Introduction
Lung cancer is the leading cause of cancer-related
deaths worldwide.[] Although the majority of patients have local advanced-stage or metastatic disease
at the time of diagnosis, the reported incidence of
early-stage non-small-cell lung carcinoma (NSCLC)
is expected to increase with the wider use of thorax computed tomography (CT) scans.[] Stereotactic
body radiotherapy (SBRT), also known as stereotactic
ablative radiotherapy, is a very effective treatment
option in patients for whom surgery carries a high
risk due to the presence of comorbidities and in those
that refuse surgical treatment. SBRT is a conformal
technique that can deliver a very high dose (i.e., ablative
dose) to the target area in one to five fractions.[]
Lung metastasis is very common in cancer patients.
In a study of 1,000 patients, during the autopsy, it was
found that 50% of deaths due to malignancies were
associated with pulmonary metastases.[] In a large
series evaluating survival after metastasectomy in
patients with lung metastasis, an unexpected 15-year
survival rate of 22% was achieved in stage 4 cases.
[]. Although metastasectomy is considered to be
the standard treatment for lung metastasis, surgical
treatment is not performed in patients with medical
comorbidities, presence of extrathoracic disease, unresectable
metastasis, or short-term disease-free survival.
SBRT is an effective treatment option in these
cases where surgery is not possible.[]
Recurrence in lung cancer is the main cause of
death regardless of tumor histology, cancer stage, and
treatment option.[] In local advanced-stage NSCLC,
the rate of locoregional recurrence was reported to be
85%.[] Surgery is the first choice for resectable recurrences,
with SBRT being recommended by the National
Comprehensive Cancer Network NCCN Guidelines in
cases where surgery is not indicated.[]
This study aimed to evaluate 59 cases that underwent
lung SBRT at the Radiation Oncology Department
of Eskişehir Osmangazi University Faculty of
Medicine between 2016 and 2019.
Methods
Patients
A total of 59 cases that underwent lung SBRT at the Radiation
Oncology Department of Eskişehir Osmangazi
University Faculty of Medicine between 2016 and 2019
were included in this study. The inclusion criteria were
being aged >18 years, having a Karnofsky Performance
Status score (KPS) of ≥60, having completed treatment,
and regularly attending the follow-up sessions.
In the early-stage lung cancer group, SBRT was not
performed in patients with a tumor larger than 5 cm
or T3 mediastinal region invasion, local lymph node
or distant metastasis, history of radiotherapy in the
planned volume, or ultracentral tumor; thus, these patients
were excluded from this study.
The cases with a hilar and/or mediastinal lymph
node of ≤1 cm in size with clinically negative Positron
Emission Tomography-CT (PET-CT) results, as well
as the cases with a >1 cm lymph node with a negative
pathology result but the presence of abnormal involvement
on PET-CT were accepted as having no cancer in
nearby lymph nodes (N0). All patients were evaluated
at the Chest Diseases Oncology Council, and SBRT
was recommended for malignant/recurrent/metastatic
cases and patients that were considered to be medically
inoperable based on the presence of the first-second
forced expiratory volume (FEV1) of ≤40%, expected
postoperative FEV1 of ≤30%, carbon monoxide diffusion
capacity of ≤40%, hypoxemia/hypercapnia, severe
pulmonary hypertension, end-organ damage, diagnosis
of diabetes mellitus, severe cerebral, cardiovascular
and peripheral vascular disease, and severe chronic
heart disease. Biopsy could not be performed in some
of the patients that were considered to be medically
inoperable due to the risk of morbidity and mortality.
After the follow-up thoracic, CT revealed that the
mass had grown and hypermetabolic activity was seen
on PET-CT, these cases were evaluated in a multidisciplinary
manner, and SBRT was planned. In line with
the recommendation given in the RTOG 0915 study,
for the cases that did not undergo a biopsy, PET-CT
was undertaken within eight weeks before SBRT.[]
Stereotactic Body Radiotherapy
The planning CT of the patients was obtained as 3D or
4D scans. The patients were immobilized in the supine
position by raising their arms above their heads on the
T-bar/Wingboard specifically designed for lung treatments.
