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New Gene Expression Test Predicts Meningioma Outcomes and Radiotherapy Responses Better Than Current Methods

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Original medical illustration for: New Gene Expression Test Predicts Meningioma Outcomes and Radiotherapy Responses Better Than Current Methods

Table of Contents

Key Points

  • A 34-gene expression biomarker predicted meningioma recurrence and survival better than the WHO 2021 grade standard in a validation cohort of 1,856 tumors from 12 institutions.
  • In a multicenter retrospective cohort, 5-year local freedom from recurrence was 92.2% for low risk, 72.6% for intermediate risk, and 19.4% for high risk.
  • In that cohort, patients with unfavorable biomarker and surgical features benefited from postoperative radiotherapy (hazard ratio 0.54), while favorable patients did not.
  • The biomarker reclassified 52.0% of meningiomas versus clinical criteria and suggested postoperative management could be refined for 29.8% of patients.
  • The test is not yet widely available in clinical practice; ask your doctor about molecular testing, radiotherapy decisions, and clinical trials.

Background: Why This Research Matters

Meningiomas are the most common primary brain tumors, accounting for 39.7% of all primary intracranial tumors (tumors that start in the brain). These tumors are the only brain tumors that are more common in women, Black patients, and elderly patients. These groups are underrepresented in brain tumor clinical trials.

Treatment options for meningiomas are largely limited to surgery and radiotherapy (radiation therapy). Systemic therapies (drugs that travel through the bloodstream) remain ineffective or experimental for this type of tumor.

Historically, the World Health Organization (WHO) has graded meningiomas based on how the tumor cells look under a microscope. This grading system looks at features such as mitotic count (the number of cells actively dividing). The grades range from 1 (least aggressive) to 3 (most aggressive).

Most WHO grade 1 meningiomas can be effectively treated with surgery or radiotherapy. However, many WHO grade 2 or grade 3 meningiomas resist treatment and cause significant neurological problems and death. Some WHO grade 1 meningiomas recur in ways that cannot be predicted from how they look under a microscope. Some WHO grade 2 or grade 3 meningiomas are unexpectedly well controlled with surgery and radiotherapy.

This uncertainty has created controversy around how to classify meningioma risk and how to treat these tumors. Two Phase III clinical trials — NRG BN-003 and EORTC 1308 — are currently randomizing patients with primary WHO grade 2 meningiomas. The trials are randomizing patients to either postoperative surveillance (watchful waiting) or postoperative radiotherapy after gross total resection (complete tumor removal).

The only multicenter prospective studies of meningioma radiotherapy that have reported data are RTOG 0539 and EORTC 22042. These Phase II clinical trials provide safety data and non-randomized results based on clinical criteria. These criteria do not predict radiotherapy responses in most retrospective studies (studies that look back at past patient data).

In 2021, the WHO revised meningioma grading criteria. The new criteria incorporate rare hotspot TERT promoter mutations (specific genetic changes). The new criteria incorporate homozygous deletion of CDKN2A/B (loss of both copies of a specific gene). The new criteria incorporate these alongside traditional microscopic features. This update reflects a growing understanding of the molecular landscape of meningiomas from diverse bioinformatic studies.

Researchers have used several molecular approaches to classify meningiomas. These include DNA sequencing. These include copy number variant (CNV) analyses (which look at gains or losses of chromosome segments). These include RNA sequencing. These include DNA methylation profiling (which looks at chemical tags on DNA that affect gene activity). Integrated systems have been proposed that combine CNVs, CDKN2A/B status, DNA methylation, and microscopic features.

It was unknown which of these diverse classification systems might best optimize risk stratification or predict postoperative radiotherapy responses for patients with meningiomas.

Knowledge of biological pathways underlying diverse cancers has generated robust targeted gene expression biomarkers. These biomarkers are recommended for risk stratification and prediction of treatment response by the National Comprehensive Cancer Network (NCCN). A small pilot study suggested that targeted gene expression profiling may be useful for meningioma risk stratification. However, an optimized gene expression biomarker — as well as its analytical validity, clinical validity, generalizability, and potential impact on postoperative meningioma management — was unknown.

How the Research Was Conducted

The researchers used knowledge of biological pathways underlying meningiomas from previous bioinformatic studies. They developed a 34-gene expression biomarker that is prognostic for clinical outcomes in a single-institution discovery cohort (a group of patients used to develop the test).

