Fig 4 - uploaded by Francesco Perri
Content may be subject to copyright.
Basal cell carcinoma of nasal root and internal canthus of left eye. CT scan: the lesion involves the skin and the medial aspect of the orbit (a); Six weeks after ECT: the lesion disappeared with good healing of the skin (b); Six weeks after ECT: CT scan shows evident reduction of previous lesion (c).
Source publication
Purpose:
To describe outcomes of Electrochemotherapy as palliative treatment in patients with advanced head and neck (H&N) tumours.
Methods:
Ninety-three patients (120 treatment sessions) with H&N recurrent and/or metastatic neoplasm were treated. Treatment response was assessed 4 weeks after ECT with clinical examination and two months after th...
Context in source publication
Context 1
... toxicities related to ECT were seen except for slight edema in the site of electrode implant, which disappeared one week after the procedure. Fig. 4 is shown a case of basal cell carcinoma of nasal root and internal canthus of left eye treated with ECT. The lesion disappeared 6 weeks after the ...
Similar publications
Effects of disease progression on healthcare resource utilization (HRU) and costs among multiple myeloma (MM) patients with ≥1 line of therapy (LOT) and without receipt of stem cell transplant were estimated using large US claims database. Disease progression was defined as advancement to the next LOT, bone metastasis, hypercalcemia, soft tissue pl...
Citations
... More specifically, for small tumours (< 3 cm) the difference in response rate in ulcerated versus non-ulcerated lesions was not statistically significant. In larger malignancies, non-ulcerated tumours showed better responses to ECT than ulcerated ones [13][14][15][16] . EURECA group reported positive results of ECT performed in patients with primary, recurrent, or metastatic skin cancers of the head and neck, which were not suitable for other standard therapeutic approaches. ...
SUMMARY
Head and neck cancers are mostly represented by squamous cell carcinoma. Despite effective treatment of primary tumours, local recurrences and metastases are frequent, with up to a 60% risk of local and 30% of distant failure. Moreover, second primary tumours sometimes occur in these patients (2-3% per year). Treatment of recurrences, metastases, and second primary tumours can be extremely challenging for Otorhinolaryngologists, es- pecially in patients who have already been treated with radiotherapy, previous surgery, or both. Electrochemotherapy represents an effective and valid option in these cases.
KEY WORDS: electrochemotherapy, metastatic, palliative, head and neck, cancer
... The DAHANCA 32, a clinical phase 2 study published in 2018, demonstrated promising results of recurrent mucosal head and neck tumor treatment using ECT. All 26 patients included in the study were pretreated with radiotherapy and had no other curative (87). In both studies, the median survival rate was 9 months (72, 87). ...
... One of the largest recent studies was conducted by Longo et al. in 2019 (87). In this setting, all 93 patients had a recurrent and/or metastatic disease and were treated with at least two chemotherapy and/or radiotherapy lines and were not suitable for surgery or chemo/radiotherapy. ...
... The treatment response based on tumor size was 89.5% CR for lesions of 4 cm or smaller and 16.7% for tumors larger than 4 cm. Similar results were demonstrated by Longo et al. (87). This study found that smaller tumors respond better to ECT (>3 cm OR rate 88%, <3 m OR rate 68%) without depending on tumor histology. ...
