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1. Treatment patterns and survival outcomes of patients admitted to the intensive care unit due to immune-related adverse events of immune checkpoint inhibitors

Author: Lin, Lishi, Houwink, Aletta P. I., van Dieren, Jolanda M., Wolthuis, Esther K., van Thienen, Johannes V., van der Heijden, Michiel S., Haanen, John B. A. G., Beijnen, Jos H., Huitema, Alwin D. R., Lin, Lishi, Houwink, Aletta P. I., van Dieren, Jolanda M., Wolthuis, Esther K., van Thienen, Johannes V., van der Heijden, Michiel S., Haanen, John B. A. G., Beijnen, Jos H., and Huitema, Alwin D. R.
Abstract: IntroductionSevere immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective study, we determined the incidence, treatment patterns and survival outcomes of this patient population at a comprehensive cancer center.MethodsAll patients admitted to the ICU due to irAEs from ICI treatment between January 2015 and July 2022 were included. Descriptive statistics were reported on patient characteristics and treatment patterns during hospital admission. Overall survival (OS) from the time of ICU discharge to death was estimated using the Kaplan-Meier method.ResultsOver the study period, 5561 patients received at least one ICI administration, of which 32 patients (0.6%) were admitted to the ICU due to irAEs. Twenty patients were treated with anti-PD-1 plus anti-CTLA-4 treatment, whereas 12 patients were treated with ICI monotherapy. The type of irAEs were de novo diabetes-related ketoacidosis (n = 8), immune-related gastrointestinal toxicity (n = 8), myocarditis or myositis (n = 10), nephritis (n = 3), pneumonitis (n = 2), and myelitis (n = 1). The median duration of ICU admission was 3 days (interquartile range: 2-6 days). Three patients died during ICU admission. The median OS of the patients who were discharged from the ICU was 18 months (95% confidence interval, 5.0-NA).ConclusionThe incidence of irAEs leading to ICU admission in patients treated with ICI was low in this study. ICU mortality due to irAEs was low and a subset of this patient population even had long-term survival.
Published: 2024

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

Author: MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y F L, Boers-Sonderen, Marye J, Stokkel, Marcel P M, de Wit-van der Veen, Linda J, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, Fischer, Jitha, Boellaard, Ronald, de Vos, Filip Y F L, Boers-Sonderen, Marye J, Stokkel, Marcel P M, de Wit-van der Veen, Linda J, and Haanen, John B A G
Published: 2024

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

Author: MS Medische Oncologie, Cancer, Infection & Immunity, Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A J M van den, Haanen, John B, Aarts, Maureen J B, Berkmortel, Franchette W P J van den, Blank, Christiaan U, Boers-Sonderen, Marye J, Groot, Jan Willem B de, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, A M, Veldt, Astrid A M van der, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, Kapiteijn, Ellen, MS Medische Oncologie, Cancer, Infection & Immunity, Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A J M van den, Haanen, John B, Aarts, Maureen J B, Berkmortel, Franchette W P J van den, Blank, Christiaan U, Boers-Sonderen, Marye J, Groot, Jan Willem B de, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, Stevense-den Boer, A M, Veldt, Astrid A M van der, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn P M, and Kapiteijn, Ellen
Published: 2024

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

Author: Cancer, MS Medische Oncologie, Medisch Oncologische Disciplines, Pathologie Pathologen staf, Infection & Immunity, 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., Suijkerbuijk, Karijn P.M., Wouters, Michel W.J.M., Cancer, MS Medische Oncologie, Medisch Oncologische Disciplines, Pathologie Pathologen staf, Infection & Immunity, 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., Suijkerbuijk, Karijn P.M., and Wouters, Michel W.J.M.
Published: 2024

