Primary dermal melanoma (PDM) is a rare subtype of cutaneous melanoma, with involvement of the dermis/subcutaneous tissue or both, but no involvement of the epidermis. PDM could not be distinguished histologically from metastasis of primary cutaneous melanoma. PDM has a longer life expectancy compared to cutaneous metastatic melanoma. Therefore, it is important to recognize PDM and make a correct diagnosis. We present a case of primary dermal melanoma on the left leg of a 38-year-old woman.

BackgroundAdjuvant immunotherapy and targeted therapy are now the standard of care for patients with resected stage IIIA–IV melanoma. However, little is known regarding its efficacy in real-world patients who were not represented in these landmark trials.MethodsThis retrospective study included all patients with resected stage IIIA–IV melanoma who received adjuvant systemic therapy between January 1 2018 and December 31 2020, in two Canadian academic cancer. Primary outcome was the proportion of trial non-eligible patients in the real-world setting. Survival and safety analyses were also conducted.ResultsOf the total 113 patient, 99 (88%) were trial non-eligible patients. Most common reasons for trial non-eligible criteria was having no baseline CLND (72%), followed by outside of treatment window >12 weeks (30%), stage IIIA (14%), unknown primary (9%), stage IV (14%), and baseline AD on immunosuppressants (3%). There were no significant RFS (P = 0.731) or OS (P = 0.110) differences in the overall population of trial eligible vs. non-eligible. Safety profiles were similar between the trial eligible vs. non-eligible groups.ConclusionOur study suggested a high proportion of real-world patients would have been deemed non-eligible for clinical trials. Regardless, adjuvant systemic therapy delivered similar survival and toxicity outcomes in both groups.

Melanoma ManagementVol. 8, No. 1 Letter in ReplyOpen AccessLetter in reply: increase of sentinel lymph node melanoma staging in The Netherlands; still room and need for further improvementEric A Deckers, Marieke WJ Louwman, Schelto Kruijff & Harald J HoekstraEric A Deckers https://orcid.org/0000-0001-6206-207XDepartment of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, Marieke WJ LouwmanNetherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands, Schelto KruijffDepartment of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands & Harald J Hoekstra *Author for correspondence: E-mail Address: h.j.hoekstra@umcg.nlhttps://orcid.org/0000-0001-9550-4997Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsPublished Online:23 Nov 2020https://doi.org/10.2217/mmt-2020-0021AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: elderlyhead and neckmelanomasentinel lymph nodesocioeconomic statusstagingThe proportion of sentinel lymph node biopsy (SLNB)-staged melanoma patients increased in The Netherlands, according to The Netherlands Cancer Registry, from 24% (2004) to 55% (2011) to 65% (2016) [1–3]. It is important to note that very large regional differences were observed in The Netherlands, 74% SLNBs in the northeast of The Netherlands compared with 56% in the rest of The Netherlands (p < 0.01). It is remarkable to see that in 2015 and 2016 no further increase was seen in SLNB staging in the northeast of The Netherlands, in contrast to the rest of The Netherlands [3].The Imperial College Healthcare NHS Trust in London mentions interesting data in the letter to the editor [7]. It is encouraging to see that the percentage of SLNBs has increased from 46% (2016) to 88% (2018). The latter percentage is even better than the 74% in the Northeast of The Netherlands. It is important to mention that these percentage of SLNBs are not completely comparable, since the percentage of 74% in the Northeast of the Netherlands is based on 14 hospitals (at 17 locations) with SLNB percentages ranging per hospital from 47 to 97%.Following our expectation, the application of the SLNB staging, according to the 8th edition American Joint Committee on Cancer guidelines, also in The Netherlands, will continue to increase now that more effective systemic treatment for stage 3 disease has become available. The main question is which SLNB positive patients (stage IIIA) might benefit from the adjuvant immunotherapy or targeted therapy.Sentinel node tumor burden, according to the Rotterdam and/or Dewar criteria are important prognostic factors for survival and also predictive factor for additional positive (nonsentinel) lymph nodes [4]. Distinguishing metastatic melanoma from benign common nevi (CN) and melanophages can be a diagnostic challenge [5]. The 8th American Joint Committee on Cancer staging edition does not account for sentinel node (SN) tumor burden. On the contrary, the maximum diameter of the largest tumor lesion in the SN (1.0 vs >1.0 mm) is used for participation in adjuvant clinical trials. Stratifying by tumor ulceration and SN tumor burden resulted in four positive SN groups from which low-, intermediate- and high-risk prognostic classes could be derived and guided adjuvant therapy in clinical practice [6].It should be taken in to account that there are still no data available to demonstrate that adjuvant systemic immunotherapy or targeted therapy in SLNB in intermediate- and high-risk SLNB positive patients with microscopic disease will contribute to a significantly improved and cost-effective disease-free and overall survival. For the time being, SLNB will only be able to contribute to optimal melanoma staging, in case of a positive SLNB, regional tumor control.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Open accessThis work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

