Medical Imaging and Radiotherapy Journal (MIRTJ) 38 (1) 17
Case report
RADIOSURGERY FOR MULTIPLE BRAIN METASTASES IN 
NON-SMALL CELL LUNG CANCER – PARADIGM SHIFT
André LARANJA1,*, Dora GOMES1, Sofi a CONDE1, Artur AGUIAR1, Luísa ROLIM2, Luísa CARVALHO1, 
Andreia PIRES1 
1 Department of External Radiotherapy, Instituto Português de Oncologia Francisco Gentil, Porto, Portugal
2 Department of Radiotherapy, Instituto Português de Oncologia Francisco Gentil, Coimbra, Portugal
* Corresponding author: andrelaranja79@hotmail.com, andre.laranja@ipoporto.min-saude.pt
Received: 31. 5. 2021
Accepted: 8. 9. 2021
https://doi.org/10.47724/MIRTJ.2021.i01.a002
ABSTRACT
Purpose: The purpose of this paper is to present a case 
of multiple brain metastases treated with LINAC-based 
radiosurgery (SRS).
Materials and methods: Case report and a summary review 
of pertinent literature regarding SRS for multiple brain 
metastases.
Results / Case Study: This case presents a patient with non-
small cell lung cancer diagnosed with nine brain metastases 
who was treated with SRS. During follow-up, all brain lesions 
showed complete response with minimal impact on the 
patient’s quality of life.
Discussion and Conclusion: The role of SRS is expanding, 
and recent published trials have showed promising results 
supporting its use in patients with more than four brain 
metastases.  As our case suggests, SRS can be an eff ective and 
safe treatment for these patients and should be considered by 
physicians when they are presented with a similar case.
Keywords: Stereotactic; Radiotherapy; Radiosurgery; Brain 
metastases
Medical Imaging and Radiotherapy Journal (MIRTJ) 38 (1)
INTRODUCTION
Brain metastases (BM) from non-small cell lung cancer 
(NSCLC) occur in approximately 10% of patients at the time of 
diagnosis, and this proportion is even higher in patients with 
advanced-stage disease (approximately 30%) (1).  BM can lead 
to serious complications related to neurological deterioration 
and a diminished quality of life (QoL).
Treatment options include surgical resection, radiotherapy 
(RT) (whole-brain radiotherapy (WBRT) and, in selected 
patients, stereotactic radiosurgery (SRS)) or a combination 
of both. Historically, SRS has been reserved for patients with 
one to four BMs. However, over the last decade, this treatment 
modality has become more widely available, and evidence 
from recent clinical investigations has shown promising 
results supporting the use of SRS in patients with more than 
four BM (2,3,4). 
The authors present a clinical case report of a patient with 
NSCLC treated with SRS for nine BM, with a complete clinical 
response in all brain lesions.
MATERIALS AND METHODS
All the clinical information was based on medical records, 
imagiologic fi ndings, patient interview and physical 
examination. 
A Linear accelerator TrueBeamTM STx with 120 HD multileaf 
collimator was used for SRS delivery.
The authors conducted a brief search on Pubmed, SCOPUS 
and Clinical Key database, with MESH terms: “Stereotacic 
radiosurgery” and “multiple brain metastases”. The authors 
reviewed publications since 2010.
CASE STUDY
A 62-year-old man with a Karnofsky Performance Status (KPS) 
score of 100% was diagnosed in September 2012 with lung 
adenocarcinoma stage III-B according to the TNM staging 
system, 7th edition (5). The patient underwent concomitant 
chemoradiotherapy until October 2012. The chemotherapy 
regimen consisted of paclitaxel and carboplatin, and radiation 
therapy was administered at a dose of 66 Gy for the primary 
18 Medical Imaging and Radiotherapy Journal (MIRTJ) 38 (1)
tumour and regional lymph nodes. One month after RT, a 
follow-up CT showed disease progression in the lung, and 
the patient was treated with systemic chemotherapy with 
cisplatin and pemetrexed, followed by maintenance with 
pemetrexed until January 2014. Due to the local progression 
of the pulmonary lesions, pemetrexed was stopped and 
docetaxel was initiated until June 2014.  
In December 2018, the patient developed neurological 
symptoms (syncope, tremor, and speech disorders). After 
admission to the emergency room, he underwent brain 
computed tomography (CT), which revealed two ring-
enhancing lesions with surrounding oedema in the occipital 
and frontoparietal lobes. 
An additional brain Magnetic Resonance Imaging (MRI) was 
performed that revealed nine suspected lesions (shown in Fig. 
