An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma.

In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

Calcium electroporation of esophageal cancer induces gene expression changes: a sub-study of a phase I clinical trial.

PURPOSE: In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment. METHODS: In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples. RESULTS: Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21, ANGPTL4, and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased. CONCLUSION: This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes.

Neo-train: study protocol and feasibility results for a two-arm randomized controlled trial investigating the effect of supervised exercise during neoadjuvant chemotherapy on tumour response in patients with breast cancer.

BACKGROUND: Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. METHODS: This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1-2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21-29), at surgery (approximately week 21-30) and 3 months post-surgery (approximately 33-42 weeks from baseline). DISCUSSION: This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation.

The 4th World Congress of Electroporation (Copenhagen, 9-13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.

Calcium electroporation in cutaneous metastases - A non-randomised phase II multicentre clinical trial.

BACKGROUND: Cutaneous metastases can cause distressing symptoms and be challenging to treat. Local therapies are essential in management. Calcium electroporation uses calcium and electrical pulses to selectively kill cancer cells. This multicentre study aimed to define response in cutaneous metastases across different cancer types. METHODS: Patients with tumours ≤3 cm of any histology were included (stable or progressing on current therapy ≥2 months), at three centres. Tumours were treated with 220 mM calcium chloride injection and manual application of eight 0.1 ms pulses with 1 kV/cm and 1Hz with a handheld electrode, in local or general anaesthesia. Clinical response was evaluated after 1, 2, 3, 4, 5, 6, and 12 months. Primary endpoint was response at two months. The overall response rate (ORR) was partial- and complete responses of treated tumours. MR-imaging and qualitative interviews were performed in respective subsets. RESULTS: Nineteen patients with disseminated cancer (breast n = 4, lung n = 5, pancreatic n = 1, colorectal n = 2, gastric n = 1, and endometrial cancer n = 1) were enrolled, and 58 metastases were treated (50 once, 8 retreated). The ORR was 36% (95% CI 22-53) after two months. Best ORR was 51% (CR 42%; PR 9%). Previous irradiation improved outcomes (p = 0.0004). Adverse events were minimal. Median pain score was reduced after two months (p = 0.017). Treatment may relieve symptoms according to qualitative interviews. MRI showed restriction in treated tissue. CONCLUSION: The majority of tumours were treated only once with calcium electroporation, achieving an ORR of 36% after two months and best ORR of 51%. Efficacy, symptom-relief and safety support calcium electroporation as a palliative treatment option for cutaneous metastases.

Efficacy of Electrochemotherapy in Breast Cancer Patients of Different Receptor Status: The INSPECT Experience.

Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ (p = 0.0297) and HR+ (p = 0.0094), while overall survival was affected by time to local progression in all groups (p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions.

Patient-Related Characteristics Associated with Treatment Modifications and Suboptimal Relative Dose Intensity of Neoadjuvant Chemotherapy in Patients with Breast Cancer-A Retrospective Study.

BACKGROUND: Reduced relative dose intensity (RDI) of neoadjuvant chemotherapy (NACT) in patients with breast cancer may compromise treatment outcome and survival. We examined patient-related characteristics associated with treatment modifications and suboptimal RDI and tumour response in patients with breast cancer. METHODS: In this observational study, electronic medical records were reviewed retrospectively for female patients with breast cancer scheduled for NACT at a university hospital in Denmark between 2017 and 2019. The RDI (ratio of delivered dose intensity in relation to standard dose intensity) was calculated. Multivariate logistic regression analyses examined associations of sociodemographics, general health and clinical cancer characteristics with dose reductions, dose delays, discontinuation of NACT and suboptimal RDI < 85%. RESULTS: Among 122 included patients, 43%, 42% and 28% experienced dose reductions, dose delays ≥3 days and discontinuation, respectively. A total of 25% received an RDI < 85%. Comorbidity, taking long-term medications and being overweight were statistically significantly associated with treatment modifications, while age ≥ 65 years and comorbidity were associated with RDI < 85%. Around one third of all patients had radiologic (36%) or pathologic (35%) complete tumour response, with no statistically significant differences by RDI < or ≥85% irrespective of breast cancer subtype. CONCLUSIONS: While most patients had RDI ≥85%, still one out of four patients received an RDI < 85%. Further investigations of possible supportive care initiatives to improve patients' treatment tolerability are needed, particularly among subgroups of older age or with comorbidity.

