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RADIATION
RESEARCH
104, S-13-S-19 (1985)
Treatment planning optimization involves selection of an acceptable plan that controls the local and regional spread of cancer without causing normal tissue complications (1). To fully optimize a treatment plan (maximize the tumor dose without
exceeding an acceptable complication probability), a method is needed to determine
the complication probabilities for the different normal tissues which will be affected
by the treatment.
Sophisticated treatment planning, particularly for particle beam therapy, involves
three-dimensional calculations or a series of two-dimensional calculations using adjacent slices of CT data (2). To evaluate a given plan, the radiotherapistmust integrate
the information presented by series of isodose distributions superimposed on the CT
images. All the slices, which demonstrate the target volume and the critical tissues,
must be examined to ascertain that the target is adequately treated and the normal
tissues are adequately spared. Heavy charged-particlebeams offer a means for sparing
normal tissues from irradiation that is not available with conventional radiations.
Decisions to maximally spare normal structures must be tempered by the possibility
of not adequately treating normal tissues bearing occult disease.
If dose-volume histograms are calculated from the data presented in the isodose
distributions, the degree of uniformity or nonuniformity of the irradiation may be
S-13
0033-7587/85$3.00
S-14
JOHN T. LYMAN
quickly assessed because a single histogram can present dose uniformity information
which is contained in a number of sets of isodose distributions (3).1'2 The histograms
give another way to look at the plan and may give some additional information that
is not readily apparent when using the isodose distributions. A high-dose region in
the histogram may represent a high-dose region that is related to a single CT slice or
may represent a contiguous region related to adjacent CT slices or even a number of
isolated high-dose regions related to the same or different slices. The isodose distributions are needed to determine the location of the high-dose regions. Therefore the
dose-volume histogramsdo not substitutefor the isodose distributionsin the evaluation
of a treatment plan, but augment them.
The purpose of this study is to develop a method to estimate the complication
probability of a normal tissue structure from a dose-volume histogram and data from
a population of radiation therapy patients. The estimates of the complication probability can then be used to optimize a treatment plan. The identification of the optimal
plan is also subject to clinical judgment of the acceptability of the plan and the risk/
benefit for each individual patient. This approach is being explored in the optimization
of heavy-charged-particle treatment plans. An evaluation of several representative
cases has led to some generalized conclusions which may provide guidance to the
radiotherapist in assessing appropriate treatment plans. The techniques developed in
this work are equally applicable to optimization of treatment plans for other radiations.
METHODS
Datafromthe literaturewhichmightaid in thisrankingarevaluesof the tolerancedoseof varioustissues
(4-6). Tolerancedosesare usuallygivenas a functionof beamarea,or lengthof the irradiatedportionof
structure,or fractionof the organtreated.Thesedata,whicharepartof the folkloreof radiotherapy,
arefor
treatmentwith low-LETradiationsand a conventionalfractionschedule.Thesevalueswerederivedfrom
observationof patientswho weretreatedbeforethe daysof sophisticatedtreatmentplanning.Thereforeit
mustbe assumedthattherecouldbe significanterrorsin the estimationof theportionof theorganortissue
which receivedthe irradiationand in the uniformityof the irradiation.These data, which are the best
available,are not as completeor as firmas desirable.
The bestexampleof the tolerancedose (in Gy) is forthe heart(TableI). The dataforthe partial-volume
irradiations
arefromRubinet al. (5), whilethe remainingpointrepresents
thecollectivejudgmentof several
experiencedtherapistswho are participatingin an NCI-sponsored
projectto evaluateparticletreatment
plans.The TD50and TD5are the dosesthat wouldresultin 50 and 5%complicationprobabilitiesafter5
years,respectively,and representtwo points on what is assumedto be a sigmoid-shaped
dose-response
curve.These data imply that the complicationprobabilityis a functionof both the percentagevolume
irradiatedand the absorbeddose receivedby the volume.Thereare manyotherfactorsthat are involved,
most noticeablythe fractionationscheme;however,forthe momentthisand all theseotherfactorswill be
heldconstant.
Datafor otherpartialvolumesand tolerancelevelscan be obtainedby interpolationor extrapolation.
A
fullsetof datacanbe represented
surfacethatrepresents
theprobability
of complication
by a three-dimensional
as a functionof both the volumeand the dose (Fig. 1).This surfacewasdeterminedby assumingthat the
volumedependencecouldbe represented
by a power-lawrelationship(7, 8).
