shifting paradigm in precision radiotherapy - mri-guided radiotherapy poon_hksh_shifting... ·...

This presentation is for scientific discussion only – Please do not distribute following this meeting.

Shifting paradigm in precision radiotherapy - MRI-guided radiotherapy

Dr. Darren MC Poon

Honorary Consultant

Hong Kong Sanatorium & Hospital Honorary Clinical Associate Professor

Chinese University of Hong Kong

Vice-president of Hong Kong Society of Uro-Oncology 1

http://www.google.com.hk/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjNvKXP067QAhWExLwKHa-zCvwQjRwIBw&url=http://www.mect.cuhk.edu.hk/cfd2014/&psig=AFQjCNH7E-PADMqCCPY_1iratv4JvyRNDA&ust=1479433020460396


Disclosure

• Advisory board: Janssen, Ipsen, Astellas, MSD, Merck • Speaker honorarium: Roche, BMS, Merck, Pfizer, MSD, Ferrings, Ipsen • Research grant: Astellas

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MRI-guided RT : Excellent soft tissue contrast and image

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CT MRI

Re-SBRT for L5 post. metastasis

SBRT CA prostate Intra-prostatic lesion Boost

HCC with prior RT to L spine

Localized CA prostate


MRI-guided RT - Potential benefits

Precise Image-guidance

Online Adaptive Planning

Beam-On Imaging For real-time monitoring

Functional imaging For response assessment

MRI-guided RT

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Image-guidance: Cornerstone for precision RT

• IGRT (186 pts, 2008-09) vs non-IGRT (190 pts, 2006-07) • IGRT group: Daily tracking by fiducial markers. Otherwise

same dose and margin among 2 groups • Late G2 or above GU toxicities:

– 10.4% (IGRT) vs 20% (non-IGRT) p=0.02

• 3 yr PSA relapse-free survival in high risk patients: – 97% (IGRT) vs 77.7% (non-IGRT) p=0.05


Image-guidance: Cornerstone for precision RT

Kilburn et al. Image guided radiation therapy may result in improved local control in locally advanced lung cancer patients. Pract Radiat Oncol. 2016


Intra- & Inter-fractionation variation in targets and OARs Current IGRT vs MRI-Linac

LPTM

RL19

1009

v1.

0

Current Image-guided RT Fiducials - Cyberknife - ExacTrac CBCT - Tomotherapy - VMAT

MRI-Linac Online Plan adaptation







MRI-guided RT

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Elekta’s Unity (MRI-Linac) Overview 9


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HKSH MRI-simulator and MRI-Linac (Unity)


Workflow for MR-Linac 11


Online Plan Adaptation 12


Multi-disciplinary team for MR Linac 13

Oncologist

Physicists

RTT RTT

Dosimetrist

Decision: ATS vs ATP Target contouring Plan Verification

QA

Patient setup MRI acquisition Image registration Plan optimization

Monaco MRTC QA terminal


1st fraction ATP

8.27 cm3 (CT Plan)

3rd fraction ATP

2nd fraction ATP

Contours from CT plan on Day 1 Pre-Tx MR Contours from CT plan on Day 3 Pre-Tx MR

Contours from CT plan on Day 2 Pre-Tx MR

GTV= 8.278cm3

GTV= 6.089cm3

GTV= 3.602cm3

MRI-guided Radiotherapy - Adaptive SBRT for oligorecurrence

8Gy x 5frs = 40Gy


4th fraction ATP

5th fraction ATP

Offline ATS reference plan based on 3rd fraction MR

ATP to offline ATS plan

GTV= 2.324cm3

GTV= 3.602cm3 GTV= 1.764cm3

Contours from ATS plan on Day 4 Pre-Tx MR

Contours from ATS plan on Day 5 Pre-Tx MR Contours generated based on Day 3 Pre-Tx MR


8Gy x 5frs = 40Gy



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8Gy x 5frs = 40Gy


MRI-guided Radiotherapy - Adaptive prostate SBRT

1ST fraction ATP

145.38 cm3 (CT Plan)


7.25Gy x 5frs to whole prostate; 8Gy x 5frs to the IDL (intra-prostatic dominant lesion)