The researchers then performed clinical and analytical validation of the gene expression biomarker using independent meningiomas from a large multicenter retrospective cohort. They compared biomarker performance across contemporary meningioma classification systems and clinical contexts using a total of 4,898 bioinformatic assays.

The study included several key groups:

  • Discovery cohort: 173 meningiomas used to develop the 34-gene expression biomarker and risk score
  • Analytical validation cohort: 1,219 meningiomas from 8 institutions, used to test reproducibility and reliability
  • Multicenter retrospective clinical validation cohort: 866 meningiomas from 6 institutions (572 frozen samples, 294 FFPE samples)
  • Prospective clinical trial cohort: 103 meningiomas from patients enrolled on the RTOG 0539 clinical trial

The researchers also provided investigator-blinded, independent validation of the gene expression biomarker. This means the researchers analyzing the samples did not know the patients' clinical outcomes, preventing bias.

Developing the Gene Expression Biomarker

Targeted gene expression profiling of 173 meningiomas in the discovery cohort resulted in a 34-gene expression biomarker. This biomarker produces a continuous risk score between 0 and 1. The researchers converted this continuous score into discrete low, intermediate, and high risk groups for Kaplan Meier analyses (a statistical method for measuring survival over time).

The gene expression biomarker was well distributed across intracranial meningioma locations (locations within the skull) and recurring somatic short variants (genetic mutations found in the tumor). The biomarker was prognostic for local freedom from recurrence (LFFR, meaning the tumor did not come back where it started) and overall survival (OS, meaning how long patients lived).

The gene expression biomarker model, risk score, and cutoffs were locked and applied without alteration to multicenter retrospective and prospective validation cohorts from 12 institutions. Locking the model means the researchers did not change it after seeing the validation results, which prevents bias.

The genes included in the biomarker are involved in several important cellular functions:

  • Cell cycle and epigenetic regulation: CDK6, CDKN2A, CDC20, CKS2, CHEK1, EZH2, MYBL1
  • Mitotic stability (proper cell division): KIF20A
  • Genes located on recurrent CNVs: LINC02593 on chromosome 1p, TMEM30B on 14q, USF1 on 1q, ARID1B on 6q
  • Immune-related genes: CCL21, CD3E
  • Previously identified prognostic markers in meningioma: PGR, IGF2, COL1A1

Inspection of the genes comprising the biomarker across the cellular architecture of meningiomas from single-cell RNA sequencing revealed that some biomarker genes are enriched in meningioma cells. Other biomarker genes are expressed by the tumor microenvironment (the normal cells and structures surrounding the tumor).

Analytical Validation: Testing Reliability

Analytical validity refers to how reliably a test produces the same results under different conditions. The researchers established analytical validity using the multicenter analytical validation cohort of 1,219 meningiomas from 8 institutions.

The researchers tested several conditions:

  • Reproducibility over time: Test-retest conditions generated concordant (agreeing) gene expression risk scores
  • Reproducibility across laboratories: Different centers generated concordant gene expression risk scores
  • Paired frozen and FFPE samples: Frozen and FFPE (formalin-fixed, paraffin-embedded, a common way to preserve tissue) meningiomas generated concordant gene expression risk scores
  • Different quantification approaches: Both RNA sequencing and microarray approaches were tractable and discriminatory for meningioma outcomes when used to assess the 34-gene signature

With regard to cross-platform interoperability (whether different testing platforms give the same answer), the researchers found a limitation. DNA methylation profiling was only able to predict the gene expression risk score to a moderate degree. This means DNA methylation testing is not a perfect substitute for the gene expression biomarker.

Clinical Validation: Testing Accuracy in Real Patients

In the multicenter retrospective clinical validation cohort of 866 meningiomas from 6 institutions, the gene expression biomarker achieved a concordance index (c-index) of 0.78 for LFFR and 0.78 for OS. The c-index measures how well a test predicts outcomes; 0.5 is random chance and 1.0 is perfect prediction.

The gene expression biomarker delineated clinically meaningful low, intermediate, and high risk groups. The 5-year LFFR rates were:

  • Low risk: 92.2% (95% CI 88.3–96.2%)
  • Intermediate risk: 72.6% (95% CI 67.8–77.8%)
  • High risk: 19.4% (95% CI 13.5–28.0%)

These results mean that patients in the low risk group had a 92.2% chance of remaining free from local recurrence at 5 years. Patients in the high risk group had only a 19.4% chance of remaining free from local recurrence at 5 years.

