RTOG 0813
Seamless Phase I/II Study of Stereotactic Lung
Radiotherapy (SBRT) For Early Stage, Centrally
Located, Non-Small Cell Lung Cancer (NSCLC) In
Medically Inoperable Patients
Seth R. Duffy, BSPH
Image Source: http://www.ikwilstoppenmetroken.nu/aantal-doden-longkanker-omlaag-door-screening/
Radiation Therapy Oncology Group (RTOG)

RTOG 0813 saw its inception and activation in February of 2009

Served as one of the forerunners in the emergence of SBRT treatment techniques

SBRT is unique in that it delivers hypofractionated treatments of high-doses

Clinical locations (209) approved through a rigorous approval process by the RTOG headquarters
Epidemiology: Lung Cancer



The Leading Cause of
Cancer-Related Deaths
in the United States
and Globally.
Most Common Cancer
World-Wide Since
1985. (Incidence and
Mortality)
5-Year Survival Rate
of 15.6%.


Median Age of
Diagnosis is 71 Years
of Age.
Adenocarcinoma has
replaced squamous
cell as the most
prevalent type of
NSCLC (2013).
Citation [5]
Inclusion Criteria for Potential Participants
Eligible (Accepted)

Pathologically Proven Diagnosis of
NSCLC

Staging of T1-2, N0, M0

Non-Small Cell Lung Cancer

Tumor Size ≤ 5cm

Not A Candidate for Surgical Resection


Deemed Medically Inoperable By An
Experienced Thoracic Surgeon
Exclusion (Denied)


Measurable Disease

Patient Provision of Informed Consent

At Least 9 Forms of Consent

Also Continued Consent Throughout The Trial
Zubrod Performance Status Outside 0-2
Range

4 Weeks Prior to Registration

Excess Pleural Effusion

Pregnant or Positive Serum


Tumor Within The Zone of The Proximal
Bronchial Tree

Not 18 Years Of Age
Prior Invasive Malignancy Within The Past 2
Years


Within 72 Hours of Registration
Other Than Melanomatous Skin Cancer
Previously Irradiated Region of Study
(Causing Overlap)

Excessive Comorbidities

No Concurrent therapy

Including Standard Fractionated RT or Surgery or
Systemic Chemotherapy
Protocol Objectives In RTOG 0813
What does this clinical trial hope to accomplish?
Phase I
Portion:

Phase II
Portion:

Secondary
Objectives:



Tertiary
Objectives:

