Gerger, A.

Kapp, K.S.

Krenn-Pilko, S.

Langsenlehner, T.

Langsenlehner, U.

Pichler, Martin

Stojakovic, T.

Thurner, E.M.

English

Pichler, M.

Elsevier - Publisher Connector 

PO-0682: External validation of the derived neutrophil-tolymphocyte ratio as a prognostic factor in breast cancer patients 

OPUS Augsburg

3rd ESTRO Forum 2015                                                                                                                                         S333  in patients treated for left-sided breast cancer without breath-hold were higher when compared to those with right-sided breast cancers and to those with left-sided breast cancer treated with breath-hold. See the Table and the Figure. Group Mean CAC  LAD_baseline Mean CAC  Overall_baseline  Mean CAC  LAD_3 years Mean CAC  Overall_3 years  R (n=20) 14.5 (0-105) 80.1 (0-825)  29.9 (0-255) 138 (0-1334)  L-BH (n=18) 49.3 (0-334) 75.2(0-477)  77.3 (0-634) 138.3 (0-1055)  L+BH (n=61) 19.3 (0-401) 35.7 (0-645)  28.8 (0-509) 64.9 (0-1039)     Figure left and middle: Mean calcium score increase in time for the LAD and overall CAC score. Figure right: Mean CAC score: LAD minus RCA. Blue solid line: Left-sided breast cancer patients, group L-BH. Black dashed line: Right-sided breast cancer patients, group R. Red dotted line: Left-sided breast cancer patients treated in breath-hold, group L+BH. Note: the scales in the figure differ. Conclusions: Breath-hold in breast conserving radiotherapy leads to a less pronounced increase of CT based CAC scores. Therefore, breath-hold is probably useful to prevent the development of radiation-induced coronary artery disease. The drawbacks of our study were the small numbers and the relatively short follow-up period.    PO-0681   Re-irradiation with hyperthermia for loco-regional recurrent breast cancer: A systematic review and meta-analysis N.R. Datta1, E. Puric1, D. Klingbiel2, S. Bodis1 1Kantonsspital Aarau, Radio-Onkologie, Aarau, Switzerland  2Swiss Group of Clinical Cancer Research (SAKK) Coordinating Centre, Department of Statistics, Bern, Switzerland   Purpose/Objective: Loco-regional recurrences in post-irradiated breast cancers pose a major therapeutic challenge and could severely compromise patients' quality of life. Since in most cases, patients usually have co-existing systemic disseminated disease, a sustainable complete local regression of the recurrences, without treatment induced morbidity could provide an effective palliation and improve theirquality of life. Local hyperthermia (HT) along with moderate doses of re-irradiation (ReRT)has been used in various single-arm (ReRT+HT) and two-arm clinical trials (randomized and nonrandomized, ReRTvs. ReRT+HT). The present study conducts a systematic review and meta-analysis on the outcome of these trials. Materials and Methods: Using the appropriate MeSH and Boolean function, a detailed search was conductedas per the PRISMA guidelines. 2,047 abstracts were screenedfrom the 10 databases used for search (Fig). Only those studies which had received prior loco-regional RT as a part of their primary management and were treated with ReRT and HT alone were considered. Patients who had undergone surgery for the loco-regional recurrences were subjected to concurrent chemotherapy were not considered. End point evaluation was complete loco-regional response (CR) following ReRT and HT.    Results: A total of 43 full papers were shortlisted and reviewed after extensive database search, and 24studies were selected for detailed review based on pre-defined selection criteria. Six of these were two-arm (randomized, n=4; nonrandomized, n=2) while 18 were single-arm studies resulting in a total of 1,319 patients of which 1,162 received ReRT and HT.  