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

Author: van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van Breeschoten, Jesper, van den Berkmortel, Franchette W.P.J., de Groot, Jan-Willem B., Hospers, Geke A.P., Ismail, Rawa K., Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Blokx, Willeke A.M., Wouters, Michel W.J.M., and Suijkerbuijk, Karijn P.M.
Published: 2024
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2. Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

Author: Van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Blank, Christian U., Boers-Sonderen, Marye J., van Eijs, Mick J.M., de Groot, Jan-Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., and Blokx, Willeke A.M.
Published: 2023
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3. Population mortality in advanced melanoma patients with and without response and progression; data from the Dutch Melanoma Treatment Registry

Author: van Breeschoten, Jesper, van den Eertwegh, Alfons J.M., Hilarius, Doranne L., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Manevski, Damjan, Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., and de Wreede, Liesbeth C.
Published: 2023
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4. Adjuvant treatment with anti‐PD‐1 in acral melanoma: A nationwide study.

Author: Bloem, Manja, van Not, Olivier J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Blokx, Willeke A. M., Boers‐Sonderen, Marye J., Bonenkamp, Johannes J., de Groot, Jan‐Willem B., Haanen, John B., Hospers, Geke A. P., Kapiteijn, Ellen W., de Meza, Melissa M., Piersma, Djura, van Rijn, Rozemarijn S., Stevense‐den Boer, Marion A. M., van der Veldt, Astrid A. M., Vreugdenhil, Gerard, van den Eertwegh, Alfons J. M., and Suijkerbuijk, Karijn P. M.
Subjects: IMMUNE checkpoint inhibitors, IMMUNOLOGICAL adjuvants, OVERALL survival, REGRESSION analysis, MELANOMA
Abstract: 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. We analyzed recurrence‐free survival (RFS), distant metastasis‐free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5–29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p =.002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HRadj 1.53; 95% CI: 1.07–2.17; p =.019). Two‐year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p =.050). Two‐year OS was significantly lower in AM (71.5% vs. 84.3%; p =.027). The results of this study suggest a poorer outcome of adjuvant‐treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high‐risk AM. [ABSTRACT FROM AUTHOR]
Published: 2024
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5. BRAF/MEK inhibitor rechallenge in advanced melanoma patients

Author: Van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Blank, Christian U., Boers-Sonderen, Marye J., de Groot, Jan Willem W.B., Hospers, Geke A.P., Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J., van der Veldt, Astrid A.M., Wouters, Michel W.J.M., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., Van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Blank, Christian U., Boers-Sonderen, Marye J., de Groot, Jan Willem W.B., Hospers, Geke A.P., Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J., van der Veldt, Astrid A.M., Wouters, Michel W.J.M., Blokx, Willeke A.M., and Suijkerbuijk, Karijn P.M.
Abstract: 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 authors analyzed objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for both first treatment and rechallenge. They performed a multivariable logistic regression and a multivariable Cox proportional hazards model to assess factors associated with response and survival. Results: The authors included 468 patients in the largest cohort to date who underwent at least two treatment episodes of BRAFi(/MEKi). Following rechallenge, ORR was 43%, median PFS was 4.6 months (95% confidence interval [CI], 4.1–5.2), and median OS was 8.2 months (95% CI, 7.2–9.4). Median PFS after rechallenge for patients who discontinued first BRAFi(/MEKi) treatment due to progression was 3.1 months (95% CI, 2.7–4.0) versus 5.2 months (95% CI, 4.5–5.9) for patients who discontinued treatment for other reasons. Discontinuing first treatment due to progression and lactate dehydrogenase (LDH) levels greater than two times the upper limit of normal were associated with lower odds of response and worse PFS and OS. Symptomatic brain metastases were associated with worse survival, whereas a longer treatment interval between first treatment and rechallenge was associated with better survival. Responding to the first BRAFi(/MEKi) treatment was not associated with response or survival. Conclusions: This study confirms that patients benefit from rechallenge. Elevated LDH levels, symptomatic brain metastases, and discontinuing first BRAFi(/MEKi) treatment due to progression are associated with less benefit from rechallenge. A prolonged treatment interval is associated with more benefit from rechallenge.
Published: 2024

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

Author: van Duin, Isabella A. J., Verheijden, Rik J., van Diest, Paul J., Blokx, Willeke A. M., El-Sharouni, Mary-Ann, Verhoeff, Joost J. C., Leiner, Tim, van den Eertwegh, Alfonsus J. M., de Groot, Jan Willem B., van Not, Olivier J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Haanen, John B. A. G., Hospers, Geke A. P., Piersma, Djura, van Rijn, Rozemarijn S., van Der Veldt, Astrid A. M., Vreugdenhil, Gerard, Wouters, Michel W. J. M., Stevense-den Boer, Marion A. M., Boers-Sonderen, Marye J., Kapiteijn, Ellen, Suijkerbuijk, Karijn P. M., Elias, Sjoerd G., van Duin, Isabella A. J., Verheijden, Rik J., van Diest, Paul J., Blokx, Willeke A. M., El-Sharouni, Mary-Ann, Verhoeff, Joost J. C., Leiner, Tim, van den Eertwegh, Alfonsus J. M., de Groot, Jan Willem B., van Not, Olivier J., Aarts, Maureen J. B., van den Berkmortel, Franchette W. P. J., Blank, Christian U., Haanen, John B. A. G., Hospers, Geke A. P., Piersma, Djura, van Rijn, Rozemarijn S., van Der Veldt, Astrid A. M., Vreugdenhil, Gerard, Wouters, Michel W. J. M., Stevense-den Boer, Marion A. M., Boers-Sonderen, Marye J., Kapiteijn, Ellen, Suijkerbuijk, Karijn P. M., and Elias, Sjoerd G.
Abstract: 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. Our prediction model for predicting response within 6 months after ICI initiation was internally validated with bootstrap resampling. Performance evaluation included calibration, discrimination and internal–external cross-validation. Included patients received anti-PD-1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. The model included serum lactate dehydrogenase, World Health Organization performance score, type and line of ICI, disease stage and time to first distant recurrence—all at start of ICI—, and location and type of primary melanoma, the presence of satellites and/or in-transit metastases at primary diagnosis and sex. The over-optimism adjusted area under the receiver operating characteristic was 0.66 (95% CI: 0.64–0.66). The range of predicted response probabilities was 7%–81%. Based on these probabilities, patients were categorized into quartiles. Compared to the lowest response quartile, patients in the highest quartile had a significantly longer median progression-free survival (20.0 vs 2.8 months; P <.001) and median overall survival (62.0 vs 8.0 months; P <.001). Our prediction model, based on routinely available clinical variables and primary melanoma characteristics, predicts response to ICI in patients with advanced melanoma and discriminates well between treated patients with a very good and very poor prognosis.
Published: 2024

