Deep learning on CT scans to predict checkpoint inhibitor treatment outcomes in advanced melanoma.

Immune checkpoint inhibitor (ICI) treatment has proven successful for advanced melanoma, but is associated with potentially severe toxicity and high costs. Accurate biomarkers for response are lacking. The present work is the first to investigate the value of deep learning on CT imaging of metastatic lesions for predicting ICI treatment outcomes in advanced melanoma.

Treatment sequence with tebentafusp and immune checkpoint inhibitors in patients with metastatic uveal melanoma and metastatic GNA11/GNAQ mutant melanocytic tumors.

Background: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.

Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma.

Blood based immune biomarkers associated with clinical frailty scale in older patients with melanoma receiving checkpoint inhibitor immunotherapy.

Introduction: Immunotherapy with checkpoint inhibition (ICI) is increasingly prescribed to older patients with cancer. High age, especially in combination with frailty, has been associated to immune senescence, which is the age-related decline in immune function, thereby possibly hindering ICI effectiveness. This cross-sectional study aimed to assess whether blood cell immune senescence markers are associated with age, frailty and response to anti-PD-1 treatment in older patients with metastatic melanoma.

Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors.

The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. Addressing the need for an easily applicable diagnostic tool, we conducted a retrospective study of 61 PitNETs operated at a tertiary care center. All cases were subtyped according to the 2022 WHO Classification of Endocrine Tumors.

Arterial inflammation on [F]FDG PET/CT in melanoma patients treated with and without immune checkpoint inhibitors: CHECK-FLAME I.

Background And Aims: Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment. However, ICIs may increase the immune response to non-tumor cells, possibly resulting in increased arterial inflammation, raising the risk of atherosclerotic events. Nevertheless, malignancies may induce a pro-inflammatory state and the association between ICIs and arterial inflammation remains to be clarified.

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.

Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients.

: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. : This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment.

Baseline tumor-infiltrating lymphocyte patterns and response to immune checkpoint inhibition in metastatic cutaneous melanoma.

Introduction: The presence of tumor-infiltrating lymphocytes (TILs) in melanoma has been linked to survival. Their predictive capability for immune checkpoint inhibition (ICI) response remains uncertain. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date and analyzed if this association was independent of known clinical predictors.

Autoantibody-positivity before and seroconversion during treatment with anti-PD-1 is associated with immune-related adverse events in patients with melanoma.

Introduction: Treatment with the immune checkpoint inhibitor anti-programmed cell death protein-1 (PD-1) often causes immune-related adverse events (irAEs). Since irAEs resemble autoimmune diseases, autoantibodies might play a role and could potentially be used to identify patients at risk. Therefore, we investigated the association between autoantibody-positivity and toxicity as well as clinical response in patients with melanoma treated with anti-PD-1.

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.

Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma.

Background: Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs.

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.

Management of patients with rare adult solid cancers: objectives and evaluation of European reference networks (ERN) EURACAN.

About 500,000 patients with rare adult solid cancers (RASC) are diagnosed yearly in Europe. Delays and unequal quality of management impact negatively their survival. Since 2017, European reference networks (ERN) aim to improve the quality of care of patients with rare disease.

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.

A prediction model for response to immune checkpoint inhibition in advanced melanoma.

Predicting who will benefit from treatment with immune checkpoint inhibition (ICI) in patients with advanced melanoma is challenging. We developed a multivariable prediction model for response to ICI, using routinely available clinical data including primary melanoma characteristics. We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy.

Geriatric predictors of response and adverse events in older patients with cancer treated with immune checkpoint inhibitors: A systematic review.

Background: Immunotherapy with checkpoint inhibitors (ICI) has improved cancer treatment in recent years. Older and frail patients are frequently treated with ICIs, but since they have been underrepresented in previous clinical trials, the real impact of ICI in this patient group is not well defined. The aim of this systematic review was to evaluate the evidence for associations between geriatric impairments and treatment outcomes in older patients with advanced and metastatic cancer treated with ICIs.

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.