Chung, J.B.

Eom, K.Y.

Hong, J.

Kim, I.A.

Kim, J.S.

Kim, K.S.

Seok, J.Y.

Wee, C.W.

Elsevier - Publisher Connector 

ESTRO 35  2016                                                                                                                                                  S301 
________________________________________________________________________________ 
5.2-11.5%), again with high heterogeneity (I2=81.0%) among 
studies. 
 
Conclusion: All included studies have shown some 
limitations: most of them were retrospective and all were 
non-comparative; many of them were carried out in absence 
of a rigorous methodology and only few reported a measure 
of variability for the primary endpoint. Despite these 
limitations, we can conclude that SRS appears safe and 
effective treatment for intracranial meningioma. 
 
PO-0642  
Radiosurgery without whole brain radiotherapy in brain 
metastases from non-small cell lung cancer 
P. Anselmo
1"S. Maria" Hospital- Terni, Radiation Oncology Centre, 
Oncology Department, Terni, Italy 
1, L. Chirico1, M. Muti1, M. Basagni1, F. Trippa1, R. 
Rossi1, L. Draghini1, F. Arcidiacono1, M. Italiani1, M. Casale1, 
S. Fabiani1, C. Giorgi2, E. Maranzano1 
2"S. Maria" Hospital- Terni, Oncology Department, Terni, 
Italy 
 
Purpose or Objective: patients (pts) with 1-4 brain 
metastases (BM) from non-small cell lung cancer (NSCLC) 
submitted to radiosurgery (SRS) alone were retrospectively 
evaluated. 
 
Material and Methods: 130 pts with 207 BM were identified. 
Pts were treated with a 5-MV linear accelerator fitted with a 
commercial dynamic μMLC. Doses were prescribed to 
isocentre so that at least the 90% isodose line encompassed 
the target volume. Doses were chosen according to maximum 
diameter of the tumor as suggested by RTOG Protocol 90-05. 
Male/female ratio was 90/40, median age was 64 years 
(range, 31-86). Median KPS was 100% (range, 70-100). 42/130 
(32%) pts had extracranial metastases, 83 (64%) pts had a 
controlled systemic disease, and 47 (36%) progressive 
disease. Neurologic functional score was generally good (NFS 
= 0), and only 15 (11.5%) pts had an NFS = 3 or 4. Relapse was 
defined “in-field” when more than 95% of the recurrence 
volume was within the original 50% isodose, and “out-field” 
in the other cases.  
 
Results: In 82 (63%) pts there was only one BM, in remaining 
48 (37%) 2-4 BM with a median volume of 0.8cc (range, 0.09-
25) Median prescribed dose was 23 Gy (range, 12-25). At a 
median follow-up of 67 months (range, 24-110), 123 (95%) pts 
with 197 (95%) BM were evaluable. Local control, evaluated 3 
months after SRS, was obtained in 95% of lesions: there were 
complete remission in 50 (25%), partial remission in 77 (39%), 
stable disease in 62 (31%), and progression in 13 (5%) BM. 
During follow up, 63 (51%) pts had no brain progression of 
disease, 11 (9%) had in-field relapse, 40 (33%) out-field 
relapse, and 9 (7%) in- and out-field relapse. Of 60 (49%) 
relapsing pts, 37 (62%) were retreated: 19 with SRS, 15 with 
whole brain radiotherapy (WBRT), 2 with fractionated 
stereotactic radiotherapy, and 1 with surgery and WBRT. No 
SRS-induced late toxicity was registered. At the time of 
analysis, 119/123 patients (97%) had died, 40 (34%) for brain 
progression, 72 (60%) for systemic progression and 7 (6%) for 
non-oncological causes. The median overall survival was 13 
months, deaths from brain progression occurred after a 
median time of 51 months, while from systemic progression 
after 19 months. 
 
Conclusion: SRS without upfront WBRT is an effective 
treatment of BM from NSCLC. Since that our results are 
similar to the best published data on SRS plus WBRT, SRS 
alone could be considered the treatment of choice in this 
setting. 
 