Primary RT at doses ranging from 40 to60 Gy (mean + SD: 50.6+ 6.1 Gy) was received by these patients between 37 and 72 months before being considered for ReRT. Hyperthermia was mostly delivered by microwaves (91.7%), twice a week and usually following RT (79.2%). A temperature ranging from 40.6 -43°C (42.4+ 0.7°C) was achieved during HT which lasted for a mean duration of 53.5 min. ReRT doses ranged from 24 -60 Gy (36.3 +8.1Gy) and delivered at 1.8 to 4 Gy/fr (2.85+0.9 Gy). Two-arm studies included 494 patients, and a CR of 62.8% and 39.3% was observed with ReRT+HT and ReRTrespectively, giving an odds ratio of 2.9 (95% CI: 1.8-4.6, p<0.001; Q=6.4, I2= 22.2, p=0.26). The risk ratio was 1.6 (95% CI: 1.2-2.0) in favor of achieving a CR with ReRT+HT compared to ReRT alone. For 18 single-arm studies, a CR of 64.6% was reported from the 825 patients resulting in an event rate of 0.6 (95% CI: 0.5-0.6, p<0.001; Q=33.8, I2= 49.7, p=0.008). Local control with ReRT +HT at 1 and 2 year were 57.1% and 48.5% respectively. Mean acute and late grade III/IV toxicities with ReRT +HT were reported as 13.4% and 3.9%. Conclusions: ReRT with HTsubstantially increases the probability of achieving CRs in loco-regional recurrences in pre-irradiated patients with low acute and late morbidities.      PO-0682   S334                                                                                                                                         3rd ESTRO Forum 2015  External validation of the derived neutrophil-to-lymphocyte ratio as a prognostic factor in breast cancer patients S. Krenn-Pilko1, U. Langsenlehner2, E.M. Thurner1, T. Stojakovic3, M. Pichler4, A. Gerger5, K.S. Kapp1, T. Langsenlehner1 1Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz, Austria  2Division of Internal Medicine, Outpatient Department Graz, Graz, Austria 3Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria  4MD Anderson Cancer Center, Department of Experimental Therapeutics, Texas, USA  5Division of Clinical Oncology, Department of Internal Medicine, Graz, Austria   Purpose/Objective: Existing preclinical and clinical data suggest that the presence of a systemic inflammatory response plays a critical role in the progression of several solid tumors. The derived neutrophil-to-lymphocyte ratio (dNLR) represents an easily determinable marker of systemic inflammation and has been proposed as a potential prognostic marker. The present study was performed to externally validate the prognostic relevance of an elevated pre-treatment dNLR in a large cohort of non-metastatic breast cancer patients. Materials and Methods: Data from 762 consecutive non-metastatic female breast cancer patients treated from 1999 to 2004 were evaluated. Disease-free survival (DFS), distant metastases-free survival (DMFS), and overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the prognostic relevance, univariate and multivariate Cox regression models were performed for each endpoint. Results: Applying receiver-operating characteristics (ROC) analysis, the optimal cut-off level for the dNLR was 3. In univariate analysis, a dNLR ≥3 was associated with poor DFS (HR 1.87, 95%CI 1.28-2.73, p=0.001), DMFS (HR 1.90, 95%CI 1.27-2.85, p=0.002), and OS (HR 1.67, 95%CI 1.07-2.63, p=0.025). Multivariate analysis revealed a significant association between the elevated dNLR and poor DFS (hazard ratio (HR) 1.70, 95%CI 1.09-2.65, p=0.018) and DMFS (HR 1.66, 95%CI 1.02-2.68, p=0.041) but did not show a significant association between the dNLR and OS (HR 1.54, 95%CI 0.91-2.59, p=0.106).  