Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors

Sophie H.A.E. Derks; Li Shen Ho; Stephan R. Koene; Martijn P.A. Starmans; Esther Oomen-De Hoop; Arjen Joosse; Maja J.A. De Jonge; Kishan A.T. Naipal; Joost L.M. Jongen; Martin J. Van Den Bent; Marion Smits; Astrid A.M. Van Der Veldt

doi:10.1093/noajnl/vdaf026

Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors

Sophie H.A.E. Derks, Li Shen Ho, Stephan R. Koene, Martijn P.A. Starmans, Esther Oomen-De Hoop, Arjen Joosse, Maja J.A. De Jonge, Kishan A.T. Naipal, Joost L.M. Jongen, Martin J. Van Den Bent, Marion Smits, Astrid A.M. Van Der Veldt^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background:

Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM.

Methods:

In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively.

Results:

A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥ 4 BMs and 53.7% of patients had at least one BM with a diameter ≥ 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, P < .001). On the patient level, having at least one BM ≥ 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, P < .001).

Conclusions:

Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥ 10 mm.

Original language	English
Article number	vdaf026
Journal	Neuro-Oncology Advances
Volume	7
Issue number	1
DOIs	https://doi.org/10.1093/noajnl/vdaf026
Publication status	Published - 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

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Derks, S. H. A. E., Ho, L. S., Koene, S. R., Starmans, M. P. A., Oomen-De Hoop, E., Joosse, A., De Jonge, M. J. A., Naipal, K. A. T., Jongen, J. L. M., Van Den Bent, M. J., Smits, M., & Van Der Veldt, A. A. M. (2025). Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors. Neuro-Oncology Advances, 7(1), Article vdaf026. https://doi.org/10.1093/noajnl/vdaf026

@article{072a85069ec441f1b86a0395866415b3,

title = "Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors",

abstract = "Background: Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM. Methods: In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively.Results: A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥ 4 BMs and 53.7% of patients had at least one BM with a diameter ≥ 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, P < .001). On the patient level, having at least one BM ≥ 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, P < .001).Conclusions: Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥ 10 mm.",

author = "Derks, {Sophie H.A.E.} and Ho, {Li Shen} and Koene, {Stephan R.} and Starmans, {Martijn P.A.} and {Oomen-De Hoop}, Esther and Arjen Joosse and {De Jonge}, {Maja J.A.} and Naipal, {Kishan A.T.} and Jongen, {Joost L.M.} and {Van Den Bent}, {Martin J.} and Marion Smits and {Van Der Veldt}, {Astrid A.M.}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.",

year = "2025",

doi = "10.1093/noajnl/vdaf026",

language = "English",

volume = "7",

journal = "Neuro-Oncology Advances",

issn = "2632-2498",

publisher = "Oxford University Press",

number = "1",

}

Derks, SHAE, Ho, LS, Koene, SR, Starmans, MPA , Oomen-De Hoop, E , Joosse, A , De Jonge, MJA , Naipal, KAT , Jongen, JLM, Van Den Bent, MJ, Smits, M & Van Der Veldt, AAM 2025, 'Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors', Neuro-Oncology Advances, vol. 7, no. 1, vdaf026. https://doi.org/10.1093/noajnl/vdaf026

TY - JOUR

T1 - Size matters

T2 - Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors

AU - Derks, Sophie H.A.E.

AU - Ho, Li Shen

AU - Koene, Stephan R.

AU - Starmans, Martijn P.A.

AU - Oomen-De Hoop, Esther

AU - Joosse, Arjen

AU - De Jonge, Maja J.A.

AU - Naipal, Kishan A.T.

AU - Jongen, Joost L.M.

AU - Van Den Bent, Martin J.

AU - Smits, Marion

AU - Van Der Veldt, Astrid A.M.

PY - 2025

Y1 - 2025

N2 - Background: Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM. Methods: In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively.Results: A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥ 4 BMs and 53.7% of patients had at least one BM with a diameter ≥ 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, P < .001). On the patient level, having at least one BM ≥ 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, P < .001).Conclusions: Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥ 10 mm.

AB - Background: Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM. Methods: In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively.Results: A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥ 4 BMs and 53.7% of patients had at least one BM with a diameter ≥ 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, P < .001). On the patient level, having at least one BM ≥ 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, P < .001).Conclusions: Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥ 10 mm.

UR - http://www.scopus.com/inward/record.url?scp=86000772193&partnerID=8YFLogxK

U2 - 10.1093/noajnl/vdaf026

DO - 10.1093/noajnl/vdaf026

M3 - Article

C2 - 40051662

AN - SCOPUS:86000772193

SN - 2632-2498

VL - 7

JO - Neuro-Oncology Advances

JF - Neuro-Oncology Advances

IS - 1

M1 - vdaf026

ER -

Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors

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