Health-related quality of life trajectories in melanoma patients after electrochemotherapy: real-world insights from the InspECT register.

BACKGROUND: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. OBJECTIVES: This study aimed to evaluate health-related quality of life (HRQoL) in melanoma patients pre-/post-ECT and its effect on treatment outcome. METHODS: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15,000 IU/m2 ; 1000 IU mL/cm3 ) followed by 100-microsecond, 1000-V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression-free survival (LPFS), toxicity (CTCAE v5.0), and patient-reported HRQoL at baseline, one, two, four and ten months (EuroQol [EQ-5D-3L], including 5-item utility score [EQ-5D] and visual analogue scale for self-reported health state [EQ-VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. RESULTS: Median tumour size was 2 cm. Complete response rate, G3 toxicity and one-year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%. At baseline, age-paired HRQoL did not differ from the general European population. Following ECT, both EQ-5D and EQ-VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ-5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within four months), and self-care and usual activities (throughout the follow-up) domains. Concomitant checkpoint inhibition correlated with better EQ-5D and EQ-VAS trajectories. Baseline EQ-5D was the exclusive independent predictor for complete response (RR 14.76, p=0.001). CONCLUSIONS: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self-care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information which can help identify patients most likely to respond.

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 (2008-2019).

BACKGROUND: Electrochemotherapy (ECT) is a treatment for both primary and secondary cutaneous tumours. The international Network for sharing practices on ECT group investigates treatment outcomes after ECT using a common database with defined parameters. METHODS: Twenty-eight centres across Europe prospectively uploaded data over an 11-year period. Response rates were investigated in relation to primary diagnosis, tumour size, choice of electrode type, route of bleomycin administration, electrical parameters recorded and previous irradiation in the treated field. RESULTS: Nine hundred eighty-seven patients, with 2482 tumour lesions were included in analysis. The overall response (OR) rate was 85% (complete response [CR]: 70%, partial response rate: 15%, stable disease: 11%, and progressive disease: 2%). For different histologies, OR and CR rates for metastases of malignant melanoma were 82% and 64%, basal cell carcinoma were 96% and 85%, breast cancer metastases were 77% and 62%, squamous cell carcinoma were 80% and 63% as well as Kaposi's sarcoma were 98% and 91%, respectively. Variance was demonstrated across histotypes (p < 0.0001) and in accordance with size of lesion treated (dichotomised at diameter of 3 cm (p < 0.0001). Hexagonal electrodes were generally used for larger tumours, but for tumours up to 3 cm, linear array electrodes provided better tumour control than hexagonal electrodes (80%:74%, p < 0.003). For tumours more than 2 cm, intravenous administration was superior to intratumoural (IT) administration (p < 0.05). Current recorded varied across tumour histologies and size but did not influence response rate. In previously irradiated areas, responses were selectively lower for IT administration. CONCLUSIONS: These cumulative data endorse efficiency of ECT across a broad range of histotypes. Analysis of 2482 lesions details subgroup analysis on treatment response informing future treatment choices.

Electrochemotherapy of unresectable cutaneous tumours with reduced dosages of intravenous bleomycin: analysis of 57 patients from the International Network for Sharing Practices of Electrochemotherapy registry.