Conclusions: In the present study, we confirmed the elevated pre-treatment dNLR as an independent prognostic factor that could be useful for future individual risk assessment in breast cancer patients.     PO-0683   Electron IntraOperative RadioTherapy (ELIOT) in early breast cancer: Outcome analysis of a non-randomized study L. Cazzaniga1, G. Gritti1, A. Gambirasio2, M. Källi1, F.R. Filippone1, L. Maffioletti1, L. Feltre1, R. Muni1, F. Piccoli1, S. Andreoli2, M. Fortunato2, P. Colleoni2, C. Bianchi2, P. Fenaroli3, M. Ferro3, A. Paludetti3, E. Mauri3, L. Burgoa3, M. Giovanelli3, C. Valerii3 1A.O. Papa Giovanni XXIII, Radiotherapy Department, Bergamo, Italy  2A.O. Papa Giovanni XXIII, Medical Physic, Bergamo, Italy  3A.O. Papa Giovanni XXIII, Surgery, Bergamo, Italy   Purpose/Objective: Intraoperative radiotherapy (IORT) has been proposed as alternative to external beam in early breast cancer however previous studies suggest that patient selection must be improved in order to reduce the rate of ipsilateral breast tumour recurrence (IBTR). 'Papa Giovanni XXIII' Hospital in Bergamo Italy has been authorized by Lombard Aldermanship to carry out a non-randomised study. The study was also approved by the local ethics committee. Materials and Methods: 735 procedures has been performed between February 2006 and June 2014, on 722 patients (mean age 64 years; range 48-84 years), 13 of them had doubled IORT (synchronous or metachronous). Patients inclusion/exclusion criteria were: Age > 48 years old (if postmenopausal); clinical, mammography/ultrasound diagnostic of unifocal invasive carcinoma with an ultrasound major diameter < 2.5 cm. Informed consent was mandatory. There were 41 protocol violations due the age or the nodule size, enclosed in the analysis. IORT was done by means of a 9 MeV electron beam Novac 7 linac. The prescribed dose was 21 Gy at 90 % isodose. The mean follow up is 1564 days and all patients with at least one follow up are enclosed in the analysis. The principal endpoint was the in-field and out-field (IBTR), Relapse Free Survival (RFS). The secondary endpoints were the Overall Survival (OS), Cancer Specific Survival (CSS), Metastases Free Survival (MFS), Disease Free Survival (DFS) and the acute and late toxicity rates. Survival dependence on different parameters such as nodule size, ER, PR, focality, grade, vascular invasion, Ki67>20, margins, cErbB2, has been assessed by log-rank test. Results: Observed local relapses are 52 (33 in field, 17 out-field, 2 n.o.s.), corresponding to a crude rate of 7.1 % the 5 years cumulative RFS, DFS, MFS were 92.1%, 89% and 94.7% respectively. The 5 years OS and CSS were 98.8% and 99.4% respectively. The univariate statistical analysis showed that IBRT dependence on the independent variables: nodule size, ER, PR, focality, grade, vascular invasion, Ki67>20, margins, cErbB2 was statistically significant. Dependence on the other variables such as DCIS component, histological type, pN, showed a trend but is not statistically significant. This last result may be due to the dimension of subgroups. Concerning nodule dimension, the most significant difference in IBTR occurs when a cut-off value of 15 mm is used. Grouping the patients according to ASTRO guidelines for accelerated partial breast irradiation, patients scored in the 'suitable' group showed a much better RFS as compared to 'cautionary' or 'unsuitable' group.  

