ProtonTherapy: A ballistic that will benefit patients? Pr. Xavier Geets MIRO Lab, IREC UCL Radiotherapy Dept. CUSL, Belgium

ProtonTherapy: A ballistic that will benefit patients? Pr. Xavier Geets MIRO Lab, IREC UCL Radiotherapy Dept. CUSL, Belgium

Proton Therapy, a swissknife The balistic advantage of protons P PHOTON THERAPY PROTON THERAPY

Proton vs photon: depthdose curves Depth dose curves Relative doses (%) 300 250 200 150 100 50 10 MeV photons Photons Protons Additional Dose outside the target delivered with Photons Proton Spread Out Bragg Peak Tumor 0 0 50 100 150 200 250 300 350 400 Depth in water (mm)

PencilBeamScanning (PBS) PT High conformal dose delivery technique

Proton, RBE = 1.1? AlterationRBE in end of peak

Proton radiobiology LET increases as the beam progresses in depth (SOBP) RBE increasesby 6-10% fromthe middleto the endof SOBP

Proton: improvingradiotherapy Effective eradication of all cancer cells Avoiding injury to normal tissues Differential effect Relatively more marked effect(rbe) Ballistic selectivity More conformaldose distribution Who will benefit (the most...)?

Proton Therapy, for whom? CHILDREN PHOTON PROTON

Proton Therapy, for whom? CHILDREN PEDIATRIC INDICATIONS (RIZIV) Chordoma(base of skull, spinal) Base of skull chondrosarcoma Soft Tissue Sarcoma, (para)spinal Pelvic sarcoma Rhabdomyosarcoma Ewing s sarcoma Retinoblastoma Low grade glioma Ependymoma Craniopharyngioma Epiphyseal parenchymatous tumors Estesioneuroblastoma Medulloblastoma/PNET SNC Germinoma Non-resectable osteosarcoma ETHIC and SCIENTIFIC evidences Insufficient CLINICAL evidence

Proton Therapy, for whow? (RADIORESISTANT) TUMOURS IN RADIOSENSITIVE ENVIRONMENT BS Chondrosarcoma Paraspinal Chordoma Vertebral Osteosarcoma RetroP Sarcoma Ribs Sarcoma

Proton Therapy, for whow? (RADIORESISTANT TUMOURS) IN RADIOSENSITIVE ENVIRONMENT ADULT INDICATIONS (RIZIV) Intraocular melanoma ChordomaBase of skull, sacral or paraspinal Chondrosarcoma Meningioma Intracranial AVM Medulloblastoma Carbon ions, a better alternative to proton for radioresistant tumours?

Leucistism White Giraf(Tanzanie) What about frequent tumours?

Leftbreastcancer in youngwomen Excess of myocardial Infarction (Harris et al, JCO 2006) PHOTONS PROTONS

Non-small-celllungcancer Lung/heart toxicities hamper efficient dose escalation D mean heart=33 Gy D mean heart=13 Gy Proton Therapy X-rays/IMRT Extra-doses

ExtendingcurrentPT indications 1 CLINICAL EVIDENCES? Tumour control Acute/late toxicities Qualityof life 2 TECHNICAL FEASIBILITY? Range distortion in changing anatomy Breathing motion: interplay effect

Meaningfulpatient selectionfor PT MODEL-BASED APPROACH 1 In-silico planning comparative studies 2 NTCP-derived clinical benefit Late adverse effect with long latency 3 Validation with prospective cohorts Langendijk et al, R&O 2013

Building clinicalevidences Clinical trials & prospective cohort study Ongoing clinical trials in NSCLC Long-term patient outcome

Range distortionin changinganatomy Pre-treatment Mid-treatment ANATOMY CHANGES PHOTON stable dose distribution PROTON distorded dose distribution

Facingchallenges TOWARDS AUTOMATIC ONLINE ADAPTATION Planning Treatment day Manual contouring Contours propagation Clinical indicators

Facingchallenges TOWARDS AUTOMATIC ONLINE ADAPTATION Planning Treatment day n TREATMENT DELIVERY Manual contouring Rigidcontours propagation Clinical indicators

Facingchallenges TOWARDS AUTOMATIC ONLINE ADAPTATION Planning Treatment day n DOSE RESTORATION Manual contouring Rigidcontours propagation Clinical indicators

Dose restoration: photonization Initial plan on CT1 Initial plan on CT2 Restored plan on CT2 Restored plan Initial plan (CT1) Initial plan (CT3) Fast re-optimization restoredplans have dose errors>=5% in lessthan5% of volume (TV and OAR) TREATMENT DELIVERY

Interplayeffectin PBS-PT Interference between beam and tumour motions

Motion mitigation Mechanically-assisted ventilation Regular breathing pattern breathing/tumor motions

Regularizedbreathingmode Multi-phase gating Internal motion (4D-CT) Breathing signal Multi-phase gating Spotmap@ 0% Spotmap@ 20% Spotmap@ 40% Spotmap@ 60% Spotmap@ 80%

Shallow breathing mode Reducing internal motion Adaptive Mode 10 BPM Shallow Mode 30 BPM

Coming soon Proton therapy in Belgium