Belderbose, J.

Grills, I.

Guckenberger, M.

Hope, A.

Lebesque, J.

Peulen, H.

Selvaraj, J.

Sonke, J.

Werner-Wasik, M.

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PO-0907: TCP modeling in a large cohort of NSCLC patients inclusive of geometric uncertainties 

S468                                                                                                                                         3rd ESTRO Forum 2015 
 
C.E. Olsson1, M. Thor2, J.H. Oh2, S. Elleberg Petersen3, D. 
Alsadius4, M. Høyer3, N. Pettersson5, A.C. Waldenström4, L. 
Bentzen3, J.O. Deasy2, L.P. Muren3, G. Steineck4 
1Göteborg University, Radiation Physics, Göteborg, Sweden  
2Memorial Sloan-Kettring Cancer Centre, Medical Physics, 
New York, USA  
3Aarhus University Hospital, Medical Physics/Oncology, 
Aarhus, Denmark  
4University of Gothenburg, Oncology, Göteborg, Sweden  
5Sahlgrenska University Hospital, Medical Physics and 
Biomedical Engineering, Göteborg, Sweden  
Purpose/Objective: Gastrointestinal (GI) toxicity following 
radiotherapy (RT) for prostate cancer involves the interplay 
between various GI tract structures and symptoms. The 
purpose of this study was to further improve our 
understanding of the wider range of GI toxicity by studying 
the relationship between dose to various segments of the GI 
tract and patient-reported outcomes in four previously 
identified symptom groups, labelled Leakage, Mucous, Pain, 
and Urgency. 
Materials and Methods: The three cohorts investigated in 
this study were previously treated for localized prostate 
cancer with primary or salvage external beam RT (EBRT or 
POSTOP) at two centres in 1993-2007 (N=681; time to follow-
up: 1-14 years; average age at RT: 64-70 years). Prescribed 
dose was 70-78 Gy in 2Gy fractions. Relationships between 
maximum or mean absorbed dose (Dmax or Dmean) to the most 
caudal 4 cm of the sigmoid colon (SC), the rectum (R), the 
anal sphincter region (AS), or combinations thereof (SC+R, 
SC+AS, R+AS, SC+R+AS), and single/joint symptoms in the 
previously identified symptom groups were investigated using 
logistic regression and the area under the receiver operating 
curve (Az). The symptom groups were based on factor 
analysis results (59 symptoms in total, two centre-specific 
questionnaires (Q1 and Q2))[1]. 
 
[1] XX, et al. Identifying groups of patient-reported 
gastrointestinal symptoms using factor analysis, XX 2014. 
 
Results: Among the statistically significant relationships 
identified between dose to single/joint structures and 
symptoms (p≤0.05; Fig.1.), Leakage was best predicted by AS 
Dmean, or AS+R and AS+R+SC Dmax (Az=0.68-0.73), and Mucous 
by AS Dmax (Az=0.67) or Dmean (Az=0.62). Pain was best 
predicted by AS and AS+SC Dmax (Az=0.69), or AS+R, R+SC, and 
AS+R+SC Dmean (Az=0.62) whereas Urgency was best predicted 
by AS and R Dmean (Az=0.58-0.78), or R and R+SC Dmax (Az=0.62).  
 
 
Conclusions: Our patient-reported outcome-based findings 
suggest that the anal sphincter, alone or in combination with 
other segments of the GI tract, is a key structure for a 
majority of the investigated GI symptoms. Sparing of the anal 
sphincter region, as defined separately from the rectum, has 
the potential to further reduce GI toxicity and increase the 
overall quality of life following RT for prostate cancer.  
 
PO-0907   
TCP modeling in a large cohort of NSCLC patients inclusive 
of geometric uncertainties  
J. Selvaraj1, J. Lebesque1, H. Peulen1, J. Belderbose1, M. 
Guckenberger2, M. Werner-Wasik3, A. Hope4, I. Grills5, J. 
Sonke1 
1Netherlands Cancer Institute, Radiotherapy, Amsterdam, 
The Netherlands  
2Julias-Maximilian University, Radiotherapy, Wuerzburg, 
Germany  
3Thomas Jefferson University Hospital, Radiotherapy, 
Philadelphia, USA  
4Princess Margaret Hospital, Radiotherapy, Toronto, Canada  
5Beaumont Hospital, Radiotherapy, Royal Oak, USA  
 