External validation of the derived neutrophil-tolymphocyte ratio as a prognostic factor in breast cancer patients [Poster]

S. Krenn-Pilko

U. Langsenlehner

E.M. Thurner

T. Stojakovic

M. Pichler

A. Gerger

K.S. Kapp

T. Langsenlehner

Crossref

Radiotherapy and Oncology

PO-0682: External validation of the derived neutrophil-tolymphocyte ratio as a prognostic factor in breast cancer patients

3rd ESTRO Forum 2015                                                                                                                                         S333 
 
in patients treated for left-sided breast cancer without 
breath-hold were higher when compared to those with right-
sided breast cancers and to those with left-sided breast 
cancer treated with breath-hold. See the Table and the 
Figure. 
Group 
Mean CAC  
LAD_baseline 
Mean CAC  
Overall_baseline  
Mean CAC  
LAD_3 years 
Mean CAC  
Overall_3 years  
R (n=20) 14.5 (0-105) 80.1 (0-825) 
 
29.9 (0-255) 138 (0-1334) 
 
L-BH (n=18) 49.3 (0-334) 75.2(0-477) 
 
77.3 (0-634) 138.3 (0-1055) 
 
L+BH (n=61) 19.3 (0-401) 35.7 (0-645) 
 
28.8 (0-509) 64.9 (0-1039) 
 
 
 
 
Figure left and middle: Mean calcium score increase in time 
for the LAD and overall CAC score. Figure right: Mean CAC 
score: LAD minus RCA. 
Blue solid line: Left-sided breast cancer patients, group L-BH. 
Black dashed line: Right-sided breast cancer patients, group 
R. Red dotted line: Left-sided breast cancer patients treated 
in breath-hold, group L+BH. Note: the scales in the figure 
differ. 
Conclusions: Breath-hold in breast conserving radiotherapy 
leads to a less pronounced increase of CT based CAC scores. 
Therefore, breath-hold is probably useful to prevent the 
development of radiation-induced coronary artery disease. 
The drawbacks of our study were the small numbers and the 
relatively short follow-up period. 
   
PO-0681   
Re-irradiation with hyperthermia for loco-regional 
recurrent breast cancer: A systematic review and meta-
analysis 
N.R. Datta1, E. Puric1, D. Klingbiel2, S. Bodis1 
1Kantonsspital Aarau, Radio-Onkologie, Aarau, Switzerland  
2Swiss Group of Clinical Cancer Research (SAKK) Coordinating 
Centre, Department of Statistics, Bern, Switzerland  
 
Purpose/Objective: Loco-regional recurrences in post-
irradiated breast cancers pose a major therapeutic challenge 
and could severely compromise patients' quality of life. Since 
in most cases, patients usually have co-existing systemic 
disseminated disease, a sustainable complete local regression 
of the recurrences, without treatment induced morbidity 
could provide an effective palliation and improve theirquality 
of life. Local hyperthermia (HT) along with moderate doses 
of re-irradiation (ReRT)has been used in various single-arm 
(ReRT+HT) and two-arm clinical trials (randomized and 
nonrandomized, ReRTvs. ReRT+HT). The present study 
conducts a systematic review and meta-analysis on the 
outcome of these trials. 
Materials and Methods: Using the appropriate MeSH and 
Boolean function, a detailed search was conductedas per the 
PRISMA guidelines. 2,047 abstracts were screenedfrom the 10 
databases used for search (Fig). Only those studies which had 
received prior loco-regional RT as a part of their primary 
management and were treated with ReRT and HT alone were 
considered. Patients who had undergone surgery for the loco-
regional recurrences were subjected to concurrent 
chemotherapy were not considered. End point evaluation was 
complete loco-regional response (CR) following ReRT and HT.  
 
