State of the Art: Concise Review
Stereotactic Ablative Radiotherapy for Pulmonary
Oligometastases and Oligometastatic Lung Cancer
David Benjamin Shultz, MD, PhD,* Andrea Riccardo Filippi, MD,† Juliette Thariat, MD,‡
Francoise Mornex, MD, PhD,‡ Billy W. Loo Jr, MD, PhD,* and Umberto Ricardi, MD†
Abstract: An increasing body of experience suggests that oligometas-
tasis represents a minimal metastatic state with the potential for cure or
prolonged survival in selected patients treated with radical local therapy
to all identified sites of disease. The main clinical scenarios managed
by thoracic oncology specialists are pulmonary oligometastases from
primary malignancies of other anatomic sites and primary lung cancer
with oligometastases to lung or other organs. Surgery has been a main-
stay of treatment in these situations, with remarkably favorable out-
comes following pulmonary metastasectomy in well-selected patient
cohorts. As with early stage lung cancer in patients who are medically
inoperable, stereotactic ablative radiotherapy is emerging as a promi-
nent local treatment option for oligometastatic disease. We review the
role and clinical experience of stereotactic ablative radiotherapy for
pulmonary oligometastases and oligometastatic lung cancer.
(J Thorac Oncol. 2014;9: 1426–1433)
M etastatic disease in solid malignancies has historically
been considered incurable, and the role of local thera-
pies including radiation therapy has primarily been pallia-
tive. Though metastases are generally widely disseminated, a
minimal metastatic state, dubbed oligometastasis,1,2 has been
recognized, with a distinct natural history and a prognosis
intermediate between that of localized and widely metastatic
disease.1–6 Oligometastasis may be loosely defined clinically as
a limited number of metastatic lesions in a limited number of
organs, generally identified by imaging, suggesting the poten-
tial benefit of radical local therapies. This definition has evolved
*Department of Radiation Oncology, Stanford University School of Medicine,
Stanford, CA; †Department of Oncology, University of Torino, Italy; and
‡Département de Radiothérapie, Centre Hospitalier Lyon Sud, Pierre
Bénite, France.
David Benjamin Shultz and Andrea Riccardo Filippi contributed equally to
this article.
Disclosure: B.W.L. received research support from Varian Medical Systems and
RaySearch Laboratories. All other authors declare no conflict of interest.
Address for correspondence: Billy W. Loo, Jr., MD, PhD, Department of
Radiation Oncology and Stanford Cancer Institute, Stanford University
School of Medicine, 875 Blake Wilbur Drive, Stanford, CA 94305.
E-mail: BWLoo@standford.edu; or Umberto Ricardi, MD, Department
of Oncology, University of Torino, c.so Bramante 88, 10123 Torino, Italy.
E-mail: umberto.ricardi@unito.edu
DOI: 10.1097/JTO.0000000000000317
Copyright © 2014 by the International Association for the Study of Lung
Cancer
ISSN: 1556-0864/14/0910-1426
1426 Journal of Thoracic Oncology  ®  •  Volume 9, Number 10, October 2014
with advances in diagnostic tools and systemic and local treat-
ments. Improved imaging, such as with whole body fluorode-
oxyglucose positron emission tomography (PET), has increased
the likelihood of detecting limited metastasis. Furthermore, it is
thought that the improved effectiveness of systemic therapy for
occult microscopic disease, such as with individualized targeted
therapy, may increase the chance of cure following ablation of
limited imaging-detected metastases.
Aggressive local treatment, with the goal of ablating all
known sites of disease, is an emerging treatment strategy for
oligometastatic disease. However, determining the advantages
or superiority of this approach compared to palliative systemic
therapy or best supportive care is challenging because of the
predominantly retrospective nature of existing data, which has
raised substantial concerns for selection bias (performance
status, disease-free interval, small metastatic burden) despite
the use of techniques such as propensity score analyses. The
ability to predict rapidly versus slowly progressive disease7
would be of major importance for the design of customized
therapeutic strategies and for prospective clinical trials.5,8
Perhaps the best evidence for a local ablative approach
for oligometastatic disease comes from treatment, most com-
monly surgery, of lung or liver oligometastases from colorectal
cancer, performed sequentially following systemic treatment.9
This approach has since been extended to other cancer types.
