What is the management approach for a patient with oligodendroglioma (a type of brain tumor) who has 1p deletion without 19q codeletion?

Management of Oligodendroglioma with 1p Deletion Without 19q Codeletion

A tumor with isolated 1p deletion (without 19q codeletion) should be classified and managed as an astrocytoma, not an oligodendroglioma, because the diagnosis of oligodendroglioma requires both 1p AND 19q codeletion along with IDH mutation. 1

Critical Diagnostic Clarification

The 2016 WHO classification fundamentally changed glioma diagnosis by requiring specific molecular markers:

• True oligodendroglioma requires BOTH IDH mutation AND complete 1p/19q codeletion 1
• Isolated 1p deletion (or 19q deletion alone) without the partner chromosome loss means the tumor is NOT an oligodendroglioma 1
• These tumors with only one chromosome arm deleted are classified as astrocytomas (if IDH-mutant) or fall into other categories depending on additional molecular features 1

Treatment Algorithm Based on Molecular Classification

For Grade 2 Tumors (1p deleted, 19q intact, IDH-mutant = Astrocytoma, IDH-mutant, WHO grade 2):

Initial management options: 1

• Wait-and-see approach for low-risk patients (age <40, gross total resection, minimal symptoms)
• Radiotherapy (50-54 Gy in 1.8-2 Gy fractions) followed by PCV chemotherapy for higher-risk patients (age ≥40, subtotal resection, or symptomatic disease)
• Temozolomide chemoradiotherapy is an alternative to PCV 1

For Grade 3 Tumors (1p deleted, 19q intact, IDH-mutant = Anaplastic astrocytoma, IDH-mutant, WHO grade 3):

Standard treatment: 1

• Radiotherapy (54-60 Gy in 1.8-2 Gy fractions) followed by temozolomide
• Alternative: Wait-and-see in highly selected cases with excellent performance status and complete resection 1

For Grade 3 Tumors (1p deleted, 19q intact, IDH wild-type):

Standard treatment: 1

• Radiotherapy (54-60 Gy in 1.8-2 Gy fractions) with temozolomide chemoradiotherapy
• Consider MGMT promoter methylation status to guide chemotherapy decisions 1

Evidence Supporting Different Treatment for Non-Codeleted Tumors

Key Trial Data Showing Molecular Status Matters:

RTOG 9402 trial demonstrated: 1

• Patients with 1p/19q codeletion: significant OS benefit from PCV + RT (HR 0.41, P=0.006)
• Patients with 1p/19q intact or only one deletion: NO significant OS benefit from PCV + RT (HR 0.63, P=0.17)
• The survival benefit of adding chemotherapy to radiotherapy was specific to the codeleted population 1

EORTC 26951 trial showed: 1

• Subgroups with IDH-mutant status and 1p/19q codeletion derived the most benefit from combined therapy
• Tumors with only one chromosome arm deleted (1p OR 19q, not both) had substantially less benefit from PCV 1

Critical Pitfalls to Avoid

Testing Methodology Matters:

• FISH probes for 1p/19q are sensitive but NOT 100% specific for whole arm loss 1
• For equivocal cases or high-grade tumors, confirm with loss of heterozygosity analysis or SNP array/array CGH to ensure true whole-arm codeletion 1
• Isolated 1p deletion detected by FISH may represent partial deletion, not the prognostically favorable whole-arm loss 1

Do Not Extrapolate Oligodendroglioma Data:

• The favorable prognosis and high chemosensitivity of oligodendrogliomas applies only to 1p/19q-codeleted tumors 1, 2
• Tumors with intact 1p/19q or only one deletion behave more like astrocytomas with shorter progression-free survival 3, 4
• PCV chemotherapy benefit is NOT established for tumors lacking complete 1p/19q codeletion 1

Additional Molecular Testing Required

Check ATRX status: 1

• ATRX loss and 1p/19q codeletion are virtually mutually exclusive 1
• If 1p is deleted but 19q is intact, expect ATRX loss (confirming astrocytoma lineage) 1

Confirm IDH mutation status: 1

• Start with IDH1 R132H immunohistochemistry 1
• If negative, proceed to IDH1 codon 132 and IDH2 codon 172 sequencing 1
• IDH wild-type status in a grade 2-3 glioma suggests more aggressive biology requiring consideration of glioblastoma-type treatment 1

Treatment at Progression

For recurrent disease: 1, 5

• Temozolomide or nitrosourea-based chemotherapy 1
• Consider repeat surgery if feasible with multidisciplinary consultation 5
• Bevacizumab for IDH wild-type tumors 1
• Temozolomide rechallenge if good initial response 1

Seizure Management Considerations

First-line antiepileptic therapy: 5

• Levetiracetam is preferred due to lack of drug interactions with chemotherapy 5
• Lamotrigine is an effective alternative 5
• Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) as they interfere with chemotherapy metabolism 5

For breakthrough seizures: 5

• Obtain urgent brain MRI to rule out tumor progression 5
• Check serum drug levels before escalating therapy 5
• Add second non-enzyme-inducing AED rather than switching if on therapeutic monotherapy 5