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.

Videoscopic ilioinguinal lymphadenectomy for groin lymph node metastases from melanoma.

BACKGROUND: Groin lymph node dissection for melanoma is burdened by high postoperative morbidity. Videoscopic lymphadenectomy may lower the incidence of complications, including infection, dehiscence and lymphoedema. This pilot study aimed to investigate the feasibility and postoperative outcomes of videoscopic ilioinguinal lymphadenectomy in patients with inguinal nodal melanoma metastases. METHODS: Patients with inguinal nodal metastases, with either a positive sentinel lymph node biopsy or clinically positive nodes from melanoma, were enrolled. Inguinal dissection was performed via three ports. Iliac dissection was obtained through a preperitoneal access. Intraoperative and postoperative data were collected. RESULTS: Of 23 patients selected for 24 procedures, four needed conversion to an open procedure. Median duration of surgery was 270 (i.q.r. 245-300) min. Wound-related postoperative complications occurred in four patients, although only one needed further intervention. The median number of excised lymph nodes was 21 (i.q.r. 15-25). After a median follow-up of 18 months, regional lymph node recurrence was observed in two patients. CONCLUSION: Videoscopic ilioinguinal lymphadenectomy for melanoma groin lymph node metastases is technically feasible, safe, and associated with acceptable morbidity and oncological outcome.

The number of excised lymph nodes is associated with survival of melanoma patients with lymph node metastasis.

BACKGROUND: Although the number of excised LNs has been associated with patient prognosis in many solid tumors, this association has not been widely investigated in cutaneous melanoma. This study aims to evaluate the association between the number of excised regional lymph nodes (LNs) and melanoma-specific survival. PATIENT AND METHODS: Clinico-pathological data from 2507 patients with LN metastasis treated at nine Italian centers were retrospectively collected. RESULTS: The number of excised LNs correlated with younger age (P < 0.001), male sex (P < 0.001), neck LN field (P < 0.001), LN micrometastasis (P < 0.001) and number of positive LNs (P < 0.001). The number of excised LNs was an independent prognostic factor (HR = 0.85; P = 0.002) after adjustment for other staging features. Upon subgroup analysis, the number of excised LNs had a significant prognostic value in patients bearing 1.01-2.00 mm (HR = 0.79; P = 0.032) and 2.01-4.00 mm (HR = 0.71; P < 0.001) thick melanomas, primary tumors showing ulceration (HR = 0.86; P = 0.033) and Clark level V of invasion (HR = 0.86; P = 0.010), LN micrometastasis (HR = 0.83; P = 0.014) and two to three positive LNs (HR = 0.71; P = 0.001). Finally, this study investigated the influence of the number of excised LNs on patient staging: only when ≥11 nodes were excised the AJCC N stage could stratify prognosis (P < 0.001). Considering the number of excised LNs for each lymphatic field, at least 14, 11, 10 and 12 LNs were needed to stage patients according to the AJCC N stage after a lymphadenectomy of the neck, axilla, inguinal and ilioinguinal LN fields, respectively. CONCLUSIONS: The number of excised LNs can be considered for risk stratification of patients with regional LN metastasis from cutaneous melanoma. We demonstrated that a minimum number of LNs is required for the correct staging of patients. Further research is needed to evaluate the effectiveness of the minimum number of LNs to be dissected.

Histopathological characteristics of subsequent melanomas in patients with multiple primary melanomas.

BACKGROUND: Multiple primary melanomas (MPM) occur in up to 20% of melanoma patients, and subsequent tumours seem to have a favourable histopathological pattern. OBJECTIVE: A prospectively collected cohort of 194 patients with MPM was retrospectively reviewed to investigate clinical and histopathological features of first and subsequent melanomas. METHODS: Patients with MPM who were diagnosed at our Department (1985-2011) and who attended at least a follow-up control yearly were identified. RESULTS: The number of nevi was <10, 10-50 and >50 in 8.7%, 41% and 50.3% of patients respectively. Histopathological dysplastic nevi have been diagnosed in 105 patients. During a median follow-up of 58 months, 159 (81.9%), 24 (12.3%), 7 (3.6%) and 4 (2%) patients developed 2, 3, 4 and ≥ 5 melanomas, respectively. The median time to second primary melanoma was 45 months. The second primary melanoma was diagnosed within 1-year and after 5-year from the first melanoma in 36.6% and 17.3% of patients respectively. First and second primary melanomas were in situ in 41 (21%) and 104 (54%) patients respectively (P < 0.001). Among patients with ≥ 2 invasive melanomas (N = 80), median tumour thickness and ulceration of first and second primaries were 0.91 and 0.44 mm (P <0.001), and 32% and 7.7% (P = 0.001) respectively. CONCLUSIONS: Subsequent melanomas occurred within 1-year from the appearance of the first melanoma in 36% of patients with MPM, while a late melanoma diagnosis was detected in 17% of cases. Second primary melanoma had favourable histopathological features. Our findings support long-term skin surveillance to detect subsequent melanomas at an early stage.

Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET).

BACKGROUND: The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). PATIENTS AND METHODS: The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. RESULTS: A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. CONCLUSIONS: Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

Machine learning to predict overall short-term mortality in cutaneous melanoma.

BACKGROUND: Cutaneous malignant melanoma (CMM) ranks among the ten most frequent malignancies, clinicopathological staging being of key importance to predict prognosis. Artificial intelligence (AI) has been recently applied to develop prognostically reliable staging systems for CMM. This study aims to provide a useful machine learning based tool to predict the overall CMM short-term survival. METHODS: CMM records as collected at the Veneto Cancer Registry (RTV) and at the Veneto regional health service were considered. A univariate Cox regression validated the strength and direction of each independent variable with overall mortality. A range of machine learning models (Logistic Regression classifier, Support-Vector Machine, Random Forest, Gradient Boosting, and k-Nearest Neighbors) and a Deep Neural Network were then trained to predict the 3-years mortality probability. Five-fold cross-validation and Grid Search were performed to test the best data preprocessing procedures, features selection, and to optimize models hyperparameters. A final evaluation was carried out on a separate test set in terms of balanced accuracy, precision, recall and F1 score. The best model was deployed as online tool. RESULTS: The univariate analysis confirmed the significant prognostic value of TNM staging. Adjunctive clinicopathological variables not included in the AJCC 8th melanoma staging system, i.e., sex, tumor site, histotype, growth phase, and age, were significantly linked to overall survival. Among the models, the Neural Network and the Random Forest models featured the best prognostic performance, achieving a balanced accuracy of 91% and 88%, respectively. According to the Gini importance score, age, T and M stages, mitotic count, and ulceration appeared to be the variables with the greatest impact on survival prediction. CONCLUSIONS: Using data from patients with CMM, we developed an AI algorithm with high staging reliability, on top of which a web tool was implemented ( unipd.link/melanomaprediction ). Being essentially based on routinely recorded clinicopathological variables, it can already be implemented with minimal effort and further tested in the current clinical practice, an essential phase for validating the model's accuracy beyond the original research context.

Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions.

BACKGROUND: Sarcomas represent a heterogeneous group of tumors. Accurate determination of histological diagnosis and prognostic factors is critical for the delineation of treatment strategies. The contribution of second opinion (SO) to improve diagnostic accuracy has been suggested for sarcoma but has never been established in population-based studies. METHODS: Histological data of patients diagnosed with sarcoma in Rhone-Alpes (France), Veneto (Italy) and Aquitaine (France) over a 2-year period were collected. Initial diagnoses were systematically compared with SO from regional and national experts. RESULTS: Of 2016 selected patients, 1463 (73%) matched the inclusion criteria and were analyzed. Full concordance between primary diagnosis and SO (the first pathologist and the expert reached identical conclusions) was observed in 824 (56%) cases, partial concordance (identical diagnosis of connective tumor but different grade or histological subtype) in 518 (35%) cases and complete discordance (benign versus malignant, different histological type or invalidation of the diagnosis of sarcoma) in 121 (8%) cases. The major discrepancies were related to histological grade (n = 274, 43%), histological type (n = 144, 24%), subtype (n = 18, 3%) and grade plus subtype or grade plus histological type (n = 178, 29%). CONCLUSION: More than 40% of first histological diagnoses were modified at second reading, possibly resulting in different treatment decisions.

Electrochemotherapy for disseminated superficial metastases from malignant melanoma.