The two clinical scenarios most commonly treated by thoracic
oncology specialists are pulmonary oligometastases from
non-lung primary malignancies and primary lung cancer with
or without oligometastases to the lung.
Stereotactic ablative radiotherapy (SABR), also known as
stereotactic body radiotherapy, is a rapidly emerging technique
for the treatment of oligometastatic disease. SABR’s role in the
treatment of stage I lung cancer in patients is well established
for inoperable patients,10 while for patients who can tolerate
surgery, lobectomy is the standard of care. For a third category
of patients, who are considered at high risk for complications
from a lobectomy but who might tolerate sublobar resections
or other invasive procedures such as SABR or radiofrequency
ablation, there is a lack of consensus regarding appropriate
treatment, and, as with the comparison between lobectomy and
SABR, this issue has only been explored retrospectively.11 The
attractiveness of SABR in oligometastatic disease is due to its
feasibility in an ambulatory setting, low side-effect profile,
and efficacy.12,13 SABR may be performed sequentially with
systemic therapy and is delivered in a small number of frac-
tions (usually ≤5), varying in size from 5 to more than 20 Gy
Journal of Thoracic Oncology  ®  •  Volume 9, Number 10, October 2014
each.14–18 Here, we review the use of SABR for the treatment
of pulmonary oligometastases and oligometastatic lung cancer.
PULMONARY OLIGOMETASTASES
Lessons from the Surgical Experience
In 1997, the “International Registry on Lung Metastases,”
a comprehensive research network among 18 major European
and North American thoracic surgery departments, reported the
results of 5206 lung metastasectomies, with 4572 (88%) com-
plete resections. The primary tumor was epithelial in 2260, sar-
coma in 2173, germ cell in 363, and melanoma in 328 patients.19
The actuarial survival after complete resection was 36% at 5
years, 26% at 10 years, and 22% at 15 years (median survival:
35 months); the corresponding values for incomplete resection
were 13% at 5 years and 7% at 10 years (median survival: 15
months). Among complete resections, the 5-year survival was
33% for patients with a disease-free interval (DFI: time between
initial diagnosis and onset of lung metastatic disease) below 11
months and 45% in patients with a DFI longer than 36 months;
moreover, 5-year survival was superior for patients with single
lesions (43% vs. 27%). These findings suggested a potentially
curative role for surgery in a subset of metastatic patients, such
as those with a completely resected single lesion (R0) and
extended DFI. A recent large single-institution series confirmed
these factors as prognostic,20 with a survival projection at 2 and
5 years after complete resection (achievable in 85% of patients)
of 74% and 46%, respectively. As a result of these findings,
internationally accepted selection criteria for lung metastastec-
tomy are good performance status, absence of extra-pulmonary
metastases, control of the primary tumor, possibility of com-
plete resection, and adequate respiratory function.21 All com-
prehensive series reported thus far comprise multiple primary
tumors (e.g., epithelial, mesenchymal, germ cell tumors, and
melanoma) and, among different epithelial tumors, histology
has not been shown to be a significant prognostic factor. That
being said, there are several reports from smaller series describ-
ing the results of surgical metastasectomy for colorectal can-
cer metastases. In a recent systematic review, Schlijper et al.22
included 23 surgical reports, selected by a minimum follow-up
of 24 months and a minimum of 50 patients, without regard to
previous therapies, four of which were prospective studies. In
this report, 2- and 5-year survival for metastasectomy ranged
from 64% to 88% and 29% to 71.2%, respectively.22
Role for SABR
SABR is an ideal modality for treating pulmonary metas-
tases with the goal of achieving high rates of tumor control with
minimal morbidity, noninvasively (Fig. 1). The use of SABR in
treating metastatic pulmonary nodules was a natural extension
of its established role in the treatment for early stage non–small-
cell lung cancers (NSCLC) not amenable to surgical resection.
