Proton therapy. Low Grade and Maligant Gliomas

Transcription

1 Proton therapy Low Grade and Maligant Gliomas Michelle Alonso-Basanta, MD PhD Helene Blum Assistant Professor Associate Chief of Clinical Operations Director of Quality Assurance Chief, Central Nervous System June 9, 2017

2 Disclosures IBA - speaker 2

3 Era Prior to CT 3

4 The Evolution of Photon Radiation Therapy 1960 s 1970 s 1980 s 1990 s 2000 s The First Clinac Computerized 3D CT Treatment Planning Standard Collimator The linac reduced complications compared to Co60 Cerrobend Blocking Electron Blocking Blocks were used to reduce the dose to normal tissues Multileaf Collimator MLC leads to 3D conformal therapy which allows the first dose escalation trials. Dynamic MLC and IMRT Computerized IMRT introduced which allowed escalation of dose and reduced compilations Functional Imaging High resolution IMRT IMRT Evolution evolves to smaller and smaller subfields and high resolution IMRT along with the introduction of new imaging technologies 4

5 IMRT 5

6 More conformal 6

7 IMRT 7

8 Protons 8

9 What is a Proton? Hydrogen nucleus Charge is +1 Atomic weight = amu (= 1836 times the mass of an electron) e- + Hydrogen atom proton 9

10 The Physics of Protons X-rays deliver a greater dose outside the target for the same dose within the target volume as protons Depth dose curves for protons and photons Relative Dose (%) MeV photons Protons Photons Additional Dose outside the target delivered with Photons compared to Protons Proton Spread Out Bragg Peak Tumor Depth in Water (mm)

11 Central Nervous System - US Incidence: per 100, per 100, 000 for ages 40+ From: CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in Neuro Oncol. 2016;18(suppl_5):v1-v75. doi: /neuonc/now207 Neuro Oncol The Author(s) Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please journals.permissions@oup.com. 11

12 Updated Data: RTOG 9802 ASCO

13 Updated Data: RTOG 9802 ASCO

14 Updated Data: RTOG 9802 ASCO

15 Rationale Patient population Neurocognitive changes Decreased dose to contralateral structures Dose escalation while maintaining normal tissue tolerance 15

16 Patient selection Majority of patients will be eligible Considerations: Co-morbidities Time on the table Claustrophobia (medication helps) Tumor location Proximity to critical structures Prior Radiation 16

17 Indications Consideration for protons for all histologies at this time Low grade and high grade gliomas Low grade and high grade meningiomas Schwannomas Pituitary tumors Spine tumors (bone or CNS) Base of skull tumors Chordomas Chondrosarcomas Paragangliomas 17

18 Gliomas Low grade: majority are young Localized tumors Can be small or large Early publications show that patients recover very well from acute side effects Consideration in beam arrangement: alopecia Long term effects are currently being followed under study 18

19 Contouring Margins for CTV based on clinical parameters and considerations no change from photon therapy Dosing based on clinical histology no change from photon therapy (unless on clinical trial) A dosimetric PTV is placed based on range uncertainty of the beam that is dependant on the tissue it traverses 19

20 CNS Low Grade Glioma Example Beam Arrangement Left Inferior Anterior Oblique, Left Posterior Inferior Oblique, Right Superior Posterior Oblique 20

21 Proton IMRT 21

22 CNS Low Grade Glioma DVH Comparison Proton ( ) vs IMRT ( ) 22

23 Proton IMRT 23

24 Toxicity UPENN experience Low grade gliomas and meningiomas Symptom Assessment/Grading based on National Cancer Institute Common Terminology Criteria for Adverse Events version

25 Maquilin G, AM. J Clin. Onc. E Pub 23 Feb

26 Long Term Toxicity Patients followed after treatment Neurocognitive study currently evaluating MRI changes correlated with neurocognitive testing with controls Base of skull: Endocrine, Ophthalmology, ENT colleagues essential Skin concerns: alopecia, fibrosis 26

27 Neurocognitive Assessment - Prelim Verbal Retrieval Proton RT also showed a post-treatment decline, but a stronger recovery over two years, with overall stronger memory capacity These differences between groups were on the two tests most sensitive: retrieval after interference and retrieval after time 27

