J. Biomedical Science and Engineering, 2010, 3, 351-358 JBiSE
doi:10.4236/jbise.2010.34048 Published Online April 2010 (http://www.SciRP.org/journal/jbise/).
Published Online April 2010 in SciRes. http://www.scirp.org/journal/jbise
A phase I radiation dose escalation of stereotactic body
radiotherapy for malignant lung tumors
Randi J. Cohen1, Navesh K. Sharma1, Jian Q. (Michael) Yu2, Lu Wang1, Mark K. Buyyounouski1,
Michael Unger3, Hossein Borghaei4, Earl King3, Walter Scott5, Elaine Callahan1, Benjamin J. Movsas6,
Steven J. Feigenberg7
1Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, USA;
2Department of Diagnostic Imaging, Fox Chase Cancer Center, Philadelphia, USA;
3Department of Pulmonary Medicine, Fox Chase Cancer Center, Philadelphia, USA;
4Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA;
5Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, USA;
6Department of Radiation Oncology, Henry Ford Hospital, Detroit, USA;
7Department of Radiation Oncology, University of Maryland, Baltimore, USA.
Email: sfeigenberg@umm.edu
Received 15 January 2010; revised 25 January 2010; accepted 30 January 2010.
Objectives: This Phase I study determines the maxi-
mum tolerated dose (MTD) of stereotactic body ra-
diotherapy (SBRT) for lung tumors. Methods: Eli-
gible patients had biopsy proven cancer with a maxi-
mum tumor size 5 cm. Total doses were escalated
from 40 to 48, then to 56 Gy, delivered in 4 equal
fractions administered 2 to 3 times per week on an
IRB approved protocol. SBRT was administered us-
ing 5 to 9 fixed beam arrangements with CT loca-
lization. Internal target volumes (ITV) were based on
breath hold scans or 4D CT simulation. The planning
target volume (PTV) was defined as the ITV with a
uniform 5 mm expansion. Dose limiting toxicity (DLT)
was defined as any grade 3 or higher toxicity using
the Radiation Therapy Oncology Group (RTOG)
common toxicity criteria (CTC). Results: Between
April 2004 and February 2008, 18 patients received
the prescribed treatment (40 Gy n = 6, 48 Gy n = 7,
56 Gy n = 5). Seventeen of 18 patients had non-small
cell lung cancer (1 with rectal cancer), four of whom
were treated for an oligometastasis. The median age
of the patients was 68, while the median Karnofsky
performance status was 90. The mean tumor size was
2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary
event occurred (at 48 Gy dose level) immediately
following treatment with the onset of fever and
shortness of breath that responded to antibiotics. No
other DLTs occurred. Conclusions: SBRT utilizing
patient specific target volumes without gating ap-
pears safe. The maximum tolerated dose was not
Keywords: Stereotactic Body Radiotherapy; Phase I;
Dose Escalation; Prospective; Lung Cancer
The standard therapy for early stage non-small cell lung
cancer (NSCLC) is surgery [1]. Radiation therapy (RT)
can similarly cure early stage NSCLC, but has less
favorable outcomes due to competing causes of death,
lack of pathologic staging and/or less efficacious treatment.
With conventional radiation doses (i.e. 60-70 Gy) local
failure is considerable and may be underestimated based
on the method of follow-up with the highest failure rate
reported by bronchoscopy. [2] Due to this unacceptable
local failure rate, many institutions have designed trials
to improve local control. [3-5] At the University of Mi-
chigan, Martel et al. [6] determined that the total rad-
iation dose required to achieve a > 50% probability of
local control using conventional fractionation (i.e. 2 Gy
per fraction) was > 84 Gy and a phase I study was com-
pleted treating tumors to over 100 Gy. The major problem
with this treatment strategy is the duration of therapy (2
to 2 ½ months). As an alternative, investigators have
evaluated accelerating the dose of radiation through
hypofractionation [7] which increases the radiobiologic
effective dose by decreasing treatment time.