Endoscopic calcium electroporation for colorectal cancer: a phase I study.

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Qualitative Investigation of Experience and Quality of Life in Patients Treated with Calcium Electroporation for Cutaneous Metastases.

(1) Background: Calcium electroporation is a novel cancer treatment. It includes injecting calcium-solution and applying electric pulses to tumour tissue. Data on quality of life for patients with cutaneous metastases treated with calcium electroporation is limited. We evaluated quality of life in patients with skin metastases treated with calcium electroporation using qualitative interviews. (2) Methods: This investigation featured a subgroup from a non-randomised phase II study (CaEP-R) at Zealand University Hospital, Denmark, studying response to calcium electroporation in cutaneous metastasis (ClinicalTrials no. NCT04225767). Participants were interviewed at baseline before calcium electroporation treatment and after two months. Data was analysed phenomenologically; (3) Results: Interviews were conducted February 2020-November 2021. Nine patients were included, of which seven participated in both interviews. All seven patients expected treated tumours to disappear, symptom relief and minimal side effects. Most patients requested peer accounts. All patients found the treatment uncomfortable but acceptable; all thought their fears of electric pulses exceeded their experience. All would repeat the treatment if effective. Successful treatment had a positive effect on pain, symptomatic wounds, sleep, vigour and social inclination; (4) Conclusions: Calcium electroporation enhanced health-related quality of life by reducing symptoms and increasing social inclination. Peer accounts provide patients with a shortcut to confidence in treatment on top of doctors' recommendations.

ProTarget: a Danish Nationwide Clinical Trial on Targeted Cancer Treatment based on genomic profiling - a national, phase 2, prospective, multi-drug, non-randomized, open-label basket trial.

BACKGROUND: An increasing number of trials indicate that treatment outcomes in cancer patients with metastatic disease are improved when targeted treatments are matched with druggable genomic alterations in individual patients (pts). An estimated 30-80% of advanced solid tumors harbor actionable genomic alterations. However, the efficacy of personalized cancer treatment is still scarcely investigated in larger, controlled trials due to the low frequency and heterogenous distribution of druggable alterations among different histologic tumor types. Therefore, the overall effect of targeted cancer treatment on clinical outcomes still needs investigation. STUDY DESIGN/METHODS: ProTarget is a national, non-randomized, multi-drug, open-label, pan-cancer phase 2 trial aiming to investigate the anti-tumor activity and toxicity of currently 13 commercially available, EMA-approved targeted therapies outside the labeled indication for treatment of advanced malignant diseases, harboring specific actionable genomic alterations. The trial involves the Danish National Molecular Tumor Board for confirmation of drug-variant matches. Key inclusion criteria include a) measurable disease (RECIST v.1.1), b) ECOG performance status 0-2, and c) an actionable genomic alteration matching one of the study drugs. Key exclusion criteria include a) cancer type within the EMA-approved label of the selected drug, and b) genomic alterations known to confer drug resistance. Initial drug dose, schedule and dose modifications are according to the EMA-approved label. The primary endpoint is objective response or stable disease at 16 weeks. Pts are assigned to cohorts defined by the selected drug, genomic alteration, and tumor histology type. Cohorts are monitored according to a Simon's two-stage-based design. Response is assessed every 8 weeks for the first 24 weeks, then every 12 weeks. The trial is designed similar to the Dutch DRUP and the ASCO TAPUR trials and is a partner in the Nordic Precision Cancer Medicine Trial Network. In ProTarget, serial fresh tumor and liquid biopsies are mandatory and collected for extensive translational research including whole genome sequencing, array analysis, and RNA sequencing. DISCUSSION: The ProTarget trial will identify new predictive biomarkers for targeted treatments and provide new data and essential insights in molecular pathways involved in e.g., resistance mechanisms and thereby potentially evolve and expand the personalized cancer treatment strategy. PROTOCOL VERSION: 16, 09-MAY-2022. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04341181. Secondary Identifying No: ML41742. EudraCT No: 2019-004771-40.

Calcium Electroporation for Management of Cutaneous Metastases in HER2-Positive Breast Cancer: A Case Report.