The gene expression biomarker remained well-calibrated in meningiomas from individual clinical validation institutions. Well-calibrated means the predicted risk matched the actual observed risk.

The gene expression biomarker was prognostic for LFFR and OS in several clinical situations:

  • Among meningiomas presenting in primary or recurrent settings
  • After gross total resection (GTR, complete removal) or subtotal resection (STR, partial removal)
  • Across WHO grades using histological criteria (WHO 2016) or histological and molecular criteria (WHO 2021)

The gene expression biomarker remained independently prognostic on multivariate analysis. Multivariate analysis is a statistical method that accounts for multiple factors at once. The analysis incorporated meningioma setting (primary or recurrent), extent of resection, and WHO grade.

The gene expression biomarker was also prognostic for LFFR and OS within strata from other meningioma molecular classification systems. These systems are based on DNA methylation probes, groups, subgroups, or families, or based on gene expression types, integrated score, or integrated grade. The gene expression biomarker remained independently prognostic on multivariate analyses incorporating each of the 9 other meningioma classification systems.

Comparing the Biomarker to Other Classification Systems

The researchers compared the gene expression biomarker to 9 other meningioma classification systems. These systems are based on molecular criteria, molecular and histological criteria, or WHO criteria. The researchers used pairwise model combinations for this comparison.

The gene expression biomarker provided additional prognostic information for LFFR and OS in combination with each of the 9 other systems tested. No other meningioma classification system provided additional prognostic information for LFFR in combination with the gene expression biomarker. Only WHO 2021 grade provided additional prognostic information for OS.

The gene expression biomarker achieved the lowest Brier error score over time for LFFR across meningioma classification systems. The Brier score measures the accuracy of probabilistic predictions; a lower score means better accuracy. The gene expression biomarker had an error score comparable to WHO 2021 grade and integrated grade over time for OS.

The gene expression biomarker achieved the highest 5-year area under the curve (AUC) for LFFR (0.81) and OS (0.80) across meningioma classification systems. The AUC is a measure of how well a test can distinguish between patients who will and will not have a specific outcome.

The improvement in AUC compared to the next best performing system (integrated grade) was +0.07 for LFFR (95% CI 0.02–0.12, P<0.001). The improvement compared to the current standard of care (WHO 2021 grade) was +0.11 for LFFR (95% CI 0.07–0.17, P<0.001). A P value less than 0.001 means there is less than a 0.1% chance that this result occurred by random chance.

To translate these findings into clinical practice, the researchers generated nomograms. Nomograms are visual tools that predict the probability of a specific outcome. These nomograms predict 5-year LFFR or OS based on meningioma gene expression risk score, setting (primary or recurrent), extent of resection, and WHO grade.

Predicting Radiotherapy Responses

The researchers sought to incorporate the gene expression biomarker into a clinical framework consistent with contemporary NCCN and European Association of Neuro-Oncology (EANO) guidelines. The researchers stratified meningiomas treated with surgical monotherapy (surgery alone). The researchers stratified meningiomas in the multicenter retrospective clinical validation cohort. They stratified by extent of resection and gene expression risk score.

This stratification resulted in a range of clinical subgroups spanning the spectrum of recurrence risk. The 5-year LFFR ranged from 96.1% for gene expression low risk meningiomas with GTR (complete removal) to 9.8% for gene expression high risk meningiomas with STR (partial removal).

Based on these combined biomarker and surgical strata, the researchers distinguished favorable and unfavorable meningiomas:

  • Favorable: Gene expression low risk with any resection, or gene expression intermediate risk with GTR
  • Unfavorable: Gene expression intermediate risk with STR, or gene expression high risk with any resection

In clinical practice, meningiomas with unfavorable histological features or STR are often treated with postoperative radiotherapy based on retrospective data. NRG BN-003 and EORTC 1308 represent important prospective studies of radiotherapy for meningioma. However, these trials were initiated before the development of biomarkers for meningioma risk stratification. These trials do not incorporate biomarkers that could potentially elucidate postoperative radiotherapy responses.

In the multicenter retrospective clinical validation cohort, the gene expression biomarker remained prognostic for primary meningioma outcomes among patients receiving fractionated postoperative radiotherapy. Fractionated radiotherapy means the radiation is given in multiple smaller doses rather than one large dose. The biomarker was also prognostic among patients with primary WHO grade 2 meningiomas with GTR who may have been eligible for NRG BN-003 or EORTC 1308.

