1 s2.0 S245210942100097X Main
1 s2.0 S245210942100097X Main
1 s2.0 S245210942100097X Main
Scientific Article
Received February 22, 2021; revised May 12, 2021; accepted June 8, 2021
Abstract
Purpose: This work was to establish an uncomplicated tumor control probability (UTCP) model using hepatocellular carcinoma
(HCC) stereotactic body radiation therapy (SBRT) clinical data in our institution. The model was then used to analyze the current
dose prescription method and to seek the opportunity for improvement.
Methods and Materials: A tumor control probability (TCP) model was generated based on local clinical data using the maximum
likelihood method. A UTCP model was then formed by combining the established TCP model with the normal tissue complication
probability model based on the study by Dawson et al. The authors investigated the dependence of maximum achievable UTCP on
planning target volume equivalent uniform dose (EUD) at various ratio between planning target volume EUD and normal liver EUD
(T/N EUD ratios). A new term uncomplicated tumor control efficiency (UTCE) was also introduced to analyze the outcome. A UTCE
value of 1 implied that the theoretical maximum UTCP for the corresponding T/N EUD ratio was achieved.
Results: The UTCE of the HCC SBRT patients based on the current dose prescription method was found to be 0.93 § 0.05. It was
found that the UTCE could be increased to 0.99 § 0.03 by using a new dose prescription scheme, for which the UTCP could be
maximized while keeping the normal tissue complication probability value smaller than 5%.
Conclusions: The dose prescription method of the current HCC SBRT in our institution was analyzed using a UTCP model established
based on local clinical data. It was shown that there could be a potential to increase the prescription dose of HCC SBRT. A new dose
prescription scheme was proposed to achieve better UTCP. Additional clinical trials would be required to validate the proposed dose
prescription scheme in the future.
© 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
fractions depending on the normal liver (excluding Where pi was the TCP for patient i, D50 was the EUD that
all GTVs) mean dose, following the Radiation Ther- led to 50% tumor control probability, Di was the PTV
apy Oncology Group (RTOG) 1112 dose prescription EUD of patient i and k was a parameter that controlled
approach.11 For a typical treatment plan, the isodose the slope of the TCP curve.
line of 80% was used for dose prescription and the The TCP modeling was implemented using MATLAB
center of the GTV was boosted to around 100% iso- 2019a in the present study (The MathWorks, Inc, Natick,
dose line. The dose constraints to organs at risk were MA). Maximum likelihood method was used to itera-
also adopted following RTOG 1112. tively adjust the parameters of a in Eq. (2) and k and D50
in Eq. (3) such that maximum likelihood of the patient i
is obtained in Eq. (4).
X
Statistical analysis for factors affecting tumor l¼ log pi Ri ð1 pi Þð1Ri Þ ð4Þ
local control i
dose and a was the radiobiological parameter. Parameters EUD was the equivalent uniform dose of an organ.
vi and Di could be obtained using the BED-converted TD50 was the tolerance dose for a homogeneous irradia-
DVHs. Parameter a would be found during the fitting pro- tion to an organ which would result in 50% risk of com-
cess of the TCP model. plication. Parameter m determined the gradient of the
The calculated PTV EUD then was used for modeling dose response at TD50. Parameter n determined the vol-
of TCP using a logistic function12,13 in Eq. (3), ume effect which related the tolerance doses of uniform
1 whole organ irradiation to uniform partial organ irradia-
pi ¼ TCPi ¼ k ð3Þ
tion. TD50, n and m were 39.8, 0.97, and 0.12,
1 þ D50
Di respectively in the study by Dawson et al.19
4 M.L.M. Cheung et al Advances in Radiation Oncology: September−October 2021
increased to 0.99 § 0.03 compared with 0.93 § 0.05 of TCP. Two cases had a decrease in PTV EUD and TCP.
the original prescription scheme (Fig 4). This was because the original liver NTCP of these 2 cases
were >5%. Therefore, the PTV EUD was decreased such
that the liver NTCP was kept within 5%.
Discussion The UTCE of the cases using the new dose prescrip-
tion schemes were closer to one than the original dose
UTCP had been used in other investigations together prescription scheme except those with T/N EUD ratio
with parameters such as quality adjusted life years to pre- less than 1.9 owing to the limit of 5% NTCP. The average
dict the overall outcome of the different treatment UTCE of the cases using the new dose schemes was
plans.24 It had been applied to other SBRT evaluations boosted up to 0.99 § 0.03, comparing to 0.93 § 0.05 of
such as non-small cell lung cancer.25 With its usefulness, the RTOG 1112 dose prescription scheme.
building local UTCP model and using it to evaluate HCC
SBRT treatments locally as well as to seek room for
potential dose escalation were the purpose of this study. Conclusions
A 6-month TCP model was fitted using local clinical
cases and the fitted value of D50 was 67.4 GyBED. Lausch
There was a dose-response relationship for the patients
et al reported a 2 Gy Equivalent D50 of 53 Gy (63.6
undergoing HCC SBRT in our institution. A TCP model
GyBED) for a 6-month TCP model.7 Jang et al reported a
fitted with clinical data of local HCC SBRT patients was
3-fraction D50 of 34.9 Gy (75.5 GyBED) for a 2-year TCP
combined with a published NTCP model to form a new
model.8 Our fitted value of D50 was found to be more
UTCP model. Current dose prescription method used in
comparable to the 6-month model of Lausch et al.
our institution was analyzed using the newly established
The fitted TCP model was then combined with the
UTCP model to evaluate if theoretical maximum UTCP
NTCP model proposed by Dawson et al to form the
was achieved. It was suggested that there could be a
UTCP model to assess if maximum theoretical UTCP
potential to increase the current prescription dose for
had been achieved under the current dose prescription
HCC SBRT to obtain higher UTCP. A new dose prescrip-
protocol based on RTOG 1112 and to see whether there
tion scheme was proposed accordingly in this study and
was any room for dose escalation. For cases with a T/N
further clinical trials would be required to validate the
EUD ratio greater than 2.5, most of the cases already
proposed dose prescription scheme in the future.
reached the highest level of dose prescription following
the RTOG 1112 scheme (100 GyBED corresponding to 50
Gy physical dose). Therefore, there was no more increase
in the PTV EUD with further increase in the T/N EUD Acknowledgments
ratio above the value of 2.5 in Figure 2. The prescription
dose seemed to be far below the values to achieve opti- We would like to thank all colleagues involved in this
mal UTCP. research project for their kind efforts in the process of
A new prescription scheme was proposed to increase data collection, paper reviewing, and research guidance.
the overall UTCE and keep the liver NTCP within 5%.
Under the new prescription scheme, a higher T/N EUD
ratio resulted in a higher percentage increase PTV EUD Supplementary materials
in general (Fig 5). It was because the cases with a low T/
N EUD ratio usually had higher normal liver EUD, limit- Supplementary material associated with this article
ing the potential to increase dose prescription. Also, the can be found in the online version at https://doi.org/
higher T/N EUD ratio cases were originally limited by 10.1016/j.adro.2021.100739.
the RTOG 1112 highest dose prescription level of 50 Gy,
which was far from the optimal prescription dose to
achieve theoretical maximum UTCP.
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