In oligometastatic disease, pulmonary lesions treated with
SABR have a 1-year local control rate of 70% to 95%12,18,23–28; a
more limited number of studies, reporting single-fraction sched-
ules, showed similar local control rates, especially for smaller
tumors.29–31 All published series included a broad spectrum of
different primary tumors, with the most represented histological
Copyright © 2014 by the International Association for the Study of Lung Cancer
SABR for Pulmonary Oligometastases and OLC
FIGURE 1.  Stereotactic ablative radiotherapy (SABR) for oligo-
metastatic lung cancer. A 58-year-old woman treated with SABR
for 2 lung metastases from colorectal caner (26 Gy in a single
fraction each, prescribed to the 80% isodose line, over 2 days).
subtypes being colorectal and lung cancer. Table 1 summarizes
the results of clinical trials published over the last 10 years. The
predominant clinical presentation was a single lung metastasis,
with more limited reports of patients with two to five pulmo-
nary nodules. Siva et al.32 reviewed several studies on SABR for
lung metastases, with a total of 488 patients treated with a wide
range of technical approaches and different dose-fractionation
schedules, and demonstrated a 2-year weighted overall survival
of approximately 50%. Furthermore, in a prospective pilot study
on oligometastatic patients (<5 lesions), survival at 3 years was
around 30% and at 5 years did not exceed 25%.5
Few consistent prognostic factors have emerged from
various studies to guide appropriate patient selection for
the treatment of oligometastatic pulmonary tumors. In two
sequential reports by Milano et al.3,5 that included oligomet-
astatic patients with less than five lesions in various organs
including lung, the subgroup of breast cancer patients experi-
enced superior rates of survival,3 while among non-breast epi-
thelial subtypes, no significant differences were recorded. DFI
(here defined as the interval between the initial diagnosis and
the start of a local therapy for lung lesions) appears to have
an impact for SABR, but results are unclear. Norihisa et al.18
found that DFI longer than 3 years was associated with better
overall survival, and Filippi et al.29 reported that patients with
a DFI longer than 2 years had better cancer-specific survival,
on both univariate and multivariate analyses. Conversely,
other studies failed to show a survival difference according
to DFI.23,24 Tumor volume appears to be prognostic, with bet-
ter outcomes in smaller tumors (<3.3 cc for gross tumor vol-
ume).23 Many patients included in these retrospective series,
especially those with more than two pulmonary nodules,
also received systemic therapy, either prior to or immediately
after SABR, or at the time of a second progression. Few have
been treated with further local therapies (including a second
SABR) for oligometastatic recurrence or progression and it is
difficult to estimate the contribution of these factors on sur-
vival. Reported 1- or 2-year progression-free survival (PFS)
rates following SABR are highly variable, ranging from 25%
to 70% and reflect the intrinsic heterogeneity of this patient
1427
Shultz et al. Journal of Thoracic Oncology  ®  •  Volume 9, Number 10, October 2014

TABLE 1.  Clinical Trials of Stereotactic Ablative Radiotherapy for Pulmonary Oligometastatic Disease
No. of No. of Median Follow-
Reference Patients Targets Radiation Dose Up (Months) Outcomes
Fractionated/Single Fraction SABR
Onimaru et al.27 20 32 48 Gy/8 fx, 60 Gy/8 fx 18 48% 2-yr OS, 69.6% 3-yr LC for 48 Gy,
100% 3-yr LC for 60 Gy
Yoon et al.26 53 80 30 Gy/3 fx, 40 Gy/4 fx, 48 Gy/4 fx 14 70% LC for 30 Gy, 77% for 40 Gy,
100% LC for 48 Gy, 51% all 2-yr OS
Okunieff et al.28 50 125 50 Gy/10 fx, 48 Gy/6 fx, 57 Gy/3 fx 18.7 91% 3-yr LC, 50% 2-yr OS
Norihisa et al.18 34 43 48 Gy/4 fx, 60 Gy/5 fx, at isocenter 27 90% 2-yr LC, 84% 2-yr OS
