Factors associated with melanoma-related limb lymphoedema.

BACKGROUND: Melanoma-related limb lymphoedema is a well-known late effect following sentinel node biopsy (SNB), and lymph node dissection (LND) in patients treated of melanoma. However, data on associated risk factors are sparse. This study aimed to investigate factors associated with melanoma-related limb lymphoedema. METHODS: The present cross-sectional single-center clinical study included patients between 18 and 75 years with American Joint Committee on Cancer Stages I-III melanoma treated with wide local excision (WLE) and unilateral axillary or inguinal SNB and/or completion LND (CLND) or therapeutic LND (TLND). The diagnosis of secondary unilateral limb lymphoedema was based on the history, symptoms, and physical examination and staged according to the International Society of Lymphology (ISL). Data on factors associated with lymphoedema were analysed with binary logistic regression models. RESULTS: In total, 642 patients were eligible, of which 435 (68%) patients participated in the study. Among these 431 patients, 109 (25%) had lymphoedema of which 48 (44%), and 61 (56%) were classified with ISL Stages I and II-III, respectively. Multivariate analyses identified primary tumour on the limb (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.17-4.56; p value .017), inguinal surgery (OR, 6.91; 95% CI, 3.49-14.11; p value <.0001), LND (OR, 6.45; 95% CI, 3.18-13.57; p value <.0001), and persistent pain at the site of lymph node surgery as factors associated with lymphoedema (OR, 3.52; 95% CI, 1.54-8.19; p value .003). Multivariable analysis of ISL Stage II-III lymphoedema further identified limb cellulitis to be associated with lymphoedema (OR 5.74; 95% CI, 2.11-15.99; p value .0006). CONCLUSIONS: Melanoma-related limb lymphoedema is associated with inguinal surgery, LND, primary tumour on the limb, persistent pain at the site of lymph node surgery, and cellulitis of the limb. This study highlights the importance of increasing awareness, improving prevention, and treatment of melanoma-related limb lymphoedema.

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.

Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

AIM: To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. METHODS: HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. RESULTS: A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. CONCLUSIONS: The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema.

Volume and Tissue Composition Changes Measured with Dual-Energy X-Ray Absorptiometry in Melanoma-Related Limb Lymphedema.

Abstracts Background: The aim of this cross-sectional study was to investigate the volume, fat mass, and lean mass in both upper and lower limbs measured with dual-energy X-ray absorptiometry (DXA) in melanoma patients with melanoma-related limb lymphedema. METHODS AND RESULTS: Four hundred thirty-one patients who had undergone surgical treatment with wide local excision and unilateral axillary or inguinal sentinel lymph node biopsy and/or complete lymph node dissection participated in a survey, and they underwent clinical examination and measurements of their upper or lower limbs with DXA. Limb lymphedema was diagnosed on the basis of history and characteristic physical findings on the clinical examination. The inter-limb differences in volume, fat mass, and lean mass measured with DXA were categorized as none/mild, moderate, or severe according to reference values (taking handedness into account for the upper limbs). Of the 431 patients, 109 (25%) had clinical melanoma-related limb lymphedema corresponding to 23 (10%) who had undergone axillary nodal surgery and 86 (45%) who had undergone inguinal nodal surgery. The majority of patients developed lymphedema within the first year (90%) after surgery, and the majority of lymphedemas were categorized as mild. The increase in the volume of limbs with lymphedema was primarily due to an increase in fat mass. CONCLUSION: There is a high prevalence of melanoma-related limb lymphedema. The increase in volume in the limb with lymphedema is primarily due to an increase in fat mass. This increase in fat mass in limbs with lymphedema is important for the understanding of the pathophysiology and may be important in the treatment of lymphedema.

Gene therapy for patients with advanced solid tumors: a phase I study using gene electrotransfer to muscle with the integrin inhibitor plasmid AMEP.

BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide) was investigated in a phase I dose escalation study. Primary objective was safety. MATERIAL AND METHODS: Patients with metastatic or locally advanced solid tumors, without further standard treatments available, were treated with once-only gene electrotransfer of plasmid AMEP to the femoral muscle. Safety was monitored by adverse events registration, visual analog scale (VAS) after procedure and magnetic resonance imaging (MRI) of treated muscles. Pharmacokinetics of plasmid AMEP in plasma and urine was determined by quantitative polymerase chain reaction. Response was evaluated by positron emission tomography-computed tomography (PET-CT) scans. RESULTS: Seven patients were enrolled and treated at dose levels from 50 to 250 µg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could not be detected, which could be due to the limit of detection. No objective responses were seen. CONCLUSIONS: Gene electrotransfer of plasmid AMEP was found to be safe and tolerable. No objective responses were observed but other DNA drugs may be tested in the future using this procedure.