We report a case of successful treatment of cutaneous metastases in HER2-positive breast cancer with calcium electroporation (CaEP), in addition to trastuzumab, over a period of 5 years. CaEP is performed in local or general anesthesia, by injecting calcium chloride intratumorally and then electroporating cells in the area. Using a handheld needle electrode, a series of short, high-voltage electric pulses are delivered, which transiently permeabilizes cell membranes, causing toxic intracellular calcium levels. The treatment causes cancer cell death, while normal cells are less affected, making the treatment useful for local management of cutaneous lesions. This case presents a 66-year-old female, who had mastectomy surgery followed by adjuvant chemo- and radiotherapy for an ER-negative, HER2-positive breast cancer on her right side in 2003, and a mastectomy followed by endocrine therapy for an ER-positive, HER2 normal breast cancer on her left side in 2006. In 2015, the patient presented local cutaneous recurrence of the ER-negative, HER2-positive breast cancer. The patient was treated with trastuzumab alone, trastuzumab emtansine (TDM1), and a combination of trastuzumab and CaEP. TDM1 was found to have a slightly better effect on the cutaneous metastases than trastuzumab, but the side effects of TDM1 were not acceptable to the patient. The combination of continuous HER2-inhibition and intermittent CaEP, when needed, has been effective in keeping the cutaneous metastases under control for 5 years, and presumably more tolerable for the patient than chemotherapy. An interesting finding was local sparing of calcium electroporated skin from new recurrences, otherwise seen in the general area, which could be a sign of local immunity. This warrants further studies investigating local immunomodulation following CaEP. The patient reported appreciation of a treatment option without chemotherapy, and satisfaction with the outcome of the combination of HER2 inhibition and CaEP treatment. CaEP treatment is currently phase II treatment, and mechanisms and possible applications still need investigation. This novel anticancer treatment could potentially benefit many patients, due to its efficacy, low cost, and accessibility. This case provides observations, which may inspire future trials with CaEP for skin metastases of HER2-positive breast cancer.

Palliative Treatment of Esophageal Cancer Using Calcium Electroporation.

Calcium electroporation (CaEP) is a novel cancer therapy wherein high intracellular calcium levels, facilitated by reversible electroporation, trigger tumor necrosis. This study aimed to establish safety with CaEP within esophageal cancer. Patients with non-curable esophageal cancer were included at Copenhagen University Hospital Rigshospitalet in 2021 and 2022. In an outpatient setting, calcium gluconate was injected intratumorally followed by reversible electroporation applied with an endoscopic electrode. The primary endpoint was the prevalence of adverse events, followed by palliation of dysphagia. All patients were evaluated with CT and upper endoscopies up to two months after treatment. The trial was registered at ClinicalTrials.gov (NCT04958044). Eight patients were treated. One serious adverse event (anemia, requiring a single blood transfusion) and three adverse events (mild retrosternal pain (two) and oral thrush (one)) were registered. Initially, six patients suffered from dysphagia: two reported dysphagia relief and four reported no change. From the imaging evaluation, one patient had a partial response, three patients had no response, and four patients had progression. Six months after treatment, the patient who responded well was still in good condition and without the need for further oncological treatment. CaEP was conducted in eight patients with only a few side effects. This study opens the way for larger studies evaluating tumor regression and symptom palliation.

Electrochemotherapy for the treatment of cutaneous squamous cell carcinoma: The INSPECT experience (2008-2020).

Introduction: Cutaneous squamous cell carcinoma (cSCC) is a frequent skin cancer with a high risk of recurrence characterized by tumor infiltration and, in advanced cases, a poor prognosis. ECT (electrochemotherapy) is an alternative treatment option for locally advanced or recurrent cSCC that is unsuitable for surgical resection. In this study, we aimed to evaluate the data in the InspECT (International Network for Sharing Practice on ECT) registry of the referral centers and to clarify the indications for the use of ECT as a treatment modality for cSCC. Materials and methods: Patients with primary, recurrent or locally advanced cSCC from 18 European centers were included. They underwent at least one ECT session with bleomycin between February 2008 and November 2020, which was performed following the European Standard Operating Procedures. Results: The analysis included 162 patients (mean age of 80 years; median, 1 lesion/patient). Side effects were mainly local and mild (hyperpigmentation, 11%; ulceration, 11%; suppuration, 4%). The response to treatment per patient was 62% complete and 21% partial. In the multivariate model, intravenous drug administration and small tumor size showed a significant association with a positive outcome (objective response). One-year local progression-free survival was significantly better (p<0.001) in patients with primary tumors (80% (95% C.I. 70%-90%) than in patients with locally advanced disease (49% (95% C.I. 30%-68%). Conclusion: In the present study, ECT showed antitumor activity and a favorable safety profile in patients with complex cSCC for whom there was no widely accepted standard of care. Better results were obtained in primary and small tumors (<3 cm) using intravenous bleomycin administration.

