Search

Is there nowadays any benefit of continuing the practice of routine wide local excision (WLE) for primary stage I/II cutaneous melanoma?WLE aims to eradicate potential microsatellites around melanomas and thereby reduce local recurrence rates and improve overall survival. Six large prospective randomised trials investigated WLE versus wider WLE, they all failed to show any effect on overall survival (OS).A literature search was performed to identify data on outcome after omitting WLE. Additionally circumstantial evidence was gathered from pathology studies and outcomes of modified surgical techniques, as well as publications on morbidity.No prospective and one retrospective study was found. The retrospective study showed no difference in OS after correction for confounding factors. Pathology studies showed a low incidence of residual melanoma in WLE specimen (0-4.2%). Mohs surgery does not show a difference in recurrence rates or OS. WLE is associated with considerable postoperative morbidity, which increases with wider excision margins.There is no solid prospective evidence to support the classic dogma of a 2-step approach with the use of WLE for primary cutaneous melanoma that has been completely excised on diagnostic excision biopsy. We recommend to setup and conduct a prospective randomised trial to compare the classical 2-step approach with WLE to a complete diagnostic excision only to abolish the routine practice of WLE in the future.

BACKGROUND: The extent of surgical management of regional lymph nodes in the treatment of cutaneous head and neck melanoma on and anterior to O'Brien's watershed line is controversial. By comparing patients' cohorts of two separate melanoma expert centers we investigate the effectiveness of comprehensive versus (super-) selective neck dissection approach.METHODS: Sixty patients with macroscopic (palpable) neck node metastases (N2b) from anterior scalp and face melanoma were retrospectively studied. Forty therapeutic modified radical neck dissections (MRND; levels I-V) combined with elective parotidectomy from The Netherlands Cancer Institute (NCI) were compared with 16 (super-) selective neck dissections [(S)SND; 3-4 levels] and 4 solely MRNDs from Erasmus Medical Center (EMC). Cohorts were analyzed for site of recurrence, overall survival (OS), melanoma-specific survival (MSS), and disease-free survival (DFS).RESULTS: Clinical characteristics of patients were equal in both groups. In the NCI cohort 62.5% (n = 25) of patients recurred versus 65% (n = 13) in the EMC cohort. None of the NCI recurrences affected the parotid gland in contrast to 3 patients in the EMC group. Survival characteristics were not different between the two groups: OS (p = 0.56), MSS (p = 0.98), DFS (p = 0.92).CONCLUSION: This study does not support to continue the practice of routine elective parotidectomy and MRND in melanoma patients undergoing a lymph node dissection for macroscopic (palpable) nodal disease and justifies (S)SND.

Background Patients with synchronous clinical stage III melanoma can present with primary melanoma lesions, locally recurrent melanoma or in-transit metastases. Neoadjuvant ipilimumab plus nivolumab induces high pathologic response rates and an impressive relapse-free survival in patients with nodal macroscopic stage III melanoma. Whether primary site melanoma and in-transit metastases respond similarly to lymph node metastases with neoadjuvant immunotherapy is largely unknown. Such data would clarify whether surgical excision of these melanoma lesions should be performed before neoadjuvant therapy or whether it could be deferred and performed in conjunction with lymphadenectomy following neoadjuvant immunotherapy. Patients Patients with synchronous clinical stage III melanoma were identified from the OpACIN, OpACIN-neo and PRADO neoadjuvant trials, where all patients were treated with ipilimumab plus nivolumab. An additional case treated outside those clinical trials was included. Results Seven patients were identified; six patients had a concordant response in primary site melanoma lesions or in-transit metastasis and the lymph node metastases. One patient had concordant progression in both the primary and nodal tumour lesions and developed stage IV disease during neoadjuvant treatment, and thus, no resection was performed. Conclusion Pathologic response following neoadjuvant ipilimumab plus nivolumab in primary site melanoma lesions or in-transit metastasis is concordant with a response in the lymph node metastases, indicating that there may be no need to perform upfront surgery to these melanoma lesions prior to neoadjuvant treatment.

Advances in the treatment of metastatic melanoma have improved responses and survival. However, many patients continue to experience resistance or toxicity to treatment, highlighting a crucial need to identify biomarkers and understand mechanisms of response and toxicity. Neoadjuvant therapy for regional metastases might improve operability and clinical outcomes over upfront surgery and adjuvant therapy, and has become an established role for drug development and biomarker discovery in other cancers (including locally advanced breast cancer, head and neck squamous cell carcinomas, gastroesophageal cancer, and anal cancer). Patients with clinically detectable stage III melanoma are ideal candidates for neoadjuvant therapy, because they represent a high-risk patient population with poor outcomes when treated with upfront surgery alone. Neoadjuvant therapy is now an active area of research for melanoma with numerous completed and ongoing trials (since 2014) with disparate designs, endpoints, and analyses under investigation. We have, therefore, established the International Neoadjuvant Melanoma Consortium with experts in medical oncology, surgical oncology, pathology, radiation oncology, radiology, and translational research to develop recommendations for investigating neoadjuvant therapy in melanoma to align future trial designs and correlative analyses. Alignment and consistency of neoadjuvant trials will facilitate optimal data organisation for future regulatory review and strengthen translational research across the melanoma disease continuum.

