Update Guidelines for progressive Glioblastoma by Congress of Neurological Surgeon in 2022 Imaging Gadolinium contrast-enhanced magnetic resonance imaging (MRI) is recommended for diagnosis of progressive glioblastoma multiforme (pGBM). Diffusion-weighted imaging should be considered as part of the standard MRI sequences used. 18-Fluorodeoxyglucose (FDG) is not recommended for routine diagnosis. Techniques using newer radiotracers may assist in the diagnosis. Role of Cytoreductive Surgery Cytoreductive surgery is recommended for patients with symptomatic pGBM. It is also recommended to improve overall survival in pGBM patients. Pathology Testing Repeat assessment of 06-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase status is not indicated. Programmed death ligand (PDL) 1/mismatch repair enzyme activity is not a useful component of standard diagnostic testing. If epidermal growth factor receptor amplification was not previously measured, its assessment at progression may be of diagnostic value. Large panel sequencing may be considered in patients who are eligible for or interested in molecularly guided therapy or clinical trials. Use of Cytotoxic Agents Benefit may be derived from treatment with temozolomide (TMZ; especially with progression after > 5 months off TMZ). Fotemustine is suggested in elderly patients with methylated MGMT promoter status. Tumor treatment fields (TTFs) with other chemotherapy may be considered for adult patients. The following are not suggested: (1) TMZ combined with other cytotoxic agents as standalone therapy; (2) other chemotherapeutic agents (including platinum compounds and topoisomerase inhibitors); (3) other cytotoxic therapies (eg, perillyl alcohol or ketogenic diet) as standalone therapy; and (4) oncolytic virotherapy. Role of Radiation Therapy Reirradiation should be considered for patients with pGBM; it can be safely used in elderly patients. Value of Targeted Therapy and Immunotherapy Bevacizumab does not provide increased overall survival when used to treat pGBM. There is not sufficient evidence to identify benefits and harms associated with its use in combination with other agents.
Dear prof Stanley kim first i would like to thank you for update and useful lecture. . Second I would like to please ask your permission to me to use some slides to use it in my lecture as radiation oncologist working at national oncology centre in Yement to present it in Neurosurgical Conference in Yemen on this month . With my best regards
On June 22, 2022, the Food and Drug Administration granted accelerated approval to dabrafenib (Tafinlar, Novartis) in combination with trametinib (Mekinist, Novartis) for the treatment of adult and pediatric patients ≥ 6 years of age with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options, which includes high grade gliomas. Dabrafenib in combination with trametinib is not indicated for patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition. Dabrafenib is not indicated for patients with wild-type BRAF solid tumors. The safety and efficacy were evaluated in 131 adult patients from open-label, multiple cohort trials BRF117019 (NCT02034110) and NCI-MATCH (NCT02465060), 36 pediatric patients from CTMT212X2101 (NCT02124772), and supported by results in COMBI-d, COMBI-v, and BRF113928 (studies in melanoma and lung cancer already described in product labeling). Study BRF117019 enrolled patients with BRAF V600E mutation positive specific solid tumors including high grade glioma (HGG), biliary tract cancer, low grade glioma (LGG), adenocarcinoma of small intestine, gastrointestinal stromal tumor, and anaplastic thyroid cancer (ATC). NCI-MATCH Subprotocol H enrolled adult patients with BRAF V600E mutation positive solid tumors except patients with melanoma, thyroid cancer, or CRC. Parts C and D of Study CTMT212X2101 enrolled 36 pediatric patients with BRAF V600 refractory or recurrent LGG or HGG. The major efficacy outcome measure of these studies was overall response rate (ORR) using standard response criteria. For the 131 adult patients, a total of 54 (41%, 95% CI: 33, 50) experienced an objective response. The studies enrolled patients with 24 tumor types, including different subtypes of LGG and HGG. Among the highest representative tumor types, ORR was 46% (95% CI: 31, 61) for biliary tract cancer, 33% (95% CI: 20, 48) for high grade glioma (combined) and 50% (95% CI: 23, 77) for low grade glioma (combined). For the 36 pediatric patients, the ORR was 25% (95% CI: 12, 42); DOR was ≥6 months for 78% of patients and ≥24 months for 44% of patients. The most common (≥20%) adverse reactions in adult patients were pyrexia, fatigue, nausea, rash, chills, headache, hemorrhage, cough, vomiting, constipation, diarrhea, myalgia, arthralgia, and edema. The most common (≥20%) adverse reactions in pediatric patients were pyrexia, rash, vomiting, fatigue, dry skin, cough, diarrhea, dermatitis acneiform, headache, abdominal pain, nausea, hemorrhage, constipation, and paronychia. The recommended dabrafenib dose in adult patients is 150 mg (two 75 mg capsules) orally twice daily in combination with trametinib 2 mg orally once daily. The recommended doses for dabrafenib and trametinib in pediatric patients are based on body weight. A recommended dose has not been established in patients who weigh less than 26 kg.
On March 16, 2023, the Food and Drug Administration approved dabrafenib (Tafinlar, Novartis) with trametinib (Mekinist, Novartis) for pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy. The FDA also approved new oral formulations of both drugs suitable for patients who cannot swallow pills. This represents the first FDA approval of a systemic therapy for the first-line treatment of pediatric patients with LGG with a BRAF V600E mutation. View full prescribing information for Tafinlar and Mekinist. Efficacy was evaluated in Study CDRB436G2201 (NCT02684058), a multicenter, open-label trial in patients with LGG (WHO grades 1 and 2) requiring first systemic therapy. Patients were randomized 2:1 to dabrafenib plus trametinib (D+T) or carboplatin plus vincristine (C+V). BRAF mutation status was identified prospectively by local or central laboratory tests. Retrospective testing of available tumor samples by the central laboratory was also performed to evaluate mutation status. Patients received age- and weight-based dosing of D+T until they were no longer deriving benefit or experienced unacceptable toxicity. C+V were dosed based on body surface area at 175 mg/m2 and 1.5 mg/m2 (0.05 mg/kg for patients < 12 kg), respectively, as one 10-week induction course, followed by eight 6-week cycles of maintenance therapy. The major efficacy outcome measure was overall response rate (ORR) by independent review based on RANO LGG (2017) criteria. Additional efficacy outcome measures were progression- free survival (PFS) and overall survival (OS). The primary analysis was performed when all patients had completed at least 32 weeks of therapy. In the LGG cohort, 110 patients were randomized to D+T (n=73) or C+V (n=37). ORR was 46.6% (95% CI: 34.8, 58.6) in the D+T arm and 10.8% (95% CI: 3.0, 25.4) for those receiving C+V (p= 2%) Grade 3 or 4 laboratory abnormalities were decreased neutrophil count (20%), increased alanine aminotransferase (3.1%), and aspartate aminotransferase increased (3.1%). The recommended doses for dabrafenib and trametinib in pediatric patients are based on body weight; dabrafenib is administered orally twice daily and trametinib is administered orally once daily. Dabrafenib and trametinib are administered until disease progression or unacceptable toxicity.
I was diagnosed with GBM4 6 years ago, but thankfully I had an immune response to the growing tumour in my right temporal lobe. The calcified cancer was surgically removed, and that was that 🤷🏻♂️
Now, not much. Just getting on with life tbh. It’s over 7 years ago now, not 6 as I said. Just had a scan after two years, and there’s still nothing there in my right temporal lobe, so all good 😊
Now, not much. Just getting on with life tbh. It’s over 7 years ago now, not 6 as I said. Just had a scan after two years, and there’s still nothing there in my right temporal lobe, so all good 😊
