This document discusses lung stereotactic body radiotherapy (SBRT) for the treatment of early stage non-small cell lung cancer (NSCLC). It covers treatment indications for SBRT, methods used to account for tumor motion including 4DCT planning and respiratory gating, treatment planning guidelines, evidence from studies showing high rates of local control and survival, and results from RTOG trials of SBRT for lung cancer. In particular, it highlights that SBRT achieves local control rates of 85-95% and overall survival rates of 50-95% at 3-5 years for early stage NSCLC.

1. LUNG SBRT
Dr. Rituparna Biswas
Senior Resident
Radiation Oncology, BRA IRCH, AIIMS

2. Introduction
• Early stage lung cancer may often be not amenable for surgery due to
poor underlying lung function.
• While conventional radiation therapy may be utilized, respiratory motion
often implies inclusion of large volumes of normal lung.
• This poses a significant challenge for utilising SBRT, where sharp
gradients and short treatment schedules benefit these patients.

3. Treatment Indications
• SBRT is currently employed in NSCLC. SBRT has no established role in
small cell lung cancer.
 Most established SBRT criteria include N0 patients with <5 cm,
peripherally located tumors, but tumors may be more cautiously treated
with expanded criteria of larger size (<7 cm), central location, multiple
synchronous lesions, and chest wall invasion (T3N0) with historically
inferior results.
• SBRT has a developing role as a boost following definitive chemoradiation
in management of locally advanced NSCLC, for re-irradiation of locally
recurrent disease, and for treatment of intrathoracic oligometastases from
various primary histologies

4. Methods to Reduce the Impact of the Tumor Motion
Most methods reduce all
margins except the margin
from GTV to CTV.

5. The following methods have been applied to reduce the impact of
respiratory tumor motion on dose distribution:
(1) patient-specific treatment volumes based on tumor motion observed
during planning CT scans (4DCT-based ITV),
(2) forced shallow breathing with abdominal compression,
(3) breath-hold methods,
(4) respiratory gating methods, and
(5) real time tumor tracking.

6. 4DCT-Based Internal Gross Tumor Volume (ITV)
The breathing cycle is divided into distinct bins (e.g., peak exhale, mid inhale, peak inhale, mid exhale). Images
are sorted into these image bins depending on the phase of the breathing cycle in which they were acquired, yielding a 4D CT
data set.

7. 4DCT-Based Internal Gross Tumor Volume (ITV)
• Ideally, ITV should be delineated by manually contouring GTV in all 10
breath phases of a 4D scan image sets, which is the most accurate tool to
determine ITV, but it is a labor-intensive task.
• To reduce the workload of contouring multiple GTVs, one solution is to
contour only two extreme phases at end-inhalation and end-exhalation and
then to sum of the two becoming ITV.
• Other is to use the post-processing tools of maximum intensity projection
(MIP). MIP-based ITV delineation is performed on a single 3-D CT data set,
where each pixel in this set represents the brightest object encountered by
corresponding voxels in all volumetric 4D CT data sets.
A disadvantage of an MIP-defined mGTV is that in regions where the
background and tumor have similar Hounsfield units, the tumor is less clearly
defined. This situation includes nodal volumes within the hilum or mediastinum,
tumors located near the diaphragm, and tumors surrounded by atelectasis.

8. Forced Shallow Breathing with Abdominal Compression
The whole body frame
with abdominal
immobilization. Green
arrow, the whole body
frame; red arrow, the
abdominal compression
plate

9. A detailed picture of
the whole body frame
with abdominal
immobilization. Yellow
arrow, abdominal plate;
green arrow, screw to
regulate the degree of
abdominal
compression

10. A CT scan slice
through the whole
body frame. Red
arrow, the whole
body frame; yellow
arrow, abdominal
plate; green arrow,
screw to regulate the
degree of abdominal
compression

11. Breath-Hold Methods
• Radiation is only delivered when the tumor is not moving during the breath hold.
• Active breathing control- ABC apparatus can be used to suspend breathing at any pre-
determined position along the normal breathing cycle.
• In the DIBH technique, the patient is initially maintained at quiet tidal breathing, followed
by a deep inspiration, a deep expiration, a second deep inspiration, and breath hold.
• Different methods to monitor lung inflation levels:
1. Differential pressure pneumotachograph spirometer
2. self-gated DIBH
• To familiarize the patient with the procedure, a training session is given a few days before
the planned simulation.
• Breath-holding techniques may be poorly tolerated by patients with mediocre lung
function

12. • Respiratory gating involves administration of radiation within a particular window of the
patient’s breathing cycle.
• Requires monitoring patient’s respiratory motion using either an external or internal fiducial
markers
• Commercially available respiratory gating systems are the Varian RPM system and the
BrainLAB ExacTracGating system.
Respiratory gating methods

13. • The RPM gating system uses an external IR marker as a surrogate for tumor
motion and may not necessarily correlate with internal motion
• In contrast, the ExacTracGating system combines the capability to track
externally placed markers in three dimensions with a digital radiography
system capable of locating internally placed fiducials.