Background Locally advanced (unresectable or high risk of R1 resection) regionally metastatic melanoma occurs in approximately 5% of patients with regionally metastatic disease. Cytoreductive treatment with sufficient downsizing of the tumor could enable radical resection in these patients. BRAF + MEK combination treatment has shown quick responses in most patients with BRAF-mutated melanoma. The aim of the present study, therefore, was to evaluate the ability of short-term cytoreductive neoadjuvant BRAF + MEK inhibition to allow for complete surgical resection in patients with BRAF-mutated, locally advanced stage III or oligometastatic stage IV melanoma. Patients and Methods The REDUCTOR (cytoreductive treatment of dabrafenib combined with trametinib to allow complete surgical resection in patients with BRAF mutated, prior unresectable stage III or IV melanoma) trial is a phase II trial in which 25 patients with BRAF-mutated, locally advanced, stage III or oligometastatic stage IV melanoma (≤ 3 metastases) will receive neoadjuvant cytoreductive dabrafenib and trametinib combination therapy. The patients will be treated for 8 weeks. The positron emission tomography/computed tomography response evaluation will occur at 2 and 8 weeks. In the case of sufficient tumor downsizing, surgery will be performed. Biopsies for translational research purposes will occur at baseline and 2 weeks, and the dissection specimen will be stored at 8 weeks. Conclusion The primary endpoint of the present trial is the percentage of patients in whom an R0 resection (microscopically radical) can be performed, as evaluated by pathologic examination. The secondary endpoints are recurrence-free survival, time to next treatment, and overall survival. Translational research will focus primarily on the assessment of treatment-induced changes in exome mutations within the tumor and changes in gene expression profiles.

Background: Cutaneous malignant melanoma causes the majority of skin cancer related deaths and features increasing incidence and mortality rates in the Netherlands. Conditional survival analysis is performed on patients who survived the preceding year(s). Methods: Patients with invasive melanoma, as recorded in the population-based Netherlands Cancer Registry, were included. To assess prognosis of melanoma survivors according to gender and Breslow thickness, conditional five-year relative survival was calculated for lymph node negative melanoma patients and conditional one-year relative survival was analysed for melanoma patients with and without nodal involvement. Findings: Between 1994 and 2008, 40,050 patients developed a melanoma (stage I-III, of whom 6% with nodal involvement). Six to 8 years after diagnosis, survival of patients with a 1-2 mm (T2) thick melanoma equalised the general population. Conditional five-year relative survival for patients with > 4 mm thick (T4) melanomas increased from about 60% at diagnosis to 90% at 7 years after diagnosis. Largest improvements were found in patients with thick melanomas and female patients with nodal involvement. Interpretation: The prognosis for melanoma survivors improved with each additional year of survival after diagnosis, except for patients with a

Locoregional treatment is often insufficient to guarantee long-term disease-free survival (DFS) in American Joint Committee on Cancer stage IIIB melanoma, and, in order to improve survival, effective neoadjuvant and adjuvant strategies are needed . Selecting patients for these strategies requires risk stratification, for which clinical and molecular biomarkers can be used. We aimed to detect clinical biomarkers to identify high-risk stage IIIB melanoma patients.We performed retrospective analysis of stage IIIB melanoma patients who underwent lymph node dissection (LND) in our institution between 2000 and 2015. Sentinel node-positive patients with ulcerated primary tumors, as well as patients with clinically detectable nodal metastasis with non-ulcerated tumors, were included. Baseline characteristics, melanoma-specific survival (MSS), and DFS were assessed, and prognostic factors for recurrence and survival were analyzed, using univariate and multivariate analysis.Overall, 250 patients were included. Median follow-up was 52 months (interquartile range 29-108 months), median MSS was 141 months, and median DFS was 36 months. Five- and 10-year MSS was 59 and 52 %, respectively, and 5- and 10-year DFS was 47 and 41 %, respectively. Age50 years, Breslow thickness2 versus ≤2 mm, and N2 versus N1 disease all carried an increased risk of death by melanoma. Age50 years and extracapsular extension carried an increased risk of disease recurrence after LND.Age50 years, Breslow thickness2 mm and N2 versus N1 disease are prognostic factors for poor survival in stage IIIB melanoma. These characteristics can be used to further stratify risk of death by melanoma in this already high-risk patient population and to help select the appropriate population for adjuvant therapy (trials).

However, we would like to expressa great concern regarding the pathology protocols,which were used. The authors claim to have used theEuropean Organisation for Research and Treatment ofCancer (EORTC) Melanoma Group (MG) protocol.However there is an internal contradiction between theabstract and methods in their description of this proto-col and furthermore neither of the methods describedadequately reflects the EORTC protocol. There appearsto be a misunderstanding between the meaning of stepsand levels. A step is the distance between levels, a level isa section or sections stained to represent that level. TheEORTC protocol as it has evolved consists of six pairsof sections, each stained with haematoxylin–eosin andS100. These are separated by steps at 50 lm thickness,so there are five steps and six levels whereas in theabstract there is a description of five sections 50 m apartand in the methods there is a description of six levels50 m apart. It was then stated that the first five levelswere treated differently. Furthermore in Fig. 1 there isagain confusion between the words steps and sectionsor levels.Despite this confusion we would like to acknowledgethat increased sampling will lead to increased detectionrates, as it was also demonstrated by the study by Cooket al. The extensive protocol identified 33.8% versus 25.2for the EORTC MG protocol, this is close to the detec-tion rate achieved by RT-PCR.