Glioma, including glioblastoma

Adult-type diffuse gliomas comprise IDH-mutant astrocytoma, IDH-mutant and 1p/19q-codeleted oligodendroglioma, and IDH-wildtype glioblastoma. IDH-mutant grade 4 astrocytoma is not called glioblastoma in the current classification. Pediatric-type and circumscribed gliomas have separate categories and can require different treatment.

Grade describes biological behavior within the tumor type, not a stage showing spread through the body. New diagnostic guidance also cautions against automatically calling an apparently low-grade tumor glioblastoma from a TERT promoter mutation alone; age, tissue, imaging and additional molecular findings matter.

Contrast MRI shows location, enhancement, swelling and proximity to critical structures. Surgery or biopsy usually supplies tissue for an integrated pathology report. If imaging, age and pathology do not fit together, expert neuropathology review and sometimes DNA methylation profiling can clarify the diagnosis.

IDH helps define tumor identity; whole-arm 1p/19q codeletion is required for oligodendroglioma. MGMT promoter methylation helps estimate benefit from alkylating chemotherapy in glioblastoma. H3 and BRAF testing is selected according to tumor type and location. A mutation found in tumor tissue does not automatically mean an inherited condition.

The goal is maximal safe resection. Mapping, awake techniques or intraoperative imaging may help when speech or movement pathways are close to the tumor. Leaving a small amount to protect essential function can be a deliberate decision; a deeper or less accessible tumor may be better sampled by biopsy.

A postoperative MRI provides a baseline. A scan showing no visible residual diffuse glioma does not prove that every infiltrating cell has been removed. Subsequent treatment depends on the molecular diagnosis, grade, symptoms and recovery.

Selected grade 2 tumors can be monitored after surgery when the team judges that radiotherapy and chemotherapy can safely be deferred. This requires scheduled MRI and symptom review. Growth, residual burden, neurologic symptoms and individual risk can favor earlier treatment.

When treatment is needed, radiotherapy plus PCV chemotherapy has an established role in grade 2–3 oligodendroglioma; temozolomide may be an alternative when PCV toxicity is a concern. For grade 3 IDH-mutant astrocytoma, radiotherapy followed by adjuvant temozolomide is a standard pathway. Grade 4 disease needs its own multidisciplinary plan.

Vorasidenib targets susceptible IDH1/2 mutations. Its US indication covers patients aged 12 or older with grade 2 astrocytoma or oligodendroglioma after surgery, including biopsy. The EU indication is more specific: predominantly non-enhancing tumors, specified IDH1/2 mutations, age at least 12 and weight at least 40 kg, surgery only, and no immediate need for radiotherapy or chemotherapy.

The randomized evidence supports delaying progression and the next intervention in a selected postoperative population. It does not establish a replacement for necessary chemoradiotherapy in grade 3–4 disease or prove the same benefit after prior radiotherapy/chemotherapy. Liver tests, interactions and reproductive planning require attention.

For suitable patients, treatment usually combines safe surgery, radiotherapy with temozolomide, then adjuvant temozolomide. Frailty and neurologic function influence whether a shorter radiotherapy course or a less intensive plan is preferable. MGMT status is especially useful when weighing chemotherapy in older or frailer patients; it should be interpreted with the assay and clinical situation.

Tumor treating fields can be discussed with maintenance temozolomide in eligible newly diagnosed supratentorial glioblastoma. This requires wearable scalp arrays and sustained use, with skin care and daily-life implications. It is an additional option, not a substitute for the underlying treatment plan.

For H3 K27M-mutant diffuse midline glioma progressing after prior therapy, dordaviprone has US accelerated approval from age one. The broader diagnostic term H3 K27-altered is not identical to the mutation-specific drug indication. The supporting response analysis was small and excluded DIPG and primary spinal tumors; those limitations do not rewrite the label, but matter when discussing expected benefit. ECG/electrolyte monitoring and interaction review are needed.

BRAF V600E mutation and BRAF fusion are different findings. US pediatric low-grade options include dabrafenib/trametinib from age one for BRAF V600E tumors needing systemic therapy, and accelerated-approved tovorafenib from six months for relapsed/refractory tumors with qualifying BRAF fusion, rearrangement or V600 mutation. These approvals should not be generalized to every adult glioma.

Enhancement after radiotherapy may reflect treatment effects rather than active tumor. The team compares scans over time, symptoms and steroid use; advanced imaging or selected repeat tissue sampling may help. New weakness, confusion or seizures still require prompt assessment rather than assuming pseudoprogression.

At confirmed recurrence, options can include a trial, selected repeat surgery or reirradiation, chemotherapy and symptom-directed treatment. Bevacizumab may reduce edema in some settings without an established overall-survival gain. CAR-T, vaccines and viral therapies remain investigational for glioblastoma; a promising early response is not proof of durable benefit.

Record seizures, speech or memory changes, falls and steroid use. Antiseizure treatment is appropriate after seizures; routine long-term preventive treatment is not established for everyone who has never had one. Steroids can relieve tumor-related swelling but require a clinician-guided dose and taper.

Physiotherapy, speech/occupational therapy and cognitive support can be as important as the scan result. Discuss fatigue, mood, driving restrictions, work and caregiver needs. Early palliative support helps manage symptoms alongside tumor treatment.

Bring the integrated pathology report and molecular results, tissue availability, pre/postoperative and follow-up MRI files, operation notes, radiotherapy plan, systemic treatment history and current medicines. Include your priorities for communication, mobility, work and independence.

Ask which finding determines the diagnosis, whether more testing would change management, what safe surgery can achieve, and why treatment should start now or can be deferred. If discussing a trial, clarify its phase, eligibility, travel burden and effects on standard care.