Stereotactic radiosurgery is an extreme version of
hypofractionation that has become an established alter-
native to surgery for selecting brain tumors. [8] More
recently, this technique has been adopted for treating
tumors outside the brain. [9-18] Unlike radiosurgery for
intracranial targets, stereotactic body radiotherapy (SB-
RT) is complicated by less precise target definition and
internal organ motion, which requires a margin to ensure
R. J. Cohen et al. / J. Biomedical Science and Engineering 3 (2010) 351-358
Copyright © 2010 SciRes. JBiSE
coverage of the target volume. Solutions include improv-
ing immobilization (i.e. stereotactic body frames), re-
ducing or monitoring internal organ motion (i.e. respira-
tory gating, active breathing control, or breath holding),
reducing daily set-up uncertainties (i.e. Computed To-
mography, CT, localization prior to treatment, elec-
tronic portal imaging with fiducial markers placed in the
tumor) or fractionation. Even with all of these innovative
techniques, most investigators use axial margins of at
least 5 mm and a cranial-caudal margin of 5 to 10 mm
around the gross tumor volume (GTV) to account for
set-up error and organ motion (i.e. planning target vol-
ume, PTV) [9,18] with no additional margin for sub-
clinical disease (i.e. clinical target volume, CTV).
When this study was developed, there were only two
prospective phase I studies in the literature. Herfarth
et al. [19] published results using SBRT in the liver in
2001. Timmerman et al. [16] reported their initial results
at ASCO in 2002 for medically inoperable non-small cell
lung cancer (NSCLC) patients with tumors < 7 cm and
no evidence of lymph node involvement. The patients
were treated with 3 fractions over 7 to 8 days starting at
800 cGy per fraction which was escalated to 2000 cGy
per fraction. Only 2 of 36 patients developed grade 3
pulmonary toxicity (one T1 and one T2 tumor) and the
maximum tolerated dose (MTD) was not reached. Patients
were immobilized in a stereotactic body frame as
originnally described by Blomgren and Lax, [9] who
defined the PTV as an expansion of 5 mm in the axial
dimension and 1 cm in the cranial caudal directions.
Fukumoto et al. [10] estimated the target volume by
obtaining 3 CT scans during different respiratory phases,
simulating a “slow CT” technique. The first scan was
performed during normal respiration, while the 2nd and
3rd were obtained during maximum inhalation and exha-
lation, respectively. The combination of the 3 scans
accurately described the gross tumor volume and its tumor
specific motion. Unlike our curren t trial, Fukumoto et al.,
did not use a stereotactic body frame for simulation and
treatment nor did they perform imaging prior to treatment
to improve daily localization and reprodu cibility. In their
trial, the PTV was created by adding 10 mm margins to
the GTV. Patients were treated with a very conformal
technique to a total dose of 48 or 60 Gy in 8 fractions.
This technique is ideal for a frail patient population
because it limits treatment time and reduces patient
Given the limited data in 2002, a phase I study was
designed to examine the role of SBRT using 3D image
guided radiotherapy and tumor specific targets motion
(“slow CT”). The primary goal at the initiation of this
study was to develop a treatment equivalent to approxi-
mately 70 Gy at conventional fraction ation with planned
dose escalations to 100 Gy (as treated in the Michigan
series) with a 4 fraction regimen. The following paper
describes the final results of our phase I dose escalation
Prior to the enrollment of any patient, the protocol and
consent form were reviewed and approved by an internal
Research Review Committee and Institutional Research
Review Board at Fox Chase Cancer Center. Patients
described in this manuscript willingly participated on
this prospective series. To be included in the study,
patients had to have one or two tumors in the lung
(primary NSCLC or metastatic) with a maximum diameter
of 5 cm. Patients were required to undergo a pathologic
diagnosis prior to enrollment. Local recurrences following
wedge resections were allowed if biopsy-proven. Patients
had to have a Karnofsky Performance Status of 60 or
higher. Central tumors were not excluded. Pulmonary
function tests were obtained pr ior to radiotherapy, although
there was no restriction based on pulmonary status. Of
the 18 patients, 13 were unfit for surgical treatment due
to poor pulmonary function and/or other medical co-
morbidities and five refused surgery.
2.1. Treatment Policy
Patients were immobilized in a FDA approved stereotactic
body frame (Integra Radionics, Burlington, MA, USA)
that employs a rigid frame and vacuum pillow. This
particular immobilizatio n device does not use abdominal
compression to limit respiratory motion. Patient initial
positioning was reproduced based on tattoo s at the upper
and lower level of the vacuum pillow as well as at the
isocenter. Planning CT scans in the stereotactic body fra-
me were obtained to get stereotactic co ordinates. For ten
patients, three CT scans were obtained: one during nor-
mal respiration, one during maximum end expiration,
and one during maximum end inspiration, as per Fuku moto
et al., [10] to obtain an accurate representation of the
tumor motion (i.e. internal target volume, ITV) during
the respiratory cycle. CT scans were fused on their bony
landmarks. The last seven patients underwent a 4 dimen-
sional CT (4DCT) simulation to generate an ITV.
