1. Update on FLUKA use at CNAO Giuseppe Magro (PhD Student) and Andrea Mairani (HIT and CNAO) Pavia, Dec 16, 2014

2. www.cnao.it  Daily support to the clinical activity  (Recalculation of TP and/or TP-Verifications)  Plan robustness  Completion of partial treatments  RBE comparison: NIRS vs. CNAO in carbon ion therapy  Eye treatments with active scanning  Towards “new” ion species Outline Page 2 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO

3. www.cnao.it  FLUKA used to investigate the impact of different sources of uncertainty on proton beam ranges and dose distributions for typical scanned proton patient treatment plans  ±3% error in the CT grey levels (range uncertainty)  maximum translation of 1 mm and maximum rotations of 1 ° (setup uncertainty)  SFUD vs IMPT (  most critical!) Plan robustness in scanned p-RT Page 3 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO

4. www.cnao.it Completion of partial treatments (I)  Treatment plans of carbon-ion radiotherapy are usually made on the assumption that the beams are delivered instantaneously irrespective to the dose delivery time as well as the interruption time  The advanced therapeutic techniques such as a hypofractionation and a respiratory gating usually require more time to deliver a fractioned dose than conventional techniques  “…If the fraction time prolongs to 30 min or longer, the biological effectiveness is significantly influenced in carbon-ion radiotherapy, especially with high-prescribed doses…” (Inaniwa et al, 2013)  The purpose of this study is to investigate the effects of dose- delivery time structure on biological effectiveness in carbon-ion radiotherapy on a macroscopic time-scale (i.e., days)  Possible scenarios: machine failures, patient pain, … Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 4

5. www.cnao.it Completion of partial treatments (II) Possible choices + = linear sum of bio-doses x = bio-sum of phys.-doses = “instantaneous” delivery Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 5

6. www.cnao.it Completion of partial treatments (III)  What’s on going?  Dependence on the number and/or the orientation of the treatment fields, exploring different solutions for the same patient  More complex cases (highly disomogenous distributions, SFUD or IMPT optimization dependence,...)  MCTP to optimize voxel by voxel the rest of the dose to be delivered  N.B. :  Dose prescription ultimately represents a clinical task under the responsibility of the radiation oncologist, the presented analysis intends to be a quantitative and objective way to assist present and future clinical decisions Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 6

7. www.cnao.it  In carbon ion RT there is an urgent clinical need to develop objective tools for the conversion of RBE-weighted doses based on different models  Simple concept: less dose where LET is higher  NIRS: uniform RBE weighted dose (plateau/proximal/middle/distal)  CNAO: LEM I model  FLUKA interfaced with LEM I (Mairani et al, 2010)  Clinically oriented method to compare NIRS-based and LEM-based GyE systems, minimizing differences in physical dose distributions between treatment plans RBE comparison: NIRS vs. CNAO (I) Page 7 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Phase I “Reference” target volumes of cubic and spherical shapes NOW  Phase II Confirm findings on LEM-based prescription doses currently adopted in clinical practice at CNAO on real patients cases

8. www.cnao.it  Possible solution with FLUKA  Modeling of the NIRS beamlines  MC simulation of NIRS physical doses (clinical data)  NIRS RBE-weighted dose according to LEM I  FLUKA interfaced with LEM I RBE comparison: NIRS vs. CNAO (II) Page 8 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Patient-specific Vacuum window Collimator Al Scatter (300A,0370 WEPL 300A,033C) AIR vacuum Main monitor WEPL 0.022 cm Ridge filter 7 cm 300A,0380 Range shifter (300A,0360) WEPL 0.8543 cm Sub monitor WEPL 0.089 cm

9. www.cnao.it RBE comparison: NIRS vs. CNAO (III) Page 9 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO  Patient-specific components

10. www.cnao.it RBE comparison: NIRS vs. CNAO (IV) Page 10 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO NIRS FLUKA Phys. DoseEff. Dose

11. www.cnao.it  CNAO is currently moving to activate a clinical trial for ocular cancer treatments with scanned beams  Fully active 3D – Dose Delivery System Eye-treatments with active scanning (I) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 11

12. www.cnao.it Eye-treatments with active scanning (II) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 12  Eyeplan ® (Goitein and Miller 1983, Sheen 1994)  Geometrical approximation of the eye (no CT/MR info)  Average eye density  Beam lateral widening in tissues is neglected (no PB algorithm)  Our aim: to use the existing image-based approach (CT/MR/PET)  full TPS characterization 1H1H

13. www.cnao.it Eye-treatments with active scanning (III) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 13  Siemens Syngo ® TPS  dosimetric accuracy demonstrated for volumes ranging from 20 cc to 3000 cc (Molinelli et al 2013)  general-purpose  not dedicated to ocular treatments and cannot handle a patient-specific collimator  most critical validated case is a 3x3x3 cc volume in a water phantom at 25 cm in depth  far from a typical condition of an ocular treatment  Monte Carlo benchmarking (FLUKA)  Homogeneous water cubes  Real patients CT scans

14. www.cnao.it Eye-treatments with active scanning (IV) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 14

15. www.cnao.it Eye-treatments with active scanning (V) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 15

16. www.cnao.it Eye-treatments with active scanning (VI) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 16 The accuracy of MC simulations in reproducing experimental results has been confirmed by relative deviations from measured data lower than 3% for ALL cases analyzed

17. www.cnao.it Eye-treatments with active scanning (VII) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 17  Monte Carlo Treatment Planning (Mairani et al 2013)  The use of MC simulations to verify and validate TPS results proved to be useful for clinical applications of scanned proton therapy to eye treatments

18. www.cnao.it Eye-treatments with active scanning (VIII) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 18 New DDDs now used to characterize the first CNAO “Eye-line” configuration …

19. www.cnao.it Eye-treatments with active scanning (X) Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Page 19 In the very next days, results on lateral penumbra …

20. www.cnao.it  CNAO phase I enlargment of the facility: experimental room + 3 rd source for other particles Towards «new» ion species (I) Page 20 Pavia, Dec 16, 2014 Update on FLUKA use at CNAO Already implemented and validated CNAO beamline MC modelisation to have a “premilinary look” to the physical properties of new ion species …

21. www.cnao.it Towards «new» ion species (II) Page 21  Beam size at the Isocenter  MC simulation of the CNAO beamline Pavia, Dec 16, 2014 Update on FLUKA use at CNAO

22. www.cnao.it Towards «new» ion species (III) Page 22 p - 142.7 MeV/u 4 He - 143.2 MeV/u (+ 2 RiFi) 12 C - 272.2 MeV/u (+ 2 RiFi) 16 O - 324.2 MeV/u (+ 2 RiFi)  Lateral spread in water of MC-calculated pencil beams with the similar FWHM at the entrance (Bragg-Peaks around 14 cm in depth) … waiting for real experiments! Pavia, Dec 16, 2014 Update on FLUKA use at CNAO

23. Thank you “Real progress happens only when advantages of a new technology become available to everybody” H. Ford