Dexamethasone Use in Neuro-Oncology: Balancing Efficacy and Toxicity

Dexamethasone Use in Neuro-Oncology: Balancing Efficacy and Toxicity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Dexamethasone Use in Neuro-Oncology: Balancing Efficacy and Toxicity Bunmi Adedotun, Michael Adebayo, Sacha Chiuta, Olatomiwa Olukoya This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7942114/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Corticosteroids are widely used in neuro-oncology, with dexamethasone the preferred option for symptom control. However, optimal dosing remains unclear. This review evaluated high- versus low-dose dexamethasone regimens in adults with brain and spinal tumours. Methods A systematic review was conducted in accordance with PRISMA-P guidelines. Ovid (MEDLINE, Embase, Emcare), PubMed, and the Cochrane Library were searched from inception to July 2025. Eligible studies compared low- with higher-dose regimens in adults with brain or spinal tumours. Outcomes included neurological improvement, adverse effects, and survival. Results From 742 citations, four studies (n = 249) were included: three randomised controlled trials and one retrospective cohort. In brain metastases, low-dose dexamethasone (4–8 mg/day) was as effective as 16 mg/day for short-term functional improvement, while higher doses increased toxicity. The retrospective cohort showed most patients improved within 24–48 hours on modest cumulative doses (~ 17 mg), with no added benefit from higher or prolonged treatment. In metastatic spinal cord compression (MSCC), high- and low-dose dexamethasone regimens achieved comparable neurological and pain outcomes, though higher doses were associated with more adverse events. Conclusions Current evidence suggests low-dose dexamethasone regimens are as effective as high-dose regimens for most patients, while higher doses increase toxicity. As neurological improvement typically occurs within 24–48 hours, prolonged high-dose therapy may offer limited additional value. Further multicentre studies are required to establish optimal dosing, duration, and tapering. Neurosurgery Oncology Brain metastases Corticosteroids Dexamethasone Metastatic spinal cord compression Neuro-oncology Steroid dosing Figures Figure 1 Introduction In the 1950s, Glen E. Arth synthesised dexamethasone, a 16-alpha-methylated analogue of cortisone, initially developed for the treatment of rheumatoid arthritis. Joseph Galicich, then a neurosurgery resident, recognised its potential in neurosurgery and administered it to patients following craniotomy for tumour removal. He observed improvements in paresis, resolution of midline shift, and reduced mortality, prompting clinical trials that established dexamethasone as a cornerstone in neurosurgical care [ 1 ]. Since then, corticosteroids have become integral to neuro-oncology, with most patients with brain tumours receiving them at some point during treatment. However, corticosteroid-related side effects are common and can markedly impair quality of life [ 2 ]. Perilesional oedema, a form of vasogenic oedema resulting from blood–brain barrier disruption and increased vascular permeability, exacerbates tumour mass effect, raises intracranial pressure, and contributes to neurological decline [ 3 ]. Empirical administration of corticosteroids 1–2 days before neurosurgery can reduce oedema, intracranial pressure, and neurological symptoms, but prolonged exposure is associated with significant dose- and duration-dependent adverse effects, including endocrine disturbances, gastric ulcers, steroid-induced diabetes, myopathy, osteoporosis, psychiatric disorders, cataracts, and Cushing’s syndrome [ 4 ]. Dexamethasone, noted for its potent anti-inflammatory and immunosuppressive properties, remains the preferred corticosteroid for reducing neurological symptoms and minimising treatment-related side effects [ 5 ]. It is also widely used in metastatic spinal cord compression (MSCC) to reduce tumour volume and spinal cord swelling, relieve pressure, and improve neurological function [ 6 ]. Despite their routine use during surgery, radiotherapy, and chemotherapy, evidence guiding optimal corticosteroid dosing, duration, and tapering to balance efficacy and toxicity remains limited, with few clinical trials addressing this [ 4 ]. This review explores optimal dexamethasone dosing strategies in patients with brain and spinal tumours, focusing on oedema severity and its impact on outcomes such as symptom relief and surgical success. Methods Study design We conducted a systematic review in accordance with PRISMA-P guidelines to evaluate optimal steroid dosing strategies in adults with brain or spinal tumours, including metastatic spinal cord compression. Our primary outcomes of interest were relief of peritumoural oedema, improvement in neurological symptoms, adverse effects, and overall survival. Eligibility criteria We included full-text, peer-reviewed original studies involving adult patients (≥ 18 years) with primary or metastatic brain or spinal cord tumours, including epidural spinal tumours and metastatic spinal cord compression (MSCC). Eligible studies assessed corticosteroid use (specifically dexamethasone) in adults with brain tumours or spinal tumour, reporting on neurological symptom control, functional outcomes, adverse effects, or survival. We excluded reviews, editorials, letters, conference abstracts, case reports, preprints, animal