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

Author: Cancer, MS Medische Oncologie, Pathologie, Pathologie Pathologen staf, Pathologie Groep Van Diest, MS Radiotherapie, Brain, Circulatory Health, MS Radiologie, Infection & Immunity, Epi Kanker Team C, JC onderzoeksprogramma Kanker, van Duin, Isabella A J, Verheijden, Rik J, van Diest, Paul J, Blokx, Willeke A M, El-Sharouni, Mary-Ann, Verhoeff, Joost J C, Leiner, Tim, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Haanen, John B A G, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Stevense-den Boer, Marion A M, Boers-Sonderen, Marye J, Kapiteijn, Ellen, Suijkerbuijk, Karijn P M, Elias, Sjoerd G, Cancer, MS Medische Oncologie, Pathologie, Pathologie Pathologen staf, Pathologie Groep Van Diest, MS Radiotherapie, Brain, Circulatory Health, MS Radiologie, Infection & Immunity, Epi Kanker Team C, JC onderzoeksprogramma Kanker, van Duin, Isabella A J, Verheijden, Rik J, van Diest, Paul J, Blokx, Willeke A M, El-Sharouni, Mary-Ann, Verhoeff, Joost J C, Leiner, Tim, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Haanen, John B A G, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Stevense-den Boer, Marion A M, Boers-Sonderen, Marye J, Kapiteijn, Ellen, Suijkerbuijk, Karijn P M, and Elias, Sjoerd G
Published: 2024

8. BRAF/MEK inhibitor rechallenge in advanced melanoma patients

Author: Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan Willem W B, Hospers, Geke AP, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J, van der Veldt, Astrid A M, Wouters, Michel W J M, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan Willem W B, Hospers, Geke AP, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, Stevense-den Boer, Marion, Verheijden, Rik J, van der Veldt, Astrid A M, Wouters, Michel W J M, Blokx, Willeke A M, and Suijkerbuijk, Karijn P M
Published: 2024

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

Author: Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van Breeschoten, Jesper, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van Breeschoten, Jesper, van den Berkmortel, Franchette W P J, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M
Published: 2024

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

Author: van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van Breeschoten, Jesper, van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Ismail, Rawa K., Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Blokx, Willeke A.M., Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van Breeschoten, Jesper, van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Ismail, Rawa K., Kapiteijn, Ellen, Bloem, Manja, De Meza, Melissa M., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Blokx, Willeke A.M., Wouters, Michel W.J.M., and Suijkerbuijk, Karijn P.M.
Abstract: 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. Baseline characteristics and overall survival (OS) were compared between the different years of diagnosis. A multivariable Cox proportional hazards model was used to estimate the association between year of diagnosis and OS. Findings: For this cohort study, we included 6260 systemically treated advanced melanoma patients. At baseline, there was an increase over the years in age, the percentage of patients with an ECOG PS ≥ 2, with brain metastases, and a synchronous diagnosis of primary and unresectable melanoma. Median OS increased from 11.2 months (95% CI 10.0–12.4) for patients diagnosed in 2013 to 32.0 months (95% CI 26.6–36.7) for patients diagnosed in 2019. Median OS was remarkably lower for patients diagnosed in 2020 (26.6 months; 95% CI 23.9–35.1) and 2021 (24.0 months; 95% CI 20.4-NR). Patients diagnosed in 2020 and 2021 had a higher hazard of death compared to patients diagnosed in 2019, although this was not significant. The multivariable Cox regression showed a lower hazard of death for the years of diagnosis after 2013. In contrast, patients diagnosed in 2020 and 2021 had a higher hazard of death compared to patients diagnosed in 2019. Interpretation: After a continuous survival improvement for advanced melanoma patients between 2013 and 2019, outcomes of patients diagnosed in 2020 and 2021 seem poorer. This trend of decreased survival remained after correcting for known prognostic factors and previous neoadjuvant or adjuvant treatment, suggesting that it is explained by unmeasured factors, which—considering the timing—could be COVID-19-related. Funding
Published: 2024

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

Author: van Breeschoten, Jesper, Ismail, Rawa K., Wouters, Michel W.J.M., Hilarius, Doranne L., de Wreede, Liesbeth C., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Suijkerbuijk, Karijn P.M., and van den Eertwegh, Alfons J.M.
Published: 2022
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12. A prediction model for response to immune checkpoint inhibition in advanced melanoma

Author: van Duin, Isabella A. J., primary, Verheijden, Rik J., additional, van Diest, Paul J., additional, Blokx, Willeke A. M., additional, El‐Sharouni, Mary‐Ann, additional, Verhoeff, Joost J. C., additional, Leiner, Tim, additional, van den Eertwegh, Alfonsus J. M., additional, de Groot, Jan Willem B., additional, van Not, Olivier J., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Wouters, Michel W. J. M., additional, Stevense‐den Boer, Marion A. M., additional, Boers‐Sonderen, Marye J., additional, Kapiteijn, Ellen, additional, Suijkerbuijk, Karijn P. M., additional, and Elias, Sjoerd G., additional
Published: 2024
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13. BRAF/MEK inhibitor rechallenge in advanced melanoma patients

Author: Van Not, Olivier J., primary, van den Eertwegh, Alfons J. M., additional, Haanen, John B., additional, van Rijn, Rozemarijn S., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Boers‐Sonderen, Marye J., additional, de Groot, Jan Willem W. B., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen, additional, Bloem, Manja, additional, Piersma, Djura, additional, Stevense‐den Boer, Marion, additional, Verheijden, Rik J., additional, van der Veldt, Astrid A. M., additional, Wouters, Michel W. J. M., additional, Blokx, Willeke A. M., additional, and Suijkerbuijk, Karijn P. M., additional
Published: 2024
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14. Real-world Outcomes of Ipilimumab Plus Nivolumab Combination Therapy in a Nation-wide Cohort of Advanced Melanoma Patients in the Netherlands