5. Long-Term Survival in Patients With Advanced Melanoma

Author: MS Medische Oncologie, Cancer, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Groningen, University, Bloem, Manja, 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 J W B, Jan Willem, Hospers, Geke A P, Kapiteijn, Ellen, Leeneman, Brenda, D, Piersma, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil G, Gerard, Wouters, Michel W J M, Blokx, Willeke A M, Suijkerbuijk, Karijn P M, MS Medische Oncologie, Cancer, Pathologie Pathologen staf, Infection & Immunity, van Not, Olivier J, van den Eertwegh, Alfons J M, Groningen, University, Bloem, Manja, 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 J W B, Jan Willem, Hospers, Geke A P, Kapiteijn, Ellen, Leeneman, Brenda, D, Piersma, Stevense-den Boer, Marion, van der Veldt, Astrid A M, Vreugdenhil G, Gerard, Wouters, Michel W J M, Blokx, Willeke A M, and Suijkerbuijk, Karijn P M
Published: 2024

6. A proof-of-concept study of sequential treatment with the HDAC inhibitor vorinostat following BRAF and MEK inhibitors in BRAFV600mutated melanoma

Author: Apotheek O&O&O, Cancer, Embaby, Alaa, Huijberts, Sanne C F A, Wang, Liqin, Leite de Oliveira, Rodrigo, Rosing, Hilde, Nuijen, Bastiaan, Sanders, Joyce, Hofland, Ingrid, van Steenis, Charlaine, Kluin, Roelof J C, Lieftink, Cor, Smith, Christopher G, Blank, Christian U, van Thienen, Johannes V, Haanen, John B A G, Steeghs, Neeltje, Opdam, Frans L, Beijnen, Jos H, Huitema, Alwin D R, Bernards, Rene, Schellens, Jan H M, Wilgenhof, Sofie, Apotheek O&O&O, Cancer, Embaby, Alaa, Huijberts, Sanne C F A, Wang, Liqin, Leite de Oliveira, Rodrigo, Rosing, Hilde, Nuijen, Bastiaan, Sanders, Joyce, Hofland, Ingrid, van Steenis, Charlaine, Kluin, Roelof J C, Lieftink, Cor, Smith, Christopher G, Blank, Christian U, van Thienen, Johannes V, Haanen, John B A G, Steeghs, Neeltje, Opdam, Frans L, Beijnen, Jos H, Huitema, Alwin D R, Bernards, Rene, Schellens, Jan H M, and Wilgenhof, Sofie
Published: 2024

7. 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., Suijkerbuijk, Karijn P. M., Wouters, Michel W. J. M., 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., Suijkerbuijk, Karijn P. M., and Wouters, Michel W. J. M.
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.
Published: 2024

8. Long-Term Survival in Patients With Advanced Melanoma

Author: van Not, Olivier J., van den Eertwegh, Alfons J.M., Jalving, Hilde, Bloem, Manja, 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 J W B, Jan Willem, Hospers, Geke A.P., Kapiteijn, Ellen, Leeneman, Brenda, D, Piersma, Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Vreugdenhil G, Gerard, Wouters, Michel W.J.M., Blokx, Willeke A.M., Suijkerbuijk, Karijn P.M., van Not, Olivier J., van den Eertwegh, Alfons J.M., Jalving, Hilde, Bloem, Manja, 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 J W B, Jan Willem, Hospers, Geke A.P., Kapiteijn, Ellen, Leeneman, Brenda, D, Piersma, Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Vreugdenhil G, Gerard, Wouters, Michel W.J.M., Blokx, Willeke A.M., and Suijkerbuijk, Karijn P.M.
Abstract: IMPORTANCE: Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival. OBJECTIVE: To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023. EXPOSURES: Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab. MAIN OUTCOMES AND MEASURES: Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR).RESULTS: A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69). CONCLUSIONS AND RELEVANCE: This cohort study of
Published: 2024