Head and neck cancer continues to be among the most prevalent types of cancer globally, yet it can be managed with appropriate treatment approaches. Presently, chemotherapy and radiotherapy stand as the primary treatment modalities for various groups and regions affected by head and neck cancer. Nonetheless, these treatments are linked to adverse side effects in patients. Moreover, due to tumor resistance to multiple drugs (both intrinsic and extrinsic) and radiotherapy, along with numerous other factors, recurrences or metastases often occur. Electrochemotherapy (ECT) emerges as a clinically proven alternative that offers high efficacy, localized effect, and diminished negative factors. Electrochemotherapy involves the treatment of solid tumors by combining a non-permeable cytotoxic drug, such as bleomycin, with a locally administered pulsed electric field (PEF). It is crucial to employ this method effectively by utilizing optimal PEF protocols and drugs at concentrations that do not possess inherent cytotoxic properties. This review emphasizes an examination of diverse clinical practices of ECT concerning head and neck cancer. It specifically delves into the treatment procedure, the choice of anti- cancer drugs, pre-treatment planning, PEF protocols, and electroporation electrodes as well as the efficacy of tumor response to the treatment and encountered obstacles. We have also highlighted the significance of assessing the spatial electric field distribution in both tumor and adjacent tissues prior to treatment as it plays a pivotal role in determining treatment success. Finally, we compare the ECT methodology to conventional treatments to highlight the potential for improvement and to facilitate popularization of the technique in the area of head and neck cancers where it is not widespread yet while it is not the case with other cancer types.
... All studies provided information regarding choice of electrode and 51 describe response to treatment. The four studies that do not aim to evaluate tumour response are included in the Table 1 but are excluded from the forest plot in Figure 2 [55,69,71,72]. One of these studies focuses on pain associated to ECT [55], one on mucosal tumours compared to cutaneous tumours [69], one describes the cost-effectiveness of ECT [71] and the last one describes the possibilities of ECT as a neoadjuvant treatment [72]. Figure 2 depicts all studies included in this review. ...
... The four studies that do not aim to evaluate tumour response are included in the Table 1 but are excluded from the forest plot in Figure 2 [55,69,71,72]. One of these studies focuses on pain associated to ECT [55], one on mucosal tumours compared to cutaneous tumours [69], one describes the cost-effectiveness of ECT [71] and the last one describes the possibilities of ECT as a neoadjuvant treatment [72]. Figure 2 depicts all studies included in this review. These data suggest that despite the many parameters investigated in the studies, the ORR remains high, with a mean of 81.5% [CI 76.3; 87.5] and a standard deviation (SD) of 18.76. ...
... Thirty-six out of the 55 studies mention a reduced QOL being an issue in patients with cutaneous malignancies. In the ESOPE from 2006, QOL is mentioned in their patient monitoring and included in the case report forms [5], however only eight studies have since performed an assessment of QOL using either EORTC, EQ-5D, PGA or SQOLIT questionnaires [8,34,39,47,56,65,69,71]. ECT is often performed as a palliative treatment and it is therefore important to evaluate if the treatment leads to an improvement or deterioration of QOL. ...
Background
Electrochemotherapy (ECT) is an established treatment for primary and secondary cutaneous tumours. The method combines chemotherapy with electroporation, thus increasing the cytotoxic effect of the chemotherapeutic drug. Bleomycin is the drug of choice for ECT, as it is already well established as a treatment for several cancer types and has the largest increase in efficacy after electroporation, enhancing the cytotoxic effect several hundred fold. The response rates of ECT have over the past 30 years been high and consistent. Case based reports point out that the efficacy possibly can be maintained even when the dose of bleomycin is reduced. Consequently in 2018, studies began investigating reducing the bleomycin dose.
Aim
The purpose of this review is to summarise all data published using intravenous bleomycin for cutaneous malignancies and is to our knowledge the first review to examine the use of a reduced bleomycin dose in ECT.
Methods
This study is a systematic review. Fifty-five clinical studies investigating ECT with intravenous bleomycin for patients with cutaneous malignancies were included.
Results
Studies published from 1993 to 2021 investigating the effect of ECT include 3729 patients and indicate a consistent and high response with a mean objective response rate (ORR) of 81.5%. Interestingly, studies using lower doses of bleomycin observe a similar ORR (85.5%), opening the possibility that a lower dose may not be inferior.
Conclusion
This study gives an overview of published studies on ECT with intravenous bleomycin for patients with cutaneous malignancies, including the use of a reduced bleomycin dose, as preparation for a randomised study.