studies, non-English articles, and studies that did not report dosing strategies or relevant clinical outcomes such as oedema reduction, neurological improvement, surgical readiness, survival, or adverse effects. Search strategy: We systematically searched the following databases from inception to July 2025: Ovid platform (searched 5 July 2025), including Embase, MEDLINE, and Emcare PubMed and Cochrane Library (searched 6 July 2025) We used a combination of MeSH terms and free-text keywords, including: dexamethasone,” “brain tumour,” “spinal tumour,” “epidural spinal tumour,” “metastatic spinal cord compression,” “peritumoral oedema,” “vasogenic oedema,” “glucocorticoid,” “corticosteroid,” “high dose,” “low dose,” “taper,” “brain neoplasm,” “spinal neoplasm,” “brain cancer,” and “spinal cancer. We applied filters to limit results to English-language and human studies. Study selection: Records were deduplicated using Zotero and screened in Rayyan. Two independent reviewers assessed titles and abstracts using predefined eligibility criteria, with disagreements resolved by consensus. Full texts of potentially relevant studies were reviewed for inclusion based on dexamethasone use in adult patients with brain or spinal tumours, including MSCC. Studies had to report dosing strategies and at least one clinical outcome of interest. The selection process followed PRISMA-P guidelines and is summarised in a PRISMA flow diagram. Results Study Selection A total of 742 records were retrieved: 524 from Ovid, 164 from PubMed, and 54 from Cochrane Library Initial deduplication in Zotero removed 91 records, leaving 651 for screening. These were imported into Rayyan, where an additional 66 duplicate records were removed, resulting in 585 records for title and abstract screening. Two independent reviewers screened all records. After this stage, 12 full-text articles were assessed for eligibility. Following full-text review and application of inclusion/exclusion criteria, 4 studies were included in the final analysis. The complete study selection process is illustrated in the PRISMA flow diagram ( Fig. 1 ) . Description of included studies The four included studies involved a total of 249 adult patients: two studies included patients with brain metastases, and two included patients with metastatic spinal cord compression. Two studies were conducted in the Netherlands, one in the USA, and one in Australia. Three studies were randomised controlled trials (RCTs), and one was a retrospective cohort study. In brain metastases, doses of 4 mg/day, 8 mg/day, and 16 mg/day oral dexamethasone, as well as variable pre-operative regimens ( 16 mg/day), were assessed. In MSCC, regimens included 10 mg IV vs 100 mg IV bolus (both followed by 16 mg/day orally) and 96 mg/day IV vs 16 mg/day IV during radiotherapy. Routes included intravenous and oral administration, with bolus and tapering schedules. Treatment durations ranged from a single bolus to four weeks. Outcomes assessed included neurological improvement, functional status, survival, and adverse events. Dexamethasone Dosing in Brain Tumours Vecht et al. (1994) conducted two double-blind RCTs (n = 96 randomised; 89 evaluable) in adults with CT proven brain metastases and Karnofsky performance scores (KPS) ≤ 80. The first series compared 8 mg/day vs 16 mg/day; the second compared 4 mg/day vs 16 mg/day. At day 7, short-term KPS improvements were similar across groups (8 mg 60% vs 16 mg 54%; 4 mg 67% vs 16 mg 70%; p > 0.05). By day 28, the 8 mg/day group showed lower improvement than the 16 mg/day group (53% vs 81%), likely due to early tapering before radiotherapy, whereas 4 mg/day remained comparable to 16 mg/day (p = 0.56), as indicated by overlapping 90% confidence intervals. Low-dose dexamethasone (4–8 mg/day) was as effective as high-dose for functional improvement, with fewer toxicities. Steroid-related toxicities including cushingoid features, ankle oedema, and proximal muscle weakness were significantly more frequent in the 16 mg/day arms (p < 0.03). Dropouts and deaths were numerically higher in the high-dose groups. Across both series, 4 mg/day (3 dropouts, 1 death) and 8 mg/day (7 dropouts, 3 deaths) groups had fewer events than 16 mg/day groups (14 dropouts, 7 deaths). No causal relationship to dexamethasone was reported [ 7 ]. Bowden et al. (2023) conducted a single-centre retrospective cohort study (n = 96) evaluating varied preoperative dexamethasone regimens ( 16 mg/day, or bolus + 16 mg/day; mean cumulative dose 42.7 mg over 2.7 days). Neurological improvement was observed in 38.5% of patients preoperatively and 82.3% at follow-up, with responders maintaining benefit more consistently than non-responders (100% vs 71%; p < 0.001). Preoperative motor deficits improved most frequently (46.9%), whereas language (31.6%) and visual field deficits (7.7%) were less responsive. No significant differences were noted between dose regimens, cumulative doses, or treatment duration. Among responders, symptomatic improvement occurred after a mean cumulative dose of 17.3 mg (range 4–34 mg) within 23.9 hours (range 6–48 hours). These findings suggest that short-course, lower-dose dexamethasone is sufficient for preoperative neurological benefit, with higher or prolonged dosing offering no additional advantage. Adverse effects were not reported, limiting any conclusions on the safety of different dexamethasone regimens [ 8 ]. Dexamethasone Dosing in Spinal Tumours Two