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European Journal of Gynaecological Oncology  2021, Vol. 42 Issue (4): 662-672    DOI: 10.31083/j.ejgo4204102
Original Research Previous articles | Next articles
A novel application of calcium electroporation to cutaneous manifestations of gynaecological cancer
Yousra Ahmed-Salim1, Srdjan Saso2, *(), Hannah E Meehan3, Nicolas Galazis4, David L Phelps5, Benjamin P Jones6, Maxine Chan5, Mehar Chawla7, Kostas Lathouras8, Hani Gabra9, Christina Fotopoulou10, Sadaf Ghaem-Maghami10, James Richard Smith8
1Department of Obstetrics and Gynaecology, The Hillingdon Hospitals NHS Foundation Trust, UB8 3NN London, UK
2Department of Gynaecological Oncology, Institute of Reproductive & Developmental Biology, Imperial College London, W12 0HS London, UK
3Department of Obstetrics and Gynaecology, Imperial College NHS Healthcare Trust, W12 0HS London, UK
4Department of Obstetrics and Gynaecology, St Mary’s Hospital, W2 1NY London, UK
5Department of Gynaecological Oncology, Imperial College NHS Trust, W12 0HS London, UK
6Division of Surgery and Cancer, Imperial College London, W12 0HS London, UK
7Department of Obstetrics and Gynaecology, North Middlesex NHS Trust, N18 1QX London, UK
8West London Gynaecological Cancer Centre, Queen Charlotte’s Hospital, Imperial College London, W12 0HS London, UK
9Department of Medical Oncology, Imperial College London, W12 0HS London, UK
10West London Gynaecological Cancer Centre, Queen Charlotte’s Hospital, Imperial College London, W12 0HS London, UK
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Abstract  

Objective: Calcium electroporation (CaEP) is a new technique whereby intracellular concentrations of calcium are elevated by transient permeabilisation of the cell membrane using high-voltage electrical pulses. Tumour necrosis is induced with little damage to healthy tissue. Within gynaecological cancer, vulval cancer and vulval intraepithelial neoplasia (VIN) pose challenges for treatment, given the high recurrence rate, persistent symptoms and repeated resections required. In certain cases, CaEP may provide a suitable alternative. Methods: We present a case series of six patients with recurrent vulval squamous cell carcinoma (n = 2), VIN III (n = 2) and metastatic ovarian cancer (n = 2), five of whom were treated with CaEP. This is the first known application of CaEP to gynaecological cancers. Results: The median follow-up time was 14 months (range 2–18 months). Within the cohort of patients, CaEP was applied a total of 10 times, achieving a complete response five times and partial response four times. Symptoms improved within six weeks for eight episodes following CaEP application. Beyond six weeks, symptoms eventually recurred in all patients and four patients required more than one CaEP procedure. CaEP was useful for palliation of distressing symptoms in one case of metastatic ovarian cancer. No intra-operative or post-operative complications have been reported to date. Conclusion: CaEP may be a promising short-term treatment in selected patients with recurrent VIN and vulval cancer, where other treatments had failed. If validated, it could provide an acceptable alternative where surgery is unacceptable. Long term follow-up is required to evaluate effects on recurrence.

Key words:  Calcium;      Electroporation      Ovarian cancer      Vulval cancer      VIN     
Submitted:  12 December 2020      Revised:  08 March 2021      Accepted:  12 March 2021      Published:  15 August 2021     
*Corresponding Author(s):  Srdjan Saso     E-mail:  srdjan.saso01@imperial.ac.uk

Cite this article: 

Yousra Ahmed-Salim, Srdjan Saso, Hannah E Meehan, Nicolas Galazis, David L Phelps, Benjamin P Jones, Maxine Chan, Mehar Chawla, Kostas Lathouras, Hani Gabra, Christina Fotopoulou, Sadaf Ghaem-Maghami, James Richard Smith. A novel application of calcium electroporation to cutaneous manifestations of gynaecological cancer. European Journal of Gynaecological Oncology, 2021, 42(4): 662-672.

URL: 

https://ejgo.imrpress.com/EN/10.31083/j.ejgo4204102     OR     https://ejgo.imrpress.com/EN/Y2021/V42/I4/662

Fig. 1.  There is no associated patient. (A) ePORE handheld device with needle electrodes adjusted to 20 mm length. (B) ePORE electrical generator during procedure.

