2010 Tomotherapy G.Guidi

FISICA E RADIOTERAPIA NUOVE FRONTIERE TRA HIGH TECH E POST GENOMICA - TOMOTHERAPY: NUOVE POSSIBILITÀ TECNICHE PER NUOVE RISPOSTE A QUESITI CLINICI - G.Guidi, et.al – Medical Physics Dpt. Azienda Ospedaliero - Universitaria di Modena - Policlinico “ Fight” with the doctor... ...with Tomo will be possible? Doctor Physicist Special Thanks to Dr.Amadori for part of this presentation … and the good friendship during this years…. Email: [email_address] Email2: gabrieleguidi@yahoo.com Phone: +390594225699

MODENA HUB-SPOKE PROJECT (RADIATION ONCOLOGY HEALTH SERVICES)

4D RADIATION THERAPY …. VISION (4DRT & 4D TOMOTHERAPY) TOSHIBA 4D LARGE BORE + VISION RT TOMOTHERAPY + VISIONRT 4D LINAC + ABC (ACTIVE BREATHING CONTROL)

3D-IGRT HEALTH TECHNOLOGY ASSESSMENTS (13 REGIONAL RADIATION THERAPY CENTERS COLLABORATION)

… .. 1 Month MADISON, Wis.--(BUSINESS WIRE)--Sept. 10, 2008— TomoTherapy Incorporated (NASDAQ: TOMO) “ ....Thanks to the perfect cooperation and planning between the hospital and TomoTherapy, we took delivery of our TomoTherapy system and just 30 days later we were already imaging and treating our first patient.“ (S. Cencetti - MO) FROM TRUCK (WITH TRICK) …. TO CLINICAL USE 30/04/2008

…… preliminary data are consistent with a better tolerance and lower acute toxicity of Tomotherapy treatment compared with other standard treatments using LINAC (3DCRT – IMRT – RCS - SBRT) CLINICAL PRACTICE & RESEARCH AREA Total Body Irradiation Mesothelioma H-N Lymphoma Pancreas Prostate Radiosurgery Craniospinal Re-Irradiation Lung Total Lymphoid Irradiation Lung - SBRT Bilateral Breast Multiple Lesions

MESOTHELIOMA ( SIB: PTV1 60 : 2,4Gy / Fx 25 - PTV2 50 : 2,0Gy / Fx 25) or (Standard: PTV 50 : 2.0 Gy / Fx 25) Muticenter Intercomparison for Treatment of the Mesothelioma with IMRT and Tomotherapy. G. Guidi, et al Med. Phys. Vol. 36, Issue 6, pag.2666, (June 2009) Collaboration with aTrep (Proton Center), Brescia and Florence Heart liver Right Kidney PTV 50 PTV 60 Esophagus Stomach Esophagus Heart PTV 50 Omolateral Left Kidney

UNRESECATBLE PANCREATIC CANCER SIB: PTV 61,6 : 2,2 Gy / Fx 28 - PTV 50,4 : 1,8 Gy / Fx 28 Right kidney Left Kidney Liver Stomach Small Bowel S.Cord

RE-IRRADIATION: PELVIS SARCOMA PREVIUSLY TREATED ( 3DCRT : 50 Gy / 25 Fx + HDR Brachytherapy : 10 Gy / 2 Fx ) FOR ENDOMETRIAL CARCINOMA Rectum Bladder Small Bowel

RE-IRRADIATION: HEAD & NECK (Standard: 54 Gy / 27 Fx - Hyper-fractionation: 54Gy / 36Fx)

TEMPORAL LESIONS CLOSE TO VITALS OAR (PTV1:55GY/30FX - PTV2 :66GY/30FX) Brainstem Optical Nerve<56Gy Cord<35Gy

RADIOSURGERY RE-TREATMENT (16-22Gy / Fx @ 95% of the Volume) (PREVIOUS WBRT 30 Gy / 10 FX + RS WITH MicroMLC+LINAC 18 Gy /1 Fx – CORD DOSE : 42 Gy ) Cord: 10 Gy < 0,03 %

