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.

High-dose sequential chemotherapy (HDS) versus PEB chemotherapy as first-line treatment of patients with poor prognosis germ-cell tumors: mature results of an Italian randomized phase II study.

BACKGROUND: In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS: From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS: The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.

Immediate lengthening temporalis myoplasty for facial palsy reconstruction following facial nerve inclusive total parotidectomy.

Immediate lengthening temporalis myoplasty (Labbé procedure) for immediate dynamic facial reanimation after nerve-inclusive parotidectomy in the elderly population is undocumented in the literature. The aim of this work was to determine whether the Labbé approach could achieve immediate, good functional and static results in elderly patients with acquired facial palsy. A retrospective analysis of five patients with parotid malignancies involving the facial nerve who underwent parotidectomy and an immediate Labbé procedure was performed. The House-Brackmann and Sunnybrook scores for facial palsy were used as objective measurements of the functional outcome. All patients underwent total parotidectomy, neck dissection, Labbé procedure, immediate temporary tarsorrhaphy, brow lift, and postoperative radiotherapy. Mean patient age was 83 (range 73-87) years. The average resected tumour size was 3.54 cm. The mean duration of surgery was 324 min and length of hospital stay 4 days. All patients experienced an improvement in House-Brackmann of one grade postoperative (grade V to IV in four, grade VI to V in one); the Sunnybrook score improved by 31 points on average (mean preoperative 3.8 vs postoperative 34.8). An immediate Labbé procedure following ablative parotid malignancy resection is a reliable and safe reconstructive procedure in a carefully selected elderly population, providing acceptable immediate static and dynamic hemifacial mimetic function and eliminating an additional facial palsy correction procedure.

The pedicled submental flap in facial reconstruction.

Submental flap (SF) is a reconstructive technique that can be utilised for reconstruction of medium to large oral cavity defects, head and neck cancer, and pharyngocutaneous fistula. The submental artery island flap is pedicled on the submental artery and veins. The vascular pedicle has a length of up to 8cm. If it is further dissected to its origin from the facial artery, the pedicle can be lengthened by an additional 1-2cm to reach the lateral canthus and zygomatic arch. The use of SF for the reconstruction of head and neck defects has re-emerged over the past decade due to various reasons. We present a series of four case reports of head and neck cancers including a basal cell carcinoma, squamous cell carcinoma, and Merkel tumour, where the SF technique was used to successfully reconstruct the resultant facial defect. The advantages and disadvantages of the SF are discussed with a brief literature review.

A very severe case of rhinophyma requiring a three-stage reconstruction with a forehead flap.

Rhinophyma is a skin condition that affects the nose. It is often characterised by a large, red, bulbous nose. It can have a physical, psychological and social impact on the patient. Management options include conservative medical therapy such as retinoids or surgical excision followed by reconstruction as required. The reconstruction options can range from a dermal substitute full-thickness skin graft to local flaps, depending on the wound bed. We present a severe case of rhinophyma that required a complex reconstruction with a three-stage forehead flap because of the mass effect and the wound that resulted from the surgical excision of an extremely large and troublesome rhinophyma.

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.

Ultrasound-guided percutaneous irreversible electroporation of hepatic and abdominal tumors not eligible for surgery or thermal ablation: a western report on safety and efficacy.

PURPOSE: To report our first results on sixteen patients affected by liver and abdominal malignant tumors, unfit for surgery or thermal ablation, treated with US-guided percutaneous irreversible electroporation (IRE). METHODS: From June 2014 to December 2016, all patients meeting the inclusion criteria (malignant hepatic or abdominal tumors not eligible for resection or thermal ablation) and not meeting the exclusion criteria (heart arrhythmia, pro-hemorrhagic hematological alterations, tumor size > 8 cm, presence of a biliary metallic stent) referred to our institutions were prospectively enrolled to undergo percutaneous US-guided irreversible electroporation (IRE). Sixteen patients (age range 59-68 years, mean 63; 7 females) with 18 tumors (diameter range 1.3-7.5 cm) fulfilled the inclusion criteria and were included in the study. Data concerning efficacy (tested by a 1-week CEUS and a 4-week enhanced CT and/or enhanced MRI) and safety were recorded during a 18-month follow up. RESULTS: All patients completed a 35-50-min procedure without complications. One patient with 6 cm Klatskin tumor also underwent a second session for 1 month. A 1-week CEUS and a 4-week e-CT and/or e-MRI arterial phase contrast enhancement analysis showed an overall reduction of arterial flow with confirmation of unenhanced lesions for seven nodules. After 1-18 months of follow up, no major complications were recorded and no tumor-related death occurred. The lesions of two patients disappeared 3 and 6 months after their treatment, respectively. CONCLUSIONS: IRE is a promising ablation modality in the treatment of malignant hepatic and abdominal tumors unsuitable for resection or thermal ablation.