To determine the maximal tolerated dose (MTD) of SBRT for centrallylocated NSCLC and the efficacy of that dose in patients who are not
operative candidates. (8/20/10)
To estimate the primary tumor control rate at the MTD of SBRT.
To estimate rates of ≥ grade 3 CTCAE, v. 4 adverse events other than a
dose-limiting toxicity (DLT) which is possibly, probably, or definitely
related to treatment and which occurs within 1 year from the start of
SBRT.
To estimate rates of late adverse events (> 1 year from starting SBRT)
To estimate primary tumor control and progression-free and overall
survival rates for patients treated with this regimen.
See Reference Section 2.0 in RTOG 0813
Protocol Section 6.1
Stereotactic Dose Fractionation
Patients are to be treated with 5 fractions of radiation, on an every other day basis (2-3
treatments per week with a minimum of 40 hours between treatments).
The [red box] indicates the protocol starting dose, “Level 5”, from which dose
escalation in future patients (or dose-limiting) will occur.
Pre-Treatment Planning Preparation
Protocol Section 6.2-6.3
Technical Factors
-Only X-ray photon beams of
energies 4-10 MV
-Minimum field dimensions of 3.5
cm is required to account for
uncertainties in beam
commissioning
-Heterogeneity corrections must
be utilized when planning
with IMRT
-Reliable abdominal compression,
accelerator beam gating,
tumor tracking, and active
breath-holding techniques
may all be utilized once
approved by the PI and
Study Co-Chairs
Simulation
Localization
-Achieving the most comfortable,
stable patient positioning possible
is important
-Isocenter, or reference point,
port localization images must
be taken at each treatment
on the specific linac to
deliver treatment
-Stereotactic body frames, with
large rigid pillows, may be used
~AP and Lateral
-GTV volume must not deviate
beyond the confines of the PTV as
defined by the physician
-Verification CT scans and portal
films may be taken at the
discretion of the institution /
physician
-CT simulation should be the
primary imaging modality and
should be performed with IV
contrast
-The 3-D fixed coordinate system
should be defined by
reliable fiducial markers.
-≤ 3.00 mm scan slice thickness
-Helical and 4DCT are both
acceptable imaging methods
~Radiopaque markers, rods,
or even metallic seeds
placed within the tumor itself
Dosimetry & Treatment Planning
Protocol Section 6.4-6.5
Critical Structures
Esophagus
Spinal Cord
The esophagus is a hollow transporting
structure that assists in the digestion of
solids and liquids. Measures 25-30cm in
length. This structure is contoured to
include the fatty surrounding tissues as
well.
Spanning between the foramen magnum
to the L1-L2 interspace, the spinal cord
is one of the most essential structures
within the human body. This protocol
outlines that this structure be contoured
to the bony limits of the spinal canal.
Great Vessels
Heart / Pericardium
Five great vessels enter and leave the
heart: the superior and inferior vena
cava, the pulmonary artery, the
pulmonary vein and the aorta. The
primary function of which are to circulate
blood (oxygenated and deoxygenated).
The human heart is comprised of four
chambers: the right atrium and ventricle
and the left atrium and ventricle.
The pericardium is a fluid filled sac that
Surrounds the heart and the proximal
ends of the aorta, vena cava, and
pulmonary artery.
2cm Margin
The Proximal Bronchial Tree
Defined as: The distal trachea (2cm following the proximal trachea), the carina, and the
two major mainstem bronchi, portions of the upper lobe bronchi, the intermedius
bronchus, the right middle lobe bronchus, the linguar bronchus, and the right and left
lower lobe bronchus.
Although this structure is not extensively evaluated upon dose received, it plays an
important role in delineation of who is eligible for this protocol versus who is not eligible.
Critical Structures
Skin
While often overlooked, the skin is
essential to the human body because it
not only protects the underlying tissues
and organs but also assists in the body’s
regulation of temperature as well as
giving sensations of touch, hot, and cold.
Non-Adjacent Wall
The Non-Adjacent Wall structure is
something specific to this protocol that
accounts for dose-spillage past the
midline of the body and into the half
where the disease does not exist.
Trachea
Whole Lung
Approximately 11.5cm in length and 2.5
cm in diameter. The trachea provides a
path for respiration to occur. This
function is further assisted (and
strengthened) by tracheal cartilages.
The whole lung encompasses both right
and left lungs, per protocol request. This
also includes collapsed lungs. All GTV
must be removed from this structure’s
contour. The Lungs are essential to
respiration and must be correctly
contoured and monitored.
Image From: http://www.nlm.nih.gov/medlineplus/ency/imagepages/9129.htm
The Brachial Plexus
The brachial plexus has been described as: A beautiful, intricate, and complex structure
that comprises the connections of the spinal nerves to their terminal branches in the upper
extremity.”[8]
 Clinically divided into five unique zones but not within this protocol
 Emerges from the posterior triangle of the neck, bordering the sternocleidomastoid

Delineation of Target Volumes
RTOG 0831 Section 6.4 and ICRU-62
GTV
CTV
Gross Tumor Volume
Defined As: The Visible, Palpable,
Known Disease Region as
Determined by an
Experienced Oncologist.
Contoured As: Gross Disease
Clinical Target Volume
Planning Target Volume
Defined As: A Tissue Volume
of the GTV and any
Suspected Microscopic
Disease
Defined As: The Geometrical Concept
that Encompasses the Previous
Structures with Treatment Planning in
Mind.
Contoured As: GTV+Microscopic
Contoured As: GTV (or ITV) + 0.5cm
in the axial plane &
1.0cm in the longitudinal
plane
ITV
Internal Target Volume
ITV
PTV
PTV
Defined As: The Expansion of the
CTV to account for
internal movement.
(ex. Respiration)
Contoured As: GTV+CTV+Motion
Non-Coplanar
Beam
Arrangement
Beams Eye
View
3D Conformal Treatment Planning
Section 6.4.2.1
3-Dimensional beam arrangements, both co-planar and non-coplanar, can be used.
This protocol specifies that 10 or more static, non-opposing, beams should be utilized.
The field size and shape should correspond identically to the PTV within the BEV.
All normalization is done to the center of the PTV and all hotspots must remain inside it.
Image From: www.IMRTCenter.com
IMRT Treatment Planning
Section 6.4.2.2
IMRT should only be chosen when 3D conformal planning does not adequately address
target coverage, OAR dose limits, or dose spillage concerns.
The protocol recommends about two to three segments per beam to avoid complex beam
fluence issues.
Dose spillage directly relates to the dose gradients observed at/past the PTV edges.
Plan Evaluation