STOMACH (PTV1: 53.75GY/ 25FX – PTV2: 45GY/25FX) Liver 20%Vol<30Gy Kidneys 20%Vol<22Gy Cord<22Gy

HEAD & NECK WITH CONCOMITANT CHT + RT (SIB) 66 Gy IN 30 / Fx (2,2 Gy/Fx) TO T AND N+ 54 Gy IN 30 / Fx (1,8 Gy/Fx) TO RIGHT CERVICAL NODES RELAPSE TO ORIGINAL SITE AND TO LEFT CERVICAL NODES FROM SQUAMOS CARCINOMA OF LEFT BODY TONGUE ( R C T2 N2B M0) PREVIUSLY MANAGED WITH SURGERY ALONE Vocal Cord Parotid PTV 66 PTV 54 Cord

Standard Treatment @ Modena Linac 6MV Prone Position Multiple field junction 3 Split-beam (1cm for each day) No-Coplanar Beam Multiple Isocenter (no SSD=100cm) PTV Margin 1cm Conformal field Portal verification of each junction Procedure time 35 - 45min PAEDIATRIC CRANIO – SPINAL (Linac) ..not anymore used after the Tomotherapy installation..

Tomotherapy Simulation Prone Position No Multiple field junction No Split-beam No-Coplanar Beam No Multiple Isocenter PTV Evaluation Margin 1cm Margin 0cm High Conformal MVCT verification and adjustment Procedure time 20-30min TOMOTHERAPY VS. LINAC Lung, Hearth, Liver, Eyes, and Kidneys less dose/volume; for Hearth and Liver decrease the DMax Optical Nerve : same Dmax but less dose/volume Lens: increase the Dmax Dose, but under the max toxicity value (also with Complete Block Option) PAEDIATRIC CRANIO – SPINAL (Tomotherapy)

Cranio Spinal - Clinical Tx Supine position Immobilization device (Mask) Target and Margin definition OAR objective Optimize verification time Optimize treatment time Analyze dosimetric accuracy Treat patients CRANIO SPINAL TODAY (20-36Gy)

SECONDARY LUNG CANCER RELAPSED AFTER RFA MULTIMODALITY IMAGE FUSION (SIB: BTV 55 Gy / 5 Fx - PTV 40 Gy / 5 Fx ) Healthy Right Lung: 20 Gy to 10 % BTV PTV Right Bronchus

AIR CAVITY EFFECTS VS. ADAPTIVE RADIATION THERAPY VS. MOTION EFFECT Air Cavity: Density equal 0 g/cm 3 Can create problem to the calculation? During the treatment cycle can change the anatomy Results? The previous plan can be different than the current delivery Using an Adaptive RT approach and a DVH analysis can show an idea of the current mistake and possible missing. Be careful, could be not perfect!!!! Breathing cycle effects and artifact – Organ deformation MVCT density table modification due to the target degradation Fusion algorithm (mutual information) can smooth some effect due the voxel volume considered Some software trick of image concatenation

Result : difference of 0.08Gy (1%) for one fraction of 5Gy The problem is the reliability and stability of the MVCT during the time… The degradation of the target can change the data… (UNDER INVESTIGATION) MVCT SUITABLE FOR ADAPTIVE RT : DOSIMETRIC EVALUATIONS

SPINAL SARCOMA (PTV 70 Gy / 35 FX) VERTEBRA (PTV 30Gy) PALLIATIVE CASES

SPINAL METAL PROSTHESIS (Using MVCT) H&N in 30Fx (PTV1:70Gy - PTV2:64 Gy - PTV3:54 Gy )

ABDOMINAL TREATMENT (PTV 22,5 GY / 15 FX ) Kidney R. Liver Cord Kidney L.