However, in the absence of biomarker stratification, primary WHO grade 2 meningiomas with GTR did not benefit from postoperative radiotherapy in the multicenter retrospective clinical validation cohort. This means that without the biomarker, doctors could not tell which patients would benefit from radiotherapy.

To determine if the gene expression biomarker could predict meningioma radiotherapy responses, the researchers stratified primary WHO grade 2 meningiomas based on favorable versus unfavorable biomarker and surgical criteria. The results showed:

  • Unfavorable primary WHO grade 2 meningiomas: Benefited from postoperative radiotherapy (HR 0.33, 95% CI 0.14–0.76, P=0.009)
  • Favorable primary WHO grade 2 meningiomas: Did not benefit from postoperative radiotherapy (P=0.88)

A hazard ratio (HR) of 0.33 means that patients in the unfavorable group who received radiotherapy had a 67% lower risk of recurrence compared to those who did not receive radiotherapy.

The researchers then applied the same biomarker and surgical strata across all WHO grades in the multicenter retrospective clinical validation cohort. They used propensity matching based on gene expression risk score, extent of resection, and WHO grade. Propensity matching is a statistical technique that creates comparable groups of patients. The results showed:

  • Unfavorable meningiomas: Benefited from postoperative radiotherapy (HR 0.54, 95% CI 0.37–0.78, P=0.0001)
  • Favorable meningiomas: Did not benefit from postoperative radiotherapy (P=0.42)

RTOG 0539 was a Phase II multicenter prospective trial that enrolled patients with meningiomas from 78 institutions. The trial assigned patients into 3 clinical risk groups:

  1. Low clinical risk: Primary WHO grade 1 meningiomas after any resection
  2. Intermediate clinical risk: Recurrent WHO grade 1 meningiomas after any resection, or primary WHO grade 2 meningiomas after GTR
  3. High clinical risk: WHO grade 3 meningiomas after any resection, recurrent WHO grade 2 meningiomas after any resection, and primary WHO grade 2 meningiomas after STR

Intermediate and high clinical risk patients enrolled on RTOG 0539 received postoperative radiotherapy. Low clinical risk patients underwent postoperative surveillance (watchful waiting).

To determine how the gene expression biomarker could potentially refine postoperative management, the researchers assigned meningiomas in the multicenter retrospective clinical validation cohort to RTOG 0539 clinical risk groups. They then compared these assignments to gene expression biomarker risk groups.

The gene expression biomarker improved discrimination of meningioma outcomes across clinical groups used for postoperative radiotherapy stratification in RTOG 0539. The biomarker re-classified 52.0% of meningiomas compared to clinical criteria. This included downstaging 21.3% of intermediate clinical risk patients who would have received postoperative radiotherapy on RTOG 0539. Downstaging means the biomarker identified these patients as lower risk than the clinical criteria suggested.

The researchers used favorable versus unfavorable biomarker and surgical strata that predict radiotherapy responses. These data suggest that postoperative management could have been refined for 29.8% of patients in the multicenter retrospective clinical validation cohort. This is compared to clinical criteria from RTOG 0539.

Validation in a Prospective Clinical Trial

The researchers performed investigator-blinded, independent validation of the gene expression biomarker using meningiomas and clinical data that were prospectively collected from patients enrolled on RTOG 0539 itself. This prospective cohort included 103 patients.

In comparison to clinical risk groups used to allocate patients to postoperative radiotherapy or postoperative surveillance on this study, the gene expression biomarker re-classified 39.8% of meningiomas from RTOG 0539. This included downstaging 30.3% of intermediate clinical risk patients who received postoperative radiotherapy.

The gene expression biomarker was prognostic for progression free survival (PFS, meaning the time before the tumor grew or came back) and overall survival (OS) in patients from RTOG 0539. The biomarker was well calibrated with 5-year PFS rates of:

  • Low risk: 92.0%
  • Intermediate risk: 76.5%
  • High risk: 38.6%

Moreover, the gene expression biomarker remained independently prognostic on multivariate analysis incorporating meningioma setting (primary or recurrent), extent of resection, and WHO grade using data from RTOG 0539.

Clinical Implications: What This Means for Patients

The researchers used targeted gene expression profiling to develop and validate a polygenic biomarker (a test that looks at multiple genes). The polygenic biomarker provides additional information for meningioma outcomes compared to other classification systems. This includes prediction of postoperative radiotherapy responses.

