patients had the 8 week endoscopy performed, where data are not available frames are left dark.
Fig. 3
Fig. 3
Imaging treatment response. 18F-FDG PET/MRI from patient number 5. From left to right: MRI; 18F-FDG PET; 18F-FDG PET/MRI; MIP*-PET. The arrows show the tumor area; the circle shows the treated area at 8 weeks. Due to stenosis, the distal part could not be treated. In the treated area there is no sign of residual tumor and treatment sequelae is seen as fibrosis. There is no significant change in 18F-FDG activity (SUVmax at baseline 7,59, SUVmax at 8 weeks 7,06). *Maximun intensity projection

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