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BackgroundFor patients with sentinel lymph node (SLN)‐positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease‐specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown.MethodsIn a retrospective cohort of SLN‐positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all‐site recurrence‐free survival (RFS), isolated nodal RFS, distant metastasis‐free survival (DMFS), and DSS using Kaplan‐Meier curves and Cox proportional hazard models.ResultsAmong 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty‐nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti–PD‐1 immunotherapy. After a median follow‐up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty‐eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk‐adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15‐0.88), but not all‐site RFS (HR, 0.68; 95% CI, 0.45‐1.02). Adjuvant therapy improved all‐site RFS (HR, 0.52; 95% CI, 0.47‐0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment.ConclusionsActive surveillance has been adopted for most SLN‐positive patients. At initial assessment, real‐world outcomes align with randomized trial findings, including in adjuvant therapy recipients.Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real‐world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up‐front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

Introduction: Secondary Central Nervous System Lymphoma (SCNSL) is the spread of a lymphoma to the CNS, the primary focus of which is situated elsewhere in the body. Most commonly, it is a non-Hodgkin lymphoma which either presents as a CNS involvement due to systemic relapse or progression, or as an isolated relapse in the CNS despite systemic remission. Traditionally, it has been treated by intrathecal or systemic chemotherapy and/or WBRT (Whole-brain radiation therapy) but recently, the use of high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has shown encouraging results. We present a systematic review of literature displaying the treatment outcomes of HDT/ASCT in SCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on July 08 2020 on PubMed, Cochrane Library and Clinicaltrials.Gov by using the relevant MeSH terms of high-dose chemotherapy, autologous stem cell transplantation, CNS lymphoma, efficacy and safety. Following screening by 2 reviewers, we selected 12 published studies (n=353) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 232/353 patients eventually underwent sequential HDT+ASCT who were evaluable for treatment response out of which 190 patients had SCNSL (see table 1). Carmustine (BCNU) based HDT: BCNU based regimens have been the most extensively studied HDT among SCNSL patients (n=81). Korfel et al. in a phase 2 trial (2013, n=30) used HDT combination of BCNU, thiotepa and etoposide followed by ASCT in SCNSL patients. No patient was given whole brain radiation therapy (WBRT). The results yielded a PR of 8%, CR of 63% and 2-year OS of 63%. 1 toxicity related mortality (TRM) was noted and >grade 4 adverse effects included infection (4%) and stomatitis (13%). Ferreri et al. (2015, n=38) in a phase 2 trial use HDT with BCNU plus thiotepa on 38 patients 20 of whom underwent subsequent ASCT. The results showed CR of 100%, event free survival (EFS) of 40% ±9% and OS of 41% ±8% at 5 years with four patients suffering TRM. Thiotepa, busulfan and cyclophosphamide (TBC) based HDT: The combination based on TBC has been a popular option for SCNSL patients (n=53). In a retrospective analysis by Welch et al. (2014, n=17), TBC combination followed by sequential ASCT was studied in both primary and SCNSL patients (primary malignancy being diffuse large B-cell lymphoma) and the collective results showed complete response (CR) of 100%, PFS of 93% (95% CI: 61-99%) and OS of 93% (95% CI: 61-99%) at 3 years. In addition to the excellent efficacy response, no TRM or grade 4 toxicities were documented. Chen et al. (2015, n=12) in a phase 2 trial used HDT with rituximab and TBC (R-TBC) combination followed by ASCT rescue in 12 SCNSL patients. At 2 years, the progression free survival (PFS) was 51% (95% CI: 18-77%) and overall survival (OS) was 83% (95% CI: 48-96%). Two patients developed neurotoxicity and one TRM was recorded. Methotrexate (MTX) based HDT: MTX based combinations have also been widely used as HDT preceding ASCT in SCNSL patients (n=51). Fischer et al. (2008, n=20) studied HDT of MTX plus ifosfamide (IFO) in a retrospective analysis which showed PR of 30%, CR of 60% and median OS of 8.7 months and two TRM (due to sepsis in neutropenia) in SCNSL patients. Lee et al. (2015, n=31) in a prospective cohort study evaluated HDT with MTX based multidrug combination with ASCT in SCNSL patients which yielded a PR of 41.6%, CR of 50% and OS of 9 months (95% CI: 5-12 months). Five patients had suffered TRM. Conclusion: The combination of HDT with ASCT has yielded promising treatment outcomes both in terms of favorable efficacy rates and reduced rates of toxicity in SCNSL patients proving to be a comparable alternative to traditionally used chemo-radiation. However, the data at present is limited to few phase 2 trials with some being displayed collectively with data of primary CNS lymphoma patients. There is an increased need to carry out randomized phase 3 trials exclusively on SCNSL patients to better predict the efficacy and safety profile of HDT/ASCT in these patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.