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NTCP1
NTCP1
NTCP1
Journal of
Oncology
ISSUE 17 JANUARY 2015
Table of Contents
Case Reports
The external auditory canal as an unusual site for metastasis of breast carcinoma: A case report............................................. 85
B.A. Baraka, B.J. Al Bahrani, S.S. Al Kharusi, I. Mehdi, A.M. Nada, N.H. Al Rahabi
Primary Mixed Cellularity Classical Hodgkin lymphoma of the Lumbar spine – An unusual presentation............................. 88
K.R. Anila, R. A. Nair, S. Prem, K. Ramachandran
Subdural hematoma during therapy of gastro-intestinal stromal tumor (GIST) with Imatinib mesylate................................. 92
J. Feki, G. Marrekchi, T. Boudawara, N. Rekik, S. Maatoug, Z. Boudawara, M. Frikha
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The use of radiobiological plan evaluation metrics in IMRT, A. Surega , et. al.
from the dosimetric data. The correlation can other software programs developed were based
be quantified using statistical methods like on LKB, Relative seriality and Poisson models
Spearman method. have their inherent errors in execution. For e.g.:
the DVH file format from the TPS was not found
Materials and methods to be compatiblwe with the program execution
The evaluation of treatment plans with the which resulted in run time errors. The eudmodel
surrogate measure of the DV criteria were code is useful in calculating both TCP and NTCP
replaced by actual biological indices which can whereas other programs calculate either TCP or
reflect the clinical goals of radiotherapy (1-4). NTCP based on the model used.
Various radiobiological models for predicting
the efficacy of radiotherapy were devised (5-9). A Generalized Equivalent Uniform Dose (gEUD)
number of software programs were developed In 1997, Niemierko proposed a concept
by different researchers based on various which uses a single metric for reporting non-
radiobiological models in the past decade to uniform tumor dose distributions. Conventional
analyze the dose response relations (10-15) but radiotherapy involves dose distributions which
their clinical usage was limited. Generalized tend to be uniform across the target volume.
Equivalent Uniform Dose (gEUD) concept High end radiotherapy such as IMRT results in
of radiobiological modeling is more robust rather inhomogeneous dose distributions. EUD
in reporting and analyzing the IMRT dose is defined as the uniform dose that, if delivered
distributions which are heterogeneous in nature over the same number of fractions to the target
(16)
. A free Matlab code for computing the Tumor volume as the non-uniform dose distribution of
Control Probability (TCP) and Normal Tissue interest, yields the same radiobiological effect.
Complication Probability (NTCP) based on It is the uniform dose which leads to the same
gEUD concept was developed by Gay et al (17). probability of injury in normal tissue or tumor
It can use the DVH parameters (Di, vi) available control in tumors as the examined inhomogeneous
from treatment plans. dose distribution. A phenomenological formula
The EUD concept assumes that any two dose was proposed by Niemierko extending the
distributions are equivalent if they cause the same EUD concept to normal tissues referred to as
radiobiological effect in the tissues irradiated. generalized EUD (gEUD) (6).
The TCP and NTCP calculations are based mainly
on two equations and the same model unlike
gEUD = (∑iviDia) 1/a 1
other models which are separately formulated
for TCP and NTCP calculations. Emami et al
have noted that normal tissue tolerance data fit Where,
excellently with the model parameters. But the
vi = Fractional organ volume receiving a dose Di
tolerance doses estimated by Emami et al are
applicable to conventional therapy evaluation a=Volume effect describing tissue specific parameter
only. The published QUANTEC (Quantitative (-ve for tumor, +ve for serial organs)
Analysis of Normal Tissue Effects in the Clinic) Normal Tissue Complication Probability
report lists the normal tissue tolerance doses for (NTCP)
three dimensional conformal therapies. Hence
they can be used in the clinical cases to arrive NTCP is the probability that a given dose
at the TCP and NTCP estimates for IMRT plan of radiation will cause an organ or structure
evaluation. to experience complications considering the
specific biological cells of the organ or structure.