... Mikro-nanosaniye puls sürelerinin darbeli elektrik alanları (PEF'ler) geri dönüştürülebilir elektroporasyona yol açarak kemoterapotiklerin yan etkilerini azaltır. Aynı zamanda kullanım dozunu ve kemoterapotik direncini de azaltabilir (45,46,48,49). ...
... ECT'nin baş ve boyun kanserinde bleomisin ile apoptoz benzeri hücre ölümünü, pankreas kanserinde bleomisin, sisplatin ve oksaliplatin ile nekroptoz ve kolon kanserinde bleomisin ile uygulandığında piroptoz benzeri immünojenik hücre ölümü kanıtı oluşturduğu gösterilmiştir (46,47). IRE ve ECT, immünomodülatör ilaçlarla kombine edildiğinde elektroimmünoterapi olarak adlandırılır. ...
Son bir kaç dekatta tümör ablasyon yöntemleri kanser hastaları için ümit ve�rici tedaviler olarak ortaya çıkmıştır. Bu tedaviler genellikle cerrahi rezeksiyonun
mümkün olmadığı, kemoterapötiklerin etkisiz veya dirençli olduğu bölgelerdeki
tümörleri tedavi etmek için kullanılmaktadır.
Girişimsel onkolojik radyolojide lokal bölgesel tedaviler ablatif ve intraarteri�yel yönlendirmeli tedavilerden oluşur. Özellikle ablasyon teknolojisindeki geliş�meler ile daha büyük boyutlardaki tümörler daha güvenli bir şekilde ablate edil�mektedir. Bu bölümde tedavi amacıyla kullanılan cihazların teknolojik olarak
son ürünlerinden ve ürünlerin fizyolojik, mekanik, elektrik teknolojilerinden ve
nano teknolojilerden söz edilecektir. Son olarak da bu tedavilerin sık görülen
kanserlerdeki endikasyonlarından, uygulama şeklinden ve komplikasyonların�dan bahsedilecektir.
... Mikro-nanosaniye puls sürelerinin darbeli elektrik alanları (PEF'ler) geri dönüştürülebilir elektroporasyona yol açarak kemoterapotiklerin yan etkilerini azaltır. Aynı zamanda kullanım dozunu ve kemoterapotik direncini de azaltabilir (17)(18)(20)(21)(22). ...
Sağlık sistemlerinin güçlendirilmesi; sağlık hizmetlerinin ve teknolojilerinin iyileştirilmesi, sunulması ve sürekli ardışık inovatif süreçleri içerir. İhtiyaç temelli inovasyon bu süreci hızlandırmaktadır. Sağlık ürün ve hizmetlerinin inovatif yönü ile geliştirilerek sunulması, sağlık yeniliğinde bütüncül bir yaklaşımın ayrılmaz bileşenleridir. Sağlık inovasyonunu, finansal olarak sürdürülebilir çözümlerle geliştirip büyütmek için de kritik öneme sahiptir. Sağlık inovasyonuna yaklaşımımız bu nedenle bütünseldir. Sağlıktaki tıkanan düğüme ve karmaşık zorluklara çözümler geliştirmek için bilimsel / teknolojik, sosyal ve ticari inovasyonun koordineli uygulaması ile yeni nesil inovatif hekimlik anlayışının dijital bir güncelleme ile yakın zamanda karşımıza gelmesi kaçınılmaz olacaktır.
... ECT procedure and the patient selection were performed according to the ESOPE (European Standard Operating procedure of Electrochemotherapy) guidelines 32,33 . All patients were treated under general anesthesia and a specific pain management protocol was employed 31 . ...
... Treatment was completed within 8 to 40 minutes after the bleomycin injection 32,33 . ...
RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurremt and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies.
PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treat- ment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR.
RESULTS: In the context of the univariate anal- ysis, tumor size significantly influenced the re- sponse to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centime- ters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A dif- ference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the me- dian current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%.
CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in ad- vanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.
