M. Madu

Sentinel node biopsy in melanoma: Current controversies addressed

Sentinel node biopsy (SNB) is the most accurate staging tool for melanoma patients. The procedure is indicated especially for intermediate thickness melanoma (pT2/3). SNB can be of value in thin melanoma (>0.75 mm in thickness), with adverse prognostic factors, and in thick melanomas (pT4), although T4 patients are already at high risk of disease progression. Completion lymph node dissection (CLND) after positive SN yields additional non-sentinel lymph nodes (NSNs) in 20% of cases. Several factors are predictive for NSN positivity, such as primary tumor characteristics and SN tumor burden. The most used and best validated tumor burden parameter is the maximum diameter of the SN metastasis. Others are the microanatomic location of the metastasis in the SN and tumor penetrative depth. These parameters might be used to stratify risk and select patients for either adjuvant treatment trials (diameter >1 mm), or refraining from treatment (minimal SN tumor burden). There is no undisputed evidence for an overall treatment-related benefit for SNB-based management, although benefit has been suggested for a subgroup of node positive patients with intermediate-thickness melanomas. The DeCOG-SLT study failed to demonstrate a survival benefit for CLND after a positive SN. Results of the MSLT-2 and EORTC 1208 (MINITUB) trial, that both assess the role of CLND in SN positive patients have to be awaited. There might be a role for US-FNAC in melanoma staging. New SN visualization techniques can help allow easier identification of SNs in complex areas, shorten operation time and possibly reduce the amount of false-negative SNBs.

Optimal extent of completion lymphadenectomy for patients with melanoma and a positive sentinel node in the groin

The optimal extent of groin completion lymph node dissection (CLND) (inguinal or ilioinguinal dissection) in patients with melanoma is controversial. The aim of this study was to evaluate whether the extent of groin CLND after a positive sentinel node biopsy (SNB) is associated with improved outcome.

Clinical prognostic markers in stage IIIC melanoma

Although the EORTC 18071‐trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients.

Pet/ct surveillance detects asymptomatic recurrences in stage Iiib and Iiic melanoma patients: a prospective cohort study.

AJCC stage IIIB and IIIC melanoma patients are at risk for disease relapse or progression. The advent of effective systemic therapies has made curative treatment of progressive disease a possibility. As resection of oligometastatic disease can confer a survival benefit and as immunotherapy is possibly most effective in a low tumor load setting, there is a likely benefit to early detection of progression. The aim of this pilot study was to evaluate a PET/computed tomography (CT) surveillance schedule for resected stage IIIB and IIIC melanoma. From 1–2015, stage IIIB and IIIC melanoma patients at our institution underwent 6-monthly surveillance with PET/CT, together with 3-monthly S100B assessment. When symptoms or elevated S100B were detected, an additional PET/CT was performed. Descriptive statistics were used to evaluate outcomes for this surveillance schedule. Fifty-one patients were followed up, 27 patients developed a recurrence before surveillance imaging, five were detected by an elevated S100B, and one patient was not scanned according to protocol. Eighteen patients were included. Thirty-two scans were acquired. Eleven relapses were suspected on PET/CT. Ten scans were true positive, one case was false positive, and one case was false negative. All recurrences detected by PET/CT were asymptomatic at that time, with a normal range of S100B. The number of scans needed to find one asymptomatic relapse was 3.6. PET/CT surveillance imaging seems to be an effective strategy for detecting asymptomatic recurrence in stage IIIB and IIIC melanoma patients in the first year after complete surgical resection.