randomised controlled trials evaluated the impact of dexamethasone dose on neurological and functional outcomes in metastatic spinal cord compression (MSCC). Vecht et al. (1989) conducted a multicentre RCT across four Dutch centres (n = 37) comparing a high-dose (100 mg IV) with a conventional-dose (10 mg IV) dexamethasone bolus, both followed by 16 mg/day orally. Participants had radiologically confirmed MSCC on myelography with contrast obstruction and a histological diagnosis of malignancy. Pain relief occurred rapidly in both groups (mean pain scores decreased from ~ 5.2 to 1.4 at one week; p < 0.001), but no significant differences were observed in ambulation, bladder function, or survival. Both regimens achieved comparable symptom improvement, indicating no additional clinical benefit from the higher bolus dose [ 9 ]. Graham et al. (2006) (TROG 01.05 Superdex) randomised patients with MSCC receiving palliative radiotherapy to 96 mg/day IV or 16 mg/day IV dexamethasone for 5 days, followed by tapering. The primary endpoint was ambulation at 30 days. Although pain scores improved significantly within 24 hours in both groups, the difference between regimens was not significant (p = 0.23). Median survival was 2.4 months for high-dose and 2.1 months for standard-dose therapy. Adverse events were more frequent in the 96 mg/day group, including gastrointestinal and infectious complications. Collectively, these trials demonstrate that very high-dose dexamethasone regimens confer no additional benefit in ambulation, pain control, or survival compared with conventional-dose therapy, while increasing the risk of treatment-related toxicity. These findings support the use of moderate-dose protocols (e.g., 16 mg/day) as both effective and safer for managing MSCC [ 10 ]. Discussion This systematic review highlights persistent variation in dexamethasone prescribing for neuro-oncology and the limited high-quality evidence addressing optimal dosing. Historical and contemporary practice supports corticosteroid use for symptom control in brain tumours and metastatic spinal cord compression, yet regimen choice remains inconsistent across centres and clinicians [ 11 ]. Our review found that for brain and spinal tumours, low-to-moderate dexamethasone regimens achieve comparable short-term functional and symptomatic benefits to higher-dose strategies, while higher doses are associated with increased steroid-related toxicity. These findings are consistent with prior work demonstrating clear symptomatic benefit of dexamethasone compared with no steroid therapy, but also significant adverse effects with prolonged or high-dose exposure [ 12 ]. Clinically, these results suggest that modest dexamethasone dosing with reassessment within 24–48 hours is both effective and safer. Routine escalation to very high bolus or prolonged high-dose regimens appears unwarranted in most patients. This interpretation aligns with existing clinical guidelines, which acknowledge corticosteroids as effective for symptom relief in brain metastases but emphasise the absence of robust evidence defining optimal dose, duration, or tapering [ 6 , 12 ]. Limitations Several limitations temper the strength of these conclusions. Only four eligible studies (three RCTs and one retrospective cohort) met the inclusion criteria, encompassing heterogeneous patient populations (brain metastases vs. MSCC), dosing regimens (oral vs. IV, bolus vs. daily, variable tapering), and outcome measures (KPS, ambulation, pain, survival), which precluded quantitative synthesis. The studies were generally small, with short follow-up, limiting assessment of long-term recovery and adverse effects. Although validated neurological and functional measures such as the Medical Research Council (MRC) muscle strength scale, Karnofsky Performance Status (KPS), and Functional Independence Measure (FIM) exist, their application across studies has been inconsistent. Adverse events were inconsistently reported and rarely assessed using standardised criteria, such as the Common Terminology Criteria for Adverse Events (CTCAE) [ 13 ]. The studies were conducted in only three countries (the United States, Australia, and the Netherlands), which may limit generalisability. Restricting inclusion to English-language, peer-reviewed literature may also have excluded relevant data. Implications for Practice Within these constraints, initiating low-to-moderate dexamethasone doses and avoiding unnecessary escalation appears prudent. Early response assessment enables timely tapering and minimises exposure to adverse effects such as hyperglycaemia, myopathy, mood disturbance, and Cushingoid features. Although this approach appears effective and safer than high-dose regimens, further high-quality studies are needed to refine optimal use. Future Research Future studies should be large international, multicentre, prospective, randomised trials comparing low- and high-dose dexamethasone regimens. They should clarify optimal dosing, duration, and tapering, and consistently use standardised neurological, functional, and adverse-event outcomes. Stratifying patients by tumour type, baseline function, and definitive treatment plan will improve generalisability and help identify the lowest effective dose with minimal toxicity. Declarations Competing Interests: The authors declare that they have no known financial or personal relationships that could have appeared to influence the work reported in this paper. Funding: The authors declare that no funding, grants, or other support were received for the preparation of this manuscript. