Melanoma:New Insights in Follow-up & Staging

With a rising incidence of melanoma worldwide, the number of patients in clinical follow-up will keep on rising as well. In an era of economic cuts, this growing number of patients can become a great burden for health care institutions. The unpredictable character of melanoma makes it difficult to manage and standardize follow-up regimes. This thesis focuses on different aspects of melanoma follow-up. The MELFO-study, a randomized, clinical trial, comparing a reduced follow-up schedule to the currently advised high-intensity surveillance for melanoma patients. After 1 year, this did not negatively affect patients’ mental well-being, nor the detection rate of recurrences, and seems economically favorable. Patients’ preferences regarding information and education on melanoma and self-inspection of the skin and lymph nodes were questioned, after watching instructional YouTube videos. Patients’ knowledge on melanoma and their own tumor characteristics appeared to be insufficient, showing the importance of patient-tailored education. Although the sentinel lymph node biopsy (SLNB) is a generally accepted diagnostic procedure, regional differences in standardly performing the SLNB throughout the Netherlands were found. Factors associated with an increased risk of additional lymph node metastases after SLNB were identified, from which a prediction tool for patient selection for subsequent surgery (completion lymph node dissection) was distracted. The protein S-100B is currently the most specific tumormarker for melanoma. Falsely elevated S-100B blood-levels were measured after performing a venipuncture with a subcutaneous route in healthy volunteers. However, this possible adipocyte contamination in regular venipunctures does not seem to be of clinical relevance for melanoma patients

Double venipuncture is not required for adequate S-100B determination in melanoma patients

S-100B is used in melanoma follow-up. This serum biomarker is also present in adipocytes; therefore, subcutaneous adipocytes trapped in the needle before performing a venipuncture could contaminate the serum. The aim was to study the influence of adipocyte contamination on blood samples used for S-100B analysis, possibly resulting in falsely elevated S-100B values. A total of 294 serum samples were collected from 147 American Joint Committee on Cancer staging stage III melanoma patients. The mean difference between the first (dummy) and second tubes was 0.003 μg/l (p = 0.077), with a decrease in the second tube. Compared with the second tube, the S-100B level was higher in the first tube in 33.3% of the samples, equal in 36.8% of the samples and lower in 29.9% of the samples. No significant difference between the two consecutively drawn tubes was found. There seems to be no necessity of implementing a dummy tube system for accurate S-100B determination in melanoma patients

The MELFO-Study:Prospective, Randomized, Clinical Trial for the Evaluation of a Stage-adjusted Reduced Follow-up Schedule in Cutaneous Melanoma Patients-Results after 1 Year

Guidelines for evidence-based follow-up in melanoma patients are not available. This study examined whether a reduced follow-up schedule affects: patient-reported outcome measures, detection of recurrences, and follow-up costs.This multicenter trial included 180 patients treated for AJCC stage IB-II cutaneous melanoma, who were randomized in a conventional follow-up schedule group (CSG, 4 visits first year, n = 93) or experimental follow-up schedule group (ESG, 1-3 visits first year, n = 87). Patients completed the State-Trait Anxiety Inventory, cancer worry scale, impact of events scale, and a health-related quality of life questionnaire (HRQoL, RAND-36). Physicians registered clinicopathologic features and the number of outpatient clinic visits.Sociodemographic and illness-related characteristics were equal in both groups. After 1-year follow-up, the ESG reported significantly less cancer-related stress response symptoms than the CSG (p = 0.01), and comparable anxiety, mental HRQoL, and cancer-related worry. Mean cancer-related worry and stress response symptoms decreased over time (p &lt;0.001), whereas mental HRQoL increased over time (p &lt;0.001) in all melanoma patients. Recurrence rate was 9 % in both groups, mostly patient-detected and not physician-detected (CSG 63 %, ESG 43 %, p = 0.45). Hospital costs of 1-year follow-up were reduced by 45 % in the ESG compared to the CSG.This study shows that the stage-adjusted, reduced follow-up schedule did not negatively affect melanoma patients' mental well-being and the detection of recurrences compared with conventional follow-up as dictated by the Dutch guideline, at 1 year after diagnosis. Additionally, reduced follow-up was associated with significant hospital cost reduction.</p