... A recent review about ECT in mucosal head and neck cancer showed that it was used with a palliative intent in 78% of cases with an overall objective response rate of 73% [3]. Longo et al. observed an objective response in 45% of subjects (5% CR, 40% PR) with advanced skin and mucosal head and neck tumors [17]. On the other hand, Pichi et al. showed a 100% overall response (8% CR, 92% PR) in patients with recurrent large lesions of skin or mucosa [18]. ...
Background:
Primary or recurrent head and neck cancer of skin or mucosa represents a challenge for clinicians and could be debilitating for the patient. Electrochemotherapy (ECT) emerged as a local ablative procedure for cutaneous and mucosal head and neck tumors. The aim of this observational study was the evaluation of quality of life (QoL) after ECT in patients without other surgical or radiation options as curative treatment.
Materials and methods:
The procedure was performed according the ESOPE (European Standard Operating procedure of Electrochemotherapy) protocol. Twenty-seven patients were evaluated before ECT (T0) and 1 (T1), 3 (T2), and 6 (T3) months after the procedure. QoL was assessed by means of the EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires.
Results:
The objective tumor response rate was 48% (11% CR, 37% PR). Bleeding control was achieved in 7/7 patients who experienced bleeding prior to ECT. QoL improvement was observed after the procedure. In particular, global health status and social functioning were higher after ECT (p 0.026 and 0.043), while pain, pain-killers use and appetite loss decreased (p 0.045, 0.025 and 0.002).
Conclusion:
ECT represents a safe and effective treatment for skin and mucosal head and neck tumors without other curative options. It ensures a good pain and bleeding control without worsening of QoL.
... Electrochemotherapy is used not only for cutaneous metastasis but also for primary tumors [59]. Patients who underwent cardiac surgery, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), or who have comorbidities such as diabetes can be treated by ECT [60,61]. Its efficacy is well demonstrated for cutaneous and subcutaneous primary and metastatic melanomas [62], primary and metastatic basal cell carcinoma [63,64], primary and metastatic squamous cell carcinoma [65,66], keratoacanthoma [67], ungual warts [68], Kaposi's sarcoma [3,69], Merkel cell carcinoma [70], cutaneous primary and metastatic lesions of breast cancer [62,71], soft tissue sarcoma (STS) [72], cutaneous B-cell lymphoma [73,74], superficial angiosarcoma [75], locally advanced and metastatic angiosarcoma [76], and as palliative therapy for tumor complications [77][78][79]. ...
Electrochemotherapy (ECT) is an effective bioelectrochemical procedure that uses controlled electrical pulses to facilitate the increase of intracellular concentration of certain substances (electropermeabilization/ reversible electroporation). ECT using antitumor drugs such as bleomycin and cisplatin is a minimally invasive targeted therapy that can be used as an alternative for oncologic patients not eligible for surgery or other standard therapies. Even though ECT is mainly applied as palliative care for metastases, it may also be used for primary tumors that are unresectable due to size and location. Skin neoplasms are the main clinical indication of ECT, the procedure reporting good curative results and high efficiency across all tumor types, including melanoma. In daily practice, there are many cases in which the patient’s quality of life can be significantly improved by a safe procedure such as ECT. Its popularity must be increased because it has a safe profile and minor local adverse reactions. The method can be used by dermatologists, oncologists, and surgeons. The aim of this paper is to review recent literature concerning electrochemotherapy and other clinical applications of electroporation for the targeted therapy of metastatic melanoma.
... The main endpoints of the trial were quality of life, pain, and bleeding control, while the secondary endpoints were ORR and disease control rate (DCR, i.e., the sum of the stable disease, partial responses and complete responses). As results, an optimal control of bleeding and pain were achieved, and more interestingly, a DCR rate of 79% was seen [61]. In a phase II trial, Plaschke et al. treated 36 patients with recurrent/metastatic SCCHN with the same ECT regimen (bleomycin based), and as results, an ORR rate of 56% was reached [62]. ...
