Guideline sources The following summarized guidelines for the evaluation and management of diffuse glioma are prepared by our editorial team based on guidelines from the European Association of Neuro- Oncology (EANO 2021). 1 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Screening and diagnosis https://web.pathway.md/diseases/recBe9Tc1A8oSfRI1 1/3 6/29/23, 10:17 PM Diffuse glioma Pathway Screening: recognize that screening and prevention have no major role for patients with gliomas. B 2. Classification and risk stratification Classification: use the most recent WHO Classification of Tumors of the CNS for glioma classification, complemented by cIMPACT-NOW. B 3. Diagnostic investigations History and physical examination: assess the Karnofsky performance score and neurological function, as well as the patient's age, individual risks, and benefits for clinical decision-making. B Diagnostic imaging: Obtain MRI without and with gadolinium contrast as the first choice diagnostic imaging modality. B Suspect pseudoprogression in patients with an increase of abnormalities on neuroimaging in the first months after local therapeutic interventions (including radiotherapy) and after experimental local treatments. B 4. Diagnostic procedures Tissue diagnosis: perform resection or biopsy in the standard of care of patients with IDH- mutant astrocytomas, WHO grade 2 requiring further treatment, or grade 3. B Show 2 more Analysis of biopsy specimens: obtain routine immunohistochemistry for mutant IDH-1 R132H protein and nuclear expression of ATRX in the diagnostic evaluation of patients with diffuse gliomas. B Show 7 more 5. Medical management Chemotherapy: offer chemotherapy with procarbazine, lomustine and vincristine polychemotherapy after resection or biopsy in the standard of care of patients with IDH-mutant astrocytomas, WHO grade 2 requiring further treatment. B Show 5 more 6. Therapeutic procedures Radiotherapy: perform field radiotherapy after resection or biopsy in the standard of care for patients with IDH-mutant astrocytomas, WHO grade 2 requiring further treatment or grade 3. B Show 2 more https://web.pathway.md/diseases/recBe9Tc1A8oSfRI1 2/3 6/29/23, 10:17 PM Diffuse glioma Pathway 7. Surgical interventions Surgical resection: perform resection as feasible or biopsy followed by involved field radiotherapy and maintenance chemotherapy in the standard of care of patients with IDH- mutant astrocytomas, WHO grade 2 requiring further treatment, or grade 3. B Show 2 more 8. Specific circumstances Elderly patients: offer radiotherapy (such as 2.66 Gy for 15 sessions) or chemotherapy with temozolomide (5 out of 28 days) based on MGMT promoter methylation status in elderly patients with IDH-wild-type glioblastoma ineligible for combined chemoradiotherapy. B 9. Patient education Genetic counseling: refer patients with relevant germline variants or suspected hereditary cancer syndromes for genetic counseling and, subsequently, for possible molecular genetic testing. B 10. Follow-up and surveillance Management of recurrent gliomas: recognize that standards of care of patients with IDH- wild-type glioblastomas are less well defined at recurrence. B Show 3 more Studies 2023 INDIGO In patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery, vorasidenib was superior to placebo with respect to median progression-free survival. Ingo K Mellinghoff et al. N Engl J Med. 2023 Jun 4. Online ahead of print. References 1. Michael Weller, Martin van den Bent, Matthias Preusser et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021 Mar;18 3 170 186. Open https://web.pathway.md/diseases/recBe9Tc1A8oSfRI1 3/3