The gene expression biomarker is independently prognostic across all clinical, histological, and molecular contexts tested. This includes WHO 2021 grade, the current standard of care.

When incorporated into clinical risk groups defined by contemporary trials that are consistent with consensus NCCN and EANO guidelines, the gene expression biomarker potentially refines postoperative management for 29.8% of patients.

DNA methylation profiling, CNV analysis, DNA sequencing, and RNA sequencing have improved understanding of meningioma biology. Unsupervised bioinformatic analyses paired with mechanistic and functional approaches have identified molecular groups and subgroups of meningiomas with distinct biologic drivers, therapeutic vulnerabilities, and clinical outcomes. Supervised bioinformatic models incorporating clinical endpoints have refined risk stratification for meningioma local recurrence.

The gene expression biomarker reported here provides additional prognostic information for local recurrence and overall survival when combined with all unsupervised or supervised meningioma molecular classification systems tested. These findings are concordant with pan-cancer analyses examining gene expression, CNV, DNA methylation, protein expression, and DNA sequencing data in 10,884 patients. These pan-cancer analyses suggest gene expression encodes the greatest prognostic information across cancer types.

Efforts to reduce molecular classification of meningioma to one or several immunohistochemical stains (tests that detect specific proteins in tissue) have thus far not been reproducible. Such qualitative or semi-quantitative protein expression biomarkers may not fully capture the quantitative signal of a gene expression-based continuous risk score.

Current indications for postoperative radiotherapy for patients with meningiomas are controversial. This is particularly true for patients with primary WHO grade 2 meningiomas who are randomized to postoperative surveillance or postoperative radiotherapy on NRG BN-003 and EORTC 1308 after GTR.

Conflicting retrospective series have variably reported a benefit or no benefit from radiotherapy in this setting. This has fueled debate and inspired these international Phase III clinical trials of radiotherapy for patients with meningiomas.

The gene expression biomarker reported here improves risk stratification for primary WHO grade 2 meningiomas. The biomarker may identify favorable WHO grade 2 meningiomas where postoperative radiotherapy could be safely omitted in favor of close surveillance.

The gene expression biomarker also identifies primary WHO grade 1 meningiomas with elevated risk of recurrence. Most meningiomas are WHO grade 1 and are often considered benign. However, the researchers found that 6.4% of primary WHO grade 1 meningiomas in the multicenter retrospective clinical validation cohort were classified as gene expression high risk.

Limitations: What the Study Could Not Prove

The functional interactions among the genes included in the biomarker are incompletely understood. The biomarker includes a long non-coding RNA (a type of RNA that does not code for proteins). The interactions among the cell types in meningiomas are also incompletely understood. The relationships of these genes to meningioma histological variants are not fully known.

The study was primarily retrospective, meaning it looked back at past patient data. The prospective validation was limited to 103 patients from RTOG 0539. Larger prospective studies are needed to confirm the findings.

The researchers note that DNA methylation profiling was only able to predict the gene expression risk score to a moderate degree. This means DNA methylation testing is not a perfect substitute for the gene expression biomarker.

The study did not directly compare the gene expression biomarker to the current standard of care in a prospective randomized trial. Such a trial would be needed to definitively prove that using the biomarker improves patient outcomes.

Recommendations for Patients

If you or a loved one has been diagnosed with a meningioma, here are key points to discuss with your medical team:

  1. Ask about molecular testing: The gene expression biomarker described in this study is not yet widely available in clinical practice. Ask your doctor whether molecular testing of your tumor could provide useful information for your treatment plan.
  2. Discuss radiotherapy decisions: If you have a WHO grade 2 meningioma that was completely removed, ask your doctor about the risks and benefits of postoperative radiotherapy versus close surveillance. This study suggests that some patients may benefit from radiotherapy while others may not.
  3. Seek specialized care: Meningiomas are complex tumors. Consider seeking care at a center with expertise in brain tumors and access to clinical trials.
  4. Ask about clinical trials: The NRG BN-003 and EORTC 1308 trials are ongoing. Ask your doctor if you might be eligible for these or other clinical trials.
  5. Understand your risk group: If molecular testing is available, ask your doctor to explain which risk group your tumor falls into and what that means for your prognosis and treatment options.

The gene expression biomarker is not yet part of routine clinical care. However, this research represents an important step toward more personalized treatment for patients with meningiomas. The ability to predict which patients will benefit from radiotherapy could spare some patients from unnecessary treatment and its side effects, while ensuring that others receive the treatment they need.