Allogeneic stem cell transplantation following reduced-intensity conditioning can induce durable clinical and molecular remissions in relapsed lymphomas: pre-transplant disease status and histotype heavily influence outcome.

The safety and efficacy of reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas remains unresolved. We conducted a prospective, multicentered, phase II trial. A total of 170 relapsed/refractory lymphomas received a RIC regimen followed by SCT from sibling donors. The primary study end point was non-relapse mortality (NRM). Histologies were non-Hodgkin's lymphomas (NHL) (indolent (LG-NHL), n=63; aggressive (HG-NHL), n=61; mantle cell lymphoma (MCL), n=14) and Hodgkin's disease (HD, n=32). Median follow-up was 33 months (range, 12-82). The results show that frequencies were as follows: cumulative NRM at 3 years, 14%; acute and chronic graft-versus-host disease (GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69% for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058); and 3-year relapse incidence, 29, 31, 35 and 81%, respectively (P<0.001). Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHL.

Schwannomatosis: multiple schwannomas of the upper limb.

Schwannomas (also known as neurilemmomas) are neoplasms of the peripheral nerve sheaths. They are the most common benign tumour of peripheral nerves, yet they account for only 5% of all soft tissue tumours. Their incidence in the upper limb is variable, as is their clinical presentation. We present an unusual case of multiple schwannomas in the upper limb so that other surgeons can share our experience and suggest the correct diagnosis when confronted with a similar case.

Education of trainees, training and fellowships for head and neck oncologic and surgical training in the UK: United Kingdom National Multidisciplinary Guidelines.

Since the previous edition of these guidelines, significant changes have taken place in the training and assessment of surgeons and oncologists who treat patients with head and neck cancer. For those intending to become head and neck surgeons, a fellowship in head and neck surgery is virtually mandatory. This paper summarises the current career structure to specialise in head and neck oncology and surgery in the UK. Recommendation • Trainees applying for head and neck surgical oncology consultant posts should have completed additional training in the subspecialty.

Gene transfer into human dendritic antigen-presenting cells by vaccinia virus and adenovirus vectors.

In a search for means to deliver exogenous gene(s) into human dendritic cells (DCs) from the perspective of tumor-specific vaccination, we have evaluated two recombinant viruses, both of which carry a reporter gene which is namely a modified vaccinia virus Ankara (MVA) and an adenovirus, as possible expression vectors. The recombinant MVA-P11 LZ vector carries the Escherichia coli lacZ gene coding for the enzyme beta-galactosidase, and the recombinant Ad-MFG-AP vector carries a modified membrane-exposed alkaline phosphatase (AP) gene. DCs were generated ex vivo in the presence of tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, stem cell factor, and flk-2/flt-3 ligand taken from CD34+ hematopoietic progenitors that were mobilized into the peripheral blood of cancer patients treated with high-dose cyclophosphamide and filgrastim. The target cells used for gene delivery were either CD34+ cells that had been subsequently induced to differentiate into mature DCs or DCs transduced after ex vivo generation from CD34+ cells. The results showed that: (a) infection of CD34+ cell derived-DCs (mature DCs) with either viral vector resulted in the efficient synthesis of recombinant protein, and (b) CD34+ cells were permissive for the expression of the recombinant reporter gene after infection with Ad-MFG-AP but not after infection with MVA-P11 LZ. In conclusion, these results suggest that vaccinia and adenovirus vectors are candidate to act as vehicles in genetically engineering human DCs.

Treatment of advanced renal cell cancer with sequential intravenous recombinant interleukin-2 and subcutaneous alpha-interferon.