CT plan CTV-Prostate volume = 145.38 cm3

ATS plan CTV-Prostate volume = 151.73 cm3


ATS

2nd fraction ATS

Contours generated based on Day 2 Pre-Tx MR




3rd fraction ATS

ATS CTV-Prostate volume = 170.21 cm3

ATS ref plan CTV-Prostate volume = 151.73 cm3

Contours from ATS ref plan on Day 3 Pre-Tx MR

ATS

Contours generated based on Day 3 Pre-Tx MR








MRI-guided RT

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MRI-guided Radiotherapy - Pancreatic SBRT

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51/M Inoperable Pancreatic NET Dose fractionation: ITV : 35Gy in 5frs (4mm all except 10mm Sup/Inf from GTV) PTV: 33Gy in 5frs (5mm from ITV) ATS for all 5 fractions Average Treatment time was 70mins

Abdominal compression belt


MRI-guided Radiotherapy - Pancreatic SBRT

PET-CT scan (Post-RT 2 months): Ga-88 DOTATATE SUV uptake 55.3 to 39.4

CT scan (Post-RT 4 months): Size: Pancreatic tumour: 4.4 x 2cm to 2.4 x 1.6cm







MRI-guided RT

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Functional MRI: Potential Response Monitoring with DW-MRI

DW-MRI measures random Brownian motion of water molecules within tumour

Advanced tumour with disorganized cellular membranes and complicated macromolecular structures which impede the diffusion of water molecules

Effective treatments result in the loss of cellular membrane and macromolecular structure integrities results in increased diffusion within the tumour (diffusability increased)

Densely packed solid tumour Treatment-induced cell death ↑Diffusability

Treatment


Potential Response Monitoring and adapative planning with DW-MRI

Weekly therapeutic response monitoring by DW-MRI Correlate sequential Apparent Diffusion Coefficient (ADC) maps

Sequential ADC Maps

Baseline Week 1 Week 2 Week 3 Post Treatment

Adaptive RT with ADC map Register ADC map with Unity treatment plan Quantitative dose painting by number (DPBN) adaption Auto-segmentation on ADC map to generate boost target volume for ATS Additional boost to resisting tumour to improve tumour control


Functional MRI: Dynamic-contrast enhanced (DCE-MRI)

Ktrans map with DCE-MRI

M/59 Stage T1N1M0 Received whole course of RT with 74.2Gy/35fr in June 2020 Planning for residual tumour boost with MRL (2Gy x 10frs) Functional MRI to identify the most resisting portion of tumour


Further NP boost or not? 28

Pre-Tx

Treated After 9fr

This presentation is for scientific discussion only – Please do not distribute following this meeting. 30 *3 sites in China are also clinical as part of the CFDA trial

Unity MR-Linac Consortium LP

TMR

L190

910

x2


• N: 58 (Till Oct 2020)

Clinical experience with MRI Linac @ HKSH


Stereotactic body RT (SBRT) for localized prostate cancer

SBRT

Conventional IMRT

Conventional RT 38 fractions (2Gy/fr) over 7.5 weeks

Stereotactic body RT (SBRT) 5 fractions (7-8Gy/fr) over 2-3weeks

-More convenient (esp. old age pt) -More radiobiologically favorable, potentially improve outcome (prostate sensitive to high dose/fraction)


Ultra-hypofractionation (SBRT) vs conventional RT 33

Widmark et al. Lancet 2019; Brand et al. Lancet Oncology 2019

6.1Gy x 7fr vs 2Gy x 39frs, n=1200 7.25Gy x 5fr vs 2Gy x 39frs or 3.1Gy x 20frs, n=874

FFS: 7frs ~ 39frs

Similar acute GI/GU toxcity


Phase II open-labelled randomized SBRT vs IMRT study (NCT02339701)

Inclusion criteria: Patients with low or intermediate risk ( i.e. T1-T2c and PSA < 20 and Gleason score < 8) clinically localized prostate cancer with

the risk of pelvic node metastasis ≤ 15% as calculated by Roach’s formula Stratification according to

Risk group ( low vs intermediate) Sample size: 64

Conventional IMRT* 76Gy/38frs/7.5wks Primary end point:

• 1 yr HRQOL as measured by EPIC

Secondary end points (ITT):

• Acute and late toxicity • Biochemical FFS • Disease-specific survival • Overall survival

Efficacy endpoints (ITT)

SBRT*

36.25Gy/5frs/ 10-14days

R A N D O M I Z E D

1:1

• Low or intermediate risk prostate cancer

•T1-T2c • GS < 8 •PSA < 20

Patients

P.I.: Dr. Darren MC Poon

*Image-guidance with fiducial markers matching is mandatory for both arms.