Using a Siemens Somatom Definition AS® CT
device, a 1-3-mm image was obtained covering the
area between the cricoid cartilage and the upper border
of the L2 vertebra.
In cases undergoing a 3D-CT, the scan was performed
in normal respiration, deep inspiration, and
deep expiration, and the gross tumor volume (GTV)
was contoured on all three CTs, and the fusion of all
GTVs was achieved. For the planning target volume
(PTV), the margins for GTV were set at 0.5 axially and
1 cm craniocaudally. The external respiratory monitoring
system [Real-time Position Management (RPM)
System, Varian ® Medical Systems, Palo Alto, CA, USA]
was used to perform 4D-CT. The RPM system uses an
infrared tracking camera that monitors the external
marker placed in the upper abdomen of the patient
to determine the phases of the respiratory cycle. The
breathing cycle is divided into 10 segments (10% each) and consists of expiration and inspiration phases. The
number of phases and which phases to be selected in
the treatment were determined by the physician during
the contouring stage. After GTV contouring in the
phases to be used in the treatment, the fusion of all
GTVs was obtained, and PTV was obtained by setting
the margin to 0.5 cm in all directions.
In 3D-CT and 4D-CT scans, GTV was contoured
using a lung window, and a soft tissue window was also
utilized to prevent the inclusion of vascular, atelectasis,
or mediastinal and chest wall structures adjacent
to GTV. The lungs, heart, main vessels, trachea, ipsilateral
bronchial system, skin, ribs, brachial plexus, spinal
cord, esophagus, and other organs at risk depending on
tumor localization, such as the liver and stomach were
contoured.
The most commonly used SBRT scheme is 50 Gy
in 5 fractions. The median radiotherapy dose was 50
(30-60) Gy, the median fraction dose was 10 (4-12) Gy,
and the median number of fractions was five (5-13).
Normal tissue dose constraints are given in Table 1.
Table 1: Normal tissue dose constraints
Evaluation of the Treatment Response and Follow-up
A thoracic CT was performed within one to three
months after radiotherapy, and the PET-CT was undertaken
three months after radiotherapy. The patients"
responses to treatment were evaluated using a multidisciplinary
approach. As recommended in the RTOG
0915 study, a second PET-CT was performed at the end
of the first-year follow-up.[]
Statistical Analysis
SPSS v. 21.0 for Windows was used in statistical analyses.
The Shapiro-Wilk test was conducted to investigate
the suitability of the data for normal distribution.
Parametric tests were employed for the analysis of the normally distributed data and non-parametric tests for
those that did not fit the normal distribution. The independent
samples t-test was used for the comparisons
between the groups, and the non-parametric Wilcoxon
signed-rank test for the evaluation of the pre- and posttest
data. The Kaplan-Meier survival analysis was performed
to calculate the inter-group survival durations,
and the differences were determined using the log-rank
statistics. The Cox proportional regression method was
utilized to investigate the effects of prognostic variables
on survival. Frequency tables were generated to display
numbers and percentages, and the data were summarized
as mean±SD and median (Q1; Q3) values. P<0.05
was considered statistically significant.
Results
The median age was 69 (48-85) years. Patient characteristics
are summarized in Table 2. Thirty-two of the multicases
had early-stage lung cancer, 21 had recurrent
lung cancer, and six had lung metastasis. Of the six
cases with lung metastases, two cases were primary laryngeal
cancer, two cases were primary breast cancer,
and the remaining two cases were primary colorectal cancer. The tumor characteristics are presented in
Table 3. Nine patients had a centrally located lesion.
Eleven patients had lesions close to the chest wall.