Starting from in vitro studies suggesting synergistic antitumour activity against renal cell cancer (RCC) of recombinant interleukin-2 (rIL-2) and alpha-interferon (IFN), a phase II trial was initiated to test the clinical activity of this combination. The two cytokines were administered sequentially, with the aim of reducing the risk of additive toxicity and enhancing the immunological reaction against the tumour. The original treatment schedule consisted of rIL-2 18 x 10(6) U/m2/day by continuous intravenous infusion for 120 h days 1-5, and alpha-IFN 2b, at a flat dose of 9 x 10(6) U by subcutaneous or intramuscular injection thrice in a week, from day 8 to 28. Treatment was planned to be continued for six or more 28-day cycles, depending on clinical response. 12 patients were treated according to this schedule; as some cardiovascular toxicity was experienced in this set of patients, 11 further patients were treated with half-dose rIL-2 (i.e. 9 x 10(6) U/m2/day). 17 out of 23 enrolled patients completed at least one cycle of treatment and were evaluated for response. We observed six major responses [one complete response (CR) + five partial responses (PR)] for an objective response rate of 35% [95% confidence interval (CI) 17-59%]. 5 additional patients achieved stabilisation of disease; one of them reached CR after surgical extirpation of a lung mass. Sites of response included lung, nodes and bone. Duration of response is 12+ months for CR; 17, 16, 12+, 9 and 9 months for PRs. Median survival is 16 months. Response was not significantly different between full-dose and half-dose rIL-2. Considering stable disease (SD) as responses, there seemed to be a higher chance of response for patients with smaller tumour burden (P = 0.032). The toxicity of rIL-2 treatment, mainly cardiovascular, was substantial; 9 patients experienced severe cardiotoxicity, consisting of major arrhythmias, myocardial ischaemia, reduction of ejection fraction measured with heart radionuclide scan, and were excluded from continuing treatment. Other rIL-2-related toxicities forcing exclusion from the study were severe thrombocytopenia (1 case), and generalised exfoliative dermatitis requiring steroids (1 case). Otherwise, treatment was well tolerated; rIL-2-related toxicities promptly recovered after rIL-2 discontinuation in the majority of cases, and no treatment-related deaths were reported. The half-dose rIL-2 regimen was significantly less toxic in terms of hypotension (P = 0.014), fever (P = 0.014), oliguria (P = 0.042), serum creatinine elevation (P = 0.009) and prothrombin time elongation (P = 0.038).(ABSTRACT TRUNCATED AT 400 WORDS)

Cells with clonal light chains are present in peripheral blood at diagnosis and in apheretic stem cell harvests of primary amyloidosis.

In primary systemic amyloidosis, small numbers of bone marrow plasma cells secrete monoclonal light chains that form extracellular fibrils (amyloid) in various organs. Evidence limited to a few cases suggests that rare clonal elements can also be found in the peripheral blood (PB), and this may be relevant in PB stem cell autotransplantation. Since up to 40% of amyloid clones do not synthesize heavy chains, in order to detect tumor cells with high specificity and sensitivity we developed a seminested allele-specific oligonucleotide polymerase chain reaction for tumor light chains. Clone-related sequences were detected in DNA and/or cDNA from the PB cells of eight of 10 patients at diagnosis and from apheretic collections of three of four cases undergoing PB progenitor autotransplantation. Since there are experimental data suggesting that circulating tumor cells may be involved in the growth of the amyloidogenic clone and may be chemoresistant, these findings are relevant to the use of leukapheresis purging strategies for PB progenitor autotransplantation in amyloidosis.

High-dose ara-C with autologous peripheral blood progenitor cell support induces a marked progenitor cell mobilization: an indication for patients at risk for low mobilization.