Table 1.  A summary of pathology, treatment history, treatment intent, results including complications and follow up for all of the six patients.
Patient Type of lesion Past treatment Date CaEP provided Treatment intent Histology (pre-CaEP) Macroscopic response Microscopic response Symptomatic response Complications
A: Age 44 VIN III 1. PlasmaJet® ablation x2, 2015, 2016 1st CaEP: July 2019 Curative July 2019: VIN III and PAIN (peri-anal intraepithelial neoplasia) Complete response N/A At 4 weeks: vulval pain significantly reduced None
2. Cervical cone excisions No biopsies taken after CaEP At 3 months: mild discomfort in two areas (perianal and clitoral) Discharged the same day
B/G: previous vulval cancer 3. Vulvectomy (clitoral sparing) and a bilateral V-Y ad- 2nd CaEP: Dec 2019 Curative December 2019—VIN II, HPV change and AIN II Partial response N/A At 6 weeks: partial-symptoms resolved None
vancement flap 2017 (technique used to repair cutaneous defects whereby V-shaped incision is made and broad base of V is advanced into the defect, which is then closed in a Y-shape, for better cosmesis) Reduction in clitoral lesion, remaining erythema and thickening in perianal lesion No biopsies taken after CaEP from clitoral lesion, residual symptoms in perianal lesion Discharged the same day
4. Local excision 2018 3rd CaEP: Curative August 2020—severe dys- N/A—awaiting follow-up N/A N/A None
Aug 2020 plasia in all biopsies. No evidence of invasion in late Sept 2020 Discharged the same day
B: Age 48 Metastatic chest wall deposit—FIGO Stage III mucinous ovarian cancer Primary debulking surgery 2015 Aug-19 Palliative August 2019: Mucinous ovarian carcinoma metastatic deposit Complete response N/A Partial, but transient: reduction in pain before abscess formation 10 days later None
Radiotherapy for recurrence 2018 No biopsies taken after CaEP Voice hoarseness persisted however Discharged the same day
Secondary debulking surgery 2018
Brachytherapy 2019
Chemotherapy 2019
C: Age 80 VIN III + vulval SCC 1. Radical vulvectomy and bilateral groin node dissection for stage III squamous cell carcinoma of the vulva 1996 1st CaEP: March 2019 Curative March 2019: vulval squamous cell carcinoma Complete response Complete response Yes None
2. Repeat vulvectomy for recurrence 2013 Biopsies May 2019 (2 months post-CaEP): no evidence of malignancy Discharged the same day
B/G: FIGO stage III vulval SCC 3. Chemoradiotherapy + lymph node excision secondary to a right inguinal lymph node recurrence 2016 2nd CaEP: Sept 2019 Curative September 2019: well-differentiated vulval squamous carcinoma + VIN III Partial response N/A Discomfort still present, especially in the groin None
4. Partial vulvectomy + bilateral VY advancement flaps for recurrence 2017 Macroscopic carcinosis still present in some areas No biopsies taken after CaEP Discharged the same day
(wound became infected and healed poorly) 3rd CaEP: October 2019 Curative October 2019: Differentiated VIN + granulating tissue Complete response Recurrent disease at 3 months 2 weeks: yes, reduced pain None
3 months: recurrence of symptoms Discharged the same day
D: Age 50 VIN III recurrent Local excision 2016 1st CaEP: September 2019 Curative September 2019 (pre-CaEP): VIN III Partial response N/A 4 weeks: pain free. Occasional itching (much reduced) None
At 4 weeks: right upper vulva-single 1 mm spot on labium minus of possible macroscopic VIN
At 5 months: progressive disease No biopsies taken after CaEP 6 months: intense pruritis in labia (area not previously electroporated) + bladder urgency Discharged the same day
PlasmaJet® treatment x2 2016, x2 2017, 2018 2nd CaEP intended for: March 2020 Curative N/A—Procedure rescheduled due to COVID-19 N/A N/A N/A N/A
E: Age 72 FIGO stage III serous ovarian cancer Chemotherapy 2019 Abandoned (could not safely be carried out) Palliative N/A N/A N/A N/A N/A
F: Age 75 FIGO stage III Vulval SCC 1. Chemotherapy for both lung and vulval cancer 2019 1st CaEP: September 2019 Palliative September 2019 (pre-CaEP): vulval squamous cell carcinoma Complete response N/A Pain free for 4 weeks None
B/G No biopsies taken after CaEP Increased mobility
At 1 month: recurrence of pain Discharged the same day
T4N2M1a lung cancer 2. Radiotherapy of pelvis alone 2nd CaEP: October 2019 N/A—no biopsies taken pre-CaEP Partial response N/A Reduction in pain and anxiety None
Mild, residual, possible macroscopic VIN present No biopsies taken after CaEP Discharged the same day
Key. B/G, diagnosis background.
Fig. 2.  Patient B. (A) Pre-sternal lesion before CaEP. (B) Resolution of the lesion after CaEP. (C) CT image of pre-sternal lesion before CaEP. (D) CT image of the lesion after CaEP.

Fig. 3.  Patient C. (A) CaCl2 solution injection to the superficial lesion. (B) Electroporation of the superficial lesion.

Fig. 4.  Patient F. (A) Large tumour affecting mostly the right lower vagina and vulva. (B) Patient F: Intra-operative ultrasound on the right vulval lesion.

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