PAEDIATRIC TREATMENTS (14 Gy / 2 Fx) – 2 YEARS OLD REDUCE THE NUMBER OF ANESTHESIA Tomotherapy advantages vs. MicroMLC or Cone systems No systems collision Low integral dose (3 Gy dose is showed) Concomitant anesthesia and patient monitoring very easy No dose at the contra lateral lung (trick during planning) Fast treatment (20minutes) Easy spare of the organ at risks Breathing effect during 3DCRT and MicroMLC treatment Lung Cord

PANCREAS (50.4 Gy / 28 Fx) PTV Liver Cord Kidney

RECURRENT MENINGIOMA - RS 45 Gy /3 Fx – BRAINSTEM : 3 Gy ( PREVIOUS TREATMENT 54 Gy – BRAINSTEM 54 Gy) PTV Brainstem Cord Kidney

LUNG LESION (PTV1: 60 Gy / 30Fx – PTV2: 54Gy / 30 Fx) PTV2 Cord Esophagus PTV1 Heart Lungs

LUNG LESION + BILATERAL ILA + MEDIASTINUM (PTV66 Gy /33 Fx – PTV60 Gy / 33 Fx – PTV54 Gy /33Fx) PTV66 Cord Esophagus PTV54 Heart Lungs PTV60

SBRT MULTIPLE LUNG LESIONS (48 GY / 4FX) PTV1 Cord Ribs PTV2 Lungs

PELVIS (PTV1 63Gy – PTV2: 50.4Gy / 28 Fx) Prostate (PTV1 54Gy – PTV2: 70Gy / 28 Fx) PTV1 Bladder Rectum PTV2

BILATERAL CHEST WALL + SUVRACLAVEAR (50 Gy /25 Fx) PTV1 Lungs Heart PTV2

BAD SETUP IMMOBILIZATION – BAD PLAN APPROACH JUST FOR TRAINING !!! NOT REAL CASES Tomotherapy use a rotational delivery treatment, everything must be where is suppose to be during the planning Arms effect on the attenuation and improper dose at soft tissue Thorax bad fixation and breathing influences Leg and longitudinal alignment (MVCT correction could be complicate between upper and lower movement) Shoulder movement during the treatment or day by day positioning Bad overlap priority of the structures consideration can create unexpected error during treatment and DVH could not show this error

In memory of Marco Corni (2008) RESEARCH RESULTS: TOTAL BODY IRRADIATION USING TOMOTHERAPY

TBI RESEARCH: HIGH DOSERATE EFFECT IN MICE (TOMOTHERAPY 880-900cGy/min) (STUDY UNDER DEFINITION) Idea by G.Guidi, F.Bertoni 2008, 2009, 2010

Our data analysis shows that: Immobilization systems are adequate: 3-fixing point thermoplastic masks for brain treatments (no invasive devices) 5-fixing point masks with shoulder immobilization for head & Neck treatments Thermoplastic masks with abdominal compression for thorax & abdomen treatments Reduced margins of CTV-PTV may be proposed with very low risk of geographic missing: < 3 mm for brain < 5 mm for head & neck < 10 mm for thoracic & abdominal Senseless reduction of the margin could be very dangerous for the future outcomes of the patients IMMOBILIZATION SYSTEM AND SET-UP ERRORS

MANAGEMENT AND OPTIMIZATION HOW CAN I SAVE TIME …… (RADIOSURGERY) Equivalence??? 2 Radiosurgery using Tomotherapy = Same LINAC Occupation Time = 40 minutes at the LINAC available for 3DCRT = 4 Patients? 6 Patients (2 RS+4 pts. 3DCRT) treated at the center vs. 2 RS using 2 LINACs during the same time 1 -3 “Easy” Lesions 35 -45 min (Room Time occupation) 3 “Complex” Lesions 20-25 min (Room Time Occupation)

MANAGEMENT AND OPTIMIZATION HOW CAN I SAVE TIME …… (STEREOTACTIC BODY RADIATION THERAPY) Equivalence??? 2 SBRT using Tomotherapy = Same LINAC Occupation Time = 50 minutes at the LINAC available for 3DCRT = 5 Patients? 7 Patients (2 SBRT+5 pts. 3DCRT) treated at the center vs. 2 SBRT using 2 LINACs during the same time 25 min 45-60 min

