Simon S Lo, M.D.Director of Radiosurgery Services and Neurologic Radiation OncologyUniversity Hospital Seidman Cancer CenterAssociate Professor of Radiation OncologyCase Western Reserve University Cleveland, OHUSA

Clinical Aspects of LINAC-based Stereotactic Body Radiation Therapy

University Hospitals Seidman Cancer Center, Case Western Reserve University

Conflicts of interest: None

Financial Disclosure: None

Disclosure:

Chair, American College of Radiology Appropriateness Criteria Expert Panel in Bone Metastasis

Stereotactic Body Radiation Therapy(Also known as Stereotactic Ablative Radiotherapy)

• SBRT utilizes ultra-high ablative doses of radiation, typically 10-20 Gy per fraction, delivered to the planning treatment volume in 1-5 fractions

• A “spin-off” of Gamma Knife radiosurgery• First started in Sweden (Lax and Blomgren)

and Japan (Uematsu) based on LINAC

What is LINAC-based SBRT?

• In actual fact, all devices, except proton beam machines, used to delivered photon-based SBRT are LINACs

• Practically, SBRT delivered using any LINAC except CyberKnife can be referred to as LINAC-based SBRT

University Hospitals Seidman Cancer Center, Case Western Reserve University

Courtesy of Dr. Eric Chang, USC

Clinical applications

• Stage I non-small cell lung cancer• Oligometastases in lung and liver• Primary liver tumors including HCC• Prostate cancer• Pancreatic cancer• Spinal metastases

Newer clinical applications

• Renal cell cancer• Benign spinal tumors• Adrenal metastases• Head and neck cancer• Spinal cord compression• Breast cancer• Gynecologic cancer

Characteristics of SBRT/ SABR

• Secure robust immobilization avoiding patient movement for the typical long treatment sessions

• Accurate repositioning from simulation to treatment• Rigorous accounting of organ motion• Minimization of normal tissue exposure attained by using

multiple (eg, 10 or more) or large-angle arcing small aperture fields

• Stereotactic registration (ie, via fiducial markers or surrogates) of tumor targets and normal tissue avoidance structures to the treatment delivery machine

• Ablative dose fractionation delivered to the patient with subcentimeter accuracy

Timmerman et al. JCO 2007

Robotic vs. LINAC-based SBRT

University Hospitals Seidman Cancer Center

Technical aspects

• Immobilization:

• Body frames• Vacuum pillows• Thermoplastic device • Frameless system

• Select the right device for the right disease site!

UH Seidman Cancer Center

Immobilization

UH Seidman Cancer Center

Immobilization

Immobilization

• University of Toronto study

• Evacuated cushion vs. Semirigid vacuum body fixation vs. Thermoplastic S-frame

• 84 patients with 102 spinal metastases• 4 sets of CBCT: Localization, verification,

mid-treatment, and post-treatment• No correction for rotation (≤2⁰)

Li et al. IJROBP 2012

Immobilization

Li et al. IJROBP 2012

Method of immobilization

Margins needed for verification CBCT

Margins needed for mid-treatment CBCT

Margins needed for post-treatment CBCT

Evacuated cushion (N = 24)

≤ 2 mm ≤ 2 mm > 2 mm (R-L and C-C)

Vacuum fixation (N = 60)

≤ 2 mm ≤ 2 mm ≤ 2 mm

Themoplastic S-frame (N = 18)

≤ 2 mm ≤ 2 mm > 2 mm (R-L and A-P)

Respiratory motion control

• Motion dampening- Abdominal compression, ABC

• Motion gating- Fiducials• Motion tracking- Fiducials and Synchrony

with CyberKnife

Timmerman JCO 2006; Lo NRCO 2010

UH Seidman Cancer Center

Abdominal Compression

Slide courtesy of Robert D. Timmerman, M.D.

UH Seidman Cancer Center

Motion management

Giuliani and Bezjak. In: Stereotactic Body Radiation Therapy: Lung Cancer (Eds: Lo, Teh, Mayr, Machtay). Future Medicine, UK.

UH Seidman Cancer Center

Factor in tumor motion

• Generic PTV expansion

• 4D CT (Internal Target Volume)

• 3 phase CT (free breathing, deep expiration and deep inspiration)

University Hospitals Seidman Cancer Center

Factor in tumor motion

GTV- Light blue

ITV- Purple

PTV- Red

University Hospitals Seidman Cancer Center

Factor in tumor motion

GTVGTV

PTVPTV

Abdominal compression- Verify under fluoroscopyIU/ Karolinska technique- GTV + 0.5 cm radially and 1.0 cm sup-inf = PTV

UH Seidman Cancer Center

Treatment planning

Slide courtesy of Robert D. Timmerman, M.D.

UH Seidman Cancer Center

Treatment planning

3DCRT techniqueIsotropic isodose distribution

UH Seidman Cancer Center

Treatment planning

Kuijper et al. RTO 2010

UH Seidman Cancer Center

Treatment planning

No significance difference in delivery time compared to IMRT if 2-3 arcs used for VMAT

