Micropos Medical Ab · NGM:MPOS
Micropos Medical Ab — Technical Presentation (May 2024)
35 slides from Micropos Medical Ab's technical presentation, May 2024
Slide 1: Lessons from the PACE-B study & why we need the PRECISION study
Lessons from the PACE- B study & why we need the PRECISION study Professor Duncan McLaren Consultant Clinical Oncologist Edinburgh Cancer Centre & University of Edinburgh
Slide 2: PACE-B acute toxicity
PACE- B • Acute RTOG G2+ GU tox at 12wks SBRT= 36.25Gy in5# v 62Gy in 20# CRT + ADT 27% CRT v 23% SBRT p=0.16 ns PACE B Acute Toxicity • Acute RTOG G2+ GI tox at 12wks 12% CRT v 10% SBRT p= 0.30 ns • Suggestion that Cyberknife lower RTOG acute GU 2+ v Linac 12% CyberK v 31% Linac p<0.001 sig • Sligh
Slide 3: How significant is acute GU toxicity
How significant is acute GU toxicity RTOG Acute GU toxicity scores Grade 1= twice frequency of pre-treatment urination or twice frequency of nocturia/ dysuria- not requiring meds Grade 2= less than an hour between urination (12-16 times per day) nocturia 5-8 times , dysuria, urgency, bladder spasms
Slide 4: PACE-B late toxicity
• Late RTOG G2+ GU toxicity at 24 mths PACE B Late Toxicity 2% CRT v 3% SBRT p= 0.39 ns • Late RTOG G2+ GI toxicity 3% CRT v 2% SBRT p= 0.32 ns Updated at 5 years • Late RTOG G2+ GU toxicity 3.2% CRT v 5.5% SBRT p= 0.14 ns • Late RTOG G2+ GI toxicity 0.29% CRT v 0.28% SBRT p= 0.99ns
Slide 5: How significant is late GU toxicity
How significant is Late GU toxicity Late GU Toxicity RTOG RTOG Late GU toxicity scores GRADE 1 2 3 4 Slight epithelial Moderate frequency; Severe frequency & Necrosis/contracted atrophy; minor generalized dysuria; severe bladder (capacity < Bladder telangiectasia telangiectasia; telangiectasia (ofte
Slide 6: PACE-B 5-year results
PACE -B • 874 pts n=441 CRT v n=433 SBRT 5- year results • Median age 69.8 years (IQR 65.4-74.0) • Median PSA 8.1 (IQR 6.3-11) v 7.9 (IQR 5.5-10.9) • NCCN low risk = 9.3% v NCCN intermediate = 90.7% • Median FU 73.1 months (IQR 62.6-84) • 5-yr BCFS • 94.6% (95%CI 91.9-96.4%) CRF • 95.7% (95%CI 93.2-
Slide 7: Cancers 2023, 15, 1288
Cancers 2023, 15, 1288. https://doi.org/10.3390/cancers15041288 https://www.mdpi.com/journal/cancers
Slide 8: Baseline demographics and clinical characteristics
Cancer Centre ‘OD Western General Hospital Ox> Edinburgh +t Table 1. Baseline demographics and clinical characteristics. P| SAN GERARDO eae Fractionated or Moderately apy <5 Lypofractionated Radiotherapy (n = 428) Median age in years 69 (65-73) 69 (65-73) NCCN risk group low 35 (8%) 43 (10%) interme
Slide 9: Baseline characteristics continued
Edinburgh HSGt (@) Et Cancer Centre HOSPITAL Western General Hospital SAN GERARDO ji Conventional Stereotactic Body Sisal ex Stance Radiotherapy Group ao ne (n = 414) Hypofractionat Radiotherapy (n = 428) Pre-randomisation use of anti-cholinergic Yes 17 (4%) 15 (4%) No 397 (96%) 413 (96%) Fiducial m
Slide 10: Logistic regression for late GU toxicity after SBRT
Table 2. Univariable and multivariable logistic regression model to identify covariates associated with CTCAE late genitourinary toxicity after SBRT. Covariates Level CTCAE Grade 2+ GU Late Toxicity (6-24 Months) CTCAE Persistent Grade 2+ GU Late Toxicity No Yes Univariable Multivariable No Yes Univ
Slide 11: Logistic regression covariates continued
Covariates Level CTCAE Grade 2+ GU Late Toxicity (6-24 Months) CTCAE Persistent Grade 2+ GU Late Toxicity No Yes Univariable Multivariable No Yes Univariable Multivariable (n= 282) (n= 132) (n= 404) (n=341)_ | (n=73) (n= 404) N(ior N(hor | OROS%CD OR (05% Nor | N(%)or | OR(O5% OR 05% Median Median f
