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high grade glioma.pptx

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high grade glioma.pptx

  1. 1. Medhat Mustafa, MD, Department of Neurosurgery Suez Canal University, Ismailia, Egypt
  2. 2. Glioblastoma Multiforme
  3. 3. Objectives:  Describe the etiology of high-grade gliomas.  Outline the pathogenesis and appropriate evaluation of high-grade gliomas.  Desribe the presentation  Review the management options available for lhigh-grade gliomas.  Identify interprofessional team strategies for improving care coordination and communication to advance cancer, high-grade gliomas, and improve outcomes.
  4. 4. Background Of the estimated 17,000 primary brain tumors diagnosed in the United States each year, approximately 60% are gliomas. Gliomas comprise a heterogeneous group of neoplasms that differ in location within the central nervous system, in age and sex distribution, in growth potential, in extent of invasiveness, in morphological features, in tendency for progression, and in response to treatments.
  5. 5. Etiology The etiology of glioblastoma remains unknown in most cases. Familial gliomas account for approximately 5% of malignant gliomas, and less than 1% of gliomas are associated with a known genetic syndrome (eg, neurofibromatosis, Turcot syndrome, or Li-Fraumeni syndrome) Studies of association with head injury, N-nitroso compounds, occupational hazards, and electromagnetic field exposure have been inconclusive
  6. 6. Epidemiology Glioblastoma multiforme is the most frequent primary brain tumor, accounting for approximately 12-15% of all intracranial neoplasms and 50-60% of all astrocytic tumors. In most European and North American countries, incidence is approximately 2-3 new cases per 100,000 people per year Overall incidence is very similar among countries. Glioblastoma multiformes are slightly more common in the United States, Scandinavia, and Israel than in Asia.
  7. 7. Glioblastoma multiforme may manifest in persons of any age, but it affects adults preferentially, with a peak incidence at 45-70 years males had a slight preponderance over females, with a male-to-female ratio of 3:2
  8. 8. Pathophysiology Glioblastomas can be classified as primary or secondary. Primary glioblastoma multiforme accounts for the vast majority of cases (60%) in adults older than 50 years. These tumors manifest de novo (ie, without clinical or histopathologic evidence of a preexisting, less-malignant precursor lesion), and patients presenting after a short clinical history, usually less than 3 months.
  9. 9. Secondary glioblastoma multiformes (40%) typically develop in younger patients (< 45 y) through malignant progression from a low-grade astrocytoma (WHO grade II) or anaplastic astrocytoma (WHO grade III). The time required for this progression varies considerably, ranging from less than 1 year to more than 10 years, with a mean interval of 4-5 years
  10. 10. Increasing evidence indicates that primary and secondary glioblastomas constitute distinct disease entities that evolve through different genetic pathways, affect patients at different ages, and differ in response to some of the present therapies
  11. 11. Glioblastoma multiformes occur most often in the subcortical white matter of the cerebral hemispheres. In a series of 987 glioblastomas from University Hospital Zurich, the most frequently affected sites were the temporal (31%), parietal (24%), frontal (23%), and occipital (16%) lobes. Combined frontotemporal location is particularly typical.
  12. 12. Tumor infiltration often extends into the adjacent cortex or the basal ganglia. When a tumor in the frontal cortex spreads across the corpus callosum into the contralateral hemisphere, it creates the appearance of a bilateral symmetric lesion, hence the term butterfly glioma. Sites for glioblastomas that are much less common are the brainstem (which often is found in affected children), the cerebellum, and the spinal cord.
  13. 13. Some of the more common genetic abnormalities are described as follows Mutations in p53, a tumor suppressor gene Epidermal growth factor receptor (EGFR) gene Platelet-derived growth factor–alpha (PDGF-alpha) gene PTEN: PTEN (also known as MMAC and TEP1) encodes a tyrosine phosphatase located at band 10q23.3
  14. 14. Presentation The clinical history of patients with glioblastoma multiformes (GBMs) usually is short, spanning less than 3 months in more than 50% of patients, unless the neoplasm developed from a lower-grade astrocytoma.
  15. 15. The most common presentation of patients with glioblastomas is a slowly progressive neurologic deficit, usually motor weakness. However, the most common symptom experienced by patients is headache. Alternatively, patients may present with generalized symptoms of increased intracranial pressure (ICP), including headaches, nausea and vomiting, and cognitive impairment. Seizures are another common presenting symptom.
