Frontiers in Diagnosis and Treatment of Gliomas


ROLE OF SYSTEMIC THERAPY IN GLIOMA MANAGEMENT

Iyavut Thaipisuttikul, MD

Chulalongkorn Comprehensive Cancer Center, King Chulalongkorn Memorial Hospital, Bangkok, Thailand


SYNOPSIS

Diffuse gliomas are a group of primary brain tumors which consists of infiltrative astrocytic and oligodendroglial tumors. Surgical management, radiotherapy (RT) and systemic therapy are the mainstay for glioma treatment. The role of systemic therapy for gliomas has become significant since the publish of the landmark Stupp’s trial (EORTC 26981–22981/NCIC CE3) in 2005. Despite advances in the understanding of glioma biology, the current standard therapy for glioblastoma still consists of maximal surgical resection followed by concomitant radio-chemotherapy and adjuvant therapy with temozolomide (TMZ). The result of this approach, however, is still far from optimal. The new glioma classification which integrates molecular diagnostics into routine histopathological method plays important role in tumor management under various circumstances. Treatment decision for glioblastoma in elderly may depend on the result of MGMT promoter methylation testing. The addition of adjuvant PCV chemotherapy to RT has become a standard of care for IDH-mutant low-grade glioma and IDH-mutant/1p/19q-codeleted anaplastic oligodendroglioma in many regions of the world.  There is evidence from CATNON trial to support the use of 12-cycle adjuvant temozolomide chemotherapy after RT for IDH-mutant, 1p/19q-non-codeleted anaplastic astrocytoma. Whether treatment with TMZ as in Stupp’s regimen for glioblastoma can be used for IDH-mutant/1p/19q-codeleted anaplastic oligodendroglioma is still pending the result of modified CODEL trial.

There is no standard of care for treatment of recurrent gliomas. Treatment decisions depend on tumor location, grading of tumor at recurrence, treatment received at initial diagnosis and performance status. Systemic therapy is often the only available option for recurrent glioblastoma due to the risk of retreatment with surgery and RT. Cytotoxic chemotherapy can be used such as re-challenged TMZ, nitrosoureas, platinum, and oral etoposide. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor, was approved by U.S. FDA for use in recurrent glioblastoma in 2009. The initial radiographic response and disease control are transient. Most patients develop tumor progression after a median of 3–5 months.

More recently, there is excitement that immunotherapy, such as immune checkpoint inhibitors, peptide vaccines, DC vaccines and adoptive t cell therapy may be an effective option for glioma patients. Benefits and adverse effects of are still being explored in clinical trials.


PATHOLOGICAL DIAGNOSIS OF GLIOMAS

Professor Shanop Shuangshoti, MD

Department of Pathology and Chulalongkorn GenePRO Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.


SYNOPSIS

Since the recent World Health Organization (WHO) classification of Tumors of the Central Nervous System (CNS) issued in 2016, molecular parameters have been incorporated into the classification and routine diagnosis of gliomas. In adults, IDH mutation has linked diffuse astrocytomas to oligodendrogliomas, and separated them from other astrocytic tumors e.g. pilocytic astrocytoma. IDH mutation test by immunostain and/or molecular assay is now required for diagnosis of diffuse gliomas. 1p/19q co-deletion and IDH mutation are now needed to establish the diagnosis of oligodendroglial tumors. With ancillary tests, most of the cases previously diagnosed as mixed gliomas (oligoastrocytoma and anaplastic oligoastrocytoma) could be re-classified into either oligodendroglial or astrocytic linage. Thus, the diagnosis of “mixed glioma” is discourage. Epithelioid glioblastoma has been shown to carry BRAF 600E mutation in about haft of the cases. Diffuse midline glioma, H3 K27M-mutant (WHO grade IV) with various morphological features from low- to high-grade, and RELA fusion–positive ependymoma, have been proposed.   More recently, cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) has been established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. The term “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” has been introduced for diffuse and anaplastic astrocytic gliomas without IDH mutation but demonstrate at least one of the following genetic features: EGFR amplification, whole chromosome 7 gain and whole chromosome 10 loss (+7/-10), and TERT promoter mutation. The term “diffuse midline glioma, H3 K27M–mutant” is now restricted to tumors that are diffuse/infiltrating, midline gliomas, with H3 K27M-mutant, and should not be applied to other tumors (e.g., ependymomas) that carry H3 K27M mutation. Several other genetic features are being evaluated in gliomas, and more molecular tests will be required for diagnosis and classification of CNS tumors in the next WHO book.  In Thailand, molecular diagnosis has largely been driven by drugs. Not infrequently, molecular signatures with impact on diagnosis and prognosis are ignored. Cost of tests and re-imbursement issue appear to be one of the important factors.

Event Hours(1)

  • Lotus 3-4

    02:45 pm – 04:00 pm

    Speakers:
    1. Dr. Iyavut Thaipisuttikul (CU)
    2. Prof. Jiraporn Laothamatas (CRA)
    3. Assoc. Prof. Mantana Dhanachai (Rama)
    4. Asst. Prof. Sarun nunta-aree (SI)
    5. Prof. Shanop Shuangshoti (CU)

    Moderator:
    Assoc. Prof. Sith sathornsumetee (SI)

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