BACKGROUND: The aim of the study was to determine predictive factors for effectiveness, toxicity and local disease control in patients with malignant melanoma treated with bleomycin-based electrochemotherapy (ECT). METHODS: Electrochemotherapy was offered to patients with superficially disseminated melanoma metastases unsuitable for resection and unresponsive to chemotherapy. RESULTS: Eighty-five patients were treated with up to six ECT cycles with minimal, mainly dermatological, toxicity. One month after the first ECT, an objective response was observed in 80 patients (94 per cent). After retreatment because of a partial response in 39 patients, a complete response was achieved in 19 patients. Among the 41 (48 per cent) complete responders at first ECT, 19 patients received a second cycle because of new lesions after a median of 6 (range 2-14) months. After a median follow-up of 26 months, six patients experienced local recurrence with a 2-year local progression-free survival rate of 87 per cent. In multivariable analysis, significant predictive factors for response were tumour size (odds ratio (OR) 0·23, 95 per cent confidence interval (c.i.) 0·19 to 0·86; P = 0·003) and number of lesions (OR 0·38, 0·28 to 0·88; P = 0·002). An increasing number of electrode applications (hazard ratio (HR) 2·18, 95 per cent c.i. 1·22 to 3·44; P = 0·041) and ECT cycles (HR 0·46, 0·22 to 0·95; P = 0·005) were predictors of local control. There were no predictors of toxicity. Melanoma thickness and lower limb location of metastases were prognostic for survival. CONCLUSION: The most suitable candidates for ECT were patients with few and small metastases on the lower limb treated with multiple electrode applications and ECT cycles.

Prognosis in patients with sentinel node-positive melanoma without immediate completion lymph node dissection.

BACKGROUND: The therapeutic value of immediate completion lymph node dissection (CLND) for sentinel node (SN)-positive melanoma is unknown. The aim of this study was to evaluate the impact of immediate CLND on the outcome of patients with SN-positive melanoma. METHODS: Patients with SN metastases treated between 1993 and 2008 at ten cancer centres from the European Organization for Research and Treatment of Cancer Melanoma Group were included in this retrospective study. Maximum tumour size, intranodal location and penetrative depth of SN metastases were measured. Outcome in those who had CLND was compared with that in patients who did not undergo completion lymphadenectomy. RESULTS: Of 1174 patients with SN-positive melanoma, 1113 (94.8 per cent) underwent CLND and 61 (5.2 per cent) did not. Median follow-up for the two groups was 34 and 48 months respectively. In univariable survival analysis, CLND did not significantly influence disease-specific survival (hazard ratio (HR) 0.89, 95 per cent confidence interval 0.58 to 1.37; P = 0.600). However, patients who did not undergo CLND had more favourable prognostic factors. Matched-pair analysis, with matching for age, Breslow thickness, tumour ulceration and SN tumour burden, showed that CLND had no influence on survival (HR 0.86, 0.46 to 1.61; P = 0.640). After adjusting for prognostic factors in multivariable survival analyses, no difference in survival was found. CONCLUSION: In these two cohorts of patients with SN-positive melanoma and prognostic heterogeneity, outcome was not influenced by CLND.

Hyperthermic isolated perfusion with tumor necrosis factor-alpha and doxorubicin for the treatment of limb-threatening soft tissue sarcoma: the experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO).

BACKGROUND: Tumor necrosis factor-alpha (TNFalpha)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFalpha dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFalpha. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFalpha dose and doxorubicin (Dx). PATIENTS AND METHODS: HILP with TNFalpha (at a dosage of either 1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. RESULTS: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFalpha dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. CONCLUSION: HILP with 1 mg of TNFalpha is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.

Prognostic factors influencing tumor response, locoregional control and survival, in melanoma patients with multiple limb in-transit metastases treated with TNFalpha-based isolated limb perfusion.

BACKGROUND: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNFalpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable dose (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFalpha was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNFalpha-based ILP and identify prognostic factors for response, locoregional control and survival. PATIENTS AND METHODS: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>or=10 nodules3 cm) in 42.5% of the patients and unresectable in 33% . Forty patients were treated with a TNFalpha dosage of >1 mg and 73 with 1 mg. Patients with tumors in the upper and lower limbs were submitted to ILP via axillary and iliac vessels, respectively. TNFalpha was injected in the arterial line of an extracorporeal circuit at the pre-established dose, followed by melphalan (13 and 10 mg/l of limb volume for the upper and lower limbs, respectively) 30 minutes later. RESULTS: Complete responses (CR) and partial responses (PR) were 63% and 24.5%, respectively, with an objective response (OR) of 87.5%. No change (NC) was observed in only 12.5% of the patients. Upon multivariate analysis, only bulky disease maintained its independent value for tumor response with an odds ratio of 4.07 and a p-value of 0.02. The 5-year locoregional disease-free survival was 42.7%. Upon multivariate analysis, the only prognostic factors were stage, age and bulky disease. The 5-year overall survival was 49%. Multivariate analysis showed that only sex, stage and CR maintained their independent values. CONCLUSION: TNFalpha-based ILP was proven to be an effective treatment for melanoma patients with in-transit metastases. The TNFalpha dosage of 1 mg was as effective as 3-4 mg, with lower toxicity and cost. We propose that TNFalpha and melphalan-based ILP should be employed for bulky tumors or after failure of melphalan-based ILP.