BACKGROUND: Electrochemotherapy (ECT) is currently used to treat unresectable superficial tumours of different histotypes through the combination of cytotoxic chemotherapy and local application of electric pulses. In 2006, a collaborative project defined the ESOPE (European Standard Operating Procedures of Electrochemotherapy) guidelines to standardize the procedure. The International Network for Sharing Practices of Electrochemotherapy (InspECT) aims to refine the ESOPE and improve clinical practice. Limiting patient exposure to systemic chemotherapy would be advisable to ameliorate ECT safety profile. OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of ECT with reduced chemotherapy dosages. METHODS: In a retrospective analysis of a prospectively maintained database (InspECT registry), we evaluated the outcome of patients who received ECT with reduced dosages of bleomycin (7500, 10 000 or 13 500 IU/m2 , instead of the standard dose of 15 000 IU/m2 ). Tumour response in melanoma patients was compared with melanoma patients of the InspECT registry who received the standard dose of bleomycin. RESULTS: We identified 57 patients with 147 tumours (melanoma, 38.6%; squamous cell carcinoma, 22.8%; basal cell carcinoma, 17.5%; breast cancer 7%; Kaposi sarcoma 7%; other histotypes, 7.1%). Per-tumour complete response (CR) rate at 60 days was 70.1% (partial, 16.3%); per-patient CR was 57.9% (partial, 21.1%). Local pain was the most frequently reported side-effect (n = 22 patients [39%]), mostly mild; two patients experienced flu-like symptoms, one patient nausea. We observed the same CR rate (55%) in patients with melanoma treated by reduced or conventional bleomycin dosages (P = 1.00). CONCLUSIONS: Electrochemotherapy performed with reduced bleomycin dosages could be as effective as with currently recommended dose. Patients with impaired renal function or candidate to multiple ECT cycles could benefit from a reduced dose protocol. Our findings need prospective confirmation before being adopted in clinical practice.

Electrochemotherapy in the treatment of metastatic malignant melanoma: a prospective cohort study by InspECT.

BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. METHODS: Thirteen cancer centres in the International Network for Sharing Practices on Electrochemotherapy consecutively and prospectively uploaded data to a common database. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia. RESULTS: In total, 151 patients with metastatic melanoma were identified from the database, 114 of whom had follow-up data of 60 days or more. Eighty-four of these patients (74%) experienced an overall response (OR = complete response + partial response). Overall, 394 lesions were treated, of which 306 (78%) showed OR, with 229 showing complete response (58%). In multivariate analysis, factors positively associated with overall response were coverage of deep margins, absence of visceral metastases, presence of lymphoedema and treatment of nonirradiated areas. Factors significantly associated with complete response to ECT treatment were coverage of deep margins, previous irradiation of the treated area and tumour size (< 3 cm). One-year overall survival in this cohort of patients was 67% (95% confidence interval 57-77%), while melanoma-specific survival was 74% (95% confidence interval 64-84%). No serious adverse events were reported, and the treatment was in general very well tolerated. CONCLUSIONS: ECT is a highly effective local treatment for melanoma metastases in the skin, with no severe adverse effects noted in this study. In the presence of certain clinical factors, ECT may be considered for local tumour control as an alternative to established local treatments, or as an adjunct to systemic treatments.

Prospective multicentre cohort study on 9154 surgical procedures to assess the risk of postoperative bleeding - a DESSI study.

BACKGROUND: To date, there is still a debate how to deal with patients receiving antithrombotic agents prior to surgical procedures on the skin. OBJECTIVE: To prospectively assess complications after dermatosurgical interventions, especially bleeding, depending on anticoagulation therapy. METHODS: Patients underwent surgery consecutively as scheduled, without randomization, whether or not they were currently taking anticoagulants. Nine institutions of the DESSI (DErmatoSurgical Study Initiative) working group documented patient data prospectively on a standardized study sheet prior to and after 9154 dermatosurgical interventions. RESULTS: Bleeding complications were observed in 7.14% of cases (654/9154 surgeries). A severe bleed requiring intervention by a physician occurred in 83 surgeries (0.91%). In multivariate analysis, INR, length of the defect, perioperative antibiotic treatment, current treatment with anticoagulation therapy, age and surgery on hidradenitis suppurativa/acne inversa (HS/AI) were significant parameters independently influencing the risk of bleeding. Discontinuation of phenprocoumon therapy and subsequent switching to low molecular weight heparin was associated with the highest risk of bleeding (9.26%). CONCLUSION: Bleeding complications in skin surgery are generally rare. Even if slightly increased complication rates are found in patients taking anticoagulants during skin surgery, platelet inhibitors should not be stopped prior to surgery. If a surgical procedure in patients on a combination therapy of 2 or more antiplatelet cannot be postponed, it should be conducted with the patient remaining on combination therapy. Discontinuation of DOACs is recommended 24 h prior to surgery. Bridging of phenprocoumon should be terminated. In patients with a bleeding history, the INR value should be within the therapeutic range.