15. Detecting the patient’s breathing pattern
using an IR camera system with reflecting
markers attached to the skin.
The system can trigger each of two
isocentrically aimed diagnostic X-ray
units at a user-defined point in the
breathing cycle
From these two images the 3D location of
an internally placed radio-opaque fiducial
marker can be determined.
The patient can then be moved into the
correct treatment position based on the
position of the internal markers.
ExacTrac Gating system

16. Real-Time Tumor Tracking
The CyberKnife.
White arrow, linear
accelerator; black
arrow, robot; red
arrow, one of
the 2 X-ray tubes;
green arrow, one of the
2 flat panels; blue
arrow, Synchrony
camera

17. • The imaging system consists of 2 diagnostic X-ray sources mounted to the ceiling
paired with amorphous silicon detectors to acquire live digital radiographic images of
the tumor, or tumor localizing surrogates such as the skull, spine, or fiducial markers.
• 3 LEDs are placed on the patient’s chest or abdomen to provide the external breathing
signal. The motion of these LEDs due to respiration is registered by a digital camera
array (the Synchrony camera).
• The tumor is localized by reconstructing the 3D position of the tumor or the fiducial
markers, which are automatically segmented in the X-ray images. The reconstructed
position is compared with the position in the planning CT scan.
Advantage:
An ITV is not required.

18. Simulation, Treatment Planning, Constraints and Prescription
• Treatment planning CT scan is performed with intravenous contrast
• 4D CT scans, exhale or inhale CT scan combined or not combined with a
contrast enhanced planning CT scan
• Scanned from his/her teeth to the middle of his/her abdomen
• Axial imaging has a slice thickness of 1.5–3 mm.
• The planning CT is transferred to the treatment planning system (TPS).
• The GTV is contoured using the lung window.
• CTV / ITV = GTV + 0–10 mm (in RTOG protocols , GTV and CTV have been
considered identical on CT planning with zero expansion margin added).
• PTV = CTV / ITV + 3–10 mm
Current RTOG guidelines are:
 Non-4DCT planning, PTV = GTV + 5 mm axial and 10 mm longitudinal
anisotropic margins.
 4DCT planning, PTV = ITV + 5 mm isotropic margin

19. • The OARs consist of both lungs, esophagus, the heart, central airway,
chestwall, brachial plexus, skin and the spinal cord.
• Usually, inverse treatment planning is used
• The number of beams varies between 7 and 15 using conventional IG-IMRT
techniques or up to 150 beams using stereotactic radiotherapy with the
CyberKnife
• Treatment planning guidelines (adapted from RTOG 0618).
 VRx dose ≥95 % PTV , V90 ≥99 % PTV.
 High dose region (≥105 % Rx dose) should fall within the PTV .
 Conformality Index goal ≤1.2.

20. Distinction of peripheral vs central tumors

21. Dose Prescription
• Goal is tumor BED10> 100. Adaptive dosimetry for histology -, volume-,
location-, and context-based lesions (primary vs. metastatic) are under
investigation.
• Current dose fractionation schema largely employs 1–5 fractions.
 Peripheral Lung Tumors
Common accepted schemas : 25–34 Gy × 1 fraction, 18-20 Gy × 3 fractions, 12
Gy × 4 fractions, 10 Gy × 5 fractions.
 Central Lung Tumors
accepted schema : 10 Gy × 5 fractions (BED10 dose limited to reduce toxicity of
central structures: large airways, heart , esophagus , and spinal cord ).

22. Recommended dose
constraints for SBRT lung
lesion target planning
assuming no prior regional
radiotherapy
(TG101, Benedict et al.,
2010; RTOG 0618).

23. EVIDENCES

24. Selected studies of SBRT treated NSCLC patients

27. • In a nutshell, these studies show local control rates of 85–95 % at 3–5 years,
and overall survival rates of 50–95 % at 3–5 years for early-stage NSCLC
managed with SBRT.

