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.

Histopathological tumor response following neoadjuvant hyperthermic isolated limb perfusion in extremity soft tissue sarcomas: Evaluation of the EORTC-STBSG response score.

INTRODUCTION: This study aims to evaluate the applicability and prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) histopathological response score in extremity soft tissue sarcoma (ESTS) patients treated with neoadjuvant hyperthermic isolated limb perfusion (HILP) and delayed surgical resection. METHODS: Patients treated between 1991 and 2016 were included. The histopathological tumor response was established in accordance with the EORTC-STBSG response score. The distribution of patients was assorted according to the 5-tier histopathological response score for tumor grade, histological subtype and HILP regimen. Predictors for local recurrence free survival (LRFS) and overall survival (OS) were identified through Kaplan-Meier and Cox regression analyses. RESULTS: Ninety-one patients were included and their resection specimens were reanalyzed. Which resulted in 11 Grade A (12.1%), ten Grade B (11.0%), 15 Grade C (16.5%), 22 Grade D (24.2%) and 33 Grade E (36.3%) responses found among the series. The histopathological response was significantly influenced by the HILP regimen used, p = 0.033. Median follow-up was 65.0 (18.0-157.0) months. The histopathological response was not associated with LRFS nor OS. Resection margins, HILP regimen and adjuvant radiotherapy were associated with LRFS. Patients' age, tumor grade, tumor size and histological subtype were predictors for OS. CONCLUSIONS: The EORTC-STBSG response score is applicable for determining the histopathological response to neoadjuvant ESTS treatment. However, this response does not seem to predict LRFS nor OS in locally advanced ESTS.

Hyperthermic isolated limb perfusion, preoperative radiotherapy, and surgery (PRS) a new limb saving treatment strategy for locally advanced sarcomas.

BACKGROUND: This feasibility study presents the results of a new intensive treatment regimen for locally advanced extremity soft tissue sarcomas (ESTS), consisting of hyperthermic isolated limb perfusion (HILP), preoperative external beam radiotherapy (EBRT), and surgical resection. METHODS: From 2011 to 2016, 11 high grade locally advanced ESTS patients underwent this treatment regimen. Preoperative EBRT (12 × 3 Gy) started <4 weeks following the HILP (TNF-α and melphalan) and the surgical resection was planned to take place <2 weeks following the end of the EBRT. RESULTS: All patients completed the treatment. After a median follow-up of 32 (23-50) months, the limb was saved in 10 patients (91%), 1 patient (9%) developed a local recurrence, 5 patients (45%) developed distant metastases, and 3 patients (27%) died of their disease. During follow-up two patients (18%) developed a pathologic fracture of the treated limb and three patients (27%) developed a major wound complication requiring surgical intervention. The median overall treatment time (OTT) was 56 (49-69) days. CONCLUSIONS: This intensive treatment regimen is feasible and safe in locally advanced ESTS, and it achieves oncological results that are comparable with conventional HILP treatment. In addition, the major wound complication risk is comparable and the OTT is reduced.

[Improved compliance with the 'Melanoma' treatment guideline]. / Betere navolging van de richtlijn 'Melanoom'.

OBJECTIVE: To evaluate the level of compliance with the revised treatment guideline for melanoma (2005) and the extent to which the points of concern from the previous guideline evaluation in 2001 had been implemented. DESIGN: Retrospective observational cohort study. METHOD: The evaluation was performed using data from the pathology reports of patients diagnosed with melanoma of the skin between 1 April and 30 September 2007 at hospitals that fall under the Comprehensive Cancer Centres for the South and West of the Netherlands. RESULTS: In 85% of the patients the melanoma was treated according to the guideline in two sessions: a diagnostic excision followed by a therapeutic re-excision. These figures were 69% for melanoma in situ, and 87% for invasive melanoma. The other patients were treated in one session. In the pathology reports of the patients with an invasive melanoma the rates of pathological documentation were: margin of the diagnostic excision: 64%, Breslow thickness: 97%, presence or absence of ulceration: 77%. In the Comprehensive Cancer Care Centre West Netherlands region, the margin of re-excision was determined: this margin satisfied the guideline in 86% of patients with an invasive melanoma. CONCLUSION: Compared to the previous guideline evaluation in 2001, the excision policy had improved. In the pathology report, the excision margin and the presence or absence of ulceration should be better documented.