 
Results: A total of 43 full papers were shortlisted and 
reviewed after extensive database search, and 24studies 
were selected for detailed review based on pre-defined 
selection criteria. Six of these were two-arm (randomized, 
n=4; nonrandomized, n=2) while 18 were single-arm studies 
resulting in a total of 1,319 patients of which 1,162 received 
ReRT and HT.  
Primary RT at doses ranging from 40 to60 Gy (mean + SD: 
50.6+ 6.1 Gy) was received by these patients between 37 and 
72 months before being considered for ReRT. Hyperthermia 
was mostly delivered by microwaves (91.7%), twice a week 
and usually following RT (79.2%). A temperature ranging from 
40.6 -43°C (42.4+ 0.7°C) was achieved during HT which 
lasted for a mean duration of 53.5 min. ReRT doses ranged 
from 24 -60 Gy (36.3 +8.1Gy) and delivered at 1.8 to 4 Gy/fr 
(2.85+0.9 Gy). 
Two-arm studies included 494 patients, and a CR of 62.8% 
and 39.3% was observed with ReRT+HT and ReRTrespectively, 
giving an odds ratio of 2.9 (95% CI: 1.8-4.6, p<0.001; Q=6.4, 
I2= 22.2, p=0.26). The risk ratio was 1.6 (95% CI: 1.2-2.0) in 
favor of achieving a CR with ReRT+HT compared to ReRT 
alone. For 18 single-arm studies, a CR of 64.6% was reported 
from the 825 patients resulting in an event rate of 0.6 (95% 
CI: 0.5-0.6, p<0.001; Q=33.8, I2= 49.7, p=0.008). Local 
control with ReRT +HT at 1 and 2 year were 57.1% and 48.5% 
respectively. Mean acute and late grade III/IV toxicities with 
ReRT +HT were reported as 13.4% and 3.9%. 
Conclusions: ReRT with HTsubstantially increases the 
probability of achieving CRs in loco-regional recurrences in 
pre-irradiated patients with low acute and late morbidities.  
   
 
PO-0682   
S334                                                                                                                                         3rd ESTRO Forum 2015 
 
External validation of the derived neutrophil-to-
lymphocyte ratio as a prognostic factor in breast cancer 
patients 
S. Krenn-Pilko1, U. Langsenlehner2, E.M. Thurner1, T. 
Stojakovic3, M. Pichler4, A. Gerger5, K.S. Kapp1, T. 
Langsenlehner1 
1Department of Therapeutic Radiology and Oncology, Medical 
University of Graz, Graz, Austria  
2Division of Internal Medicine, Outpatient Department Graz, 
Graz, Austria 
3Clinical Institute of Medical and Chemical Laboratory 
Diagnostics, Medical University of Graz, Graz, Austria  
4MD Anderson Cancer Center, Department of Experimental 
Therapeutics, Texas, USA  
5Division of Clinical Oncology, Department of Internal 
Medicine, Graz, Austria  
 
Purpose/Objective: Existing preclinical and clinical data 
suggest that the presence of a systemic inflammatory 
response plays a critical role in the progression of several 
solid tumors. The derived neutrophil-to-lymphocyte ratio 
(dNLR) represents an easily determinable marker of systemic 
inflammation and has been proposed as a potential 
prognostic marker. The present study was performed to 
externally validate the prognostic relevance of an elevated 
pre-treatment dNLR in a large cohort of non-metastatic 
breast cancer patients. 
Materials and Methods: Data from 762 consecutive non-
metastatic female breast cancer patients treated from 1999 
to 2004 were evaluated. Disease-free survival (DFS), distant 
metastases-free survival (DMFS), and overall survival (OS) 
were assessed using the Kaplan-Meier method. To evaluate 
the prognostic relevance, univariate and multivariate Cox 
regression models were performed for each endpoint. 
Results: Applying receiver-operating characteristics (ROC) 
analysis, the optimal cut-off level for the dNLR was 3. In 
univariate analysis, a dNLR ≥3 was associated with poor DFS 
(HR 1.87, 95%CI 1.28-2.73, p=0.001), DMFS (HR 1.90, 95%CI 
1.27-2.85, p=0.002), and OS (HR 1.67, 95%CI 1.07-2.63, 
p=0.025). Multivariate analysis revealed a significant 
association between the elevated dNLR and poor DFS (hazard 
ratio (HR) 1.70, 95%CI 1.09-2.65, p=0.018) and DMFS (HR 
1.66, 95%CI 1.02-2.68, p=0.041) but did not show a significant 
association between the dNLR and OS (HR 1.54, 95%CI 0.91-
2.59, p=0.106).  
Conclusions: In the present study, we confirmed the 
elevated pre-treatment dNLR as an independent prognostic 
factor that could be useful for future individual risk 
assessment in breast cancer patients.  
   