Author: van Zeijl, Michiel C T, van Breeschoten, Jesper, de Wreede, Liesbeth C, Wouters, Michel W J M, Hilarius, Doranne L, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, Haanen, John B A G, van den Eertwegh, Alfons J M, Internal medicine, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Medical oncology, AII - Cancer immunology, CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Medical Oncology, and Radiology & Nuclear Medicine
Subjects: Pharmacology, Cancer Research, Ipilimumab plus nivolumab, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Immunology, real world, Brain Neoplasms/drug therapy, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], population-based, Nivolumab/therapeutic use, POOLED ANALYSIS, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, Melanoma/pathology, SURVIVAL, Immunology and Allergy, Humans, METASTATIC MELANOMA, immunotherapy, Ipilimumab/therapeutic use, Netherlands
Abstract: Item does not contain fulltext 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. We evaluated response status at 3, 6, 12, 18, and 24 months. OS and PFS were estimated with the Kaplan-Meier method. Separate analyses were performed for patients with or without brain metastases and for patients who met the inclusion criteria of the Checkmate-067 trial. In total, 709 patients received first-line ipilimumab plus nivolumab. Three hundred sixty (50.7%) patients experienced grade 3-4 adverse events, with 211 of the (58.6%) patients requiring hospital admission. The median treatment duration was 42 days (IQR = 31-139). At 24 months, disease control was achieved in 37% of patients. Median PFS since the start of treatment was 6.6 months (95% CI: 5.3-8.7), and median OS was 28.7 months (95% CI: 20.7-42.2). CheckMate-067 trial-like patients had a 4-year OS of 50% (95% CI: 43-59). Among patients with no asymptomatic or symptomatic brain metastases, the 4-year OS probabilities were 48% (95% CI: 41-55), 45% (95% CI: 35-57), and 32% (95% CI: 23-46). Ipilimumab plus nivolumab can achieve long-term survival in advanced melanoma patients in a real-world setting, including patients not represented in the CheckMate-067 trial. However, the proportion of patients with disease control in the real world is lower compared with clinical trials.
Published: 2023

15. BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Author: van Not, Olivier J., Blokx, Willeke A.M., van den Eertwegh, Alfons J.M., de Meza, Melissa M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Boers-Sonderen, Marye J., Jansen, Anne M.L., Wouters, Michel W.J.M., and Suijkerbuijk, Karijn P.M.
Published: 2022
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16. A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

Author: van Not, Olivier J., primary, Wind, Thijs T., additional, Ismail, Rawa K., additional, Bhattacharya, Arkajyoti, additional, Jalving, Mathilde, additional, Blank, Christian U., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Boers-Sonderen, Marye J., additional, van den Eertwegh, Alfonsus J. M., additional, de Groot, Jan Willem B., additional, Haanen, John B., additional, Kapiteijn, Ellen, additional, Bloem, Manja, additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Stevense-den Boer, Marion, additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Wouters, Michel W. J. M., additional, Blokx, Willeke A. M., additional, Suijkerbuijk, Karijn P. M., additional, Fehrmann, Rudolf S. N., additional, and Hospers, Geke A. P., additional
Published: 2023
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17. Adjuvant treatment of in‐transit melanoma: Narrowing the knowledge gap left by clinical trials

Author: de Meza, Melissa M., primary, Blokx, Willeke A. M., additional, Bonenkamp, Han J., additional, Blank, Cristian U., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Boers‐Sonderen, Marye J., additional, de Groot, Jan Willem B., additional, Haanen, John B., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen W., additional, van Not, Olivier J., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Stevense‐Den Boer, Marion A., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, van den Eertwegh, Alfons J. M., additional, Suijkerbuijk, Karijn P. M., additional, and Wouters, Michel W. J. M., additional
Published: 2023
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18. Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

Author: van Duin, Isabella A. J., primary, Elias, Sjoerd G., additional, van den Eertwegh, Alfonsus J. M., additional, de Groot, Jan Willem B., additional, Blokx, Willeke A. M., additional, van Diest, Paul J., additional, Leiner, Tim, additional, Verhoeff, Joost J. C., additional, Verheijden, Rik J., additional, van Not, Olivier J., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Kamphuis, Anna M., additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Wouters, Michel W. J. M., additional, Stevense‐den Boer, Marion A. M., additional, Boers‐Sonderen, Marye J., additional, Kapiteijn, Ellen, additional, and Suijkerbuijk, Karijn P. M., additional
Published: 2023
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19. A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

Author: van Not, Olivier J., Wind, Thijs T., Ismail, Rawa K., Bhattacharya, Arkajyoti, Jalving, Mathilde, Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Boers-Sonderen, Marye J., van den Eertwegh, Alfonsus J.M., de Groot, Jan Willem B., Haanen, John B., Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Wouters, Michel W.J.M., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., Fehrmann, Rudolf S.N., Hospers, Geke A.P., van Not, Olivier J., Wind, Thijs T., Ismail, Rawa K., Bhattacharya, Arkajyoti, Jalving, Mathilde, Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Boers-Sonderen, Marye J., van den Eertwegh, Alfonsus J.M., de Groot, Jan Willem B., Haanen, John B., Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Wouters, Michel W.J.M., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., Fehrmann, Rudolf S.N., and Hospers, Geke A.P.
Abstract: 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. Patients were included from the time of the treatment of BM with ICIs. Survival tree analysis was performed with clinicopathological parameters as potential classifiers and overall survival (OS) as the response variable. In total, 1278 patients were included. Most patients were treated with ipilimumab–nivolumab combination therapy (45%). The survival tree analysis resulted in 31 subgroups. The median OS ranged from 2.7 months to 35.7 months. The strongest clinical parameter associated with survival in advanced melanoma patients with BM was the serum lactate dehydrogenase (LDH) level. Patients with elevated LDH levels and symptomatic BM had the worst prognosis. The clinicopathological classifiers identified in this study can contribute to optimizing clinical studies and can aid doctors in giving an indication of the patients’ survival based on their baseline and disease characteristics.
Published: 2023

20. Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

Author: van Duin, Isabella A J, Elias, Sjoerd G, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, Blokx, Willeke A M, van Diest, Paul J, Leiner, Tim, Verhoeff, Joost J C, Verheijden, Rik J, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Haanen, John B A G, Hospers, Geke A P, Kamphuis, Anna M, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Stevense-den Boer, Marion A M, Boers-Sonderen, Marye J, Kapiteijn, Ellen, Suijkerbuijk, Karijn P M, van Duin, Isabella A J, Elias, Sjoerd G, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, Blokx, Willeke A M, van Diest, Paul J, Leiner, Tim, Verhoeff, Joost J C, Verheijden, Rik J, van Not, Olivier J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Haanen, John B A G, Hospers, Geke A P, Kamphuis, Anna M, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Stevense-den Boer, Marion A M, Boers-Sonderen, Marye J, Kapiteijn, Ellen, and Suijkerbuijk, Karijn P M
Abstract: Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.
Published: 2023