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Data availability: All data generated or analysed during this study are included in this published article and its supplementary information. CRediT Authorship Contribution Statement Bunmi Adedotun: Writing – original draft, Writing – review & editing, Investigation, Data curation, Project administration, Methodology, Visualisation, Validation. Michael Adebayo: Writing – original draft, Investigation, Data curation, Validation. Sacha Chiuta: Writing – original draft, Investigation, Data curation, Validation. Olatomiwa Olukoya: Conceptualisation, Supervision, Writing – review & editing, Project administration, Validation. References Vazquez S, Gold J, Spirollari E, Akmal S, Hanft SJ (2023) The story of dexamethasone and how it became one of the most widely used drugs in neurosurgery. J Neurosurg 140(4):1191–1197. 10.3171/2023.9.JNS231099 PMID:38000066 Barbero-Bordallo N, Gómez-Vicente L (2019) Use of steroids in neuro-oncology. Rev Neurol 68(9):389–397. 10.33588/rn.6809.2019083 Ohmura K, Tomita H, Hara A (2023) Peritumoral edema in gliomas: a review of mechanisms and management. Biomedicines 11(10):2731. 10.3390/biomedicines11102731 Elnoby AS, Nassar HS (2021) Corticosteroid-associated hypothalamic–pituitary–adrenal axis suppression in brain tumours: a focus on dosing and tapering. J Pharm Pract Res 51:300–306. 10.1002/jppr.1730 Palombi L, Marchetti P, Salvati M, Osti MF, Frati L, Frati A (2018) Interventions to reduce neurological symptoms in patients with GBM receiving radiotherapy: from theory to clinical practice. Anticancer Res 38(4):2423–2427. 10.21873/anticanres.12494 PMID:29599372 National Institute for Health and Care Excellence (NICE). Evidence reviews for corticosteroids: spinal metastases and metastatic spinal cord compression. London: NICE (2023) Sep (NICE Guideline, No. 234.) Available from: https://www.ncbi.nlm.nih.gov/books/NBK595818/ Vecht CJ, Hovestadt A, Verbiest HB, van Vliet JJ, van Putten WL (1994) Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. Neurology 44(4):675–680 Bowden SG, Lopez Ramos CG, Cheaney B, Richie E, Yaghi NK, Munger DN et al (2023) Response to preoperative dexamethasone predicts postoperative neurological improvement of focal neurological deficits in patients with brain metastases. Neurosurgery 92(6):1227–1233 Vecht CJ, Haaxma-Reiche H, van Putten WL, de Visser M, Vries EP, Twijnstra A (1989) Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal cord compression. Neurology 39(9):1255–1257 Graham PH, Capp A, Delaney G, Goozee G, Hickey B, Turner S et al (2006) A pilot randomised comparison of dexamethasone 96 mg vs 16 mg per day for malignant spinal-cord compression treated by radiotherapy: TROG 01.05 Superdex study. Clin Oncol (R Coll Radiol) 18(1):70–76 Stenning A, O'Brien DF, Adams H, Peterson D, Sokolowski C, Ibrahim A et al (2021) Variation in dexamethasone prescribing in neuro-oncology: a review of current practice and influencing factors. World Neurosurg 155:e579–e586. 10.1016/j.wneu.2021.09.053 Ryken TC, McDermott M, Robinson PD, Ammirati M, Andrews DW, Asher AL et al (2010) The role of steroids in the treatment of adults with metastatic brain tumors: a systematic review and evidence-based clinical practice guideline. J Neurooncol 96(1):103–114. 10.1007/s11060-009-0065-7 National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v6.0. Bethesda (MD): U.S. Department of Health and Human Services (2025) Jul 22. Available from: https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v6.pdf Additional Declarations The authors declare no competing interests. Supplementary Files Papercharacteristics.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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13:41:21","extension":"html","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":60206,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7942114/v1/07ecc2ceb76512c5993da652.html"},{"id":94666274,"identity":"0c51bdbb-f781-4dbf-9d25-7cae2da508ea","added_by":"auto","created_at":"2025-10-29 12:33:42","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":96617,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eThe flowchart of the selection process of studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA).\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7942114/v1/934b0ba9f38c08ed71baadd0.jpg"},{"id":94728345,"identity":"79ad9a8b-3726-4cf2-8fac-7c0f095814b8","added_by":"auto","created_at":"2025-10-30 07:03:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":705645,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7942114/v1/15d106cb-5c4a-4120-a992-99d60354d4b2.pdf"},{"id":94672736,"identity":"6b1ed752-bfe2-4381-a561-4648257546cc","added_by":"auto","created_at":"2025-10-29 13:40:54","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25099,"visible":true,"origin":"","legend":"","description":"","filename":"Papercharacteristics.docx","url":"https://assets-eu.researchsquare.com/files/rs-7942114/v1/60244d1c994a1cc6459bb465.