The impact of sentinel node dissection on disease-free and overall tumour-specific survival in melanoma patients: a single centre group-matched analysis of 1192 patients.

BACKGROUND: Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence, removal of potential lymph node micrometastasis will alter survival outcome. OBJECTIVE: The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus SLND group to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma. METHODS AND MATERIALS: A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumour thickness and localization of primary tumour. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in; and hence, subject to change over time. RESULTS: Kaplan-Meier testing revealed significant differences in survival in favour of the SLND group. Mean overall tumour-specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group respectively (P-value: 0.024). Disease-free survival (log-rank test: 0.003) and time to lymph node progression (P-value: <0.01) also differed significantly between the two groups. CONCLUSION: SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumour-specific survival of melanoma patients.

Morphologic features of basal cell carcinoma using the en-face mode in frequency domain optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has become a valuable non-invasive tool in the in vivo diagnosis of non-melanoma skin cancer, especially of basal cell carcinoma (BCC). Due to an updated software-supported algorithm, a new en-face mode - similar to the horizontal en-face mode in high-definition OCT and reflectance confocal microscopy - surface-parallel imaging is possible which, in combination with the established slice mode of frequency domain (FD-)OCT, may offer additional information in the diagnosis of BCC. OBJECTIVES: To define characteristic morphologic features of BCC using the new en-face mode in addition to the conventional cross-sectional imaging mode for three-dimensional imaging of BCC in FD-OCT. METHODS: A total of 33 BCC were examined preoperatively by imaging in en-face mode as well as cross-sectional mode in FD-OCT. Characteristic features were evaluated and correlated with histopathology findings. RESULTS: Features established in the cross-sectional imaging mode as well as additional features were present in the en-face mode of FD-OCT: lobulated structures (100%), dark peritumoral rim (75%), bright peritumoral stroma (96%), branching vessels (90%), compressed fibrous bundles between lobulated nests ('star shaped') (78%), and intranodular small bright dots (51%). These features were also evaluated according to the histopathological subtype. In the en-face mode, the lobulated structures with compressed fibrous bundles of the BCC were more distinct than in the slice mode. CONCLUSION: FD-OCT with a new depiction for horizontal and vertical imaging modes offers additional information in the diagnosis of BCC, especially in nodular BCC, and enhances the possibility of the evaluation of morphologic tumour features.

[Dermatologic surgery on the scalp]. / Dermatochirurgie am Capillitium.

Soft tissue defects of the scalp can be closed with varying techniques depending on size and depth of the defect. While small and superficial defects can be closed primarily or be left open for secondary intention healing, larger and deeper defects may need flaps or skin grafts. Extensive defects may require combined flaps or vacuum assisted closure techniques. Defects of the periosteum with denuded skull bone must be treated immediately to avoid bony complications. Usually, the tabula externa is fenestrated with holes or abraded totally to create better healing conditions. Granulation tissue may be induced on the properly prepared skull with vacuum-assisted closure, by using collagen sheets or with dermal skin substitutes. New developments in tissue engineering will surely provide new techniques for dealing with deep and extensive soft tissue defects.

Ex vivo high-definition optical coherence tomography of basal cell carcinoma compared to frozen-section histology in micrographic surgery: a pilot study.

BACKGROUND: Micrographic surgery is an established, but time-consuming operating procedure for facial basal cell carcinoma (BCC). A new high-definition (HD) optical coherence tomography (OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode allows a fast and non-invasive in vivo examination of BCC. OBJECTIVES: To compare the diagnosis of BCC in excised tissue ex vivo by high-definition optical coherence tomography (HD-OCT) with the findings of frozen-section histology in micrographic surgery. METHODS: Twenty freshly excised BCC were examined by HD-OCT in the en-face and slice imaging mode divided into four sections each in concordance with the four excision margins of histography, and subsequently processed for conventional micrographic evaluation. RESULTS: A total of 80 HD-OCT images of 20 BCCs were evaluated and in 45% (9/20) HD-OCT correlated perfectly with the histography results. The sensitivity and specificity for the 80 evaluated HD-OCT images were 74% and 64% respectively. CONCLUSIONS: High-definition optical coherence tomography allows the postoperative identification of BCC in excised tissue ex vivo, but has still limitations in the recognition of tumour margins in comparison with the micrographic evaluation of frozen sections.

