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.

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.

Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1-Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms.

INTRODUCTION: Pegargiminase (ADI-PEG 20; ADI) degrades arginine and potentiates pemetrexed (Pem) cytotoxicity in argininosuccinate synthetase 1 (ASS1)-deficient malignant pleural mesothelioma (MPM). We conducted a phase 1 dose-expansion study at the recommended phase 2 dose of ADI-PEG 20 with Pem and cisplatin (ADIPemCis), to further evaluate arginine-lowering therapy in ASS1-deficient MPM and explore the mechanisms of resistance. METHODS: A total of 32 patients with ASS1-deficient MPM (11 epithelioid; 10 biphasic;11 sarcomatoid) who were chemonaive received weekly intramuscular pegargiminase (36 mg/m2) with Pem (500 mg/m2) and cisplatin (75 mg/m2) intravenously, every 3 weeks (six cycles maximum). Maintenance pegargiminase was permitted until disease progression or withdrawal. Safety, pharmacodynamics, immunogenicity, and efficacy were determined. Biopsies were performed in progressing patients to explore the mechanisms of resistance to pegargiminase. RESULTS: The treatment was well tolerated. Most adverse events were of grade 1/2, whereas four nonhematologic grade 3/4 adverse events related to pegargiminase were reversible. Plasma arginine decreased whereas citrulline increased; this was maintained by 18 weeks of ADIPemCis therapy. The disease control rate in 31 assessed patients was 93.5% (n = 29 of 31; 95% confidence interval [CI]: 78.6%-99.2%), with a partial response rate of 35.5% (n = 11 of 31; 95% CI: 19.2%-54.6%). The median progression-free and overall survivals were 5.6 (95% CI: 4.0-6.0) and 10.1 (95% CI: 6.1-11.1) months, respectively. Progression biopsies on pegargiminase revealed a statistically significant influx of macrophages (n = 6; p = 0.0255) and patchy tumoral ASS1 reexpression (n = 2 of 6). In addition, we observed increased tumoral programmed death-ligand 1-an ADI-PEG 20 inducible gene-and the formation of CD3-positive T lymphocyte aggregates on disease progression (n = 2 of 5). CONCLUSIONS: The dose expansion of ADIPemCis confirmed the high clinical activity and good tolerability in ASS1-deficient poor-prognosis mesothelioma, underpinning an ongoing phase 3 study (ClinicalTrials.govNCT02709512). Notably, resistance to pegargiminase correlated with marked macrophage recruitment and-along with the tumor immune microenvironment-warrants further study to optimize arginine deprivation for the treatment of mesothelioma.

Prospective study of sentinel lymph node biopsy for conjunctival melanoma.

BACKGROUND: To report our experience with sentinel lymph node biopsy for staging patients with conjunctival melanoma. METHODS: A prospective review of patients with conjunctival melanoma who underwent sentinel lymph node biopsy at St Bartholomew's Hospital from May 2008 to May 2012. The selection criterion for sentinel node biopsy depended on the tumour thickness (≥2 mm) and location of the conjunctival melanoma. The main outcome measures were the incidence of sentinel lymph node positivity and the procedure-related complications. RESULTS: In 4 years, 26 out of 70 patients met the selection criteria for sentinel lymph node biopsy. 4 patients declined and 22 patients consented for the procedure. Technetium-99m failed to identify a sentinel lymph node in four of the 22 patients (18%). Of the remaining 18 patients, two were found to have subclinical micrometastasis in regional lymph nodes. Median follow-up was 20 months (range 6-36 months). No false-negative events were observed. Complications of the procedure included transient blue staining of the epibulbar surface in five patients and transient facial nerve palsy in one patient. CONCLUSIONS: Sentinel lymph node biopsy is a safe procedure with minimal complications. It should be considered for the staging of conjunctival melanomas, especially melanomas in non-limbal location or conjunctival melanomas ≥2 mm thick.

Nurse-led management of hypertrophic and keloid scars.

Keloid and hypertrophic scars are difficult to treat, and their management requires a structured approach with input from a multidisciplinary team. Typically, patients are treated in busy, general clinics--an environment that is not suitable for these patients, whose treatment can take considerable time and requires emotional support. The development of a dedicated, nurse-led keloid scar clinic covering scar management and skin camouflage is described, the benefits of which have been evaluated. Results to date show that it is cost-effective, that it has reduced the non-attendance rate at the clinic, and that it improves compliance and has led to better resolution of scars in a shorter time than previously.