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EANO GUIDELINES FOR MANAGEMENT OF MENINGIOMA

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EANO GUIDELINES FOR MANAGEMENT OF MENINGIOMA

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This seminar is presented as a part of weekly journal club and seminar regularly conducted at Apollo hospital,Kolkata Department of Radiation oncology.

This seminar is presented as a part of weekly journal club and seminar regularly conducted at Apollo hospital,Kolkata Department of Radiation oncology.

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EANO GUIDELINES FOR MANAGEMENT OF MENINGIOMA

  1. 1. EANO guidelines for the diagnosis and treatment of meningiomas DR TANWEER SHAHID CONSULTANT,RADIATION ONCOLOGY APOLLO GLENEAGLES HOSPITALS,KOLKATA
  2. 2. INTRODUCTION Meningiomas: MC primary intracranial tumours.  Classified into grades : WHO grade I,II and III : On the basis of local invasiveness and cellular features of atypia. T/T by surgery alone, particularly patients with WHO grade I tumours in favourable locations (eg, convexity meningiomas, and easily accessible skull-base meningiomas). Beyond surgery, various radiotherapy approaches are often used to increase local control, especially if surgery alone seems insufficient
  3. 3. Introduction… • Meningioma : Originates from arachnoid cap cells. •Account for about one third of all brain tumors (CBTRUS, 2015). • Incidence increases with age. •Many histological subtypes and differ in their level of malignant behavior. •WHO classifies them in 3 grades, which have distinct prognostic properties. •Malignant meningiomas (WHO grade III) are rare, but aggressive.
  4. 4. Cause… 40% and 80% of meningiomas contain an abnormal chromosome 22. This chromosome is normally involved in suppressing tumor growth. The cause of this abnormality is not known. Previous radiation to the head. History of breast cancer. NF type 2 :Multiple meningiomas. Hormonal. Meningiomas may grow faster during pregnancy.
  5. 5. Location… Most common locations for meningiomas (in descending order) are: • Parasagittal dura. •Convexities. •Sphenoid wing. •CP angle cistern. •Olfactory groove. •Planum sphenoidale. •90% occur supratentorially. •1% of meningiomas outside CNS.
  6. 6. DIAGNOSTIC TOOLS MRI ◦ Dural tail, edema CT SCAN: ◦ Hyperostosis, intratumoral calcifications ANGIOGRAPHY: ◦ embolization is a consideration ◦ tumor blush
  7. 7. CECT… CT is valuable for the detection of calcification within the tumour, hyperostosis of adjacent bone, and intraosseous tumour growth, especially in skull-base meningiomas.  Extra axial mass, well-defined, smooth-contoured, which displaces the normal brain tissue. Sometimes meningiomas can be multilobulated or calcified.  Isointense with the normal brain tissue. Enhance uniformly with I.V contrast. This is more typical of benign meningiomas. Characteristics suggestive of aggressive behavior are:  indistinct margins,  marked edema,  mushroom-like projections from tumor,  deep brain parenchymal infiltration  Heterogenous enhancement
  8. 8. CECT…
  9. 9. MRI… MRI is preferred , as it is superior in demonstrating dural origin, as well as vascularity, edema, sinus and bone invasion.  Present as solitary round tumours, with close contact to the duramater and strong enhancement with contrast. Thickening of the duramater at the perimeter of the tumour (so-called dural tail) is displayed by T1 with gadolinium. Isointense or hypointense to gray matter on T1. Isointense or hyperintense on T2 weighted images. Areas of necrosis and calcification do not enhance.
  10. 10. MRI…
  11. 11. OTHER MODALITIES TO COMPLEMENT DIAGNOSIS Conventional cerebral angiography: No routine role in the diagnosis of meningioma, but can be used as an adjunct to treatment planning in selected cases.(eg. complex skull base meningioma) Expression of somatostatin receptor 2 can be used to discriminate them from healthy tissue, using peptide ligands such as  ⁶⁸Ga-Dotatate or  ⁹⁰Y-Dotatoc as PET tracers.
  12. 12. TREATMENT OPTIONS SURGERY ◦ Objective: total removal of the meningioma, dural attachment and bone involved with the tumor ◦ Priority: preserve and improve neurological function RADIOTHERAPY ◦ Indications: ◦ Residual tumor left at operation ◦ Recurrence ◦ Tumors could not be treated surgically ◦ Malignant histology
  13. 13. OVERVIEW  Meningiomas: MC intracranial tumours BUT the level of evidence to provide recommendations for the diagnosis and t/t is low compared with other tumours such as HGG .  Meningioma task force of the European Association of Neuro- Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals.