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

Author: de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-Den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-Den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M
Abstract: 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. Patients were divided into three groups: nodal disease only, ITM only and ITM and nodal disease. Recurrence patterns, recurrence-free survival (RFS) and overall survival (OS) at 12-months were analyzed. In our study population of 1037 patients, 66.8% had nodal disease only, 16.7% had ITM only and 16.2% had ITM with nodal disease. RFS at 12-months was comparable in the nodal only and ITM only group (72.2% vs70.1%, P = .97) but lower in ITM and nodal disease patients (57.8%; P = .01, P < .01). Locoregional metastases occurred as first recurrence in 38.9% nodal disease only, 71.9% of ITM-only and 44.0% of ITM and nodal disease patients. Distant recurrences occurred in 42.3%, 18.8% and 36.0%, respectively (P = .02). 12-months OS was not significantly different for nodal disease only patients compared with ITM-only (94.4% vs 97.6%, P = .06) but was significantly higher for ITM-only compared with ITM and nodal disease patients (97.6% vs 91.0%, P < .01). In conclusion, we showed that in the adjuvant setting, RFS rates in ITM-only patients are similar to non-ITM, though better than in ITM and nodal disease patients. Adjuvant-treated ITM-only patients less often experience distant recurrences and have a superior OS compared with ITM and nodal disease patients.
Published: 2023

22. Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma:A Propensity-Matched Outcome Analysis

Author: De Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Johannes J, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, De Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Van Not, Olivier J, Piersma, Djura, Van Rijn, Rozemarijn S, Stevense-den Boer, Marion, Van der Veldt, Astrid A M, Vreugdenhil, Gerard, Van den Eertwegh, Alfonsus J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, De Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Johannes J, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, De Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen, Van Not, Olivier J, Piersma, Djura, Van Rijn, Rozemarijn S, Stevense-den Boer, Marion, Van der Veldt, Astrid A M, Vreugdenhil, Gerard, Van den Eertwegh, Alfonsus J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M
Abstract: 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. For this study, stage III BRAF V600 mutant cutaneous melanoma patients treated with adjuvant BRAF/MEK-inhibition or anti-PD-1 were identified from the Dutch Melanoma Treatment Registry. BRAF/MEK- and anti-PD-1-treated patients were matched based on propensity scores, and RFS at 12 and 18 months were estimated. Between 1 July 2018 and 31 December 2021, 717 patients were identified. Of these, 114 patients with complete records were treated with BRAF/MEK therapy and 532 with anti-PD-1. Comorbidities (p = 0.04) and geographical region (p < 0.01) were associated with treatment choice. In 45.6% of BRAF/MEK-treated patients, treatment was prematurely discontinued. Grade ≥ 3 toxicity occurred in 11.5% of patients and was the most common cause of early discontinuation (71.1%). At 12 and 18 months, RFS in BRAF/MEK-treated patients was 85% and 70%, compared to 68% and 68% in matched anti-PD-1-treated patients (p = 0.03). In conclusion, comorbidities and geographical region determine the choice of adjuvant treatment in patients with resected stage III BRAF-mutant melanoma. With the currently limited follow-up, BRAF/MEK-treated patients have better RFS at 12 months than matched anti-PD-1-treated patients, but this difference is no longer observed at 18 months. Therefore, longer follow-up data are necessary to estimate long-term effectiveness.
Published: 2023

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

Author: MS Medische Oncologie, Cancer, Infection & Immunity, van Zeijl, Michiel C T, van Breeschoten, Jesper, de Wreede, Liesbeth C, Wouters, Michel W J M, Hilarius, Doranne L, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, Haanen, John B A G, van den Eertwegh, Alfons J M, MS Medische Oncologie, Cancer, Infection & Immunity, van Zeijl, Michiel C T, van Breeschoten, Jesper, de Wreede, Liesbeth C, Wouters, Michel W J M, Hilarius, Doranne L, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, Haanen, John B A G, and van den Eertwegh, Alfons J M
Published: 2023

24. A Survival Tree of Advanced Melanoma Patients with Brain Metastases Treated with Immune Checkpoint Inhibitors

Author: Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, Wind, Thijs T, Ismail, Rawa K, Bhattacharya, Arkajyoti, Jalving, Mathilde, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, Haanen, John B, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, Fehrmann, Rudolf S N, Hospers, Geke A P, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, Wind, Thijs T, Ismail, Rawa K, Bhattacharya, Arkajyoti, Jalving, Mathilde, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, Haanen, John B, Kapiteijn, Ellen, Bloem, Manja, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, Fehrmann, Rudolf S N, and Hospers, Geke A P
Published: 2023

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

Author: MS Medische Oncologie, Cancer, Infection & Immunity, Pathologie Pathologen staf, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Blokx, Willeke A M, MS Medische Oncologie, Cancer, Infection & Immunity, Pathologie Pathologen staf, Van Not, Olivier J, van den Eertwegh, Alfons J M, Haanen, John B, van Rijn, Rozemarijn S, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van Eijs, Mick J M, de Groot, Jan-Willem B, Hospers, Geke A P, Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, and Blokx, Willeke A M
Published: 2023

26. Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Author: Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, De Meza, Melissa M., Blokx, Willeke A.M., Bonenkamp, Johannes J., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Boers-Sonderen, Marye J., De Groot, Jan Willem B., Haanen, John B.A.G., Hospers, Geke A.P., Kapiteijn, Ellen, Van Not, Olivier J., Piersma, Djura, Van Rijn, Rozemarijn S., Stevense-den Boer, Marion, Van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Van den Eertwegh, Alfonsus J.M., Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, De Meza, Melissa M., Blokx, Willeke A.M., Bonenkamp, Johannes J., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Boers-Sonderen, Marye J., De Groot, Jan Willem B., Haanen, John B.A.G., Hospers, Geke A.P., Kapiteijn, Ellen, Van Not, Olivier J., Piersma, Djura, Van Rijn, Rozemarijn S., Stevense-den Boer, Marion, Van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Van den Eertwegh, Alfonsus J.M., Suijkerbuijk, Karijn P.M., and Wouters, Michel W.J.M.
Published: 2023

27. Adjuvant Treatment of In-Transit Melanoma: Narrowing the Knowledge Gap Left by Clinical Trials

Author: Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, de Meza, Melissa M, Blokx, Willeke A M, Bonenkamp, Han J, Blank, Cristian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Boers-Sonderen, Marye J, de Groot, Jan Willem B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, van den Eertwegh, Alfons J M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M
Published: 2023

28. Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

Author: Hart- en Vaatziekten Team A, Epi Kanker Team C, Cancer, JC onderzoeksprogramma Kanker, Pathologie Pathologen staf, Pathologie, MS Radiologie, Circulatory Health, MS Radiotherapie, MS Medische Oncologie, Infection & Immunity, van Duin, Isabella A.J., Elias, Sjoerd G., van den Eertwegh, Alfonsus J.M., de Groot, Jan Willem B., Blokx, Willeke A.M., van Diest, Paul J., Leiner, Tim, Verhoeff, Joost J.C., Verheijden, Rik J., van Not, Olivier J., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Blank, Christian U., Haanen, John B.A.G., Hospers, Geke A.P., Kamphuis, Anna M., Piersma, Djura, van Rijn, Rozemarijn S., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Wouters, Michel W.J.M., Stevense-den Boer, Marion A.M., Boers-Sonderen, Marye J., Kapiteijn, Ellen, Suijkerbuijk, Karijn P.M., Hart- en Vaatziekten Team A, Epi Kanker Team C, Cancer, JC onderzoeksprogramma Kanker, Pathologie Pathologen staf, Pathologie, MS Radiologie, Circulatory Health, MS Radiotherapie, MS Medische Oncologie, Infection & Immunity, van Duin, Isabella A.J., Elias, Sjoerd G., van den Eertwegh, Alfonsus J.M., de Groot, Jan Willem B., Blokx, Willeke A.M., van Diest, Paul J., Leiner, Tim, Verhoeff, Joost J.C., Verheijden, Rik J., van Not, Olivier J., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Blank, Christian U., Haanen, John B.A.G., Hospers, Geke A.P., Kamphuis, Anna M., Piersma, Djura, van Rijn, Rozemarijn S., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Wouters, Michel W.J.M., Stevense-den Boer, Marion A.M., Boers-Sonderen, Marye J., Kapiteijn, Ellen, and Suijkerbuijk, Karijn P.M.
Published: 2023

29. Population mortality in advanced melanoma patients with and without response and progression; data from the Dutch Melanoma Treatment Registry

Author: MS Medische Oncologie, Cancer, Infection & Immunity, van Breeschoten, Jesper, van den Eertwegh, Alfons J.M., Hilarius, Doranne L., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Manevski, Damjan, Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., de Wreede, Liesbeth C., MS Medische Oncologie, Cancer, Infection & Immunity, van Breeschoten, Jesper, van den Eertwegh, Alfons J.M., Hilarius, Doranne L., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Manevski, Damjan, Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., and de Wreede, Liesbeth C.
Published: 2023

30. Adjuvant BRAF-MEK Inhibitors versus Anti PD-1 Therapy in Stage III Melanoma: A Propensity-Matched Outcome Analysis

Author: De Meza, Melissa M., primary, Blokx, Willeke A. M., additional, Bonenkamp, Johannes J., additional, Blank, Christian U., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Boers-Sonderen, Marye J., additional, De Groot, Jan Willem B., additional, Haanen, John B. A. G., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen, additional, Van Not, Olivier J., additional, Piersma, Djura, additional, Van Rijn, Rozemarijn S., additional, Stevense-den Boer, Marion, additional, Van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Van den Eertwegh, Alfonsus J. M., additional, Suijkerbuijk, Karijn P. M., additional, and Wouters, Michel W. J. M., additional
Published: 2023
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31. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author: Rohaan, Maartje W., primary, Borch, Troels H., additional, van den Berg, Joost H., additional, Met, Özcan, additional, Kessels, Rob, additional, Geukes Foppen, Marnix H., additional, Stoltenborg Granhøj, Joachim, additional, Nuijen, Bastiaan, additional, Nijenhuis, Cynthia, additional, Jedema, Inge, additional, van Zon, Maaike, additional, Scheij, Saskia, additional, Beijnen, Jos H., additional, Hansen, Marten, additional, Voermans, Carlijn, additional, Noringriis, Inge M., additional, Monberg, Tine J., additional, Holmstroem, Rikke B., additional, Wever, Lidwina D.V., additional, van Dijk, Marloes, additional, Grijpink-Ongering, Lindsay G., additional, Valkenet, Ludy H.M., additional, Torres Acosta, Alejandro, additional, Karger, Matthias, additional, Borgers, Jessica S.W., additional, ten Ham, Renske M.T., additional, Retèl, Valesca P., additional, van Harten, Wim H., additional, Lalezari, Ferry, additional, van Tinteren, Harm, additional, van der Veldt, Astrid A.M., additional, Hospers, Geke A.P., additional, Stevense-den Boer, Marion A.M., additional, Suijkerbuijk, Karijn P.M., additional, Aarts, Maureen J.B., additional, Piersma, Djura, additional, van den Eertwegh, Alfons J.M., additional, de Groot, Jan-Willem B., additional, Vreugdenhil, Gerard, additional, Kapiteijn, Ellen, additional, Boers-Sonderen, Marye J., additional, Fiets, W. Edward, additional, van den Berkmortel, Franchette W.P.J., additional, Ellebaek, Eva, additional, Hölmich, Lisbet R., additional, van Akkooi, Alexander C.J., additional, van Houdt, Winan J., additional, Wouters, Michel W.J.M., additional, van Thienen, Johannes V., additional, Blank, Christian U., additional, Meerveld-Eggink, Aafke, additional, Klobuch, Sebastian, additional, Wilgenhof, Sofie, additional, Schumacher, Ton N., additional, Donia, Marco, additional, Svane, Inge Marie, additional, and Haanen, John B.A.G., additional
Published: 2022
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32. Association of Immune-Related Adverse Event Management With Survival in Patients With Advanced Melanoma

Author: van Not, Olivier J., primary, Verheijden, Rik J., additional, van den Eertwegh, Alfonsus J. M., additional, Haanen, John B. A. G., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, Blank, Christian U., additional, Boers-Sonderen, Marye J., additional, de Groot, Jan-Willem B., additional, Hospers, Geke A. P., additional, Kamphuis, Anna M., additional, Kapiteijn, Ellen, additional, May, Anne M., additional, de Meza, Melissa M., additional, Piersma, Djura, additional, van Rijn, Rozemarijn, additional, Stevense-den Boer, Marion A., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Blokx, Willeke A. M., additional, Wouters, Michel J. M., additional, and Suijkerbuijk, Karijn P. M., additional
Published: 2022
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33. Management of checkpoint inhibitor toxicity and survival in patients with advanced melanoma.

Author: van Not, Olivier Jules, primary, Verheijden, Rik Jasper, additional, van den Eertwegh, Alfonsus Johannes Maria, additional, Haanen, John B. A. G., additional, Blank, Christian U., additional, Aarts, Maureen J.B., additional, Van Den Berkmortel, Franchette, additional, de Groot, Jan Willem, additional, Hospers, Geke, additional, Kapiteijn, Ellen, additional, de Meza, Melissa Melanie, additional, Piersma, Djura, additional, Van Rijn, Rozemarijn, additional, Stevense - den Boer, Marion, additional, Van Der Veldt, Astrid Aplonia Maria, additional, Vreugdenhil, Gerard, additional, Boers-Sonderen, Marye J., additional, Blokx, Willeke, additional, Wouters, Michel W.J.M., additional, and Suijkerbuijk, Karijn, additional
Published: 2022
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34. Adjuvant treatment of in-transit melanoma: Addressing the knowledge gap left by clinical trials.