Participant
Safety and
Wellbeing
Remains
Constant
Throughout This
Protocol:
Plan evaluation can be performed by referencing
the strict guidelines set forth by the RTOG.
Tables throughout section 6.5 highlight the specific
PTV dose coverage needs, the hot spot restrictions,
as well as recommendations for dose gradients near
organs at risk.
Necessitating
Thorough Plan
Evaluation
Figure From RTOG 0813 Sect. 6.5
Conformality & Dose Tolerance
Section 6.5
Exceeding a max
dose point is a
protocol violation,
however the other
doses are suggested
limits supported by
current (2010)
research.
-PTV coverage tables
indicate specific
tolerable deviations
based on PTV size
(cc). [Table 1]
Deviation from the
specified PTV limits
is against protocol
standards.
Tables Directly From RTOG Protocol 0813
In The End, Who Will Benefit From This Clinical Trial?
Patients
The Field of Radiation Oncology
Participating Institutions
Image From: www.themedicalbag.com
Patients
- Patients in RTOG Clinical Protocol 0813 receive SBRT treatments that deliver highly
conformal, effective doses of radiation that can contribute to a longer, disease free,
life.
- SBRT is still used in 2015 and has contributed to some of the best clinical outcomes in
patients with NSCLC, increased 5-year survival and local control improvements. [6]
Image From: http://www.radonc.com/wp-content/uploads/2011/08/Patient-Linear-Accelerator1.jpg
The Field of Radiation Oncology
-Clinical trials contribute the the field of radiation oncology as a whole because they
provide detailed information on current treatment options, emerging techniques, as
well as in-depth comparisons that are only possible through these types of studies.
-Without clinical trials such as RTOG 0813, the field would not evolve at such a rapid
pace, further exemplifying the necessity these trials pose to the field.
Participating Institutions
- Every participating institution has gone through a rigorous registration and approval
process that not only demonstrates they are capable of carrying out the procedure but also
that they are capable of delivering a high-quality procedure consistently.
- This prestige is something that attracts new staff, patients, and potential trial participants to
the facility.
THANK YOU FOR WATCHING!
REFERENCES:
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2015.
2. Boundless. Anatomy and physiology: great vessels of the heart. https://www.boundless.com/physiology/textbooks/boundless-anatomy-andphysiology-textbook/the-cardiovascular-system-18/the-heart-172/great-vessels-of-the-heart-866-9331/. June, 2015. Accessed June, 2015.
3. Healthline Medical Team. Healthline body maps: esophagus. http://www.healthline.com/human-body-maps/esophagus. February, 2015.
Accessed June, 2015.
4. Nachum N. The university of Texas Medical School E-Textbook for neurosciences - Chapter 3: anatomy of the spinal cord.
http://neuroscience.uth.tmc.edu/s2/chapter03.html. 2015. Accessed June, 2015.
5. Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epideminology, etiology, and prevention. Clin Chest Med 2013;32:605-644.
http://dx.doi.org/10.1016/j.ccm.2011.09.001
6. Allibhai Z,Taremi M, Bezjak A, Brade A, et al. The impact of tumor size on outcomes after stereotactic body radiation therapy for medically
inoperable early-stage non-small cell lung cancer. Int J Rad Onc, Bio, Phys 2013;87:1064-1070.
http://dx.doi.org/10.1016/j.ijrobp.2013.08.020
7. RTOG 0813: Seamless phase I/II study of stereotactic lung radiotherapy (SBRT) for early stage, centrally location, non-small cell lung cancer
(NSCLC) in medically inoperable patients. (Last Update: 6/8/15)
PI: Bezjak A. Princess Margaret Hospital / University of Toronto
8. Chung KC, Yang LJ, Mcgillicuddy JE. Practical management of pediatric and adult brachial plexus palsies. New York, NY: Edinburgh
Publishing;2012. ISBN-13: 9781437705751.