Efficacy of isolated limb perfusion (ILP) in patients with Merkel cell carcinoma (MCC): A multicenter experience

BACKGROUND Merkel cell carcinoma (MCC) is a rare and potentially aggressive neuroendocrine tumor of the skin, with a propensity for locoregional metastases. In two expert referral centers, isolated limb perfusion (ILP) is used to obtain locoregional control in selected locoregionally advanced MCC patients. This study describes our experience. METHOD Patients who underwent ILP for MCC were analyzed. ILP was performed with melphalan and tumor necrosis factor (TNF) combination therapy. Depending on the institution, either a normothermic or a hyperthermic temperature regimen was used. Baseline characteristics, toxicity data, locoregional progression-free survival (LPFS) and overall survival (OS) were assessed. RESULTS Four males and 6 females with a median age of 78 years (IQR 61-84 years) were included. Four patients underwent ILP for upper extremity disease and 6 for lower extremity disease. All patients received combination therapy with Melphalan and TNF, one patient with the addition of interferon-gamma. No signs of systemic toxicity were present post-ILP. Severe locoregional toxicity (compartment syndrome) occurred in 1 patient and 1 elderly patient with extensive atherosclerosis had to undergo transfemoral amputation due to critical ischemia. Eight patients could be included for response evaluation. The overall response rate (ORR) was 87.5% with a complete response (CR) rate of 62.5%. Two long-term responses of 53 months and 71 months were observed. Median LPFS was 5 months and median OS was 54 months. CONCLUSION ILP shows a high CR rate that can be durable. Therefore, ILP should be considered an effective treatment modality for locally advanced MCC.

Comment: Detailed Pathologic Examination of Completion Node Dissection Specimens and Outcome for Melanoma Patients with Minimal (< 0.1 mm) Sentinel Lymph Node Metastases

We read with interest the recent article by Holtkamp et al. and the accompanying editorial by Alistair Cochran. The authors re-assessed 21 tumor-negative completion lymph node dissection (CLND) specimens of patients with minimal tumor burden sentinel node (SN) for the presence of non–sentinel-node (NSLN) metastases using a more detailed pathology protocol with increased sampling and immunostaining rather than bivalving and hematoxylin and eosin (H&E) staining alone. Only 1 of 343 assessed NSLNs was found to harbor a metastasis. On the basis of these results, the authors concluded that nodal clearance is the safest option for patients with minimal SN tumor burden. The authors state that other studies on minimal SN tumor burden are underpowered or lack follow-up evaluation. However, already in 2009, we showed in a multicenter study that patients with an SN tumor burden smaller than 0.1 mm (n = 67) had a mean follow-up period of 61 months and a median follow-up period of 57 months. The 5-year melanoma-specific survival (MSS) rate was 94%, and NSLN positivity occurred in 5% of the patients. In the current study, we retrospectively analyzed a cohort of patients with minimal SN tumor burden treated at our institution from 2004 to the present, In this study, 11 patients did not undergo CLND and were observed. For this group, the mean follow-up period was 6.4 years, and the median follow-up period was 6.5 years. The estimated 5-year survival rate was 87.5%. No nodal recurrences were seen in this cohort. However, one patient died of distant metastases (without nodal recurrence), and another is alive at this writing with irresectable satellite and in-transit metastases. This is identical to clinical behavior observed in SN-negative patients. Therefore, we find the authors’ conclusions to be incorrect; First, only 0.29% of the examined NSLNs contained a metastasis in a more detailed examination, which demonstrates a negligible benefit from the more detailed protocol. This undermines the authors’ hypothesis that the NSLN positivity rate was underestimated in previous studies about this subject. Second, six patients experienced disease recurrence, and five patients died of melanoma metastases. None of these patients had additional nodal metastases in the CLND. Thus, these patients did not benefit from CLND. Our small cohort without CLND demonstrated the same recurrence pattern. Currently, the accrual of the Multicenter Selective Lymphadenectomy Trial II (MSLT-2) has been completed, and the results are pending. At the same time, the European Organisation for Research and Treatment of Cancer (EORTC) 1208 study (Minitub, NCT01942603), which is a prospective registry of minimal SN tumor burden, still is ongoing at this writing. Until these trials have demonstrated unequivocal significant results in favor for CLND, nodal observation with ultrasound still is to be considered a viable alternative to CLND, especially for patients with minimal SN tumor burden. Considering the potentially serious complications of a CLND, surgeons can decide that it is in their patients best interest to refrain from surgery when minimal SN tumor burden is found. Society of Surgical Oncology 2017