Slide 12: MVA for any G2+ GU toxicity
MVA for any G2+ GU toxicity MVA factors Odds Ratio OR range P value Baseline G2+ 4.27 1.41-13.04 P=0.01 Worst acute G2+ 3.70 2.39-5.98 P<0.0001 Fiducial markers 2.44 1.35-4.40 P=0.002 Conventional Linac 2.30 1.34-3.94 P=0.002 The area under the receiver operating characteristic (ROC) curve (AUC) for
Slide 13: MVA for persisting G2+ GU toxicity
MVA for persisting G2+ GU toxicity MVA factors Odds Ratio OR range P value Baseline G2+ 5.95 2.1-16.9 P=0.001 Worst acute G2+ 4.26 2.36-7.68 P<0.001 Fiducial markers 2.41 1.14-5.11 P=0.02 Conventional Linac 1.89 0.98-3.68 P=0.06 The AUC for the multivariable model to predict persistent grade 2+ late
Slide 14: Logistic regression for late GI toxicity after SBRT
Table 4. Univariable and multivariable logistic regression model to identify covariates associated with late CTCAE gastrointestinal toxicity after SBRT. carats Tara CTCAE Grade 2+ GI Late Toxicity (6-24 Months) CTCAE Grade 2+ GI Persistent GI Late Toxicity | No ‘Yes Univariable Multivariable No ‘Yes
Slide 15: Table 4 continued
Table 4. Cont. Covariates Level CTCAE Grade 2+ GI Late Toxicity (6-24 Months) CTCAE Grade 2+ Gl Persistent GI Late Toxicity No Yes Univariable Multivariable No Yes Univariable (n=357) | (n=51) (n= 413) (n=392) | (n=22) N(o)or | N(h)or | OR@%C)| p | ORM%C)) p N(h)or | Noor | ORWS%C) p Median Median v
Slide 16: MVA for worse G2+ GI toxicity
MVA for worse G2+ GI toxicity MVA factors Odds Ratio OR range P value Baseline G2+ NA NA NA Worst acute G2+ 3.68 1.89-7.17 P<0.0001 Fiducial markers 0.73 0.35-1.54 P=0.41 Conventional Linac 1.67 0.77-3.60 P=0.19
Slide 17: Univariate analysis for persisting G2+ GI toxicity
Univariate Analysis for persisting G2+ GI toxicity MVA factors Odds Ratio OR range P value Baseline G2+ NA NA NA Worst acute G2+ 4.15 1.70-10.17 P=0.002 Fiducial markers 0.51 0.21-1.22 P=0.13 Conventional Linac 6.74 1.54-29.45 P=0.01
Slide 18: What can we conclude from these data?
What can we conclude from these data? 1 Baseline G2+ GU toxicity predicts for late G2+ GU toxicity- (avoid treating with SBRT or temper expectations) 2 Acute G2+ GU toxicity predicts for late G2+ GU toxicity - (minimise risk- spare urethra & bladder) 3 Acute G2+ GI toxicity predicts for late G2+ GI
Slide 19: PRECISION Study
PRECISION Study- A Phase II study of 3 fractions of Prostate SBRT with RayPilot & HypoCath image guidance for men with NCCN low or intermediate risk prostate cancer Professor Duncan McLaren & Dr Stefano Arcangeli Consultant Oncologists at Edinburgh & Monza
Slide 20: Rationale
Rationale • Acute toxicity predicts for the risk of late toxicity • Linac based VMAT the most common method of treatment delivery of extreme hypo-fractionation • Optimise Linac performance with continuous motion management (RayPilot with HypoCath guidance) • Tighter margins, urethral sparing and con
Slide 21: Iso-effective dose for prostate cancer
Iso effective for Prostate Cancer alpha/beta 2-1.5 α/β=5 α/β= 4 α/β= 3 α/β=2 α/β= 1.5 EQD2 EQD2 EQD2 EQD2 EQD2 PACE B 36.25Gy in 5# Bladder/ Urethra α/β Rectum α/β Prostate α/β PTV 63 70 74 84 91 40Gy in 5# CTV 74 80 88 100 109 PRECISION 28.5Gy in 3# PTV 59 64 71 82 90 31.5Gy in 3# CTV 70 76 85 98 1
Slide 22: Iso-effective dose for prostate cancer
Iso effective for Prostate Cancer alpha/beta 2-1.5 α/β=5 α/β= 4 α/β= 3 α/β=2 α/β= 1.5 EQD2 EQD2 EQD2 EQD2 EQD2 PACE B 36.25Gy in 5# Bladder/ Urethra α/β Rectum α/β Prostate α/β PTV 63 70 74 84 91 40Gy in 5# CTV 74 80 88 100 109 PRECISION 28.5Gy in 3# PTV 59 64 71 82 90 31.5Gy in 3# CTV 70 76 85 98 1
