Electrochemotherapy in Basal & Squamous Cell Carcinoma of Head & Neck; A Prospective Study

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Abstract Background Electrochemotherapy (ECT), a nonthermal locoregional modality, has emerged as a promising alternative for management of basal and squamous cell carcinoma (BCC & SCC) in head and neck (H&N). It can address their substantial therapeutic challenges due to proximity to vital structures and high rates of functional and aesthetic impairment following conventional treatments. This study aimed to evaluate the efficacy, safety, survival outcomes, and quality-of-life benefits of ECT in a diverse cohort of H&N cancer patients. Method A prospective clinical study was conducted on 70 patients with cutaneous, soft tissue, and mucosal BCC / SCC of the H&N, who underwent ECT either as single mode modality or in combination with other therapeutic procedures. Logistic regression and Kaplan–Meier analysis were used to identify predictive response factors and survival assessment. Result The overall objective response rate of the tumors to ECT was 94.2%, with complete remission in 52.9% of patients. Tumor size ≤ 3 cm, BCC histology, primary presentation, and intratumoral injection were significantly associated with higher complete response rates (p < 0.001). One-year local progression-free survival (LPFS) and overall survival (OS) were 94.2% and 87.1%, respectively. The adverse events were mild and transient. In addition, significant post-treatment improvements were observed in pain, physical function, aesthetic and psychosocial well-being. Conclusion The results reinforce the clinical value of ECT and suggest that with appropriate patient selection and protocol optimization, its efficacy can be significantly enhanced across a broad range of H&N cancers.
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Electrochemotherapy in Basal & Squamous Cell Carcinoma of Head & Neck; A Prospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Electrochemotherapy in Basal & Squamous Cell Carcinoma of Head & Neck; A Prospective Study Farrokh Heidari, Mahdis Bayat, Alireza Namvari, Seyyed Mojtaba Yazdanparast, and 19 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7626682/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Electrochemotherapy (ECT), a nonthermal locoregional modality, has emerged as a promising alternative for management of basal and squamous cell carcinoma (BCC & SCC) in head and neck (H&N). It can address their substantial therapeutic challenges due to proximity to vital structures and high rates of functional and aesthetic impairment following conventional treatments. This study aimed to evaluate the efficacy, safety, survival outcomes, and quality-of-life benefits of ECT in a diverse cohort of H&N cancer patients. Method A prospective clinical study was conducted on 70 patients with cutaneous, soft tissue, and mucosal BCC / SCC of the H&N, who underwent ECT either as single mode modality or in combination with other therapeutic procedures. Logistic regression and Kaplan–Meier analysis were used to identify predictive response factors and survival assessment. Result The overall objective response rate of the tumors to ECT was 94.2%, with complete remission in 52.9% of patients. Tumor size ≤ 3 cm, BCC histology, primary presentation, and intratumoral injection were significantly associated with higher complete response rates (p < 0.001). One-year local progression-free survival (LPFS) and overall survival (OS) were 94.2% and 87.1%, respectively. The adverse events were mild and transient. In addition, significant post-treatment improvements were observed in pain, physical function, aesthetic and psychosocial well-being. Conclusion The results reinforce the clinical value of ECT and suggest that with appropriate patient selection and protocol optimization, its efficacy can be significantly enhanced across a broad range of H&N cancers. Biological sciences/Cancer Health sciences/Oncology Electrochemotherapy (ECT) Basal Cell Carcinoma (BCC) Squamous Cell Carcinoma (SCC) Head and Neck Cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 1. INTRODUCTION Basal and squamous cell carcinoma (BCC & SCC) are indeed the most frequent types of malignant lesions found in the cutaneous or mucosal regions of head and neck (H&N) (1–3). Despite significant advances in conventional treatments of these lesions, their incidence is rising rapidly and can produce substantial local destruction along with disfigurement (4). Approximately 50% of patients with H&N cancers experienced recurrence after standard therapeutic approaches include surgery, radiotherapy (RT), and systemic chemotherapy (CT) (5, 6). In addition, conventional methods can pose treatment-induced functional impairments in speech and swallowing, sever aesthetic complications and psychosocial dysfunctions for these patients (7, 8). The proximity to critical anatomical structures and complexity in obtaining free surgical margins, still remain as pitfalls in surgical management of H&N malignancies, lead to compromising the risk of local progression (9–12). In this regard, significant attention must be paid to the potential adverse effects of RT on adjacent vital structures like cranial nerves, brainstem, and cerebral tissue particularly in tumors located near the nasal cavity (13). Besides refinement in surgical techniques, RT, and development of systemic therapies for enhancing treatment efficacy, yet recurrent mucosal tumors continue to present significant therapeutic issues (14). In some cases, specifically recurrent patients, curative intents are no longer accessible, due to impossibility of surgery and RT. Moreover, elderly patients or ones who have serious comorbidities may be excluded from alternative palliative methods, leading to high morbidity and mortality rate (15–17). Given these challenges, sustained disease control requires highly precise treatment and minimally invasive locoregional modalities, that ensure effective tumor control while preserving surrounding tissue integrity and patient’s quality of life. In recent years, electrochemotherapy (ECT) has emerged as an innovative targeted therapeutic approach, which enhances efficacy and alleviate complications of cancer patient’s treatments (18). Electrochemotherapy, a nonthermal local ablative intraoperative strategy, increases cell membrane permeabilization temporarily, thereby improving the intracellular accumulation of chemotherapeutic agents, even at lower doses than standard regimens (19–21). Therefore, it amplifies selective cytotoxicity while sparing adjacent normal structures, making it particularly appropriate for H&N tumors due to cosmetic and functional concerns (22). Clinical researches illustrated up to 95% and 80% response rates with ECT in cutaneous BCC and SCC lesions respectively (23–25). Moreover, its effectiveness extends to soft tissue and deep-seated malignancies of various histology’s (26). This synergistic approach demonstrates proper local tumor control and tumor-related symptoms amelioration in both curative and palliative intent (27–29). The present prospective study conducted to comprehensively assess the efficacy, survival, aesthetic and functional outcomes of ECT in management of cutaneous, soft tissue, and mucosal malignancies of H&N. This comparison is important for the acceptance of this therapy as a first-line topical ablative treatment. 2. METHODS 2.1. Study Design In this prospective cohort study, patients with different types of tumors in H&N, who were candidates for ECT at the two tertiary cancer centers namely Imam Khomeini and Amir Alam Hospitals, were recruited between August 2021 to April 2025. All the test protocols and methods were performed in accordance with the relevant guidelines and regulations of the institutional review board of Tehran University of Medical Science ethical committee which approved the study (IR. TUMS.IKHC. REC.1401.125), and the clinical trial registration code number was (IRCT20190904044697N8). In addition, informed consent was obtained from all subjects and/or their legal guardian(s) for both study participation and publication of identifying information/images in an online open-access publication (when applicable). The Inclusion criteria was patients older than 18 years old with histopathology verified-measurable BCC and SCC lesions of H&N, and a life expectancy exceeding six months. Participants were selected in accordance with the ESOPE guidelines (30). The patients who were not appropriate candidates for conventional treatments due to comorbidities, advanced age, high surgical risk (risk of prolonged anesthesia, functional sequelae and poor cosmetic result) were considered for ECT. All cases were reviewed by a multidisciplinary tumor board, including otorhinolaryngologist and H&N surgeon, chemo-radiotherapist, pathologist, and radiologist. Exclusion criteria comprised patients’ unwillingness, clinically significant arrhythmia, epilepsy, severe lung cystic fibrosis, sepsis, allergy to bleomycin, chronic renal dysfunction (creatinine > 150 mmol/L), severe coagulation disorders, pregnancy or lactation, patients with incomplete follow up data and patients with previous administration to bleomycin exceeding the maximum cumulative dose of 400,000 IU, and renal insufficiency. The most excluded cases in present study were patients who have unwillingness in selecting this therapeutic method due to the novelty of ECT in our country. Overall, a total of 90 patients were included in the study, among whom 20 cases were excluded and the study was reported by 70 cases. (Fig. 1 ). The non-primary, recurrent and metastatic patients had been treated by routine therapeutic approaches including surgery and chemoradiotherapy previously. Treatment free interval of at least 4 weeks was considered after previously applied chemo- or radiotherapy to the target lesions. Patients with primary persistent or recurrent tumors as well as metastatic lesions were treated with palliative intent, while the ones with primary tumors were treated with curative intent. 2.2. Baseline & Follow-Up Assessments All patients had complete demographic data and underwent comprehensive preclinical evaluations, including tumor histopathology and staging, manual measurement of tumor size using calipers and ultrasonography to enhance measurement precision, a complete hematological profile (comprising complete blood count, biochemical profile, inflammatory markers, and electrolyte levels), as well as diagnostic imaging through magnetic resonance imaging (MRI) and/or metastases works up due to tumor pathology and involved primary site location. After the intervention patients followed continuously, and monitored for local response, complications and toxicity. The follow up protocol for every patient was demonstrated in Table 1 . These assessments covered pain intensity, quality of life, and scar characteristics using validated measurement tools. Pain severity was measured using the Numeric Rating Scale (NRS) (31, 32), and quality of life was assessed using the EQ-5D and EORTC QLQ-C30/QLQ-H&N35 questionnaires (33–35). Scar characteristics were evaluated using the Manchester Scar Scale (MSS, 5–18), Visual Analog Scale (VAS, 0–100), and the Vancouver Scar Scale (VSS, 0–13) (36–38). Table 1 Scheduling of follow-ups and ECT sessions Days 0 3 7 30 60 90 120 180 Session 1st - - 2nd (optional) - 3rd (optional) 4th (optional) - Follow-up x x x x x x x x Local tumor response assessment was based on the RECIST Criteria in solid tumors after the ECT treatment protocol at 2 month follow up: complete remission (CR) as total resolution of the tumor, partial remission (PR) as ≥ 30% reduction in tumor diameter, stable disease (SD) < 30% reduction of tumor diameter or < 20% increase of tumor diameter, and progressive disease (PD) ≥ 20% increase in tumor diameter (39). Patients with PR were considered for a second ECT session. Cases of SD or disease progression were re-evaluated by the tumor board to determine the next course of action. We have calculated the local progression free survival (LPFS) from the first ECT session to the first recurrence or to the death of the patient. Alternatively, the length of the LPFS right censored to the end of the study in alive patients with no recurrence. Furthermore, the adverse events were recorded at each follow-up visit using the Common Terminology Criteria (CTCAE) (40). 