Purpose/Objective: Tumor control probability (TCP) model 
parameters for NSCLC have been only obtained from outcome 
data of conventionally or SBRT regiments thus far. Moreover, 
TCP model parameters in the literature were typically 
derived using the CTV prescription dose or dose-volume 
histograms (DVHs) which do not reflect the presence of 
geometric uncertainties, especially in SBRT where the dose 
heterogeneity is often high. In this study, GTV and PTV DVHs 
and local control data of both conventional and SBRT 
treatments were used to derive optimal TCP model 
3rd ESTRO Forum 2015                                                                                                                                         S469 
 
parameters, including geometric uncertainties, from a large 
cohort of patients. 
Materials and Methods: Multi-institutional data of 693 NSCLC 
patients of which 530 SBRT (stage-I) , and 163 treated with 
concurrent chemoradiation (CCRT) with volumetric image 
guidance in all fractions with DVHs of PTV and GTV and their 
corresponding local control rates at two year were available 
for this analysis. The prescription dose in the CCRT regiment 
was 24x2.75Gy with daily low-dose Cisplatin. The sensitizing 
effect of chemotherapy was accounted for in the TCP model 
by using a correction factor of 1.17 to total surviving fraction 
of cells at the end of treatment. In the SBRT patients, doses 
varying from 37.5 to 60 Gy were delivered in two to 10 
fractions. The median follow-up was 1.13 and 1.5 years 
respectively in the CCRT and SBRT regiments. In method one 
of this study, the DVH and volume of the GTV is used to 
estimate the population average radiosensitivity ( ),its 
standard deviation (σα) and equivalent uniform dose (EUD) ‘a’ 
parameters in the ‘Marsden TCP’ model. In method two, the 
dose of the PTV and the volume of the GTV (to calculate the 
total clonogens in the GTV) were used to account for day-to-
day geometric uncertainties. The α/β value and clonogen 
density was fixed to 10 Gy and 1e7 cells/cc respectively in 
both methods. The two methods were compared with the 
Akaike information criterion (AIC). To test the validity of the 
combined SBRT+CCRT TCP modeling, these two regiments 
were also modelled with separate , σα and ‘a’ 
parameters. The likelihood-ratio test was used to calculate 
the p-value between the separate and combined models. 
Results: The best-fit parameters are given in table 1 along 
with their 95% confidence intervals calculated with profile-
likelihood method for both methods. The , σα are almost 
equal in both methods while the EUD ‘a’ parameter 
approaching PTV mean dose and GTV minimum dose. The PTV 
based model was superior to the GTV based model with an 
AIC difference of 32.8 units. Separate analysis of SBRT and 
CCRT did not yield a superior TCP model (p=0.28).  
 
 
 
 
Conclusions: The tumor control probability of 
chemoradiation and SBRT regiments were successfully 
described by a single model. Separate analysis of 
chemoradiation and SBRT regiments did not improve the 
model. An EUD approaching the PTV mean dose best 
described the TCP indicating that geometric uncertainties 
play a role despite accurate image guidance.  
   
PO-0908   
Corpora cavernosa dose and patient-reported sexual 
dysfunction in prostate cancer radiotherapy 
J. Deasy1, M. Thor1, C.E. Olsson2, J.H. Oh1, D. Alsadius3, N. 
Pettersson4, G. Steineck5 
1Memorial Sloan Kettering Cancer Centre, Medical Physics, 
NYC, USA  
2University of Gothenburg, Radiation Physics, Gothenburg, 
Sweden  
3University of Gothenburg, Oncology, Gothenburg, Sweden  
4Sahlgrenska University Hospital, Medical Physics and 
Biomedical Engineering, Gothenburg, Sweden  
5University of Gothenburg, Division of Clinical Cancer 
Epidemiology/Department of Oncology, Gothenburg, Sweden  
 
Purpose/Objective: Dose-response modelling of sexual 
dysfunction after radiotherapy (RT) for prostate cancer has 
so far mainly focused on relationships between dose to the 
penile bulb (PB) and erectile dysfunction. However, 
radiation-induced sexual dysfunction involves the interplay 
between various symptoms and critical structures. In this 
study we hypothesized that dose to the corpora cavernosa 
(CC), alone or in combination with the PB (CC+PB), better 
explains the occurrence of interacting symptoms on sexual 
dysfunction than dose to the PB exclusively.  
Materials and Methods: To identify interacting symptoms, 
i.e. symptom groups, we applied factor analysis (FA) to 16 
patient-reported symptoms on sexual dysfunction in three 
cohorts (N=372). The investigated subjects were previously 
treated for localized prostate cancer either with primary or 
salvage external beam RT (EBRT or POSTOP), or EBRT 
combined with brachytherapy in 1993-2006 (time to follow-
up: 1-14 years; average age at RT: 64-70 years). Prescribed 
dose was 70 Gy@2.0 Gy/fraction. The ability of maximum and 
mean absorbed dose (Dmax or Dmean; population median of 
Dmean: CC=50 Gy, PB=67 Gy, CC+PB=51 Gy) in CC, PB, and 
CC+PB to predict single/joint symptoms in identified 
symptom groups was studied for EBRT and POSTOP (logistic 


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PO-0907: TCP modeling in a large cohort of NSCLC patients inclusive of geometric uncertainties

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