radixact synchrony: preliminary clinical experience from

Radixact Synchrony: Preliminary Clinical Experience from University of Turin

Umberto Ricardi

University of Turin

Department of Oncology – Radiation Oncology AOU Città della Salute e della Scienza di Torino

Department of Oncology – Radiation Oncology

AOU Città della Salute e della Scienza di Torino

18 RO

16 Residents

9 MP

2 Dosimetrists

22 RTT

3000 new patients per year; 450 brachy procedures

• Technological advances in treatment planning and delivery provide unique opportunities for improving effectiveness of RT

• Absolute “radioresistance” does not exist: treatment failure occurs if and only if… – the biologically equivalent dose is not

sufficiently high OR … – there is disease outside the high-dose volume

Radiation therapy is Precision Medicine

• Halperin’s first rule of pediatric radiation oncologist

−Don’t miss the tumor

• Halperin’s second rule of pediatric radiation oncologist- a corollary to the first rule

– In general, most tumors are radioresistant if they are not in treatment beam

Notable Treatment Sites Thorax Abdomen (liver, pancreas, etc.) Popular Management Strategies • Free breathing PTV expansion (larger volumes)

• Motion reduction Abdominal compression or breath holding

• Beam Gating/ABC treat only during specific times of the

respiratory cycle

• Real time motion compensation Dynamic tumor tracking

SABR

Motion Management Sites and Techniques

Conventional (ITV-PTV based) • Contour and treat full tumor

Accelerator beam gating • Patient breathes normally;

beam only on while patient is in a certain phase of the respiratory cycle

Active breathing control • Patient holds breath in a

certain position; beam only on in that phase of the respiratory cycle

Dynamic tumor tracking • Patient breathes normally;

tumor is tracked; beam always on and moves with tumor

Respiratory Motion Management

Key challenge: Hitting moving targets

Current “motion management” for precise RT

Motion Management Objectives

Do you account for motion? Do you ignore motion?

Do you compensate for it?

Do you synchronize with it?

Motion assessment (4D-CT) VMAT Image guidance (4D CBCT)

Enablers of Technologically Targeted RT

UNIVERSITA’ DEGLI STUDI DI TORINO

ALL FACILITATING SABR

Breath cycle

Stereotactic Body Radiation Therapy (SBRT) Stereotactic ABlative Radiotherapy (SABR)

A technique for delivering external beam radiotherapy o with a high degree of accuracy to an extra-cranial target, o using high doses of irradiation, o in 1-8 treatment fractions

S. Senan, U. Ricardi, M. Guckemberger, K.E. Rosenzweig, and N. Ohri: Stage I NSCLC and oligometastatic disease The IASLC Multidisciplinary approach to Thoracic Oncology, 2017

[Ricardi et al, Phys Med 2017]

ESMO Guidelines (Postmus PE et al, Annals of Oncology 2017) • SABR is the non-surgical treatment of choice for stage I NSCLC

(BED>100 Gy) ASTRO Guidelines (Videtic GMM et al, PRO 2017) • SABR delivers ablative doses in 1 to 5 fractions • Schedules using from 6 to 10 fractions with a BED of > 100 Gy

with stereotactic tehniques are also possible

NCCN Guidelines (Version 8. 2020) • SABR is recommended in stage I-IIA for patients medically

inoperable or who refuse to have surgery • SABR is also an appropriate option for patients with high

surgical risk

SABR: guidelines

UNIVERSITA’ DEGLI STUDI DI TORINO

SABR in oligometastatic disease

Treat metastatic disease for cure (or at least significant prolongation of survival)

New indication for radiotherapy

Unlike surgery, SABR works in concert with systemic therapy

Not as COSTLY vs. surgery in toxicity and invasiveness

More palatable for those who ultimately progress

Potential SABR Toxicity Depends on Tumor Site

• Fatigue

• Rib fracture, chest wall pain

• Skin Erythema/fibrosis

• Fatigue • Pneumonitis, atelectasis

hemoptysis, fibrosis • Rib fracture, chest wall pain

54 Gy /3 fr T1 lesions, not adjacent to chest wall

60 Gy/8 fr central lesions with limited overlap with mediastinum (50 Gy/10fr ultracentral lesions- selected patients)

55 Gy /5 fr or 50 Gy/5 fr T1 lesions with broad chest wall contact, and T2 lesions

«Risk adapted» protocol @ University of Turin

Lung SABR protocol @ University of Turin

MANDATORY (minimum) REQUIREMENTS RECOMMENDED

Equipment Staff training Patient selection Treatment

planning Dose-

fractionation Image guidance Follow-up Quality

assurance

[Guckenberger M, Radioth Oncol 2017]