Eudmodel.m is a Matlab code available as It is used in treatment planning as an evaluation
an open source from the literature. It is a user tool to differentiate among treatment plans.
friendly program which needs processed DVH
data from any treatment planning system. The
NTCP=1/ (1+ (TD50/EUD)) 4γ50
2
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G. J. O. Issue 17, 2015
were transferred to Eclipse treatment planning
TD50: Tolerance dose for a 50% complication system (Varian Medical Systems Inc, USA,
rate at a specific time interval (eg: 5 years Emami Version 8.2). Among the 50 patients, 15 patients
et al data) (18, 19). were diagnosed with brain tumors, 20 were with
head and neck carcinoma and remaining 15 were
γ50: is a unit-less model parameter that is cervical cancer patients (Table 2). Evenly spaced
specific to the normal structure or tumor of gantry angle arrangement around the patient
interest and describes the slope of the Dose anatomy was planned and inversely optimized
Response curve. (17, 18) All normal tissues have with Anisotropic Analytical Algorithm (Version:
a limit as to the amount of radiation they can v11.0.31). Dose was calculated with a grid size
receive and still remain functional which is of about 2mm and the Dose Volume Histograms
defined as Radiation Tolerance. was generated for each case.
Tumor Control Probability (TCP) The DV parameters such as TVref (Reference
Tumor control probability is a radiobiological target volume receiving the prescribed dose), TV
estimate that takes tissue parameters into (Target volume delineated), D95 (Dose received
consideration to estimate the regression/relapse by 95% of tumor volume) and D5 (Dose received
of malignancy after irradiation. TCP thought to by 5% of tumor volume) of the corresponding
be more relevant in evaluating the tumor control target volume (Brain, Head &Neck and Cervix)
compared to dosimetric parameters. were obtained from the DVH data.
The Conformity Index (CI) which is a
dosimetric quality metric was calculated using
TCP=1/ (1+ (TCD50/EUD)) 4γ50 3
the formula (22):
17
The use of radiobiological plan evaluation metrics in IMRT, A. Surega , et. al.
From the data, the X and Y coordinates matrix into the EUD program in the MATLAB
corresponding to the Biologically Effective Dose environment for computing the radiobiological
(Di) and Volume (vi) (Voxel element of 2mm metrics such as TCPs and NTCPs. The input
calculation grid) were then fed as a two column variable DVH was created by typing dvh = ( ) in
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G. J. O. Issue 17, 2015
The correlation data between the dose volume and 95% respectively. No severe normal tissue
parameters for the ten normal structures and their complications such as Grade 3 or Grade 4 are
corresponding Normal Tissue Complication observed.
Probabilities were tabulated (Table 3). The
parallel organs such as parotids and optic nerves Discussion
evaluated with the maximum doses were found to The dose constraints recommended by
be in good correlation with the NTCPs computed. physicians are usually of the type “no more
(RP:p=0.002, LP:p=0.06; RON:p=0.0007, than x Gray, to no more than y percentile of the
LON:p=0.02) . The NTCP correlation with the organ”. From the available DVH information of
maximum dose obtained for the serial organs BS the treatment planning system, treatment plans
p=004; NB p=0.03; SC p=0.09; Bladder p=0.97; are evaluated based on the dosimetric parameters
Rectum p=0.21. (Tolerance Doses) alone. DVHs happen to be the
A follow up study of the 50 IMRT patients only available plan evaluation tool with which the
was conducted with a median duration of 28 probability risks cannot be assessed completely.
months. Local control of the disease for the sites The Conformity index (CI) of Brain, Head
such as Brain, H&N and Pelvis are 90%, 75% & Neck and Cervix cases listed in Table 2
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G. J. O. Issue 17, 2015
gives the idea of tumor coverage with the dose tolerance values (TD50) published in Emami et
prescribed by the oncologists. It helps them to al data.
comparatively score the various treatment plans The conformity index is widely used to rank
for the same patient and select the best one to the treatment plans on the basis of target volume
execute. But this type of evaluation is based dose coverage. It merely depends on the radiation
only on the photon beam energy used for the beam used and the radiotherapy technique
irradiation and the D-V constraints. The tumor followed. But the TCP calculation is based on
coverage assessed using the CI should ideally be the radiobiological parameters describing the
one indicating the 100% coverage by the physical volume effect (a) of irradiation, dose response
dose distribution or the reference isodose line. slope factor γ50, 50% tumor control dose
This evaluation method does not depend on the (TCD50) and Equivalent Uniform Dose (EUD).
tumor type and their volume effect. Hence there From this study, CI is found to be correlating with
is a need for an external evaluation tool for the the estimated TCP from the statistical analysis.
ultimate assessment of biological outcomes with Hence the calculation of Conformity Index can
the help of probability estimates such as TCP determine the plan quality effectively similar to
and NTCP. TCP estimates.