MACHINE TIME MANAGEMENT PHILOSOPHY OF THE CLINICAL AND TIME MANAGEMENT Complex cases treated at the Tomotherapy Unit….. … .Treatment time is not a must… … Room time occupation is not a must…. … Plan must cover the clinical requirements…. … with Tomo I have to obtain something otherwise complicate at the LINACs By G.Guidi, F.Bertoni 2008 Global Average: 25,6 ± 8,7 minutes 14,8 3,2 8,2 5,3 1,3 2,3 40 13 23 Prostate 15,6 7,6 11 6,2 2,5 3,5 50 23 35 Thorax 14 3,4 8 6,7 1,4 3,2 53 13 26,2 H-N Max Min Average Max Min Average Max Min Average Beam-On Time MVCT Time Room Time Site

4DCT - MOTION MANAGEMENT 4DPET - MULTI MODALITY IMAGE FUSION

ADAPTIVE RADIATION THERAPY AND MOTION MANAGEMENT (4D-ART: RESEARCH AREA) Target Motion

…… During treatment, the weight loss of 11 kg has changed the anatomy……. The dosimetric evaluation calculated for re-contoured volumes on MVCT shows….. 20 % of left parotid gland vol. received 0,01 Gy / Fx less 5% of PTV vol. received 0,01 Gy /F less and a maximum of 0,06 Gy /F more (  1%Vol) H&N ADAPTIVE CALCULATION STRATEGIES (Case I)

H&N ADAPTIVE CALCULATION STRATEGIES (Case II) …… During treatment, the weight loss of 15 kg has changed the anatomy……. The dosimetric evaluation shows high dose increase anywhere… … The MVCT Daily check can guaranties the quality of the treatment changing and re-planning before any dosimetric error 5% of PTV vol. received from 0.06 to 0,1 Gy /Fx anywhere

GATING vs. TRACKING (Breathing Model) Tracking XRay XRay Tracking XRay XRay 1° Point Of View (Create Model) 2° Point Of View (Reproduce the Model) What’s happen inside? With Tracking, you don’t know! What’s happen inside? You need Marker May be the Xray doesn't see the tumours You need makers!! Asynchrony of the model, means a mistake You don’t see anything inside.... .....you believe in your model

GATING VS. TRACKING Breathing Surrogates are the worst way to treat patients Tracking XRay XRay Tracking XRay XRay Outside Point Of View Inside Point Of View What’s happen inside? With Tracking you don’t know Need to synchronize the beam If you lost the synchronization, than you will not treat any tumours You don’t see anything inside.... ... you believe than you treat the tumours

THE DUEL...... Same Patients Same Doctor Same Contours Same Constrains Same Target Objectives Different Point of View Which is the best plan? Lele

DVHs COMPARISON (AHHGGGG!!!!......) May be, compare DVH is not the best way to compare technologies... ....and for sure is not the right way to compare the clinical outcome Doctor must look at the clinical outcome!! Technologies will show to you what you want!!!

ESCHER : DIFFERENT POINT OF VIEW

OVERDOSED – UNDERDOSED (LOW DOSE LEVEL) Lung Dx: Overdosed Target: Underdosed Objectives (1°PoV) Save Healthy Lung Minimize Integral Dose OARs Objectives Treat Target Objectives (2°PoV) Target Objectives OARs Objectives Save Healthy Lung Minimize Integral Dose

OVERDOSED – UNDERDOSED (HIGH DOSE LEVELS) Objectives (1°PoV) Save Healthy Lung Minimize Integral Dose OARs Objectives Treat Target Objectives (2°PoV) Target Objectives OARs Objectives Save Healthy Lung Minimize Integral Dose Lung Sin: Overdosed Target: Underdosed

PATIENT SYSTEMATIC & RANDOM SETUP ERROR EFFECT (2mm of shift close to the tumours) LUNG

LUNG ADAPTIVE DOSE CALCULATION ( … NOT EVERYTHING IS PERFECT… ) ISSUE UNDER INVESTIGATION: Dosimetric error due to the algorithm? Target delineation Target Movement (Intra/Inter fraction) Dose Lung Estimation Dose at the interface (Bone/Lung/Fat) Volume effect (image down sampling) MVCT vs. kVCT Treatment Dose Output Plan Optimization and Parameters? Operators Doctor Physicist Therapist … but the patient can have daily dose check of the dose delivered and the plan can be optimized during the cycle…