Microscopic histological characteristics of soft tissue sarcomas: analysis of tissue features and electrical resistance.

Tissue electrical conductivity is correlated with tissue characteristics. In this work, some soft tissue sarcomas (STS) excised from patients have been evaluated in terms of histological characteristics (cell size and density) and electrical resistance. The electrical resistance has been measured using the ex vivo study on soft tissue tumors electrical characteristics (ESTTE) protocol proposed by the authors in order to study electrical resistance of surgical samples excised by patients in a fixed measurement setup. The measurement setup includes a voltage pulse generator (700 V, 100 µs long at 5 kHz, period 200 µs) and an electrode with 7 needles, 20 mm-long, with the same distance arranged in a fixed hexagonal geometry. In the ESTTE protocol, the same voltage pulse sequence is applied to each different tumor mass and the corresponding resistance has been evaluated from voltage and current recorded by the equipment. For each tumor mass, a histological sample of the volume treated by means of voltage pulses has been taken for histological analysis. Each mass has been studied in order to identify the sarcoma type. For each histological sample, an image at 20× or 40× of magnification was acquired. In this work, the electrical resistance measured for each tumor has been correlated with tissue characteristics like the type, size and density of cells. This work presents a preliminary study to explore possible correlations between tissue characteristics and electrical resistance of STS. These results can be helpful to adjust the pulse voltage intensity in order to improve the electrochemotherapy efficacy on some histotype of STS.

Measuring the quality of melanoma surgery - Highlighting issues with standardization and quality assurance of care in surgical oncology.

In an attempt to ensure high standards of cancer care, there is increasing interest in determining and monitoring the quality of interventions in surgical oncology. In recent years, this has been particularly the case for melanoma surgery. The vast majority of patients with melanoma undergo surgery. Usually, this is with combinations of wide excision, sentinel lymph node biopsy and lymphadenectomy. The indications for these procedures evolved during a time when no effective systemic adjuvant therapy was available, and whilst the rationale has been sound, the justification for differences in extent and thoroughness has generally been supported by inadequate or low-level evidence. This has led to a substantial variation among melanoma centres or even among surgeons within a centre in how these procedures are done. With recent rapid progress in the efficacy of systemic treatments that are impacting on overall survival, the prospect of long-term survival in these previously high risk patients means that more than ever long-term locoregional control of melanoma is imperative. Furthermore, the understanding of effects of systemic therapy on locoregional disease will only be interpretable if surgeons use standardized, high quality techniques. This article focuses on standardization and evolution of quality indicators for melanoma surgery and how these might have a positive impact on patient care.

Isolated limb perfusion for the management limb threatening soft tissue sarcomas: The role of histological type on clinical outcomes.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) is an effective neoadjuvant treatment to avoid amputation in patients with locally advanced extremity soft tissue sarcomas (STS). We aimed to investigate whether STS histological type plays a role in predicting clinical outcomes. METHODS: This study reports a retrospective analysis of 125 patients with limb threatening STS (liposarcoma, n = 41; malignant peripheral nerve sheath tumor, n = 20; leiomyosarcoma, n = 20; miscellany, n = 44), who underwent HILP from 1990 through 2015 at our institution. The following endpoints were evaluated: tumor response (assessed by radiological imaging and histology), limb sparing rate, local progression-free survival (LPFS) and overall survival (OS). RESULTS: On average, overall (complete + partial) tumor response was significantly greater in patients affected with liposarcoma as compared to those with other histotypes (radiological response rate: 38/41, 92.7% vs 66/84, 78.6%, P-value: 0.048; mean histological necrosis: 83.6% vs 52.9%, P < 0.0001). Limb sparing rate was also higher among patients with liposarcoma as compared to other histotypes (39/41, 95.1% vs 62/84, 73.8%, P-value: 0.005). As regards survival, LPFS was similar across tumor types, whereas OS resulted significantly worse in patients with limb leiomyosarcoma (log-rank P-value: 0.009). CONCLUSIONS: HILP is a very effective treatment modality for limb threatening STS. In our series, liposarcoma appears to be the histological type most sensitive to HILP in terms of tumor response and thus limb sparing, which might help clinicians in the patient selection process.