[Recurrent fibrosarcomatous dermatofibrosarcoma protuberans. Ultrasound imaging]. / Rezidiv eines fibrosarkomatösen Dermatofibrosarcoma protuberans. Sonographische Darstellung.

Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor of intermediate malignancy with a locally aggressive growth behavior with a high rate of recurrence. Wide local excision with histographic margin control as well as regular follow-ups including clinical as well as ultrasound examination are crucial to detect local recurrence or metastasis. Ultrasound imaging can not only identify recurrences but also asses their extent. We report on a patient with a relapse of fibrosarcomatous DFSP, which could be demonstrated by ultrasound imaging.

Rapid wound healing of scalp wounds devoid of periosteum with milling of the outer table and split-thickness skin grafting.

BACKGROUND: Excision of large scalp tumours may result in exposed bone devoid of periosteum. The resultant surgical defects may be too large to close by either primary closure or local cutaneous flap. The denuded bone usually precludes the immediate placement of a skin graft. OBJECTIVES: To describe our experience with milling the outer cortical table of the skull in order to promote granulation and hasten wound healing. METHODS: In 11 patients, we expanded existing techniques of exposing diploic veins in the cancellous bone by completely milling the exposed outer table of the scalp bone with a rose head burr driven by a pneumatic power drill. After induction of punctate bleeding a split-skin graft was placed in the same session and secured with a tie-over foam dressing. Dressing was removed 7 days after surgery. All patients received perioperative antibiotics. Informed consent was obtained prior to the procedure. RESULTS: In all 11 patients a healing of the split-thickness skin graft was observed within 1 week. CONCLUSIONS: The combination of extensive exposure of cancellous bone and an immediate split-thickness skin graft reduces convalescence time from multiple weeks to 7 days. This is beneficial in older patients sparing them from frequent visits to the doctor. Furthermore, early closure may reduce the risk of infection.

[Basal cell carcinomas in radiotherapy-treated port wine stains. An ideal indication for Mohs surgery]. / Basalzellkarzinome auf mit Radiotherapie vorbehandelten vaskulären Malformationen. Eine ideale Indikation für mikroskopisch kontrollierte Chirurgie.

BACKGROUND: Early treatment of port wine stains with ionizing radiation can lead to the development of often multifocal basal cell carcinomas (BCC) after decades. In most cases it is clinically impossible to distinguish between the tumor and the underlying vascular malformation and to decide where to set surgical margins. PATIENTS AND METHODS: We report on a series of three patients with BCC overlying a port wine stain that had previously been treated with radiation therapy in early childhood. In all patients Mohs surgery was performed to insure complete excision of the BCC. RESULTS: In our patients, development of BCC occurred about 20 to 40 years after radiation therapy. Clinically - without the help of Mohs surgery - the borders of the BCC could not have been detected due to the underlying nevi flammei in all cases. CONCLUSIONS: BCC overlying a port wine stain previously treated with radiation therapy is a rare but ideal indication for Mohs surgery. In addition we recommend regular clinical follow-ups to detect recurrent or additional BCC as early as possible.

[Perioperative antibiotic prophylaxis in dermatologic surgery. Update 2009]. / Perioperative Antibiotikaprophylaxe in der Dermatochirurgie. Update 2009.

As specific data and studies concerning perioperative antibiotic prophylaxis in dermatologic surgery are scarce, recommendations to date mainly draw on findings from other medical disciplines and use them analogously. Three main factors are essential in the decision process: 1st How contaminated is the wound (or will it be)? 2nd Where is the lesion located and what kind of procedure is intended? 3rd Is the patient among the highest risk group for endocarditis? An algorithm is presented incorporating these key features. The preferred antibiotic for perioperative prophylaxis is a first generation or second generation oral cephalosporin, a beta-lactamase resistant penicillin (isoxazolyl penicillin) or amoxicillin/clavulanic acid. The prophylaxis is administered in the highest possible single dose within 2 hours before and 3 hours after surgery. Penicillin or cephalosporin can be substituted with clindamycin or erythromycin in case of known drug allergies. There is insufficient data on the pros and cons of preoperative hair removal. Should hair removal be necessary, clipping is preferred to shaving.