A high-dose (HD) chemotherapy scheme was designed for the collection of large numbers of peripheral blood progenitor cells (PBPC) in lymphoma patients who were candidates for myeloablative therapy with autograft. The scheme included the sequential administration of HD cyclophosphamide (CY) (7 g/m(2)) and HD ara-C (2 g/m(2) twice a day for 6 consecutive days), followed by final consolidation with PBPC autograft. PBPC harvests were scheduled following both HD CY and HD ara-C. To minimize hematologic toxicity, small aliquots of PBPC (20 circulating CD34(+) cells/microl, whereas the remaining 19 'low-mobilizer' patients did not reach this cut-off value. In spite of poor mobilization after HD CY, 16 out of 19 low mobilizers provided good harvests following HD ara-C; overall, median collected CD34(+) cells x 10(6)/kg were 1.4 (0-3.1) and 10.2 (0-37) after HD CY and HD ara-C, respectively (P = 0.00007). Similar patterns were observed when PBPC were evaluated by CFU-GM/kg. Complete and durable hemopoietic reconstitution followed autograft with post HD ara-C PBPC. Within the high-mobilizer group, 88 patients received HD ara-C and 79 (90%) still showed high mobilization; overall, median collected CD34(+)cells x 10(6)/kg were 17.8 (range 3-94) and 19 (range 0-107) after HD CY and HD ara-C respectively (P = NS). Thus, the scheme allowed sufficient PBPC collections for autografting in low mobilizer patients; in addition, the scheme could be considered whenever extensive chemotherapy debulking is needed prior to PBPC collection.

Intrapleural administration of interleukin-2 and LAK cells in locally advanced non-small-cell lung cancer. A case report.

AIMS AND BACKGROUND: The systemic administration of recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells is ineffective in non-small-cell lung cancer (NSCLC). However, there is some evidence that their intrapleural administration could be effective, since it increases the concentrations of the cytokine and the effector cells in the tumor area, thereby obtaining greater antitumor activity. STUDY DESIGN: We report the case of a patient affected by a locally advanced lung adenocarcinoma with pleural effusion (T4 N0 M0-stage IIIb) treated with repetitive courses consisting of a priming continuous i.v. infusion (48 h) of rIL-2 (18 MIU/m2/day) intraplural administration of LAK cells (3-9 x 10(9)/day), in a single daily bolus, for 3 consecutive days and concomitant administration of rIL-2 (1.8-7.2 x 10(6) IU/day), for 5 days. RESULTS: We observed early disappearance of neoplastic cells in the pleural effusion, progressive decrease until disappearance of the pleural effusion, cavitation of the primary lesion during the treatment, and its stabilization for 9 months until progression. Radiologic changes were accompanied by a marked eosinophilia (up to 50 x 10(9)/L), and the intrapleural route of administration of rIL-2 induced a relevant increase in eosinophil count in peripheral blood. Immunologic changes in lymphocyte subpopulation phenotypes were also observed. The performance status of the patient improved, and she was still alive and eupnoic 25 months from the diagnosis and 23 months from the start of treatment. CONCLUSIONS: This case suggests a therapeutic role for intrapleural rIL-2, and we believe that the relationship among intrapleural administration of rIL-2 and LAK cells, the development of peripheral eosinophilia, and clinical response should be further investigated.

Anal cancer masked by benign lesions.

Three cases of anal cancer, masked by benign lesions are reported. Local resection was performed, in all cases, and complementary radiotherapy, in two. Postoperative follow-up did not show cancer recurrence.

Approach to the sterilization with gamma rays of a drug. Note I: Treatment technique and effects at zero time.

Authors, considering a possible use of the sterilizing treatment with gamma rays for the productive process of a drug, performed a series of practical treatment tests. To this purpose, they used a single molecule, stable in time and with an easy analytical approach. The examined active principle is the injectable salt of acetylcarnitine chloride. For tests, they used irradiating doses by 2.5-5.0-7.5 Mrads in order to point out the process possible effects. The treatment, even at highest dosages, did not show damages to the molecule that could prevent from going on with the investigation.

Time stability of a drug molecule sterilized through gamma rays.

In a previous work, we studied the possibility to process a drug molecule through a gamma rays sterilizing treatment. Optimal process conditions were studied and the related effects on the treated molecule were analyzed, as well. From obtained results, we concluded that there are not any contraindications to apply this sterilization process to the molecule treated. In this second paper we examined the time stability of the active ingredient treated with a gamma rays sterilization process. Among treated and untreated samples, stored in the refrigerator as well as room temperature, or slightly above, we did not observe any time-related in behaviour differences. Instead, samples stored at higher temperature (80 degrees C) showed behavioural differences between gamma treated and gamma untreated samples. This phenomenon, that at the beginning we found unexplainable, subsequently could be explained owing to further tests of "molecule stabilization" with temperature.