role of RT in pediatric CNS Tumors .pptx

basic principals of radiation therapy,its types,dna damage ,radiation machines including c0 60 and linac, ,RT mechanism, latest advances including 3dcrt.vmat, and role of rt in pediatric cns tumors.especially for pediatric oncologists

1. RADIATION THERAPY AND ITS ROLE IN PEDIATRIC CNS TUMORS Dr Sadia Sadiq Consultant Radiation Oncologist INMOL

2. OUTLINE Pediatric CNS tumors epidemiology Radiation Therapy, Types , Techniques T he RT planning process Role of RT in common pediatric malignant brain tumor histologies RT-associated toxicities, and long term follow up

3. The relative proportion of different tumor types in different age groups (a) Children up to age 15 years (b) Young people aged 15–24 years

4. Distribution of all primary CNS tumors A ) children ages 0–14 years old B ) adolescents and young adults 15–39 years CBTRUS: US Cancer Statistics - NPCR and SEER, 2014–2018)

5. Gliomas are most common Medulloblastoma is 2 nd most common Ependymoma is 3 rd most common Other histologies make up 11% Craniopharyngioma make up 5% INMOL CANCER REGISTRY 2015-23 n=358

6. Gliomas Brainstem glioma is most common Pilocytic astrocytoma is 2 nd most common GBM is 3 rd most common

7. When people hear the word “radiation” they often think… The reality of medical use of radiation therapy is very different

8. Radiations..

9. Biological effects of Radiation..DNA Damage

10. THE EVOLUTION OF RADIATION THERAPY Discovery of X-Rays 1895 Discovery of Radioactivity 1896 Isolation of Polonium and Radium 1898 X-ray machine 1 st patient treated( Ca Breast) 1896 Brachytherapy Early 1900s C0-60 1951

11. THE EVOLUTION OF RADIATION THERAPY Multileaf Collimator Dynamic MLC and IMRT 1960’s The First Clinac 1970’s 1980’s 1990’s 2000’s Cerrobend Blocking Electron Blocking Functional Imaging High resolution I MRT Blocks were used to reduce the dose to normal tissues MLC leads to 3D conformal therapy which allows the dose e e s s c c a l a l a a t t i i o n o n Computerized IMRT introduced which allowed escalation of dose and reduced compilations Computerized 3D CT Treatment Planning Standard Collimator The linac reduced complications compared to Co60

12. Co -60 and LINAC

13. Advances in Radiation Therapy - The New Pyramid GTV Precise localization Geographic miss P TV NORMAL TISSUE CTV

14. Transition from 2D to IMRT 2D 3DCRT IMRT Goal : Delivery of high dose to the tumour and a lower dose to the OAR 15

15. Limitations of 3D-CRT 16

16. VMAT Provides dose distributions that are equivalent or better than current IMRT techniques. VMAT is capable to modulated by leaf speed, dose rate variation and gantry rotation simultaneously. VMAT can improve patient comfort by dramatically reducing the amount of time (reduced by 7 minutes ) patients spend on the treatment couch (less movements'…. 17

17. The patient /target position correction - 3D-3D matching , where on-board imaging (CBCT /MVCT ) is shifted/rotated in three dimensions to match planning CT Increased radiation exposure from diagnostic imaging if the reliance is on CT or X-ray imaging. MRI-based image guidance is being investigated. . on-board cone-beam CT ( CBCT ) imaging (KV) M V C T IMAGE-GUIDED RADIATION THERAPY (IGRT)

18. ADAPTATIVE RADIOTHERAPY C hanging the radiation treatment plan delivered to a patient during a course of radiotherapy to account for Temporal changes in anatomy (e.g. tumor shrinkage/growth, weight loss or internal motion

19. Originally designed to brain tumors, stereotactic radiotherapy is now available for lesions throughout the body. +++ Hight technical precision with Submillimeter accuracy using a set of convergent microbeams The large dose per fraction lessens the therapeutic ratio for normal tissues and increases the risk of radio necrosis unless cases are very carefully selected. highly concentrated and precise beams SBRT WITH CYBERKNIFE® 20

20. Proton Therapy

21. Single beam dose profiles for Photons and Protons

22. Comparison of dose distributions for a patient undergoing craniospinal irradiation 3DCRT IMRT PBRT

23. The Multidisciplinary Care

24. The Radiotherapy   Team ◆ paediatric radiation oncologists ◆ specialist paediatric therapeutic radiographers ◆ mould room staff ◆ play specialists ◆ dosimetrists ◆ physicists. It will also be supported by appropriate administrative and clerical staff.

25. RT Process

26. 1. Information and  Consent ◆ what radiotherapy is in principle ◆ why it might be useful ◆ what alternatives there might be ◆ specific imaging for treatment planning ◆ immobilization ◆ whether anaesthesia might be needed ◆ the duration of treatment, each day and overall ◆ the likely short-term side effects ◆ the possible long-term complications of treatment

27. Working Toy Models

28. 2.Positioning and Immobilization Treatment planning Scans Good immobilization is essential for precision radiotherapy Care should be taken to ensure that the planning CT scan covers not only the likely target volume but also in full any organs at risk. All relevant prior imaging must be available and may be fused in the planning system as appropriate for the case.