PO-0643  
Stereotactic hypofractionation in combination with 
radiosurgery in the treatment of brain metastases 
P. Ivanov
1International Institute of Biological Systems, Radiosurgery, 
Saint-Petersburg, Russian Federation 
1, I. Zubatkina1, G. Andreev1 
 
Purpose or Objective: To estimate the clinical results of 
hypofractionated stereotactic radiotherapy (HSR) alone or in 
combination with stereotactic radiosurgery (SRS) for the 
treatment of brain metastases using different radiation 
devices, which provide precise delivery of a high radiation 
dose to the target. 
 
Material and Methods: Between November 2010 and July 
2015, 257 patients with brain metastases were treated by 
HSR alone or simultaneous application of two stereotactic 
radiation techniques (SRS plus HSR) at the Radiosurgical 
Centre of IIBS (Saint Petersburg, Russia). Radiation treatment 
was performed with Gamma Knife 4C and Perfexion (Elekta 
AB, Stockholm, Sweden), Cyber Knife (Accuray, Sunnyvale, 
CA, USA) and linear accelerator TrueBeam STX (Varian 
Medical Systems, Palo Alto, CA) equipped with the BrainLAB 
Exac Trac system. The indications for HSR were determined 
by the presence of large volume lesions or proximity to 
critical brain structures. Patients with multiple brain 
metastases were subjected to a combination of HSR and SRS. 
Radiation schemes were selected depending on the number 
of metastases, size, location, proximity to critical brain 
structures, histological type of primary cancer and the 
patient’s general condition. SRS was performed with the 
marginal dose of 18 – 24 Gy at 40 – 90 % isodose and HSR was 
performed with the total dose of 24, 27 or 30 Gy in 3 
fractions. Following treatment the patients underwent 
control MRI examination with standard protocols (2 mm T2 
and 1 mm T1 with double contrast enhancement) at 8 weeks 
and then every 3 months. The median follow-up period was 6 
months. 
 
Results: The study revealed that the application of 
hypofractionated stereotactic radiotherapy for the treatment 
of large volume or critically located brain metastases 
provides a high level of local control (12-month local control 
rate was 83 %). Complications in the form of radiation 
necrosis occured in 15 % of patients at a median of 6 months 
after treatment. The median overall survival for the entire 
patient cohort was 9 months. There was no statistically 
significant difference in the median survival of the patients 
receiving HSR alone and those receiving HSR plus SRS. The 
best results were obtained in patients belonging to the first 
RPA-class who achieved two-year survival in 70 % of the 
cases. The advantage of combining SRS and HSR is the 
possibility to deliver high radiation doses to large volume 
lesions, without exceeding the brain’s tolerance. HSR allows 
one to achieve a rapid shrinkage of large volume tumors, 
which considerably improves the patient’s neurological 
condition. 
 
Conclusion: High-dose stereotactic radiation is a safe and 
effective method for controlling brain metastases. A 
combined application of SRS and HSR is a viable treatment 
strategy for patients with multiple brain metastases who 
have at least one large lesion or a lesion located in/near 
critical brain structures. 
 
PO-0644  
Hippocampal sparing brain radiotherapy using VMAT to the 
primary brain tumour 
K.S. Kim
1Seoul National University College of Medicine, Radiation 
Oncology, Seoul, Korea Republic of 
1, C.W. Wee1, J.Y. Seok2, J. Hong2, J.B. Chung2, K.Y. 
Eom2, J.S. Kim2, I.A. Kim2 
2Seoul National University Bundang Hospital, Radiation 
Oncology, Seongnamsi, Korea Republic of 
 
Purpose or Objective: We hypothesized that hippocampal-
sparing radiotherapy using volumetric modulated arc therapy 
(VMAT) could preserve cognitive function of the patients with 
primary brain tumor treated with brain radiotherapy.  
 
Material and Methods: We prospectively collected patients 
who were diagnosed with primary brain tumor and treated 
with brain radiotherapy from March 2014 to April 2015. Brain 
radiotherapy was delivered using VMAT planning technique 
with inclined head position. Optimization criteria for the 
S302                                                                                                                                                    ESTRO 35 2016 
______________________________________________________________________________________________________ 
hippocampus dose was Dmax less than 17Gy without 
compromising the coverage of planning target volume (PTV) 
and other organs at risk were prioritized over hippocampal 
constraint. The mini-mental state examination (MMSE) and 
Seoul verbal learning test for total recall, delayed recall and 
recognition (SVLT-TR, DR, R) were performed at baseline and 
at 7 and 13 or 16 months after radiotherapy.  
 
