Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model

Ibtissam Acem; Ewout W Steyerberg; Marta Spreafico; Dirk J Grünhagen; Dario Callegaro; Robert J Spinner; Courtney Pendleton; J Henk Coert; Rosalba Miceli; Giulia Abruzzese; Uta E Flucke; Willem-Bart M Slooff; Thijs van Dalen; Lukas B Been; Han J Bonenkamp; Monique H M E Anten; Martinus P G Broen; Marc H A Bemelmans; Jos A M Bramer; Gerard R Schaap; Arthur J Kievit; Jos van der Hage; Winan J van Houdt; Michiel A J van de Sande; Alessandro Gronchi; Cornelis Verhoef; Enrico Martin

doi:10.1093/noajnl/vdae083

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model

Neurooncol Adv. 2024 Jun 5;6(1):vdae083. doi: 10.1093/noajnl/vdae083. eCollection 2024 Jan-Dec.

Authors

Ibtissam Acem^{1

2}, Ewout W Steyerberg³, Marta Spreafico⁴, Dirk J Grünhagen¹, Dario Callegaro⁵, Robert J Spinner⁶, Courtney Pendleton⁷, J Henk Coert⁸, Rosalba Miceli⁹, Giulia Abruzzese⁵, Uta E Flucke¹⁰, Willem-Bart M Slooff¹¹, Thijs van Dalen¹, Lukas B Been¹², Han J Bonenkamp¹³, Monique H M E Anten¹⁴, Martinus P G Broen¹⁴, Marc H A Bemelmans¹⁵, Jos A M Bramer¹⁶, Gerard R Schaap¹⁶, Arthur J Kievit¹⁶, Jos van der Hage¹⁷, Winan J van Houdt¹⁸, Michiel A J van de Sande², Alessandro Gronchi⁵, Cornelis Verhoef¹, Enrico Martin⁸

Affiliations

¹ Department of Surgical Oncology and Gastrointestinal Surgery,Erasmus MC Cancer Institute, >Rotterdam, The Netherlands.
² Department of Orthopedic Oncology, Leiden University Medical Centre, >Leiden, The Netherlands.
³ Department of Biomedical Data Sciences, Leiden University Medical Centre, >Leiden, The Netherlands.
⁴ Department of Medical Statistics, Mathematical Institute, Leiden University, >Leiden, The Netherlands.
⁵ Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, >Milan, Italy.
⁶ Department of Neurosurgery, Mayo Clinic, >Rochester, Minnesota, USA.
⁷ Department of Neurosurgery, Stony Brook University School of Medicine, Stony Brook, New York, USA.
⁸ Department of Reconstructive Surgery, University Medical Centre Utrecht, >Utrecht, The Netherlands.
⁹ Department of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, >Milan, Italy.
¹⁰ Department of Pathology, Radboud University Medical Centre, >Nijmegen, The Netherlands.
¹¹ Department of Neurosurgery, University Medical Centre Utrecht, >Utrecht, The Netherlands.
¹² Department of Surgical Oncology, University Medical Centre Groningen, Groningen, The Netherlands.
¹³ Department of Surgical Oncology, Radboud University Medical Centre, >Nijmegen, The Netherlands.
¹⁴ Department of Neurology, Maastricht University Medical Centre, >Maastricht, The Netherlands.
¹⁵ Department of Surgical Oncology, Maastricht University Medical Centre, >Maastricht, The Netherlands.
¹⁶ Department of Orthopedic Surgery, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
¹⁷ Department of Surgical Oncology, Leiden University Medical Centre, Leiden, The Netherlands.
¹⁸ Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Abstract

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS).

Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model.

Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions.

Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Keywords: internal–external validation; malignant peripheral nerve sheath tumors; model performance; neurofibromatosis 1; prognosis.