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.

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.

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.

Chronic myeloid leukemia presenting as compartment syndrome with acute loss of upper limb function.

Hematological malignancies rarely present with spontaneous haematomas (Lakhotia et al., 2015 [1]). Although cutaneous and mucous membrane bleeds do occur in chronic myeloid leukemia (CML) due to quantitative or qualitative platelet abnormalities, deep soft tissue bleeds are rare (Lakhotia et al., 2015 [1]). We report the case of a 49 year old man presenting with an acute hematoma of the left biceps brachii causing compartment syndrome of his left upper limb leading to flaccid paralysis. He underwent surgical evacuation of the hematoma and investigations revealed that he had CML with leukemic infiltration in the biceps brachii.

Scar orientation: Principles in plastic surgery.

For biopsy proven skin cancers that are deemed to be high risk, a wide local excision (WLE) is recommended to reduce the risk of local recurrence. For this reason, it is pragmatic to account for the likelihood of a WLE at the time of the initial biopsy. We illustrate a staged approach to excision of lesions to facilitate this, bearing in mind the optimal reconstruction is primary closure. In our experience as plastic surgeons, having to perform a locoregional flap or skin graft prevents the opportunity to perform a local anesthetic procedure. This increases the risk of postoperative complications, especially if adjuvant radiotherapy further exposes reconstructed tissues to radiation toxicity. Collectively, this often results in an inferior aesthetic outcome. We value the referrals from allied colleagues and want to share the principles we adhere to when planning an excision biopsy, which aid in the delivery of the optimal reconstruction.

Electrochemotherapy for advanced cutaneous angiosarcoma: A European register-based cohort study from the International Network for Sharing Practices of electrochemotherapy (InspECT).

BACKGROUND: Cutaneous angiosarcoma (cAS) is a highly aggressive malignancy that challenges the radicality of surgical treatment. Electrochemotherapy (ECT), a skin-directed treatment based on cytotoxic chemotherapy combined with local electric pulses, may be an intraoperative adjunct and a new opportunity in the therapeutic strategy. This cohort study reports the experience with ECT as an option. METHODS: Data on patients with locally-advanced/metastatic cAS who underwent ECT between October 2013 and October 2018 at eight European centres were prospectively submitted to the InspECT (International network for sharing practices of ECT) register. Patients received therapy according to the European Standard Operating Procedures of ECT (ESOPE). Treatment feasibility was assessed based on tumour coverage with electrodes and recorded tissue current; treatment toxicity and tumour response were graded according to CTCAE v5.0 and RECIST v1.1 criteria, respectively; patient-reported outcomes (PRO) were evaluated using a visual analogue score (VAS) for pain, acceptance of retreatment and the EQ-5D questionnaire. RESULTS: We enrolled 20 patients with advanced cAS in the scalp/face (n = 7), breast/trunk (n = 10) or limbs (n = 3). Target tumours (n = 51) had a median size of 2.3 cm (range, 1-20). We administered 24 ECT courses using 1-4 cm treatment safety margin around tumours. In five patients, ECT was combined/sequenced with surgery. Median tissue current was 3 A (range, 1.5-10), tumour margins coverage rate was 75% (15/20 patients). The objective response rate (ORR) was 80% (complete, 40%). Grade-3 toxicity included skin ulceration (15%) and pain (10%), with no significant change of PRO scores. Bleeding control was achieved in 13/14 patients with ulcerated tumours. With a median overall survival of 12.5 months, the local progression-free survival (LPFS) was 10.9 months. CONCLUSION: ECT produces sustained response rate with minimal side effects and should be considered an option for advanced cAS. Palliative benefits include patient tolerability, local haemostasis and durable local control. Definition of optimal timing, treatment safety margins and combination with surgery need further investigation.

Unusual "Dumbbell"-Shaped Hibernoma.

Hibernoma is considered as a rare soft tissue benign tumor originating from brown fat. Few cases have been described so far in the literature; hibernoma was first described by Merkel in 1906, but it was named by Gery in 1914. We present the case of 33-year-old woman who presented with a palpable lump over superior aspect of her thigh associated with pain. Magnetic resonance imaging examination reported a "dumbbell"-shaped soft tissue tumor involving the right side of the pelvis and adductor compartment passing through the obturator foramen into the adductor compartment infiltrating the hip joint. Clinical and imaging features initially suggested liposarcoma, but ultrasound-guided biopsy and final surgical resection yielded the diagnosis of hibernoma. This rare soft tissue tumor can imitate malignancy, but magnetic resonance imaging and possibly guided biopsy are essential for preoperative planning as surgical resection remains the best management pathway.

Nothing is impossible: radiation induced angiosarcoma of breast in a male patient.

