Jonathan W. Lischalk, M.D.Department of Radiation MedicineGeorgetown University Hospital

Clinical Value Of Motion Synchronization For Lung SBRT

Disclaimer & Disclosure

• The views expressed in this presentation are those of the presenter and do not necessarily reflect the views or policies of Accuray Incorporated or its subsidiaries. No official endorsement by Accuray Incorporated or any of its subsidiaries of any vendor, products or services contained in this presentation is intended or should be inferred

• An honorarium is provided by Accuray Incorporated for this presentation

Outline• Thoracic tumor motion and motion

management strategies• Is pre-treatment 4D-CT scan enough?• Tumor motion synchronization • Georgetown CyberKnife® thoracic experience

– Early stage non-small cell lung cancer (ES-NSCLC) long-term results

– Central / Ultra-central thoracic treatment– Thoracic re-irradiation

Epidemiology

American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018.

Epidemiology

American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018.

SBRT as Standard of Care

Expanding literature also supports the use of SBRT in the high-risk medically operable and even medically operable patient population

Thoracic Tumor Motion

• Respiratory motion during SBRT increases positional uncertainty leading to:– Underdose of the tumor– Overdose of adjacent organs at risk (OAR)

• Respiratory motion is traditionally assessed with pretreatment 4D-CT scan

Thoracic Motion Depends on Location

Sonke JJ et al., IJROBP, 2008 v:70 i:2 ; p:590 -598, *Guckenberger M et al., Acta Oncol, 2006 v:45 i:7; p:897 -906. Worm ES et al., Acta Oncol, 2010 v:49 i:7; p:1177 -1183 **Yu H et al., Radiotherapy and Oncology, 2012;104(1):33-8.

Thoracic Motion depends on stage, location and BMI*,**

Motion Depends on Location and BMI

Guckenberger M et al., Acta Oncol, 2006 v:45 i:7; p:897-906Worm ES et al., Acta Oncol, 2010 v:49 i:7; p:1177-1183

Thoracic Motion Depends on Stage

Yu HZ et al., Radiotherapy and Oncology, 2012;104(1):33 -8.

Patient-specific Motion Analysis

Underberg RWM et al., IJROBP, 2004 v:60 i:4; p:1283-1290

Motion Management

• Standard motion management strategies:– Motion encompassment (i.e. ITV)– Motion mitigation (e.g. abdominal compression)– Breath-hold technique (e.g. DIBH*, MIBH**, ABC***)– Respiratory gating – Tumor motion synchronization

* Deep Inspiration Breath Hold** Maximum Inspiration Breath Hold** Activated Breathing Control

Motion Management Strategies

• Challenges of management strategies:– Motion encompassment: dependent on 4D -CT scan

accuracy, larger target volume (ITV)– Abdominal compression: patient discomfort, reproducibility– Breath-hold technique: active patient participation, trained

therapist, system dependency, patient discomfort – Respiratory gating: system integration, external surrogate

dependency – Tumor motion synchronization : fiducials are required if lung

optimized treatment is not used (LOT), optical surface tracking may not represent internal motion

Outline• Thoracic tumor motion and motion management

strategies• Is pre -treatment 4D -CT scan enough?• Tumor motion synchronization • Georgetown CyberKnife® thoracic experience

– Early s tage non-small cell lung cancer (ES-NSCLC) long-term results

– Central / Ultra-central thoracic treatment– Thoracic re-irradiation

Axis of Motion as Assessed by 4D-CT

Lischalk et al., PRO, 2016 v:6 i:3; p:176 -182

4D-CT Does Not Capture Real-time Maximal Tumor Deviations

Lischalk et al., PRO, 2016 v:6 i:3; p:176 -182

Fractional Undercoverage by 4D-CT

Lischalk et al., PRO, 2016 v:6 i:3; p:176 -182

Outline• Thoracic tumor motion and motion management

strategies• Is pre-treatment 4D-CT scan enough?• Tumor motion synchronization• Georgetown CyberKnife® thoracic experience

– Early s tage non-small cell lung cancer (ES-NSCLC) long-term results

– Central / Ultra-central thoracic treatment– Thoracic re-irradiation

Thoracic Tumor Motion

Photo Courtesy of Georgetown

CyberKnife® Tumor Motion Synchronization

Image provided by Accuray

CyberKnife® Tumor Motion Synchronization

Patient set-up time minimized by efficient respiratory modeling workflow

Impact of Motion Synchronization

• Motion synchronization accuracy consequences– Precludes the necessity of ITV creation– Minimizes underdose of the tumor– Minimizes overdose of adjacent OARs

• Thoracic clinical optimization– Definitive ES-NSCLC– Ablative management of central thoracic tumors– Thoracic re-irradiation

Fiducial Placement• Fiducial placement techniques:

– Percutaneous– Bronchoscopic

• Bronchoscopic placement allows for:– Lower risk of pneumothorax– Mediastinal staging– Fiducial placement

• Fiducials: – Gold seeds, platinum coils, gold seeds

with coils

Alternatively, lung optimized treatment (LOT) allows CyberKnife® to synchronize treatments to the majority of lung targets without the need of implanted fiducialsImage provided by Accuray

CyberKnife® for ES-NSCLC

Outline• Thoracic tumor motion and motion management

strategies• Is pre-treatment 4D-CT scan enough?• Tumor motion synchronization• Georgetown CyberKnife ® thoracic experience