Results: A total of 41 patients were accrued. Median age was 
48 years (range 26-76) and 51.2 % of the patients were male. 
Eighteen patients (43.9%) had WHO grade I or II tumor 
whereas 23 patients (56.1%) had grade III or IV tumor. Median 
volume of PTV was 192.8 cc (range 33.4-522.6) and median 
prescribed dose was 60Gy (range 46-66). Concurrent 
chemotherapy was given to 18 patients (43.9%). Median 
D100% and Dmax to the contralateral hippocampus were 
7.7Gy (range 0.6-24.8) and 16.6 Gy (range 3.56-60.4) 
respectively. Mean dose to contralateral hippocampus could 
be spared to less than 21 Gy in 39 patients with median value 
of 11.6 Gy (range 0.3-37.3) which was lower compared to 
previous documentation. Median value of maximal dose to 
lenses and eyeballs were 4.3 Gy (0.4-8.1) and 13.7 Gy (0.5-
46.6) respectively. At median follow up of 7.8 months (range 
0-14.8), median progression-free survival and overall survival 
were not reached. Cognitive function tests at 7 months were 
analyzable in 12 patients. For these patients, MMSE, SVLT-TR, 
SVLT-DR and SVLT-R at 7 months showed improved results 
compared to the baseline with 2.0% (95% CI, -0.8% to 4.7%), 
11.0% (95% CI, 3.3% to 18.8%), 20.1% (-5.5% to 45.8%) and -
0.6% (95% CI, -6.6% to 8.2%) increase respectively. No grade 4 
or 5 toxicity was reported.  
 
Conclusion: Hippocampus could be spared effectively in 
radiotherapy to primary brain tumors using VMAT. Despite 
limited follow up data, cognitive function tests of the 
patients showed promising results. Further follow up data 
would clarify the effect of hippocampal sparing on the 
cognitive function of the patients treated with radiotherapy 
for primary brain tumor.  
 
PO-0645  
18F-FET PET and MRI for treatment planning in 
glioblastoma 
M. Harat
1The Franciszek Lukaszczyk Oncology Centre, Radiotherapy, 
Bydgoszcz, Poland 
1, B. Malkowski2, Z. Okońska3, R. Makarewicz4 
2The Franciszek Lukaszczyk Oncology Centre, Nuclear 
Medicine, Bydgoszcz, Poland 
3The Franciszek Lukaszczyk Oncology Centre, Medical 
Physics, Bydgoszcz, Poland 
4The Franciszek Lukaszczyk Oncology Centre, Oncology and 
Brachytherapy, Bydgoszcz, Poland 
 
Purpose or Objective: To analyze pre-treatment MRI- and 
18F-fluoroethylthyrosine-PET- (FET-PET) based target 
volumes and patterns of failure following radiotherapy (RT) 
with concurrent temozolomide (TMZ) for primary 
glioblastoma multiforme (GBM). 
 
Material and Methods: Thirty-four patients with primary GBM 
were treated using MRI based treatment volumes (GTVrm). 
Before treatment patients underwent FET PET/CT scans and 
biological tumor volume (GTVpet) were contoured but not 
used for target definition. Progression were defined 
according to RANO criteria. Tumor progression and pre-
treatment MRI and PET scans were co-registered to the 
radiation dose map. Failures were classified based on 
location of primary GTVs and dose delivered at the site of 
failure. We investigated volumetric size and uniformity of 
MRI- vs. FET-PET/CT-derived GTVs and progression patterns 
assessed by means of FET PET/CT and MRI. 
 
Results: FET-PET based GTVs measured 10 minutes after 
radionuclide injection (a.r.i.) (median 37.3 cm3) were larger 
than GTVs measured 60 minutes a.r.i. (median 27,7 cm3). 
GTVpet were significantly larger than corresponding MRI 
based GTVs (median 19,3 cm3). The congruence of MRI and 
FET signals for the identification of glioblastoma GTVs is poor 
with mean uniformity index of 0.4 (p=0,0). 74% of failures 
were located inside primary GTVpet. 68% of failures occured 
within the 95% isodose line, and 9% within 60 Gy isodose. 
 