2.3. ECT Procedure & Patients’ Management Electrochemotherapy was undertaken in accordance with the updated 2018 ESOPE guidelines (30). The electroporation device (OncoPore, Iran) was applied for the treatment and procedures were performed under local or general anesthesia based on the tumor location. Bleomycin was administered either intravenously or intratumorally (15,000 IU/m2 body surface area, dissolved in sterile water with a concentration of 1000 IU/ml, for 30–60 seconds, 8 minutes before the application of electric pulses), depending on tumor characteristics and patient-specific factors. Electrode type was selected based on lesion depth: hexagonal needle electrodes, hexagonal array electrodes, square array electrodes and single needle electrodes were used for superficial and deep-seated tumors based on the tumor’s locations ( Figure S1 ). Moreover, plate electrodes applied for marginal or small superficial ones. For each treatment site, the standard protocol of a train with eight square-wave pulses for 1–3 times (100 µs duration, 1000 V/cm field intensity, 5000 Hz frequency) was applied. Post-treatment care included 24-hour intravenous hydration with isotonic saline (2–3 L/day), broad-spectrum antibiotics (Ciprofloxacin 500 mg every 12 hours and Cephalexin 500 mg every 6 hours), and analgesic agents (Gabapentin 300 mg/day and Acetaminophen 500 mg every 12 hours). To reduce delayed inflammatory responses commonly observed after tissue necrosis, anti-inflammatory therapy was initiated on day 7 post-treatment and continued for 5 days. This regimen included Betamethasone LA (0.3 mg/kg, administered twice with a 4-day interval) and Naproxen (5 mg/kg every 12 hours), which significantly relief the pain in correlation with reduced ESR level of the patients. In cases of toxicity events or tissue necrosis, routine therapeutic approaches were performed accompanied with debridement of the necrotic area with sterile saline solution. 2.4. Statistical Analysis The results were analyzed by using IBM SPSS ver. 26 (IBM Corp., Armonk, NY, USA), and GraphPad Prism 8.0 (GraphPad Software, USA). Categorical data were presented as frequencies and percentages, and continuous data as means with ranges. Tables and statistical graphs were applied to describe the variables. The Chi-square test was used for categorical comparisons, and longitudinal data were analyzed using repeated measures ANOVA. The mean values were compared between two groups utilizing the independent or paired t-test, as well as using non-parametric tests, like the Mann-Whitney U-test. ROC analysis was used to evaluate the predictive performance of proposed model. Kaplan–Meier survival analysis was employed to estimate overall survival (OS) and LPFS, with 95% confidence intervals. A p-value lower than 0.05 was considered statistically significant. 3. RESULTS 3.1. Patients In this clinical trial a total of 70 patients, 48 men and 22 women with a mean age of 68.2 ± 18.5 (Min-Max = 23–98), underwent electrochemotherapy for malignant lesions in H&N region. The patient’s demographic data was presented in Table 2 . Table 2- Patient’s Demographics Gender N (%) Male 48 (68.6) Female 22 (31.4) Age Group Mean ± SD 68.2 ± 18.5 80 20 (28.6) Lesion Per Patient Single 58 (82.9) Multiple 12 (17.1) Family History Yes 15 (21.4) No 47 (67.1) Unknown 8 (11.5) Smoking Yes 11 (15.7) No 59 (84.3) 3.2. Tumor’s Characteristics & ECT Profiles Most participants (82.9%) presented with a single lesion, and according to the study protocol, only one target lesion (the largest one) was taken into consideration for the evaluation of tumor response to ECT (Table 3 ). Among the 70 ECT treated lesions, 36 were SCC, and the other 34 ones were BCC. Tumors were categorized into smaller and larger than 3 cm in diameter (0.1 to 15 cm), the larger lesions comprising 34.3% of all the treated nodules (Table 3 ). Regarding the tumor types, cutaneous tumors accounted for 68.6% of cases, followed by soft tissue and mucosal ones. In terms of depth, 38.6% extended ≤ 5 mm, whereas 35.7% exceeded 10 mm. Many patients had a history of prior treatments: 38.6% had undergone surgery, 35.7% had received RT, and 24.3% had been treated with CT. ECT was administered using intravenous (IV) bleomycin in 55.7% of patients and intratumoral (IT) injection in 44.3%. The majority of post ECT side effects were mild and transient, including erythema (47.9%), localized pain (24.3%), and inflammation (20.7%) (Table 3 ). More serious events were rare, dysphagia (4.9%) and mild tumor lysis syndrome (TLS) (2.2%) occurred in isolated cases. In cases of extensive full thickness lesions of oropharynx and tongue, we observed massive tumor necrosis (three patients). In these cases, neither surgical intervention nor advanced TLS management was required. Importantly, no systemic toxicities or treatment-related deaths were reported. Table 3 Tumors Characteristics Presentation N (%) Primary 36 (51.4) Recurrence 29 (41.4) Metastatic 5 (7.1) Tumor Category Cutaneous 48 (68.6) Soft Tissue & Mucosal 22 (32.4) Tumor Histotype BCC 34 (48.6) SCC 36 (51.4) Size Groups 3 24 (34.3) Invasion Depth (mm) ≤ 5 27 (38.6) 5–10 18 (25.7) ≥ 10 25 (35.7) Stage of Disease 1 10 (14.3) 2 21 (30.0) 3 11 (15.7) 4 28 (40.0) Previous Surgical Treatment Yes 27 (38.6) No 43 (61.4) Previous Radiotherapy Yes 25 (35.7) No 45 (64.3) Previous Chemotherapy Yes 17 (24.3) No 53 (75.7) ECT Intent Curative 57 (81.4) Palliative 13 (18.6) Bleomycin Administration IT 31 (44.3) IV 39 (55.7) Anesthesia Method Local 27 (38.6) General 43 (61.4) Adverse Effects Erythema 67 (47.9) Pain 34 (24.3) Inflammation 29 (20.7) Dysphagia 7 (4.9) TLS 3 (2.2) The patients with primary tumor, BCC histotype, and smaller size underwent ECT with curative intent more than palliative aims ( p = 0.001, p = 0.001, and p = 0.02 respectively). As well as, multiple ECT sessions were more common among patients with SCC histotype and recurrent/metastatic and larger tumors ( p = 0.005, p = 0.02 and p = 0.03 respectively) ( Table 4 ) . Table 4 - ECT Characteristics P-Value Tumor Size Tumor Histotype Presentation Variables N (%) >3 cm ≤3 cm SCC BCC Metastatic Recurrence Primary <0.05* ECT Intent 16 (66.7) 41 (89.1) 24 (66.7) 33 (97.1) 1 (20.0) 24 (82.8) 32 (88.9) Curative 8 (33.3) 5 (10.9) 12 (33.3) 1 (2.9) 4 (80.0) 5 (17.2) 4 (11.1) Palliative <0.05* ECT Cycle 1 (4.2) 10 (21.7) 2 (5.6) 9 (26.5) 0 (0.0) 2 (6.9) 9 (25.0) 1 14 (58.3) 29 (63.0) 21 (58.3) 22 (64.7) 2 (40.0) 21 (72.4) 20 (55.6) 2 9 (37.5) 7 (15.3) 13 (36.1) 3 (8.8) 3 (60.0) 6 (20.7) 7 (19.4) ≥3 3.3. Tumor Response Clinical response was assessed two months after treatment, based on RECIST criteria. Overall, 94.2% of patients responded to ECT. CR was achieved in 52.9% of patients, while 38.6% showed PR. Stable disease was noted in only four cases (5.7%), and no progressive disease was reported ( Table 5 ). Regarding tumor presentation, for the 36 primary tumors, the percentage of CR was 75%, PR 25%, and no SD. In 34 recurrent/metastatic tumors, the percentage for CR was 35.3%, PR 52.9%, and SD 11.8%. All Patients with smaller tumors (≤ 3 cm) had significantly higher CR rates compared to those with larger lesions (76.1% vs. 16.7%, p < 0.001). In addition, patients treated with palliative intent showed PR or SD, while those treated with curative intent achieved CR in 68.4% of cases ( p < 0.001). For more elaboration, the tumors response was also reported based on tumors’ histotype categorization ( Table 5 ). The lesion size has significant association with tumor response ( p = 0.03 for BCC and p = 0.009 for SCC ones). Similarly, there is a significant correlation between ECT outcome and the procedure intent ( p = 0.04 for BCC and p = 0.001 for SCC ones). In fact, BCC tumors were more curative than SCC ones, with CR observed in 81.8% versus 50.0%, respectively. In considering the tumors presentation, it showed only significant effect on response of SCC lesions ( p = 0.02 for SCC vs p = 0.06 for BCC ones). Table 5- Tumor RECIST Variables N (%) Presentation ECT Intent Tumor Size P-Value Primary Recurrence Metastatic curative Palliative ≤ 3 cm > 3 cm Total Patients < 0.001* CR 27 (75.0) 11 (37.9) 1 (20.0) 39 (68.4) 0 (0.0) 35 (76.1) 4 (16.7) PR 9 (25.0) 16 (55.2) 2 (40.0) 16 (28.1) 11 (84.6) 11 (23.9) 16 (66.6) SD 0 (0.0) 2 (6.9) 2 (40.0) 2 (3.5) 2 (15.4) 0 (0.0) 4 (16.7) BCC < 0.05* CR 18 (90.0) 9 (64.3) 0 (0.0) 27 (81.8) 0 (0.0) 26 (83.9) 1 (33.3) PR 2 (10.0) 5 (35.7) 0 (0.0) 6 (18.2) 1(100.0) 5 (16.1) 2 (66.7) SD 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) SCC < 0.05* CR 9 (56.3) 2 (13.4) 1 (20.0) 12 (50.0) 0 (0.0) 9 (60.0) 3 (14.3) PR 7 (43.8) 11(73.3) 2 (40.0) 10 (41.7) 10 (83.3) 6 (40.0) 14 (66.7) SD 0 (0.0) 2 (13.3) 2 (40.0) 2 (8.3) 2 (16.7) 0 (0.0) 4 (19.0) Univariate logistic regression analysis of factors affecting tumor response post-ECT revealed significant correlations with lesion characteristics, disease presentation and methods of bleomycin administration, as details were reported in Table 6 . The size of the lesion has a significant effect on the tumor response, such that the chance of CR in a patient with a tumor size is higher than a patient with a tumor size > 3 cm (OR = 0.06, p < 0.001). The chance of complete tumor response in patients with BCC is significantly higher than in patients with SCC (OR = 0.13, p < 0.001). Moreover, primary tumors responded better than secondary (recurrent/metastatic) ones (OR = 0.18, p < 0.001). As well as, the diverse methods of bleomycin administration have a significant effect on tumor remission (OR = 0.13, p 3 ≤ 3 0.06 0.01–0.22 0.001* Tumor Histotype SCC BCC 0.13 0.04–0.38 0.001* Injection Route IV IT 0.13 0.04–0.14 0.001* Figure 4 illustrates four examples of patients who undergone electrochemotherapy and achieved complete tumor response. Figure 5 illustrate the radiologic assessment of a patient with SCC of tongue who refused traditional treatments due to schizophrenia. He underwent one session of ECT and showed 13×4 mm size reduction. 3.4. Pain, Quality of Life & Cosmetic Outcomes Post-ECT pain scores had not shown any significant effect on pain levels in patients with no or mild pain before the procedure. Although, during follow-up, the percentage of patients with no pain significantly increased (70–80% at 1 months). The univariate analysis of factors affecting the pain score of post operation revealed that pain in the first month after ECT was significantly higher in patients who had lesions with previous RT (OR = 5.25, p = 0.002), larger size (OR = 4.45, p = 0.006), and SCC histotype (OR = 3.85, p = 0.01) (Table 7 ). Notably, the percentage of patients who took opioids at baseline had experienced 90% reduction in the amount of usage after treatment. Table 7 Univariate Logistic Regression Analysis of Post-ECT Pain Factor Predictor Reference Odds Ratio 95% Cis P-Value History of Previous RT + - 5.25 1.81–15.22 0.002* Lesion Size > 3 ≤ 3 4.45 1.54–12.82 0.006* Tumor Histotype SCC BCC 3.85 1.34–11.10 0.01* The analysis of quality of life demonstrated a significant progressive positive perception of well-being for the EQ-5D (Fig. 6 -A) ( p < 0.001). There was a general improvement in all domains of the QLQ-H&N35, with perception of feeling ill, psychosocial aspects, pain and oropharyngeal symptoms being the most significant (Fig. 6 -B) ( p < 0.001). In addition, a significant improvement of physical functioning, role functioning and decrease of fatigue and pain for QLQC30 (Fig. 6 -C) ( p < 0.001). Among the 37 patients with cutaneous lesions who achieved complete tumor remission, aesthetic outcomes were assessed using standardized scar scales (Fig. 7 ). The average scores on the MSS and VSS were 6.94 and 2.72, respectively indicating favorable cosmetic results. Most scars were flat or slightly raised with acceptable pigmentation and texture. 