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eDexamethasone Use in Neuro-Oncology: Balancing Efficacy and Toxicity\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn the 1950s, Glen E. Arth synthesised dexamethasone, a 16-alpha-methylated analogue of cortisone, initially developed for the treatment of rheumatoid arthritis. Joseph Galicich, then a neurosurgery resident, recognised its potential in neurosurgery and administered it to patients following craniotomy for tumour removal. He observed improvements in paresis, resolution of midline shift, and reduced mortality, prompting clinical trials that established dexamethasone as a cornerstone in neurosurgical care [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSince then, corticosteroids have become integral to neuro-oncology, with most patients with brain tumours receiving them at some point during treatment. However, corticosteroid-related side effects are common and can markedly impair quality of life [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePerilesional oedema, a form of vasogenic oedema resulting from blood\u0026ndash;brain barrier disruption and increased vascular permeability, exacerbates tumour mass effect, raises intracranial pressure, and contributes to neurological decline [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Empirical administration of corticosteroids 1\u0026ndash;2 days before neurosurgery can reduce oedema, intracranial pressure, and neurological symptoms, but prolonged exposure is associated with significant dose- and duration-dependent adverse effects, including endocrine disturbances, gastric ulcers, steroid-induced diabetes, myopathy, osteoporosis, psychiatric disorders, cataracts, and Cushing\u0026rsquo;s syndrome [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDexamethasone, noted for its potent anti-inflammatory and immunosuppressive properties, remains the preferred corticosteroid for reducing neurological symptoms and minimising treatment-related side effects [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It is also widely used in metastatic spinal cord compression (MSCC) to reduce tumour volume and spinal cord swelling, relieve pressure, and improve neurological function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite their routine use during surgery, radiotherapy, and chemotherapy, evidence guiding optimal corticosteroid dosing, duration, and tapering to balance efficacy and toxicity remains limited, with few clinical trials addressing this [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis review explores optimal dexamethasone dosing strategies in patients with brain and spinal tumours, focusing on oedema severity and its impact on outcomes such as symptom relief and surgical success.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003e We conducted a systematic review in accordance with PRISMA-P guidelines to evaluate optimal steroid dosing strategies in adults with brain or spinal tumours, including metastatic spinal cord compression. Our primary outcomes of interest were relief of peritumoural oedema, improvement in neurological symptoms, adverse effects, and overall survival.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cp\u003eWe included full-text, peer-reviewed original studies involving adult patients (\u0026ge;\u0026thinsp;18 years) with primary or metastatic brain or spinal cord tumours, including epidural spinal tumours and metastatic spinal cord compression (MSCC).\u003c/p\u003e\u003cp\u003eEligible studies assessed corticosteroid use (specifically dexamethasone) in adults with brain tumours or spinal tumour, reporting on neurological symptom control, functional outcomes, adverse effects, or survival.\u003c/p\u003e\u003cp\u003eWe excluded reviews, editorials, letters, conference abstracts, case reports, preprints, animal studies, non-English articles, and studies that did not report dosing strategies or relevant clinical outcomes such as oedema reduction, neurological improvement, surgical readiness, survival, or adverse effects.\u003c/p\u003e\n\u003ch3\u003eSearch strategy:\u003c/h3\u003e\n\u003cp\u003eWe systematically searched the following databases from inception to July 2025:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eOvid platform (searched 5 July 2025), including Embase, MEDLINE, and Emcare\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003ePubMed and Cochrane Library (searched 6 July 2025)\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eWe used a combination of MeSH terms and free-text keywords, including:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003edexamethasone,\u0026rdquo; \u0026ldquo;brain tumour,\u0026rdquo; \u0026ldquo;spinal tumour,\u0026rdquo; \u0026ldquo;epidural spinal tumour,\u0026rdquo; \u0026ldquo;metastatic spinal cord compression,\u0026rdquo; \u0026ldquo;peritumoral oedema,\u0026rdquo; \u0026ldquo;vasogenic oedema,\u0026rdquo; \u0026ldquo;glucocorticoid,\u0026rdquo; \u0026ldquo;corticosteroid,\u0026rdquo; \u0026ldquo;high dose,\u0026rdquo; \u0026ldquo;low dose,\u0026rdquo; \u0026ldquo;taper,\u0026rdquo; \u0026ldquo;brain neoplasm,\u0026rdquo; \u0026ldquo;spinal neoplasm,\u0026rdquo; \u0026ldquo;brain cancer,\u0026rdquo; and \u0026ldquo;spinal cancer.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eWe applied filters to limit results to English-language and human studies.\u003c/p\u003e\n\u003ch3\u003eStudy selection:\u003c/h3\u003e\n\u003cp\u003eRecords were deduplicated using Zotero and screened in Rayyan. Two independent reviewers assessed titles and abstracts using predefined eligibility criteria, with disagreements resolved by consensus. Full texts of potentially relevant studies were reviewed for inclusion based on dexamethasone use in adult patients with brain or spinal tumours, including MSCC. Studies had to report dosing strategies and at least one clinical outcome of interest. The selection process followed PRISMA-P guidelines and is summarised in a PRISMA flow diagram.