Conclusion: The size and geometrical location of GTVs 
differed in a majority of patients. The volume of GTVpet 
depends on time a.r.i. Tumor progression were mostly inside 
FET-PET volumes. FET PET better defined failure site then 
MRI. Finally dose inhomogenity inside GTVpet and GTVrm and 
favourable tumor control within 60Gy isodose advocates 
further studies with PET-MR based high-dose radiation 
therapy of GBM. 
 
PO-0646  
Temozolomide during radiotherapy of glioblastoma 
multiforme: daily administration improves survival 
S. Nachbichler
1Klinikum der Universität München, Klinik und Poliklinik für 
Strahlentherapie und Radioonkologie, München, Germany 
1, G. Schupp1, H. Ballhausen1, M. Niyazi1, C. 
Belka1 
 
Purpose or Objective: Temozolomide (TMZ) based 
chemoradiotherapy defines the current gold standard for the 
treatment of newly diagnosed glioblastoma. Data regarding 
the influence of TMZ dose density during chemoradiotherapy 
are currently not available. We retrospectively compared 
outcomes in patients receiving no TMZ, patients receiving 
TMZ during radiotherapy on radiotherapy days only (5/7) and 
patients receiving TMZ constantly 7 days a week (7//7).  
 
Material and Methods:  
From 2002 to 2012 a total of 432 patients with newly 
diagnosed glioblastoma received radiotherapy in our 
department. 118 patients had radiotherapy alone, 210 had 
chemoradiotherapy with temozolomide (75 mg/m²) daily (7/7 
days a week) and 104 chemoradiotherapy with temozolomide 
only on radiotherapy days (5/7 days a week, Monday till 
Friday). Radiotherapy was applied in 30 fractions to a total 
dose of 60 Gy. 
 
Results: Median survival after radiotherapy alone was 9.1 
months, compared to 12.6 months with temozolomide 5/7 
and to 15.7 months with temozolomide 7/7. The 1 year 
survival was 33% in the radiotherapy only group, 52% in the 
5/7 group and 64% in the 7/7 group. Kaplan Meier analysis 
showed a significant improvement of temozolomide 7/7 vs. 
5/7 (p=0.01 by the log-rank test), while temozolomide 5/7 
was still superior to no temozolomide at all (p=0.02). 
 
Conclusion: Our results confirm the findings of the 
EORTC/NCIC-trial by Stupp et al., establishing the daily 
temozolomide chemoradiotherapy as standard therapy for 
glioblastoma. Also a reduced temozolomide scheme can at 
first prolong the survival of glioblastoma patients, but not as 
much as the daily application. 
 
PO-0647  
Subventricular zones: new key targets for glioblastoma 
treatment 
J. Khalifa
1Institut Universitaire du Cancer de Toulouse - Oncopole, 
Radiation Oncology, Toulouse Cedex 09, France 
1, F. Tensaouti2, A. Lusque3, B. Plas4, J.A. Lotterie2, 
E. Uro-Coste5, V. Lubrano4, E. Cohen-Jonathan Moyal1 
2INSERM, U825, Toulouse, France 
3Institut Universitaire du Cancer de Toulouse - Oncopole, 
Biostatistics, Toulouse Cedex 09, France 
4CHU Purpan, Neurosurgery, Toulouse, France 
5Institut Universitaire du Cancer de Toulouse - Oncopole, 
Pathology, Toulouse Cedex 09, France 
 
Purpose or Objective: We aimed to identify subventricular 
zone (SVZ)-related prognostic factors of survival and patterns 
of relapse among patients with glioblastoma. 
 
Material and Methods: Forty-three patients with primary 
diagnosed glioblastoma treated in our Cancer Center 
between 2006 and 2010 were identified. All patients received 
surgical resection, followed by temozolomide-based 


PO-0644: Hippocampal sparing brain radiotherapy using VMAT to the primary brain tumour 

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PO-0644: Hippocampal sparing brain radiotherapy using VMAT to the primary brain tumour

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