Table 2: Patient characteristics
Table 3: Tumor characteristics
The median radiotherapy dose was 50 (30-60) Gy,
the median fraction dose was 10 (4-12) Gy, and the
median number of fractions was five (5-13). The biologically
effective dose (BED) was calculated according
to the formula of n × d (1+d/(α/β)) (n: number of fractions,
d: fraction dose, α/β: 10), and the median BED10
was found to be 100 (min: 48, max: 132) Gy.
The first response of the patients was evaluated
using the Response Evaluation Criteria in Solid Tumors
(RECIST) criteria [] using the CT performed
at one to three months after SBRT. According to these
criteria, complete response was seen in four patients
(6.8%), partial response in 41 patients (69.5%), stable
disease in nine patients (15.3%), and progressive disease
in five patients (8.5%). In cases with a pre-SBRT
PET-CT, the median of the maximum standardized
uptake value (SUVmax) was 5, while the post-SBRT
median SUVmax was reduced to 2.3. In the 16-month
follow-up after SBRT, 51 patients (86.4%) survived and
eight cases (13.6%) died of cancer. Following SBRT, the
median progression-free survival (PFS) was 12 (0-40)
months and the overall survival was 16 (3-44) months.
Progression was observed in a total of 16 cases (27.1%)
throughout the follow-up period.
The factors affecting the overall survival after SBRT
were found to be age (p=0.041), KPS (≥80) (p=0.019),
and maximum tumor diameter (≤3 cm) (p=0.033) according
to the univariate analysis, and KPS (p=0.011)
and maximum tumor diameter (p=0.007) in the multivariate analysis. The mean age was 67±7.8 years in the
surviving cases and 72±7.4 years in those that died. The
results of the Cox regression analysis for the overall
survival after SBRT are summarized in Table 4.
Table 4: Post-SBRT overall survival and Cox regression results
The variables affecting PFS after SBRT were GTV
(cc) (p=0.011) and BED10 (≥100) (p=0.043) in the
univariate analysis, and GTV (cc) (p=0.011) in the
multivariate analysis. The mean GTV (Q1-Q3) was 6.7
(1.8-14.7) cc among the surviving patients and 17.3
(4.4-27.8) cc in the mortality cases. Table 5 presents the
results of the Cox regression analysis of the variables
affecting PFS after SBRT.
Table 5: Post-SBRT progression-free survival and Cox regression results
During the follow-up, the pre- and post-treatment
PET-CT scans were available for 34 cases, for which the
low post-SBRT PET-CT tumor SUVmax values were
found to be associated with PFS (p=0.011). The median
(Q1-Q3) PET-CT SUVmax value was calculated as 4.1
(1.3-6.9) in patients that had progressive disease and
2.2 (0.3-3.2) that did not have progression.
During follow-up, none of the patients had grade
≥3 toxicity.
Discussion
Approximately 30% of newly diagnosed NSCLC cases
are stage I or II, in which the main treatment is indicated
as surgery if there are no contraindications, while
SBRT is the primary alternative in cases where surgical
resection cannot be performed.[] The population of
patients diagnosed with NSCLC is generally medically
inoperable considering the comorbidities they present
with. These patients are treated with SBRT, which has been shown to be safe and effective in prospective studies.[] Some medically inoperable patients have low
lung reserves that do not allow for a diagnostic biopsy,
given the risk of pneumothorax and even death. In this
patient group, SBRT is applied based on radiological/
clinical diagnosis without a biopsy.[] Furthermore,
although metastasectomy is the standard treatment for
lung metastases due to different types of cancer, surgery
is not possible because of medical comorbidities, extrathoracic
disease, and unresectable metastases, and
SBRT also presents as a good treatment option in these
cases.[]
Despite the efficacy of external beam radiotherapy
(EBRT) and good oncological outcomes of SBRT,
intrathoracic recurrences are observed in many cases
after radiotherapy.[] The treatment options for recurrent
NSCLC are generally limited. Resection may
not be appropriate depending on the location and extent
of the recurrence and lung function of the patient.
