Roberto Orecchia. Enlight Annual Meeting, 13th July 2013

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1 Progress and the start of the treatment of patients with carbon ions at CNAO Roberto Orecchia Full Professor of Radiation Oncology at Milan University Scientific Director at CNAO, Pavia Director of the Department of Imaging and Radiological Science at IEO, Milan Enlight Annual Meeting, 13th July Novembre

2 Hospital Bldg High-Tech Bldg Delivered End 2008 Delivered Spring 2010 November, 2001: Ministry of Health approval by law June, 2005: Start

3 CNAO Syncrotron P+ ( MeV) C-12 (400 MeV/n)

4 Extracted beam on SFH October 26, 2010: Proton Beam in Room!

5 Presented to: - Italian Ministry of Health - Lombardy Region Main Tasks: - Dosimetry characterisation - Radiobiology characterisation - Patient treatment

6 Proton beams Range: 68 to 250 MeV

7 Radiobiology Laboratory at CNAO

8 Proton Radiobiology 3 cell lines: HSG (human salivary gland tumour), T98G (human glioblastoma), V79 (Chinese hamster lung fibroblast) (16 energies) Field10x10 cm 2, 33x33 spots, scanning step 3 mm

9 RBE Protons at CNAO. E= MeV, SOBP: 6 cm The generic RBE for protons is 1.1 But, for a small volume within the distal part of a radiation field RBE increases throughout the SOBP, with an estimated range of 10-15% 9

10 115 MeV/u 209 MeV/u 115 MeV/u 400 MeV/u Carbon Ions Spectra of energy tail

11 Carbon Ions in vitro: Cells Clonogenic survival of cell lines - V79 (Chinese hamster lung fibroblast) - HSG (Human salivary gland tumor) -T98G (human glioblastoma) Group Leader: Roberto Cherubini, INFN

12 Ciocca, Mairani - CNAO RBE - Carbon Ions at CNAO. E= MeV/n, SOBP: 6 cm p2 p3 p4 p5 p1 12

13 Survival vs Depth Dose uniformity 13

14 Group Leader: Yoshiya Furusawa, NIRS, Chiba Carbon ions Animals

15

16 Set-up Horizontal beam, direction ventral - dorsal 3 animals per field

17 Comparison of RBE results (CNAO vs GSI \ NIRS)

18 Approved protocols CNAO 01/2011 V.2.0 Cordomi e condrosarcomi della base del cranio CNAO 02/2011 V.1.0 Cordomi e dei condrosarcomi del rachide feb 2011 CNAO 03/2011 V.2.0 Meningiomi intracranici CNAO S4/2011/P CNAO 05/2011 V.1.0 CNAO 06/2011 V.1.0 CNAO S7/2012/P CNAO S8/2012/P Tumori dell encefalo Recidive di neoplasie del distretto cervico-cefalico Boost di Radioterapia delle neoplasie localmente Avanzate del distretto cervico-cefalico Gliobastomi Cordomi e dei condrosarcomi del rachide recidivi set 2011 giu 2012

19 CNAO S9/2012/C CNAO S10/2012/C Carcinoma adenoideo cistico delle ghiandole salivari Ritrattamento degli adenomi pleomorfi recidivi giu 2012 CNAO S11/2012/C CNAO S12/2012/C CNAO S13/2012/C Reirradiation of recurrent rectal cancer Sarcomi (ossei e dei tessuti molli) del distretto cervico -cefalico Sarcomi (ossei e dei tessuti molli) del tronco CNAO S14/2012/C CNAO S15/2012/C CNAO S16/2012/C Recidive di neoplasie del distretto cervico-cefalico Melanomi maligni delle mucose delle prime vie aero digestive Carcinoma della prostata ad alto rischio dic 2012 CNAO S17/2012/C CNAO S18/2013/C CNAO S19/2013/C Tumori primitivi e secondari dell'orbita Tumori del pancreas Neoplasie primitive maligne del fegato Feb 2013

20 Patient work flow Medical Service Direct contact with physicians Board First examination CT/MRI/CT- PET Contouring Treatment Plan Planning verification First session