ESTRO-ACROP guidelines

AverageCT CTV

Margins: 5 mm axial 10 mm CC

Treatment delivery 4DCBCT

SABR Protocol @ University of Turin

respiratory surrogate: abdominal pressure piezo-electric belt

4DCT accurately compensate for target motion and define patient’s specific internal margins

Virtual simulation- 4DCT

Technical Advances may have an impact on safety and efficacy

July 2019

Synchrony®: A suite of technologies that allows seamless adaptation to target and patient motion in real-time during treatment delivery (July 2020)

Continuously determine the position of the moving target during treatment

Continuously reshape the treatment beam (jaw and leaf positions) to follow the target’s motion

Motion Synchronization shifts the paradigm without compromise

Synchrony®: tracking modalities

kV Imaging System Hardware For Tracking the Moving Target During Treatment

1. kV detector 2. X-ray tube 3. Generator • During treatment, collect

2D radiographs at selected gantry angles

• Locate target or surgically implanted fiducials in radiographs

Synchrony®: Treatment Room

Tracking Target Motion Between Radiographs

Irregular motion (e.g., digestive) Unpredictable Assume target maintains last

measured position until next radiograph

Respiratory motion Use a camera system to track

position of markers attached to patient surface

Build a model to correlate marker positions (LED) to internal target position

Update the model each time you acquire a radiograph

Time (seconds)

Time (seconds)

Dis

plac

emen

t (m

m)

Dis

plac

emen

t (m

m)

Synchrony®: Tracking the Moving Target

1. kV detector 2. X-ray tube 3. Generator

• During treatment, the system collect 2D radiographs at selected gantry angles

• The target or surgically implanted fiducials are located in radiographs

• Synchrony builds a model to correlate marker (LED) position to internal target position:

updating the model each time radiographs are acquired

Continously reshaping the treatment beam (jaws and leave) to follow the target motion

Synchrony® decision chart

Synchrony®: patients selection

Target

Size < 5-7 cm diameter (sphere) Shape Regular, should persist over the

course of treatment Motion < 2 cm along each translational

axis Tracking Target

Density Higher than the surrounding tissue

Visualization Available imaging angles where it’s not significantly obscured by structures

University of Torino: patients’ selection Single nodule

Peripherally located > 3 cm diameter

• 84 yo, man, PS 1 ECOG • Smoker • COPD (stage II GOLD) May 2020: Cough and hemophtysis Chest X-Ray: opacity in right upper lobe Total body CT scan (June 2020) Right upper parenchymal tumor (max diam 48 mm); no other pathologic findings CT-PET scan (July 2020): pathologic uptake in the right upper lobe lesion (SUVmax: 12)

Our first patient (July 2020) – Clinical History

First patient – Clinical History

• FEV1: 1,24 l (54%); FVC: 3.25 L (105%); DLCO: 55%

• PO2: 68.5; PCO2: 43.4; pH: 7.4

• CT-guided FNAB: not feasible (poor respiratory function, comorbidity, site) • Bronchoscopy: no evidence of endobronchial lesion; BAL negative

«Clinical proof of malignancy», not biopsy proven Stage IIA NSCLC (cT2bN0M0), right upper lobe Not amenable with surgery (poor respiratory function) SABR

respiratory surrogate: abdominal pressure piezo-electric belt

4DCT accurately compensate for target motion and define patient’s specific internal margins

Virtual simulation- 4DCT

Breath Cycle

TRACKING TARGET VOLUME

Contouring GTV phase 30%

Radixact

50 Gy = 10 Gy times 5 (80% isodose) Thoracic Stereotactic Ablative RT: Synchrony

Tumor PTV: 45x60x45mm GTV to PTV: 3mm Tumor Motion: around 5-7mm (AP) PTV (ITV): 60.78 cc vs PTV (Sync): 57.23 cc

• 71 yo, female, PS 0 ECOG • No smoker • COPD (stage I GOLD) December 2018: diagnosis of adenocarcinoma, right upper lobe, stage IV (M1a-pleural nodules) Molecular analysis: ALK nt, ROS1 nt, PDL1 0%, EGFR mut (ex 19) 9/4/2019: Osimertinib

July 2020: oligoprogressive disease (single nodule, right upper lobe, max diam 33 mm)