Simple Summary
The purpose of this manuscript is to illustrate the difficulties associated with the treatment of the patient with recurrent metastatic SCCHN. This type of patient is very heterogeneous, including very different cases both as regards the natural history and the types of treatment to be used. The authors then illustrated the possible therapeutic options available and tried to propose the best strategies to be adapted to the individual case, based on the characteristics of the patient and the disease. The main conclusion of the following work is that the multidisciplinary approach is the winning weapon in any patient.
Abstract
Squamous cell carcinoma of the head and neck (SCCHN) is a complex group of malignancies, posing several challenges to treating physicians. Most patients are diagnosed with a locally advanced disease and treated with strategies integrating surgery, chemotherapy, and radiotherapy. About 50% of these patients will experience a recurrence of disease. Recurrent/metastatic SCCHN have poor prognosis with a median survival of about 12 months despite treatments. In the last years, the strategy to manage recurrent/metastatic SCCHN has profoundly evolved. Salvage treatments (surgery or re-irradiation) are commonly employed in patients suffering from locoregional recurrences and their role has gained more and more importance in the last years. Re-irradiation, using some particularly fractionating schedules, has the dual task of reducing the tumor mass and eliciting an immune response against cancer (abscopal effect). In this review, we will analyze the main systemic and/or locoregional strategies aimed at facing the recurrent/metastatic disease, underlining the enormous importance of the multidisciplinary approach in these types of patients.
... The ECT proved to be an interesting antitumoral therapy in 93 patients with advanced chemo and radio-refractory HN neoplasms [48]. Five percent of patients experienced a complete response, 40% partial responses and 20% of the patients experienced a disease progression after the first ECT procedure. ...
... ECT is able to reduce frequent symptoms, such as pain and bleeding, especially in patients with moderate symptoms before the treatment, improving quality of life without damage to healthy tissue and with limited side effects. Moreover, ECT reduces hospitalization time and may contribute to an overall reduction in healthcare costs associated with advanced H&N cancers [48]. ...
Background:
A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) have advanced-stage disease (stages III to IVB) that do not respond to therapy despite aggressive, site-specific multimodality therapy. A great number of them will develop disease recurrence, with up to 60% risk of local failure and up to 30% risk of distant failure. Therapy can be very demanding for the patient especially when important anatomical structures are involved. For these reasons, therapies that preserve organ functionality in combination with effective local tumor control, like electrochemotherapy (ECT), are of great interest. Until few months ago, systemic cetuximab + platinum-based therapy + 5-fluorouracil represented the standard treatment for HNSCC relapses with a median overall survival of 10.1 months and an objective response rate of 36%. Recently the results of KEYNOTE-048 study were published and a new combination of monoclonal antibody named pembrolizumab and chemotherapy emerged as standard first line therapy of recurrent or metastatic tumor that overexpress tissue PDL-1 (Programmed Death 1 ligand). Nevertheless, a variable percentage from 10 to 15% of patients with recurrent/metastatic disease have a tumor that does not overexpress tissue PDL-1, and therefore, according to the results of the KEYNOTE-048 study, does not benefit from replacement of cetuximab with pembrolizumab. These patients will be treated with the "gold standard": cetuximab, cisplatin/carboplatin and 5-fluorouracil.
Aim:
To verify whether electrochemotherapy performed with bleomycin of HNSCC relapses of the oral cavity and oropharynx (single relapse on T) is able to lead to an increase in the objective response rate in comparison with the systemic treatment with cetuximab + platinum-based therapy + 5-fluorouracil in patients with PDL-1 negative tumors.
Methods:
The phase IIb study involves the enrolment of 96 patients who meet the inclusion criteria (48 in the control arm and 48 in the treatment arm). The control arm involves the treatment of HNSCC with systemic treatment (cetuximab + platinum-based therapy + 5-fluorouracil). The treatment arm involves the ECT with bleomycin. The primary objective is to verify the objective response rate of patients in the control arm compared to the treatment arm.