1, right column images): lesion 1 was 6 mm in the left side of 
the precentral gyrus; lesion 2 was 4 mm in the left side of the 
precentral gyrus; lesion 3 was 17.4 mm in the anterior left frontal 
lobe; lesion 4 was 20.8 mm in the left paramedian parietal-
occipital region; lesion 5 was 5 mm in the right paramedian 
occipital region; lesion 6 was a millimetric lesion in the right 
cerebellar hemisphere; lesions 7, 8, and 9 were millimetric 
lesions in the left cerebellar hemisphere. Lesions 1 through 5 
were associated with extensive surrounding oedema, causing 
a mass eff ect. MRI fi ndings, along with patient clinical history, 
were considered highly suggestive of BM. Steroid therapy was 
immediately initiated, and the patient was scheduled for SRS. 
For SRS treatment planning, a CT without contrast (slices of 1 
mm thickness), along with a brain gadolinium-enhanced MRI 
(1 mm slice thickness) were requested. All lesions were treated 
with LINAC-based SRS using a commercial stereotactic mask 
fi xation system in conjunction with the iPlan 4.1.1, Brainlab 
treatment planning system. Target volumes – Gross tumour 
volume (GTV), clinical target volume (CTV), planning target 
volume (PTV), and organs at risk were contoured on thin-slice 
(1 mm) gadolinium-enhanced T1-weighted axial MR imaging 
obtained 10 days prior to SRS and fused to the treatment 
planning CT. The GTVs were delineated as contrast-enhancing 
tumours demonstrated on MRI scans without CTV expansion. 
For all lesions, a 1 mm geometric expansion was created 
around the GTVs to generate the PTV. Linear accelerator 
TrueBeamTM STx with 120 HD multileaf collimator was used 
for treatment delivery, and all the lesions were treated using 
fl attening fi lter-free 6 MV photons (plan details are described 
Table 1 – Radiotherapy plan description
Volume 
(cm3)
Total Dose / 
Fractions Technique D98% CI GI Normal Brain
PTV lesion 1 and 2 1,4 24Gy / 1fr DA 23,3 Gy 1,35 5,36 V12Gy = 5,6 cm
3
PTV lesion 3 5,82 27Gy /3 fr1fr / day VMAT 26,4 Gy 0,97 4,43 V18Gy = 7,7 cm
3
PTV lesion 4 7,23 27Gy /3 fr1fr / day VMAT 26,3Gy 1,03 4,11 V18Gy = 11,8 cm
3
PTV lesion 5 0,46 24Gy / 1fr DA 21,7Gy 0,43 5,58
V12Gy = 3,8 cm
3
PTV lesion 7 0,39 24Gy / 1fr DA 22,8 Gy 0,77 5,9
PTV lesion 6 0,41 24Gy / 1fr DA 23,2 Gy 0,85 6,34
V12Gy = 8,0 cm
3PTV lesion 8 0,38 24Gy / 1fr DA 23,4 Gy 1,00 7,89
PTV lesion 9 0,36 24Gy / 1fr DA 22,0 Gy 0,47 6,67
Total  16,45
PTV: Planning target volume; fr: fraction; DA: Dynamic arcs; VMAT: Volumetric modulated arc therapy; CI: Conformity index; 
GI: Gradient index
Figure 1: Brain MRI images - lesions 1, 2 and 3. On the left MRI from 
January 2019 (before radiotherapy treatment) and on right the MRI 
from January 2021 (last imagiologic follow-up)
Le
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 1
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on
 2
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si
on
 3
Laranja A. et al./ Radiosurgery for multiple brain metastases in non-small cell lung cancer – paradigm shift
Medical Imaging and Radiotherapy Journal (MIRTJ) 38 (1) 19
Le
si
on
 4
Le
si
on
 7
 a
nd
 8
Le
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on
 5
Le
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on
 9
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 6
Figure 2: Brain MRI images - lesions 4, 5 and 6. On the left MRI from 
January 2019 (before radiotherapy treatment) and on right the MRI 
from January 2021 (last imagiologic follow)
Figure 3: Brain MRI images - lesions 7, 8 and 39. On the left MRI from 
January 2019 (before radiotherapy treatment) and on right the MRI 
from January 2021 (last imagiologic follow-up)
in Table 1). This treatment ended in January 2019, was well 
tolerated, and the patient did not experience headaches nor 
did he have any other neurological complaints.
The patient was then followed-up with periodic physical 
examinations and MRI imaging according to the protocols of 
our institution (3-4 month intervals for the fi rst year, 6 months 
for the second year, and then annually). At each visit, the 
neurological status and the severity of complications were 
scored according to the National Cancer Institute Common 
Toxicity Criteria for Adverse Events version 4.03 (6), and 
MRI scans were also performed and analysed by the same 
radiologist.
In April 2019, three months after SRS, all the cerebral lesions 
were smaller, as well as the surrounding oedema; however, 
there was disease progression in the lung and the patient 
began treatment. In September 2020, nine months after SRS, 
MRI showed complete radiologic response in all the nine brain 
lesions despite small residual gliosis. 