Brown et al.25 35 69 5 Gy/1 fx to 60 Gy/4 fx 18 77% crude LC, 72.5% 2-yr OS
Rusthoven et al.12 38 63 60 Gy/3 fx at 80% 15.4 96% 2-yr LC, 39% 2-yr OS
Wulf et al.24 41 51 30 Gy/3 fx, 36 Gy/3 fx, 26 Gy/1 fx at 100% 13 80% 1-yr LC, 33% 2-yr OS
Ricardi et al.23 61 77 45 Gy/3 fx, 26 Gy/1 fx at 80% 20.4 89% 2-yr LC, 66.5% 2-yr OS
Single Fraction SABR Only
Hof et al.30 61 71 12 to 30 Gy at isocenter 14 65.1% 2-yr OS
Filippi et al.29 67 90 26 Gy at 80% 24 88.1% 2-yr LC, 70.5% 2-yr OS

population.23–26 A recent retrospective study, to the best of our
knowledge the first designed to compare surgery with SABR
for pulmonary oligometastases, suggested comparable rates of
local control and PFS.33 In this single institutional experience
of consecutive patients, SABR was offered as a second choice
to patients not eligible for surgery. Most surgical patients
(n = 68) had colorectal cancer (57%) or sarcoma (27%), while
most SABR patients (n = 42) had colorectal (74%) or NSCLC
(14%). With a median follow-up of 43 months, overall survival
at 5 years was 41% for metastasectomy and 49% for SABR,.
These results are promising, but the absence of prospective
trials, large retrospective studies with adequate follow-up,
meta-analyses, or collaborative network observational studies
hampers our ability to evaluate the role of SABR in this set-
ting. Metastasectomy should still be regarded as the standard
therapeutic option for pulmonary oligometastases, as SABR
has not yet been evaluated in a large prospective study.
Radiobiological and Technical Aspects
The biological mechanisms of radiation-induced tumor
cell death at fraction sizes greater than 8 to 10 Gy are likely
more complex than previously thought. In addition to DNA
damage, experimental models suggest that endothelial mem-
brane alterations occur after high radiation doses, inducing
sphingomyelin-mediated endothelial apoptosis, which lead to
microvasculature dysfunction.34 A combination of radiation-
induced endothelial damage and direct tumor cell killing may
explain the “tumor ablative” effect of stereotactic radiotherapy.
Data from the treatment of primary lung cancer suggest that
biologically effective doses higher than 100 Gy (with tumors
α/β = 10 Gy) are needed to achieve a tumor control probabil-
ity of more than 90%.35 This prescription criterion can be rea-
sonably extended to metastatic lung lesions. However, some
uncertainties exist, mainly related to the variability in dose
calculation algorithms and dose prescription conventions (in
some studies, biologically effective dose values are calculated
at the periphery, while in others, the isocenter). More recent
data support the effectiveness of lower doses (prescribed to
the planning target volume margin) in primary NSCLC, using
a volume-adapted dose/fractionation schedules (with a mini-
mal dose of 80 Gy in 2 Gy equivalents).36
Technical considerations related to simulation, plan-
ning, and delivery, continue to evolve, including technical
advances in patient immobilization (frameless devices), set-
up error correction (improved image guidance), respiratory
motion management (respiratory gating, four-dimensional
CT, tumor tracking), and treatment planning. Specific dose
constraints for thoracic normal structures, adapted for differ-
ent fractionation schedules, are also widely available.37
Ongoing Trials
Current clinical trials evaluating the role for surgery
or SABR for oligometastatic cancer include patients with a
heterogeneous group of primary tumors. PulMiCC38 is a ran-
domized trial comparing surgery to active surveillance for pul-
monary oligometastases in colorectal cancer. The COMET39
phase II trial randomizes patients to standard of care versus
standard of care plus SABR for all known sites of metastatic
and primary disease (bone, adrenal, lung, brain, and liver).
