Current Status of Proton Clinical Activities at PTC H

Current Status of Proton Clinical Activities at PTC H Michael Gillin, PhD, Professor, Chief of Clinical Services Department of Radiation Physics, UT MDACC The University of Texas M.D. Anderson Cancer Center Proton Therapy Center New Old

UT MDACC Radiation Oncology UT MDACC > 24,000 patients/year > 7,000 patients per year treated in Radiation Oncology Main campus (20 linacs) PTC H 4 Regional Care Centers in greater Houston area Albuquerque, New Mexico Istanbul, Turkey > 60 radiation oncologists Filmless, paperless practice. With the exception of Istanbul, all sites, including PTC H, use the same EMR, Mosaiq V 1.6. Photon TPS Pinnacle, Proton TPS Eclipse

140 MeV Protons and 50 MeV Electrons (U of Michigan) 120.00 140 MeV proton PDD vs 50 Mev Electron PDD 100.00 80.00 Proton 140 MeV 8 cm SOBP Proton 140 MeV 10 cm SOBP Electron 50 MeV 60.00 40.00 20.00 0.00 0 50 100 150 200 250 300 Protons: Flat peak, sharp drop off. Range controlled to within 1 mm in water. What clinical sites benefit from these characteristics? Why protons? It is a positive experience.

PTC H Brief History Acceptance testing team did the AT. Clinical physics was responsible for commissioning and continuous support, beginning March, 2006. First patient with scattered beam, May, 2006 First patient with scanned beam, May, 2008 2,600 patients treated with protons (March 2011) 1250 GU patients, > 400 pediatric patients, > 400 thoracic patients > 400 scanned beam patients (SFO and SFIB), > 10 MFO

Patient Daily Census and ECA (June 2007 March 2011) ECA = [(FST-EDT)/FST] X 100 ECA: Equipment Clinical Availability FST: Facility Schedule Time; EDT: Equipment Down Time ECA Patients 5

Major Systems for Protons CT scanners: GE at PTC and GE and Philips on main campus CT number/stopping power Hitachi Treatment Delivery PROBEAT Hitachi imaging systems and Hitachi PIAS (Patient Image Analysis System) Varian Eclipse Planning, V 8.9 Anderson MU Determination for scattered beam IMPAC EMR Mosaiq V1.6 supports scattering and scanning All patients have been treated using the EMR. Gibbscam for aperture and compensator construction on Mazak milling machines.

Major Challenges for Protons Treatment Planning System TPS have been a major challenge, as they are quite immature. In June, 2011 we will have migrated to our fourth major version of TPS. Competing demands to treat patients, improving treatment techniques and program development. Digital communication between various vendors: TPS to EMR through MDACC filter to Rx Delivery to EMR Clinical physicists want to measure everything, but time is limited.

Proton Therapy Center - Houston PTC-H 3 Rotating Gantries 1 Fixed Port 1 Eye Port 1 Experimental Port Pencil Beam Scanning Port Passive Scattering Port Experimental Port Large Fixed Port Eye Port Treatment Mode Physics Mode Service Mode Accelerator System (slow cycle synchrotron)

PTC H Operations, April, 2011 110 to 130 patients per day, treated from 6 AM to 11 PM, Monday through Friday Morning QA < 30 minutes per beamline Saturday Physics time 8 AM until 8 PM Saturday night and Sunday Hitachi maintenance. 96 to 97% uptime. Most troublesome component has been the 7 MeV linac. Highly controlled environment: ~ All changes are reviewed by MDACC and Hitachi before they are made.

Selected PTC H Staff 8 clinical physicists (2 shifts), 1 accelerator physicist faculty physicists are expected to work on an every other Saturday basis. TPS requires ~ 1.5 FTE clinical physics effort 2 Clinical Physics Fellows 4 Physics Assistants (2 ea AM, 2 ea PM) 4 machinists for compensators and apertures 3 MDACC service techs + 5 Hitachi service techs + 2 Hitachi management 15+ oncologists who regularly treat patients ~ 16 RTTs two shifts 9 clinical dosimetrists, 2 research dosimetrists IT support, administrative support, bureaucrats, etc.

