Metabolic parameters on baseline and early [F]FDG PET/CT as a predictive biomarker for resistance to BRAF/MEK inhibition in advanced cutaneous BRAFV600-mutated melanoma.

Background: [F]FDG PET/CT plays a crucial role in evaluating cancer patients and assessing treatment response, including in BRAF-mutated melanoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have emerged as promising alternatives to standardized uptake value (SUV)-based measures for tumor assessment. This study evaluates the predictive value of SUVpeak, MTV, and TLG in predicting progression-free survival (PFS) in advanced BRAF-mutated melanoma treated with BRAF/MEK inhibitors.

Imaging Proliferation of Stage IV Cutaneous Melanoma With 18 F-FLT PET/CT : A Potential Noninvasive Tool for Predicting Treatment Resistance to Targeted Therapy?

Background: 18 F-FLT PET/CT visualizes cellular proliferation and may correlate more directly with tumor aggressiveness and treatment response than 18 F-FDG PET/CT in melanoma patients treated with BRAF/MEK inhibitors. We aimed to assess whether 18 F-FLT PET/CT can predict early resistance to BRAF/MEK inhibitors in addition to current clinical tools in patients with BRAF-mutated metastatic melanoma.

Patients And Methods: This explorative side study of the phase II multicenter REPOSIT trial included 19 patients with stage IV BRAF V600E/K-mutated cutaneous melanoma who underwent optional 18 F-FLT PET/CT.

Learning From Evidence: Changes in Real-World Use of Second Androgen Receptor Targeted Treatments in Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Background: Androgen receptor targeted therapies (ART) play a major role in the treatment of metastatic castration-resistant prostate cancer (mCRPC). In recent years consensus has been reached that treatment with a second ART should be avoided due to low response rates. The aim of this study was to investigate if new scientific insights led to changes in clinical daily practice in the Netherlands.

Development of a Decision Model to Estimate the Outcomes of Treatment Sequences in Advanced Melanoma.

BackgroundA decision model for patients with advanced melanoma to estimate outcomes of a wide range of treatment sequences is lacking.ObjectivesTo develop a decision model for advanced melanoma to estimate outcomes of treatment sequences in clinical practice with the aim of supporting decision making. The article focuses on methodology and long-term health benefits.

Cost-effectiveness of treatment sequences for BRAF-mutant advanced melanoma in the Netherlands using a health economic model.

Background: This study aims to evaluate the cost-effectiveness of treatment sequences for patients with advanced melanoma with a BRAF mutation in the Netherlands from a societal perspective.

Methods: A semi-Markov model with a life-time horizon has been used to evaluate cost-effectiveness of 21 treatment sequences. Real-world data from the Dutch Melanoma Treatment Registry (DMTR) were used to estimate time to progression, next treatment and death.

Long-Term Survival in Patients With Advanced Melanoma.

Importance: Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival.

Objective: To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials.

Design, Setting, And Participants: Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019.

Baseline biomarkers of efficacy and on-treatment immune-profile changes associated with bempegaldesleukin plus nivolumab.

In PIVOT IO 001 (NCT03635983), the combination of the investigational interleukin-2 agonist bempegaldesleukin (BEMPEG) with nivolumab (NIVO) had no added clinical benefit over NIVO monotherapy in unresectable/metastatic melanoma. Pre-defined baseline and on-treatment changes in selected biomarkers were analyzed to explore the potential mechanisms underlying the clinical observations. In each treatment arm, higher baseline tumor mutational burden or immune infiltration/inflammation was associated with improved efficacy compared with lower levels.

Adjuvant treatment with anti-PD-1 in acral melanoma: A nationwide study.

Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry.

Baseline and on Treatment Biodistribution Variability of 18 F-FLT Uptake in Patients With Advanced Melanoma: Brief Communication.

Purpose: This prospective study evaluates the biodistribution of 18 F-FLT PET in patients with advanced melanoma before and after treatment with BRAF/MEK inhibitors.

Patients And Methods: Eighteen BRAF-positive unresectable stage IIIc or IV melanoma patients referred for 18 F-FLT PET/CT before (BL) and during (D14) BRAF/MEK inhibition were included. 18 F-FLT accumulation in the liver, bone marrow, blood, and muscle was quantified.

Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma.

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.

Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021.

Background: The prognosis of advanced melanoma patients has significantly improved over the years. We aimed to evaluate the survival per year of diagnosis.

