Radiotherapy Advances

Not Radiotherapy

Principles IMRT IGRT Image Fusion Planning

Introduction IMRT = Intensity Modulated RadioTherapy Restriction: IMRT with photon beams IMRT: Highly conformal technique Lateral fluence modulation: More degrees of freedom

IMRT inverse treatment planning produces a prescribed dose to target while sparing healthy tissue fields with a flat intensity are replaced by non-uniform, intensity modulated beams

Intensity Modulated Radiotherapy (IMRT) IMRT takes conformal radiotherapy a stage further by using dynamic motion of the MLC leaves to produce the optimum pattern of radiation intensity across the treatment field. 9-field treatment of base of brain (red) using IMRT to shape high dose region around brain stem (blue)

Multileaf Collimators (MLCs) MLCs consist of two banks of opposed tungsten leafs which can move in and out of the treatment beam. MLCs shape the radiotherapy beam so it conforms more closely to the target.

Step 4 in the Radiotherapy Process Linear Accelerator The aim of Treatment Delivery is to treat the patient s tumour volume as accurately as possible. 4. Treatment Delivery Treatment Delivery

Image-guided Radiotherapy No matter how accurate we are in positioning the patient during planning and treatment, the target organ may stray from it s planned position due to internal organ filling, breathing etc. How can this be overcome?

Using OBI to improve treatments Images of the target in relation to the radiation field position taken prior to each. Auto-matching software compares actual target position with intended position Software calculates how treatment couch should be moved to compensate for any discrepancy.

On board imaging (OBI) Diagnostic imager attached to linac gantry can take full quality planar and CT images with the patient in the treatment position

Before seeds matched (seeds out with structures)

Seeds matched using KV/KV

Image Registration Image registration allows clinical images of the same disease site from different sources to be viewed and processed simultaneously. Most useful in radiotherapy is the combination of MRI or PET with CT.

CT / MR fusion with 3D reconstruction

Prostate Brachytherapy Game of 2 halves LRD monotherapy HDR Boost after XRT Monotherapy

Alpha/Beta Ratio

LDR 145GY to capsule 60 Day ½ life Monotherapy T1/T2 tumours only Permanent Implant 20 yr body of evidence

HDR High activity Iridium 192 source Monotherapy T1/2 or Boost T3/4 Temporary Implant Fractionated Data non randomised,retrospective,single institution

RP, EBRT or Brachytherapy for T1/2 Prostate Cancer Potters L et al., ASTRO 2012

Iodine Seeds Iodine-125 sealed source Available as loose seeds or RapidSrand Gamma emitter, 25 40 kev Half life: 59.4 days

Fraction of total dose delivered Lifetime dose from I-125 1 0.8 0.6 0.4 0.2 0 0 2 4 6 8 10 12 14 16 18 Time post implant (months)

Prostate brachytherapy technique Permanent insertion of I-125 seeds into the prostate. Main principles: Transperineal insertion Ultrasound Guidance Template system 1 or 2 hospital visits (cf. 35 visits for XBRT)

HDR Dose Prescription Doses: Monotherapy 10.5 Gy x 3 8.5-9.5 Gy x 4 6.0-7.5 Gy x 6 Boost 15 Gy x 1 (with 36-40 Gy XRT) 9.5-10.5 Gy x 2 (with 40-50 Gy XRT) 5.5-7.5 Gy x 3 (with 40-50 Gy XRT) 4.0-6.0 Gy x 4 (with 36-50 Gy XRT)

SABR/SBRT/SRS/SRT Dose Time Accuracy

Stereotactic Radiotherapy specialized type of external beam radiation therapy called stereotactic radiation uses focused radiation beams targeting a welldefined tumor, relying on detailed imaging,

Why Prostate Shorter,more convenient schedule Radiobiology Less toxicity (acute) Iso-effective Cost Effectiveness

Alpha/Beta Ratio

Pro-SABR Study A pilot study to assess acute gastro-intestinal (GI) and genitourinary (GU) toxicity in patients treated with flattening filter free (FFF) stereotactic ablative RT (SABR) for Prostate cancer.

Pilot study of 20 patients duration- 1 year Primary objective 1. Feasibility 2. Safety 3. Efficiency Primary endpoints 1. Can clinically acceptable plans be achieved in 90 % study patients. 2. Safety will be measured by incidence of RTOG grade toxicity. 3. Reduction of 50% BOT will show prostate SABR to be more efficient technique in comparison to conventional VMAT. Secondary outcome measures 1. Prostate-specific antigen response. 2. Late toxicity from week 18

Inclusion Criteria 18-80 years T1-T2 stage WHO performance status 2 PSA 20 ng/ml Gleason score 7 Histologically proven prostate adenocarcinoma No lymph nodes on CT/MRI No distant metastases No previous surgery including TURP No Previous active malignancy within last 10 years other than BCC.

Exclusion criteria Hip prosthesis Previous prostate surgery inc. TURP within last 6months. Condition that prevents implantation markers e.g concommitant warfarin. Previous active malignancy within 10 years other than BCC

Study design Hypofractionated- SABR 35 Gy in 5 fractions alternate days over 11 days. Conventional 74GY in 37 fractions Rapidarc 10x FFF Pro step -Superior indexed immobilisationimproved reproducibility.

MRI planning Scan Novel in Prostate planning at BWOSCC. Superior soft tissue definition Literature supports smaller volumes on MRI¹ No other SABR studies published have used MRI.