2 Stage Linear Accelerator Currently 20 Hz, soon 2 Hz AccSys Made in California Duoplasmatron Max. 30 Hz Ion Source Einzel lens RFQ DTL

Synchrotron Accelerator Circumferential Length: 23 meters Extraction Energy: 70 to 250 MeV Extraction Scheme Transverse RF driven with Separatrix Constant Extraction Energy resolution: 0.4 MeV Design value of the extracted particles: 0.75 x 10 11 ppp at 250 MeV

Accumulated Charge in the Synchrotron This may be the most important parameter for delivering beam to both the passive and scanning nozzles. The accumulated charge should be ~ 15 nc for all energies for passive scattering and ~ 5 nc for higher energies and ~ 3 nc for lower energies for scanned beam. Operating parameters which control this include the voltage and position of the Electro Static Inflector, which changes the injection condition in the synchrotron and the relative phase of the debuncher, which adjusts the energy and energy distribution of the 7 MeV protons in the linac. The ESI and the debuncher are tuned manually on an as needed basis.

PTC H Synchrotron Passive Scattering Passive scattering: Beam on 0.5 seconds, Beam off 1.5 seconds, low dose rates 75 to 200 cgy/min 3 snouts: large (25 cm x 25 cm), medium (18 cm x 18 cm), and small (10 cm x 10 cm) 8 Energies (250, 225, 200, 180, 160, 140, 120, and 100 MeV) A separate RMW for each snout and energy SOBP width from 2 cm to 16 cm. Range shifters to adjust depth to within 1 mm. Snout is adjustable from isocenter to 45 cm from isocenter.

120 G2_250MeV_RMW91_range28.5cm_mediumsnout@5cm 120 G2_250MeV_RMW88_range25.0 cm_largesnout@5cm 100 100 80 80 P D D 60 SOBP 4 cm, Measured 4.2 cm SOBP 10 cm, Measure 10.2 cm 40 SOBP 16 cm, Measured 16.1cm SOBP 12 cm, Measured 12.0 cm 20 SOBP 8 cm, Measured 8.1 cm SOBP 6 cm, Measured 6.1 cm 0 SOBP 14 cm, Measured 14.3 cm 0 50 100 150 200 250 300 350 Depth (mm) P D D 60 40 20 0 SOBP 4 cm, Measured 3.9 cm SOBP 6 cm, Measured 5.9 cm SOBP 8 cm, Measured 7.9 cm SOBP 10 cm, Measured 10.0 cm SOBP 12 cm, Measured 12.2 cm SOBP 14 cm, Measured 14.3 cm SOBP 16 cm, Measured 16.6 cm 0 50 100 150 200 250 300 350 Depth (mm) G2_160MeV_RMW76_range13.0cm_mediumsnout@5cm G2_160MeV_RMW4_range 11.0 cm_large Snout at 5 cm 120 100 P D D 80 60 40 20 0 SOBP 10 cm, Measured 10.6 cm SOBP 8 cm, Measured 8.2 cm SOBP 6 cm, Measured 6.1 cm SOBP 4 cm, Measured 4.0 cm 0 20 40 60 80 100 120 140 160 180 Depth (mm) PDD 120 100 80 60 40 20 SOBP 4 cm, Measured 3.8 cm SOBP 6 cm, Measured 5.8 cm SOBP 8 cm, Measured 7.8 cm SOBP 10 cm 0 0 20 40 60 80 100 120 140 160 Depth (mm)

PTC H Proton Beams Scattered Scanned Ranges: 1 mm to 324 mm in 1 mm increments using range shifters 100 to 250 MeV 8 Energies Maximum Field Size: 10x10, 18x18, 25x25 cm 2 Pulse length: 0.5 sec Time between pulses: 1.5 sec Apertures and compensators 24 different scattering conditions per beamline TPS does not provide MUs, because MDACC did not take the time to implement it. Ranges: 40 mm to 306 mm in 1 mm to 6 mm increments 72.5 to 221.8 MeV 94 energies Maximum Field Size: 30 x 30 cm 2 Maximum pulse length: 4.1 sec Time between pulses: 2.1 sec TPS, at this point in time, does not support apertures. Soon Energy Absorbers, as a new version of TPS is released. TPS provides MUs, as it is required. Per spot, MUs range from 0.005 to 0.04.