The MELFO Study:A Multicenter, Prospective, Randomized Clinical Trial on the Effects of a Reduced Stage-Adjusted Follow-Up Schedule on Cutaneous Melanoma IB-IIC Patients-Results After 3 Years

Background This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs. Methods Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB-IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG, n = 93) or experimental (ESG, n = 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory-State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales [PCS/MCS]). Three years later (T3), 110 patients (CSG, n = 56; ESG, n = 54) completed PROMs, while 42 declined (23%). Results Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (p = 0.001) in favor of the ESG, and on the RAND-36 PCS (p = 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio [HR] 0.71 [0.32-1.58]; p = 0.400) and disease-free survival (HR 1.24 [0.42-3.71]; p = 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG. Conclusion These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB-IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline

A review of animal models for portal vein embolization

Portal vein embolization (PVE) is a preoperative intervention to increase the future remnant liver (FRL) through regeneration of the non-embolized liver lobes. This review assesses all the relevant animal models of PVE available, to guide researchers who intend to study PVE. We performed a systematic literature search in Medline and Pubmed, from 1993-June 2013, using search headings "PVE" and "portal vein ligation". Articles were included when meeting the selection criteria: experimental animal study on PVE or portal vein ligation and experiments described in 5 animals or more. Sixty-one articles were selected, describing six different animal models. Most articles reported experiments with rats, rabbits, and pigs. In rats, the increase in wet-weight ratio of the non-occluded liver or total liver weight is greatest in the first 7 d with values ranging from 75%-80.5% on day 7. The volume increase of FRL in the rabbit model is greatest in the first 7 d with values ranging from 33.6%-80% on day 7. In pigs, the largest gain in volume of the FRL was seen in the first 2 wk. The choice of the model depends on the specific aim of the study. Evaluating the increase in liver volume and liver function after PVE, larger animals as the pig, rabbit, or the dog is useful because of the possibility to apply computed tomography volumetry. To evaluate mechanisms of regeneration after PVE, the rat model is useful, because of the variety of antibodies commercially availabl

Follow-up Schedule for Patients With Sentinel Node-negative Cutaneous Melanoma (The MELFO Study) An International Phase III Randomized Clinical Trial

Objectives and Design: The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines. Background: Evidence-based guidelines for the follow-up of sentinel node-negative melanoma patients are lacking. Methods: Overall, 388 adult patients diagnosed with sentinel node-negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016. The conventional schedule group (control: n=196) was reviewed as per current national guidelines. The experimental schedule group (n=192) was reviewed in a reduced-frequency schedule. Quality of life was the primary outcome measurement. Detection rates and survival outcomes were recorded. Patient satisfaction rates and compliance with allocated schedules were compared. Results: At 5 years, both arms expressed high satisfaction with their regimens (>97%). This study found no significant group effect on any patient-reported outcome measure scores between the follow-up protocols. In total, 75/388 (19.4%) patients recurred, with no difference in incidence found between the 2 arms (hazard ratio=0.87, 95% confidence interval: 0.54-1.39, P=0.57). Self-examination was the method of detection for 25 experimental patients and 32 control patients (75.8% vs. 76.2%; P=0.41). This study found no difference in any survival outcomes between the 2 study arms (disease-free survival: hazard ratio=1.00, 95% confidence interval: 0.49-2.07, P=0.99). Conclusions: A reduced-intensity, American Joint Committee on Cancer (AJCC) stage-adjusted follow-up schedule for sentinel node-negative melanoma patients is a safe strategy, and patient self-examination is effective for recurrence detection with no evidence of diagnostic delay. Patients' acceptance is very high