  16. 16. Imaging Studies Magnetic resonance imaging (MRI) Magnetic resonance imaging (MRI) with and without contrast is the study of choice These lesions typically have an enhancing ring observed on T1-weighted images and a broad surrounding zone of edema apparent on T2- weighted images.. A T1-weighted axial MRI without intravenous contrast. This image demonstrates a hemorrhagic multicentric tumor (glioblastoma multiforme [GBM]) in the right temporal lobe. Effacement of the ventricular system is present on the right, and mild impingement of the right medial temporal lobe can be observed on the midbrain
  17. 17. The central hypodense core represents necrosis, the contrast- enhancing ring is composed of highly dense neoplastic cells with abnormal vessels permeable to contrast agents, and the peripheral zone of nonenhancing low attenuation is vasogenic edema containing varying numbers of invasive tumor cells A T1-weighted coronal MRI with intravenous contrast. This image demonstrates the lesion (glioblastoma multiforme [GBM]) within the medial temporal lobe and the stereotypical pattern of contrast enhancement
  18. 18. A T2-weighted axial MRI. The tumor (glioblastoma multiforme [GBM]) and surrounding white matter within the right temporal lobe show increased signal intensity compared to a healthy brain
  19. 19. A fluid-attenuated inversion recovery (FLAIR) axial MRI. This image is similar to the T2-weighted image and demonstrates extensive edema in a patient with glioblastoma multiforme (GBM).
  20. 20. Several pathological studies have clearly shown that the area of enhancement does not represent the outer tumor border because infiltrating glioma cells can be identified easily within, and occasionally beyond, a 2-cm margin
  21. 21. Positron emission tomography (PET) scans and magnetic resonance (MR) spectroscopy can be helpful to identify glioblastomas in difficult cases, such as those associated with radiation necrosis or hemorrhage.
  22. 22. On PET scans, increased regional glucose metabolism closely correlates with cellularity and reduced survival. MR spectroscopy demonstrates an increase in the choline-to-creatine peak ratio, an increased lactate peak, and decreased N- acetylaspartate (NAA) peak in areas with glioblastomas
  23. 23. Magnetic resonance (MR) spectroscopy is representative of a glioblastoma multiforme (GBM), demonstrating a high peak ratio of choline (CHO) to creatine (CR), a decreased N-acetylaspartate (NAA) peak, and an increased lactate (LAC) peak.
  24. 24. Histologic Findings Glioblastoma multiformes are composed of poorly differentiated, often pleomorphic astrocytic cells with marked nuclear atypia and brisk mitotic activity. Necrosis is an essential diagnostic feature, and prominent microvascular proliferation is common
  25. 25. Undoubtedly, glial fibrillary acidic protein (GFAP) remains the most valuable marker for neoplastic astrocytes. Although immunostaining is variable and tends to decrease with progressive dedifferentiation, many cells remain immunopositive for GFAP even in the most aggressive glioblastomas. Vimentin and fibronectin expression are common but less specific
  26. 26. The regional heterogeneity of glioblastomas is remarkable and makes histopathological diagnosis a serious challenge when it is based solely on stereotactic needle biopsies. Tumor heterogeneity is also likely to play a significant role in explaining the meager success of all treatment modalities, including radiation, chemotherapy, and immunotherapy.
  27. 27. Completely staging most glioblastomas is neither practical nor possible because these tumors do not have clearly defined margins. Rather, they exhibit well-known tendencies to invade locally and spread along compact white matter pathways, such as the corpus callosum, internal capsule, optic radiation, anterior commissure, fornix, and subependymal regions. Such spread may create the appearance of multiple glioblastomas or multicentric gliomas on imaging studies
  28. 28. Careful histological analyses have indicated that only 2-7% of glioblastomas are truly multiple independent tumors rather than distant spread from a primary site.
  29. 29. Despite its rapid infiltrative growth, the glioblastoma tends not to invade the subarachnoid space and, consequently, rarely metastasizes via cerebrospinal fluid (CSF).