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStudy Selection\u003c/h2\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eA total of 742 records were retrieved: 524 from Ovid, 164 from PubMed, and 54 from Cochrane Library\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eInitial deduplication in Zotero removed 91 records, leaving 651 for screening. These were imported into Rayyan, where an additional 66 duplicate records were removed, resulting in 585 records for title and abstract screening.\u003c/p\u003e\u003cp\u003eTwo independent reviewers screened all records. After this stage, 12 full-text articles were assessed for eligibility. Following full-text review and application of inclusion/exclusion criteria, 4 studies were included in the final analysis.\u003c/p\u003e\u003cp\u003eThe complete study selection process is illustrated in the PRISMA flow diagram \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDescription of included studies\u003c/h3\u003e\n\u003cp\u003eThe four included studies involved a total of 249 adult patients: two studies included patients with brain metastases, and two included patients with metastatic spinal cord compression. Two studies were conducted in the Netherlands, one in the USA, and one in Australia. Three studies were randomised controlled trials (RCTs), and one was a retrospective cohort study.\u003c/p\u003e\u003cp\u003eIn brain metastases, doses of 4 mg/day, 8 mg/day, and 16 mg/day oral dexamethasone, as well as variable pre-operative regimens (\u0026lt;\u0026thinsp;16 mg/day to \u0026gt;\u0026thinsp;16 mg/day), were assessed.\u003c/p\u003e\u003cp\u003eIn MSCC, regimens included 10 mg IV vs 100 mg IV bolus (both followed by 16 mg/day orally) and 96 mg/day IV vs 16 mg/day IV during radiotherapy.\u003c/p\u003e\u003cp\u003eRoutes included intravenous and oral administration, with bolus and tapering schedules. Treatment durations ranged from a single bolus to four weeks. Outcomes assessed included neurological improvement, functional status, survival, and adverse events.\u003c/p\u003e\n\u003ch3\u003eDexamethasone Dosing in Brain Tumours\u003c/h3\u003e\n\u003cp\u003e\u003cb\u003eVecht et al. (1994)\u003c/b\u003e conducted two double-blind RCTs (n\u0026thinsp;=\u0026thinsp;96 randomised; 89 evaluable) in adults with CT proven brain metastases and Karnofsky performance scores (KPS)\u0026thinsp;\u0026le;\u0026thinsp;80. The first series compared 8 mg/day vs 16 mg/day; the second compared 4 mg/day vs 16 mg/day.\u003c/p\u003e\u003cp\u003eAt day 7, short-term KPS improvements were similar across groups (8 mg 60% vs 16 mg 54%; 4 mg 67% vs 16 mg 70%; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). By day 28, the 8 mg/day group showed lower improvement than the 16 mg/day group (53% vs 81%), likely due to early tapering before radiotherapy, whereas 4 mg/day remained comparable to 16 mg/day (p\u0026thinsp;=\u0026thinsp;0.56), as indicated by overlapping 90% confidence intervals.\u003c/p\u003e\u003cp\u003eLow-dose dexamethasone (4\u0026ndash;8 mg/day) was as effective as high-dose for functional improvement, with fewer toxicities.\u003c/p\u003e\u003cp\u003eSteroid-related toxicities including cushingoid features, ankle oedema, and proximal muscle weakness were significantly more frequent in the 16 mg/day arms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.03).\u003c/p\u003e\u003cp\u003eDropouts and deaths were numerically higher in the high-dose groups. Across both series, 4 mg/day (3 dropouts, 1 death) and 8 mg/day (7 dropouts, 3 deaths) groups had fewer events than 16 mg/day groups (14 dropouts, 7 deaths). No causal relationship to dexamethasone was reported [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eBowden et al. (2023)\u003c/b\u003e conducted a single-centre retrospective cohort study (n\u0026thinsp;=\u0026thinsp;96) evaluating varied preoperative dexamethasone regimens (\u0026lt;\u0026thinsp;16 mg/day, 16 mg/day, \u0026gt;\u0026thinsp;16 mg/day, or bolus\u0026thinsp;+\u0026thinsp;16 mg/day; mean cumulative dose 42.7 mg over 2.7 days).\u003c/p\u003e\u003cp\u003eNeurological improvement was observed in 38.5% of patients preoperatively and 82.3% at follow-up, with responders maintaining benefit more consistently than non-responders (100% vs 71%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Preoperative motor deficits improved most frequently (46.9%), whereas language (31.6%) and visual field deficits (7.7%) were less responsive.\u003c/p\u003e\u003cp\u003eNo significant differences were noted between dose regimens, cumulative doses, or treatment duration. Among responders, symptomatic improvement occurred after a mean cumulative dose of 17.3 mg (range 4\u0026ndash;34 mg) within 23.9 hours (range 6\u0026ndash;48 hours).\u003c/p\u003e\u003cp\u003eThese findings suggest that short-course, lower-dose dexamethasone is sufficient for preoperative neurological benefit, with higher or prolonged dosing offering no additional advantage.\u003c/p\u003e\u003cp\u003eAdverse effects were not reported, limiting any conclusions on the safety of different dexamethasone regimens [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eDexamethasone Dosing in Spinal Tumours\u003c/h2\u003e\u003cp\u003eTwo randomised controlled trials evaluated the impact of dexamethasone dose on neurological and functional outcomes in metastatic spinal cord compression (MSCC).