The primary endpoint is overall survival, and secondary end-
points include quality of life, toxicity, PFS, local control, and
number of cycles of further systemic therapy. The SAFRON40
trial is a phase II randomized study comparing stereotactic
radiotherapy and radiosurgery in oligometastatic pulmonary
metastases. The primary endpoints are safety and toxicity.
Finally, NCT0118563941 is a single-arm Phase II clinical trial,
evaluating the role for SABR in NSCLC patients with a maxi-
mum of 5 metastatic sites, following primary chemotherapy.
These innovative studies will better clarify the efficacy of local
ablative strategies for the treatment of oligometastatic disease.
OLIGOMETASTATIC NSCLC AND SABR
Definition of Oligometastatic NSCLC
Definitive therapy for early stage NSCLC, through surgery
or SABR, achieves 5-year survival rates in excess of 70%.42,43

1428 Copyright © 2014 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology  ®  •  Volume 9, Number 10, October 2014
Conversely, disease that has spread to regional lymph nodes, treated
with chemotherapy in combination with either surgery, radiother-
apy, or both, is difficult to eradicate and Stage IV disease treated
exclusively with chemotherapy is considered incurable, with
median survival rates of 13–14 months.44,45 Recently, oligometa-
static NSCLC (OLC), presenting with one to five synchronous or
metachronous metastatic lesions, has emerged as a putatively dis-
tinct disease state.46 Locally ablative therapies are often used to
treat OLC; however, the subset of patients within the spectrum of
OLC who benefit from these interventions to metastatic sites or the
primary lesion has not been conclusively identified. These issues
are reflected by the heterogeneous survival outcomes reported in
several retrospective and a limited number or prospective studies.
One example of the latter, a single-arm phase II study, enrolled 39
patients presenting with stage IV disease with four or less synchro-
nous sites of distant metastasis.47 The primary lesion was treated
with radiotherapy alone or in combination with chemotherapy, and
all sites of distant metastasis were treated with surgery or abla-
tive radiotherapy. Median survival was 13.5 months, though six
patients were progression free after 2 years. Within the larger body
of retrospective literature, median survival among OLC patients
with controlled primary tumors in a recent systematic review
was 19 months and aggressive treatment to the primary tumor
improved OS, supporting the hypothesis that OLC represents a
clinically distinct and potentially curable disease.48 Currently, the
NCCN recommends surgical resection or SABR as an option for
NSCLC presenting or progressing with solitary sites of metastasis
to the brain or adrenals, though in the latter case only when the lung
cancer is considered curable based on T and N staging.49
The Role for SABR
The role for SABR, as an alternative to surgery, in the
definitive management of early stage lung cancers, has been
well established. Although lobectomy remains the standard of
care for patients who are surgical candidates, in patients who
are medically inoperable, SABR provides primary tumor con-
trol rates that are comparable to lobectomy.10 SABR for primary
early stage lung cancer is definitive and differs from radio-
therapy for advanced stage but potentially curable disease (T3,
node positive), in that a smaller number of fractions (1–8) are
used to deliver larger per fraction doses to the primary tumor
only, without chemotherapy. Identical techniques can be used to
ablate metastatic tumors within or outside of the lungs in OLC.
