Recurrent Glioblastoma Management Guidelines

Diagnosis and Assessment

The National Comprehensive Cancer Network recommends gadolinium-enhanced MRI with diffusion-weighted imaging as the standard diagnostic tool for detecting recurrent glioblastoma 2
Pseudo-progression should be considered if MRI changes are noted within 6-9 months after radiotherapy, requiring careful evaluation to avoid unnecessary interventions 1, 4
Distinguishing between true progression and treatment-related changes may require advanced imaging techniques such as amino acid PET in cases of diagnostic uncertainty 5, 6
Regular follow-up with MRI every 2-3 months is recommended for surveillance after initial treatment 1, 7

The American College of Surgeons recommends repeat cytoreductive surgery to improve overall survival in selected patients with recurrent glioblastoma 2
Surgical resection should be considered for patients with symptomatic but circumscribed relapses diagnosed at least 6 months after initial surgery, large symptomatic lesions causing mass effect, good performance status, and possibility of gross total resection 1, 2, 7
Second surgery earlier than 6 months after initial surgery increases the risk of intervention based on pseudoprogression and is unlikely to provide durable benefit 1
The decision for re-operation should only be made after multidisciplinary consultation 8

The European Society for Medical Oncology recommends lomustine as a standard treatment option for recurrent glioblastoma with confirmed single-agent efficacy 4, 6
Bevacizumab provides high response rates with a steroid-sparing effect, though the effect on overall survival remains uncertain 5, 4
Bevacizumab plus lomustine combination may improve progression-free survival compared to lomustine alone but does not significantly improve overall survival and increases the risk of severe adverse events 4
Temozolomide rechallenge may be considered in patients with MGMT promoter-methylated tumors who had a prolonged interval since completion of initial temozolomide therapy 3

Re-irradiation may be considered for selected patients with small recurrent tumors using different modalities (brachytherapy, stereotactic radiotherapy) 8
The benefit of re-irradiation remains uncertain due to limited prospective and comparative trials 4

The National Comprehensive Cancer Network recommends considering targeted therapies such as dabrafenib/trametinib or vemurafenib for BRAF V600E-mutated tumors 7
TRK fusion-positive tumors may respond to larotrectinib or entrectinib 7
Hypermutant tumors may be candidates for immune checkpoint inhibitors such as nivolumab or pembrolizumab 7
ALK rearrangement-positive tumors may benefit from lorlatinib or alectinib 7

The American Society of Clinical Oncology recommends palliative and best supportive care for patients with poor performance status, large or multifocal lesions, inability to consent to treatment, or cases where aggressive therapy is unlikely to provide meaningful survival benefit 7, 3, 1
Recommended regimens for palliation include oral etoposide, bevacizumab, or nitrosoureas (lomustine or carmustine) 7
Corticosteroids may be used to manage symptomatic cerebral edema, with efforts to taper as early as possible 5

The National Comprehensive Cancer Network recommends enrollment in clinical trials whenever possible for patients with recurrent glioblastoma 7, 3
Consider phase 0 or preoperative clinical trials before resection when available 7
Molecular testing of tumor tissue may help determine eligibility for targeted therapy trials 7