Palliation of dysphagia in patients with non-curable esophageal cancer - a retrospective Danish study from a highly specialized center.

PURPOSE: A majority of the patients with esophageal cancer (EC) suffer from dysphagia. Several endoscopic treatment options are available such as stent placement, argon plasma coagulation, and esophageal dilatation. This study aimed to map the use of endoscopic dysphagia relieving interventions and secondly investigate possible impact on survival. METHODS: Data was collected at the Dept. of Surgery & Transplantation, Rigshospitalet, Denmark. Patients with non-curable EC referred from 2016 to 2019 were included. Type of dysphagia treatment, complications and the need for repeated treatments, and survival were registered. RESULTS: In the study, 601 patients were included. Forty-five percent were treated with an endoscopic procedure due to dysphagia (82% had a stent placed). The median time from diagnosis to intervention was 24 days. The overall complication rate was 35% (38% in the stent group and 20% in the non-stent group, p = 0.03) and 13% of the patients were readmitted due to a complication. After 26% of the procedures, a repeated treatment was required. Patients having an endoscopic intervention had a worsened survival prognosis compared with the patients in the non-intervention group (HR: 2.17, 95% CI: 1.80-2.61, p < 0.001). In the sub analysis where only patients who had an intervention was included, a survival difference in favor of the non-stent group was found (HR: 0.61, 95% CI: 0.43-0.86, p = 0.005). CONCLUSION: In this cohort, the incidence of endoscopic procedures was high, complication rates were considerable, and many the patients required a second treatment. A survival difference was seen, where the patients who had a stent placed seemed to have the worst survival outcomes. However, the causal relationship is yet to be determined why the results must be interpreted carefully. New interventions and tailored approaches that may positively affect functional and long-term oncological outcomes are highly warranted and this should preferably be investigated in randomized clinical trials.

Electrochemotherapy with intravenous bleomycin for patients with cutaneous malignancies, across tumour histology: a systematic review.

BACKGROUND: Electrochemotherapy (ECT) is an established treatment for primary and secondary cutaneous tumours. The method combines chemotherapy with electroporation, thus increasing the cytotoxic effect of the chemotherapeutic drug. Bleomycin is the drug of choice for ECT, as it is already well established as a treatment for several cancer types and has the largest increase in efficacy after electroporation, enhancing the cytotoxic effect several hundred fold. The response rates of ECT have over the past 30 years been high and consistent. Case based reports point out that the efficacy possibly can be maintained even when the dose of bleomycin is reduced. Consequently in 2018, studies began investigating reducing the bleomycin dose. AIM: The purpose of this review is to summarise all data published using intravenous bleomycin for cutaneous malignancies and is to our knowledge the first review to examine the use of a reduced bleomycin dose in ECT. METHODS: This study is a systematic review. Fifty-five clinical studies investigating ECT with intravenous bleomycin for patients with cutaneous malignancies were included. RESULTS: Studies published from 1993 to 2021 investigating the effect of ECT include 3729 patients and indicate a consistent and high response with a mean objective response rate (ORR) of 81.5%. Interestingly, studies using lower doses of bleomycin observe a similar ORR (85.5%), opening the possibility that a lower dose may not be inferior. CONCLUSION: This study gives an overview of published studies on ECT with intravenous bleomycin for patients with cutaneous malignancies, including the use of a reduced bleomycin dose, as preparation for a randomised study.

Exercise suppresses tumor growth independent of high fat food intake and associated immune dysfunction.

Epidemiological data suggest that exercise training protects from cancer independent of BMI. Here, we aimed to elucidate mechanisms involved in voluntary wheel running-dependent control of tumor growth across chow and high-fat diets. Access to running wheels decreased tumor growth in B16F10 tumor-bearing on chow (- 50%) or high-fat diets (- 75%, p < 0.001), however, tumor growth was augmented in high-fat fed mice (+ 53%, p < 0.001). Tumor growth correlated with serum glucose (p < 0.01), leptin (p < 0.01), and ghrelin levels (p < 0.01), but not with serum insulin levels. Voluntary wheel running increased immune recognition of tumors as determined by microarray analysis and gene expression analysis of markers of macrophages, NK and T cells, but the induction of markers of macrophages and NK cells was attenuated with high-fat feeding. Moreover, we found that the regulator of innate immunity, ZBP1, was induced by wheel running, attenuated by high-fat feeding and associated with innate immune recognition in the B16F10 tumors. We observed no effects of ZBP1 on cell cycle arrest, or exercise-regulated necrosis in the tumors of running mice. Taken together, our data support epidemiological findings showing that exercise suppresses tumor growth independent of BMI, however, our data suggest that high-fat feeding attenuates exercise-mediated immune recognition of tumors.