  30. 30. Hematogenous spread to extraneural tissues is very rare in patients who have not had previous surgical intervention, and penetration of the dura, venous sinuses, and bone is exceptional
  31. 31. Treatment The treatment of glioblastomas remains difficult in that no contemporary treatments are curative While overall mortality rates remain high, improved understanding of the molecular mechanisms and gene mutations combined with clinical trials are leading to more promising and tailored therapeutic approaches
  32. 32. Multiple challenges remain, including tumor heterogeneity tumor location in a region where it is beyond the reach of local control and rapid, aggressive tumor relapse. Therefore, the treatment of patients with malignant gliomas remains palliative and encompasses surgery, radiotherapy, and chemotherapy..
  33. 33. Because glioblastomas cannot be cured with surgery, the surgical goals are to establish a pathological diagnosis, relieve mass effect, and, if possible, achieve a gross total resection to facilitate adjuvant therapy
  34. 34. Upon initial diagnosis of glioblastoma multiforme (GBM), standard treatment consists of maximal surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy with temozolomide
  35. 35. While patients are in the hospital, they should receive postoperative imaging to determine the extent of surgical resection. Surgical resection is evaluated best within 3 days of surgery by using contrast-enhanced MRI. Contrast enhancement during this period accurately reflects residual tumor
  36. 36. For patients older than 70 years, less aggressive therapy is sometimes employed, using radiation or temozolomide alone A study by Scott et al found that elderly patients with glioblastoma who underwent radiotherapy had improved cancer-specific survival and overall survival compared with those who did not undergo radiotherapy treatment
  37. 37. Evidence suggests that in patients over 60 years old, treatment with temozolomide is associated with longer survival than treatment with standard radiotherapy, and for those over 70 years old, temozolomide or hypofractionated radiotherapy is associated with prolonged survival than treatment with standard fractionated radiotherapy
  38. 38. Median time to recurrence after standard therapy is 6.9 months. For recurrent glioblastoma multiforme, surgery is appropriate in selected patients, and various radiotherapeutic, chemotherapeutic, biologic, or investigational therapies are also employed
  39. 39. Most glioblastomas recur in and around the original tumor bed, but contralateral and distant recurrences are not uncommon, especially with lesions near the corpus callosum.
  40. 40. Reoperation is generally considered in the face of a life-threatening recurrent mass, particularly if radionecrosis rather than recurrent tumor is suspected as the cause of clinical and radiographic deterioration
  41. 41. Positron emission tomography (PET) scans and magnetic resonance (MR) spectroscopy have proven useful in discriminating between those 2 entities
  42. 42. The extent of surgery (biopsy vs resection) has been shown in a number of studies to affect length of survival
  43. 43. patients with high-grade gliomas who had a gross total resection had a 2-year survival rate of 19%, while those with a subtotal resection had a 2-year survival rate of 0%.
  44. 44. The use of functional MRI and diffusion tensor imaging (DTI) in preoperative planning, as well as ultrasound, CT scans, and MRI with direct stimulation during surgery, has allowed for multimodal neuronavigation and the integration of patient- specific anatomic and functional data. Despite these technologies, differentiating between normal brain and residual tumor continues to be a major challenge
  45. 45. Oral aminolevulinic acid (ALA; Gleolan) was approved by the US Food and Drug Administration (FDA) in 2017 as an adjunct for visualization of malignant tissue during surgery in patients with malignant glioma (suspected WHO grades III or IV on preoperative imaging).
  46. 46. During surgery, an operating microscope adapted with a blue-emitting light source and filters for excitation light of wavelength 375-440 nm, and observation at wavelengths of 620-710 nm is used to visualize PpIX (an ALA metabolite) accumulation in tumor cells that shows up as red fluorescence
  47. 47. Fluorescence-guided surgery (FGS), an emerging technology that combines detection devices with fluorescent contrast agents, may provide more complete and precise resection of gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate for FGS of glioma and other tumor types.
  48. 48. Even with advances in surgical resection, the prognosis for patients with GBM remains poor
  49. 49. Aside from extent of surgical resection, other factors have been associated with increased and overall survival Patient age and Karnofsky Performance Status are widely recognized as prognostic factors, with lower age and higher performance status conferring longer survival
  50. 50. Tumors greater than 5–6 cm and those that cross the mid-line have been associated with negative outcomes . Supratentorial and cerebellar tumors, which are more amenable to surgical treatment, carry a better prognosis than tumors in the brainstem or diencephalon