28 Neurocognitive Assessment Cerebellar Tests of Implicit Cognition Patients were compared to controls who did not have radiation Test of perception of timing functions (P=0.01), with controls performing better than patients in estimating whether a time interval was faster or slower than a standard Reaction time was slower for patients than controls, with more patients demonstrating lower rates of implicit learning (P<0.009) Audiovisual attentional shift test: Differences were not found between groups or over time in this test, except at the longest interstimulus intervals (ISI) in only the auditory input, not the visual 28

29 High Grade Glioma WHO Grade IV (Glioblastoma Multiforme) currently being done in recurrent and upfront setting on national protocols Anaplastic gliomas (WHO Grade III) are being treated Margins clinically remain the same Sparing of contralateral structures Challenge: constraints are still difficult to meet based on the location of the target to the OARs 29

30 CNS - Anaplastic Astrocytoma Example Beam Arrangement Left Anterior Oblique, Superior Anterior Oblique 30

31 Proton vs Photon in GBM 31

32 Re-Irradiation Challenge in any setting Toxicity is still discussed as there has been radiation given prior However, can achieve adequate dosing for re-irradiation and minimize OARs 32

33 Glioblastoma Treated with Rapid Arc (photons) 33

34 Glioblastoma 1.5 years later, area of progression, underwent surgery Re-irradiation only area of recurrence with protons 34

35 Plan Sum 35

36 Retreatment for CNS Protons can provide an opportunity for re-irradiation in the brain where there would not be a good option with photons Example patient below previously received 3 courses of radiation in the brain. One course was treated with Cyberknife and records were unattainable Displayed below is the sum of the first 2 courses of radiation (minimum color wash dose set to 40Gy) with the current CTV, prescribed to 50.4Gy. 36

37 Retreatment for CNS 37

38 Retreatment for CNS Proton Beam Arrangement Goal: Minimize dose to cord, brainstem, left optic structures Beam Arrangement: Left Lateral, Left Superior Oblique 38

39 Retreatment CNS Example patient below had been previously treated to the same site PBS Beam Arrangement: Right Lateral and Vertex Beam Vertex chosen so that both beams did not point their distal edge toward the left eye 39

40 Challenges Clinical judgment still needed Individualized care: Best plan for the patient Balance comparison plans on a scale: OARs at risk Choice of beam arrangement Comprehensive discussion with patient as to expectations 40

41 Current TRIALS Currently 132 OPEN proton trials on for brain 42 actively enrolling 12 of which are for glioma At Penn Medicine for Brain/Skull Base Open: Low grade gliomas closed BN001 - GBM Meningiomas and hemangiopericytomas dose escalation Chordomas/Chondrosarcomas interim analysis Spring 2017 Neurocognitive Study (Brain and BOS) Analysis Fall 2017 Quality of Life Protocol 41

42 Collaborators 2017 Radiation Oncology Physics/Dosimetry James Metz Robert A. Lustig Goldie Kurtz Jay F. Dorsey Alexander Lin Peter Ahn J. Nicholas Lukens James Kolker Suneel Nagda Geoffrey Geiger NeuroRadiology Laurie Loevner Kim Learned Ron Wolf John Woo Suyash Mohan Linda Bagley Harish Poptani (London) Ragini Verma Christos Davatzikos Neurosurgery M. Sean Grady John Y.K. Lee Donald O Rourke Steven Brem Timothy Lucas Eric Zager Neil Malhotra James Schuster Paul Marcotte Neuro-Ophthalmology Grant Liu Madhura Tamhankar Neuropathology Zissimos Mourelatos MacLean Nasrallah Neurology Amy Pruitt Raymond Price Danielle Becker NeuroInterventional Bryan Pukenas Robert W. Hurst NeuroOncology Arati Desai Gerald Linette Stephen Bagley Otorhinolaryngology Bert O Malley James Palmer Jason Newman Nithin Adappa Christopher Rassekh David Kennedy Douglas Bigelow Michael Ruckenstein Neuropsychiatry Carol Armstrong Cardiology Douglas Jacoby Endocrinology Julia Kharlip Peter Snyder 42

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44 Thank You 44