Kuijper et al. RTO 2010

UH Seidman Cancer Center

Treatment planning

UH Seidman Cancer Center

Treatment planning

UH Seidman Cancer Center

Normal Tissue Constraints

Lo et al. Clinical Oncology 2012

UH Seidman Cancer Center

Normal Tissue Constraints

Lo et al. Clinical Oncology 2012

UH Seidman Cancer Center

Normal Tissue Constraints

Lo et al. Clinical Oncology 2012

UH Seidman Cancer Center

Image-guidance

MV CBCT

UH Seidman Cancer Center

Image-guidance

kV CBCT- Courtesy of Dr. Arjun Sahgal, U of Toronto

UH Seidman Cancer Center

Image-guidance

ExacTrac- Courtesy of Dr. Bin Teh

UH Seidman Cancer Center

Image-guidance

• CBCT vs. stereoscopic X-rays (ExacTrac)• Duke University study• Phantom study: Translational and rotational

discrepancies of < 1 mm and < 1o

Patient study: Translational and rotational discrepancies of < 2 mm and < 1.5o

Chang et al. Radiotherapy and Oncology 2010

UH Seidman Cancer Center

Image-guidance

Type of CBCT Resolution Metallic artifacts

kV CT Better Worse

MV CT Worse Better

Intrafractional monitoring

• Stereoscopic X-ray• Mid-way CT-on-rail• Mid-way kV or MV CBCT • Mid-way MVCT

Comparison of CyberKnife-based and LINAC-based SBRT

1. No real time tracking2. Very robust

immobilization is crucial especially for spinal SBRT

3. Mid-way OBI is needed to ensure positional accuracy

4. More manual work is needed for patient set-up

1. Better for posteriorlylocated lesions

2. Better from donut-shaped targets

3. More flexible beam angles4. Faster treatment delivery

especially for newer machines

5. Volumetric verification available

6. Better availability

LINAC-based

1. No posterior or posterior oblique beams

2. Long treatment delivery time

3. No volumetric verification4. Less availability

1. Near real time tracking2. Process is more

automated3. Very robust

immobilization not absolutely necessary

CyberKnife-based

Cons Pros Device

Stage I NSCLC

University Cancer Center

Hadziahmetovic et al. Discovery Medicine 2010

Lung oligometastasis

University Cancer Center

Lo et al. Nature Reviews Clinical Oncology 2011 (Authors retain ownership of copyright of contents)

Liver oligometastasis

University Cancer Center

Lo et al. Nature Reviews Clinical Oncology 2011 (Authors retain ownership of copyright of contents)

Hepatocellular carcinoma

University Cancer CenterLo et al. Discovery Medicine 2010

Prostate cancer

University Cancer CenterCourtesy of Dr. Andrew Loblaw, Odette Cancer Centre, University of Toronto

Pancreatic cancer

University Cancer Center

Chuong et al. IJROBP 2013

Spinal oligometastasis

University Cancer CenterLo et al. Discovery Medicine 2010

Spinal oligometastasis

University Cancer Center

Study/ Patient group

No. of patients/ sites

Apparatus used

Dose Follow-up Outcomes Toxicities

Wang (MDACC phase I/II trial)

149/ 166 LINAC 30 Gy in 5 fxs or 27 Gyin 3 fxs

15.9 months Absence of pain increased from 26% to 54% at 6 months1 and 2 year PFS: 80.5% and 72.4%

No grade 4 toxicities

Garg(MDACC phase I/II trial)

61/ 63 non-cervical lesions

LINAC 16-24 Gy in 1 fx

20 months 18-month actuarial imaging LC: 88%18-month OS: 64%

Two grade 3 or higher toxicities

Wang et a. Lancet Oncol 2012 and Garg et al. Cancer 2012

Renal Cell Carcinoma

University Cancer Center

From Teh et al. Renal Cell Carcinoma. In: Lo, Teh, Lu, Schefter. Stereotactic Body Radiation Therapy 2013. Springer.

Toxicities

• Chest: Chest wall toxicities, radiation pneumonitis, skin toxicities, brachial plexopathy, esophageal toxicities, and airway collapse

• Abdomen: Gastric/ duodenal ulcer, and RILD• Spine: Radiation myelopathy, vertebral

compression fracture, and pain flare

University Cancer Center

Toxicities

University Cancer Center

77 year old female with T1 N0 M0 non-small cell lung cancer was treated with 54 Gy in 3 fractions using SBRT (Left upper). She had no symptoms, but repeat imaging 6 months post treatment showed wedge like collapse of the segment just distal to her lesion (Right upper). A PET scan showed no uptake. A bronchoscopy showed airway irritation and mucous plugging, but brushings and washings showed no tumor cells (Right).

Courtesy of Professor Robert Timmerman

Toxicities

University Cancer Center

SBRT in 3 fractions to a total dose of 60 Gy

Courtesy of Professor Robert Timmerman

Toxicities

University Cancer Center

Courtesy of Professor Robert Timmerman

SBRT for stage I NSCLC in phase I trial; skin dose 24 Gy in 3 fxs; wet desquamation 6 weeks after SBRT (above and right); reaction resolved 3 months after SBRT (upper right)

Toxicities

University Cancer Center

Sahgal et al. IJROBP 2012

Toxicities

University Cancer Center

Sahgal et al. IJROBP 2012

gLQ model

gLQ model

gLQ model

Huang et al. Future Oncology 2013

Conclusions

• SBRT is one of the standard options for medically inoperable stage I NSCLC and oligometastases in the lung, liver and spine

• Other emerging applications include prostate cancer, renal cell cancer, pancreatic cancer, HCC, and recurrent head and neck cancer

• Multiple devices can be used to deliver SBRT

Conclusions

• Compared to CyberKnife, LINAC-based SBRT requires more manual work

• There are pros and cons to CyberKnife-based and LINAC-based SBRT

• Provided that all the basic principles are followed, it is possible to deliver high quality SBRT treatments with a LINAC with image-guidance features

Conclusions

• The experience of the team is likely more important than the actual device used

• When switching from CyberKnife-based to LINAC-based SBRT, it is crucial not to be too off-guard!