Frequently Asked Questions

What is a 34-gene expression biomarker for meningioma?

It is a molecular test that measures the activity of 34 specific genes in a meningioma sample. In a validation cohort of 1,856 meningiomas from 12 institutions across 3 continents, it predicted 5-year local recurrence and overall survival better than the World Health Organization 2021 grade standard. It is not yet widely available in routine clinical care.

How accurate is this gene expression test for predicting meningioma recurrence?

In a validation cohort of 1,856 meningiomas from 12 institutions, the test achieved a 5-year area under the curve of 0.81 for local recurrence and 0.80 for overall survival. An area under the curve of 0.5 is random chance and 1.0 is perfect prediction. It outperformed the World Health Organization 2021 grade standard.

Can this test tell whether I will benefit from radiotherapy after meningioma surgery?

In a multicenter retrospective cohort, patients with unfavorable biomarker and surgical features benefited from postoperative radiotherapy (hazard ratio 0.54, 95% CI 0.37–0.78, P=0.0001), while those with favorable features did not (P=0.42). The test is not yet part of routine care, so discuss radiotherapy decisions with your doctor.

What do the low, intermediate, and high risk groups mean for my prognosis?

In a multicenter retrospective cohort of 866 meningiomas, 5-year local freedom from recurrence was 92.2% for low risk, 72.6% for intermediate risk, and 19.4% for high risk. This means patients in the low risk group had a 92.2% chance of remaining free from local recurrence at 5 years, while high risk patients had a 19.4% chance.

Could this test spare some patients from unnecessary radiotherapy?

In a multicenter retrospective cohort, the biomarker reclassified 52.0% of meningiomas compared to clinical criteria, including downstaging 21.3% of intermediate clinical risk patients who would have received postoperative radiotherapy. The researchers suggested postoperative management could have been refined for 29.8% of patients. The test is not yet part of routine care.

Is this gene expression test available now for patients with meningioma?

No. The gene expression biomarker described is not yet widely available in clinical practice and is not part of routine clinical care. If you have been diagnosed with a meningioma, ask your doctor whether molecular testing of your tumor could provide useful information for your treatment plan, and ask about clinical trials.

What should I discuss with my doctor if I have a WHO grade 2 meningioma that was completely removed?

Ask your doctor about the risks and benefits of postoperative radiotherapy versus close surveillance. In a multicenter retrospective cohort, primary WHO grade 2 meningiomas with complete removal did not benefit from postoperative radiotherapy without biomarker stratification, but unfavorable biomarker and surgical features identified those who did benefit (hazard ratio 0.33, 95% CI 0.14–0.76, P=0.009).

I have a WHO grade 2 meningioma that was completely removed — when should I seek a second opinion about whether I need postoperative radiotherapy?

A 34-gene expression biomarker identifies which meningiomas benefit from postoperative radiotherapy. Unfavorable tumors (intermediate risk with partial removal, or high risk with any removal) benefited (HR 0.54), while favorable tumors did not. Without biomarker stratification, primary WHO grade 2 meningiomas with complete removal showed no radiotherapy benefit, and postoperative management could be refined for 29.8% of patients. Because radiotherapy decisions for completely removed grade 2 meningiomas are controversial, a second opinion can help clarify whether testing and radiotherapy are appropriate. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses

Authors: William C. Chen, Abrar Choudhury, Mark W. Youngblood, Mei‐Yin C. Polley, Calixto‐Hope G. Lucas, Kanish Mirchia, et al.

Journal: Nature Medicine, 29(12): 3067–3076

Publication date: December 2023

DOI: 10.1038/s41591-023-02586-z

Corresponding authors: David R. Raleigh, MD, PhD (University of California, San Francisco); Stephen T. Magill, MD, PhD (Northwestern University); William C. Chen, MD (University of California, San Francisco)

Institutions involved: 12 institutions across 3 continents, including the University of California, San Francisco

Funding and disclosures: WCC and DRR are the inventors on patent PCT/US 21/70288 describing the use of targeted gene expression profiling to predict meningioma outcomes and radiotherapy responses. MP has received honoraria for lectures, consultation, or advisory board participation from several for-profit companies. The remaining authors declare no competing interests.

This patient-friendly article is based on peer-reviewed research published in Nature Medicine. It is intended for educational purposes and should not replace consultation with a qualified healthcare provider.