PTC H Machine QA Scattered Beam System works. 99.999% of patients are started on time. EMR is used for 100% of patients. 24 hours are required to make apertures and compensators. This has been incorporated into normal clinical workflow. Proton production shop: 5+ days/week Physics in-room activities: Saturdays and late at night and 5:30 AM morning QA Annual machine QA very time consuming 40 to 100 hours on Saturdays. G1 16 different beams, G2 24 different beams, F2 3 different beams. There are annual reviews going on all year long.

Patient Specific QA 5 cm/10 cm water box Which is designed to hold a Farmer type chamber. We also use a Markus or a pinpoint chamber. Solid water plates to obtain the desired depths. Note brass apertures and no compensator The Physics Miracle transforming treatment plans into treatment delivery parameters, including MUs. Generally physics spends 1 to 2 hours after planning is finished to review and prepare for treatment. 27 field cranial spinal patients may require 8 to 10 hours.

PTC H Patient QA Scattered Beam All MUs are based upon measurements 1 8 hours images Physics plan review including 0.5 hr Verification plan creation 0.5 hr MU determination 0.1 hr Aperture/compensator QA 0.1 hr Physical collision check 0.2 hr EMR sign off 2 to 10* hours Total physics time per patient * Cranial spinal patients require substantial physics time

Cranial spinal patient supine ~15 to 20 cranial spinal patients are treated per year. Each new field requires new apertures. Spinal fields change each week.

Machine QA Scattered Beam - Daily ICRU 78 PTC H Practice Interlocks/Communication Room lasers Aperture alignment Pt positioning system Depth dose and lateral profiles Dose monitor cal Individual patient treatment calibration and range checks Interlocks/Communication N/A lasers not used First Rx aperture film Couch movement 1 energy, 3 points, review output from segmented chamber measured field size Dose vs. MU standard condition Part of patient QA, but not range checks Data flow from EMR to RX delivery and imaging systems X-ray system alignment

Machine QA Scattered Beam - Weekly ICRU 78 PTC H Practice Patient position and imaging systems Beam line apparatus Respiratory gating Dose delivered to randomly selected patients Imaging systems daily check of x- ray/proton alignment.? What apparatus Soon RPM will be connected to Hitachi Every patient every field

Machine QA Scattered Beam - Annual ICRU 78 PTC H Practice X-ray positioning and alignment systems CT Hounsfield number calibration Comprehensive tests of therapy equipment: Monitor chambers, timers, beam-delivery termination and control interlocks, stray radiation, gantry isocenter, depth-dose and lateral profiles, baseline date for daily QA checks. X-ray positioning and alignment systems CT Hounsfield number calibration all CT scanners Comprehensive tests of therapy equipment: Monitor chambers, beamdelivery termination and control interlocks, gantry isocenter, depth-dose and lateral profiles, baseline for daily QA checks.

The setup of Gantry rotation isocenter versus couch mechanical isocenter using 2mm sphere in X-ray mode. The cage x-ray tube and FPD are extended. They must be retracted before we can move the gantry. This safety requirement is a pain.

G1 2010 Medium Scatter Range and SOBP Widths Annual Note different SOBP widths Range: within 2 mm of baseline SOBP: within 5 mm of baseline

G1 Distal Penumbra 80% to 20% 2010 vs. Commissioning

G1 Annual Independent Output Check Radiological Physics Center

Patient Treat Field Output Measurement G1 Example of a typical form used to established the MUs for scattered beam treatments.