21 January - December contacts January - April contacts

22 CNAO P/01. Chordoma/ low grade chondrosarcoma. Skull base Post op, Recurrent, Inoperable M0N0 Contouring based on CT and MR fusion Dose chordoma: 74 GyE in 37 frs, 2 GyE x fr, 5 frs x week Dose chondrosarcoma: 70 GyE in 35 frs, 2 GyE x fr, 5 frs x week

23 Chondrosarcoma G2

24 Optical & X-ray tracking systems for set-up verification

25 Contouring with image fusion TC/RM T1 post gadolinium sequences in T2

26 Dose prescription: 70 Gy (RBE) in 35 sessions 2 Gy each (RBE) Constraints: Brain stem: surface 64 Gy (RBE) middle 53 Gy (RBE) Optic chiasm: max. dose 56 (RBE) mean dose 50 (RBE) Optic nerve: max. dose 54 (RBE) mean dose 50 (RBE)

27 Dose distribution RBE value 1.1

28 3D Real-time IR Optical Tracking (OTS) Real time reconstruction of spherical markers and surfaces Sub-millimeter accuracy : peak 3D errors <0.5 mm 3D data Hz X-ray Patient Verification System (PVS) 2 X-ray tubes (deployable), 2 flat panels (deployable) Supporting structure rotation: ±180 Rotation and deployment accuracy: ± 0.15mm, ± 0.1 Patient Positioning System (PPS) Automatic couch or chair docking Absolute accuracy: 0.3 mm 22 September 2011

29 CNAO Protocol P/01: closed 13th February patients enrolled 14 males/16 females 53 ys median age (range 15-75) 26 chordomas/4 chondrosarcomas: 7 radical surgery 23 subtotal surgery/biopsy CE Label 2 No Interruption of treatment No Grade 3-4 toxicity No Progression of disease (SD)

30 percentuale del volume iniziale (%) 120 Changes in size (volume cc) 100 Before treatment End of treatment Follow-up of changes by MR Mesi 3 Months after and every 3 months

31 Last session Skin Toxicity G1

32 G1 Skin toxicity 32

33 Chordoma Dose 74 Gy (RBE)

34 13 November 2012 Local recurrence of adenoideocistic carcinoma involving pterigopalatina fossae, orbital apex, right cavernous sinus and medium skull, already treated with surgery and RT (60 Gy) in 1995

35 NIRS CNAO Collaboration Prescription doses (GyE) (16 fractions, 4 fractions per week) NIRS dose CNAO dose Opposed ports Orthogonal ports Single port Indication q.e. q.e. q.e. MC Cube s Spheres Cubes Spheres Cubes Spheres Head and neck non mesenchymal cancer Skull base chordoma and chondrosarcoma Head and neck non mesenchymal cancer Spinal chordoma and chondrosarcoma Head and neck sarcoma Bone and soft tissue sarcoma Fossati P et al, Dose prescription in carbon ion radiotherapy: a planning study to compare NIRS and LEM approaches with a clinically-oriented strategy. Phys Med Biol, 2012

36 Carbon ion 12 fractions of 4.1 GyE each, 4 frs x week, 49.2 GyE total Boost with 4 additional fractions, same fractionation 3 fixed fields by IMPT

37 Dose distribution

38 6 November March 2013

39 6 November March 2013

40 Skin Toxicity 6 December 2012 End od the treatment 12 March 2013

41 G2 Skin toxicity

42 What in the next future? protons Chordoma & chondrosarcoma skull base & spine (clinical use) Mixed beam in squamous cell carcinoma of the H&N Eye melanoma (new!) carbon ions Comparative study in chordoma & chondrosarcoma Sarcomas & mucosal melanoma Salivary gland tumors Prostate cancer (advanced) Pancreatic tumors

43 Multidisciplinary approach for poor prognosis sinonasal tumors Induction chemotherapy, concomitant radiochemotherapy, and surgery, if operable Endpoints: increase PFS (P), OS, decrease late toxicity, preserve visual functionality Techniques: IMRT, V-Mat or Helical up to Gy, plus boost (18-21 Gy) with PBT or CIRT (anticipated) Functional & molecular imaging Biological markers on biopsy: P53, P16, EMT (Epithelialmesenchimal Transition), Radioresistance (SPK-II)

44 PARTNER Particle Training Network for European Radiotherapy ENVISION European NoVel Imaging Systems for ION therapy

45 Thank you very much!!!

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