\u003c/p\u003e\u003cp\u003e\u003cb\u003eVecht et al. (1989)\u003c/b\u003e conducted a multicentre RCT across four Dutch centres (n\u0026thinsp;=\u0026thinsp;37) comparing a high-dose (100 mg IV) with a conventional-dose (10 mg IV) dexamethasone bolus, both followed by 16 mg/day orally. Participants had radiologically confirmed MSCC on myelography with contrast obstruction and a histological diagnosis of malignancy. Pain relief occurred rapidly in both groups (mean pain scores decreased from ~\u0026thinsp;5.2 to 1.4 at one week; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), but no significant differences were observed in ambulation, bladder function, or survival. Both regimens achieved comparable symptom improvement, indicating no additional clinical benefit from the higher bolus dose [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eGraham et al. (2006)\u003c/b\u003e (TROG 01.05 Superdex) randomised patients with MSCC receiving palliative radiotherapy to 96 mg/day IV or 16 mg/day IV dexamethasone for 5 days, followed by tapering. The primary endpoint was ambulation at 30 days. Although pain scores improved significantly within 24 hours in both groups, the difference between regimens was not significant (p\u0026thinsp;=\u0026thinsp;0.23). Median survival was 2.4 months for high-dose and 2.1 months for standard-dose therapy. Adverse events were more frequent in the 96 mg/day group, including gastrointestinal and infectious complications.\u003c/p\u003e\u003cp\u003eCollectively, these trials demonstrate that very high-dose dexamethasone regimens confer no additional benefit in ambulation, pain control, or survival compared with conventional-dose therapy, while increasing the risk of treatment-related toxicity. These findings support the use of moderate-dose protocols (e.g., 16 mg/day) as both effective and safer for managing MSCC [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis systematic review highlights persistent variation in dexamethasone prescribing for neuro-oncology and the limited high-quality evidence addressing optimal dosing. Historical and contemporary practice supports corticosteroid use for symptom control in brain tumours and metastatic spinal cord compression, yet regimen choice remains inconsistent across centres and clinicians [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur review found that for brain and spinal tumours, low-to-moderate dexamethasone regimens achieve comparable short-term functional and symptomatic benefits to higher-dose strategies, while higher doses are associated with increased steroid-related toxicity. These findings are consistent with prior work demonstrating clear symptomatic benefit of dexamethasone compared with no steroid therapy, but also significant adverse effects with prolonged or high-dose exposure [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eClinically, these results suggest that modest dexamethasone dosing with reassessment within 24\u0026ndash;48 hours is both effective and safer. Routine escalation to very high bolus or prolonged high-dose regimens appears unwarranted in most patients.\u003c/p\u003e\u003cp\u003eThis interpretation aligns with existing clinical guidelines, which acknowledge corticosteroids as effective for symptom relief in brain metastases but emphasise the absence of robust evidence defining optimal dose, duration, or tapering [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eSeveral limitations temper the strength of these conclusions. Only four eligible studies (three RCTs and one retrospective cohort) met the inclusion criteria, encompassing heterogeneous patient populations (brain metastases vs. MSCC), dosing regimens (oral vs. IV, bolus vs. daily, variable tapering), and outcome measures (KPS, ambulation, pain, survival), which precluded quantitative synthesis.\u003c/p\u003e\u003cp\u003eThe studies were generally small, with short follow-up, limiting assessment of long-term recovery and adverse effects.\u003c/p\u003e\u003cp\u003eAlthough validated neurological and functional measures such as the Medical Research Council (MRC) muscle strength scale, Karnofsky Performance Status (KPS), and Functional Independence Measure (FIM) exist, their application across studies has been inconsistent. Adverse events were inconsistently reported and rarely assessed using standardised criteria, such as the Common Terminology Criteria for Adverse Events (CTCAE) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe studies were conducted in only three countries (the United States, Australia, and the Netherlands), which may limit generalisability.\u003c/p\u003e\u003cp\u003eRestricting inclusion to English-language, peer-reviewed literature may also have excluded relevant data.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eImplications for Practice\u003c/h2\u003e\u003cp\u003eWithin these constraints, initiating low-to-moderate dexamethasone doses and avoiding unnecessary escalation appears prudent. Early response assessment enables timely tapering and minimises exposure to adverse effects such as hyperglycaemia, myopathy, mood disturbance, and Cushingoid features. Although this approach appears effective and safer than high-dose regimens, further high-quality studies are needed to refine optimal use.