Glioma lecture about a type cancer presentation

Glioma lecture about a type cancer presentation

1. Glioma By Zeyad Ahmed Safwat

2. Gliomas Diverse group of tumors originating from glial cells in the brain and spinal cord. Represent the most common primary brain tumor within the central nervous system. In the United States, there are  6 cases of gliomas diagnosed per 100,000 individuals every year.

3. Glioma grades Gliomas can be well-circumscribed or diffusely infiltrative tumors More recently, gliomas have been classified based on molecular and genetic markers. Gliomas range from grade 1 tumors ( ie , pilocytic astrocytomas ) to grade 4 tumors ( ie , glioblastoma). (WHO grading system)

4. Molecular and genetic markers Gliomas are subdivided based on 2 molecular markers: isocitrate-dehydrogenase (IDH) 1p/19q co-deletion others such as alpha-thalassemia X-linked intellectual disability mutations and mutations in TP53 Astrocytomas : IDH mutant (sole diagnosis) Oligodendrogliomas: IDH mutant and 1p/19q co-deletion. Glioblastomas: IDH wildtype (no longer classified as mutant)

5. Commonality of different tumour types in different age groups Astrocytomas : Originate from astrocytes. Low-grade tumors are more common in children , while high-grade neoplasms are more common in adults. Oligodendrogliomas : These gliomas originate from oligodendrocytes and are less infiltrating than astrocytomas . They are commonly found in middle-aged adults. 

6. Commonality of different tumour types in different age groups Ependymomas:  These gliomas originate from ependymal cells. They are more common in young children.

7. Epidemiology General trend: Brain tumors are somewhat uncommon considering one individual in 165 will be diagnosed with a brain tumor in their lifetime. However, trends from 1970s onwards have shown an increased diagnosis of brain tumors in developed countries. with a world age standardized incidence rate that ranges from 4.3 to 18.6 per 100,000 per year

8. Epidemiological trends in the USA In the US : an estimated 80,000 to 90,000 newly diagnosed cases of primary brain tumors each year in the United States, with approximately  25% being gliomas .   6 cases of gliomas diagnosed per 100,000 individuals every year.

9. Epidemiological trends in Saudi Arabia A significant increase in the incidence of CNS cancers, with rates increasing from 1.1 to 3.63 per 100,000 population. In Saudi Arabia, CNS cancers are relatively rare compared to global statistics, with metastatic carcinoma and high-grade gliomas being the most prevalent.

10. Epidemiological trends of brain tumours in the UAE The expatriate population had higher percentage of brain tumors (72%) than the locals. However, the average annual incidence rate (per 100,000) of primary brain tumors was higher among UAE local population compared to expatriates (1.07: 0.35). Diffuse astrocytic and oligodendroglial tumors were the most commonly diagnosed tumors overall.

11. Epidemiological trends of brain tumours in the UAE Global brain tumour incidence has increased in recent decades, mainly due to improved diagnostic techniques. In the UAE, however , no consistent upward trend is observed . Case numbers and incidence rates peaked in 2008 (48 cases, 1.04 per 100,000), followed by a decline.

12. Treatment and prognosis of IDH-mutant, 1p/19q- codeleted oligodendrogliomas in adults Vorasidenib : An FDA approved IDH1/2 inhibitor targeting IDH-mutant gliomas. Shown to prolong progression-free survival in patients with residual grade 2 tumors and delaying radiation therapy (RT) and chemotherapy. PCV Regimen (Procarbazine, Lomustine , Vincristine): Frequently used in combination with RT. Proven to improve survival rates in both grade 2 and 3 oligodendrogliomas.

13. Treatment and prognosis of IDH-mutant, 1p/19q- codeleted oligodendrogliomas in adults Temozolomide : An alternative chemotherapy agent to PCV, often favored for its ease of administration and better tolerance. Ivosidenib , Olutasidenib , Safusidenib : Other IDH inhibitors under investigation for IDH-mutant gliomas, showing potential in early trials.

14. Management of recurrent high-grade gliomas Despite the survival benefit associated with adjuvant radiation and chemotherapy, the majority of patients relapse following initial therapy. Therapy is not curative, so treatment decisions for patients with recurrent or progressive high-grade glioma must be individualized

15. LOCALIZED THERAPY Reoperation Reirradiation External beam delivery techniques Brachytherapy Laser interstitial thermal therapy (LITT)

16. SYSTEMIC THERAPY Choice of therapy: bevacizumab ( mAb targeting VEGF-A ) Nitrosoureas (e.g. Lomustine ) and temozolomide ( Alkylating agent) rechallenge No single agent has been shown to be clearly superior to another. The addition of bevacizumab to lomustine improved progression-free but not overall survival compared with lomustine alone, and toxicity was higher with combination therapy.

17. Genotype-directed therapies TRK fusion-positive tumors , Two TRK inhibitors: larotrectinib and entrectinib Approved in the United States and elsewhere for use in adults and children with TRK fusion-positive solid tumors without a known acquired resistance mutation.

18. Genotype-directed therapies BRAF V600E-mutant tumors Reported in approximately 3% of glioblastomas Benefit from the combination of dabrafenib and trametinib was shown in the phase 2 open-label ROAR trial. Granted tissue-agnostic approval by the FDA in June 2022 in patients ≥6 years of age with unresectable or metastatic BRAF V600E-mutant solid tumors that have progressed on previous treatment.

19. Recently approved product Voranigo ( Vorasidenib ) Inhibits the enzymes isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) . Approved for medical use in the United States in August 2024 by FDA for grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 mutation.

20. Glioma Disease Emerging Drugs ONC 201( Dordaviprone ): Chimerix Orally administered small molecule dopamine receptor D2 (DRD2) antagonist and caseinolytic protease ( ClpP ) agonist. For recurrent gliomas that harbor the H3 K27M mutation. ( poor prognosis gliomas( around 8 months )). Currently, the drug is in Phase III stage for the treatment of Glioma.

21. Glioma Disease Emerging Drugs Enzastaurin : Denovo BioPharma An orally available investigational first-in-class small molecule , serine/threonine kinase inhibitor of the PKC beta, PI3K, and AKT pathway. Received Orphan Drug Designation in DLBCL and Glioblastoma multiforme (GBM) from the FDA and EMA and Fast Track Designation from the FDA.

22. Glioma Disease Emerging Drugs Potential combination Denovo BioPharma has initiated a biomarker guided Phase III clinical study evaluating the DB102 ( enzastaurin ) in combination with temozolomide and radiation as first line therapy to treat newly-diagnosed Glioblastoma multiforme (GBM).

23. Glioma Disease Emerging Drugs MDNA55: Medicenna Therapeutics, Inc. An Empowered Superkine developed as a therapeutic for recurrent glioblastoma multiforme ( rGBM ), a molecular trojan horse. Currently, the drug is in phase II stage of its clinical trial for the treatment of Glioma.

24. Glioma Disease Emerging Drugs Safusidenib : AnHeart Therapeutics Novel, selective, potent, oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) For the treatment of IDH1-mutant gliomas One of the most common types of adult primary brain cancer . It strongly inhibits mutant IDH1 but not wild-type IDH1. Currently, the drug is in phase II stage of its clinical trial for the treatment of Glioma.