Methods: All systemically treated patients diagnosed with advanced melanoma from 2013 to 2021 were included from the Dutch Melanoma Treatment Registry.

BRAF/MEK inhibitor rechallenge in advanced melanoma patients.

Background: Effectivity of BRAF(/MEK) inhibitor rechallenge has been described in prior studies. However, structured data are largely lacking.

Methods: Data from all advanced melanoma patients treated with BRAFi(/MEKi) rechallenge were retrieved from the Dutch Melanoma Treatment Registry.

The Predictive Value of FDG PET/CT for Determining Progression-Free Survival in Advanced Stage III-IV BRAF -Mutated Melanoma Patients Treated With Targeted Therapy-What Can Be Learned From Progression?

Purpose: The aims of this study were to investigate whether (early) PERCIST response monitoring with 18 F-FDG PET/CT is predictive for progression-free survival (PFS) in unresectable stage III or IV melanoma patients treated with BRAF/MEK inhibitor (MEKi) and to define dissemination patterns at progression with a lesion-based evaluation in direct comparison to baseline to improve our understanding of 18 F-FDG PET/CT during BRAF/MEKi.

Patients And Methods: This prospective multicenter single-arm study included 70 patients with unresectable stage III/IV BRAF -mutated melanoma who underwent contrast-enhanced CT and 18 F-FDG PET/CT at baseline and 2 and 7 weeks during treatment with vemurafenib plus cobimetinib and at progression if possible. Tumor response assessment was done with RECIST1.

Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands.

In phase III trials, ipilimumab plus nivolumab combination therapy is highly efficacious for advanced melanoma, despite many treatment-related grades 3-4 adverse events. Here, we report real-world safety and survival outcomes of ipilimumab plus nivolumab for advanced melanoma. Patients with advanced melanoma who received first-line ipilimumab plus nivolumab between January 1, 2015 and June 30, 2021 were selected from the Dutch Melanoma Treatment Registry.

Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies.

Background: Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease- or treatment-related T- or B-cell dysfunction.

Methods: All advanced melanoma patients treated with anti-PD-1-based treatment or targeted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry.

Adjuvant treatment of in-transit melanoma: Narrowing the knowledge gap left by clinical trials.

Few clinical trials address efficacy of adjuvant systemic treatment in patients with in-transit melanoma (ITM). This study describes adjuvant systemic therapy of ITM patients beyond clinical trials. In this study, we included stage III adjuvant-treated melanoma patients registered in the nationwide Dutch Melanoma Treatment Registry between July 2018 and December 2020.

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

Background: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma.

Methods: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight).

and Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma.

Purpose: Little is known about the effect of specific gene mutations on efficacy of immune checkpoint inhibitors in patients with advanced melanoma.

Materials And Methods: All patients with advanced melanoma treated with first-line anti-PD-1 or ipilimumab-nivolumab between 2012 and 2021 in the nationwide Dutch Melanoma Treatment Registry were included in this cohort study. Objective response rate, progression-free survival (PFS), and overall survival (OS) were analyzed according to and status.

End-of-Life Use of Systemic Therapy in Patients With Advanced Melanoma: A Nationwide Cohort Study.

Purpose: The introduction of immune checkpoint inhibitors and targeted therapies improved the overall survival of patients with advanced melanoma. It is not known how often these costly treatments with potential serious side effects are ineffectively applied in the last phase of life. This study aimed to investigate the start of a new systemic therapy within 45 and 90 days of death in Dutch patients with advanced melanoma.

Local delivery of low-dose anti-CTLA-4 to the melanoma lymphatic basin leads to systemic T reduction and effector T cell activation.

Preclinical studies show that locoregional CTLA-4 blockade is equally effective in inducing tumor eradication as systemic delivery, without the added risk of immune-related side effects. This efficacy is related to access of the CTLA-4 blocking antibodies to tumor-draining lymph nodes (TDLNs). Local delivery of anti-CTLA-4 after surgical removal of primary melanoma, before sentinel lymph node biopsy (SLNB), provides a unique setting to clinically assess the role of TDLN in the biological efficacy of locoregional CTLA-4 blockade.

Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study.

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM).

Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry.

Symptomatic Skeletal Events and the Use of Bone Health Agents in a Real-World Treated Metastatic Castration Resistant Prostate Cancer Population: Results From the CAPRI-Study in the Netherlands.

Background: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population.