[13,20,21] One patient underwent both 4DCT simulation
and scans using the breath holding technique. Axial images
were obtained every 2.5 or 3 mm through the entire
thorax. The GTV was identified on each of the axial CT
imaging using pulmonary windows. Only the solid
tumor component was targeted. Spiculations were not
For patient’s simulated with multiphase CT scans
(inspiration, expiration, and free breathing), the ITV was
defined by combining the GTVs outlined in each of the
three CT scans. When 4DCT was used, the ITV was
defined from a reconstructed data set generated using the
maximum-intensity-projection (MIP) protocol. MIP cr-
eates a 3D CT scan which represents the greatest voxel
R. J. Cohen et al. / J. Biomedical Science and Engineering 3 (2010) 351-358
Copyright © 2010 SciRes. JBiSE
intensity values throughout the 4D CT data-set. The
CTV was defined as the ITV with no additional margin
to account for subclinical disease. The PTV incorporated
the ITV plus 5 mm in all directions to account for set-up
error. Final patient positioning was achieved using CT
localization prior to each treatment using the PRIMATOM
sliding CT gantry (Siemens Medical Solutions, Concord,
CA, USA) for fifteen patients and on board cone beam
CT technology (Varian Medical Systems, Palo Alto, CA,
USA) for three patients.
Treatment planning was delivered using the Radionics™
stereotactic planning system (Integra Radionics) using 5
to 9 coplanar or non-coplanar, non-opposing beams. No
patient was treated using intensity modulation. The
distance between the block edge and the PTV for each of
the beams eye’s view was 3 to 4 mm to ensure the 90%
isodose line would cover the PTV (i.e. dose prescribed
to 90% isodose line). This will allow a very steep fall off
in the dose outside of the PTV potentially maximizing
the benefit of a rapid fall off in the dose while minimizing
the hot spots in the surrounding normal tissue.[22]
Heterogeneity corrections were used.
As part of the dose escalation protocol, the first cohort
of patients received 4000 cGy in 4 fractions with the
radiation delivered on non-consecutive days either 2 or 3
times a week at 1000 cGy per fraction. This dose was
chosen since it was radiobiologically equivalent to
approximately 70 Gy at 2 Gy per fract i on, t he dose ut il ized off
study at our institution. Biologically equivalent doses (BED)
were calculated using the formula BED = nd (1 + d/(α/β)),
where n = number of fractions; d = daily fraction size;
and α/β = 10. The total treatment dose of each subse-
quent cohort was escalated an addition al 800 cGy at 200
cGy per fraction, i.e., 4800 cGy and then 5600 cGy in 4
fractions. The final dose was cho sen as it is similar to the
highest dose reached on the University of Michigan 3D
dose escalation trial [4]. A three month period of obser-
vation after the sixth patient in each of the first two co-
horts was performed prior to escalating the dose to en-
sure no adverse events occurred.
The primary endpoint of the study was to determine the
maximum tolerated dose (MTD) for treating malignant
tumors of the lung with SBRT. The secondary endpoint
was to determine the response rate, local control and
PET response at 3 months (for those treated definitely)
for these patient s un dergoin g SBRT.
2.2. Statistics
The dose escalation followed the method described in
Babb et al. [23] and shown to be Bayesian-feasible, Bay-
esian-optimal and consistent by Zacks et al. [24]. The
dose for each cohort was determined so that, on the basis
of all available data, the probability that it exceeds the
MTD is equal to a pre-specified value α. For the first
cohort α = 0.25, for the second cohort α = 0.35, and for
the third coho rt α = 0.5. A maximum of 18 patients were
planned for accrual to this trial.
2.3. Follow-Up after Treatment
All patients underwent a CT scan and pulmonary function
tests one month following therapy. A PET scan was
obtained prior to and 3 months following treatment for
patients treated with curative intent with primary NSCLC
to determine the biologic response which potentially
could act as an early surrogate of local failure (reported
elsewhere). Subsequently, CT scans were obtained every
3 months until 2 years. Other investigations were obtained
based on clinical indication. Progressive disease was
defined per the RECIST criteria: [25] at least a 20%
increase in the sum of longest diameter (LD) of the
treated lesion taking as reference the smallest sum LD
recorded since the treatment started.
