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Multicenter Study
. 2025 Apr 1;8(4):e254689.
doi: 10.1001/jamanetworkopen.2025.4689.

Practice Variation in Perioperative Dexamethasone Use and Outcomes in Brain Metastasis Resection

David Wasilewski  1   2   3 , Tommaso Araceli  4   5 , Artem Rafaelian  6 , Matthias Demetz  7 , Benedikt Asey  8 , Tunc-Faik Ersoy  9 , Alice Dauth  10 , Anne Neumeister  11 , Ricarda Peukert  1 , Paul Pöser  1 , Christopher Krämer  1 , Jan Bukatz  1 , Zoe Shaked  1 , Claudius Jelgersma  1 , Anton Früh  1   12 , Ran Xu  1   12 , Martin Misch  1   2 , David Capper  3   13 , Felix Ehret  3   12   14 , Nikolaj Frost  2   15 , Lars Bullinger  2   3   16 , Ulrich Keilholz  2   3   16 , Christian Senft  11 , Leon Schmidt  10 , Harald Krenzlin  10 , Florian Ringel  10 , Anne Pohrt  17 , Hanno S Meyer  8 , Jens Gempt  8 , Johannes Kerschbaumer  7 , Christian Freyschlag  7 , Claudius Thomé  7 , Matthias Simon  9 , Daniel Dubinski  6 , Thomas Freiman  6 , Nils Ole Schmidt  4   5 , Martin Proescholdt  4   5 , Peter Vajkoczy  1   2 , Julia Onken  1   2   3   12
Affiliations
Multicenter Study

Practice Variation in Perioperative Dexamethasone Use and Outcomes in Brain Metastasis Resection

David Wasilewski et al. JAMA Netw Open. .

Abstract

Importance: Variations in perioperative dexamethasone dosing are common in brain metastasis resection, but their impact on patient outcomes remains unclear.

Objective: To evaluate the association between perioperative dexamethasone dosing and patient outcomes, focusing on overall survival (OS) and progression-free survival (PFS).

Design, setting, and participants: This retrospective multicenter comparative effectiveness study used data collected from January 2010 to December 2023. Patients with symptomatic brain metastases undergoing primary surgical resection at 7 neurological centers in Germany and 1 in Austria and who had complete records of perioperative dexamethasone dosing were included. Propensity score matching (PSM) was used to control for confounders. Analysis was conducted from March to June 2024.

Exposures: Cumulative perioperative dexamethasone administration over 27 days, dichotomized at 122 mg using maximally selected rank statistics.

Main outcomes and measures: The primary outcome was OS. Secondary outcomes included extracranial PFS (ecPFS) and intracranial PFS (icPFS) as well as incidence of wound revision surgery after brain metastasis resection. Hazard ratios (HRs) were calculated using Cox proportional hazards models.

Results: A total of 1064 patients were included in the analysis. The median (IQR) age was 64 (56-72) years, with 489 female patients (49%) and 541 male patients (51%). Non-small cell lung cancer (NSCLC) was the most common tumor entity (564 patients [53%]), followed by breast cancer (146 patients [14%]) and melanoma (138 patients [13%]). After PSM, patients receiving cumulative dexamethasone doses less than 122 mg had a median OS of 19.1 (95% CI, 15.2-22.4) months compared with 12.0 (95% CI, 9.1-14.7) months for those receiving 122 mg or more (P = .002). Multivariable analysis showed an independent association between higher cumulative dexamethasone doses and reduced OS (HR, 1.40; 95% CI, 1.18-1.66; P < .001). Secondary analyses demonstrated consistent findings with icPFS and ecPFS and a dose-response association between cumulative dexamethasone and hazard for death.

Conclusions and relevance: In this study, higher cumulative perioperative dexamethasone was associated with reduced OS, icPFS, and ecPFS in patients undergoing brain metastasis resection. These findings suggest that stricter dosing protocols could improve outcomes. Prospective trials are warranted to confirm these associations and guide evidence-based practice.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Ehret reported receiving grants from German Cancer Aid and Accuray Inc and nonfinancial travel support from ZAP Surgical Systems Inc outside the submitted work. Dr Frost reported receiving personal fees from AbbVie, Amgen, AstraZeneca, BeiGene, BerlinChemie, BMS, Boehringer Ingelheim, Daiichi Sankyo, Janssen Oncology, Eli Lilly and Co, Merck Serono, MSD, Novartis, Pfizer, Roche, Regeneron, and Takeda; nonfinancial travel support from BMS, Janssen Oncology, Roche, and Regeneron; and grants from Roche outside the submitted work. Dr Bullinger reported receiving grants from Bayer and Jazz Pharmaceuticals and receiving personal fees from AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Daiichi Sankyo, Gilead, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Otsuka, Pfizer, Sanofi, and Servier outside the submitted work. Dr Keilholz reported receiving grants from AstraZeneca, personal fees from Merck, and nonfinancial travel support from Novartis outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Estimates for Patient Outcomes Overall and According to the Cut Point for Perioperative Dexamethasone Before Matching
Kaplan-Meier curves and associated risk tables for the total cohort and median overall survival (A), extracranial progression-free survival (B), and intracranial progression-free survival (C). Kaplan-Meier curves and associated risk table displaying median overall survival (D), extracranial progression-free survival (E), and intracranial progression-free survival (F) before matching grouped into low (<122 mg) and high (≥122 mg) doses of dexamethasone. The cutoff of 122 mg was selected via maximally selected rank statistics (eFigure 9 in Supplement 1).
Figure 2.
Figure 2.. Distribution of Propensity Scores and Standardized Mean Differences for Matching Variables
A loveplot displaying the standardized mean differences before (unadjusted in orange) and after propensity score matching (adjusted in blue) of each variable included into matching between treatment groups (A) and distribution of propensity scores (B). ds-GPA indicates disease-specific graded prognostic assessment; and NSCLC, non–small cell lung cancer.
Figure 3.
Figure 3.. Kaplan-Meier Estimates for Patient Outcome by the Cut Point for Perioperative Dexamethasone After Matching
Kaplan-Meier curves and associated risk table displaying median overall survival (A), extracranial progression-free survival (B), and intracranial progression-free survival (C) for the total cohort of patients after matching grouped into low (<122 mg) and high (≥122 mg) doses of dexamethasone. The cutoff of 122 mg was selected via maximally selected rank statistics (eFigure 9 in Supplement 1).
Figure 4.
Figure 4.. Multivariable Cox Regression for Patient Outcome After Matching
Forest plots depict the hazard ratios and 95% CIs for overall survival (OS) (A), extracranial progression-free survival (ecPFS) (B), and intracranial PFS (icPFS) (C) for matched patient data; factors included into these models were dexamethasone dose, based on the 122-mg cut point; tumor volume; edema volume; disease-specific graded prognostic assessment (ds-GPA, dichotomized into GPA ≥2 and <2); presence of underlying other diseases; and type or class of adjuvant (postoperative) therapy.
See this image and copyright information in PMC

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