3.5. Survival Outcomes The 1-year LPFS and OS rates of all patients were 94.2% and 87.1%, respectively. The median follow-up of 70 patients included in the LPFS analysis, was 7.36 (mean: 7.25 ± 3.26) months. During follow-up, 4 (5.71%) recurrences occurred among patients (Fig. 8 -A). The dimensions of the lesions in these cases were more than 3 cm in 2 patients, and ≤ 3 cm in 2 ones. Based on Kaplan–Meier analysis for LPFS, the BCC group had significant better survival rate compared to SCC group (CI: 11.08–12.11) (Fig. 8 -B) ( p = 0.02). Three patients had SCC tumor, and one of them had BCC lesion. The median follow-up of 70 patients included in the OS analysis, was 6.85 (mean: 6.92 ± 3.32) months. During follow-up, 9 (12.86%) deaths occurred among patients (Fig. 8 -D). Similarly, based on Kaplan–Meier analysis for OS, the BCC group had significant better survival rate compared to SCC group (CI: 10.06–11.51) (Fig. 8 -E) ( p = 0.003). As well as, the analysis of the 1-year LPFS and OS made on the whole cohort of patients for the subgroup of patients with CR illustrated in Fig. 8 -C &F . Among CR patients, we observed only one recurrence and one death event. 4. DISCUSSION This prospective study provides compelling evidence that ECT offers a safe, effective, and function-preserving approach for the management of BCC and SCC tumors in H&N. The obtained results demonstrated an overall objective response rate of 94.2% with CR in more than half of the patients, consistent with prior multicenter cohort studies (41–43). Among multiple factors associated with tumor’s features which have impact on response rates, ones with size ≤ 3 cm demonstrated significant CR rates 76.1% ( Table 5 ), due to the homogeneous electric field distribution, improved drug penetration in lesions, and preserved vascular architecture in smaller nodules (44, 45). Regarding tumor histotype, BCC tumors showed more than 30% beter response rate with proper survival outcomes than SCC ones, aligned with the lower progressive index and local proliferative nature seen in BCC lesions (41, 46–48). These observations emphasize the beneficial of applying ECT as a first-line approach, lead to enhancing therapeutic outcomes before tumors reach advanced sizes as discussed in recent meta analyses (11). In addition, treatment intent and prior therapeutic history were critical determinants of tumor response. Patients undergoing ECT with curative intent achieved significantly higher CR rates 68.4% than those treated palliatively (49). Similarly, primary tumors showed superior responsiveness in comparison with non-primary tumors 75.0% vs 35.3% ( Table 5 ), which is in line with previous studies, due to the cumulative impact of prior therapies on the tumor microenvironment including vascularity disruption and stromal fibrosis (41, 50). These findings reinforce ECT’s role particularly in H&N, where anatomic complexity and functional considerations often limit conventional interventions (51, 52). Similar to their studies (53,54), intravenous bleomycin remains standard in our work ( Table 6 ), while intertumoral injection was used in patients with single small nodules (< 3cm) or for just bleeding control in cases with severe pulmonary respiratory disease. Over and above, one-year survival analysis illustrated high LPFS and OS rates were 94.2% and 87.1%, respectively (Fig. 8 ), indicating effectiveness of ECT procedure settled in our centers, even in advanced, recurrent, and previously treated cases. Notably, patients with complete remission showed very low recurrence and mortality rates highlighting its curative potential. As well as, in palliative intents, ECT significantly alleviated tumor-related symptoms and serves as an effective disease control modality. Moreover, the obtained results also confirmed that ECT is a safe procedure even in elderly or comorbid populations, with predominantly mild and self-limiting adverse effects including erythema, pain, and transient local inflammation (55, 56). It is noteworthy that systemic toxicity, dysphagia, or TLS were rare and manageable (Table 3 ) (21, 57). Besides oncologic outcomes, the findings underscore the significant quality-of-life and aesthetic benefits of ECT. The tongue SCC case whose radiological image was shown in Fig. 5 not only showed partial reduction in tumor size but also presented drastic change in quality of life (pain reduction and bleeding control) which demonstrates the appropriate efficacy of ECT. Patients experienced sustained improvements in pain, emotional well-being, and functional aspects such as speech, swallowing, and appearance, as measured by validated tools (QLQ-H\&N35, EQ-5D) (Fig. 6 ) (55, 58). Although immediate post-treatment pain was not completely relief due to requirement to immunotherapeutic reactions (we do not order NSAIDs up to 4 days after ECT), pain levels declined over subsequent weeks without requiring increased analgesic usage and decreasing the opioid consumption (19, 59). Post-ECT pain severity is affected by several factors such as tumor size, location, SCC histology, and prior irradiation, suggesting the need for targeted pain management in at-risk patients (Table 7 ). It is worth noting that in patients with mouth mucosal SCCs we must be aware about the air way of the patient and if it was required considerations such as tracheostomy or corticosteroid administration must be considered. These conditions may be happened so rare but it must be concerned specifically in cases with large tumors in borders between tongue and laryngeal entrance. Aesthetic outcomes in patients with complete cutaneous responses were consistently favorable low mean score; MSS 6.94, VSS 2.72, and VAS 26.89, with scars demonstrating acceptable pigmentation, pliability, and vascularity (Fig. 7 ). The obtained results suggest ECT as an appropriate alternative for conventional invasive techniques, to address the function and appearance complications of patients with H&N malignancies. We are capable in treating margins of the tumor with no damage on normal peripheral tissues which is a distinguished specifications of this method in H&N tumors. Despite the promising outcomes, there were some limitations including the single-arm non comparative investigation, and relatively short follow-up duration. While the high response and survival rates are encouraging, longer-term surveillance is necessary to ascertain durability of remission and potential late-onset adverse effects. Therefore, more clinical trials would be helpful in clarifying the role of ECT in the management of H&N cancers. 5. CONCLUSION In conclusion, ECT is an effective and safe treatment for H&N cancers, with high response rates, acceptable aesthetic and functional outcomes, improvement in quality of life, and minimal complications. With the increasing use of ECT and advances in technology, it has the potential to become a cornerstone of locoregional treatment in H&N oncology with both curative and palliative intents, particularly in settings where traditional approaches carry significant morbidity or are no longer feasible. Declarations ACKNOWLEDGEMENTS & FUNDING This work received no financial support. CONFLICT OF INTEREST All the authors declare that they have no conflicts of interest. AUTHOR CONTRIBUTIONS F.H : Investigation, Data Curation, Project administration; M.B : Investigation, Data Curation, Software, Writing-Reviewing & Editing, Project administration; A.N : Investigation, S.M.Y : Investigation, Methodology; S.M : Investigation, Supervision; F.R.P : Investigation, Data Gathering; A.Gh : Investigation, Data Gathering ; N.M : Investigation, Data Gathering; N.H : Data Gathering, Writing-Reviewing & Editing; S.M : Investigation, Data Gathering; N.SH : Investigation, Data Gathering; S.M.S.M : Investigation; O.N : Investigation, Supervision; H.M : Investigation, Supervision; N.SH : Investigation, Data Gathering; F.F : Investigation, Supervision; S.H.S.A : Investigation, Supervision; A.M : Investigation; S.M.S : Data Gathering; B.M : Data Gathering; S.R.M : Investigation, Supervision; E.K : Investigation, Supervision; M.A : Conceptualization, Methodology, Supervision, Resources, Project administration, Data curation, Writing-Reviewing and Editing, Software. 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14:15:14","extension":"html","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":145475,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/53a98866de715f80f05ee2fa.html"},{"id":93842220,"identity":"6be0a337-f1ea-4ce0-b41e-c3e6b20b0f42","added_by":"auto","created_at":"2025-10-18 14:15:13","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":107473,"visible":true,"origin":"","legend":"\u003cp\u003ePatients Consort due to the consensus of multidisciplinary tumor board (MDT)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/7e5799093ccbc08522b8ced0.png"},{"id":93842221,"identity":"e1aa3fa5-b318-4cac-ab99-b1556db5476b","added_by":"auto","created_at":"2025-10-18 14:15:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":618713,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA)\u003c/strong\u003e Distribution of tumors location \u0026amp; patient’s samples as described here: \u003cstrong\u003e1)\u003c/strong\u003e A 40-year-old male presented with a SCC mass of lower lip (size: 10×8×7 mm), infiltrated to the muscles. A complete remission of tumor was achieved after 2 sessions of ECT using a plate probe.\u003cstrong\u003e 2) \u003c/strong\u003eA 54-year-old male presented with a nasal mass diagnosed as BCC (size: 20×15mm) with invasion to the nasal bone. The weekly follow-up revealed complete clinical resolution of the nasal tumor after 2 sessions of ECT using a hexagonal probe. \u003cstrong\u003e3)\u003c/strong\u003e A 88-year-old male presented with an active, hemorrhagic SCC mass involving the lower eyelid (size: 60×60×60 mm), \u0026amp; a complete clinical response was achieved 4 weeks after treatment by applying 1 session ECT using a plate probe. \u003cstrong\u003e4)\u003c/strong\u003e A 90-year-old male presented with an active, bleeding scalp mass (size: 20×20×30 mm) persisting for approximately 1 year. ECT was administered once using hexagonal \u0026amp; plate probes, \u0026amp; a CR was achieved two weeks after treatment \u0026amp; was maintained for 5 months.\u003cstrong\u003e 5) \u003c/strong\u003eA\u003cstrong\u003e \u003c/strong\u003e80-year-old male with SCC of the right ear (size: 6×3×2 mm), referred with active bleeding from the lesion. 2 sessions of ECT were performed using a hexagonal probe, leads to resolving bleeding within 2 weeks, \u0026amp; a CR was achieved at 4 weeks post-treatment.