Author: de Meza, Melissa Melanie, primary, Blokx, Willeke, additional, Bonenkamp, Han J., additional, Blank, Christian U., additional, Aarts, Maureen J.B., additional, Van Den Berkmortel, Franchette, additional, Boers-Sonderen, Marye J., additional, de Groot, Jan Willem, additional, Haanen, John B. A. G., additional, Hospers, Geke, additional, Kapiteijn, Ellen, additional, van Not, Olivier Jules, additional, Piersma, Djura, additional, Van Rijn, Rozemarijn, additional, Stevense - den Boer, Marion, additional, Van Der Veldt, Astrid Aplonia Maria, additional, Vreugdenhil, Gerard, additional, van den Eertwegh, Alfonsus Johannes Maria, additional, Suijkerbuijk, Karijn, additional, and Wouters, Michel W.J.M., additional
Published: 2022
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35. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author: Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, Haanen, John B A G, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, and Haanen, John B A G
Abstract: 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). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. Results A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. Conclusions In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than amon
Published: 2022

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

Author: van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M
Abstract: 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. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8–5.6) than patients with CM (10.1 months; 95%CI: 8.5–12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26–2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15–2.06; P = 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.
Published: 2022

37. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

Author: Rohaan, Maartje W., Borch, Troels H., Van Den Berg, Joost H., Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H., Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, Van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H., Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M., Monberg, Tine J., Holmstroem, Rikke B., Wever, Lidwina D.V., Van Dijk, Marloes, Grijpink-Ongering, Lindsay G., Valkenet, Ludy H.M., Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S.W., Ten Ham, Renske M.T., Retèl, Valesca P., Van Harten, Wim H., Lalezari, Ferry, Van Tinteren, Harm, Van Der Veldt, Astrid A.M., Hospers, Geke A.P., Stevense-Den Boer, Marion A.M., Suijkerbuijk, Karijn P.M., Aarts, Maureen J.B., Piersma, Djura, Van Den Eertwegh, Alfons J.M., De Groot, Jan Willem B., Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J., Fiets, W. Edward, Van Den Berkmortel, Franchette W.P.J., Ellebaek, Eva, Hölmich, Lisbet R., Van Akkooi, Alexander C.J., Van Houdt, Winan J., Wouters, Michel W.J.M., Van Thienen, Johannes V., Blank, Christian U., Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N., Donia, Marco, Svane, Inge Marie, Haanen, John B.A.G., Rohaan, Maartje W., Borch, Troels H., Van Den Berg, Joost H., Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H., Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, Van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H., Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M., Monberg, Tine J., Holmstroem, Rikke B., Wever, Lidwina D.V., Van Dijk, Marloes, Grijpink-Ongering, Lindsay G., Valkenet, Ludy H.M., Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S.W., Ten Ham, Renske M.T., Retèl, Valesca P., Van Harten, Wim H., Lalezari, Ferry, Van Tinteren, Harm, Van Der Veldt, Astrid A.M., Hospers, Geke A.P., Stevense-Den Boer, Marion A.M., Suijkerbuijk, Karijn P.M., Aarts, Maureen J.B., Piersma, Djura, Van Den Eertwegh, Alfons J.M., De Groot, Jan Willem B., Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J., Fiets, W. Edward, Van Den Berkmortel, Franchette W.P.J., Ellebaek, Eva, Hölmich, Lisbet R., Van Akkooi, Alexander C.J., Van Houdt, Winan J., Wouters, Michel W.J.M., Van Thienen, Johannes V., Blank, Christian U., Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N., Donia, Marco, Svane, Inge Marie, and Haanen, John B.A.G.
Abstract: 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). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. Results A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. Conclusions In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than amon
Published: 2022

38. The unfavorable effects of COVID-19 on Dutch advanced melanoma care

Author: van Not, Olivier J., van Breeschoten, Jesper, van den Eertwegh, Alfonsus J.M., Hilarius, Doranne L., De Meza, Melissa M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Ismail, Rawa K., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., van Not, Olivier J., van Breeschoten, Jesper, van den Eertwegh, Alfonsus J.M., Hilarius, Doranne L., De Meza, Melissa M., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Ismail, Rawa K., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers-Sonderen, Marye J., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., and Wouters, Michel W.J.M.
Abstract: The COVID-19 pandemic had a severe impact on medical care. Our study aims to investigate the impact of COVID-19 on advanced melanoma care in the Netherlands. We selected patients diagnosed with irresectable stage IIIc and IV melanoma during the first and second COVID-19 wave and compared them with patients diagnosed within the same time frame in 2018 and 2019. Patients were divided into three geographical regions. We investigated baseline characteristics, time from diagnosis until start of systemic therapy and postponement of anti-PD-1 courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P-value <.05). Anti-PD-1 courses were postponed in 20.0% vs 3.0% of patients in the first wave compared to the control period. Significantly more patients had courses postponed in the south during the first wave compared to other regions (34.8% vs 11.5% vs 22.3%, P-value <.001). Significantly more patients diagnosed during the second wave had brain metastases and worse performance status compared to the control period. In conclusion, advanced melanoma care in the Netherlands was severely affected by the COVID-19 pandemic. In the south, the start of systemic treatment for advanced melanoma was more often delayed, and treatment courses were more frequently postponed. During the second wave, patients were diagnosed with poorer patient and tumor characteristics. Longer follow-up is needed to establish the impact on patient outcomes.
Published: 2022

39. Association of Immune-Related Adverse Event Management With Survival in Patients With Advanced Melanoma

Author: MS Medische Oncologie, Cancer, Epi Kanker, JC onderzoeksprogramma Kanker, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, Verheijden, Rik J, van den Eertwegh, Alfonsus J M, Haanen, John B A G, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan-Willem B, Hospers, Geke A P, Kamphuis, Anna M, Kapiteijn, Ellen, May, Anne M, de Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Blokx, Willeke A M, Wouters, Michel J M, Suijkerbuijk, Karijn P M, MS Medische Oncologie, Cancer, Epi Kanker, JC onderzoeksprogramma Kanker, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, Verheijden, Rik J, van den Eertwegh, Alfonsus J M, Haanen, John B A G, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan-Willem B, Hospers, Geke A P, Kamphuis, Anna M, Kapiteijn, Ellen, May, Anne M, de Meza, Melissa M, Piersma, Djura, van Rijn, Rozemarijn, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Blokx, Willeke A M, Wouters, Michel J M, and Suijkerbuijk, Karijn P M
Published: 2022

40. Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma

Author: HEE, MS Medische Oncologie, Cancer, Infection & Immunity, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, Haanen, John B A G, HEE, MS Medische Oncologie, Cancer, Infection & Immunity, Rohaan, Maartje W, Borch, Troels H, van den Berg, Joost H, Met, Özcan, Kessels, Rob, Geukes Foppen, Marnix H, Stoltenborg Granhøj, Joachim, Nuijen, Bastiaan, Nijenhuis, Cynthia, Jedema, Inge, van Zon, Maaike, Scheij, Saskia, Beijnen, Jos H, Hansen, Marten, Voermans, Carlijn, Noringriis, Inge M, Monberg, Tine J, Holmstroem, Rikke B, Wever, Lidwina D V, van Dijk, Marloes, Grijpink-Ongering, Lindsay G, Valkenet, Ludy H M, Torres Acosta, Alejandro, Karger, Matthias, Borgers, Jessica S W, Ten Ham, Renske M T, Retèl, Valesca P, van Harten, Wim H, Lalezari, Ferry, van Tinteren, Harm, van der Veldt, Astrid A M, Hospers, Geke A P, Stevense-den Boer, Marion A M, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, Piersma, Djura, van den Eertwegh, Alfons J M, de Groot, Jan-Willem B, Vreugdenhil, Gerard, Kapiteijn, Ellen, Boers-Sonderen, Marye J, Fiets, W Edward, van den Berkmortel, Franchette W P J, Ellebaek, Eva, Hölmich, Lisbet R, van Akkooi, Alexander C J, van Houdt, Winan J, Wouters, Michel W J M, van Thienen, Johannes V, Blank, Christian U, Meerveld-Eggink, Aafke, Klobuch, Sebastian, Wilgenhof, Sofie, Schumacher, Ton N, Donia, Marco, Svane, Inge Marie, and Haanen, John B A G
Published: 2022

41. BRAF and NRAS Mutation Status and Response to Checkpoint Inhibition in Advanced Melanoma

Author: Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Pathologie Moleculair, Infection & Immunity, van Not, Olivier J, Blokx, Willeke A M, van den Eertwegh, Alfons J M, de Meza, Melissa M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Boers-Sonderen, Marye J, Jansen, Anne M L, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Cancer, MS Medische Oncologie, Pathologie Pathologen staf, Pathologie Moleculair, Infection & Immunity, van Not, Olivier J, Blokx, Willeke A M, van den Eertwegh, Alfons J M, de Meza, Melissa M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Boers-Sonderen, Marye J, Jansen, Anne M L, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M
Published: 2022

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

Author: MS Medische Oncologie, Cancer, Infection & Immunity, van Breeschoten, Jesper, Ismail, Rawa K, Wouters, Michel W J M, Hilarius, Doranne L, de Wreede, Liesbeth C, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, UMC, Amsterdam, MS Medische Oncologie, Cancer, Infection & Immunity, van Breeschoten, Jesper, Ismail, Rawa K, Wouters, Michel W J M, Hilarius, Doranne L, de Wreede, Liesbeth C, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Suijkerbuijk, Karijn P M, and UMC, Amsterdam
Published: 2022

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

Author: Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, van Not, Olivier J, de Meza, Melissa M, van den Eertwegh, Alfons J M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, van Breeschoten, Jesper, de Groot, Jan-Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Roos S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Bonenkamp, Han J, Boers-Sonderen, Marye J, Blokx, Willeke A M, Wouters, Michel W J M, and Suijkerbuijk, Karijn P M
Published: 2022

44. The unfavorable effects of COVID-19 on Dutch advanced melanoma care

Author: Pathologie Pathologen staf, MS Medische Oncologie, Infection & Immunity, Cancer, Van Not, Olivier J, van Breeschoten, Jesper, van den Eertwegh, Alfonsus J M, Hilarius, Doranne L, De Meza, Melissa M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, Wouters, Michel W J M, Pathologie Pathologen staf, MS Medische Oncologie, Infection & Immunity, Cancer, Van Not, Olivier J, van Breeschoten, Jesper, van den Eertwegh, Alfonsus J M, Hilarius, Doranne L, De Meza, Melissa M, Haanen, John B, Blank, Christian U, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, de Groot, Jan Willem B, Hospers, Geke A P, Ismail, Rawa K, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, Marion A M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Boers-Sonderen, Marye J, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, and Wouters, Michel W J M
Published: 2022

45. Association of Immune-Related Adverse Event Management with Survival in Patients with Advanced Melanoma

Author: Van Not, Olivier J., Verheijden, Rik J., Van Den Eertwegh, Alfonsus J.M., Haanen, John B.A.G., Aarts, Maureen J.B., Van Den Berkmortel, Franchette W.P.J., Blank, Christian U., Boers-Sonderen, Marye J., De Groot, Jan Willem B., Hospers, Geke A.P., Kamphuis, Anna M., Kapiteijn, Ellen, May, Anne M., De Meza, Melissa M., Piersma, Djura, Van Rijn, Rozemarijn, Stevense-Den Boer, Marion A., Van Der Veldt, Astrid A.M., Vreugdenhil, Gerard, Blokx, Willeke A.M., Wouters, Michel J.M., Suijkerbuijk, Karijn P.M., Van Not, Olivier J., Verheijden, Rik J., Van Den Eertwegh, Alfonsus J.M., Haanen, John B.A.G., Aarts, Maureen J.B., Van Den Berkmortel, Franchette W.P.J., Blank, Christian U., Boers-Sonderen, Marye J., De Groot, Jan Willem B., Hospers, Geke A.P., Kamphuis, Anna M., Kapiteijn, Ellen, May, Anne M., De Meza, Melissa M., Piersma, Djura, Van Rijn, Rozemarijn, Stevense-Den Boer, Marion A., Van Der Veldt, Astrid A.M., Vreugdenhil, Gerard, Blokx, Willeke A.M., Wouters, Michel J.M., and Suijkerbuijk, Karijn P.M.
Abstract: 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. Design, Setting, and Participants: This population-based, multicenter cohort study included patients with advanced melanoma experiencing grade 3 and higher irAEs after treatment with first-line ipilimumab and nivolumab between 2015 and 2021. Data were collected from the Dutch Melanoma Treatment Registry. Median follow-up was 23.6 months. Main Outcomes and Measures: The PFS, OS, and MSS were analyzed according to toxic effect management regimen. Cox proportional hazard regression was used to assess factors associated with PFS and OS. Results: Of 771 patients treated with ipilimumab and nivolumab, 350 patients (median [IQR] age, 60.0 [51.0-68.0] years; 206 [58.9%] male) were treated with immunosuppression for severe irAEs. Of these patients, 235 received steroids alone, and 115 received steroids with second-line immunosuppressants. Colitis and hepatitis were the most frequently reported types of toxic effects. Except for type of toxic effect, no statistically significant differences existed at baseline. Median PFS was statistically significantly longer for patients treated with steroids alone compared with patients treated with steroids plus second-line immunosuppressants (11.3 [95% CI, 9.6-19.6] months vs 5.4 [95% CI, 4.5-12.4] months; P =.01). Median OS was also statistically significantly longer for the group receiving steroids alone compared with those receiving steroids plus second-line immunosuppressants (46.1 months [95% CI, 39.0 months-not reached (NR)] vs
Published: 2022