No increase of melanoma after kidney transplantation in the northern part of The Netherlands.

One medical problem of renal transplant patients who receive immunosuppression therapy is the development of a malignancy during the long-term follow-up. Existing studies, however, are not in agreement over whether patients who undergo renal transplantation have an increased risk of melanoma. The aim of this study was to determine the risk of melanoma in renal transplantation patients in the northern part of The Netherlands. We linked a cohort of 1,125 patients who received a renal transplantation in the University Medical Centre Groningen between 1989 and 2003 with the Cancer Registry of the Comprehensive Cancer Centre North-Netherlands, to identify all the melanoma patients in this cohort. The risk for melanoma after renal transplantation was calculated using the Standardized Incidence Ratio and the absolute excess risk. With a mean follow-up of 7.26 +/- 4.48 years, one patient developed a melanoma after the renal transplantation; the number of melanoma patients was among the lowest compared with other studies. The absolute excess risk for melanoma after renal transplantation was 0.5/10,000 person-years. Although several epidemiologic studies have shown that the risk of melanoma is increased in renal transplantation patients who receive immunosuppression therapy to prevent allograft rejection, this significant increase was not found in this study. The low net immunosuppressive agents given might be responsible for this low number of melanomas.

Quality of life after hyperthermic isolated limb perfusion for locally advanced extremity soft tissue sarcoma.

BACKGROUND: Quality of life (QoL) and posttraumatic stress symptoms (PTSS) were studied in patients with soft tissue sarcoma (STS) of the extremities treated with isolated limb perfusion and delayed resection, with or without adjuvant irradiation. METHODS: Forty-one patients received a questionnaire that included the RAND-36 and Impact of Event Scale. RESULTS: Thirty-nine STS survivors (16 [41%] male and 23 [59%] female; median age, 59 years; range, 15-78 years) participated in the questionnaire survey (response rate, 95%). The median age at perfusion was 49 years (range, 14-72 years). No significant differences were found in mean scores between STS survivors and the reference group with the exception of a worse physical functioning. Patients with amputations showed significantly worse physical and social functioning and more role limitations than patients whose limbs were saved. Eleven patients (28%) had a PTSS score of 0, and eight patients (20.5%) had a score>or=26, which suggested the need for psychological counseling. None of these eight patients had lost a limb. Patients who indicated that the choice of treatment was made by the surgeon rather than collaboratively showed significantly decreased social functioning, more role limitations, and intrusion. Greater treatment satisfaction was significantly related to better social functioning, more vitality, better general health perception, less intrusion, avoidance, and total Impact of Event Scale scores. CONCLUSIONS: Even though STS survivors' QoL was different from that of a reference group only in physical functioning, one fifth of the patients had PTSS. An amputation, the physician's decision rather than the patient's decision for the perfusion treatment and a low satisfaction with the performed treatment negatively influenced QoL.

Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma: the value of adjuvant radiotherapy.

BACKGROUND: The aim was to investigate the value of adjuvant radiotherapy for locally advanced soft tissue sarcoma after hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan followed by limb-saving surgery. METHODS: From 1991 to 2003, 73 patients (median age, 54 years; range, 14-80 years) underwent 77 ILPs, followed by resection in 68 patients (93%). Radiotherapy was administered in case of marginally or microscopically positive resection margins. Local recurrences were scored and calculated according to the Kaplan-Meier method and log-rank test. RESULTS: After residual tumor mass resection, 58% received radiotherapy (external beam radiotherapy [EBRT]+ group), and 42% did not (EBRT- group). The median follow-up was 28 months (range, 2-159 months). A significantly better local control rate was observed in the EBRT+ compared with the EBRT- group (P<.0001). When only R0 resections in patients without metastasis were considered, the significance remained between groups (P=.0003). In the EBRT- group, an R1 or R2 resection resulted in earlier relapse of local disease compared with R0 resections (P=.0475). CONCLUSIONS: Adjuvant EBRT reduces the risk for local recurrence after delayed resection in soft tissue sarcoma patients treated with ILP and tumor necrosis factor and is indicated when resection margins are close or microscopically positive. It also seems beneficial after an R0 resection.