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

Author: Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A. J.M.van den, Haanen, John B., Aarts, Maureen J.B., Berkmortel, Franchette W.P.J.van den, Blank, Christiaan U., Boers-Sonderen, Marye J., Groot, Jan Willem B.de, Hospers, Geke A.P., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, A. M., Veldt, Astrid A.M.van der, Vreugdenhil, Gerard, Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., Kapiteijn, Ellen, Rauwerdink, Daan Jan Willem, Not, Olivier van, de Meza, Melissa, Doorn, Remco van, Hage, Jos van der, Eertwegh, A. J.M.van den, Haanen, John B., Aarts, Maureen J.B., Berkmortel, Franchette W.P.J.van den, Blank, Christiaan U., Boers-Sonderen, Marye J., Groot, Jan Willem B.de, Hospers, Geke A.P., Piersma, Djura, van Rijn, Rozemarijn S., Stevense-den Boer, A. M., Veldt, Astrid A.M.van der, Vreugdenhil, Gerard, Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., and Kapiteijn, Ellen
Abstract: Introduction: 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. Methods: 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. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in a
Published: 2024

10. 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

11. 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

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

Author: MS Medische Oncologie, Cancer, Infection & Immunity, CMM Groep Van Mil, Leek, Lindsay V M, Notohardjo, Jessica C L, de Joode, Karlijn, Velker, Eline L, Haanen, John B A G, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, de Groot, Jan Willem B, Kapiteijn, Ellen, van den Berkmortel, Franchette W P J, Westgeest, Hans M, de Gruijl, Tanja D, Retel, Valesca P, Cuppen, Edwin, van der Veldt, Astrid A M, Labots, Mariette, Voest, Emile E, van de Haar, Joris, van den Eertwegh, Alfons J M, MS Medische Oncologie, Cancer, Infection & Immunity, CMM Groep Van Mil, Leek, Lindsay V M, Notohardjo, Jessica C L, de Joode, Karlijn, Velker, Eline L, Haanen, John B A G, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, de Groot, Jan Willem B, Kapiteijn, Ellen, van den Berkmortel, Franchette W P J, Westgeest, Hans M, de Gruijl, Tanja D, Retel, Valesca P, Cuppen, Edwin, van der Veldt, Astrid A M, Labots, Mariette, Voest, Emile E, van de Haar, Joris, and van den Eertwegh, Alfons J M
Published: 2024

13. 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

14. Cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: prospective real-world data from the DRUG Access Protocol

Author: MS Medische Oncologie, Cancer, Verkerk, Karlijn, Geurts, Birgit S, Zeverijn, Laurien J, van der Noort, Vincent, Verheul, Henk M W, Haanen, John B A G, van der Veldt, Astrid A M, Eskens, Ferry A L M, Aarts, Maureen J B, van Herpen, Carla M L, Jalving, Mathilde, Gietema, Jourik A, Devriese, Lot A, Labots, Mariette, Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar, Smit, Egbert F, Bloemendal, Haiko J, MS Medische Oncologie, Cancer, Verkerk, Karlijn, Geurts, Birgit S, Zeverijn, Laurien J, van der Noort, Vincent, Verheul, Henk M W, Haanen, John B A G, van der Veldt, Astrid A M, Eskens, Ferry A L M, Aarts, Maureen J B, van Herpen, Carla M L, Jalving, Mathilde, Gietema, Jourik A, Devriese, Lot A, Labots, Mariette, Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar, Smit, Egbert F, and Bloemendal, Haiko J
Published: 2024

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

Author: MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, Haanen, John B A G, MS Medische Oncologie, Brain, Cancer, van der Hiel, Bernies, Aalbersberg, Else A, van den Eertwegh, Alfons J M, de Wit-van der Veen, Linda J, Stokkel, Marcel P M, Lopez-Yurda, Marta, Boellaard, Ronald, Kapiteijn, Ellen W, Hospers, Geke A P, Aarts, Maureen J B, de Vos, Filip Y F L, Boers-Sonderen, Marye J, van der Veldt, Astrid A M, de Groot, Jan Willem B, and Haanen, John B A G
Published: 2024