Second patient – Clinical History

TRACKING TARGET VOLUME

Contouring GTV phase 30%

50 Gy = 10 Gy times 5 (80% isodose)

Thoracic Stereotactic Ablative RT: Synchrony

Tumor PTV: 30x60x33mm GTV to PTV 3mm Tumor motion: 5-7mm (AP) PTV (ITV): 32 cc PTV (Sync): 26.1 cc V40 Bronchial Tree (VMAT): 1.37 cc V40 Bronchial Tree (Radixact): 0.5 cc

Radixact

September 2020- November 2020: 3 patients treated with Synchrony (total: 5 patients)

V. D., 83 yo, female, PS 0 ECOG • Previous history of widely resected thigh SCC (with left inguinal adenopathy,

treated with exclusive RT) • November 2019: nodule in right upper lobe (not biopsy proven), PET + • Observation • PET-CT (september 2020): CR inguinal region, PD right upper lobe (SUVmax 6), diam 33 mm

50 Gy in 5 fx (80% isodose)


Radixact

A. L., 77 yo, female, PS 0 ECOG • Previous rhabdomyosarcoma (left

thigh) treated with surgery + RT • September 2020: metastatic

pulmonary lesion • CT whole body (10/2020): PD ML

nodule (30 mm)

50 Gy in 5 fractions (80% isodose)


Radixact

L. L., 75 yo, male, PS 0 ECOG • Previous urothelial bladder cancer • November 2020: diagnosis of nodule in left upper lobe (not biopsy

proven), PET + (SUVmax 7.5), 30 mm diam • No surgical indication (respiratory function)

55 Gy = 11 Gy times 5 (80% isodose)


Radixact

Left Brachial Plexus: Dmax (0.03 cc): 29.8 Gy Linac vs 28.6 Radixact

Synchrony: delivery workflow

Patient must be informed about all the processes they will undergo during RT • RESPIRATORY TRAINING before CT

simulation

• Patient should maintain NATURAL BREATH Synchrony will be able to build a provisional model more easily


SIMULATION To test Synchrony capability to buid a predictive model referred to patient’s respiratory pattern Treatment beam is disabled You can acquire MVCT followed by KV images (2D radiographs) in order to check target motion

To test: JAWS MLC LEAVES GANTRY ROTATION COUCH MOVEMENT


SIMULATION allows to verify: SYNCHRONY CAPABILITY to predict target position 2D RADIOGRAPHS CONSISTENCY (angles are settled

during planning): Rx should be able to show the target among different structures (up to 6 Rx per gantry rotation)

Patient’s COMPLIANCE

SCORE WHEEL: Angles in which the target is well visualized (planning phase)


LIGHT BOX connected to the COUCH

CABLES from Light Box connected to LED markers

At least

TWO OF THE THREE MARKERS MUST BE VISIBLE

to the camera at all times


LED MARKERS placed on patient’s thorax (respiratory movement)


REFERENCE POST LED marker attached to the couch TO EXCLUDE COUCH MOTION IN LED AMPLITUDE GRAPHIC

Synchrony: delivery workflow MV CT acquisition register match check position corrections couch moves


o LED well placed and visualized

o Regular breathing pattern

o MVCT less than 1 min

Radixact is ready to treat


The localization algorithm searches

within this region on the radiographs to identify

the target

PREPARE to acquire Kv Images in order to build model

Model was built in LESS THAN 1 MIN

Jaws and MLC leaves

ADAPTED TO TARGET

•Target WELL VISUALIZED throughout the treatment

BUILD MODEL


Target Visualization


POTENTIAL DIFF THE QUALITY OF THE MODEL

Increases if the patient’s breathing cycle does not fit the

model well

MEASURED Δ MODEL ACCURACY

Patient is not breathing predictably

Parameters


Treatment workflow 1° patient (in room time: 24 minutes)

Treatment workflow 1° patient (in room time: 22 minutes)

Follow up

July 2020 October 2020

Synchrony®: Pulmonary Target Tracking Conclusions Easy to use/ Reliable Patient’s selection is crucial in this phase of clinical

implementation Useful to reduce exposure of healthy tissues and

improving safety of curative treatment also in patients more clinically fragile (elderly, poor respiratory function) maybe also for ”Hybrid treatment”: SABR + moderately hypofx on mediastinum

Synchrony® at Turin University

Prostate

Liver, Pancreas

Lung SABR

Productivity, Flexibility, Reliability

radixact synchrony: preliminary clinical experience from

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