Thierry M. Muanza, MSc, MD, FRCPC,, McGill University Segal Cancer Centre, Jewish General Hospital Montreal, QC, Canada

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1 Thierry M. Muanza, MSc, MD, FRCPC,, McGill University Segal Cancer Centre, Jewish General Hospital Montreal, QC, Canada

2 Déclarations Aucun conflit d intérêt

3 Objectifs d apprentissage Évolution de la radiothérapie pour les tumeurs du SNC Tumeurs Statistiques Radiothérapie Imagerie/planification Hydrontherapie: particules chargées TTF: champ traitant les tumeurs Essais cliniques

4 Canadian Cancer Statistics 2017

5 Canadian Cancer Statistics 2017

6 Statistiques Canadiennes 2017 Tumeurs du SNC 3,000 Canadians will be diagnosed with brain and spinal cord cancer. 2,400 Canadians will die from brain and spinal cord cancer. 1,700 men will be diagnosed with brain and spinal cord cancer and 1,350 will die from it. 1,300 women will be diagnosed with brain and spinal cord cancer and 1,050 will die from it.

7 Tumeurs du SNC Primary astrocytes oligodendrocytes ependymal cells Secondary Metastasis Lung, breast, melanoma, renal cell etc Low-grade (noncancerous) tumours grow slowly High-grade (cancerous) tumours grow quickly

8 Histopatholigical classification nuclear atypia mitosis, WHO Pilocytic astrocytoma WHO Grade I St Anne/Mayo criteria 0 criterion endothelial proliferatio n-'piled-up' endothelial cells. NOT hypervascularity Diffuse astrocytoma Anaplastic astrocytoma II III 1 criterion (a) 2 criteria (a+b necrosis. Glioblastom a IV 3-4 criteria (a+b[+/- c]+d)

9 Classification WHO 2016

10 Response to Therapy Inactive methylated MGMT Active unmethylated MGMT

11 IDH mutation and survival GBM

12 Radiothérapie

13 Chromosomal Damage Apoptosis Reproductive death Necrosis

14 Tumor Oxygenation

15 Effect of Oxygen

16 Re-oxygenation

17 Percent Depth Dose

18 Radiotherapy delivery : External beam radiotherapy: Photons: X-rays: Linear accelerators. γ-rays: Cobalt machines. Particles: Electrons. Neutrons. Protons. Brachytherapy: Interstitial. Intracavitary.

19 Linear Accelerator

20

21 LINAC

22 Radiotherapy indications CNS tumors Benign: Meningioma Acoustic schwannoma Pituitary adenoma Malignant Primary: astrocytoma, oligodendroglioma, ependymoma Secondary: Metastasis lung, breast, melanoma

23 Patient referral to oncology Investigations Cancer staging Multidisciplinary Tumor Board Radiotherapy Treatment Sequence History, physical examination, imaging, biopsy, pathology T = tumor size N = lymph node extension M = metastasis Surgeon, radiation oncologist, medical oncologist, pathologist & radiologist CT simulation: immobilisation, isocenter, marking CT planning: image fusion (US/MRI/PET) Target volumes delineation Treatment planning/dosimetry Treatment recommendations / clinical trials

24 XRT Treatment Volumes

25 Timing and clinical manifestation of radiation injury 1. Acute clinical period 2. Sub-acute period 3. Chronic clinical period 4. Late clinical period 0-6 months 6-12 months 1-5 years

26 Acute versus late injury Timing depends on cell cycle kinetics Clinical importance: reversible versus irreversible Correlation between acute and late complications

27 Factors affecting radiation damage 1. Volume to be irradiated 2. Total dose 3. Fraction size 4. Concomitant treatment

28 Total body irradiation Dose Effects Group I Gy Minimal Group II Gy Mild N/V Group III 4-6 Gy Hemopoietic Group IV 6-14 Gy GI Group V > 50 Gy CNS

29 Radiation-Induced Malignancy 1. There is no threshold 2. Long latent period 3. Within the radiation ports 4. Different organ sensitivity Thyroid, breast, lungs Skeletal muscle

30 Dose Volume Histogram

31 Types de Radiothérapie Three-dimensional conformal radiation therapy (3D-CRT): 3D-CRT uses the results of imaging tests such as MRI and special computers to map the location of the tumor precisely. Several radiation beams are then shaped and aimed at the tumor from different directions. Each beam alone is fairly weak, which makes it less likely to damage normal tissues, but the beams converge at the tumor to give a higher dose of radiation there.