16. 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

17. 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

18. 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

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

Author: Not, Olivier J. van, Eertwegh, Alfons J. van den, Haanen, John B., Rijn, R.S. van, Aarts, M.J., Berkmortel, Franchette, Boers-Sonderen, M.J., Suijkerbuijk, Karijn P.M., Blokx, Willeke A.M., Not, Olivier J. van, Eertwegh, Alfons J. van den, Haanen, John B., Rijn, R.S. van, Aarts, M.J., Berkmortel, Franchette, Boers-Sonderen, M.J., Suijkerbuijk, Karijn P.M., and Blokx, Willeke A.M.
Abstract: Item does not contain fulltext
Published: 2023

20. 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

21. 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., Blokx, Willeke A.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., 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.
Abstract: 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. Progression-free survival (PFS) and melanoma-specific survival (MSS) were analysed for patients with HM (HM+) and without HM (HM−). A cox model was used to account for confounders associated with PFS and MSS. Results: In total, 4638 advanced melanoma patients received first-line anti-PD-1 monotherapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated patients, the median PFS was 2.8 months for HM+ and 9.9 months for HM− (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM− (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HRadj 1.62; 95% confidence interval [95% CI] 1.15–2.29; p = 0.006) and melanoma-related death (HRadj 1.74; 95% CI 1.09–2.78; p = 0.020). Median PFS and MSS for first-line BRAF(/MEK-) inhibitor-treated HM+ and HM− patients were not significantly different. Conclusions: Patients with HM and advanced melanoma show significantly worse melanoma-related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM.
Published: 2023

22. 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

23. 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

24. 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

25. 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., de Wreede, Liesbeth C., 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.
Abstract: Introduction: When analysing patient survival, one is often interested in cause of death. Little is known about the presence of population mortality in advanced melanoma patients. The aim of this study was to assess population mortality after different response states in advanced melanoma patients in the Netherlands, and analyse the contribution of disease and population mortality for different age groups. Methods: We selected patients diagnosed between 2013 and 2019 with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry. A multi-state model with response states integrating population mortality was fitted. One-year landmark analyses were performed to assess outcomes after each response state. Results: Overall, 5119 patients were selected. Five-year probabilities of melanoma-related mortality in patients alive in complete response at one year after diagnosis increased with age, and was 17.2% (95% confidence interval: 13.0–21.4) for patients aged <65 years and 28.7% (95% confidence interval: 24.3–33.1) in patients aged ≥80 years. Population mortality only played a large role for older patients (75 years and above) alive at 1 year after diagnosis with a partial or complete response. Conclusion: Even though survival outcomes of advanced melanoma patients have improved over the last decade, the vast majority of patients still die due to melanoma-related mortality.
Published: 2023

26. 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

27. 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

28. 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

29. 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

30. 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

31. Failure to validate existing clinical prediction scale for response to PD-1 monotherapy in advanced melanoma in national cohort study

Author: MS Medische Oncologie, Cancer, Infection & Immunity, van der Kooij, Monique K, Joosse, Arjen, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, Dekkers, Olaf M, Kapiteijn, Ellen, MS Medische Oncologie, Cancer, Infection & Immunity, van der Kooij, Monique K, Joosse, Arjen, Suijkerbuijk, Karijn P M, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, van den Eertwegh, Alfonsus J M, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, Dekkers, Olaf M, and Kapiteijn, Ellen
Published: 2023

32. ASO Visual Abstract: Is a History of Optimal Staging by SLNB in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author: Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, van Akkooi, Alexander C J, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, and van Akkooi, Alexander C J
Published: 2023

33. Is a History of Optimal Staging by Sentinel Lymph Node Biopsy in the Era Prior to Adjuvant Therapy Associated with Improved Outcome Once Melanoma Patients have Progressed to Advanced Disease?