28. RTOG Trials Of SBRT Lung
RTOG 0236
RTOG 0618
RTOG 0813
RTOG 0915

29. RTOG 0236 (Timmerman et al. 2010, Stanic et al. 2014).
• Phase II multicenter trial
• 55 patients with medically inoperable early-stage (<5 cm) peripheral NSCLC
(44 stage IA, 11 stage IB),
• treated with 54 Gy in 3 fractions SBRT.
• Three year primary tumor and involved lobe control was 98 %.
• Rate of distant failure 22 % at 3 years.
• OS 56 % at 3 years.
• Grade 3 and 4 toxicities were 12.7 % and 3.5 %, respectively.
• Poor baseline PFT not predictive of SBRT-related toxicity.

30. RTOG 0618 (Timmerman et al. 2013).
• Phase II trial
• 33 patients with medically operable early-stage peripheral NSCLC (<5 cm),
• treated with 60 Gy in 3 fractions.
• Completed accrual in 2010 with results presented at ASCO 2013
• showing estimated 2 years primary tumor failure rate of 7.8 %, with a median
follow-up of 25 months.
• Local failure , including ipsilateral lobe, was 19.2 %. PFS and OS at 2 years
were estimated at 65.4 % and 84.4 %.
• Grade 3 toxicity was 16 %.

31. RTOG 0813:
• Phase I/II dose-escalation trial
• 71 pts: Medically inoperable centrally
located early-stage NSCLC (<5 cm).
• Dose escalated to 60 Gy in 5
fractions. Closed to accrual at 120
patients in 2013.
Conclusion:
• local control at 2 yrs ; treated with the
two highest doses levels (11.5-12
Gy/fr x 5 fr) were high,
• G3+ toxicity rates were acceptable.
• Two-year OS rates of 70% were
comparable to pts with peripheral
early stage tumors.

32. RTOG 0915:(Videtic et al. 2013).
• Phase II randomized trial
• 34 Gy in 1 fraction vs. 48 Gy in 4 fractions for medially inoperable early-
stage peripheral NSCLC (<5 cm).
• Study completed accrual in 2011 with 94 patients.
• At 1 year, LC 97.1 % vs. 97.6 %; OS 85.4 % vs. 91.1 %, and PFS 78.0 % vs.
84.4 %. Adverse events were 9.8 % vs. 13.3 %.
• Based on the favorable toxicity, the 34 Gy in 1 fraction arm will be compared
to the 54 Gy in 3 fractions arm of RTOG 0236 in a phase III setting.

33. Selected studies of SBRT
for metastatic lung lesions

34. Studies show local control rates of largely 80–90 %
at 2 years, and overall survival rates of 30–85 % at
2 years for patients with pulmonary metastases
managed with SBRT

35. Role as Boost for Locally Advanced Lung Cancer
• Studies have suggested a role for dose escalation as part of conventional
chemoradiation in locally advanced lung cancer,for which SBRT may be of
utility.
 Karam et al. (2013)- LC and OS at 1 year were 76 % and 78 %, respectively
 Feddock J et al. (2013)- LC was 82.9 %
Recurrence/Re-irradiation
• Studies have suggested a role in patients with recurrent lung cancer or
metachronous primary NSCLC
 Reyngold et al. (2013)- Median RFS -13.8 months and median survival - 22
months.
 Liu et al. (2012)- LC and OS at 2 years were 42 % and 74 %

36. Common acute toxicities (<6 weeks):
• Fatigue
• Cough/ dyspnea
• Chest pain-May be related to regional pleuritis and/or pericarditis and is generally self-limited.
• Pneumonitis
• Esophagitis
• Dermatitis
Common late toxicities (>6 weeks):
• Persistent cough / dyspnea
• Radiation pneumonitis
• Brachial plexopathy- Apical lung tumors associated with greater risk of brachial plexus injury
• Chest wall pain and rib fracture-More common in patients with peripheral lesions.
• Radiation skin ulcer
• Esophageal stricture and tracheoesophageal fistula-Historically rare complication observed
with treatment of mediastinal lymphadenopathy in locally advanced lung cancer .
• Vasculopathy- (seen in re-irradiation setting of central lesions)

37. Guidelines to read for SBRT in early stage NSCLC:
1. American Society for Radiation Oncology (ASTRO) and American College of Radiology
(ACR) on SBRT.
2. ESTRO ACROP consensus guideline (2017)
3. European Organisation for Research and Treatment of Cancer (EORTC) on high precision
radiotherapy
3. American Association of Physicists in Medicine (AAPM) on SBRT
4. UK SABR guidelines
5. Canadian Association of Radiation Oncology (CARO) on practice guideline for lung, liver
and spine SBRT
6. German Society for Radiotherapy and Oncology (DEGRO) on SBRT practice for early
stage NSCLC
7. Canadian Comité de l’évolution des pratiques en oncologie (CEPO) on SBRT for early
stage NSCLC

38. Thank you