Between April 2004 and February 2008, 18 patients with
19 tumors received the prescribed treatment. Patient
characteristics of this cohort are described in Table 1.
Seventeen of the 18 patients had NSCLC, while one
patient had metastatic rectal cancer. The rectal cancer
patient had stable extra-pulmonary disease and was
treated to 2 lung metastases during the same session. Four
patients with NSCLC were treated for oligometastatic
disease. The me dian age of the patients was 68 years (range
48 to 82), while the median Karnofsky performance
status was 90 (range 60 to 100). The mean tumor size
was 2.0 cm (range 0.9 to 4.5 cm). Prior to SBRT, half of
patients treated had received prior radiotherapy, surgery
and/or chemotherapy to the lung. Six patients were on
oxygen prior to SBRT. The mean pre-treatment FEV1
was 1.41 liters (range 0.49 to 2.6 L), while the mean
DLCO was 52% of predicted (range 30 to 90%). The
mean post-treatment pulmonary function tests were not
significantly different from the pre-treatment tests (mean
FEV1 = 1.25 L, mean DLCO = 50.8%).
With a median follow-up of 24 months (range 3 mon-
ths to 48 months), most patients (72%) did not expe-
rience any adverse side effects during or following treat-
ment. No patients experienced chest wall pain, rib frac-
ture, esophageal stricture, nausea, subcutaneous fibrosis
or brachial plexopathy. The most common grade 2 or
higher side effect reported was fatigue, which was seen
in 3 patients between one and three months following
the completion of treatment. Two patients experience
grade 2 erythema within the first month following
Two patients experienced pneumonitis, one that was
grade 2 and one that was grade 3. Both patients had been
previously treated with chemotherapy and radiation prior
to SBRT for an oligometastasis. The one grade 3 event
R. J. Cohen et al. / J. Biomedical Science and Engineering 3 (2010) 351-358
Copyright © 2010 SciRes. JBiSE
Table 1. Patient characteristics.
Pt # Age Race Gen-
Location Histology Stage at
Pre & Post
Post Tx
1 74 W M 40 GyLung LUL
Squamous Cell
Carcinoma T4N0M0Chemo YES No0.95 0.92 44 461.7
2 69 W M 40 GyLung LLL
noma T1N0M0None YESNo1.06 1.28 30 311.5
3 52 W F 40 GyLung LUL
Large Cell
Carcinoma T2N2M0 Surgery
Radiation No No1.81 1.70 54 561
4 79 W F 40 GyLung RML
Alveolar Ca T1N0M0SurgeryNo No0.91 0.82 59 622
5 71 W M 40 GyLung RUL
noma T1N0M0RadiationNo No2.26 X 43 X1
6 61 W F 40 GyLung LUL
noma T1N0M0None No No1.14 1.18 38 352
7 48 W F 48 GyLung RUL
Squamous Cell
Carcinoma T1N0M0 Surgery,
Chemo YESYES1.41 1.22 42 521.4
8 57 W M 48 GyLung RUL
noma T2N1M0 Surgery,
Chemo YESNo2.6 X 64 X2.1
9 69 W F 48 GyLung RUL
noma T1N0M0None YESNo0.94 1.05 40 491.5
10 80 W M 48 GyLung RUL
Squamous Cell
Carcinoma T1N0M0None No No1.62 1.73 68 752.3
11 65 W F 48 GyRectum
2 lesions
in LUL Adenocarci-
noma T3N0M0SurgeryNo No0.69 0.68 43 393.1,
12 78 W M 48 GyLung LUL
Squamous Cell
Carcinoma T1N0M0None No No1.99 X 90 X1.1
13 82 W M 48 GyLung RLL
Squamous Cell
Carcinoma T1N0M0None No No0.71 X 67 X2.7
14 68 W M 56 GyLung RLL
Squamous Cell
Carcinoma T2N0M0SurgeryYESNo2.4 2.38 70 672.5
15 74 B M 56 GyLung RUL
Alveolar Ca T2N0M0None No No1.47 X 52 X4.5
16 59 B F 56 GyLung RUL
noma T1N0M0None No No0.49 0.51 33 241.7
17 68 W M 56 GyLung LLL
Squamous Cell
Carcinoma T1N0M0None No No1.8 1.59 64 571.2
18 69 W F 56 GyLung RLL
Non-Small Cell
NOS T1N0M0SurgeryNo No1.13 1.18 46 68 3.1
W: White B: Black X: One month p ost-SBRT PFTs not performed
LUL: Left Upper Lobe LLL: Left Lower Lobe RML: Right Middle Lobe
RUL: Right Upper Lobe RLL: Righe Lower Lobe
was previously treated for an advanced non-small lung
cancer requiring induction chemotherapy and radiation
followed by left sided pneumonectomy. She developed a
second primary versus an oligometastasis in the contra-
lateral right upper lobe that was treated with a wedge
resection. She had a biopsy-proven local recurrence in
the staple line, which was treated to 4800 cGy (see Figure
1 which illustrates the dose distribution). A fever developed
R. J. Cohen et al. / J. Biomedical Science and Engineering 3 (2010) 351-358
Copyright © 2010 SciRes. JBiSE
Figure 1. This is an axial CT image from the patient’s simul-
ation illustrating the prescription isodose line (48 Gy), as well
as 90%, 50% and 20% of the prescription. This patient had
prior induction chemoradiation followed by a pneumonectomy.