Pristine Bragg Peak TPS Input Data Also in air spot profiles Monte Carlo Calculated and Measured Normalization Dose in Gy/MU versus range Normalization measurements: 2 cm depth, 8 cm chamber 94 Energies: Ranges from 4.0 cm to 30.6 cm

Spots are not pencils. Low energy spots have issues. FWHM Gillin et al. Med Phys 2010

Scanned Beam Patient QA A 3D Dosimetry Challenge SFO, SFIB, MFO SFO Single Field Optimization SFIB Single Field Integrated Boost MFO Multi-Field Optimization Currently 1 MFO patient every other week 3D dosimetric system(s) needed to meet this 3D challenge Standards for patient QA are evolving 4 + minutes are required to run a field from the EMR, which includes uploading from EMR, Rx machine preparation, Rx delivery, and downloading to EMR

Terminology In treatment planning of spot scanning proton therapy (SSPT), the weight of each spot is optimized using an inverse planning process with or without dose constraints to the target volumes and critical structures. Multi-field optimization (MFO) Intensity modulated proton therapy (IMPT) All spots from all fields are optimized simultaneously Single field optimization (SFO) - Each field is optimized to deliver the prescribed dose to target volume: Single field uniform dose (SFUD) Single field integrated boost (SFIB)

Scanned Beam Patient QA 2D measurements are routinely made with the Matrixx ion chamber array and solid water Note Energy Absorber (EA) in snout, which will be supported in the Spring, 2011 clinical release of Eclipse and will eliminate the need for many low energy beams.

Scanned Beam Patient QA SFO, SFIB, MFO 1 to 4 hrs Physics plan review ~ 1 hr EMR QA Rx Delivery ~ 1 hr Verification plan 1 to 6 hrs 2D % DD in multiple plans 1 hr % DD using Advanced Markus Chamber 4 to 12 hrs Total per patient First MFO patient 120 hrs +. Patient not treated with MFO technique, based upon Physics recommendation

Machine QA Scanned Beam - Daily ICRU 78 PTC H Practice Dose rate and monitor issues Performance of beam position monitors Depth dose curve in a water phantom Calibration of primary dose monitor Interlocks/Communication Monitors 3 energies per day 5 spot positions Depth dose in a water phantom Not done Dose at several spots and depths Data flow between EMR and delivery system Alignment of the proton central ray and the x-ray system

Machine QA Scanned Beam - Weekly ICRU 78 PTC H Practice Qualitative 3-D check of the outline and range of dose distribution for one patient s irradiation field in water phantom Definition of 3D check needs to be established. Output check for three standard 1 liter patterns, which involve all energies a single point measurement. Quantitative 2D QA is performed on each patient at several depths

Machine QA Scanned Beam Semi-annual ICRU 78 PTC H Practice Calibration of primary dose monitor and the phase space of the beam tunes What is the phased space of beam tunes? Clinical physics understands that beam tunes are related to the operating conditions of the accelerator. Beam steering is the use of the bending magnets to steer the beam to the center of the nozzle for each gantry angle. Weekly primary monitor calibration checks. Beam steering is performed weekly to align the spot to the central ray. Pause or alarm signals are a regular occurrence. Tuning the synchrotron may be performed daily. Spot size and position are checked with each spot delivered.

Machine QA Scanned Beam Annual ICRU 78 PTC H Practice Check of the beam characteristics Calibration of the whole dosimetry system, performance of the scanning system in terms of dose linearity and dose rate dependence. Check mechanicals Check imaging system Check of the beam characteristics Calibration of the whole dosimetry system, performance of the scanning system in terms of dose linearity and dose rate dependence. End effect for very small MUs.

End Effect for G3 0.005 MU to 0.04 MU The maximum number of MUs for the discrete spot scanning beam is 0.04, while the minimum is 0.005. The end effect was studied using the Bragg Peak chamber at a depth of 2 cm for both the lowest energy beam and the highest energy beam. The same number of MU s (10) were delivered using 0.005 MU/spot (2000 spots), 0.01 MU/spot (1000 spots), and 0.04 MU per spot (250 spots). Ionization was measured and the results were normalized to the readings for 0.04 MU/spot. The measured outputs were within one percent the same. Thus, within the allowed range of spots, there is no significant difference in the dose delivered, independent of the dose per spot. Gillin et al. Med. Phys. 2010

G3 Annual %DD Measured on 5 Different Beams Energy Requested Range Measured Range MeV cm cm 221.8 30.6 30.7 201.0 25.8 25.9 185.7 20.5 20.6 96.4 7.0 7.0 72.6 4.0 4.0 Point by point measurements for a set number of MUs is the general approach. Ranges are confirmed for only a limited number of energies.