Author: Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, van Akkooi, Alexander C J, Pathologie Pathologen staf, Cancer, MS Medische Oncologie, Infection & Immunity, Blankenstein, Stephanie A, Bonenkamp, Johannes J, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Blokx, Willeke A M, Boers-Sonderen, Marye J, van den Eertwegh, Alfons J M, Franken, Margreet G, de Groot, Jan Willem B, Haanen, John B A G, Hospers, Geke A P, Kapiteijn, Ellen W, van Not, Olivier J, Piersma, Djura, van Rijn, Rozemarijn S, Suijkerbuijk, Karijn P M, van der Veldt, Astrid A M, Vreugdenhil, Gerard, Westgeest, Hans M, Wouters, Michel W J M, and van Akkooi, Alexander C J
Published: 2023

34. Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Author: Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, Wouters, Michel W J M, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, and Wouters, Michel W J M
Abstract: Recent results of patients with advanced melanoma treated with first-line BRAF-MEK inhibitors in clinical trials showed 5-year survival in one-third of patients with a median overall survival (OS) of more than 2 years. This study aimed to investigate these patients' real-world survival and identify the characteristics of long-term survivors. The study population consisted of patients with advanced cutaneous melanoma with a BRAF-V600 mutated tumor who were treated with first-line BRAF-MEK inhibitors between 2013 and 2017. Long-term survival was defined as a minimum OS of 2 years from start therapy. The median progression-free survival (mPFS) and median OS (mOS) of real-world patients ( n = 435) were respectively 8.0 (95% CI, 6.8-9.4) and 11.7 (95% CI, 10.3-13.5) months. Two-year survival was reached by 28% of the patients, 22% reached 3-year survival and 19% reached 4-year survival. Real-world patients often had brain metastases (41%), stage IV M1c disease (87%), ECOG PS ≥2 (21%), ≥3 organ sites (62%) and elevated LDH of ≥250 U/I (49%). Trial-eligible real-world patients had an mOS of 17.9 months. Patients surviving more than 2 years ( n = 116) more often had an ECOG PS ≤1 (83%), normal LDH (60%), no brain metastases (60%), no liver metastases (63%) and <3 organ sites (60%). Long-term survival of real-world patients treated with first-line BRAF-MEK inhibitors is significantly lower than that of trial patients, which is probably explained by poorer baseline characteristics of patients treated in daily practice. Long-term survivors generally had more favorable characteristics with regard to age, LDH level and metastatic sites, compared to patients not reaching long-term survival.
Published: 2022

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

Author: Not, Olivier J. van, Meza, Melissa M. de, Eertwegh, A.J. van den, Haanen, John B., Blank, Christian U., Aarts, M.J., Bonenkamp, H., Boers-Sonderen, M.J., Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., Not, Olivier J. van, Meza, Melissa M. de, Eertwegh, A.J. van den, Haanen, John B., Blank, Christian U., Aarts, M.J., Bonenkamp, H., Boers-Sonderen, M.J., Wouters, Michel W.J.M., and Suijkerbuijk, Karijn P.M.
Abstract: Item does not contain fulltext
Published: 2022

36. Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, Wouters, Michel W J M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, and Wouters, Michel W J M
Published: 2022

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

Author: Breeschoten, Jesper van, Ismail, Rawa K., Wouters, Michel W.J.M., Hilarius, Doranne L., Wreede, Liesbeth C. de, Haanen, John B., Boers-Sonderen, M.J., Suijkerbuijk, Karijn P.M., Eertwegh, Alfons J. van den, Breeschoten, Jesper van, Ismail, Rawa K., Wouters, Michel W.J.M., Hilarius, Doranne L., Wreede, Liesbeth C. de, Haanen, John B., Boers-Sonderen, M.J., Suijkerbuijk, Karijn P.M., and Eertwegh, Alfons J. van den
Abstract: Item does not contain fulltext
Published: 2022

38. Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry

Author: Rauwerdink, Daan, Doorn, Remco van, Hage, Jos van der, Eertwegh, Alfons J. van den, Haanen, John B. A. G., Aarts, M.J., Boers-Sonderen, M.J., Kooij, M.K. van der, Kapiteijn, E., Rauwerdink, Daan, Doorn, Remco van, Hage, Jos van der, Eertwegh, Alfons J. van den, Haanen, John B. A. G., Aarts, M.J., Boers-Sonderen, M.J., Kooij, M.K. van der, and Kapiteijn, E.
Abstract: Item does not contain fulltext
Published: 2022