She subsequently developed a second primary in the right
upper lobe. This was treated with a wedge resection, which
recurred locally. Her centrally-located, biopsy-proven local
recurrence in the staple line was treated to 48 Gy.
Figure 2. These CT slices were obtained one week following
admission to the hospital which was required due to the devel-
opment of fever of 103°F and shortness of breath one day
following SBRT while on oral antibiotics. These images dem-
onstrate the trilobar pneumonia.
after the first fraction. She was empirically treated with
oral antibiotics and the fever resolved. The day after the
final fraction, she developed a fever up to 103°F with
increasing shortness of breath. She required admission to
the hospital and a stay in the ICU for a tr i-lobar pneu monia
(see Figure 2). She remained hospitalized for a week
and responded to intravenous antibiotics and supportive
care. Her res pirat ory funct ion co ntinued to im prove over tim e,
although she remained intermittently oxygen dependent
16 months following treatment. Unfortunately, she de-
veloped a failure on the staple line 2 cm from the site
No patient who received 56 Gy developed a sympt-
omatic pulmonary injury, although one patient developed
asymptomatic distal atelectasis for a peripherally treated
tumor six months following radiation.
3.1. Local Control
Six patients developed a local failure. There were no
marginal failures outside of the original PTV. Only two
of the local failures were biopsy proven. One of the
patients was treated for a gross recurrence following a
wedge resection and developed a recurrence on the
staple line 2 cm from the treated lesion. The second bi-
opsy-proven failure occurred in patient number 1, who
had very poor pulmonary function and presented with 2
tumors in the same lobe (i.e. T4). That individual was
initially treated palliatively with chemotherapy alone
(six cycles of carboplatin and paclitaxel). The smaller tu-
mor resolved and the larger tumor shrank from 4 to 2 cm.
The post-chemotherapy volume of the larger tumor was
treated on study. Six months following this second treat-
ment, an area of nodularity developed outside the origi-
nal PTV, but retrospectly was in the original pre-chemo-
therapy GTV. The tumor that initially resolved on
chemotherapy returned 14 months later. That lesion was
treated off-study with SBRT.
There are many reports on SBRT in the literature although
there are very few prospective trials. The morbidity results
in our study are lower than recently published trials and
seem more impressive in light of this heavily pretreated
population. One could argue that the only grade 3 event
described in this trial may not relate to the radiotherapy.
Baumann et al. [26] reported a 21% incidence of
grade 3 toxicities of the 60 patients treated at the Karo-
linska University Hospital in Sweden. They prescribed
45 Gy in 3 fractions to the 67% isodose line (19 Gy
when corrected to 80%) [26,27]. Fakiris et al. [28] up-
dated the Indiana University phase II trial demonstrating
an 11.4% rate of grade 3 to 5 events occurring in pe-
ripherally located tumors and 27.3% in their centrally
loca ted patients. The dose in the Indiana experience was
60 Gy in 3 fractions prescribed to the 80% isodose line.
However, since heterogeneity corrections were not used,
the actual prescribed dose has now been reported to be
closer to 18 Gy per fraction. [16]
Nagata et al. [14] reported a phase I/II study using 48 G y
in 4 fractions in 45 patients with no grade 3 or higher
pulmonary events and excellent local control. In the
largest series reported, Onishi et al. [29,30] reported a
2.4% incidence of grade 3 and 4 pneumonitis and no
grade 5 events. In fact, there have been only 14 (0.6%)
reported grade 5 events from a Japanese National Survey
out of 2104 patients treated (personal communication)
compared to 5 of 70 treated on the phase II experience
R. J. Cohen et al. / J. Biomedical Science and Engineering 3 (2010) 351-358
Copyright © 2010 SciRes. JBiSE
from Indiana.