\u003cstrong\u003e 6)\u003c/strong\u003e A 88-year-old female presented with a recurrent large mass diagnosed as SCC (size: 53×42×13 mm, located in the right preauricular region \u0026amp; extending to the skin over the maxillozygomatic area. Metastatic involvement of lymph nodes was noted in levels II \u0026amp; III of the right cervical chain. The patient previously underwent 2 surgical resections for similar lesions. ECT was administered with palliative intent. The primary lesion was treated using a hexagonal probe, while 2 metastatic lymph nodes were treated using a plate electrode. Partial tumor control was achieved 2 weeks post-treatment. The response was sustained for a period of 8 weeks.\u003cstrong\u003e7)\u003c/strong\u003e A 33-year-old female with history of previous partial tongue resection surgery \u0026amp; completed 30 sessions of RT, came with a large SCC tumor (size: 10×8 mm), persistent pain \u0026amp; was considered a candidate for total glossectomy at the time of referral. After 3 sessions of ECT using hexagonal probe, the tongue was preserved.\u003cstrong\u003e B)\u003c/strong\u003e Schematics of tumor electroporation procedure \u0026amp; ECT Device.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/5c34bfdd9ef9d20ac07c76b1.png"},{"id":93843692,"identity":"8d949257-8121-43bf-a957-269752aff0cd","added_by":"auto","created_at":"2025-10-18 14:31:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":62720,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eROC curve of model using multiple variables to predict complete tumor response after ECT. Variables in model included presentation (primary vs non-primary), lesion size (\u0026gt; 3 vs ≤ 3 cm), tumor histotype (BCC vs SCC), \u0026amp; Bleomycin injection route (IT vs IV), AUC was 0.86.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/5657a8edcb953253f86bbee4.png"},{"id":93842232,"identity":"d6038b3a-a774-4b79-89c2-20e7ac04af4c","added_by":"auto","created_at":"2025-10-18 14:15:14","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":846685,"visible":true,"origin":"","legend":"\u003cp\u003eFour examples of patients who undergone electrochemotherapy.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/99962b4cd88cfd6566ec7e80.png"},{"id":93842228,"identity":"96130d38-96e5-4a51-9191-f425d9cc4f33","added_by":"auto","created_at":"2025-10-18 14:15:14","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":556080,"visible":true,"origin":"","legend":"\u003cp\u003eComputed Tomography with IV Contrast. A 24-year-old male with T4a SCC of the tongue demonstrated a partial response following ECT, with significant tumor shrinkage observed after five months, particularly in the anterior and right-sided areas. This reduction indicates that ECT effectively targeted the tumor locally.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/8a457379a2e97642de25a7e2.png"},{"id":93842930,"identity":"50341b3d-0a78-4acf-8b34-e782cbd2834a","added_by":"auto","created_at":"2025-10-18 14:23:14","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":377764,"visible":true,"origin":"","legend":"\u003cp\u003eQuality of life outcomes of patients. \u003cstrong\u003eA)\u003c/strong\u003e EQ-5D mean values at baseline and at each follow-up visit. \u003cstrong\u003eB)\u003c/strong\u003e QLQ-H\u0026amp;N35 mean values at baseline and at each follow-up visit. \u003cstrong\u003eC)\u003c/strong\u003e QLQ-C30 mean values at baseline and at each follow-up visit.\u003csub\u003e(ns: not significant,**p-value\u0026lt;0.001, ***p-value\u0026lt;0.0001, ****p-value\u0026lt;0.00001).\u003c/sub\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/ddadd090df0cb355d1f086bc.png"},{"id":93842931,"identity":"5a12d09a-dc11-4805-83b6-1c4dc440e131","added_by":"auto","created_at":"2025-10-18 14:23:14","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":116162,"visible":true,"origin":"","legend":"\u003cp\u003eAesthetic outcomes of 37 patients with complete tumor response. \u003cstrong\u003eA)\u003c/strong\u003e Graph illustrating the Visual Analog Scale score for each patient. \u003cstrong\u003eB)\u003c/strong\u003e Graph illustrating the Manchester Scar Scale score for each patient. \u003cstrong\u003eC)\u003c/strong\u003e Graph illustrating the Vancouver Scar Scale score for each patient.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/ffb1808ca0b0f4d821795dba.png"},{"id":93843693,"identity":"ffa4fdac-75cb-4d6f-8bfa-a946daf284ac","added_by":"auto","created_at":"2025-10-18 14:31:14","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":196256,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA)\u003c/strong\u003e Kaplan Mier curve of LPFS in whole patients. \u003cstrong\u003eB)\u003c/strong\u003e Kaplan Mier curve of LPFS in whole patients categorized by tumor histotype. \u003cstrong\u003eC)\u003c/strong\u003e Kaplan Mier curve of LPFS in CR patients. \u003cstrong\u003eD)\u003c/strong\u003e Kaplan Mier curve of OS in whole patients. \u003cstrong\u003eE)\u003c/strong\u003e Kaplan Mier curve of OS in whole patients categorized by tumor histotype. \u003cstrong\u003eF)\u003c/strong\u003eKaplan Mier curve of OS in CR patients.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/6337daa5c072601291164ea3.png"},{"id":98624239,"identity":"100bb2b9-9a59-41b9-ad9d-33de41b68d1b","added_by":"auto","created_at":"2025-12-19 17:08:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4487643,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/9f5cc5fe-e3a1-446c-a2e3-a2172614f3af.pdf"},{"id":93842222,"identity":"b83ee0e9-de9b-46c8-8089-1ea1462a496a","added_by":"auto","created_at":"2025-10-18 14:15:13","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":115191,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryECT.docx","url":"https://assets-eu.researchsquare.com/files/rs-7626682/v1/28d550a9623b16f6b1786cbb.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Electrochemotherapy in Basal \u0026 Squamous Cell Carcinoma of Head \u0026 Neck; A Prospective Study","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eBasal and squamous cell carcinoma (BCC \u0026amp; SCC) are indeed the most frequent types of malignant lesions found in the cutaneous or mucosal regions of head and neck (H\u0026amp;N) (1\u0026ndash;3). Despite significant advances in conventional treatments of these lesions, their incidence is rising rapidly and can produce substantial local destruction along with disfigurement (4). Approximately 50% of patients with H\u0026amp;N cancers experienced recurrence after standard therapeutic approaches include surgery, radiotherapy (RT), and systemic chemotherapy (CT) (5, 6). In addition, conventional methods can pose treatment-induced functional impairments in speech and swallowing, sever aesthetic complications and psychosocial dysfunctions for these patients (7, 8).\u003c/p\u003e\u003cp\u003eThe proximity to critical anatomical structures and complexity in obtaining free surgical margins, still remain as pitfalls in surgical management of H\u0026amp;N malignancies, lead to compromising the risk of local progression (9\u0026ndash;12). In this regard, significant attention must be paid to the potential adverse effects of RT on adjacent vital structures like cranial nerves, brainstem, and cerebral tissue particularly in tumors located near the nasal cavity (13). Besides refinement in surgical techniques, RT, and development of systemic therapies for enhancing treatment efficacy, yet recurrent mucosal tumors continue to present significant therapeutic issues (14). In some cases, specifically recurrent patients, curative intents are no longer accessible, due to impossibility of surgery and RT. Moreover, elderly patients or ones who have serious comorbidities may be excluded from alternative palliative methods, leading to high morbidity and mortality rate (15\u0026ndash;17). Given these challenges, sustained disease control requires highly precise treatment and minimally invasive locoregional modalities, that ensure effective tumor control while preserving surrounding tissue integrity and patient\u0026rsquo;s quality of life.\u003c/p\u003e\u003cp\u003eIn recent years, electrochemotherapy (ECT) has emerged as an innovative targeted therapeutic approach, which enhances efficacy and alleviate complications of cancer patient\u0026rsquo;s treatments (18). Electrochemotherapy, a nonthermal local ablative intraoperative strategy, increases cell membrane permeabilization temporarily, thereby improving the intracellular accumulation of chemotherapeutic agents, even at lower doses than standard regimens (19\u0026ndash;21). Therefore, it amplifies selective cytotoxicity while sparing adjacent normal structures, making it particularly appropriate for H\u0026amp;N tumors due to cosmetic and functional concerns (22). Clinical researches illustrated up to 95% and 80% response rates with ECT in cutaneous BCC and SCC lesions respectively (23\u0026ndash;25). Moreover, its effectiveness extends to soft tissue and deep-seated malignancies of various histology\u0026rsquo;s (26). This synergistic approach demonstrates proper local tumor control and tumor-related symptoms amelioration in both curative and palliative intent (27\u0026ndash;29).\u003c/p\u003e\u003cp\u003eThe present prospective study conducted to comprehensively assess the efficacy, survival, aesthetic and functional outcomes of ECT in management of cutaneous, soft tissue, and mucosal malignancies of H\u0026amp;N. This comparison is important for the acceptance of this therapy as a first-line topical ablative treatment.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Study Design\u003c/h2\u003e\u003cp\u003eIn this prospective cohort study, patients with different types of tumors in H\u0026amp;N, who were candidates for ECT at the two tertiary cancer centers namely Imam Khomeini and Amir Alam Hospitals, were recruited between August 2021 to April 2025. All the test protocols and methods were performed in accordance with the relevant guidelines and regulations of the institutional review board of Tehran University of Medical Science ethical committee which approved the study (IR. TUMS.IKHC. REC.1401.125), and the clinical trial registration code number was (IRCT20190904044697N8). In addition, informed consent was obtained from all subjects and/or their legal guardian(s) for both study participation and publication of identifying information/images in an online open-access publication (when applicable).\u003c/p\u003e\u003cp\u003eThe Inclusion criteria was patients older than 18 years old with histopathology verified-measurable BCC and SCC lesions of H\u0026amp;N, and a life expectancy exceeding six months. Participants were selected in accordance with the ESOPE guidelines (30). The patients who were not appropriate candidates for conventional treatments due to comorbidities, advanced age, high surgical risk (risk of prolonged anesthesia, functional sequelae and poor cosmetic result) were considered for ECT. All cases were reviewed by a multidisciplinary tumor board, including otorhinolaryngologist and H\u0026amp;N surgeon, chemo-radiotherapist, pathologist, and radiologist. Exclusion criteria comprised patients\u0026rsquo; unwillingness, clinically significant arrhythmia, epilepsy, severe lung cystic fibrosis, sepsis, allergy to bleomycin, chronic renal dysfunction (creatinine\u0026thinsp;\u0026gt;\u0026thinsp;150 mmol/L), severe coagulation disorders, pregnancy or lactation, patients with incomplete follow up data and patients with previous administration to bleomycin exceeding the maximum cumulative dose of 400,000 IU, and renal insufficiency. The most excluded cases in present study were patients who have unwillingness in selecting this therapeutic method due to the novelty of ECT in our country. Overall, a total of 90 patients were included in the study, among whom 20 cases were excluded and the study was reported by 70 cases. