Piero Fossati

1. Treatment delivery from the patient perspective: potential indication, set-up and organ motion issues at CNAO Piero Fossati ESF Exploratory Workshop on Advanced Instrumentation for Cancer Diagnosis and Treatment Oxford, United Kingdom, 23 – 26 September 2008

2. We all know how nice it is to have the Bragg peak Goitein et al, Physics today, 2002 Courtesy of Dr. Ando, NIRS

3. We all know how nice it is to have a high RBE (and only where you need it) CIRT 7 years later Vertebral osteosarcoma Imai et al., Lancet Oncology 2006

4. We can hope in good clinical results if we are able to deliver this radiation, with nice physical and biological properties, to the target • We have to know where the target is • No matter how good our beam, if the target is not where we thought we will not kill the tumor

5. Missing the target

6. Why should the target be elsewhere? • Mispositioning (interfraction) • Organ motion (intrafraction) • Shape change (interfraction)

7. This issues are much more critical in hadrontherapy (compared to photons RT) because of: • Steeper gradients • Dose distribution heavily dependent on tissue density • Hypofractionation

8. Organ motion is even more critical when active scanning is used (risk of hot and cold spots): For the CNAO delivery system spot size will be of millimiters (4 - 10) and time scale will be of milliseconds.

9. What has been done until now ? • What do we plan to do at CNAO ? • What would we like to do but do not know how?

10. Delivery system at CNAO • Fixed vertical and horizontal beams • Active spot scanning (no passive spread beam)

11. 1 - Precise positioning • Always an issue (for all body sites) • Need of fixation devices • Need of position verification devices • Need of 6 DOF position correction devices • The only issue for some body district (limb, head, spine ?) • Time consuming

12. Precise positioning • We believe that for “fixed” body sites a orthogonal KeV X-Ray imaging coupled to a robotic positioning device is necessary and sufficient. • Head and body masks, personalized cushions, bite blocks and all such devices employed in high precision photons RT can be straightforwardly transferd to hadrontherapy

13. A customized Schaer systyem will be used 13

14. 14

15. Courtesy of SEAG, RPTC 15

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17. 2 Shape change • Tumorshrinkage • Weight loss or gain • Dependent on tumorbiology • Relatively easy tocopewiththroughcloseclinicalmonitoringof the patient and frequent off lineimaging (e.g. each week forgynecologicalmalignancy) • Too late ifdiscovered in the treatment room (a checkisanywaymostnecessary)

18. 3 Organ motion • The real problem • Due to peristalsis, swallowing, heartbeat, vessels pulsation but especially BREATHING • Affects lung treatments, liver treatments, and to a lesser extent all abdominal and pelvic treatments. If the patients is in supine position (as may be necessary without a gantry) it may also affect retroperitoneal treatments

19. Breathing • A complex caotic phenomenon • Intervals of more or less regular breathing that each 5- 15 minutes change pattern and through a highly unpredictable phase reach a new temporary steady state • No reliable correlation betwen body surface and internal displacement during change of patterns • Frequency, Tidal volume, relative role of thoracic muscles and diaphragm and end expiration volume are among the parameters that can change in minutes • Elevated inter-patient and intra-patient variability • Pain and emotional status can influence breathing pattern • Displacements up to 3-4 cm can take place • Not possible to predict a priori direction and amplitude of a lung nodule displacement

20. How to deal with respiratory organ motion • Breathhold, gating, tracking, coaching, abd. pressure • Whichever you choose you need to measure motion (target position or surrogate marker) • Once you know how the target moves you can steer the beam, or decide to enlarge the irradiated volume (a simple CTV  PTV approach is not adequate) • It is mandatory to check what you are doing (a real time, in vivo dosimetry would be appreciated) • Robustness of the treatment plan should be considered (ideally as a parameter for inverse planning optimization) • Everything should happen in real time

21. Strategies • Breath hold: requires active cooperation, you cannot avoid measuring target position (to be sure it is performed correctly) • Gating: (in my opinion probably the best solution) • Tracking: much more complicated with only a small gain on time efficiency

22. Measuring target displacement • Breathingis a caoticphenomenon • Surrogate markers: air flow, body surface position (simple 1D markeroption cfr NIRS, or optoeletronicsurfacereconstructionwith or without passive markers) • Measuring the realthing: implantedmarkers and fluoroscopy, or frequentX-ray (howoften ?)