  14. 14. QUESTIONS TO ANSWER Is intervention needed for incidental meningiomas that have unclear growth kinetics? Do all suspected meningioma lesions require histological verification of the diagnosis? In cases in which RT is considered, when is the right time and what is the right fractionation approach? How will medical therapy develop in the future and what is the role of molecular profiling?
  15. 15. PURPOSE OF REVIEW Defining standards of care and outlining answers to some of these questions is the purpose of this Review.
  16. 16. LEVEL OF EVIDENCE AND RECOMMENDATION Class I :Evidence derived from prospective, RCT. Class II : Evidence derived from prospective studies, including observational studies, cohort studies, and case-control studies. Class III :Evidence derived from retrospective studies. Class IV :Evidence from uncontrolled case series, case reports, and expert opinions. Recommendation A- requires one or more class I studies or two consistent class II studies, Recommendation B-requires one or more class II studies or overwhelming class III evidence, Recommendation C- requires two or more consistent class III studies
  17. 17. WHO 2016 CLASSIFICATION
  18. 18. MANAGEMENT OUTLINE
  19. 19. Simpson Grade of Resection
  20. 20. TREATMENT OF MENINGIOMA GRADE 1- ROLE OF SURGERY  Asymptomatic: Observation (6 monthly to annually: Clinical examination and MRI ) (evidence level III, Recommendation level C)  Imaging strongly S/O Meningioma => Histological verification is not mandatory. However, exclusion of rare differential diagnoses such as metastasis is recommended (Recommendation level: good practice point)  Radiologically growth / clinical symptoms: Surgery is the First Choice (evidence level II, Recommendation level B)  Extent of resection should be confirmed by a postoperative MRI (within 48 h after surgery / after 3 months to avoid artefacts)
  21. 21. TREATMENT OF MENINGIOMA GRADE 1- ROLE OF RADIOTHERAPY Indications: Elderly patients (older than 65 years) Not safely accessible by surgery. Incomplete surgical resection
  22. 22. TYPES OF RADIOTHERAPY SRS-for small tumours Evidence**: 35 retrospective studies showed a 5-year progression-free survival of 86−100% after primary stereotactic radiosurgery. Fractionated EBRT: 50−55 Gy given in doses of 1·8−2·0 Gy per fraction can be applied (Evidence level III, Recommendation level B). **Rogers L, Barani I, Chamberlain M, et al. Meningiomas: knowledge base, treatment outcomes, and uncertainties. A RANO; review. J Neurosurg 2015; 122: 4–23.
  23. 23. TYPES OF RADIOTHERAPY Radiotherapy with subtotal resection: is associated with disease control and survival rates similar to those reported for gross total resection IMRT/ fSRT: to spare critical neurovascular structures surrounding the tumour and to reduce the risk of long-term cognitive deterioration => similar disease control to conventional radiotherapy.
  24. 24. MENINGIOMA GRADE 2. No clear radiological criteria distinguish WHO grade II meningiomas Exposure to Ionising Radiation: Increased Risk For Meningioma. Radiation-associated meningiomas: More likely to be atypical or malignant and multifocal than sporadic TERT mutations are associated with higher grade meningioma grades INCREASED RISK OF RECURRENCE THAN GRADE I
  25. 25. TREATMENT OF MENINGIOMA GRADE 2 ROLE OF SURGERY  Surgery is the first choice of treatment.  Should aim to achieve Simpson Grade I resection  (Evidence level III, recommendation level B)
  26. 26. FOLLOW UP After Total resection:  Annual MRI for 5 years => Biannual follow-ups. After subtotal resection:  MRI follow up at 6 and 12 months followed by annually.
  27. 27. TREATMENT OF MENINGIOMA GRADE 2- ROLE OF RADIOTHERAPY Role of adjuvant radiotherapy after gross complete resection????? ◦ ROAM/EORTC 1308 trial (ISRCTN71502099) : whether radiotherapy reduces the risk of or delays tumour recurrence.  Newly diagnosed Atypical Meningioma (WHO grade II)  Gross total resection (Simpson grade I–III)  early adjuvant radiotherapy (60 Gy in 30 fractions) vs. observation
  28. 28. TREATMENT OF MENINGIOMA GRADE 2- ROLE OF RADIOTHERAPY Role of adjuvant radiotherapy after partial resection??  Adjuvant radiotherapy (54–60 Gy given in 1·8−2·0 Gy per fraction) should be considered (evidence level III, recommendation level C) Fractionated RT is preferred over SRS techniques although SRS offers similar results for small tumours/ tumour residual