The radiation dose volume effects for the Normal tissue’s maximum or mean dose
whole organ irradiation were studied and obtained from the DVH are usually compared
reviewed in the QUANTEC reports for various with the Emami tolerance data to select the
normal tissues (23-26) but the follow up data was optimal plan for execution. For e.g., maximum
inadequate and further studies should be made normal brain dose is 67.46Gy which is 7.46Gy
for partial irradiation and organ movement more than the TD50 for normal brain i.e. 60Gy.
phenomenon. It can be evaluated that there may be a chance
There are eleven TCP/NTCP calculation of 50% complication resulting in brain necrosis
software programs presented in the literature. in the 5 year survival time. The exact amount of
Among them, only five are freely distributed probability for the occurrence of brain necrosis
for the research studies (three for dose response can be estimated as 24.017% using the EUD
regression analysis and two for direct TCP, NTCP based software calculation of NTCP. Similarly,
computations). Apart from the BIOPLAN (Visual a complication probability of 0.873% was
Basic workspace), developed by Nahum et al in calculated for the incidence of brain necrosis
2000, others run in MATLAB environment. The when it receives a maximum dose of 56.35Gy
free EUD based calculation program uses the (patient No.2). When there is a rival plan with
unified formula for TCP and NTCP calculations. a lesser complication probability, clinician can
Thus, it can do the computation more easily choose that plan for treatment delivery. Table 3
compared to other radiobiological models e.g.: gives the NTCP estimates of the normal tissues
Lyman Kutcher Burman (LKB) model based such as Brain Stem, Rt. Optic Nerve, Lt. Optic
software programs. LKB model calculation Nerve, Optic Chiasma and Normal brain (Glioma
requires three radiobiological parameters such Cases), Rt. Parotid, Lt. Parotid and Spinal cord
as n, m and TD50 in which the tissue specific (H&N cases) and Bladder and Rectum (Ca.
parameter (m) and the equivalent uniform dose Cervix cases).
parameter (n) have no reliable estimates. Hence The evaluation of mean doses in parotid
the uncertainty can be avoided by eliminating may be effective since there is a statistically
the use of other radiobiological parameters significant correlation found with the NTCP
with this simple EUD program which requires estimates. The complication probabilities
TCD50, TD50, EUD, a, α/β and the dosimetric for serial organs such as brain stem, normal
parameters (Di, vi). EUD model has the brain, optic chiasm are correlated well with
remarkable capability in fitting the normal tissue the maximum dose. But spinal cord, rectum
and bladder correlations deviated more with
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The use of radiobiological plan evaluation metrics in IMRT, A. Surega , et. al.
the radiobiological estimates. There may be an Index and Mean dose in case of parallel organs,
uncertainty in using maximum dose alone for the Maximum dose for the serial organs correlate
treatment plan evaluation of bladder, rectum and with their corresponding tumor control and
SC. Conventional plan evaluation tool (DVH) normal tissue complication probabilities
stops with the assessment of physical metrics calculated. The EUD concept of radiobiological
before proceeding to the treatment delivery. It model used in the software determines the TCP
has certain limitations in absolute assessment of and NTCP values that can predict the outcomes
biological outcomes because of the uncertainty precisely. Thus, two treatment plans can be
exhibited in correlating the outcomes with more compared based on TCP and NTCP along with
than one particular D-V parameter. other physical dose metrics.
Conclusion
Dosimetric parameters can be further evaluated
radiobiologically using an external work space
running under the MATLAB environment. The
dosimetric evaluation indices such as Conformity
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