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe non-primary, recurrent and metastatic patients had been treated by routine therapeutic approaches including surgery and chemoradiotherapy previously. Treatment free interval of at least 4 weeks was considered after previously applied chemo- or radiotherapy to the target lesions. Patients with primary persistent or recurrent tumors as well as metastatic lesions were treated with palliative intent, while the ones with primary tumors were treated with curative intent.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Baseline \u0026amp; Follow-Up Assessments\u003c/h2\u003e\u003cp\u003eAll patients had complete demographic data and underwent comprehensive preclinical evaluations, including tumor histopathology and staging, manual measurement of tumor size using calipers and ultrasonography to enhance measurement precision, a complete hematological profile (comprising complete blood count, biochemical profile, inflammatory markers, and electrolyte levels), as well as diagnostic imaging through magnetic resonance imaging (MRI) and/or metastases works up due to tumor pathology and involved primary site location.\u003c/p\u003e\u003cp\u003eAfter the intervention patients followed continuously, and monitored for local response, complications and toxicity. The follow up protocol for every patient was demonstrated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. These assessments covered pain intensity, quality of life, and scar characteristics using validated measurement tools. Pain severity was measured using the Numeric Rating Scale (NRS) (31, 32), and quality of life was assessed using the EQ-5D and EORTC QLQ-C30/QLQ-H\u0026amp;N35 questionnaires (33\u0026ndash;35). Scar characteristics were evaluated using the Manchester Scar Scale (MSS, 5\u0026ndash;18), Visual Analog Scale (VAS, 0\u0026ndash;100), and the Vancouver Scar Scale (VSS, 0\u0026ndash;13) (36\u0026ndash;38).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eScheduling of follow-ups and ECT sessions\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDays\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e90\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e120\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e180\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSession\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1st\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2nd (optional)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3rd\u003c/p\u003e\u003cp\u003e(optional)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e4th\u003c/p\u003e\u003cp\u003e(optional)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFollow-up\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eLocal tumor response assessment was based on the RECIST Criteria in solid tumors after the ECT treatment protocol at 2 month follow up: complete remission (CR) as total resolution of the tumor, partial remission (PR) as \u0026ge;\u0026thinsp;30% reduction in tumor diameter, stable disease (SD)\u0026thinsp;\u0026lt;\u0026thinsp;30% reduction of tumor diameter or \u0026lt;\u0026thinsp;20% increase of tumor diameter, and progressive disease (PD)\u0026thinsp;\u0026ge;\u0026thinsp;20% increase in tumor diameter (39). Patients with PR were considered for a second ECT session. Cases of SD or disease progression were re-evaluated by the tumor board to determine the next course of action. We have calculated the local progression free survival (LPFS) from the first ECT session to the first recurrence or to the death of the patient. Alternatively, the length of the LPFS right censored to the end of the study in alive patients with no recurrence.\u003c/p\u003e\u003cp\u003eFurthermore, the adverse events were recorded at each follow-up visit using the Common Terminology Criteria (CTCAE) (40).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. ECT Procedure \u0026amp; Patients\u0026rsquo; Management\u003c/h2\u003e\u003cp\u003e Electrochemotherapy was undertaken in accordance with the updated 2018 ESOPE guidelines (30). The electroporation device (OncoPore, Iran) was applied for the treatment and procedures were performed under local or general anesthesia based on the tumor location. Bleomycin was administered either intravenously or intratumorally (15,000 IU/m2 body surface area, dissolved in sterile water with a concentration of 1000 IU/ml, for 30\u0026ndash;60 seconds, 8 minutes before the application of electric pulses), depending on tumor characteristics and patient-specific factors. Electrode type was selected based on lesion depth: hexagonal needle electrodes, hexagonal array electrodes, square array electrodes and single needle electrodes were used for superficial and deep-seated tumors based on the tumor\u0026rsquo;s locations (\u003cb\u003eFigure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e\u003c/b\u003e). Moreover, plate electrodes applied for marginal or small superficial ones. For each treatment site, the standard protocol of a train with eight square-wave pulses for 1\u0026ndash;3 times (100 \u0026micro;s duration, 1000 V/cm field intensity, 5000 Hz frequency) was applied.\u003c/p\u003e\u003cp\u003ePost-treatment care included 24-hour intravenous hydration with isotonic saline (2\u0026ndash;3 L/day), broad-spectrum antibiotics (Ciprofloxacin 500 mg every 12 hours and Cephalexin 500 mg every 6 hours), and analgesic agents (Gabapentin 300 mg/day and Acetaminophen 500 mg every 12 hours). To reduce delayed inflammatory responses commonly observed after tissue necrosis, anti-inflammatory therapy was initiated on day 7 post-treatment and continued for 5 days. This regimen included Betamethasone LA (0.3 mg/kg, administered twice with a 4-day interval) and Naproxen (5 mg/kg every 12 hours), which significantly relief the pain in correlation with reduced ESR level of the patients. In cases of toxicity events or tissue necrosis, routine therapeutic approaches were performed accompanied with debridement of the necrotic area with sterile saline solution.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Statistical Analysis\u003c/h2\u003e\u003cp\u003eThe results were analyzed by using IBM SPSS ver. 26 (IBM Corp., Armonk, NY, USA), and GraphPad Prism 8.0 (GraphPad Software, USA). Categorical data were presented as frequencies and percentages, and continuous data as means with ranges. Tables and statistical graphs were applied to describe the variables. The Chi-square test was used for categorical comparisons, and longitudinal data were analyzed using repeated measures ANOVA. The mean values were compared between two groups utilizing the independent or paired t-test, as well as using non-parametric tests, like the Mann-Whitney U-test. ROC analysis was used to evaluate the predictive performance of proposed model. Kaplan\u0026ndash;Meier survival analysis was employed to estimate overall survival (OS) and LPFS, with 95% confidence intervals. A p-value lower than 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Patients\u003c/h2\u003e\u003cp\u003eIn this clinical trial a total of 70 patients, 48 men and 22 women with a mean age of 68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5 (Min-Max\u0026thinsp;=\u0026thinsp;23\u0026ndash;98), underwent electrochemotherapy for malignant lesions in H\u0026amp;N region. The patient\u0026rsquo;s demographic data was presented in \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eTable\u0026nbsp;2- Patient\u0026rsquo;s Demographics\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eN (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e48 (68.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (31.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge Group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (41.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e70\u0026ndash;80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (30.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (28.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLesion Per Patient\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSingle\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58 (82.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMultiple\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (17.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFamily History\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (21.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47 (67.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (11.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSmoking\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (15.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59 (84.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Tumor\u0026rsquo;s Characteristics \u0026amp; ECT Profiles\u003c/h2\u003e\u003cp\u003eMost participants (82.9%) presented with a single lesion, and according to the study protocol, only one target lesion (the largest one) was taken into consideration for the evaluation of tumor response to ECT (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Among the 70 ECT treated lesions, 36 were SCC, and the other 34 ones were BCC. Tumors were categorized into smaller and larger than 3 cm in diameter (0.1 to 15 cm), the larger lesions comprising 34.3% of all the treated nodules (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Regarding the tumor types, cutaneous tumors accounted for 68.6% of cases, followed by soft tissue and mucosal ones. In terms of depth, 38.6% extended\u0026thinsp;\u0026le;\u0026thinsp;5 mm, whereas 35.7% exceeded 10 mm. Many patients had a history of prior treatments: 38.6% had undergone surgery, 35.7% had received RT, and 24.3% had been treated with CT. ECT was administered using intravenous (IV) bleomycin in 55.7% of patients and intratumoral (IT) injection in 44.3%.\u003c/p\u003e\u003cp\u003eThe majority of post ECT side effects were mild and transient, including erythema (47.9%), localized pain (24.3%), and inflammation (20.7%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e). More serious events were rare, dysphagia (4.9%) and mild tumor lysis syndrome (TLS) (2.2%) occurred in isolated cases. In cases of extensive full thickness lesions of oropharynx and tongue, we observed massive tumor necrosis (three patients). In these cases, neither surgical intervention nor advanced TLS management was required. Importantly, no systemic toxicities or treatment-related deaths were reported.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTumors Characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresentation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e36 (51.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRecurrence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e29 (41.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastatic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (7.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Category\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCutaneous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e48 (68.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSoft Tissue \u0026amp; Mucosal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (32.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Histotype\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34 (48.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e36 (51.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSize Groups\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;=3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e46 (65.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24 (34.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInvasion Depth\u003c/b\u003e (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27 (38.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u0026ndash;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18 (25.