'S. R. Zink,J. R. Castro,G. T. Y. Chen,J. M. Collier,J. T. Lyman,and W. M. Saunders,Treatment
withphotonsforcarcinomaof the esophagus.Manuscript
planningstudycomparesheavyion radiotherapy
submittedto Int.J. Radiat.Oncol.Biol. Phys.
2 M. M. Austin-Seymour,
G. T. Y. Chen,J. R. Castro,W. M. Saunders,S. Pitluck,K. H. Woodruff,and
M. Kessler,Dose volumehistogramanalysisof liverradiationtolerance.Manuscriptsubmittedto Int. J.
Radiat.Oncol.Biol. Phys.
S-15
COMPLICATION
PROBABILITY
TABLEI
ToleranceDosesfor Heart
% Volume
TDso
TD5
25
60
80
55
70
45
35
100
TD(V) TD(I)/j",
(1)
whereTD(V) is the tolerancedose for a givenpartialvolume(V), TD( ) is the tolerancedose for the full
is represented
Thedosedependence
volume,andn is a fittedparameter.
bytheintegralof a normaldistribution
of a sigmoidcurve).
(one of severalpossiblerepresentations
PC
=
e-'2/2dt,
-
(2)
where t = (D - TD5o(V))/a( V)). This curve is completely defined by the mean (TD50(V)) and the standard
deviation(a(V))whichforthecurrentworkhasbeenapproximated
by m X TD5( V).Thethree-dimensional
surfacecan then be completelydefinedby the threeparameters,
TD5o(), n, and m.
tolerancedoses for the heart(in Gy) calculatedwith Eqs.(1)
Table II is an exampleof partial-volume
and (2) and parametersderivedfromthe data in TableI. Calculatedvaluesfor pointsthat correspondto
valuesin TableI are underlined.Valuesof TD5o(1),n, and m for a selectedlist of organsand tissuesare
given in TableIII.Thesevaluesare preliminaryestimatesbasedon publishedand unpublisheddata and
willemergefrom
opinions;as such,theyshouldbe usedwithcaution.It is anticipatedthatbetterparameters
treatmentplanningsystemsanddose-volumehistograms.
studiesusingthree-dimensional
Cumulativedose-volumehistogramsfora kidneyfor severalpossibletreatmentplansareshownin Fig.
2. Thesehistogramsshowthe fractionof the organwhichreceivesa dose equalto or greaterthana given
value.The histogramswerederivedfromtreatmentplansusinghelium,carbon,or neon beamswith field
all beamsproducedessentiallythe
of two, three,or fourfields.Forthe two-fieldarrangements
arrangements
samehistogram,the one withthe largestdose.Thefour-fieldarrangement
givesthe lowestdoseswithhelium
withthethree-field
occurs
This
same
neon.
which
is
lower
than
lower
than
carbon
arrangements.
ranking
being
andeventherelativerankingof thesehistograms
It is notdifficultto determinethe mostdesirabledistribution
by visualinspection.The averagedoseor the integraldosecan alsobe usedto aid in the rankings.However,
betweenthehistograms.
of thedifferences
thesemethodsdo notprovidean estimateof theclinicalsignificance
Providedthereare sufficientdatato obtainan estimateof the three-dimensional
complicationsurface,an
estimateof the probabilityfor complicationcan also be obtained,sincethesehistogramsrepresenta fairly
PC0.5-
0
1.0
Partial
0.5
Volume
\D 20
v
4U
ose (Gray)
Dose (Gray)
S-16
JOHN T. LYMAN
TABLEII
DerivedToleranceDosesfor Heart
V
TDso(V)
TD5(V)
0.200
0.250
0.300
0.350
0.400
0.450
0.500
0.550
0.600
0.650
0.700
0.750
0.800
0.850
0.900
0.950
1.000
93.7
83.8
76.5
70.8
66.2
62.5
59.5
56.5
54.1
52.0
50.1
48.4
46.9
45.5
44.2
43.0
41.9
78.3
70.0
63.9
59.2
55.4
52.2
49.5
47.2
45.2
43.4
41.8
40.4
39.1
38.0
36.9
35.9
35.0
of complication
betweenthe estimatesof the probability
irradiation.
