Is Tempus xT and xR testing clinically useful for a patient with a history of oligodendroglioma and medication-refractory seizures?

Tempus xT and xR Testing for Oligodendroglioma with Refractory Seizures

Direct Recommendation

I do not recommend approving Tempus xT and xR testing for this patient, as the essential molecular characterization (IDH mutation and 1p/19q codeletion status) has already been completed, and comprehensive genomic profiling beyond established diagnostic markers does not change management or improve outcomes in oligodendroglioma patients with medication-refractory seizures.

Rationale Based on Current Molecular Workup

Already Completed Essential Testing

• The patient's tumor has already undergone the critical molecular testing required for oligodendroglioma diagnosis and prognostication, including IDH mutation detection (positive) and 1p/19q codeletion assessment (negative by FISH) 1
• According to WHO 2016 classification standards, oligodendroglioma diagnosis requires both IDH mutation AND 1p/19q codeletion; this patient's tumor lacks the 1p/19q codeletion, which means it does not meet criteria for true oligodendroglioma and should be classified as "oligodendroglioma, NOS" or potentially reclassified as an IDH-mutant astrocytoma 1
• The 13 high-yield alterations recommended by NCCN for glioma workup per the 2021 WHO classification have likely been addressed through the existing IDH and 1p/19q testing, which represent the most clinically actionable markers 1

Limited Clinical Utility for Seizure Management

• Medication-refractory seizures in oligodendroglioma are primarily managed through tumor-directed therapy (surgery, radiation, chemotherapy) and optimized antiepileptic drug regimens, not through identification of additional genomic alterations 2, 3
• Seizure control in oligodendroglioma patients improves with tumor treatment: surgery or radiotherapy achieves seizure freedom in approximately two-thirds of patients, and chemotherapy reduces seizures in about 50% 2
• The presence of IDH1 mutation (already confirmed in this patient) is the primary molecular alteration associated with seizures in oligodendroglial tumors, and no additional genomic markers from expanded panels have been shown to guide seizure management 2
• Pharmacoresistance occurs in approximately 40% of oligodendroglioma patients despite polytherapy, but this is not predicted or modified by the genomic alterations detected on comprehensive panels like Tempus xT/xR 2

Evidence Against Broad Genomic Profiling in This Context

Lack of Established Clinical Utility

• NCCN states that the role remains uncertain for "cancer multiomic molecular profiling" in CNS tumors, and neither Tempus xT (genomics) nor xR (transcriptomics) are FDA-cleared or approved companion diagnostic devices for glioma 1
• The insurer's position limiting support to 5-50 gene panels for specific cancer types (excluding CNS tumors) and not supporting tests over 50 genes reflects the lack of evidence for clinical utility of comprehensive genomic profiling in gliomas 1
• While NGS is increasingly preferred for pathologic workup of CNS tumors, this refers to targeted panels screening for the established diagnostic and prognostic mutations (IDH, 1p/19q, MGMT, ATRX, TERT, H3 K27M), not 648-gene comprehensive panels 1

No Impact on Treatment Decisions

• For oligodendroglioma management, treatment decisions are based on grade, extent of resection, IDH mutation status, 1p/19q codeletion status, and MGMT promoter methylation—not on the hundreds of additional genes covered by Tempus xT 1
• The standard of care for anaplastic oligodendroglioma is radiotherapy and adjuvant chemotherapy; for lower-grade tumors, observation or treatment with radiotherapy and/or chemotherapy based on clinical factors—none of which require 648-gene profiling 1
• Targeted therapies for specific alterations (EGFR, BRAF, NTRK) are rare in oligodendroglioma (occurring in 3-5% or less) and remain investigational, not standard of care 1

Alternative Appropriate Testing

Consider These Instead

• MGMT promoter methylation status should be determined if not already done, as this is a validated prognostic marker that influences treatment decisions in gliomas 1
• ATRX immunohistochemistry could help refine the diagnosis, as ATRX loss is virtually mutually exclusive with 1p/19q codeletion and would support reclassification as IDH-mutant astrocytoma rather than oligodendroglioma 1
• Repeat 1p/19q assessment using loss of heterozygosity or SNP array/array CGH platforms may be warranted, as FISH probes are not 100% specific for whole arm loss and can yield false results 1

Seizure-Specific Workup

• For medication-refractory seizures, the appropriate diagnostic approach includes EEG monitoring, consideration of epilepsy surgery evaluation, and optimization of antiepileptic drug therapy with evidence-based agents like levetiracetam or valproic acid 4, 5, 2
• Metabolic and electrolyte evaluation (glucose, sodium, calcium, magnesium) should be performed to identify treatable causes of seizure exacerbation 4, 5
• Advanced neuroimaging with FDG-PET or amino acid PET tracers may help identify the epileptogenic zone for surgical planning, but this is distinct from tumor genomic profiling 1

Critical Pitfalls to Avoid

• Do not conflate research-grade comprehensive genomic profiling with clinically validated diagnostic testing—the former generates extensive data of uncertain significance that does not improve patient outcomes 1
• Avoid ordering expensive out-of-network testing when in-network alternatives can provide the clinically necessary information (MGMT, ATRX, refined 1p/19q testing)
• Recognize that the absence of 1p/19q codeletion in this patient fundamentally changes the diagnosis and prognosis—true oligodendrogliomas with 1p/19q codeletion have better outcomes and treatment responses than this patient's tumor 1, 3
• Do not assume that identifying additional genomic alterations will provide actionable targets for seizure control—the evidence shows seizure management depends on tumor control and appropriate AED selection, not molecular profiling 2