SBRT may be a good treatment option in selected cases
after weighing its potential benefits and possible risks.
[] In the 2017 consensus of the American Society of
Radiation Oncology, the role of SBRT in salvage therapy
were discussed in relation to the following three
scenarios after recurrence: conventional fractionated
radiotherapy, SBRT, and sublobar resection.[] In all
three scenarios, the quality of evidence from available
studies was considered to be low, and personalization of
treatment for each patient was recommended. In cases
where conventional fractionated EBRT is applied before
recurrence, SBRT can be undertaken because it causes
radiation damage with different biological mechanisms and prevents potential radiation resistance.[] However,
since re-radiotherapy will bring additional toxicity,
the benefits and risks should be properly weighed.
[] In cases of recurrence after resection, SBRT is a
lung-sparing treatment compared to salvage surgery
that usually involves lobectomy or pneumonectomy.
However, in these cases, it is necessary to pay attention
to toxicity, considering that the lung reserve is reduced
after surgery.[] In the presented series, the median
duration of survival was 19 months in patients that underwent
SBRT after recurrence.
Although there are many studies showing that local
control rates after SBRT are very good, the time interval
to evaluate tumor response by imaging methods is
not certain.[,] In addition, radiographic changes
occur in the lung parenchyma after high-dose radiotherapy,
and asymptomatic radiographic radiation
pneumonia is reported to occur at a rate of 60-100%
in some studies.[] [18F] -fluoro-2-deoxy-glucose
(FDG) PET-CT is frequently used for tumor staging
and post-treatment evaluation in early-stage NSCLC.
SUVmax is a quantitative measure of tumor glucose
metabolism.[] Some studies have shown an association
between pre-treatment SUVmax and overall survival.
[,] In the current study, the lower PET-CT
SUVmax values after treatment was found to be associated
with PFS in 34 cases (p=0.011). FDG PET-CT
is often used to assess post-treatment tumor response,
but the findings may be difficult to interpret due to
FDG uptake in the tumor site caused by radiation-induced
pneumonia, inflammation, and fibrosis.[,]
In addition, it has been shown that SUVmax elevation
after SBRT may persist or increase, possibly due to radiation-
induced pneumonia and fibrosis.[]
In a study conducted with 39 patients that underwent
SBRT, complete response was reported in 3% of
the patients, partial response in 43%, and stable disease
in 54% using the CT scan undertaken at 1.5 months
after SBRT, and when CT was evaluated at the fourth
month, these rates were 15%, 38%, and 46%, respectively.[] In the current study, the RECIST evaluation
performed by CT within one to three months after
SBRT revealed complete response in four patients
(6.8%), partial response in 41 patients (69.5%), stable
disease in nine patients (15.3%), progressive disease in
five patients (8.5%).
While the applicability of the BED calculation in
large doses per fraction is not clear, Onishi et al., who
used this calculation to compare dose and fractionation
schemes for SBRT, reported that BED10>100 Gy
had a significant oncologic outcomes.[] Koshy et al. also investigated the contribution of increased dose to
the overall survival using the BED calculation. Five
different SBRT schemes (cohort ratios) were applied
to 489 NSCLC patients with T1-T2N0M0: 20 Gy×3
(34%), 12 Gy×4 (16%), 18 Gy×3 (10%), 15 Gy×3 (10%)
and 16 Gy×3 (4%) fractions. The BED calculation was
performed using the linear-quadratic formula of α /
β=10. The patients were divided into high-dose SBRT
and low-dose SBRT groups with the BED values being
above and below 150 Gy. The calculated median BED
was 150 (106-166) Gy. The three-year overall survival
rates in high-and low-dose SBRT groups were 55% and
46%, respectively (p=0.03).[] There are also studies
showing that BED10<100 dose schemes reduce the local
control rate.[] In the current study, the univariate
analysis indicated that PFS was statistically significantly
higher in cases with BED10?100 compared to
those with BED10<100 (p=0.043).