Thedifferences
uniformpartial-volume
give a measureof the clinicallyimportantdifferencesbetweenthe histograms.Incidentally,with a target
will yielda clinicallysignificant
the two-fieldarrangements
dose of 66 Gy, only the histogramrepresenting
probabilityof complication.In general,the comparisonof the dose-volumehistogramsof the sameorgan
TABLEIII
Factorsfor DerivingToleranceDoses
Organ/tissue
TDso
Bladder
Bone
Brain
Brainstem
Caudaequina
Esophagus
Eye
Femoralhead
Heart
Intestine
Kidney
Liver
Lung
Mandible
Opticnerve
Parotid
Pituitary
Rectum
Spinalcord
Stomach
72.0
70.0
64.0
64.0
57.5
66.0
60.0
62.0
41.9
55.0
29.0
35.0
22.0
77.0
65.0
72.0
54.0
75.0
50.0
55.0
0.10
0.05
0.20
0.05
0.10
0.15
0.05
0.05
0.50
0.10
0.15
0.40
0.65
0.05
0.05
0.10
0.05
0.10
0.10
0.35
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
S-17
COMPLICATION
PROBABILITY
(D
E
E
0.6
0.4 0.2 -
0
0
10
30
20
40
50
60
Pc=
Pc()).
(3)
i=l
There are some important deductions that can be made from the estimates of the
complication probability as represented by Eqs. (1) and (2). If the treatment plan is
3J. T. Lymanand A. B. Wolbarst,A generalmethodof assessingcomplicationsfrom dose-volume
histograms.Manuscriptsubmittedforpublication.
S-18
JOHN T. LYMAN
0.8 -
E
06-
0.40.2 02
0
10
20
30
40
50
60
Dose (Gray)
FIG. 3. Cumulativedose-volumehistogramsfor the incidentalirradiationof a kidney.Theseare more
thanthoseof Fig.2 andthebetterdistribution
is notobvious.Estimates
of thecomplication
complexhistograms
probabilitycan aid in the selectionof the betterplan.
Individual variations in size and location of tumors can result in higher or lower
estimates of complications. If these individual variations are taken into consideration
during the treatment planning process, better (lower likelihood of complications) plans
may result. This can be considered to be a predictive assay based on patient anatomy
and the treatment plan. The result is the identification of the combination of patient
and treatment plan which have high or low likelihood for complications. This may
result in deviating from standard protocols by using a lower tumor dose for some
patients and a higher dose for other patients with similar type tumors.
This approachto optimization of treatment plans is being tested in an NCI-supported
project on the evaluation of particletreatment plans. The estimates of the complication
probabilities are also being compared with the clinical observations following heavy-
PROBABILITY
COMPLICATION
S-19
on Usesof Computers
carcinomaof the pancreas.In Proceedings,EighthInternational
Conference
in RadiationTherapy,pp. 264-268. IEEE,1984.
A direction for clinical radiation pathology: The tolerance dose. In
4. P. RUBINand G. W. CASARETT,
Frontiers of Radiation Therapy and Oncology (J. M. Vaeth, Ed.), Vol. 6, pp. 1-16. University Park
Press,Baltimore,1972.
5. P. RUBIN,R. A. COOPER,and T. L. PHILLIPS,
(Eds.), RadiationBiologyand RadiationPathology
Syllabus, Set R. T. : Radiation Oncology, pp. 2-7. American College of Radiology, Chicago, 1975.
6. L. COHEN,The tissue factor in radiation oncology. Int. J. Radiat.Oncol.Biol. Phys.8, 1771-1774
(1982).
7. H. R. WITHERS, H. D. THAMES, and L. J. PETERS, Dose fractionation and volume effects in normal
tissues and tumors. Cancer Treat. Symp. 1, 75-83 (1984).
C. G. ORTON,and R. A. PECK,Models in radiotherapy: Volume effects. Med.
8. T. E. SCHULTHEISS,
Phys. 10, 410-415 (1983).
L. M. CHIN, and G. K. SVENSSON,
9. A. B. WOLBARST,
Optimization of radiation therapy: Integral-
10. M. GOITEIN, The utility of computed tomography in radiation therapy: An estimate of outcome. Int.
J. Radiat.Oncol.Biol.Phys.5, 1799-1807(1979).
11. L. COHEN,BiophysicalModelingin RadiationOncology.CRC Press, Boca Raton, 1983.
fornormaltissueresponses.
doserateandiso-effectrelationships
Dosefractionation,
12. G. W. BARENDSEN,
Int.J. Radiat.Oncol.Biol. Phys.8, 1981-1997(1982).