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eFuture Research\u003c/h2\u003e\u003cp\u003eFuture studies should be large international, multicentre, prospective, randomised trials comparing low- and high-dose dexamethasone regimens. They should clarify optimal dosing, duration, and tapering, and consistently use standardised neurological, functional, and adverse-event outcomes. Stratifying patients by tumour type, baseline function, and definitive treatment plan will improve generalisability and help identify the lowest effective dose with minimal toxicity.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that they have no known financial or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;The authors declare that no funding, grants, or other support were received for the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003cbr\u003e\u003c/strong\u003eAll data generated or analysed during this study are included in this published article and its supplementary information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCRediT Authorship Contribution Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBunmi Adedotun:\u003c/strong\u003e Writing – original draft, Writing – review \u0026amp; editing, Investigation, Data curation, Project administration, Methodology, Visualisation, Validation.\u003cbr\u003e\u003cstrong\u003eMichael Adebayo:\u003c/strong\u003e Writing – original draft, Investigation, Data curation, Validation.\u003cbr\u003e\u003cstrong\u003eSacha Chiuta:\u003c/strong\u003e Writing – original draft, Investigation, Data curation, Validation.\u003cbr\u003e\u003cstrong\u003eOlatomiwa Olukoya:\u003c/strong\u003e Conceptualisation, Supervision, Writing – review \u0026amp; editing, Project administration, Validation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVazquez S, Gold J, Spirollari E, Akmal S, Hanft SJ (2023) The story of dexamethasone and how it became one of the most widely used drugs in neurosurgery. 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J Neurooncol 96(1):103\u0026ndash;114. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11060-009-0065-7\u003c/span\u003e\u003cspan address=\"10.1007/s11060-009-0065-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNational Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v6.0. Bethesda (MD): U.S. Department of Health and Human Services (2025) Jul 22. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v6.pdf\u003c/span\u003e\u003cspan address=\"https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v6.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Brain metastases, Corticosteroids, Dexamethasone, Metastatic spinal cord compression, Neuro-oncology, Steroid dosing","lastPublishedDoi":"10.21203/rs.3.rs-7942114/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7942114/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e\u003cp\u003eCorticosteroids are widely used in neuro-oncology, with dexamethasone the preferred option for symptom control. However, optimal dosing remains unclear. This review evaluated high- versus low-dose dexamethasone regimens in adults with brain and spinal tumours.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003e A systematic review was conducted in accordance with PRISMA-P guidelines. Ovid (MEDLINE, Embase, Emcare), PubMed, and the Cochrane Library were searched from inception to July 2025. Eligible studies compared low- with higher-dose regimens in adults with brain or spinal tumours. Outcomes included neurological improvement, adverse effects, and survival.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eFrom 742 citations, four studies (n\u0026thinsp;=\u0026thinsp;249) were included: three randomised controlled trials and one retrospective cohort. In brain metastases, low-dose dexamethasone (4\u0026ndash;8 mg/day) was as effective as 16 mg/day for short-term functional improvement, while higher doses increased toxicity. The retrospective cohort showed most patients improved within 24\u0026ndash;48 hours on modest cumulative doses (~\u0026thinsp;17 mg), with no added benefit from higher or prolonged treatment. In metastatic spinal cord compression (MSCC), high- and low-dose dexamethasone regimens achieved comparable neurological and pain outcomes, though higher doses were associated with more adverse events.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eCurrent evidence suggests low-dose dexamethasone regimens are as effective as high-dose regimens for most patients, while higher doses increase toxicity. As neurological improvement typically occurs within 24\u0026ndash;48 hours, prolonged high-dose therapy may offer limited additional value. Further multicentre studies are required to establish optimal dosing, duration, and tapering.\u003c/p\u003e","manuscriptTitle":"Dexamethasone Use in Neuro-Oncology: Balancing Efficacy and Toxicity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 12:33:37","doi":"10.21203/rs.3.rs-7942114/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"55365567-33b3-451c-b022-249a9045674b","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":56842514,"name":"Neurosurgery"},{"id":56842515,"name":"Oncology"}],"tags":[],"updatedAt":"2025-10-29T12:33:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-29 12:33:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7942114","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7942114","identity":"rs-7942114","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}