– Early stage non -small cell lung cancer (ES -NSCLC) long -term results

– Central / Ultra-central thoracic treatment– Thoracic re-irradiation

Georgetown ES-NSCLC Experience

• Multiple methods of SBRT delivery exist including fiducial-based tumor tracking, which allows for smaller treatment margins and avoidance of patient immobilization devices

• We explored the long-term clinical outcomes of this novel fiducial-based SBRT method from 2005 to 2015

Patient Population

Lischalk et al., J Radiat Oncol, August 2016 v:5 i:4; p:379-387

Median age of 75, pulmonary dysfunction the most common cause of inoperability, and most

tumors ≤ 3 cm

Treatment Characteristics

The most common dose fractionation schedule was 50 Gy in 5 fractions

Lischalk et al., J Radiat Oncol, August 2016 v:5 i:4; p:379-387

Clinical Outcomes

5-year local control: 88% 5-year locoregional control: 72%

Lischalk et al., J Radiat Oncol, August 2016 v:5 i:4; p:379-387

Clinical Outcomes

Locoregional control was improved with BED above 105 Gy

Motion synchronization achieves high target BED while minimizing treatment volume

Squamous histology correlated with worse local control

Lischalk et al., J Radiat Oncol, August 2016 v:5 i:4; p:379-387

Post-CyberKnife® PFT Changes

PFT changes after CyberKnife were minimally affected

Lischalk et al., J Radiat Oncol, August 2016 v:5 i:4; p:379-387

Outline• Thoracic tumor motion and motion management

strategies• Is pre-treatment 4D-CT scan enough?• Tumor motion synchronization• Georgetown CyberKnife ® thoracic experience

– Early s tage non-small cell lung cancer (ES-NSCLC) long-term results

– Central / Ultra -central thoracic treatment– Thoracic re-irradiation

Georgetown Central Lung Tumors Experience

• Excessive toxicity historically noted in patients with “central” tumors– Particularly when treating with 3 fraction SBRT – Moderate hypofractionation schedules have been proposed

(60Gy/8)– RTOG 0813 demonstrated no grade 3+ acute and late toxicity

for those treated with 50Gy/5– No clear data regarding management of “ultracentral” lung

tumors• We explore the clinical outcomes C yberKnife®-based SBRT for

ultracentral metastatic tumors abutting or invading the mainstem bronchus

High-risk Central Tumors

JW Lischalk et al., Radiation Oncology, 2016 v:11; p:28

SCC and ADA were the most common histologies treated

High-risk Central Tumors

Median major bronchus Dmax 46.4 Gy

1-year local control and overall survival: 70% and 75%, respectively

JW Lischalk et al., Radiation Oncology, 2016 v:11; p:28

High-risk Central Tumors

5-year complete response to CyberKnife®-SBRT for ultracentral pulmonary lesion on PET/CT

High-Risk Central Tumors

Most commonly reported grade 2 or higher toxicity was atelectasis

JW Lischalk et al., Radiation Oncology, 2016 v:11; p:28

High-Risk Central Tumors

Patients with pre-SBRT documented gross endobronchial involvement demonstrated significantly lower median overall survival (4.8 vs. 19.8 months, p = 0.029), and a trend in decreased local control (4.49 vs. 21.9 months, p = 0.085)

JW Lischalk et al., Radiation Oncology, 2016 v:11; p:28

Thoracic Re-irradiation• Advanced RT modality options exist for thoracic

reirradiation, including:– Stereotactic body radiation therapy– Proton beam radiation therapy– Altered fractionation

• We explore the clinical outcomes C yberKnife®-based re-irradiation for ultracentral (i.e. abutting main pulmonary tree and esophagus) in-field pulmonary recurrences after definitive doses of conventionally fractionated radiotherapy

Ultracentral Re-irradiation

Repka et al., Radiation Oncology, 2017 v:12 i:1; p:162

Most common histology was ADA, and most common re-irradiation

dose was 35Gy in 5 fractions

Ultracentral Re-irradiation

Repka et al., Radiation Oncology, 2017 v:12 i:1; p:162

Ultracentral Re-irradiation

1-year local control was 67% in those treated with SBRT doses ≥40 Gy

Repka et al., Radiation Oncology, 2017 v:12 i:1; p:162

Ultracentral Re-irradiation

1-year overall survival was 78% in those treated with SBRT doses ≥40 Gy

Repka et al., Radiation Oncology, 2017 v:12 i:1; p:162

Ultracentral Re-irradiation

The most common toxicities were pneumonitis and recurrent laryngeal nerve paralysis, both of which resolved prior to last follow-up. One patient

died suddenly 35 months after SBRT which was attributed to radiation toxicity (hemoptysis), although the cause of death was not formally proven.

Repka et al., Radiation Oncology, 2017 v:12 i:1; p:162

Conclusions

• Definitive treatment of ES -NSCLC: Excellent long-term outcomes are

achieved with CyberKnife®-based SBRT and allow for optimal

intrafractional motion synchronization precluding the necessity of an

ITV

• Ultracentral pulmonary masses: Can be effectively treated with

CyberKnife® -based SBRT with durable local control, but close

attention should be paid to doses to the proximal bronchial tree

• Thoracic re -irradiation: CyberKnife® is a valuable option for patients

with in-field pulmonary locoregional recurrences after receiving

definitive doses of conventionally fractionated radiotherapy, and doses

≥40 Gy are associated with improved outcomes