32 Image guided RT CT scan Glioma C+/_ MRI C+

33 Immobilization: mask

34 Immobilization: mask

35 Immobilization: stereotactic frames

36

37 Whole Brain radiotherapy: WBRT

38 Linac_Tomotherapy

39 IMRT Intensity modulated radiation therapy (IMRT): IMRT is an advanced form of 3D therapy. It uses a computer-driven machine that moves around the patient as it delivers radiation. Along with shaping the beams and aiming them at the tumor from several angles, the intensity (strength) of the beams can be adjusted to limit the dose reaching the most sensitive normal tissues. This may let the doctor deliver a higher dose to the tumor. Many major hospitals and cancer centers now use IMRT.

40

41 MLC

42 GBM IMRT plan

43 VMAT Volumetric modulated arc therapy (VMAT) is a novel radiation technique, which can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared with conventional radiotherapy techniques.

44 Proton Conformal proton beam radiation therapy: Proton beam therapy is related to 3D-CRT and uses a similar approach. But instead of using x-rays, it focuses proton beams on the tumor. Protons are positive parts of atoms. Unlike x-rays, which release energy both before and after they hit their target, protons cause little damage to tissues they pass through and then release their energy after traveling a certain distance. Doctors can use this property to deliver more radiation to the tumor and do less damage to nearby normal tissues. This approach may be more helpful for brain tumors that have distinct edges (such as chordomas), but it is not clear if it will be useful with tumors that are infiltrative or mixed with normal brain tissue (such as astrocytomas or glioblastomas). There are only a handful of proton beam centers in the United States at this time.

45 Percent Depth Dose

46

47

48

49 Radiosurgery: SRS Stereotactic radiosurgery/stereotactic radiotherapy: This type of treatment delivers a large, precise radiation dose to the tumor area in a single session (radiosurgery) or in a few sessions (radiotherapy). (There is no actual surgery in this treatment.) It may be used for some tumors in parts of the brain or spinal cord that can t be treated with surgery or when a patient isn t healthy enough for surgery.

50 SRS

51 G-knife

52 SRS

53 C-knife

54 FSRT Pituitary MacroAdenoma

55 GBM 3D plan

56 Spine SRS

57 CSI: planning

58 CSI: 3D vs. Tomotherapy

59 CSI: photon vs. proton

60 CSI_proton

61 Base of skull: photon vs proton

62 In conclusion Integration of MRI and particles therapy into mainstream radiation oncology has the potential to further our ability to target brain tumors while sparing critical regions of normal brain tissue A. Shagal, P Brown, Neuro-Oncology, 19, 2017

63 Future directions MRI-linacs TTFs Clinical trials

64 MRI Linac

65

66 Optune_TTFs

67

68 Optune_EF-14_GBM_phase III trial

69 Clinical Trials BN002 NCCTG N0577/Endorsed Study: Phase III Intergroup Study of Radiotherapy versus Temozolomide Alone versus Radiotherapy with Concomitant and Adjuvant Temozolomide for Patients with 1p/19q Codeleted Anaplastic Glioma Open III NCCTG N107C/Endorsed Study: A Phase III Trial of Post-Surgical Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiotherapy (WBRT) for Resected Metastatic Brain Disease Open III Phase I Study of Ipilimumab, Nivolumab, and the Combination in Patients With Newly Diagnosed Glioblastoma Open I BN001 Randomized Phase II Trial of Hypofractionated Dose-Escalated Photon IMRT or Proton Beam Therapy Versus Conventional Photon Irradiation With Concomitant and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Open II R

70 Clinical trials Alliance A071101/Endorsed Study: A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, ALLIANCE IND# 15380) Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resective Recurrent Glioblastoma Multiforme (GBM) Open II R ECOG E3F05/Endorsed Study: Phase III Study of Radiation Therapy with or without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas Temp Closed III Novocure EF-25 METIS The METIS trial (also known as the EF-25 trial ) is a pivotal (analogous to drug Phase III), randomized, controlled trial, designed to test the efficacy and safety of Tumor Treating Fields (TTFields), generated by a medical device, the NovoTTF-100M System [About TTFields] in patients with 1-10 newly diagnosed brain metastases from non-small cell lung cancer (NSCLC). TTFields are administered to patients concomitantly with the best standard of care treatments which would normally be used to treat lung cancer. The trial is expected to enroll a total of 270 patients.

71 Information de contact Merci

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