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

Author: Not, Olivier J. van, Meza, Melissa M. de, Eertwegh, A.J. van den, Haanen, John B., Blank, Christian U., Aarts, M.J., Bonenkamp, H., Boers-Sonderen, M.J., Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., Not, Olivier J. van, Meza, Melissa M. de, Eertwegh, A.J. van den, Haanen, John B., Blank, Christian U., Aarts, M.J., Bonenkamp, H., Boers-Sonderen, M.J., Wouters, Michel W.J.M., and Suijkerbuijk, Karijn P.M.
Abstract: Contains fulltext : 250273.pdf (Publisher’s version ) (Open Access)
Published: 2022

40. Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, Wouters, Michel W J M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, and Wouters, Michel W J M
Published: 2022

41. Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma: A Nation-Wide Study of the Dutch Melanoma Treatment Registry

Author: Rauwerdink, Daan, Doorn, Remco van, Hage, Jos van der, Eertwegh, Alfons J. van den, Haanen, John B. A. G., Aarts, M.J., Boers-Sonderen, M.J., Kooij, M.K. van der, Kapiteijn, E., Rauwerdink, Daan, Doorn, Remco van, Hage, Jos van der, Eertwegh, Alfons J. van den, Haanen, John B. A. G., Aarts, M.J., Boers-Sonderen, M.J., Kooij, M.K. van der, and Kapiteijn, E.
Abstract: Contains fulltext : 285926.pdf (Publisher’s version ) (Open Access)
Published: 2022

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

Author: Not, Olivier J. van, Meza, Melissa M. de, Eertwegh, A.J. van den, Haanen, John B., Blank, Christian U., Aarts, M.J., Bonenkamp, H., Boers-Sonderen, M.J., Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., Not, Olivier J. van, Meza, Melissa M. de, Eertwegh, A.J. van den, Haanen, John B., Blank, Christian U., Aarts, M.J., Bonenkamp, H., Boers-Sonderen, M.J., Wouters, Michel W.J.M., and Suijkerbuijk, Karijn P.M.
Abstract: Contains fulltext : 250273.pdf (Publisher’s version ) (Open Access)
Published: 2022

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

Author: Breeschoten, Jesper van, Ismail, Rawa K., Wouters, Michel W.J.M., Hilarius, Doranne L., Wreede, Liesbeth C. de, Haanen, John B., Boers-Sonderen, M.J., Suijkerbuijk, Karijn P.M., Eertwegh, Alfons J. van den, Breeschoten, Jesper van, Ismail, Rawa K., Wouters, Michel W.J.M., Hilarius, Doranne L., Wreede, Liesbeth C. de, Haanen, John B., Boers-Sonderen, M.J., Suijkerbuijk, Karijn P.M., and Eertwegh, Alfons J. van den
Abstract: Item does not contain fulltext
Published: 2022

44. Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, Wouters, Michel W J M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, and Wouters, Michel W J M
Published: 2022

45. Long-term survival of patients with advanced melanoma treated with BRAF-MEK inhibitors

Author: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, PECP - Centre for Pharmacoepidemiology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, Wouters, Michel W J M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, PECP - Centre for Pharmacoepidemiology, Ismail, Rawa K, Suijkerbuijk, Karijn P M, de Boer, Anthonius, van Dartel, Maaike, Hilarius, Doranne L, Pasmooij, Anna M J, van Zeijl, Michiel C T, Aarts, Maureen J B, van den Berkmortel, Franchette W P J, Blank, Christian U, Boers-Sonderen, Marye J, de Groot, Jan W B, Haanen, John B, Hospers, Geke A P, Kapiteijn, Ellen, Piersma, Djura, van Rijn, Rozemarijn S, van der Veldt, Astrid A M, Vreugdenhil, Art, Westgeest, Hans, van den Eertwegh, Alfons J, and Wouters, Michel W J M
Published: 2022