23. Surrogate markers Only the phase… probably not enough for spot scanning (and for stack layer?)

24. More advanced surface reconstruction Body markers Surface reconstruction

25. From the camera imagesto the surface or marker position • From the marker position to the target position • Howmanymsec ? • At the end itisonly a guess (caoticbehaviour, hysteresis) • NOT ENOUGH

26. You have to look at what you do • Fluoroscopy (radioprotection issues) • Periodic x-ray check during dose delivery to verify the external  internal model, i.e. you trust the model for a short time between cheks (how often have I to check ? Regular interval vs. adaptive interval cfr. Isaksson et al, Med Phys 2005)

27. What has been done until now (by us)? X-ray Exac trac with a custom made BH system (together with EIO and Politecnico di Milano). Accuray Synchrony (together with CDI) …..   not precise enough for spot scanning • What do we plan to do at CNAO ? ?? …. In the beginning only fixed targets

28. What would we like to do but do not know how? • ApproachsimilartoAccuraysynchronybutwithbettersurface detection and adaptivechekintervals (optimizingwhatalreadyexist)  Problemourorthogonal X rayflatpanelscannotbeboth in position when the terapeuticbeamis on • Somethingnew??

29. Can wedetect in realtimewithout extra dose to the patient the position of a lungnodule ? • Can weavoid invasive fiducialmarkerplacement ? (I believeNO) • Couldwemeasure the position ofanimplantedmarker in some other way ? Maybemeasuring the influenceofanimplantedcoil on anexternalmagneticfieldmakessense or isitonlyanignorant’s dreormeasuring the change in electriccapacitance? Isanybodyworking on this? Doesitam? Wouldit work with a ionbeam on?

30. Ifyouhavean idea youlikebesuresomebody else hadalreadyhaditquite a while ago ! 30 mm × 20 mm × 10 mm Meas. Sci. Technol. 19 (2008) 024006 (9pp) doi:10.1088/0957-0233/19/2/024006 Tracking of internal organ motion with a six degree-of-freedom MEMS sensor: concept and simulation study Manuel Bandala and Malcolm J Joyce

31. Implantable with 14 gauge needle Accuracy 0.2 mm Read out rate 10 Hz Not yet tested in clinics Balter et al, IJROBP 2005

32. We are the oneswhocould benefit mostofsuchsensors • Hadrontherapyas a community shouldsupportthoseresearches • Probablynottooambitious a goal butinvestment and focusing are required

33. Steering the beamiseasierthanmeasuring the motion • Novelapproaches are welcome • Weshouldstrivefor a continuousrealtimemeasurmentof the target position • At present I believeweneedimplantedmarkers • In the end active spot scanning may turn out tobesimplynot the best way totreatlung and liver and wemayhaveto go back to passive spreading

34. Quality assurance and in vivo dosimetry • Organ motion is difficult to deal with, we have to check what we are doing and how effective it is • In vivo dosimetry is mandatory • In vivo dosimetry can detect also shape changes that eluded clinical monitoring

35. What has been done until now (not by us)? • In beam PET What do we plan to do at CNAO ? In beam PET (cfr. FP7 call) AQUA

36. Those approaches have much in common: • They mesure something that would have happened anyway (and so no extra dose is delivered to the patient) • If the result is positive you can be sure that everything went well, if it is negative you are not sure of what went bad • The signal that can be detected bears less information respect to the actual dose distributions and therefore cold spots may be masked by a blurring effect • You know the result after the treatment session is ended, for hypofractionated treatments it may be too late

37. Same β+ activity ? Different dose

38. What would we like to do but do not know how? • When a fiducialmarkerisinserted, have a dosimeter inside it (itshouldbereadwithoutextracting the fiducialfrom the patient body). Science fiction ? • Have a protonportalimaging (or part ofit) tocheck position during dose delivery

39. Proton portal imaging ? • (CNAO can accelerate C12 to 400 MeV/u so protonscouldbemuchfaster) • Woulditbepossibleto put the Braggpeakbeyond the patient and measure the rangewithoutdelivering a high dose ?

40. How much dose ? Can we build this black box ?

41. ? • OK • Abort • Correct online?

42. Thank you for your attention