As of January 2021 (24 months after SRS), the patient had 
remained with complete response on brain MRI (shown in Fig. 
1-3, left images). At this time, the lung lesion had remained 
stable under pembrolizumab treatment, and the patient had 
remained highly functional (KPS 100%) without signifi cant 
neurological symptoms or other treatment toxicities detected.
DISCUSSION
The incidence of BM diagnosed in NSCLC patients has risen in 
recent years as a result of developments in imaging modalities, 
such as MRI, along with advances in systemic therapies, such 
as immunotherapy or targeted therapy (4). These refi nements 
increased the sensitivity of detecting smaller lesions during 
screening examinations and improved survival rates. 
Locoregional treatment options for BM have never been as 
diverse as they are now (WBRT, surgical resection, SRS, or a 
combination of treatment modalities) (1).
The fi rst investigations evaluating SRS were performed 
in patients with single lesion metastatic disease, either in 
combination with WBRT or as an alternative therapy to 
surgical resection. These results showed a lasting response 
to BM local control with minimal impact on the patients’ QoL 
(1,3). With recent awareness of the neurocognitive eff ects of 
WBRT, multiple studies have evaluated SRS combined with 
WBRT versus SRS alone for intracranial metastatic tumours. 
The results have been in favour of SRS as they have shown 
minimal neurocognitive decline and improved QoL, with no 
diff erences in overall survival (OS) (7). Current investigations 
confi rmed previous results and showed several other 
advantages of SRS over WBRT, including sparing healthy brain 
tissue, decreased time of treatment, improved tolerance to 
treatment, and reduced acute treatment-related toxicity (8).
Traditionally, SRS was used for patients with up to four BM, 
each lesion smaller than 3-4 cm, and it was usually performed 
in a single session (up to a maximum of fi ve sessions) under 
the guidance of real-time imaging (9). In fact, most of the 
previous studies used these values as reference cut-off s; 
however, current evidence in the literature has suggested a 
benefi t for patients with fi ve or more BM (4,10). A Japanese 
prospective study (11,12) included more than 1 000 patients 
Laranja A. et al./ Radiosurgery for multiple brain metastases in non-small cell lung cancer – paradigm shift
20 Medical Imaging and Radiotherapy Journal (MIRTJ) 38 (1)
divided into two groups of 2-4 and 5-10 brain metastases. 
Both groups were treated with SRS alone. In this non-
inferiority study, overall survival, local failure, distant in-brain 
recurrences, neurological death, and toxicity were found to 
be similar in both arms.  A retrospective cohort study showed 
no diff erence in survival between patients with > 10 and 
those with 2–9 brain metastases, all of whom underwent SRS 
monotherapy for all lesions (3). 
Regarding the factors that infl uence survival, studies 
suggested that the rate of new BM development, total brain 
tumour volume, and the number of metastases should be 
considered as survival predictors in patients treated with SRS 
(13,14). 
A multicenter retrospective study reported that patients 
treated with single-fraction SRS for > 4 BM, smaller total 
tumour volume, higher total dose, and lower volume of 
normal brain receiving >12 Gy were associated with increased 
survival (15). A single institutional retrospective study (16) 
included 1 017 patients with 1-10 BM treated with SRS and 
showed that tumour volume, KPS, and histology remained 
signifi cant for OS on multivariate analysis, whereas lesion 
number did not. In this study, regarding histology, NSCLC and 
the group “Other” (including small-cell lung cancer, colorectal, 
ovarian, and prostate cancer) had a worse outcome than 
breast cancer, melanoma, and renal cell carcinoma. However, 
a clear defi nition of survival predictors in this setting must be 
supported by a stronger level of evidence (17). 
Another signifi cant issue that is related to survival rate is the 
cost at which the patient’s survival is extended. One very 
recent study addressed this question by comparing health-
related QoL between patients treated with SRS with 1-4 
BM or 5-10 BM. Health-related QoL was assessed using the 
Functional Assessment of Cancer Therapy-Brain, a self-report 
questionnaire specifi c to patients with brain tumours. The 
results showed no statistical diff erences between the two 
groups, suggesting that SRS could be a useful tool for these 
patients when balancing disease control and QoL (18). 
CONCLUSION
The present case describes a successful approach for a patient 
with multiple BMs treated with SRS. Patients with multiple 
lesions, but a low overall disease volume, might be suitable 
candidates for SRS. When presented with a similar clinical 
case, all treatment options should be considered by physicians 
and they should also be individually analysed considering 
numerous specifi c factors such as patient’s performance 
status, comorbidities, lesion specifi cities (such as number and 
size of the BM), histopathologic features, and the extracranial 
tumour burden. Nevertheless, the authors believe that SRS 
should always be considered as a successful and eff ective 
approach with a few collateral eff ects.
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