Manuscript in submission Presented in ESMO Asia 2018 & ASCO GU 2019



Patient-reported QOL: EPIC score change 35


Role of Prostate RT in Metastatic Prostate Cancer 36

STAMPEDE Arm H

Parker et al. Lancet Dec 2018

N=2061 Median FU: 37 months

PTV: Prostate + 1cm (8mm post) margin Median time to start of RT after ADT: 3.2 mos


STAMPEDE Arm H : OS results 37

Parker et al. Lancet Dec 2018


SBRT Prostate protocol at HKSH

Target volume PTV margin Dose Whole prostate 5mm (3mm post)

36.25Gy (Low-Inter risk) 40Gy (High risk or Low volume metastaic)

Intraprostatic dominant lesions (IDC) Involved pelvic LNs

5mm (3mm if close to rectum or bowel) 40Gy (Low-inter risk) 33.5 - 40Gy (Node +ve disease)

Proximal 2/3 SV 5mm (3mm post) 36.25Gy (Inter to high risk)

Pelvic lymphatics 5mm margin 25Gy (High risk)

Total 5 fractions. Twice treatment per week, completed within 3 weeks

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36.25 Gy / 40 Gy (IDC Boost) 40 Gy (prostate) / 25 Gy (pelvic LN)


Asia’s First Prostate SBRT with MRI Linac

67/M Favorable intermediate risk CA prostate 8Gy x 5frs completed in Apr 2020 Pre-RT PSA 10.8 Post-RT PSA 1.91 (6 months after SBRT) G2 dysuria. Otherwise well

1. Marker-less 2. Precise image-guidance 3. Real-time adaptive planning


Prostate SBRT with MRI-Linac at HKSH

Groups Median Age

(range)

Risk / staging Acute GI toxicities Acute GU toxicities PSA response (>50% decline from

baseline)

Prostate-alone SBRT (n= 16)

70 (60-83) Low (6/16) 37.5% Inter (9/16) 62.5%

G0: (13/16) 81.2% G1: (3/16) 18.8% G2: 0 G3: nil

G0: (4/16) 24.9% G1: (9/16) 56.3% G2: (3/16) 18.8% G3: nil

(12/12) 100%

Prostate + Pelvis SBRT (n= 12)

74 (64-79) Inter (2/12) 16.7% High (10/12) 83.3%

G0: (7/12) 58.3% G1: (4/12) 33.3% G2: (1/12) 8.3% G3: nil

G0: (3/12) 25% G1: (8/12) 66.6% G2: (1/12) 8.3% G3: nil

(5/5) 100%

Prostate SBRT for metastatic disease (n= 5)

67 (45-74) N1M0 (1/5) 20% M1 (4/5) 80%

G0: (3/5) 60% G1: (2/5) 40% G2: nil G3: nil

G0: (1/5) 20% G1: (4/5) 80% G2: nil G3: nil

(3/3) 10%

Total patients (n=33) 67 (45-83) Low (6/33) 18.2% Inter (11/33) 33.3% High (10/33) 30.3% N1M0 (1/33) 3.0% M1 (4/33) 12.1%

G0: (23/33) 69.7% G1: (9/33) 27.3% G2: (1/33) 3.0% G3: nil

G0: (8/33) 24.2% G1: (21/33) 63.6% G2: (3/33) 9% G3: nil

(20/20)100%

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Rectal spacer


Phase III studies: Spacer vs no Spacer Prostate RT - Dosimetric and clinical advantages

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Rectal spacer for Prostate SBRT at HKSH

3rd case 1st case

2nd case

5th case

4th case 6th case


SBRT with Rectal spacer 45

CT MRI MRI Linac


Dosimetric comparison for SBRT with and w/o spacer

With spacer Without spacer


The way forward


MR-Linac and Respiratory motion monitoring (RMM) 48

Current MR Linac


4DCT vs 4D MRI

4DCT 4DMRI


MR-Linac SBRT treatment time at HKSH: ATP vs ATS 50

0:00 0:10 0:20 0:30 0:40 0:50 1:00 1:10 1:20200312200496200461200462200519200524200531200553200593200603200614200589200633200568200651200687200688200642200178200226200211200263200276200278200352200403200444200525200539200542200618200640200639200722200277200251200168200381200486Average