Prospective cohort study by InspECT on safety and efficacy of electrochemotherapy for cutaneous tumors and metastases depending on ulceration.

BACKGROUND: Electrochemotherapy (ECT) is an effective local treatment for cutaneous tumors. The aim of this study was to compare the effectiveness of ECT in ulcerated vs. non-ulcerated tumors and investigate the effect on tumor-associated symptoms. METHODS: Twenty cancer centers in the International Network for Sharing Practices on Electrochemotherapy (InspECT) prospectively collected data. ECT was performed following ESOPE protocol. Response was evaluated by lesion size development. Pain, symptoms, performance status (ECOG-Index) and health status (EQ-5D questionnaire) were evaluated. RESULTS: 716 patients with ulcerated (n = 302) and non-ulcerated (n = 414) cutaneous tumors and metastases were included (minimum follow-up of 45 days). Non-ulcerated lesions responded to ECT better than ulcerated lesions (complete response 65 % vs. 51 %, p = 0.0061). Only 38 % (115/302) with ulcerated lesions before ECT presented with ulcerated lesions at final follow-up. Patients with ulcerated lesions reported higher pain and more severe symptoms compared to non-ulcerated lesions, which significantly and continuously improved following ECT. In non-ulcerated lesions however, pain spiked during the treatment. No serious adverse events were reported. CONCLUSIONS: ECT is a safe and effective local treatment for cutaneous tumors. While ECT improves symptoms especially in patients with ulcerated lesions, data suggest the implementation of a perioperative pain management in non-ulcerated lesions during ECT.

Prospektive Kohortenstudie von InspECT zur Sicherheit und Wirksamkeit der Elektrochemotherapie bei Hauttumoren und Metastasen in Abhängigkeit von Ulzeration.

HINTERGRUND: Elektrochemotherapie (ECT) ist eine wirksame lokale Behandlung von Hauttumoren. Ziel dieser Studie war es, die Wirksamkeit der ECT bei ulzerierten gegenüber nichtulzerierten Tumoren zu vergleichen und den Effekt auf tumorassoziierte Symptome zu untersuchen. METHODIK: 20 Krebszentren des International Network for Sharing Practices on Electrochemotherapy (InspECT) sammelten prospektiv Daten. Die ECT wurde nach dem ESOPE-Protokoll durchgeführt. Das Therapieansprechen wurde anhand der Entwicklung der Läsionsgröße bewertet. Zusätzlich wurden Schmerzen, Symptome, Leistungsstatus (ECOG-Index) und Gesundheitszustand (EQ-5D-Fragebogen) untersucht. ERGEBNISSE: 716 Patienten mit ulzerierten (n = 302) und nichtulzerierten (n = 414) Hauttumoren und Metastasen wurden eingeschlossen (Mindest-Nachsorge 45 Tage). Nicht-ulzerierte Läsionen sprachen besser auf die ECT an als ulzerierte Läsionen (vollständiges Ansprechen: 65 % gegenüber 51 %, p = 0,0061). Nur 38 % (115/302) der Patienten mit ulzerierten Läsionen vor der ECT wiesen bei der letzten Nachuntersuchung ulzerierte Läsionen auf. Patienten mit ulzerierten Läsionen berichteten über stärkere Schmerzen und schwerere Symptome im Vergleich zu Patienten mit nichtulzerierten Läsionen, die sich nach der ECT signifikant und kontinuierlich besserten. Bei Patienten mit nichtulzerierten Läsionen hingegen nahmen die Schmerzen während der Behandlung vorübergehend zu. Es wurden keine schwerwiegenden Nebenwirkungen beobachtet. SCHLUSSFOLGERUNGEN: Die ECT ist eine sichere und wirksame lokale Behandlung von Hauttumoren. Während die ECT die Symptome insbesondere bei Patienten mit ulzerierten Läsionen verbessert, sollte auf Basis der Daten die Implementation eines perioperativen Schmerzmanagements besonders bei nichtulzerierten Läsionen während der ECT erwogen werden.