Radiographic Enhancing Progression Without Molecular or Histologic Progression in IDH-Mutant Grade 2 Astrocytoma...

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Radiology

Background:

• Central nervous system (CNS) World Health Organization (WHO) Grade 2 isocitrate dehydrogenase (IDH)-mutant astrocytomas are low-grade gliomas with potential for malignant transformation.
• Early radiographic progression can complicate treatment decisions for these tumors.

Purpose of the Study:

• To present a case of IDH-mutant Grade 2 astrocytoma with early radiographic progression despite treatment.
• To discuss the implications of histological and molecular findings in differentiating treatment effects from true tumor progression.
• To emphasize the role of re-resection and subsequent therapies in managing such cases.

Main Methods:

• Case report of a patient with IDH-mutant Grade 2 astrocytoma treated with an IDH inhibitor.
• Radiographic assessment using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria.
• Histological and molecular analysis (Ki-67, copy number alterations) of resected tumor tissue.
• Subsequent treatment with radiation therapy and temozolomide chemotherapy.

Main Results:

• The patient developed new MRI enhancement 4 months after initiating an IDH inhibitor, suggesting radiographic progression.
• Re-resection revealed the tumor retained Grade 2 designation without histological or molecular progression (stable Ki-67, unchanged copy number alterations).
• The patient remained clinically stable for over 18 months after radiation and temozolomide treatment.

Conclusions:

• Re-resection can be crucial in managing IDH-mutant gliomas presenting with radiographic progression.
• Current response assessment criteria may have limitations in distinguishing treatment effects from true tumor progression.
• Further research into novel markers is needed for personalized treatment strategies in IDH-mutant gliomas.