Other possible morbidities following SBRT are chest
wall pain and rib fracture. Onishi et al. [29] described
the multi-institutional Japanese experience and reported
a 0.8% incidence of rib fractures. The Princess Margaret
group [31] demonstrated a 48% incidence of rib fracture
in peripheral lesions treated with 54-60 Gy in 3 fractions.
Ribs in the areas of the fracture generally received 43 Gy
and the tumor was less than 5 mm from the rib. The
Colorado and Virginia groups [32] combined their ex-
perience of peripheral tumors less than 1.5 cm from the
chest wall. The risk of chest wall pain and/or fracture
correlated with the volume of chest wall receiving more
than 30 Gy. The incidence was 0% (0/4), 33% (2/6), 46%
(6/13) and 63% (5 /8) for < 10 cc, 10.1-40 cc, 40.1-120 c c
and > 120.cc, respectively. The author recommended
the use of 48 Gy in 4 fractions when the tumor was ad-
jacent to the rib. None of the patients treated on this trial
developed rib fracture or chest wall pain.
The Cleveland Clinic [33] reported the most compelling
study that evaluated two different fractionation schemas
(50 Gy in 5 fractions versus 60 Gy in 3 fractions). When
their program started, a 5 fraction regimen was used. In
2000, after the RTOG study was opened, the Timmerman
approach (60 Gy in 3 fractions) was followed . With short
follow-up, local control was similar between the two
schemas (97% versus 100%) although the chest wall
toxicity was significantly more with 60 Gy. The incidence
of chest wall pain was 4% (2/56) for 50 Gy and 18% (7/ 38)
for 60 Gy, p = 0.028. Also, given the median follow-up of
only 9 months in the 60 Gy cohorts, the morbidity is
likely to increase with further follow-up.
Brachial plexopathy (BP) is a rare event following
SBRT. The Indiana University [34] experience described
seven brachial plexus injuries. Four patients had grade 2,
two patients had grade 3 and one had grade 4 BP. The
authors tried to determine dose volu me relation of apical
tumors, which they defined as being located superior to
the arch of the aorta (37 of 273 cases). Using the subclavian
and axillary vessels as a surrogate for the brachial plexus
dose, when the dose was greater than the median dose
(26 Gy over 3 fractions) the 2 year incidence of BP was
46% versus 8% (p = 0.038) for lower doses. There were
no brachial plexus injuries in our study.
Currently, there are 2 predominant fractionation sch-
emas for SBRT of malignant lung tumors: the Japanese
approach (12 Gy × 4) [14] and the RTOG approach
developed by Timmerman (20 Gy × 3). [16,20,35] The
biologic effective dose (BED) between the 2 schemas
are drastically differen t (105.6 versus 180 G y), but there
are no clear differences in local control (85% versus
88%). The calculation of the BED from conventional
to hyopfractionated radiation schedules, however, may
be f l a w ed . [36]
Our local control appe ars similar to what others describ e
although two of the failures are important to comment
on. The tumors of patients treated in the post-operative
or post-chemotherapy sett i ng m ay be difficult to delineate.
Therefore, these patients may not be ideal candidates for
SBRT. Such is the case for the two previously described
patients who had biopsy-proven local failures-the first be-
ing the patient who had a local recurrence along a wedge
resection staple line and the second being the patient who
had a recurrence in the pre-chemotherapy volume, al-
though the post-chemotherapy volume was treated. Deter-
mining appropriate target volumes may be more diffi-
cult after either surgical intervention or chemotherapy.
Unfortunately, the larger volumes necessary to cover all
these areas of subclinical disease may increas e mor bid ity.
[37] Therefore, in post-surgical and post-chemotherapy
settings, care must be taken to weigh the risks and bene-
fits of this treatment following prior treatment.
In conclusion, SBRT utilizing patient specific target
volumes without gating appears safe. In our study, patient
simulation was carefully performed to create an ITV. A
stereotactic body frame was utilized and imaging was
obtained prior to each treatment to verify patient posi-
tion. One grade 3 pulmonary event occurred at the 48
Gy dose levels, which may be related to radiotherapy.
No other dose limiting toxicities occurred. There was
no significant decrement in pulmonary function tests
following SBRT. The maximum tolerated dose in this
study was not reached.
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