Publications by authors named "Gerard Vreugdenhil"

: 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.

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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.

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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.

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Article Synopsis
  • In a study comparing neoadjuvant (before surgery) and adjuvant (after surgery) immunotherapy for stage III melanoma, neoadjuvant treatment showed greater effectiveness.
  • The trial involved random assignment of 423 patients to receive either two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery, or surgery followed by 12 cycles of adjuvant nivolumab.
  • Results indicated a significantly higher 12-month event-free survival rate in the neoadjuvant group (83.7%) compared to the adjuvant group (57.2%), with neoadjuvant therapy leading to better patient outcomes and more major pathological responses despite a higher incidence of severe adverse events.
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Purpose: While sex differences in the incidence and mortality of colorectal cancer (CRC) are well documented, less is known about sex differences in patients' health-related quality of life (HRQoL) and psychological distress. To enhance patient-tailored care, we aimed to longitudinally examine sex differences in HRQoL and psychological distress among CRC patients from diagnosis up until 2-year follow-up.

Methods: Newly diagnosed CRC patients from four Dutch hospitals were eligible for participation.

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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.

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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.

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Introduction: The treatment landscape for metastatic hormone sensitive prostate cancer (mHSPC) is rapidly evolving. With an abundance of available treatment strategies, selecting the optimal strategy for an individual patient is becoming increasingly challenging. TripleAiM1 aims to evaluate the impact of mHSPC treatments on health-related quality of life (HRQoL) and to provide real-world data insights on diagnostics, treatment strategies, patient subgroups and related healthcare expenditure for mHSPC.

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The efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma that develop brain metastases (BM) remains unpredictable. In this study, we aimed to identify prognostic factors in patients with melanoma BM who are treated with ICIs. Data from advanced melanoma patients with BM treated with ICIs in any line between 2013 and 2020 were obtained from the Dutch Melanoma Treatment Registry.

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Purpose: A significant proportion of cancer patients suffer from chemotherapy-induced peripheral neuropathy (CIPN). This descriptive study aimed to examine patients' experience of CIPN symptoms, daily limitations, involvement of healthcare professionals, and social support.

Methods: Cross-sectional data have been collected in the Netherlands via a national online questionnaire comprising closed items only (February 2021).

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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.

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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.

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Article Synopsis
  • The introduction of BRAF/MEK inhibition and immune checkpoint inhibitors (ICI) has led to significantly better outcomes for patients with advanced melanoma.
  • A study analyzed data from the Dutch Melanoma Treatment Registry to explore the connection between the time to first distant recurrence (TFDR) and patient survival after systemic therapy.
  • Results showed that patients with longer TFDR experienced better progression-free survival (PFS) and overall survival (OS), regardless of whether they received ICI or targeted therapy, with notable differences in survival times for those with TFDR less than 2 years versus more than 5 years.
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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.

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Article Synopsis
  • The study investigates population mortality rates in advanced melanoma patients in the Netherlands, focusing on how different responses to treatment affect survival over time.
  • A total of 5119 patients diagnosed from 2013 to 2019 were analyzed, revealing that older patients have higher probabilities of dying from melanoma-related causes.
  • Although survival outcomes have improved, melanoma-related mortality remains a significant concern, particularly for patients aged 75 and above.
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Adjuvant BRAF/MEK- and anti-PD-1 inhibition have significantly improved recurrence-free survival (RFS) compared to placebo in resected stage III BRAF-mutant melanoma. However, data beyond the clinical trial setting are limited. This study describes the toxicity and survival of patients treated with adjuvant BRAF/MEK inhibitors and compares outcomes to adjuvant anti-PD-1.

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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).

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Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry.

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Importance: Management of checkpoint inhibitor-induced immune-related adverse events (irAEs) is primarily based on expert opinion. Recent studies have suggested detrimental effects of anti-tumor necrosis factor on checkpoint-inhibitor efficacy.

Objective: To determine the association of toxic effect management with progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) in patients with advanced melanoma treated with first-line ipilimumab-nivolumab combination therapy.

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  • Sentinel lymph node biopsy (SLNB) is crucial for staging in primary cutaneous melanoma, but its influence on outcomes in metastatic melanoma patients without adjuvant therapy was investigated.
  • The study analyzed data from 2,581 patients with advanced melanoma, comparing those who had SLNB before progression to those treated only with wide local excision (WLE).
  • Results showed longer melanoma-specific survival (MSS) in the SLNB group, but it was not an independent predictor of better outcomes in advanced melanoma cases.
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Purpose: Despite the detrimental impact of chronic (chemotherapy-induced) peripheral neuropathy PN on patients' lives, treatment options remain limited. We examined the association between mindfulness and chronic PN symptom severity and impairments in related patient-reported outcomes (PROs) among colorectal cancer (CRC) patients up to 2 years after diagnosis.

Methods: Newly diagnosed stage I-IV CRC patients from four Dutch hospitals were eligible for participation.

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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.

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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect among colorectal cancer (CRC) survivors, and the severity is mainly dependent on the chemotherapy dose. Nowadays, chemotherapy dose is based on body surface area, while determination based on more accurate measures of body composition may be better. This study aimed to investigate the association between body composition and long-term CIPN among CRC survivors 2-11 years after diagnosis.

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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.

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