PO-0683   
Electron IntraOperative RadioTherapy (ELIOT) in early 
breast cancer: Outcome analysis of a non-randomized 
study 
L. Cazzaniga1, G. Gritti1, A. Gambirasio2, M. Källi1, F.R. 
Filippone1, L. Maffioletti1, L. Feltre1, R. Muni1, F. Piccoli1, S. 
Andreoli2, M. Fortunato2, P. Colleoni2, C. Bianchi2, P. 
Fenaroli3, M. Ferro3, A. Paludetti3, E. Mauri3, L. Burgoa3, M. 
Giovanelli3, C. Valerii3 
1A.O. Papa Giovanni XXIII, Radiotherapy Department, 
Bergamo, Italy  
2A.O. Papa Giovanni XXIII, Medical Physic, Bergamo, Italy  
3A.O. Papa Giovanni XXIII, Surgery, Bergamo, Italy  
 
Purpose/Objective: Intraoperative radiotherapy (IORT) has 
been proposed as alternative to external beam in early breast 
cancer however previous studies suggest that patient 
selection must be improved in order to reduce the rate of 
ipsilateral breast tumour recurrence (IBTR). 'Papa Giovanni 
XXIII' Hospital in Bergamo Italy has been authorized by 
Lombard Aldermanship to carry out a non-randomised study. 
The study was also approved by the local ethics committee. 
Materials and Methods: 735 procedures has been performed 
between February 2006 and June 2014, on 722 patients 
(mean age 64 years; range 48-84 years), 13 of them had 
doubled IORT (synchronous or metachronous). 
Patients inclusion/exclusion criteria were: Age > 48 years old 
(if postmenopausal); clinical, mammography/ultrasound 
diagnostic of unifocal invasive carcinoma with an ultrasound 
major diameter < 2.5 cm. Informed consent was mandatory. 
There were 41 protocol violations due the age or the nodule 
size, enclosed in the analysis. 
IORT was done by means of a 9 MeV electron beam Novac 7 
linac. The prescribed dose was 21 Gy at 90 % isodose. The 
mean follow up is 1564 days and all patients with at least one 
follow up are enclosed in the analysis. The principal endpoint 
was the in-field and out-field (IBTR), Relapse Free Survival 
(RFS). The secondary endpoints were the Overall Survival 
(OS), Cancer Specific Survival (CSS), Metastases Free Survival 
(MFS), Disease Free Survival (DFS) and the acute and late 
toxicity rates. 
Survival dependence on different parameters such as nodule 
size, ER, PR, focality, grade, vascular invasion, Ki67>20, 
margins, cErbB2, has been assessed by log-rank test. 
Results: Observed local relapses are 52 (33 in field, 17 out-
field, 2 n.o.s.), corresponding to a crude rate of 7.1 % the 5 
years cumulative RFS, DFS, MFS were 92.1%, 89% and 94.7% 
respectively. The 5 years OS and CSS were 98.8% and 99.4% 
respectively. 
The univariate statistical analysis showed that IBRT 
dependence on the independent variables: nodule size, ER, 
PR, focality, grade, vascular invasion, Ki67>20, margins, 
cErbB2 was statistically significant. Dependence on the other 
variables such as DCIS component, histological type, pN, 
showed a trend but is not statistically significant. This last 
result may be due to the dimension of subgroups. Concerning 
nodule dimension, the most significant difference in IBTR 
occurs when a cut-off value of 15 mm is used. 
Grouping the patients according to ASTRO guidelines for 
accelerated partial breast irradiation, patients scored in the 
'suitable' group showed a much better RFS as compared to 
'cautionary' or 'unsuitable' group. 
 


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External validation of the derived neutrophil-tolymphocyte ratio as a prognostic factor in breast cancer patients [Poster]

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