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (35.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStage of Disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (14.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (30.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (15.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e28 (40.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrevious Surgical Treatment\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27 (38.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e43 (61.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrevious Radiotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (35.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e45 (64.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrevious Chemotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17 (24.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e53 (75.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eECT Intent\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCurative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57 (81.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePalliative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (18.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBleomycin Administration\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e31 (44.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e39 (55.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAnesthesia Method\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLocal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27 (38.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e43 (61.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdverse Effects\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErythema\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e67 (47.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34 (24.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInflammation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e29 (20.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDysphagia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7 (4.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTLS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (2.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe patients with primary tumor, BCC histotype, and smaller size underwent ECT with curative intent more than palliative aims (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001, and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02 respectively). As well as, multiple ECT sessions were more common among patients with SCC histotype and recurrent/metastatic and larger tumors (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03 respectively) (\u003cb\u003eTable\u0026nbsp;4\u003c/b\u003e) .\u003c/p\u003e\u003cp\u003e \u003ctable dir=\"rtl\" border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"684\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTable 4 - ECT Characteristics \u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eP-Value\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 17.5439%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eTumor Size\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 17.5439%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eTumor Histotype\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 29.8246%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003ePresentation\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 26.3158%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"LTR\"\u003eVariables\u003c/span\u003e\u003c/strong\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;N (%)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026gt;3 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026le;3 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003eSCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003eBCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003eMetastatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003eRecurrence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 26.3158%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 14.0351%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eECT Intent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e16 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e41 (89.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e24 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e33 (97.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e1 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e24 (82.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e32 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\n \u003cp dir=\"LTR\"\u003eCurative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.0351%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;8 \u0026nbsp; \u0026nbsp; (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;5 \u0026nbsp;(10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e12 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e1 \u0026nbsp; (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e4 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;5 \u0026nbsp; \u0026nbsp; (17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;4 \u0026nbsp; \u0026nbsp; (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\n \u003cp dir=\"LTR\"\u003ePalliative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.0351%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026lt;0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.0351%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eECT Cycle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e1 \u0026nbsp;(4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e10 (21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e2 \u0026nbsp; (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;9 \u0026nbsp; \u0026nbsp; (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp; \u0026nbsp;0 \u0026nbsp; (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e2 \u0026nbsp;(6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;9 \u0026nbsp; \u0026nbsp; (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\n \u003cp dir=\"LTR\"\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.0351%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e14 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e29 (63.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e21 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e22 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e2 \u0026nbsp;(40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e21 (72.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e20 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.0351%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;9 \u0026nbsp;(37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;7 \u0026nbsp; \u0026nbsp; (15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e13 (36.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e3 \u0026nbsp; (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e3 \u0026nbsp;(60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.5263%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;6 \u0026nbsp; \u0026nbsp; (20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.77193%;\"\u003e\n \u003cp dir=\"LTR\"\u003e7 \u0026nbsp;(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.2807%;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026ge;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.0351%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Tumor Response\u003c/h2\u003e\u003cp\u003eClinical response was assessed two months after treatment, based on RECIST criteria. Overall, 94.2% of patients responded to ECT. CR was achieved in 52.9% of patients, while 38.6% showed PR. Stable disease was noted in only four cases (5.7%), and no progressive disease was reported (\u003cb\u003eTable\u0026nbsp;5\u003c/b\u003e). Regarding tumor presentation, for the 36 primary tumors, the percentage of CR was 75%, PR 25%, and no SD. In 34 recurrent/metastatic tumors, the percentage for CR was 35.3%, PR 52.9%, and SD 11.8%. All Patients with smaller tumors (\u0026le;\u0026thinsp;3 cm) had significantly higher CR rates compared to those with larger lesions (76.1% vs. 16.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, patients treated with palliative intent showed PR or SD, while those treated with curative intent achieved CR in 68.4% of cases (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eFor more elaboration, the tumors response was also reported based on tumors\u0026rsquo; histotype categorization (\u003cb\u003eTable\u0026nbsp;5\u003c/b\u003e). The lesion size has significant association with tumor response (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.03 for BCC and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009 for SCC ones). Similarly, there is a significant correlation between ECT outcome and the procedure intent (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04 for BCC and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001 for SCC ones). In fact, BCC tumors were more curative than SCC ones, with CR observed in 81.8% versus 50.0%, respectively. In considering the tumors presentation, it showed only significant effect on response of SCC lesions (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02 for SCC vs \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.06 for BCC ones).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eTable\u0026nbsp;5- Tumor RECIST\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVariables\u003c/b\u003e N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u003cp\u003e\u003cb\u003ePresentation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e\u003cb\u003eECT Intent\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e\u003cb\u003eTumor Size\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eP-Value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRecurrence\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMetastatic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ecurative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePalliative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;3 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3 cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal Patients\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (75.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (37.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39 (68.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e35 (76.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 (16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (55.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16 (28.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e11 (84.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e11 (23.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e16 (66.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (6.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 (16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBCC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (90.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (64.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27 (81.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e26 (83.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (10.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (35.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (18.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1(100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e2 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSCC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (56.