Study consent seeds implanted 1 st Visit Planning Scans Bowel/bladder prep Immobilisation head support knee and ankle support 2 nd Visit CT Planning scan MRI Planning scan Identical position minimise fusion error Treatment Planning and QA CT and MRI image sets fused MRI used for delineation of target and OAR s

CT planning scan MRI planning scan

Treatment process 35 Gy over 5 alternate days Medical review each fraction RTOG toxicity scoring Enema and full bladder Prior to each fraction IGRT -Pre treatment verification CBCT Check set up position-bony match Match to gold seeds 0mm action level Online verification Correcting to sub millimetre accuracy Check OAR position before delivering treatment

Treatment Delivery Clinician online image approval Online verif to beam on ~ 12 mins 10x FFF VMAT 2 arcs Beam on time 2 mins Only UK centre using FFF in SABR Only study published Milan using FFF² Post CBCT acquired retro analysis Show Intrafraction motion-not real

Pre CBCT Seed Match Coronal view CT Ref Scan CBCT

Pre CBCT Seed Match - axial view CT Ref Scan CBCT

Follow up Phonecall week 4 clinic week 10 clinic week 18 SOC thereafter Longest follow to date week 10 Recruitment 14 patients recruited to date 2 refusals

Advantages of SABR Slot length reduction Conventional 37 x 10mins appointments SABR 5 x 40 min appointments New technology FFF delivery Treatment time greatly reduced Intrafraction motion less likely Treatment technique more conformal than published data³.

Introduction Aims/objectives Interim data: A pilot study to assess toxicity in patients treated with flattening filter free (FFF) stereotactic ablative RT (SABR) for prostate cancer. Aileen Duffton, Azmat Sadozye, Carolynn Lamb, Nick MacLeod, Lynsey Dallas, Suzanne Smith, Edi Stewart, John Foster, Lorraine Collins, Stefano Schipani, David Dodds 1 Department of Radiotherapy, Beatson West of Scotland Cancer Centre, Glasgow. 2 Department of Physics and Bioengineering, Beatson West of Scotland Cancer Centre, Glasgow 3 University of Glasgow, Glasgow The radiobiological characteristics of prostate cancer have been investigated and evidence suggests a low alpha/beta ratio. As a result, increased tumour cell kill should correlate with increased dose per fraction. 1-2 Improved tumour control rates should be possible by delivering large doses/fraction without increasing normal tissue toxicity. Although in-vivo studies have supported this, the techniques of radiation delivery have tended to use Cyberknife or other less sophisticated linear accelerator techniques. 3 This study is the first to use FFF volumetric arc therapy for prostate SABR using fiducial markers for verification and MRI/CT fusion for delineation. Results Table 1.Planning information, dose constraints and BOT Planning Clinically acceptable plans were achieved for 100% of reported patients. (Table 1) Feasibility - Can clinically acceptable plans be achieved in 90% of study patients using prostate SABR protocol by assessing PTV coverage and specified dose constraints for rectum and bladder. Safety -Measured by incidence of Radiation Therapy Oncology Group (RTOG) grade toxicity of grade 3 occuring in less than 10% of patients Efficiency - A reduction of 50% beam on time (BOT) will show prostate SABR to be more efficient technique in comparison to conventional VMAT. Methods Ethically approved safety and feasibility study including first 10 patients with;low-intermediate risk prostate cancer, PSA 20 ng/ml and a Gleason score 7. Strict inclusion/exclusion criteria met. MRI/CT image fusion used for target delineation. Patients planned using 10X FFF (2 arcs) and treated using Truebeam STX to a dose of 35Gy/5 fractions. Patients were treated on the planned delivery schedule of alternate days which resulted in an overall treatment period of 11 days. Cone-beam CT images were acquired pre and post treatment. Patients were assessed for acute and late gastro-intestinal (GI) and genito-urinary (GU) toxicity throughout treatment and at 10 and 18 weeks as well as PSA response. Planning criteria was assessed ensuring it was a clinically feasible method of planning and time of treatment delivery was recorded to assess efficiency. Table 2. Acute GI toxicity for first 10 patients Table 3. Acute GU toxicity for first 10 patients Toxicity All patients tolerated the treatment well and no GI/GU toxicity exceeded grade 2. (Table 2 and 3) Two patients experienced grade 2 GI at their 4 week follow up, this reduced to a grade 1 by their 10 week follow-up. Only 1 patient experienced grade 2 GU toxicity, this occurred at week 4 and reduced to grade 1 by week 10. The final GI acute toxicity assessment at week 10 recorded 8 patients had grade 0 and 3 patients had a grade 1. For GU, 3 patients had grade 0 and 7 patients had grade 1. Efficiency Mean treatment time for a course of conventional radiotherapy 1814.48 seconds and for SABR 603.1 seconds. This demonstrates a significant reduction in BOT of 67% for study patients (p=<0.001). (Table 1) A. B. Figure A. Example of high PTV conformality Figure B. Example of high GTV conformality Conclusion Following the assessment of the first 10 patients, the research team is satisfied that all outcomes from this study are being met. Planning data has been achieved for all patients allowing treatment using the study method to proceed. Treatment has been tolerated well by patients and acute toxicity data is well within acceptable limits. A significant reduction in BOT has also demonstrated the study technique to be efficient. Financial support Thank-you to the WeCan Development fund for supporting this project. References 1. Miralbell R, Roberts SA, Zubizarreta E, Hendry JH. Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 (0.9 2.2) gy. International Journal of Radiation Oncology*Biology*Physics. 2012 1/1;82(1):e17-24. 2. Daşu A. Is the α/β Value for Prostate Tumours Low Enough to be Safely Used in Clinical Trials? Clin Oncol 2007 6;19(5):289-301. 3.Stereotactic Ablative Radiotherapy (SABR): A Resource. SABR UK Consortium. Version 4. 2013