G3 TLD Report from RPC

ICRU 78 9.4 Examples of Periodic Checks The procedures for scanned beams are given mostly in terms of dosimetric issues, as the check of dose delivery is the most important task. Better tools are needed.

Scanned Beam Patient QA at PTC H MUs are provided by the TPS and confirmed through measurements. Before treatment at least one delivery of each field must be performed using the EMR and the delivery system, in order to upload the bending magnet currents to the EMR. The entire spot pattern is delivered for each measurement. This requires at least four minutes of beam time per measurement. Patient dose measurements to confirm the dose at a single point, as performed for IMRT, have recently been abandoned for complex dose distributions, e.g. IMPT. Zhu et al. IJRBP (in press)

Scanned Beam Patient QA Prostate + SV (SFO) March, 2011 6 page report including 2D dose pattern Table 1: Treatment field parameters Prescription Isodose line: 98.2% CTV (cc): 44.3 STV (cc): 116.3 ARLPB Nominal range: 24.83 cm SOBP 9.51 cm, Max E 198.3 MeV, Layers 19, Raw spots 1429, MU 33.38 Absolute dose at isocenter: TPS calculated physical dose (210.8/1.1 = 191.6 cgy). Measured dose 191.3 cgy.

Scanned Beam Patient QA Prostate + SV March, 2011 Central axis depth dose in a rectangular phantom a 2D ion chamber array was used for CA depth dose measurements. Calculated values were obtained from a verification plan created for a solid water phantom in the TPS. Nominal SSD is 250 cm. Three points are measured: two points inside the SOBP and one point in the high-gradient distal fall-off region.

Fish bowl measurement to confirm MU s. Point dose MU measurements

Scanned Beam Patient QA Prostate + SV March, 2011 2D dose distributions in planes perpendicular to beam direction at depths of 18.4 cm and 22.4 cm for each field. Both depths are inside the nominal SOBP. The criteria for acceptance is a works in progress. For prostate patients, 2% relative dose/2 mm works well.

Relative dose comparison Purple: 100% Orange: 95% Teal: 90% Black: 80% Blue: 20% Matrixx: Solid lines TPS: Dashed lines

CTV-45 CTV-50 GTV-54 Single Field Integrated Boost

Patient QA Scanning Beam SFIB 10 yo with infratentorial medulloblastoma. Boost portion treated with scanning beam. Right and left posterior brain boost and a PA spine boost. Depth dose measurements at two different locations for the spine boosts.

Scanned Beam Patient QA Brian and Spine Boosts (SFIB) March, 2011 Prescription Isodose line: 100% Brain CTV (cc): 205.1 STV (cc): 276.6 Spine CTV (cc): 19.1 STV (cc): 61.3 QRPPB (Brain) Nominal range: 13.61 cm SOBP 13.41 cm, Max E 136.4 MeV, Layers 43, Raw spots 2283, Post spots 3064, MU 78.78 SPAPB (Spine) Nominal range: 10.2 cm SOBP 6.97 cm, Max E 118.6 MeV, Layers 32, Raw spots 1120, Post spots 4675, MU 166.26

Point Measurements Pin Point Ion Chamber These point dose measurements are no longer being performed.

Brain SFIB Spine: 2 different axes Depth dose measurements: Red Markus chamber. Green - Matrixx

Measured versus Calculated Dose Purple 100%, Orange 90%, Teal 80%, Black 70%, Blue 10% Purple: 100% Orange: 90% Teal: 80% Black: 70% Blue: 10% Spine Field: Depth 6.4 cm Depth 10.4 cm

Patient QA Scanning Beam MFO 44 yo with chondrosarcoma of the bones of the skull and face. 3 fields: right anterior oblique, ARAPB, PA, BPAPB, and a superior-inferior vertex field, CSIPB. Prescription 70 CGE to the T_PTV70 in 35 fractions. T_GTV 10.1 cc, CTV 70 31.4 cc, T_PTV 70 57.3 cc

Measurements are in terms of absolute dose. Prior to use, Matrixx is calibrated against known dose pattern. Approximate beam time for measurements: 2 hrs. Dose measurements along defined axes with Markus and Matrixx

Superior-Inferior Vertex Field 2D Measurements in Solid Water 9.4 cm 13.4 cm 15.4 cm 17.4 cm 100% is defined has the maximum dose in each plane.