The neutrophil-to-lymphocyte ratio (NLR) is gaining traction as a biomarker with utility in a variety of malignancies including melanoma. Intact lymphocyte function is necessary for tumor surveillance and destruction, and neutrophils play a role in suppressing lymphocyte proliferation and in the induction of lymphocyte apoptosis. Early research in melanoma indicates that in high-risk localized melanoma, a high NLR is correlated with worse overall and disease-free survival. Similarly, in metastatic melanoma treated with both metastasectomy and immunotherapies, an elevated NLR is predictive of shortened overall survival and progression-free survival. Future studies incorporating NLR into more traditional melanoma prognostic markers while employing more granular outcomes, are needed to realize the full potential of NLR.

Aim:Talimogene laherparepvec (T-VEC) is an intralesional therapy for unresectable, metastatic melanoma. T-VEC real-world use in the context of anti-PD1-based therapy requires further characterization.Materials & methods:A retrospective review of T-VEC use from 1 January 2017 and 31 March 2018 for melanoma patients was conducted at seven US institutions.Results:Among 83 patients, three categories of T-VEC and anti-PD-1 therapy were identified: T-VEC used without anti-PD-1 (n = 29, 35%), T-VEC after anti-PD-1-based therapy (n = 22, 27%) and concurrent T-VEC and anti-PD-1-based therapy (n = 32, 39%). 25% of patients discontinued T-VEC therapy due to no remaining injectable lesions, 37% discontinued T-VEC due to progressive disease. Discontinuation of T-VEC did not differ by anti-PD-1-based therapy use or timing.Conclusion:In real-world settings, T-VEC may be used concurrently with or after anti-PD-1-based therapy.

Aim:We aimed to characterize the safety profile of pembrolizumab in advanced melanoma patients at our center to better reflect ‘real-world’ data on anti-PD-1 inhibitors.Materials & methods:At our institution, 58 ipilimumab-naive and 30 ipilimumab-treated patients with advanced melanoma who have received pembrolizumab between June 2014 and June 2017 were included for analysis.Results:Incidence of any-grade and grade 3/4 toxicities were 81.8% (n = 72) and 12.5% (n = 11), respectively. The most common side effects were skin-related (61.4%, n = 54) and gastrointestinal-related (51.1%, n = 45) events. In total, 25% of patients required oral steroids to manage immune-related adverse events with a median cumulative prednisolone dose of 683 mg (range: 40–3745 mg).Conclusion:Pembrolizumab is well tolerated in ‘real-world’ patients and severe toxicities can be effectively managed with systemic steroids.

Aim:We assessed the role of adjuvant interferon on relapse-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) in node-positive melanoma patients.Methods:We retrospectively reviewed 385 node-positive patients without distant metastatic disease treated from 1998 to 2015. The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph node biopsy ± completion LND (n = 270). 128 patients (33.2%) received adjuvant interferon.Results:After a median follow-up of 70 months, interferon was associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR: 0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal stage, node size, sex, primary site, adjuvant therapy and extracapsular extension. In an exploratory age-matched comparison of patients treated with (n = 67) and without (n = 233) adjuvant immunotherapy, interferon still showed improved RFS, DMFS and OS.Conclusion:Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.

The advent of targeted therapy and immunotherapy has revolutionized the management of advanced melanoma. However, these novel therapies are associated with adverse effects (AEs), of which cutaneous toxicities are the most frequently observed. These cutaneous AEs can exert significant morbidity and impact on patient quality of life, hence the recognition and management of AEs is fundamental in preventing interruption or cessation of survival-prolonging treatments. Additionally, knowledge of these AEs are necessary in order for healthcare professionals to counsel patients when starting treatment and in the initiation of AE prophylaxis. The incidence and clinical presentation of the cutaneous toxicities of novel melanoma therapies will be discussed, and treatment guidelines provided.