[Current recommendations in the treatment of basal cell carcinoma and squamous cell carcinoma of the skin]. / Aktuelle Therapieempfehlungen für das Basalzellkarzinom und Plattenepithelkarzinom der Haut.

The incidence of the most common tumors of the skin, basal cell carcinoma and squamous cell carcinoma, has risen rapidly in recent years. Dermatologists see in their daily practice many different clinical and histological variants of these tumors. They must be able to develop therapeutic strategies adapted to the tumor and the patient. Surgical excision remains the standard treatment. Micrographic histological evaluation should be employed in difficult locations, for large tumors and when there is increased risk of recurrence or metastasis. For initial or superficial lesions, other approaches such as radiation therapy, as well as curettage, cryosurgery, laser therapy and photodynamic therapy can be employed. An additional option is topical treatment with imiquimod or 5-flourouracil.

[First experiences with a new radiopharmaceutical for sentinel lymph node detection in malignant melanoma: (99m)Tc colloidal rhenium sulphide]. / Erste Erfahrungen mit einem neuen Radiopharmakon für die Wächterlymphknoten - Detektion beim malignen Melanom: (99m)Tc markiertes kolloidales Rheniumsulfid.

UNLABELLED: AIM of this study was to localize the sentinel lymph node by lymphoscintigraphy using technetium-99m colloidal rhenium sulphide (Nanocis), a new commercially available radiopharmaceutical. Due to the manufacturers' instructions it is licensed for lymphoscintigraphy. PATIENTS AND METHODS: 35 consecutive patients with histologically proved malignant melanoma, but without clinical evidence of metastases, were preoperatively examined by injecting 20-40 MBq Nanocis with (mean particle size: 100 nm; range: 50-200 nm) intradermally around the lesion. Additionally blue dye was injected intraoperatively. A hand-held gamma probe guided sentinel node biopsy. RESULTS: During surgery, the preoperatively scintigraphically detected sentinel lymph nodes were identified in 34/35 (97%) patients. The number of sentinel nodes per patient ranged from one to four (mean: n = 1.8). Histologically, metastatic involvement of the sentinel lymph node was found in 12/35 (34%) patients; the sentinel lymph node positive-rate (14/63 SLN) was 22%. Thus, it is comparable to the findings of SLN-mapping using other technetium-99m-labeled nanocolloides. CONCLUSION: (99m)Tc-bound colloidal rhenium sulphide is also suitable for sentinel node mapping.

Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease.

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan-Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1+/-2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and 67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/-5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

[Kossard frontal fibrosing alopecia in a man]. / Frontale fibrosierende Alopezie Kossard bei einem Mann.

In 1994 Steven Kossard described a new and peculiar type of hair loss that he named postmenopausal frontal fibrosing alopecia. In 6 elderly women he observed a symmetric regression of the frontal hair line. Often the eyebrows were also affected. Histology showed lichen planopilaris. There were no clinical signs of lichen planus on the rest of the body. Since the original description by Kossard, several cases of frontal fibrosing alopecia have been described--almost all of them in elderly women. We report a man with frontal fibrosing alopecia of the Kossard type.

[Lipoma of the forehead]. / Das Lipom der Stirn.

BACKGROUND AND OBJECTIVE: Lipomas should be included in the differential diagnosis of tumors located on the forehead. They require a different operative plan. PATIENTS/METHODS: Lipomas of the forehead were extirpated in ten patients. Dermatohistopathologic investigations confirmed the diagnosis lipoma in each case and exactly identified the anatomic layers surrounding the tumor. RESULTS: Histologic investigations revealed the localization of the lipoma in the submuscular layer in eight patients and in the subgaleal layer in two patients. CONCLUSIONS: Lipomas of the forehead should be differentiated into submuscular and subgaleal lipomas depending on the exact anatomic localization below the frontalis muscle or underneath the galea aponeurotica. This classification is simple and aids in operative planning.