Patient QA Scanning Beam MFO 67 yo with base of tongue carcinoma. 3 fields: right superior-inferior field (56 different energies), left superior-inferior field (58 different energies), and PA field (60 different energies). Prescription 66 CGE to CTV1, 60 CGE to CTV2 and 54 CGE to CTV3. 2D measurements at the gantry angle for each field Dose measurements in Physics Mode at 270 degrees, both depth dose profile comparison and 2D dose distribution in planes perpendicular to the beam direction.

H&N Planning IMPT(MFO) Field 1 Field 2 67 yr old male Squamous cell carcinoma Right base of tongue CTV66, CTV60 & CTV54 3 fields: G280 /C15, G80 /C345 & G180 /C0 Field 1 Field 2 Field 3

ARSPB Gantry: 280 degrees Depth 4.6 cm Calculated Dose profile Measured Gamma index map: 100% for 2% and 2 mm

BRSPB Gantry: 80 degrees Depth 7.0 cm Measured Profiles Calculated Gamma Index Map

CRSPB Gantry: 180 degrees Depth 4.5 cm Measured Profiles Calculated Gamma Index Map

ARSPB Gantry: 270 degrees Depth Dose Measurements 260 cm TSD 3 Different Axes Same depths

BRSPB Gantry: 270 degrees Depth Dose Measurements 260 cm TSD Four different axes

CRSPB Gantry: 270 degrees Depth Dose Measurements 260 cm TSD Three different axes

ARSPB Gantry: 270 degrees 2D Relative Dose Measurements 260 cm TSD Depth: 4.4 cm Depth: 6.4 cm Depth: 8.4 cm Agreement between TPS and measurement is good Depth: 10.4 cm

CRSPB Gantry: 270 degrees 2D Relative Dose Measurements 260 cm TSD Depth 10.4 cm Relative dose comparison, normalized to the highest dose in the plane. Multiple planes are studied. Absolute doses are measured along specific axes. Time intensive: Preparation time several hours, measurement time several hours, report generation time several hours, and review time 1 hour. Eclipse: Double Gaussian spot model.

Works-in-Progress AP/PA fields with Energy Absorber EA will provide for faster treatments with sharper penumbra, as higher energy protons will be used and fewer energy changes. Edvard Munch, 1893

PTC H Summary Protons demand attention to details. There is a substantial amount of clinical physics work. Time is the ultimate constraint. More efficient processes need to be developed. Commissioning new versions of the TPS with new features requires ~ 1 man year. Long term upgrades to the imaging and delivery systems remain a poorly defined challenge.

Protons: The Clinical Physics Full Employment Modality Dedicated Clinical Physics Team: Ron Zhu, Narayan Sahoo, Jim Lii, Richard Amos, Richard Wu, Falk Poenisch, Heng Li, Mengping Zhu, Craig Martin, Patrick Oliver, Brad Tailor + others who have moved on. Dedicated Physics Engineering team: Kazumichi Suzuki, Chuck Smith, MDACC engineers + Hitachi engineers Dedicated Research Team: Radhe Mohan, Uwe Titt, Xiaodong Zhang, Dragan Mirkovic + others who have moved on. In addition, PTC H is a success thanks to the contributions made by the RTT s, the CMD s, and the MD s.

Energy (MeV) Ranges (cm) (d 90%) 24 different scattering conditions Small Snout Medium Snout Large Snout 250 32.4 28.5 25.0 225 26.9 23.6 20.6 200 21.8 19.0 16.5 180 16.9 16.1 13.7 160 13.4 13.0 11.0 140 10.2 10.0 8.4 120 6.9 6.4 6.3 100 4.9 4.3 4.3

Point by Point Measurement of Depth Dose Curve 1.2 1 Series1 0.8 0.6 0.4 0.2 0 0 50 100 150 200 250 300

G1 2110 Mechanical/Radiation Tests