MVCT1 vs. MVCT2 Different target dimension? Is Day1 vs. Day2? (Interfraction) Is Time1 vs. Time2 (Intrafraction) Is the tumor shrinkage ? Is the duty cycle? (Breathing) Different dose calculation ? Where? In tumour or OAR? Change the dose due to the OARs or Tumour position? Isn’t it during the respiration breathing? Why should i do a MVCT before and after the treatment? Why should I believe at the MVCT of multiple days? Is important the Volume effect for goals of the entire treatment? … may be the best way to care the patient, is check every day using a easy way

ORGAN MOVEMENT INFLUENCES & 4D-DOSE ACCUMULATION (RESEARCH AREA) 4D DOSE RECONSTRUCTION OF THE RESPIRATORY PHASES The Dose accumulation must include the organs deformation.... ADAPTIVE is not correct!! DVH is a Dose “reconstruction” of the Volume... DVH is not a clinical outcome!! Dose Matrix (Phase 20%) + Dose Matrix (Phase 30%) + Dose Matrix (Phase 40%) + Dose Matrix (Phase 50%) + Dose Matrix (Phase 60%) + ------------------------------------ 4D Dose Reconstruction Wrong calculation... We should consider the organ deformation... ... during the treatment...

CAN I REDUCE THE MARGIN ? (WITH TOMOTHERAPY FOR US IS LIMITED AND UNDER INVESTIGATION) Courtesy of Marcel van Herk – ESTRO 2009

PROTON - THERAPY ..... (Proton-Tomo?) Few questions in my mind.....may be I need to change my mind!!! ...are we sure about the dose calculation? Is there any clinical impact or benefit vs. Tomotherapy with Photons ...we will try to investigate the problems comparing photon (using Tomo) and proton (collaboration with CNAO and ATrep) Simulation of Protons Treatment with multiple gantry angles between -20 to 120°(by G.Guidi 2009) PTV1=85Gy PTV2=60Gy Cord<40Gy I hope, one day, to work with Protons (by G.Guidi 2010)

TAKE HOME MESSAGES Tomotherapy Innovative machine Faster and relatively easily to implement Flexible for clinical routine and requirements Easy way to treat complex cases Morphological area have not or few limitations Target Delineation Organ Movement (Interfraction – Intrafraction) Organ Constrains Fractionation based on Evidence Base Medicine data Multiple approach can be done and can be found Different plan optimization parameters (Point of View) Clinical objectives 4D Tracking / Gating (Research area) TBI and TLI (Research area) Doesn't exist a best plan or a best machine DVH is not the “absolute true” Plan can not be robust due to the setup and organ movement (dose can change) Daily patient check should be a must for the future (Setup, dose and adaptive re-plan) Many issues for the physicist and physicians Dose calculation Algorithm Adaptive strategies.... Integral dose and prescription must be consider and evaluated Woman fertility (Breast and contra lateral breast) Second cancer induction Paediatric patient .... IGRT Dose is a problem, but anyone should consider the same problem for the ARC Therapy with LINAC Management Full optional should be a must also for Tomotherapy Inc. Service out of clinical time (21.00-6.00) Service full risk also for upgrade and update It is not perfect, but it’s a “good” technology to try to fight the cancer!!

ACKNOWLEDGES “… under the “Ghirlandina” Tower…. … ..new opportunities and ideas are growing … … and many people are working on it” Medical Physics Dpt . Director: T.Costi Physicist: E.Cenacchi B.Franzoni A.E.Francia G.Gottardi G.Guidi Dosimetrist L.Boni L.Morini A.Bernabei Ex-Student L.Binotti P.Ceroni Special Thanks to Elisa, Luciano & Luca Will I see a 4D Tomotherapy Treatment? In my mind: “Thank you guys, without you would not been possible this! 4D Physicist (Lele) Doctors Doctor: M.Amadori (In Mantova) P.Antognoni (In Varese) A.Bruni G.De Marco P.Giacobazzi M.Parmiggiani S.Pratissoli S.Scicolone G.Tolento E.Turco All thereapist U.O. Radiation Oncology Director: F.Bertoni

THANK YOU FOR YOUR ATTENTION AND INVITATION “ That’s too much!!!” (Praha 2009)

2010 Tomotherapy G.Guidi

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