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

Author: van Not, Olivier J., primary, de Meza, Melissa M., additional, van den Eertwegh, Alfons J.M., additional, Haanen, John B., additional, Blank, Christian U., additional, Aarts, Maureen J.B., additional, van den Berkmortel, Franchette W.P.J., additional, van Breeschoten, Jesper, additional, de Groot, Jan-Willem B., additional, Hospers, Geke A.P., additional, Ismail, Rawa K., additional, Kapiteijn, Ellen, additional, Piersma, Djura, additional, van Rijn, Roos S., additional, Stevense-den Boer, Marion A.M., additional, van der Veldt, Astrid A.M., additional, Vreugdenhil, Gerard, additional, Bonenkamp, Han J., additional, Boers-Sonderen, Marye J., additional, Blokx, Willeke A.M., additional, Wouters, Michel W.J.M., additional, and Suijkerbuijk, Karijn P.M., additional
Published: 2022
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47. Population Mortality in Advanced Melanoma Patients with and Without Response and Progression; Data from the Dutch Melanoma Treatment Registry

Author: van Breeschoten, Jesper, primary, van den Eertwegh, Alfons J.M., additional, Hilarius, Doranne L., additional, Haanen, John, additional, Blank, Christian U., additional, Aarts, Maureen J.B., additional, van den Berkmortel, Franchette W.P.J., additional, de Groot, Jan Willem B., additional, Hospers, Geke A.P., additional, Kapiteijn, Ellen, additional, Piersma, Djura P., additional, van Rijn, Rozemarijn S., additional, Stevense-den Boer, Marion A., additional, Vreugdenhil, Gerard, additional, Boers-Sonderen, Marye J., additional, Manevski, Damjan, additional, Suijkerbuijk, Karijn P.M., additional, Wouters, Michel W.J.M., additional, and de Wreede, Liesbeth C., additional
Published: 2022
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48. The unfavorable effects of COVID ‐19 on Dutch advanced melanoma care

Author: Not, Olivier J., primary, Breeschoten, Jesper, additional, Eertwegh, Alfonsus J. M., additional, Hilarius, Doranne L., additional, De Meza, Melissa M., additional, Haanen, John B., additional, Blank, Christian U., additional, Aarts, Maureen J. B., additional, Berkmortel, Franchette W. P. J., additional, Groot, Jan Willem B., additional, Hospers, Geke A. P., additional, Ismail, Rawa K., additional, Kapiteijn, Ellen, additional, Piersma, Djura, additional, Rijn, Rozemarijn S., additional, Stevense‐den Boer, Marion A. M., additional, Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Boers‐Sonderen, Marye J., additional, Blokx, Willeke A. M., additional, Suijkerbuijk, Karijn P. M., additional, and Wouters, Michel W. J. M., additional
Published: 2021
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49. Hospital Variation in Cancer Treatments and Survival OutComes of Advanced Melanoma Patients: Nationwide Quality Assurance in The Netherlands

Author: van Breeschoten, Jesper, primary, van den Eertwegh, Alfonsus J. M., additional, de Wreede, Liesbeth C., additional, Hilarius, Doranne L., additional, van Zwet, Erik W., additional, Haanen, John B., additional, Blank, Christian U., additional, Aarts, Maureen J. B., additional, van den Berkmortel, Franchette W. P. J., additional, de Groot, Jan Willem B., additional, Hospers, Geke A. P., additional, Kapiteijn, Ellen, additional, Piersma, Djura, additional, van Rijn, Rozemarijn S., additional, Stevense-den Boer, Marion A. M., additional, van der Veldt, Astrid A. M., additional, Vreugdenhil, Gerard, additional, Boers-Sonderen, Marye J., additional, Suijkerbuijk, Karijn P. M., additional, and Wouters, Michel W. J. M., additional
Published: 2021
Full Text: View/download PDF

50. Hospital variation in cancer treatments and survival outcomes of advanced melanoma patients:Nationwide quality assurance in the netherlands

Author: van Breeschoten, Jesper, van den Eertwegh, Alfonsus J.M., de Wreede, Liesbeth C., Hilarius, Doranne L., van Zwet, Erik W., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense‐Den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers‐sonderen, Marye J., Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., van Breeschoten, Jesper, van den Eertwegh, Alfonsus J.M., de Wreede, Liesbeth C., Hilarius, Doranne L., van Zwet, Erik W., Haanen, John B., Blank, Christian U., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., de Groot, Jan Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S., Stevense‐Den Boer, Marion A.M., van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Boers‐sonderen, Marye J., Suijkerbuijk, Karijn P.M., and Wouters, Michel W.J.M.
Abstract: BACKGROUND: To assure a high quality of care for patients treated in Dutch melanoma centers, hospital variation in treatment patterns and outcomes is evaluated in the Dutch Melanoma Treatment Registry. The aim of this study was to assess center variation in treatments and 2-year survival probabilities of patients diagnosed between 2013 and 2017 in the Netherlands.METHODS: We selected patients diagnosed between 2013 and 2017 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. Centers' performance on 2-year survival was evaluated using Empirical Bayes estimates calculated in a random effects model. Treatment patterns of the centers with the lowest and highest estimates for 2-year survival were compared.RESULTS: For patients diagnosed between 2014 and 2015, significant center variation in 2-year survival probabilities was observed even after correcting for case-mix and treatment with new systemic therapies. The different use of new systemic therapies partially explained the observed variation. From 2016 onwards, no significant difference in 2-year survival was observed between centers.CONCLUSION: Our data suggest that between 2014 and 2015, after correcting for patient case-mix, significant variation in 2-year survival probabilities between Dutch melanoma centers existed. The use of new systemic therapies could partially explain this variation. In 2013 and between 2016 and 2017, no significant variation between centers existed.
Published: 2021

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