Tag: Immunotherapy

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines Update for the Role of Emerging Therapies in the Management of Patients With Metastatic Brain Tumors

Neurosurgery 96:1172–1177, 2025

This 2025 CNS guideline update reviews evidence for emerging therapies in adult brain metastases, providing new recommendations on targeted therapies, immunotherapy, radiosensitizers, and laser interstitial thermal therapy, while noting insufficient evidence for some modalities. Recommendations aim to guide multidisciplinary management beyond standard surgical and radiation treatments.

• This guideline is an updated systematic review on emerging therapies for adult patients with metastatic brain tumors (MBTs), focusing on evidence-based recommendations.

• Targeted therapies and immunotherapies have the strongest new evidence, especially for NSCLC, melanoma, and breast cancer brain metastases.

• Level I recommendations include the use of specific agents such as icotinib with WBRT for EGFR-mutant NSCLC, alectinib for ALK-positive NSCLC, and dabrafenib plus trametinib for BRAFV600E-positive melanoma.

• Immune checkpoint inhibitors (e.g., ipilimumab plus nivolumab for melanoma, ICIs for NSCLC) are recommended to improve survival and intracranial control in selected patients.

• Laser interstitial thermal therapy (LITT) may be considered equivalent to craniotomy or medical management in certain cases of tumor progression or radiation necrosis after SRS.

• There is insufficient evidence to recommend interstitial modalities or high-intensity focused ultrasound (HIFU) for brain metastases.

• Future research should prioritize prospective, comparative studies for modalities like LITT and HIFU, and the guideline will be updated as new evidence emerges.

• Clinical decisions should be individualized, and participation in clinical trials is encouraged to refine treatment strategies for MBTs.

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Preoperative stereotactic radiosurgery for cerebral metastases: safe, effective, and decreases steroid dependency

J Neurosurg 141:1332–1342, 2024

Preoperative stereotactic radiosurgery (SRS) is emerging as a viable alternative to standard postoperative SRS. Studies have suggested that preoperative SRS provides comparable tumor control and overall survival (OS) and may reduce the incidence of leptomeningeal disease (LMD) and adverse radiation effects (AREs). It is unknown, however, if preoperative SRS remains effective in cohorts including large brain metastases (> 14 cm 3 ) or if preoperative SRS affects steroid taper/immunotherapy. Here, the authors report the results of a phase 2 single-arm trial assessing a prospectively acquired series of 26 patients who underwent preoperative SRS, without a volumetric cutoff, compared with a propensity score–matched concurrent cohort of 30 patients who underwent postoperative SRS to address these salient questions.

METHODS Demographics, oncological history, surgical details, and outcomes were collected from the medical records. Coprimary endpoints were local tumor control (LTC) and a composite outcome of LTC, ARE, and LMD. Additional outcomes were OS, steroid taper details, and immunotherapy resumption. For survival analyses, cohorts were propensity score matched.

RESULTS Preoperative and postoperative SRS patients were comparable in terms of age, sex, Karnofsky Performance Status score, oncological history, and operative details. Gross tumor volume (GTV) was significantly higher in the preoperative group (median 12.2 vs 5.3 cm 3 , p < 0.001). One-year LTC (preoperative SRS: 77.2% vs postoperative SRS: 82.5%, p = 0.61) and composite outcome (68.3% vs 72.7%, p = 0.38) were not significantly different between the groups. In multivariable analysis, preoperative SRS did not have a significant effect on LTC (HR 1.57 [95% CI 0.38–6.49], p = 0.536) or the composite outcome (HR 1.18 [95% CI 0.38–3.72], p = 0.771), although the confidence intervals were large. The median OS (preoperative SRS: 17.0 vs postoperative SRS: 14.0 months, p = 0.61) was not significantly different. Rates of LMD were nonsignificantly lower in the preoperative SRS group (3.8% vs 16.7%, p = 0.200). Greater GTV volume was associated with prolonged (> 10 days) steroid taper (OR 1.24 [95% CI 1.04–1.55], p = 0.032). However, in multivariable analysis, preoperative SRS markedly reduced the steroid taper length (OR 0.13 [95% CI 0.02–0.61], p = 0.016). Time to immunotherapy was shorter in the preoperative SRS group (36 [IQR 26, 76] vs OR 228 [IQR 129, 436] days, p = 0.02).

CONCLUSIONS Compared with postoperative SRS, preoperative SRS is a safe and effective strategy in the management of cerebral metastases of all sizes and provides comparable tumor control without increased adverse effects. Notably, preoperative SRS enabled rapid steroid taper, even in larger tumors. Future studies should specifically examine the interaction of preoperative SRS with steroid usage and resumption of systemic therapies and the subsequent effects on systemic progression and OS.

Clinical trial registration no.: NCT02514915 (ClinicalTrials.gov)

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Management of Progressive Glioblastoma in Adults: Update of the 2014 Guidelines

Neurosurgery 90:E112–E115, 2022

The Institute of Medicine best practice recommendation to review guidelines every 5 years is followed by the Congress of Neurological Surgeons Guidelines Committee. The aim of this work was to provide an updated literature review and evidence-based recommendations on the topic of diagnosis and treatment of patients with progressive glioblastoma (pGBM).

OBJECTIVE: To review the literature published since the last guidelines on pGBM dated 2014, with literature search ending in June 2012.

METHODS: PubMed, Embase, and Cochrane were searched for the period July 1, 2012, to March 31, 2019, using search terms and search strategies to identify pertinent abstracts. These were then screened using published exclusion/inclusion criteria to identify full-text review articles. Evidence tables were constructed using data derived from full-text reviews and recommendations made from the evidence derived.

RESULTS: From the total 8786 abstracts identified by the search, 237 full-text articles met inclusion/exclusion criteria and were included in this update. Two new level II recommendations derived from this work. For the diagnosis of patients with GBM, the use of diffusion-weighted images is recommended to be included in the magnetic resonance images with and without contrast used for surveillance to detect pGBM. For the treatment of patients with pGBM, repeat cytoreductive surgery is recommended to improve overall survival. An additional 21 level III recommendations were provided.

CONCLUSION: Recent published literature provides new recommendations for the diagnosis and treatment of pGBM. The Central Nervous System Guidelines Committee will continue to pursue timely updates to further improve the care of patients with diagnosis. https://www.cns.org/guidelines/browse-guidelines-detail/guidelines-management-ofprogressive-glioblastoma.

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Immune Checkpoint Inhibitors for Brain Metastases

 

Neurosurgery 87:E281–E288, 2020

Immune checkpoint inhibitors enhance immune recognition of tumors by interfering with the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed death 1 (PD1) pathways. In the past decade, these agents brought significant improvements to the prognostic outlook of patients with metastatic cancers. Recent data from retrospective analyses and a few prospective studies suggest that checkpoint inhibitors have activity against brainmetastases from melanoma and non small cell lung cancer, as single agents or in combination with radiotherapy. Some studies reported intracranial response rates that were comparable with systemic ones.

In this review, we provide a comprehensive summary of clinical data supporting the use of anti-CTLA4 and anti-PD1 agents in brain metastases. We also touch upon specific considerations on the assessment of intracranial responses in patients and immunotherapy-specific toxicities.

We conclude that a subset of patients with brain metastases benefit from the addition of checkpoint inhibitors to standard of care therapeutic modalities, including radiotherapy and surgery.

 

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Cancer Immunoediting in Malignant Glioma

Neurosurgery 71:201–223, 2012

Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system–tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically.

In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches.

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