There are studies evaluating the contribution of tumor
size to prognosis. In a retrospective study of 40
patients, the two-year local control rates were 90% and
70% for T1 and T2 tumors, respectively.[] In lung
SBRT studies, large tumors have been associated with
non-local recurrences and poor survival.[] In the
present study, tumor size was associated with the overall
survival according to both univariate (p=0.033) and
multivariate (p=0.007) analyses, and the overall survival
was lower in patients with large tumors. However,
in the literature, tumor volume appears to be a safer
criterion than cross-sectional measurements to evaluate
the overall survival and perform better than T-stage
in evaluating tumor burden by reflecting tumor shape
and biology more accurately.[,] In some studies,
GTV was found to correlate with local recurrence.
[,] Higher tumor volume is also considered to
reduce the overall survival associated with increased
local recurrence.[] In the current study, GTV was
associated with PFS after SBRT in both univariate and
multivariate analyses (p=0.011), but no correlation was
found between GTV and the overall survival. The studies
are summarized in Table 6.
Stereotactic body radiation therapy (SBRT) is an
effective and well-tolerated treatment. The high doses
used in thoracic SBRT may sometimes cause adverse
effects ranging from mild fatigue and transient
esophagitis to fatal events, such as pneumonitis or
hemorrhage []. In this study, during follow-up, none
of the patients had grade ≥3 toxicity.
Patients with early-stage lung cancer, recurrent disease
and lung metastases were analyzed together and
this is the limitation of this study.
Conclusion
SBRT is a new and effective treatment option for early-
stage lung cancer, lung metastasis, and lung cancer
recurrence that cannot be operated. For better local
control in cases treated with SBRT, BED10 should be
?100. The risk of local and distant recurrence should
be considered in patients presenting with large tumors.
Peer-review: Externally peer-reviewed.
Conflict of Interest: The authors declare that they have no
conflict of interest.
Ethics Committee Approval: Eskişehir Osmangazi
University Clinical Research Ethics Committee approval was
obtained. (Approval Number: 25403353-050.99-E.102462)
Financial Support: No financial support.
Authorship contributions: Concept - M.A., D.E., M.M.,
G.A., A.Ö., Ş.Y.; Design - M.A., D.E., M.M., G.A., A.Ö., Ş.Y.;
Supervision - M.A., D.E., M.M., G.A., A.Ö., Ş.Y.; Funding -
M.A., D.E., M.M., G.A., A.Ö., Ş.Y.; Materials - M.A., D.E.,
M.M., G.A., A.Ö., Ş.Y.; Data collection and/or processing
- M.A., D.E.; Data analysis and/or interpretation - M.A.,
D.E., M.M., G.A.; Literature search - M.A., D.E., M.M., G.A.,
A.Ö., Ş.Y.; Writing - M.A., D.E., M.M., G.A., A.Ö., Ş.Y.; Critical
review - M.A., D.E., M.M., G.A., A.Ö., Ş.Y.
References
Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014.
CA Cancer J Clin 2014;64(1):9-29.
Aberle DR, DeMello S, Berg CD, Black WC, Brewer B,
Church TR, et al. Results of the two incidence screenings
in the National Lung Screening Trial. N Engl J
Med 2013;369(10):920-31.
Videtic GMM, Donington J, Giuliani M, Heinzerling
J, Karas TZ, Kelsey CR, et al. Stereotactic body radiation
therapy for early-stage non-small cell lung cancer:
Executive Summary of an ASTRO Evidence-Based
Guideline. Pract Radiat Oncol 2017;7(5):295-301.
ABRAMS HL, SPIRO R, GOLDSTEIN N. Metastases
in carcinoma; analysis of 1000 autopsied cases. Cancer
1950;3(1):74-85.
Pastorino U, Buyse M, Friedel G, Ginsberg RJ, Girard
P, Goldstraw P, et al. Long-term results of lung metastasectomy:
prognostic analyses based on 5206 cases. J
Thorac Cardiovasc Surg 1997;113(1):37-49.