  29. 29. TREATMENT OF MENINGIOMA GRADE 2- ROLE OF CHEMOTHERAPY AND TARGETED THERAPY Retrospective studies and small prospective studies: (WHO grade II and III meningiomas) o Hydroxycarbamide o Cyclophosphamide/Doxorubicin/Vincristine chemotherapy, o interferon-alfa, o Megestrol acetate, Medroxyprogesterone acetate, Octreotide, Pasireotide (long-acting release), o Imatinib, Erlotinib, Gefitinib, Vatalanib, Sunitinib, o Bevacizumab. Most promising results for Bevacizumab, Vatalanib, and Sunitinib EORTC phase 2 trial (NCT02234050): efficacy of TRABECTEDIN shown promising activity in recurrent WHO grade II and grade III meningiomas.
  30. 30. FOLLOW UP MRI : every 6 months for 5 years then annually
  31. 31.  Anaplastic meningioma: irregular shape higher relative cerebral blood volume (rCBV) Recurrence risk is high Can metastasize systemically. Contain a high proportion of NF2 mutations , diffuse growth and invasion of the cortex. MENINGIOMA GRADE 3 vs GRADE 1 & 2
  32. 32. TREATMENT OF MENINGIOMA GRADE 3  Surgical resection: o should be as radical as possible (evidence level III, recommendation level C).  Adjuvant Radiotherapy: Fractionated o Dose: at least 54 Gy 1·8−2·0 Gy fractions (evidence level III, recommendation level B) Dose:  Complete resection: 54 Gy  Incomplete resection: 6o Gy. Pharmacotherapy options remain experimental; (evidence level IV, recommendation level C)
  33. 33. ONGOING TRIALS RTOG 0539 trial (NCT00895622): WHO Grade II: RT with 54 Gy in 30 fractions after gross total resection High-risk meningioma (ie, WHO Grade II recurrent disease, WHO Grade II after subtotal resection, and all WHO grade III) are receiving up to 60 Gy. EORTC 22042-26042 trial (NCT00626730): WHO Grade II and III after Gross Total resection: 60 Gy in 30 fractions After subtotal resection: 60 Gy in 30 fractions followed by Boost 10 Gy in 5 fractions to residual - Results awaited
  34. 34. FOLLOW UP MRI follow up every 6 months (every 3 months in rapidly growing cases)
  35. 35. SPINAL MENINGIOMA Surgical resection: 1st Choice to remove the tumour and decompress the spinal cord is the therapy of choice If surgical resection not possible: SRS or hypofractionated RT (recommendation level: good practice point) Adjuvant therapy is done according to WHO grade and resection.
  36. 36. RECOMMENDATIONS-TAKE HOME MESSAGE-DIAGNOSIS Radiological diagnosis of meningioma should be made by MRI Conventional angiography should be restricted to selected cases Tissue for future molecular analysis should be stored if available Histological verification of meningioma is not mandatory in all cases
  37. 37. RECOMMENDATIONS-TAKE HOME MESSAGE-TREATMENT Asymptomatic patients can be managed by observation only If t/t is indicated in meningioma of any WHO grade, Surgery is the first option Complete removal (Simpson grade I) is the primary goal of surgery Extent of resection should be confirmed by MRI Embolisation should be restricted to selected cases Radiosurgery might be the first option in small WHO Grade I meningiomas in specific locations
  38. 38. RECOMMENDATIONS-TAKE HOME MESSAGE-TREATMENT….. WHO Grade I meningioma who cannot undergo surgery : SRS or FSRT Subtotal resection in WHO Grade I: SRS or FSRT allows comprehensive tumor t/t while reducing the risk of adverse effects. WHO Grade II – Subtotal resection: should receive RT. Pharmacotherapy is experimental in any grade of meningioma and should only be considered if no further surgical or radiotherapy options exists.
  39. 39. RECOMMENDATIONS-TAKE HOME MESSAGE-FOLLOW UP WHO grade I:  First 5 years: Annually  After 5 years: every 2 years. WHO grade II :  First 5 years: Every 6 months  After annually after 5 years WHO grade III :  Every 3–6 months indefinitely
  40. 40. FUTURE DIRECTIONS Promising progress in diagnosis and t/t of meningiomas. The new WHO classification of meningioma.  Diagnosis of the extension of complex meningioma: eg, pre-treated intraosseous skull-base tumours - remains challenging. New PET tracers binding to somatostatin receptor 2 is a promising technique: Role in delineation, therapy planning & response assessment.
  41. 41. Last few words of Hope…. Surgical techniques and approaches: more refined in terms of individualised risk assessment. Skull-base meningiomas: Subtotal resection and SRS may be used more frequently to minimise treatment risk. Multidisciplinary diagnosis and therapy of meningiomas planned in dedicated brain tumour boards should become standard of care Prospective studies assessing efficacy and safety of novel systemic therapies are on their way. These studies will help to generate higher levels of evidence for future treatment concepts and hopefully improve outcomes for the minority of tumours that are still difficult to control.

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