Brain Metastases
The majority of published studies of OLC have described
the outcomes of patients with resected solitary brain metasta-
ses.48 Compared with stereotactic radiosurgery (SRS), con-
ventional surgery has the advantage of providing pathologic
confirmation of metastatic disease and imparts superior rates of
local control for larger tumors compared with SRS.50 However,
adjuvant radiation to the resection cavity using SRS or whole
brain radiotherapy (WBRT) is required following resection to
ensure acceptable rates of local control.51,52 SRS has the advan-
tage of being able to treat unresectable tumors, easily treating
multiple tumors in different regions of the central nervous sys-
tem (CNS) in a single course, of imparting acceptable rates
of local control for small- to medium-sized tumors using a
Copyright © 2014 by the International Association for the Study of Lung Cancer
SABR for Pulmonary Oligometastases and OLC
single modality, for being noninvasive, and, finally, is less toxic
than whole brain irradiation (Fig. 2).53 The survival benefit of
radiosurgery has been confirmed for a single brain metasta-
sis in a randomized Phase III clinical trial, and in that same
study, improved functional autonomy was observed in patients
with one to three brain metastases.54 In this regard, Flannery
et al.55 described 42 patients with OLC treated for a solitary,
synchronous brain metastasis. Patients had stage I–III thoracic
disease and slightly more than half were treated definitively
in the chest with chemoradiotherapy with or without surgery.
Fourteen patients had node negative T1 or T2 disease; however,
a subset analysis describing their outcomes was not reported.
For 26 patients whose thoracic disease was treated definitively,
median OS was approximately 26 months, twice that of patients
whose thoracic disease was treated with chemotherapy alone.
For their CNS tumors, all patients were treated definitively with
SRS. In all but five cases, patients died due to progression of
disease outside of the CNS, suggesting that an aggressive local
approach to brain metastasis in patients who can tolerate defini-
tive treatment for their primary disease may be appropriate.
The question of whether adjuvant WBRT should be
added to local ablative therapies to target subclinical lesions
is unresolved. WBRT improves intracranial tumor control
but carries an increased risk of neurotoxicity and may limit
available salvage options. A recently completed EORTC study
22952–26001 showed that, as with previous phase III random-
ized trials, adjuvant WBRT (after surgery or radiosurgery in
patients with one to three brain metastases) reduces intracra-
nial events and neurologic death, but fails to improve the dura-
tion of functional independence or overall survival.56
Lung Metastases
As described in preceding sections, SABR is an effective
means of treating pulmonary metastases.12 In the case of OLC,
it is often not possible to determine whether one or both lung
lesions represent primary lesions. If one or more lesions are
presumed to be metastatic, according to the AJCC 2009, lesions
in the ipsilateral or contralateral lung designate T4 or M1a
classifications, respectively, in both cases indicating a better
prognosis than extrapulmonary metastatic disease.57 Voltolini
et al. described 43 patients treated for NSCLC with synchro-
nous multiple pulmonary tumors that were completely resected,
60% of which were of identical histology, most often by wedge
resection. As high as 86% of patients had a total of two lesions
and 60% underwent staging PET scans. Median survival was 32
months. On multivariate analysis, only node-positive disease or
surgery prior to 2000, when PET was incorporated into routine
staging, was associated with decreased survival.58 Assuming
comparable rates of local control from SABR versus surgery,59
and adequate regional lymph node staging from PET-CT,60
treatment of patients with OLC restricted to lung metastasis
with SABR appears to be a reasonable option.
Adrenal Metastases
Numerous small retrospective series have described out-
comes following resection of solitary adrenal metastases in OLC
and a recent systematic review reported the results of those stud-
ies, separately describing the cohort of patients who were treated
1429
Shultz et al. Journal of Thoracic Oncology  ®  •  Volume 9, Number 10, October 2014

FIGURE 2.  Stereotactic radiosurgery (SRS) for oligometastatic non–small-cell lung cancer (NSCLC). A 63-year-old man with
initial stage III NSCLC treated 9 months previously with chemoradiation developed sudden onset seizures with left facial twitch-
ing and distortion, followed by jerking of the left arm and leg and loss of consciousness. Magnetic resonance imaging (MRI)
revealed a single lesion in the left temperoparietal region measuring 16 × 12 × 13 mm. This lesion was subsequently targeted
using a noncoplanar technique with 20 Gy delivered to the 80% isodose line in a single fraction.