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

Calculating regional tissue volume for hyperthermic isolated limb perfusion: Four methods compared.

INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) can be performed as an alternative to amputation for soft tissue sarcomas and melanomas of the extremities. Melphalan and tumor necrosis factor-alpha are used at a dosage that depends on the volume of the limb. Regional tissue volume is traditionally measured for the purposes of HILP using water displacement volumetry (WDV). Although this technique is considered the gold standard, it is time-consuming and complicated to implement, especially in obese and elderly patients. AIM: The aim of the present study was to compare the different methods described in the literature for calculating regional tissue volume in the HILP setting, and to validate an open source software. METHODS: We reviewed the charts of 22 patients (11 males and 11 females) who had non-disseminated melanoma with in-transit metastases or sarcoma of the lower limb. We calculated the volume of the limb using four different methods: WDV, tape measurements and segmentation of computed tomography images using Osirix and Oncentra Masterplan softwares. RESULTS AND CONCLUSION: The overall comparison provided a concordance correlation coefficient (CCC) of 0.92 for the calculations of whole limb volume. In particular, when Osirix was compared with Oncentra (validated for volume measures and used in radiotherapy), the concordance was near-perfect for the calculation of the whole limb volume (CCC = 0.99). With methods based on CT the user can choose a reliable plane for segmentation purposes. CT-based methods also provides the opportunity to separate the whole limb volume into defined tissue volumes (cortical bone, fat and water).

Electrical resistance of human soft tissue sarcomas: an ex vivo study on surgical specimens.

This paper presents a study about electrical resistance, which using fixed electrode geometry could be correlated to the tissue resistivity, of different histological types of human soft tissue sarcomas measured during electroporation. The same voltage pulse sequence was applied to the tumor mass shortly after surgical resection by means of a voltage pulse generator currently used in clinical practice for electrochemotherapy that uses reversible electroporation. The voltage pulses were applied by means of a standard hexagonal electrode composed by seven, 20-mm-long equispaced needles. Irrespective of tumor size, the electrode applies electric pulses to the same volume of tissue. The resistance value was computed from the voltage and current recorded by the pulse generator, and it was correlated with the histological characteristics of the tumor tissue which was assessed by a dedicated pathologist. Some differences in resistance values, which could be correlated to a difference in tissue resistivity, were noticed according to sarcoma histotype. Lipomatous tumors (i.e., those rich in adipose tissue) displayed the highest resistance values (up to 1700 Ω), whereas in the other soft tissue sarcomas, such as those originating from muscle, nerve sheath, or fibrous tissue, the electrical resistance measured was between 40 and 110 Ω. A variability in resistance was found also within the same histotype. Among lipomatous tumors, the presence of myxoid tissue between adipocytes reduced the electrical resistance (e.g., 50-100 Ω). This work represents the first step in order to explore the difference in tissue electrical properties of STS. These results may be used to verify whether tuning electric field intensity according to the specific STS histotype could improve tissue electroporation and ultimately treatment efficacy.

Evaluation of the Electroporation Efficiency of a Grid Electrode for Electrochemotherapy: From Numerical Model to In Vitro Tests.

Electrochemotherapy (ECT) is a local anticancer treatment based on the combination of chemotherapy and short, tumor-permeabilizing, voltage pulses delivered using needle electrodes or plate electrodes. The application of ECT to large skin surface tumors is time consuming due to technical limitations of currently available voltage applicators. The availability of large pulse applicators with few and more spaced needle electrodes could be useful in the clinic, since they could allow managing large and spread tumors while limiting the duration and the invasiveness of the procedure. In this article, a grid electrode with 2-cm spaced needles has been studied by means of numerical models. The electroporation efficiency has been assessed on human osteosarcoma cell line MG63 cultured in monolayer. The computational results show the distribution of the electric field in a model of the treated tissue. These results are helpful to evaluate the effect of the needle distance on the electric field distribution. Furthermore, the in vitro tests showed that the grid electrode proposed is suitable to electropore, by a single application, a cell culture covering an area of 55 cm(2). In conclusion, our data might represent substantial improvement in ECT in order to achieve a more homogeneous and time-saving treatment, with benefits for patients with cancer.

Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors.

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.