29. 3.Image Registration, Target Volume Delineation & RT Planning Delineation of the target volumes and organs at risk for radiotherapy planning is the core skill of the radiation oncologist. Peer review of volumes will reduce the risk of errors at this stage, which may lead to treatment failure, remaining undetected. A  successful planning process requires frequent and excellent communication between all team members . Consistent and standardized dose fractionation schedules should be used, except in clinical trials. Interruptions in treatment should be avoided, if possible, or compensated for when necessary.

30. 4.Follow-up during and after RT Patients should be reviewed at least weekly during treatment to monitor progress and deal with any complications. More common medical issues include: ◆ nausea and vomiting ◆ anorexia and weight loss ◆ myelosuppression ◆ neutropenia, sepsis, and other infections ◆ raised intracranial pressure ◆ mouthcare .

31. General principles of RT in Pediatric brain tumors Avoidance of RT altogether if possible. Delay RT in young children [3-8 years] by the use of chemotherapy. Use focal than Extended field RT Daily anesthesia and better immobilization helps to reduce planning target volume. Field size a little generous as kids may be un cooperative Use Image based treatment planning [ 3DCRT/IMRT] Reduce the total dose of RT Use smaller fraction size where appropriate

32. Low grade Astrocytomas Indolent clinical course OS at 10 and 15 years – 80-100% Most common type is Pilocytic astrocytoma Accounting for almost all of LGA at certain sites [ anterior optic pathway & cerebellum] Well circumscribed and frequently associated with cystic component. Hall mark microscopic feature is Rosenthal fibres .

33. Management of Low grade Astrocytomas Small asymptomatic..Observation Surgery is the mainstay of treatment..MSR Post OP adjuvant therapy not indicated RT may be indicated following incomplete resection when tumor progression compromise neurologic function. 50 – 54Gy depending upon the age of the child , location of the tumor and its relation to critical normal structures.

34. Brain stem gliomas Constitutes 20% of childhood tumors. Most common in children between 3-10 years. Tissue confirmation is frequently not feasible in infiltrating lesions. Associated with poor prognosis RT dose 54 Gy / 30#....poor PS ..39Gy/13#

35. Medulloblastoma M ost common embryonal CNS tumor in the pediatric population . 4 groups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. WNT..best prognosis and group 3.. the worst Median age at presentation is 5- 8 years High propensity for CSF dissemination [20-30 %] Hence contrast MRI of spinal axis and CSF cytology is essential.

36. Medulloblastoma Management

37. Immobilization

38. Brain and Spinal CTV

39. RT fields used in CSI

40. Dose distribution in CSI

41. Ependymomas Third most common CNS tumor in children. Can occur at any site in ventricular system or spinal canal. 5-10% has leptomeningeal seeding at time of diagnosis. MRI of whole CNS and CSF cytology are essential components of work up. ACNS0121 : 5y EFS rate of 65–70% with RT after gross or near-total resection of the tumor compared with 37% for tumors that were incompletely resected with adjuvant chemotherapy ACNS0831 :may be some EPN patients who benefit from maintenance chemotherapy

42. Management of Ependymomas Maximum surgical resection. Post OP radiation therapy is the standard is the standard of care for all children with ependymoma . RT dose : 54-59.4 Gy Post OP RT can be avoided in completely resected Ependymoma of spinal cord Supraventricular ependymomas resected with wider margin.

43. Germ cell tumors More common in Asia Accounts for 15 – 18% of all CNS tumors in children. Peak incidence is 10 -12 years. Boys affected more frequently than girls. Arise from primordial germ cells around third ventricle. NGGST more common in pineal gland region. Germinomas more common in supra sellar region. Leptomeningeal spread is 10-15%.

44. IGCT dose fractionation and target management considerations

45. Craniopharyngiomas Benign cystic epithelial tumors. Arise in sellar region from remnants of Rathke’s pouch Accounts for 5% of CNS tumors in children. Mostly ademantinomatous type Peak incidence 5-14 years.

46. Craniopharyngiomas…Role of Radiation Complete surgical resection is the standard of care. Indications of RT Incomplete resection Progression Recurrence. Dose is 50-54 Gy DFS 80-100% in most series.

47. I n Pediatric RT: Target is the Star but sparing OAR is our Art

48. LATE EFFECTS Factors affecting the risk of late effects on OARS Age of child at the time of RT Total dose of RT Dose per fraction OTT Dose rate Volume of organ treated RBE of the irradiated tissue Serial vs. parallel organ Use of chemo: concomitant/before/after Presence of existing functional compromise/ comorbs

49. QUANTEC ( QUantitative Analysis of Normal Tissue Effects in Clinic) PENTEC ( PEdiatric Normal Tissue Effects in Clinic) VS .

50. Long term effects of pediatric brain irradiation Neurocognitive and neurophysiological dysfunction. Endocrine abnormalities and hormonal imbalance Growth retardation – spinal component. Ototoxicity – especially with platinum based chemotherapy. Gonadal toxicity and reduced fertility Cerebrovascular accidents Second malignancies.

51. GH deficiency is most common after RT. (risk is 50% at 5 years for a dose >16   Gy ) Precocious puberty and thyroid deficiency may be seen at higher doses. Cortisol deficiency - uncommon DI is extremely rare after RT and usually attributed to mass effect of tumor or surgery.

52. Multidisciplinary long-term follow-up service

53. Conclusion Management of pediatric brain tumors has improved a lot in past three decades. Improved imaging, newer techniques in pathology, better neurosurgical techniques and evolution of high precision radiotherapy revolutionized the treatment Currently 5 year survival rate is estimated at 75% for all CNS tumors in 0-19 years age group.