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (13.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e3 (14.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11(73.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10 (41.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10 (83.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e6 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e14 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2 (16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4 (19.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eUnivariate logistic regression analysis of factors affecting tumor response post-ECT revealed significant correlations with lesion characteristics, disease presentation and methods of bleomycin administration, as details were reported in \u003cb\u003eTable\u0026nbsp;6\u003c/b\u003e. The size of the lesion has a significant effect on the tumor response, such that the chance of CR in a patient with a tumor size is higher than a patient with a tumor size\u0026thinsp;\u0026gt;\u0026thinsp;3 cm (OR\u0026thinsp;=\u0026thinsp;0.06, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The chance of complete tumor response in patients with BCC is significantly higher than in patients with SCC (OR\u0026thinsp;=\u0026thinsp;0.13, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Moreover, primary tumors responded better than secondary (recurrent/metastatic) ones (OR\u0026thinsp;=\u0026thinsp;0.18, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). As well as, the diverse methods of bleomycin administration have a significant effect on tumor remission (OR\u0026thinsp;=\u0026thinsp;0.13, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eTable 6- Univariate Logistic Regression Analysis of CR post ECT\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFactor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003ePredictor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eReference\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eOdds Ratio\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e95% Cis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP-Value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresentation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon-primary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePrimary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.06\u0026ndash;0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLesion Size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.01\u0026ndash;0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor Histotype\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.04\u0026ndash;0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInjection Route\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.04\u0026ndash;0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e4\u003c/span\u003e illustrates four examples of patients who undergone electrochemotherapy and achieved complete tumor response.\u003c/p\u003e\u003cp\u003eFigure 5 illustrate the radiologic assessment of a patient with SCC of tongue who refused traditional treatments due to schizophrenia. He underwent one session of ECT and showed 13×4 mm size reduction.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Pain, Quality of Life \u0026amp; Cosmetic Outcomes\u003c/h2\u003e\u003cp\u003ePost-ECT pain scores had not shown any significant effect on pain levels in patients with no or mild pain before the procedure. Although, during follow-up, the percentage of patients with no pain significantly increased (70\u0026ndash;80% at 1 months). The univariate analysis of factors affecting the pain score of post operation revealed that pain in the first month after ECT was significantly higher in patients who had lesions with previous RT (OR\u0026thinsp;=\u0026thinsp;5.25, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), larger size (OR\u0026thinsp;=\u0026thinsp;4.45, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006), and SCC histotype (OR\u0026thinsp;=\u0026thinsp;3.85, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e7\u003c/span\u003e). Notably, the percentage of patients who took opioids at baseline had experienced 90% reduction in the amount of usage after treatment.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate Logistic Regression Analysis of Post-ECT Pain\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePredictor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOdds Ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95% Cis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP-Value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of Previous RT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.81\u0026ndash;15.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.002*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLesion Size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.54\u0026ndash;12.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.006*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTumor Histotype\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eBCC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e1.34\u0026ndash;11.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.01*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe analysis of quality of life demonstrated a significant progressive positive perception of well-being for the EQ-5D (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e6\u003c/span\u003e-A) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was a general improvement in all domains of the QLQ-H\u0026amp;N35, with perception of feeling ill, psychosocial aspects, pain and oropharyngeal symptoms being the most significant (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e6\u003c/span\u003e-B) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, a significant improvement of physical functioning, role functioning and decrease of fatigue and pain for QLQC30 (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e6\u003c/span\u003e-C) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAmong the 37 patients with cutaneous lesions who achieved complete tumor remission, aesthetic outcomes were assessed using standardized scar scales (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e7\u003c/span\u003e). The average scores on the MSS and VSS were 6.94 and 2.72, respectively indicating favorable cosmetic results. Most scars were flat or slightly raised with acceptable pigmentation and texture.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.5. Survival Outcomes\u003c/h2\u003e\u003cp\u003eThe 1-year LPFS and OS rates of all patients were 94.2% and 87.1%, respectively. The median follow-up of 70 patients included in the LPFS analysis, was 7.36 (mean: 7.25\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26) months. During follow-up, 4 (5.71%) recurrences occurred among patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e-A). The dimensions of the lesions in these cases were more than 3 cm in 2 patients, and \u0026le;\u0026thinsp;3 cm in 2 ones. Based on Kaplan\u0026ndash;Meier analysis for LPFS, the BCC group had significant better survival rate compared to SCC group (CI: 11.08\u0026ndash;12.11) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e-B) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02). Three patients had SCC tumor, and one of them had BCC lesion.\u003c/p\u003e\u003cp\u003eThe median follow-up of 70 patients included in the OS analysis, was 6.85 (mean: 6.92\u0026thinsp;\u0026plusmn;\u0026thinsp;3.32) months. During follow-up, 9 (12.86%) deaths occurred among patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e-D). Similarly, based on Kaplan\u0026ndash;Meier analysis for OS, the BCC group had significant better survival rate compared to SCC group (CI: 10.06\u0026ndash;11.51) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e-E) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003).\u003c/p\u003e\u003cp\u003eAs well as, the analysis of the 1-year LPFS and OS made on the whole cohort of patients for the subgroup of patients with CR illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e-C\u003cb\u003e\u0026amp;F\u003c/b\u003e. Among CR patients, we observed only one recurrence and one death event.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eThis prospective study provides compelling evidence that ECT offers a safe, effective, and function-preserving approach for the management of BCC and SCC tumors in H\u0026amp;N. The obtained results demonstrated an overall objective response rate of 94.2% with CR in more than half of the patients, consistent with prior multicenter cohort studies (41\u0026ndash;43). Among multiple factors associated with tumor\u0026rsquo;s features which have impact on response rates, ones with size\u0026thinsp;\u0026le;\u0026thinsp;3 cm demonstrated significant CR rates 76.1% (\u003cb\u003eTable\u0026nbsp;5\u003c/b\u003e), due to the homogeneous electric field distribution, improved drug penetration in lesions, and preserved vascular architecture in smaller nodules (44, 45). Regarding tumor histotype, BCC tumors showed more than 30% beter response rate with proper survival outcomes than SCC ones, aligned with the lower progressive index and local proliferative nature seen in BCC lesions (41, 46\u0026ndash;48). These observations emphasize the beneficial of applying ECT as a first-line approach, lead to enhancing therapeutic outcomes before tumors reach advanced sizes as discussed in recent meta analyses (11).\u003c/p\u003e\u003cp\u003eIn addition, treatment intent and prior therapeutic history were critical determinants of tumor response. Patients undergoing ECT with curative intent achieved significantly higher CR rates 68.4% than those treated palliatively (49). Similarly, primary tumors showed superior responsiveness in comparison with non-primary tumors 75.0% vs 35.3% (\u003cb\u003eTable\u0026nbsp;5\u003c/b\u003e), which is in line with previous studies, due to the cumulative impact of prior therapies on the tumor microenvironment including vascularity disruption and stromal fibrosis (41, 50). These findings reinforce ECT\u0026rsquo;s role particularly in H\u0026amp;N, where anatomic complexity and functional considerations often limit conventional interventions (51, 52).\u003c/p\u003e\u003cp\u003eSimilar to their studies (53,54), intravenous bleomycin remains standard in our work (\u003cb\u003eTable\u0026nbsp;6\u003c/b\u003e), while intertumoral injection was used in patients with single small nodules (\u0026lt;\u0026thinsp;3cm) or for just bleeding control in cases with severe pulmonary respiratory disease.\u003c/p\u003e\u003cp\u003eOver and above, one-year survival analysis illustrated high LPFS and OS rates were 94.2% and 87.1%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e), indicating effectiveness of ECT procedure settled in our centers, even in advanced, recurrent, and previously treated cases. Notably, patients with complete remission showed very low recurrence and mortality rates highlighting its curative potential. As well as, in palliative intents, ECT significantly alleviated tumor-related symptoms and serves as an effective disease control modality. Moreover, the obtained results also confirmed that ECT is a safe procedure even in elderly or comorbid populations, with predominantly mild and self-limiting adverse effects including erythema, pain, and transient local inflammation (55, 56). It is noteworthy that systemic toxicity, dysphagia, or TLS were rare and manageable (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e) (21, 57).