Is Tempus xT and xR testing recommended for a patient with oligodendroglioma and a complex medical history, including medication refractory seizures and an IDH mutation?

Tempus xT and xR Testing is NOT Recommended for This Patient with Oligodendroglioma

The extensive molecular profiling offered by Tempus xT (648 genes) and xR (whole transcriptome) testing is not justified for this patient with oligodendroglioma, as the essential diagnostic and prognostic molecular markers (IDH mutation and 1p/19q status) have already been established, and there are no FDA-approved targeted therapies for oligodendroglioma that would require such broad genomic profiling.

Rationale Based on Current Guidelines and Evidence

Essential Molecular Testing Already Completed

• The patient's tumor has already been tested for the two most critical molecular markers in oligodendroglioma: IDH mutation (positive) and 1p/19q codeletion (negative by FISH) 1.
• According to WHO 2016 and 2021 classifications, a true oligodendroglioma diagnosis requires both IDH mutation AND 1p/19q codeletion 2, 3.
• This patient's tumor lacks 1p/19q codeletion, which means it does not meet diagnostic criteria for oligodendroglioma and should be reclassified as either astrocytoma, IDH-mutant or oligodendroglioma, NOS 1.

Limited Clinical Utility of Broad NGS Panels in Gliomas

The 2025 EANO guidelines provide clear direction on molecular testing in gliomas:

• Testing for most molecular alterations beyond standard diagnostic markers (IDH, 1p/19q, MGMT) is not recommended given the lack of effective therapies (ESCAT IIIA) 1.
• For alterations like RET, PTEN/PI3K, and MTAP, testing should be limited to patients in good clinical condition with available clinical trial options 1.
• High TMB and MMR deficiency testing is only relevant in specific contexts: young adults (<50 years), tumors with unusual features, or in the setting of available clinical trials 1.

No Actionable Targets for Standard Treatment

• The standard treatment paradigm for IDH-mutant gliomas consists of maximal safe resection, radiotherapy (50-60 Gy), and chemotherapy with PCV or temozolomide 1.
• None of these treatment decisions require the 648-gene panel or whole transcriptome analysis offered by Tempus xT and xR 1.
• For oligodendroglioma (or astrocytoma, IDH-mutant), treatment at progression includes temozolomide or nitrosourea, which do not require genomic profiling beyond standard markers 1.

Specific Concerns with This Testing Request

Diagnostic Clarification Needed First:

• The absence of 1p/19q codeletion by FISH requires confirmation with a more definitive method (loss of heterozygosity or SNP array/array CGH) before pursuing additional testing 1.
• FISH probes are sensitive but not 100% specific for whole arm 1p/19q loss, particularly in tumors with equivocal morphology 1.
• The tumor should be reclassified as astrocytoma, IDH-mutant if 1p/19q codeletion is definitively absent, which would change the diagnostic category but not the immediate treatment approach 1.

Clinical Trial Context:

• If the patient has exhausted standard treatment options and is considering clinical trial enrollment, targeted testing for specific trial requirements would be more appropriate than broad profiling 1.
• The 2025 EANO guidelines emphasize that testing for novel targets should be limited to patients with clinical trial options available 1.

Cost-Effectiveness and Insurance Coverage Issues

• The insurer does not support genomic sequencing panels over 50 genes for solid tumors, and CNS cancers/gliomas are not included in their list of supported cancers for gene panel testing.
• The laboratory is out-of-network, which will create significant financial burden for the patient without clear clinical benefit.
• A more cost-effective stepwise approach using targeted testing (IDH1/2, ATRX, 1p/19q) is recommended for gliomas 1.

Recommended Alternative Approach

Immediate Steps:

• Confirm 1p/19q status using SNP array or loss of heterozygosity analysis if not already done with a definitive method 1.
• Test for MGMT promoter methylation if not already performed, as this has prognostic and potentially predictive value for alkylating agent chemotherapy 1, 3.
• Consider ATRX immunohistochemistry if not done, as ATRX loss and 1p/19q codeletion are virtually mutually exclusive and can help refine diagnosis 1.

For Clinical Trial Consideration:

• If the patient is being evaluated for a specific clinical trial, obtain the trial's molecular eligibility requirements and perform only the necessary targeted testing 1.
• Screening for MTAP deletion, TMB, or MMR deficiency should only be considered in the context of available clinical trials 1.

At Disease Progression:

• Standard treatment options (temozolomide rechallenge, nitrosourea, bevacizumab) do not require broad genomic profiling 1.
• Re-biopsy at progression may be considered if there is concern for transformation to higher grade or if clinical trial enrollment is being pursued 1.