Multicenter Study

. 2025 Jun 1;117(6):1245-1252.

doi: 10.1093/jnci/djaf039.

Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study

Mark Schuiveling¹, Laurens S Ter Maat², Isabella A J Van Duin¹, Rik J Verheijden^{1

3}, Max F Troenokarso¹, Pim Moeskops⁴, Joost J C Verhoeff⁵, Sjoerd G Elias³, Wouter A C van Amsterdam⁶, Femke Burgers⁷, Franchette W P J Van den Berkmortel⁸, Marye J Boers-Sonderen⁹, Martijn F Boomsma¹⁰, Jan Willem De Groot¹¹, John B A G Haanen^{7

12

13}, Geke A P Hospers¹⁴, Djura Piersma¹⁵, Gerard Vreugdenhil¹⁶, Hans M Westgeest¹⁷, Ellen Kapiteijn¹², Mariette Labots¹⁸, Wouter B Veldhuis^{4

19}, Paul J Van Diest²⁰, Pim A De Jong¹⁹, Josien P W Pluim^{2

21}, Tim Leiner^{4

22}, Mitko Veta²¹, Karijn P M Suijkerbuijk¹

Affiliations

¹ Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
² Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Quantib (currently DeepHealth), Rotterdam, The Netherlands.
⁵ Department of Radiotherapy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Department of Data Science and Biostatistics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷ Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁸ Department of Medical Oncology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
⁹ Department of Medical Oncology, Radboudumc, Radboud University, Nijmegen, The Netherlands.
¹⁰ Department of Radiology, Isala Zwolle, Zwolle, The Netherlands.
¹¹ Isala Oncology Center, Isala Zwolle, Zwolle, The Netherlands.
¹² Department of Medical Oncology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
¹³ Melanoma Clinic, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
¹⁴ Department of Medical Oncology, UMC Groningen, University of Groningen, Groningen, The Netherlands.
¹⁵ Department of Medical Oncology, Medisch Spectrum Twente, Enschede, The Netherlands.
¹⁶ Department of Medical Oncology, Maxima Medical Center, Veldhoven, The Netherlands.
¹⁷ Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands.
¹⁸ Department of Medical Oncology, UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
¹⁹ Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
²⁰ Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
²¹ Medical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
²² Department of Radiology, Mayo Clinical, Rochester, MN, United States.

PMID: 39980388
PMCID: PMC12145918
DOI: 10.1093/jnci/djaf039

Multicenter Study

Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study

Mark Schuiveling et al. J Natl Cancer Inst. 2025.

. 2025 Jun 1;117(6):1245-1252.

doi: 10.1093/jnci/djaf039.

Authors

Affiliations

¹ Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
² Image Sciences Institute, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁴ Quantib (currently DeepHealth), Rotterdam, The Netherlands.
⁵ Department of Radiotherapy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁶ Department of Data Science and Biostatistics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷ Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁸ Department of Medical Oncology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
⁹ Department of Medical Oncology, Radboudumc, Radboud University, Nijmegen, The Netherlands.
¹⁰ Department of Radiology, Isala Zwolle, Zwolle, The Netherlands.
¹¹ Isala Oncology Center, Isala Zwolle, Zwolle, The Netherlands.
¹² Department of Medical Oncology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
¹³ Melanoma Clinic, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
¹⁴ Department of Medical Oncology, UMC Groningen, University of Groningen, Groningen, The Netherlands.
¹⁵ Department of Medical Oncology, Medisch Spectrum Twente, Enschede, The Netherlands.
¹⁶ Department of Medical Oncology, Maxima Medical Center, Veldhoven, The Netherlands.
¹⁷ Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands.
¹⁸ Department of Medical Oncology, UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
¹⁹ Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
²⁰ Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
²¹ Medical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
²² Department of Radiology, Mayo Clinical, Rochester, MN, United States.

PMID: 39980388
PMCID: PMC12145918
DOI: 10.1093/jnci/djaf039

Abstract

Background: The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to investigate body mass index (BMI) alongside computed tomography (CT)-derived body composition metrics in the largest cohort to date.

Methods: Patients treated with first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma centers in The Netherlands. From baseline CT scans, 5 body composition metrics were extracted: subcutaneous adipose tissue index, visceral adipose tissue index, skeletal muscle index, density, and gauge. These metrics were correlated in univariable and multivariable Cox proportional hazards analysis with progression-free survival, overall survival, and melanoma-specific survival (PFS, OS, and MSS).

Results: A total of 1471 eligible patients were included. Median PFS and OS were 9.1 and 38.1 months, respectively. Worse PFS was observed in underweight patients (multivariable hazard ratio [HR] = 1.86, 95% CI = 1.14 to 3.06). Furthermore, prolonged OS was observed in patients with higher skeletal muscle density (multivariable HR = 0.88, 95% CI = 0.81 to 0.97) and gauge (multivariable HR = 0.61, 95% CI = 0.82 to 0.998), whereas higher visceral adipose tissue index was associated with worse OS (multivariable HR = 1.12, 95% CI = 1.04 to 1.22). No association with survival outcomes was found for overweight, obesity, or subcutaneous adipose tissue.

Conclusion: Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with improved OS. These associations were independent of known prognostic factors, including sex, age, performance status, and extent of disease. No significant association between higher BMI and survival outcomes was observed.

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Conflict of interest statement

J.B.A.G.H. has served on advisory boards for Achilles Tx, BioNTech, BMS, CureVac, GSK, Imcyse, Immunocore, Instil Bio, Iovance Bio, Merck Serono, MSD, Molecular Partners, Neogene Tx, Novartis, Pfizer, PokeAcell, Roche/Genentech, Sanofi, Sastra Cell Therapy, Scenic, T-Knife, and TRV; has received grant support from Asher Bio, Amgen, BMS, BioNTech, MSD, Novartis, and Sastra Cell Therapy; and owns stock options in Neogene Tx and Sastra Cell Therapy. J.W.D.G. has consultancy/advisory relationships with Bristol Myers Squibb, Pierre Fabre, Servier, MSD, and Novartis. G.A.P.H. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Novartis, Sanofi, Pierre Fabre and has received research grants from Bristol-Myers Squibb, and Seerave. P.A.D.J. has a research collaboration with Philips Healthcare. M.J.B.-S. has consultancy/advisory relationships with Pierre Fabre, MSD, and Novartis. E.K. has consultancy/advisory relationships with Bristol Myers Squibb, Delcath, and Lilly, and received research grants not related to this article from Bristol Myers Squibb, Delcath, Novartis, and Pierre Fabre. All paid to the institution. P.J.V.D. has consultancy/advisory relationships with Paige, Visiopharm, Sectra, Pantarei, and Samantree paid to the institution and research grants from Pfizer, none related to current work and paid to the institute. K.P.M.S. has advisory relationships with Pierre Fabre, AbbVie, and Sairopa and received research funding from Bristol Myers Squibb, TigaTx, Philips and Genmab. T.L. has received research funding from Philips. P.M. is employed at Quantib. D.P. has advisory relationships with Novartis, Pierre Fabre en BMS and honorarium for lecturing from Novartis. Not related to current work. All remaining authors have declared no conflicts of interest.

Figures

**Figure 1.**
Definition of the included predictors and evaluated models.

**Figure 2.**
Kaplan-Meier curves for progression-free and overall survival in patients treated with immune checkpoint inhibition for advanced melanoma according to BMI subgroup. Abbreviation: BMI = body mass index.

See this image and copyright information in PMC

References

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1. Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al.Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol. 2022;40:127-137. - PMC - PubMed
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Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study

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Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study

Authors

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Conflict of interest statement

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