for solitary adrenal metastases that presented synchronously with
the primary lung tumor.61 Interestingly, a comparison of median
survival favored metachronous over synchronous metastases (12
months vs. 31 months); however, 5-year survival rates were com-
parable, at approximately 25%. A recent report described the use of
SABR for treating 13 OLC patients with a solitary adrenal metas-
tasis using doses that ranged from 20 to 40 Gy delivered in five
fractions. Median PFS was 12 months, median OS was 23 months,
and the crude rate of local control was 77%.62
Tyrosine Kinase Inhibitors and
Oligoprogressive Disease
Patients with metastatic lung cancer driven by epider-
mal growth factor receptor (EGFR) mutations or anaplastic
lymphoma kinase gene rearrangements that are treated
with the tyrosine kinase inhibitors (TKI), erlotinib, gefi-
tinib, afatinib,or crizotinib, have superior rates of survival
compared to patients with cancers without these mutations
treated with cytotoxic chemotherapies.63–66 Weickhardt et al.67
reported a single institution retrospective study of 25 patients
who developed oligoprogressive disease while being treated
with either erlotinib or crizotinib monotherapy in the CNS
alone or with four or fewer extracranial metastases. Patients
were treated with SABR, SRS, WBRT, or surgery and main-
tained on that same drug. This strategy was associated with a
median of six additional months before a second progression.
In a similar study, 18 patients with EGFR-mutant, non-CNS,
oligoprogressive disease received ablative treatment while

1430 Copyright © 2014 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology  ®  •  Volume 9, Number 10, October 2014
TABLE 2.  Ongoing Clinical Trials Examining the Role for Surgery or SABR for Oligometastatic Cancer
Study Design Eligibility
PulMICC 38
Randomized Pulmonary metastases from colorectal cancer
phase II
SABR-COMET39 Randomized All treatable metastatic sites; maximum of three
phase II tumors to any single organ system; controlled
primary tumor
SAFRON II40 Randomized A maximum of three metastases to the lung from
phase II any nonhematological malignancy
NCT0118563941 Phase II NSCLC with ≤5 metastatic sites, involving lung,
liver, adrenal, or spinal lesions; if primary
untreated, must have three mets
NCT0172516572 Randomized Three or less metastases from NSCLC
phase II
continuing TKI monotherapy. Median time to progression
was 10 months and median OS following first local treatment
was 41 months.68 Neither study contained subset analyses of
patients treated with SABR. It should be noted that oligopro-
gressive and oligometastatic disease are similar but distinct
entities; the former implies a limited number of new meta-
static lesions in a patient with disease that is otherwise con-
trolled. Furthermore, it is not considered standard of care for
patients with NSCLC that has progressed on TKI therapy to
continue that same drug, although variations to this approach
will be tested in new or ongoing trials, in which SABR is not
a component.69,70
Future Trials and Conclusions
Despite promising results from several retrospective
studies and limited prospective data, randomized evidence that
could eliminate the specter of selection bias or support stan-
dardized treatment strategies for oligometastatic cancer with
SABR or other local ablative therapies is lacking (Table 2).
A randomized Phase II trial, initiated at the University of
Chicago,71 was recently closed due to slow accrual. At least
one ongoing Phase II multiinstitutional trial is randomizing
patients with OLC to chemotherapy followed by local ablative
therapy to sites of metastasis (radiation or surgery) versus fur-
ther systemic therapy or surveillance.72 Another similar trial
using radiation alone recently completed accrual.73 We await
the results from these and other ongoing randomized control
trials to assess the value of SABR in the treatment of pulmo-
nary oligometastases and OLC.
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