Time

Patie

nt

MR-Linac treatment timeline for ATP

Setup Pre-treatment scan Registration Optimization

QA Plan Check and Approval Beam-On Time Discharge Patient

0:00 0:10 0:20 0:30 0:40 0:50 1:00 1:10 1:20 1:30 1:40 1:50 2:00 2:11

200312

200524

200593

200614

200178

200211

200444

200327

Time

Patie

nt

MR-Linac treatment timeline for ATS

Setup Pre-treatment scan Registration Contour

Optimization Verification Image QA Plan Check and Approval

Beam-On Time Discharge Patient

Workflow Average (mins) Setup 0:06

Pre-treatment scan 0:02 Registration 0:04 Optimization 0:09

QA 0:01 Plan Check and Approval 0:05

Beam-On Time 0:20 Discharge Patient 0:05

Total 0:55


Pre-treatment scan 0:02 Registration 0:05

Contour 0:22 Optimization 0:18

Verification Image 0:02 QA 0:01

Plan Check and Approval 0:06 Beam-On Time 0:19

Discharge Patient 0:05 Total 1:31


Multi-disciplinary team for MR Linac 51

Oncologist

Physicists

RTT RTT

Dosimetrist

Decision: ATS vs ATP Target contouring Plan Verification

QA

Patient setup MRI acquisition Image registration Plan optimization

Monaco MRTC QA terminal

Remote online plan evaluation and contouring (if necessary)


MR-Linac treatment time at HKSH: ATP vs ATS 52

0:00 0:10 0:20 0:30 0:40 0:50 1:00 1:10 1:20200312200496200461200462200519200524200531200553200593200603200614200589200633200568200651200687200688200642200178200226200211200263200276200278200352200403200444200525200539200542200618200640200639200722200277200251200168200381200486Average

Time

Patie

nt

MR-Linac treatment timeline for ATP

Setup Pre-treatment scan Registration Optimization

QA Plan Check and Approval Beam-On Time Discharge Patient

0:00 0:10 0:20 0:30 0:40 0:50 1:00 1:10 1:20 1:30 1:40 1:50 2:00 2:11

200312

200524

200593

200614

200178

200211

200444

200327

Time

Patie

nt

MR-Linac treatment timeline for ATS

Setup Pre-treatment scan Registration Contour

Optimization Verification Image QA Plan Check and Approval

Beam-On Time Discharge Patient


Pre-treatment scan 0:02 Registration 0:04 Optimization 0:09

QA 0:01 Plan Check and Approval 0:05

Beam-On Time 0:20 Discharge Patient 0:05

Total 0:55


Pre-treatment scan 0:02 Registration 0:05

Contour 0:22 Optimization 0:18

Verification Image 0:02 QA 0:01

Plan Check and Approval 0:06 Beam-On Time 0:19

Discharge Patient 0:05 Total 1:31


IMRT RapidArc

Daily Treatment Time P=0.0001

RapidArc 2.43 mins

Conventional IMRT 9.38 mins


Conclusion

• Paradigm-shift in precision RT with MRI-guided radiotherapy – Enhanced soft tissue contrast

• Precise image-guidance – Online adaptive planning – Real-time motion monitoring – Functional imaging for monitoring and plan adaptation

• Current Limitations and Future Research – Motion monitoring

• 4DMRI & Respiratory gating – Extensive time and manpower

• MR-Linac: Step-and-shoot IMRT to VMAT • Streamlining the logistics and the team

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Acknowledgement 55

Dosimetrists & Radiation therapists Dr George Chiu Mr Alan Mui Ms Winky Fung Ms Chloe Chan Mr Gavin Chan Ms Eunice Ng Ms Lenis Lee Ms Jocelyn Chan Mr Taki Lee Ms Stephanie Chan Ms Rita Luo Mr Ivan Leung Ms Anson Chiu Mr Wilson Leung Mr David Chan

Physicists & MR specialists Dr Ben Yu Dr KY Cheung Dr Jing Yuan Mr Tomie Lam Dr Kimi Yang Dr Leon Ho Dr Max Law Dr Cynthia Huang Mr KK Tang Ms. Alice Li Mr Stephen Wu Dr Oilei Wong


Thank you for your attention

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Email:[email protected] @DrDarrenPoon

mailto:[email protected]


shifting paradigm in precision radiotherapy - mri-guided radiotherapy poon_hksh_shifting... ·...

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