\u003c/p\u003e\u003cp\u003eBesides oncologic outcomes, the findings underscore the significant quality-of-life and aesthetic benefits of ECT. The tongue SCC case whose radiological image was shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e5\u003c/span\u003e not only showed partial reduction in tumor size but also presented drastic change in quality of life (pain reduction and bleeding control) which demonstrates the appropriate efficacy of ECT. Patients experienced sustained improvements in pain, emotional well-being, and functional aspects such as speech, swallowing, and appearance, as measured by validated tools (QLQ-H\\\u0026amp;N35, EQ-5D) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e6\u003c/span\u003e) (55, 58). Although immediate post-treatment pain was not completely relief due to requirement to immunotherapeutic reactions (we do not order NSAIDs up to 4 days after ECT), pain levels declined over subsequent weeks without requiring increased analgesic usage and decreasing the opioid consumption (19, 59). Post-ECT pain severity is affected by several factors such as tumor size, location, SCC histology, and prior irradiation, suggesting the need for targeted pain management in at-risk patients (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e7\u003c/span\u003e). It is worth noting that in patients with mouth mucosal SCCs we must be aware about the air way of the patient and if it was required considerations such as tracheostomy or corticosteroid administration must be considered. These conditions may be happened so rare but it must be concerned specifically in cases with large tumors in borders between tongue and laryngeal entrance. Aesthetic outcomes in patients with complete cutaneous responses were consistently favorable low mean score; MSS 6.94, VSS 2.72, and VAS 26.89, with scars demonstrating acceptable pigmentation, pliability, and vascularity (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e7\u003c/span\u003e). The obtained results suggest ECT as an appropriate alternative for conventional invasive techniques, to address the function and appearance complications of patients with H\u0026amp;N malignancies. We are capable in treating margins of the tumor with no damage on normal peripheral tissues which is a distinguished specifications of this method in H\u0026amp;N tumors.\u003c/p\u003e\u003cp\u003eDespite the promising outcomes, there were some limitations including the single-arm non comparative investigation, and relatively short follow-up duration. While the high response and survival rates are encouraging, longer-term surveillance is necessary to ascertain durability of remission and potential late-onset adverse effects. Therefore, more clinical trials would be helpful in clarifying the role of ECT in the management of H\u0026amp;N cancers.\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eIn conclusion, ECT is an effective and safe treatment for H\u0026amp;N cancers, with high response rates, acceptable aesthetic and functional outcomes, improvement in quality of life, and minimal complications. With the increasing use of ECT and advances in technology, it has the potential to become a cornerstone of locoregional treatment in H\u0026amp;N oncology with both curative and palliative intents, particularly in settings where traditional approaches carry significant morbidity or are no longer feasible.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eACKNOWLEDGEMENTS \u0026amp; FUNDING\u003c/p\u003e\n\u003cp\u003eThis work received no financial support.\u003c/p\u003e\n\u003cp\u003eCONFLICT OF INTEREST\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll the authors declare that they have no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAUTHOR CONTRIBUTIONS\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eF.H\u003c/strong\u003e:\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eInvestigation, Data Curation, Project administration; \u003cstrong\u003eM.B\u003c/strong\u003e: Investigation, Data Curation, Software, Writing-Reviewing \u0026amp; Editing, Project administration; \u003cstrong\u003eA.N\u003c/strong\u003e: Investigation, \u003cstrong\u003eS.M.Y\u003c/strong\u003e: Investigation, Methodology; \u003cstrong\u003eS.M\u003c/strong\u003e: Investigation, Supervision; \u0026nbsp;\u003cstrong\u003eF.R.P\u003c/strong\u003e: Investigation, Data Gathering; \u003cstrong\u003eA.Gh\u003c/strong\u003e: Investigation, Data Gathering ; \u003cstrong\u003eN.M\u003c/strong\u003e: Investigation, Data Gathering; \u003cstrong\u003eN.H\u003c/strong\u003e: Data Gathering, Writing-Reviewing \u0026amp; Editing; \u003cstrong\u003eS.M\u003c/strong\u003e: Investigation, Data Gathering; \u003cstrong\u003eN.SH\u003c/strong\u003e: Investigation, Data Gathering; \u003cstrong\u003eS.M.S.M\u003c/strong\u003e: Investigation; \u003cstrong\u003eO.N\u003c/strong\u003e: Investigation, Supervision; \u003cstrong\u003eH.M\u003c/strong\u003e: Investigation, Supervision; \u003cstrong\u003eN.SH\u003c/strong\u003e: Investigation, Data Gathering; \u003cstrong\u003eF.F\u003c/strong\u003e: Investigation, Supervision;\u003cstrong\u003e\u0026nbsp;S.H.S.A\u003c/strong\u003e: Investigation, Supervision;\u003cstrong\u003e\u0026nbsp;A.M\u003c/strong\u003e: Investigation;\u003cstrong\u003e\u0026nbsp;S.M.S\u003c/strong\u003e: Data Gathering;\u003cstrong\u003e\u0026nbsp;B.M\u003c/strong\u003e: Data Gathering;\u003cstrong\u003e\u0026nbsp;S.R.M\u003c/strong\u003e: Investigation, Supervision; \u003cstrong\u003eE.K\u003c/strong\u003e: Investigation, Supervision; \u003cstrong\u003eM.A\u003c/strong\u003e: Conceptualization, Methodology, Supervision, Resources, Project administration, Data curation, Writing-Reviewing and Editing, Software.\u003c/p\u003e\n\u003cp\u003eDATA AVAILABILITY STATEMENT\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that all data is available from the corresponding author upon a reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKallini JR, Hamed N, Khachemoune A. 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Electrochemotherapy in the treatment of head and neck cancer: current conditions and future directions. Cancers. 2021;13(6):1418.\u003c/li\u003e\n\u003cli\u003eProbst U, Fuhrmann I, Beyer L, Wiggermann P. Electrochemotherapy as a new modality in interventional oncology: a review. Technology in cancer research \u0026amp; treatment. 2018;17:1533033818785329.\u003c/li\u003e\n\u003cli\u003eCondello M, D\u0026rsquo;Avack G, Spugnini EP, Meschini S. Electrochemotherapy: An alternative strategy for improving therapy in drug-resistant SOLID tumors. Cancers. 2022;14(17):4341.\u003c/li\u003e\n\u003cli\u003eClover 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\u0026ndash;2019). European Journal of Cancer. 2020;138:30\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eCadossi R, Ronchetti M, Cadossi M. Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy. Future Oncology. 2014;10(5):877\u0026ndash;90.\u003c/li\u003e\n\u003cli\u003eSpratt DE, Gordon Spratt EA, Wu S, DeRosa A, Lee NY, Lacouture ME, et al. Efficacy of skin-directed therapy for cutaneous metastases from advanced cancer: a meta-analysis. Journal of Clinical Oncology. 2014;32(28):3144\u0026ndash;55.\u003c/li\u003e\n\u003cli\u003ePlaschke CC, Bertino G, McCaul JA, Grau JJ, de Bree R, Sersa G, et al. European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers. European Journal of Cancer. 2017;87:172\u0026ndash;81.\u003c/li\u003e\n\u003cli\u003eSersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M. Electrochemotherapy in treatment of tumours. 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ACTA Otorhinolaryngologica Italica. 2024;44(2 Suppl 1):S37.\u003c/li\u003e\n\u003cli\u003eGehl 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 oncologica. 2018;57(7):874\u0026ndash;82.\u003c/li\u003e\n\u003cli\u003eHawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual analog scale for pain (vas pain), numeric rating scale for pain (nrs pain), mcgill pain questionnaire (mpq), short‐form mcgill pain questionnaire (sf‐mpq), chronic pain grade scale (cpgs), short form‐36 bodily pain scale (sf‐36 bps), and measure of intermittent and constant osteoarthritis pain (icoap). Arthritis care \u0026amp; research. 2011;63(S11):S240\u0026ndash;S52.\u003c/li\u003e\n\u003cli\u003eGerbershagen HJ, Rothaug J, Kalkman C, Meissner W. 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Journal of Clinical Medicine. 2021;10(19):4366.\u003c/li\u003e\n\u003cli\u003ePichi B, Pellini R, Spriano G. Electrochemotherapy\u0026ndash;A locoregional therapy with well-established palliative effect in patient with large recurrent lesion of head and neck. Journal of Cranio-Maxillofacial Surgery. 2019;47(1):41\u0026ndash;6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Electrochemotherapy (ECT), Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), Head and Neck Cancer","lastPublishedDoi":"10.21203/rs.3.rs-7626682/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7626682/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eElectrochemotherapy (ECT), a nonthermal locoregional modality, has emerged as a promising alternative for management of basal and squamous cell carcinoma (BCC \u0026amp; SCC) in head and neck (H\u0026amp;N). It can address their substantial therapeutic challenges due to proximity to vital structures and high rates of functional and aesthetic impairment following conventional treatments. This study aimed to evaluate the efficacy, safety, survival outcomes, and quality-of-life benefits of ECT in a diverse cohort of H\u0026amp;N cancer patients.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eA prospective clinical study was conducted on 70 patients with cutaneous, soft tissue, and mucosal BCC / SCC of the H\u0026amp;N, who underwent ECT either as single mode modality or in combination with other therapeutic procedures. Logistic regression and Kaplan\u0026ndash;Meier analysis were used to identify predictive response factors and survival assessment.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e\u003cp\u003eThe overall objective response rate of the tumors to ECT was 94.2%, with complete remission in 52.9% of patients. Tumor size\u0026thinsp;\u0026le;\u0026thinsp;3 cm, BCC histology, primary presentation, and intratumoral injection were significantly associated with higher complete response rates (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). One-year local progression-free survival (LPFS) and overall survival (OS) were 94.2% and 87.1%, respectively. The adverse events were mild and transient. In addition, significant post-treatment improvements were observed in pain, physical function, aesthetic and psychosocial well-being.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe results reinforce the clinical value of ECT and suggest that with appropriate patient selection and protocol optimization, its efficacy can be significantly enhanced across a broad range of H\u0026amp;N cancers.\u003c/p\u003e","manuscriptTitle":"Electrochemotherapy in Basal \u0026amp; Squamous Cell Carcinoma of Head \u0026amp; Neck; A Prospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-18 14:15:09","doi":"10.21203/rs.3.rs-7626682/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba26bb42-033e-4208-bc5c-c579fcacdbdd","owner":[],"postedDate":"October 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56049545,"name":"Biological sciences/Cancer"},{"id":56049546,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-02-02T15:08:55+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-18 14:15:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7626682","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7626682","identity":"rs-7626682","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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