Ricco A, Davis J, Rate W, Yang J, Perry D, Pablo J, et al.
Lung metastases treated with stereotactic body radiotherapy:
the RSSearch® patient Registry's experience.
Radiat Oncol 2017;12(1):35.
Jeremi? B, Videtic GM. Chest reirradiation with external
beam radiotherapy for locally recurrent non-small-cell lung cancer: a review. Int J Radiat Oncol Biol
Phys 2011;80(4):969-77.
Gressen EL, Werner-Wasik M, Cohn J, Topham A,
Curran WJ Jr. Thoracic reirradiation for symptomatic
relief after prior radiotherapeutic management for
lung cancer. Am J Clin Oncol 2000;23(2):160-3.
NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines ®) Non-Small Cell Lung Cancer
Version 2. 2018. Available at: https://www.nccn.org/
professionals/physician_gls/pdf/nscl.pdf. Accessed
Mar 13, 2020.
Videtic GM, Hu C, Singh AK, Chang JY, Parker W,
Olivier KR, et al. A Randomized Phase 2 Study Comparing
2 Stereotactic Body Radiation Therapy Schedules
for Medically Inoperable Patients With Stage I Peripheral
Non-Small Cell Lung Cancer: NRG Oncology
RTOG 0915 (NCCTG N0927). Int J Radiat Oncol Biol
Phys 2015;93(4):757-64.
Wahl RL, Jacene H, Kasamon Y, Lodge MA. From
RECIST to PERCIST: Evolving Considerations for
PET response criteria in solid tumors. J Nucl Med
2009;50 (Suppl 1):122S-50S.
Baumann P, Nyman J, Hoyer M, Wennberg B, Gagliardi
G, Lax I, et al. Outcome in a prospective phase II trial
of medically inoperable stage I non-small-cell lung
cancer patients treated with stereotactic body radiotherapy.
J Clin Oncol 2009;27(20):3290-6.
Timmerman R, Paulus R, Galvin J, Michalski J,
Straube W, Bradley J, et al. Stereotactic body radiation
therapy for inoperable early stage lung cancer. JAMA
2010;303(11):1070-6.
Takeda A, Kunieda E, Sanuki N, Aoki Y, Oku Y, Handa
H. Stereotactic body radiotherapy (SBRT) for solitary
pulmonary nodules clinically diagnosed as lung
cancer with no pathological confirmation: comparison
with non-small-cell lung cancer. Lung Cancer
2012;77(1):77-82.
Boyer MJ, Ricardi U, Ball D, Salama JK. Ablative Approaches
for Pulmonary Metastases. Thorac Surg Clin
2016;26(1):19-34.
Amendola BE, Amendola MA, Perez N, Wu X, Suarez
JB. Local failure after primary radiotherapy in lung
cancer: Is there a role for SBRT?. Rep Pract Oncol Radiother
2015;20(6):440-5.
Milano MT, Kong FS, Movsas B. Stereotactic body radiotherapy
as salvage treatment for recurrence of nonsmall
cell lung cancer after prior surgery or radiotherapy.
Transl Lung Cancer Res 2019;8(1):78-87.
Milano MT, Constine LS, Okunieff P. Normal tissue
toxicity after small field hypofractionated stereotactic
body radiation. Radiat Oncol 2008;3:36.
Milano MT, Mihai A, Kong FS. Review of thoracic reirradiation
with stereotactic body radiation therapy: A focus
on toxicity risks. Pract Radiat Oncol 2018;8(4):251-65.
Kang KH, Okoye CC, Patel RB, Siva S, Biswas T, Ellis
RJ, et al. Complications from Stereotactic Body
Radiotherapy for Lung Cancer. Cancers (Basel)
2015;7(2):981-1004.
Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M,
Gomi K, et al. Hypofractionated stereotactic radiotherapy
(HypoFXSRT) for stage I non-small cell lung
cancer: updated results of 257 patients in a Japanese
multi-institutional study. J Thorac Oncol 2007;2(7
Suppl 3):S94-100.
Onishi H, Araki T, Shirato H, Nagata Y, Hiraoka M,
Gomi K, et al. Stereotactic hypofractionated high-dose
irradiation for stage I nonsmall cell lung carcinoma:
clinical outcomes in 245 subjects in a Japanese multiinstitutional
study. Cancer 2004;101(7):1623-31.
Burdick MJ, Stephans KL, Reddy CA, Djemil T, Srinivas
SM, Videtic GM. Maximum standardized uptake
value from staging FDG-PET/CT does not predict
treatment outcome for early-stage non-small-cell lung
cancer treated with stereotactic body radiotherapy. Int
J Radiat Oncol Biol Phys 2010;78(4):1033-9.
Kohutek ZA, Wu AJ, Zhang Z, Foster A, Din SU, Yorke
ED, et al. FDG-PET maximum standardized uptake
value is prognostic for recurrence and survival after
stereotactic body radiotherapy for non-small cell lung
cancer. Lung Cancer 2015;89(2):115-20.
Sasaki R, Komaki R, Macapinlac H, Erasmus J, Allen
P, Forster K, et al. [18F]fluorodeoxyglucose uptake
by positron emission tomography predicts outcome
of non-small-cell lung cancer. J Clin Oncol
2005;23(6):1136-43.
Vahdat S, Oermann EK, Collins SP, Yu X, Abedalthagafi
M, Debrito P, et al. CyberKnife radiosurgery for
inoperable stage IA non-small cell lung cancer: 18Ffluorodeoxyglucose
positron emission tomography/
computed tomography serial tumor response assessment.
J Hematol Oncol 2010;3:6.
Bollineni VR, Widder J, Pruim J, Langendijk JA, Wiegman
EM. Residual ¹?F-FDG-PET uptake 12 weeks after
stereotactic ablative radiotherapy for stage I nonsmall-
cell lung cancer predicts local control. Int J
Radiat Oncol Biol Phys 2012;83(4):e551-e5.
Hoopes DJ, Tann M, Fletcher JW, Forquer JA, Lin PF,
Lo SS, et al. FDG-PET and stereotactic body radiotherapy
(SBRT) for stage I non-small-cell lung cancer.
Lung Cancer 2007;56(2):229-34.
Mohammed N, Grills IS, Wong CY, Galerani AP, Chao
K, Welsh R, et al. Radiographic and metabolic response
rates following image-guided stereotactic radiotherapy
for lung tumors. Radiother Oncol 2011;99(1):18-22.
Koshy M, Malik R, Weichselbaum RR, Sher DJ. Increasing
radiation therapy dose is associated with improved
survival in patients undergoing stereotactic body radiation
therapy for stage I non-small-cell lung cancer. Int J
Radiat Oncol Biol Phys 2015;91(2):344-50.
Dunlap NE, Larner JM, Read PW, Kozower BD, Lau
CL, Sheng K, et al. Size matters: a comparison of T1
and T2 peripheral non-small-cell lung cancers treated
with stereotactic body radiation therapy (SBRT). J
Thorac Cardiovasc Surg 2010;140(3):583-9.
Allibhai Z, Taremi M, Bezjak A, Brade A, Hope AJ,
Sun 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
Radiat Oncol Biol Phys 2013;87(5):1064-70.
Baumann P, Nyman J, Lax I, Friesland S, Hoyer M,
Rehn Ericsson S, et al. Factors important for efficacy
of stereotactic body radiotherapy of medically inoperable
stage I lung cancer. A retrospective analysis of
patients treated in the Nordic countries. Acta Oncol
2006;45(7):787-95.
Thompson M, Rosenzweig KE. The evolving toxicity
profile of SBRT for lung cancer. Transl Lung Cancer
Res 2019;8(1):48-57.