Slide 23: EQD2 comparison PACE-B vs PRECISION
α/β=5 α/β= 4 α/β= 3 α/β=2 α/β= 1.5 EQD2 EQD2 EQD2 EQD2 EQD2 PACE B 36.25Gy in 5# Bladder α/β Rectum α/β Prostate & Urethral α/β PTV 63 70 74 84 91 40Gy in 5# CTV 74 80 88 100 109 PRECISION 28.5Gy in 3# PTV 59 64 71 82 90 31.5Gy in 3# CTV 70 76 85 98 108
Slide 24: Study population - NCCN criteria
Study population- NCCN criteria Low risk prostate cancer • T1-2a & PSA <10ng/ml & Gleason 3+3 = 6 Intermediate risk prostate cancer • T1/2 and 1 or more of PSA 10-20ng/ml or Gleason score of 3+4=7 • No TURP & suitable for SBRT • 80cc max volume • No hip replacements • No ADT
Slide 25: Study end points
Study End points • Co-Primary endpoints • Cumulative Grade 2 or worse RTOG/CTCAE v5.0 acute GU from baseline up to 12 weeks post treatment. • Cumulative Grade 2 or worse RTOG/CTCAE v5.0 acute GI toxicity from baseline up to 12 weeks post treatment. • Secondary endpoints • Grade 2 or worse RTOG/CTCAE
Slide 26: Study design
Study Design Single arm 2-stage Phase II study • Early stopping rule if acute GU or GI toxicity too high - GU toxicity: The cumulative percentage of acute Grade2+ CTCAE/RTOG GU toxicity is expected to be 31%, while an increase to 46.5% (relative increment of 50%) will be considered unacceptable. - G
Slide 27: Sample size calculation
Study Design Sample size calculate to evaluate both toxicities together to achieve the following conditions 1. The false positive error is controlled at <5% considering a true GU toxicity rate of 46.5% or higher. 2. The false positive error is controlled at <5% considering a true GI toxicity rate of
Slide 28: 100 patients required
Study population ve) aM 33 Edinburgh Cancer Centre ‘Western General Hospital Enrolling 43 pts 100 patients required Stage | < 18GU toxicities AND <8Gl toxicities 57 pts more
Slide 29: Planning workflow
Workflow Planning Planning 3 # SBRT MRI CT ViewCath, enema, fill bladder 100-150cc HypoCath day1, enema, fill bladder 100-150cc, remove HypoCath post 3rd#
Slide 30: Outlining
Outlining MRI T2 sequence soft tissue fusion with the CT using the ViewCath position Outline OAR’S as per protocol CTV= prostate alone – low risk CTV= prostate and 1cm SV intermediate risk CTV- PTV = 0.3mm sup/ant/lat and 2mm post
Slide 31: Outlining: CTV to PTV and urethra
Outlining CTV to PTV 2mm post and Urethra CTV= catheter plus 2mm 3 mm Urethra PRV = Urethra CTV plus 2 mm ant/lat/sup STEP 1 Catheter outline 6mm circle PTV = 28.5Gy ≥95% coverage CTV_Prescribed STEP 2 Urethra wall = catheter + 2mm = 31.5Gy ≥95% PRV urethra aim to keep to PTV dose STEP 3 Urethral PR
Slide 32: Planning CT and CBCT
Ory Edinburgh HSGt Cancer Centre HOSPITAL Western General Hospital SAN GERARDO Planning CT CBCT Foley catheter catheter + transmitter
Slide 33: Radiographer set up
Radiographer set up bladder STEP 1 CBCT match to catheter and check urethra within the PRV (4 mm on the catheter) STEP 2 ensure that the PTV is covered (priority is PTV coverage) STEP 3 watch tracking to ensure all within 2mm tolerance STEP 4 beam on STEP 5 interrupt if movement rectum prostate STEP
Slide 34: Where are we now
Where are we now Protocol v1.3 has been IRAS form completed and Submitted to Ethics approved by R&D approved by R&D Approved –April 2024 RedCap Database Radiotherapy evaluation Test Case for approval prior constructed and being work sheets under to opening the study updated after review construction
Slide 35: Discussion & Comments
fe) Edinburgh rss ve) CancerCentte WestenGeneralHospitl ==5§ s/s $s (= i st tt (a SAN GERARD O Discussion & Comments