Breast cancer in men is rare and only about 390 men in the UK are diagnosed with breast cancer each year with an incidence rate in the UK of 1.5 cases per 100 000 men. In addition, the increased use of radiotherapy for management of breast cancer has led to a reported increase of radiation induced angiosarcomas (RIAS) with an incidence of 0.05-0.3%. Here we report a unique and extremely rare case of RIAS of breast in a male patient. To our knowledge this is the only case in the literature of a radiation induced angiosarcoma of the breast in a male.

Electrochemotherapy for Breast Cancer-Results From the INSPECT Database.

BACKGROUND: Cutaneous recurrence from breast cancer can pose a clinical challenge. It might be the only disease site, or could be part of disseminated disease, and often profoundly affects quality of life. Electrochemotherapy is a palliative treatment using electric pulses to locally permeabilize tumor cells and thereby significantly increase bleomycin cytotoxicity. Collaborating with the International Network for Sharing Practice on ElectroChemoTherapy (INSPECT), we consecutively and prospectively accrued data on patients treated with electrochemotherapy for cutaneous metastases from breast cancer. PATIENTS AND METHODS: Patients were treated with electrochemotherapy at 10 European centers. Under either local or general anaesthesia patients were treated with either local injection (1000 IU/mL intratumoral) or systemic infusion (15,000 IU/m2) of bleomycin. RESULTS: One hundred nineteen patients were included at 10 institutions in the INSPECT network. The primary location was the chest (89%), the median diameter of the cutaneous metastases was 25 mm. Ninety patients were available for response evaluation after 2 months. Complete response was observed in 45 patients (50%), partial response in 19 (21%), stable disease in 16 (18%), and progressive disease in 7 (8%). Three patients were not evaluable. Common side effects were ulceration, long-lasting hyperpigmentation, and low-grade pain. No serious adverse events were observed. CONCLUSION: Electrochemotherapy showed high response rates after a single treatment. Electrochemotherapy has few side effects and can be used as an adjunct to systemic therapies or as a solo treatment. We therefore recommend considering electrochemotherapy for patients with cutaneous metastases.

Is superficial inguinal node dissection adequate for regional control of malignant melanoma in patients with N1 disease?

INTRODUCTION: The optimum extent of surgery for inguinal nodal metastases due to melanoma remains controversial. Recent evidence suggests a conservative superficial groin dissection (SGD) may provide adequate regional control. AIM: To evaluate patients with N1 stage disease treated with SGD to determine the recurrence rates and to evaluate whether SGD was adequate for regional control in these patients. MATERIALS AND METHODS: Patients undergoing SGD between April 2005 and April 2012 were retrospectively analysed from a prospectively collected database. RESULTS: Sixty patients were treated by SGD of which 40 had palpable disease and 20 had a positive sentinel node. Overall median follow-up was 38 months, with median follow-up for the SNB group being 29 months and that of the PD group 49 months. Three patients (5%) developed groin recurrence following SGD. All patients recurred within the superficial site of surgery; there was no deep inguinal or pelvic recurrence. Distant recurrence occurred in 22 patients (36.7%), with 21 of these patients coming from the PD group and one from the SNB group. This difference was statistically significant (p < 0.05). Overall survival at 5 years was 70.3%. Survival at 5 years in the PD group was 63.8% and in the SNB group it was 90.9%, this difference was approaching significance (p = 0.08). CONCLUSION: SGD appears adequate for local disease control in patients with N1 sentinel node positive disease. Longer term followup for N1 palpable disease is required to determine the suitability of SGD for this group of patients.

Facial paediatric desmoid fibromatosis: a case series, literature review and management algorithm.

Desmoid fibromatosis (also known as infantile or aggressive fibromatosis) is a rare soft tissue tumour that is occasionally seen in children. Although histologically benign, its growth pattern is highly aggressive often showing invasion of surrounding musculature and bone. Frequently found in cosmetically sensitive areas, complete excision can present a challenging problem. However, incomplete surgical excision is associated with high recurrence rates and although the disease responds to chemo and radiotherapy, both carry significant risks in young children. The management of four paediatric desmoid fibromatoses occurring in the midface is discussed. The recent and pertinent literature is comprehensively reviewed and an algorithm for the management of paediatric desmoid fibromatoses is proposed.

Tissue expansion for the delayed closure of large myelomeningoceles.

OBJECT: Numerous techniques for the soft-tissue closure of large myelomeningoceles have been described. When patients present for delayed repair beyond the neonatal period, the indications for surgery are both different and less immediate. METHODS: Six patients between 6 weeks and 3.5 years of age with defects ranging from 27 to 49 cm2 (mean 37 cm2) were referred to the authors' institution and were successfully treated by direct skin closure after tissue expansion. CONCLUSIONS: In this paper the authors describe the technique and advantages of expansion compared with those of locoregional flaps in this subgroup of patients with myelomeningoceles.