46. 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

47. 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

48. 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, van den Eertwegh, Alfons J M, 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
Abstract: 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.METHODS: We selected patients who were diagnosed with unresectable IIIC or stage IV melanoma, registered in the Dutch Melanoma Treatment Registry, and died between 2013 and 2019. Primary outcome was the probability of starting a new systemic therapy 45 and 90 days before death. Secondary outcomes were type of systemic therapy started, grade 3/4 adverse events (AEs), and the total costs of systemic therapies.RESULTS: Between 2013 and 2019, 3,797 patients with unresectable IIIC or stage IV melanoma were entered in the registry and died. The percentage of patients receiving a new systemic therapy within 45 and 90 days before death was significantly different between Dutch melanoma centers (varying from 6% to 23% and 20% to 46%, respectively). Thirteen percent of patients (n = 146) developed grade 3/4 AEs in the last period before death. The majority of patients with an AE required hospital admission (n = 102, 69.6%). Mean total costs of systemic therapy per cohort year of the patients who received a new systemic therapy within 90 days before death were 2.3%-2.8% of the total costs spent on melanoma therapies.CONCLUSION: The minority of Dutch patients with metastatic melanoma started a new systemic therapy in the last phase of life. However, the percentages varied between Dutch melanoma centers. Financial impact of these therapies in the last phase of life is relatively small.
Published: 2022

49. Clinical advances and ongoing trials on mRNA vaccines for cancer treatment

Author: Lorentzen, Cathrine Lund, Haanen, John B., Met, Özcan, Svane, Inge Marie, Lorentzen, Cathrine Lund, Haanen, John B., Met, Özcan, and Svane, Inge Marie
Abstract: Years of research exploring mRNA vaccines for cancer treatment in preclinical and clinical trials have set the stage for the rapid development of mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and the inherent advantage in ease of production, which rivals the best available conventional vaccine manufacture methods, renders mRNA vaccines a promising option for cancer immunotherapy. Technological advances have optimised mRNA-based vaccine stability, structure, and delivery methods, and multiple clinical trials investigating mRNA vaccine therapy are now enrolling patients with various cancer diagnoses. Although therapeutic mRNA-based cancer vaccines have not yet been approved for standard treatment, encouraging results from early clinical trials with mRNA vaccines as monotherapy and in combination with checkpoint inhibitors have been obtained. This Review summarises the latest clinical advances in mRNA-based vaccines for cancer treatment and reflects on future perspectives and challenges for this new and promising treatment approach.
Published: 2022

50. Systemic Therapy in Advanced Nodular Melanoma versus Superficial Spreading Melanoma:A Nation-Wide Study of the Dutch Melanoma Treatment Registry

Author: Rauwerdink, Daan Jan Willem, van Doorn, Remco, van der Hage, Jos, Van den Eertwegh, Alfonsus J M, Haanen, John B A G, Aarts, Maureen, Berkmortel, Franchette, Blank, Christian U, Boers-Sonderen, Marye J, De Groot, Jan Willem B, Hospers, Geke A P, de Meza, Melissa, Piersma, Djura, Van Rijn, Rozemarijn S, Stevense, Marion, Van der Veldt, Astrid, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn, van der Kooij, Monique, Kapiteijn, Ellen, Rauwerdink, Daan Jan Willem, van Doorn, Remco, van der Hage, Jos, Van den Eertwegh, Alfonsus J M, Haanen, John B A G, Aarts, Maureen, Berkmortel, Franchette, Blank, Christian U, Boers-Sonderen, Marye J, De Groot, Jan Willem B, Hospers, Geke A P, de Meza, Melissa, Piersma, Djura, Van Rijn, Rozemarijn S, Stevense, Marion, Van der Veldt, Astrid, Vreugdenhil, Gerard, Wouters, Michel W J M, Suijkerbuijk, Karijn, van der Kooij, Monique, and Kapiteijn, Ellen
Abstract: 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. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7–4.2) compared with SSM patients at 3.1 years (CI 95% 1.3–6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85–1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81–1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis.
Published: 2022

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