“Parameters for and use of NTCP models in the clinic”
References – up to 2006
General:
Burman C., G.J. Kutcher, B. Emami, M. Goitein. (1991). “Fitting of normal tissue tolerance data to an analytic
function.” Int J Radiat Oncol Biol Phys 21: 123-135.
Dawson LA, Biersack M, Lockwood G et al (2005). “Use of principal component analysis to
evaluate the partial organ tolerance of normal tissues to radiation.” Int J Radiat Oncol Biol Phys 62: 829837.
Deasy JO, Blanco AI, Clark VH (2003), “CERR: a computational environment for radiotherapy research”,
Med Phys 30: 979-985.
El Naqa I, Bradley J, Blanco AI, et al, (2006), “Multivariable modeling of radiotherapy outcomes, including
dose-volume and clinical factors”, Int Jnl Radiat Oncol Biol Phys 64: 1275-1286
Emami B., Lyman J., Brown A. et al, (1991). ”Tolerance of normal tissue to therapeutic irradiation.” Int J
Radiat Oncol Biol Phys 21: 109-122.
Glatstein E (2001). “Personal thoughts on normal tissue tolerance, or what the textbooks don’t tell
you.” Int J Radiat Oncol Biol Phys 51: 1185-1189.
Hendee WR, Hopewell J, Withers HR (1998), “Point/Counterpoint proposition: Long-term changes in
irradiated tissues are due principally to vascular damage in the tissues”, Med Phys 25: 2265-2268.
Honoré HB and Bentzen SM (2006), “A modelling study of the potential influence of low dose hypersensitivity
on radiation treatment planning”, Radiother and Oncol, in press.
Jackson A, Kutcher GJ, Yorke ED (1993), “Probability of radiation-induced complications for normal tissues
with parallel architecture subject to non-uniform irradiation”, Med Phys 20: 613-625.
Källman P, Agran A, Brahme A (1992), “Tumor and normal tissue responses to fractionated non uniform
dose delivery”, Int J Radiat Biol 62: 249-262
Kutcher GJ and Burman C (1991), “Calculation of complication probability factors for nonuniform normal
tissue irradiation: the effective volume method”, Int J Radiat Oncol Biol Phys 21: 137-146.
Lyman JT (1985) “Complication probability as assessed from dose-volume histograms”, Radiat Res Suppl 8:
S13-S19.
Moiseenko V, Battista J, Van Dyk J (2000), “Normal tissue complication probabilities: dependence on choice
of biological model and dose-volume histogram reduction scheme”, Int J Radiat Oncol Biol Phys 46: 983-993.
Nieder C., L. Milas, K.K.Ang. (2000). “Tissue tolerance to reirradiation.“ Sem Rad Onc 10, 200-209.
Niemierko A and Goitein M (1991) “Calculation of normal tissue complication probability and dose-volume
histogram reduction schemes for tissues with a critical element architecture”, Radiother Oncol 20:166-176.
Niemierko A and Goitein M (1993), “Modeling of normal tissue response to radiation: The critical volume
model”, Int J Radiat Oncol Biol Phys 25: 135-145
Niemierko A (1999), “A generalized concept of equivalent uniform dose (EUD)” (Abstract), Med Phys 26,
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Sanchez-Nieto B and Nahum AE, (2000), “Bioplan: software for the biological evaluation of radiotherapy
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Withers HR, Taylor JMG, Maciejewski B (1988) “Treatment volume and tissue tolerance”, Int J Radiat Oncol
Biol Phys 15: 751-759
Wu Q, Mohan R, Niemierko a, et al (2002), “Optimization of intensity-modulated radiotherapy plans based on
the equivalent uniform dose”, Int J Radiat Oncol Biol Phys 52: 224-235
Wu Q, Djajaputra D, Liu HH, et al (2005), “Dose sculpting with generalized equivalent uniform dose”, Med
Phys 32: 1387-1396.
Yorke ED, Kutcher GJ, Jackson A, et al (1993): “Probability of radiation-induced complications in normal
tissues with parallel architecture under conditions of uniform whole or partial organ irradiation”, Radiother Oncol 26:
226-237.
Spinal cord
Ang KK, Jiang GL, Feng Y, et al, (2001) “Extent and kinetics of recovery of occult spinal cord injury”, Int Jnl
Radiat Oncol Biol Phys 50: 1013-1020
Bijl H.P., van Luijk P., Coppes R.P. et al. (2003). “Unexpected changes of rat cervical spinal cord tolerante
caused by inhomogeneous dose distributions”. Int Jnl Radiat Oncol Biol Phys 57: 274-281.
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Bijl HP, van Luijk P, Coppes RP et al, (2006) “Influence of adjacent low-dose fields on tolerance to high
doses of protons in rat cervical spinal cord”, Int Jnl Radiat Oncol Biol Phys 64: 1204-1210.
Fowler J.F., Bentzen S.M., Bond S.J. et al, (2000) “Clinical radiation doses for spinal cord: the 1998
international questionnaire”, Radiother and Oncol 55: 295-300
Grosu A., N. Andratschke, C. Nieder and M. Molls . (2002). “Retreatment of the spinal cord with palliative
radiotherapy.” Int J Radiat Oncol Biol Phys 52:1288-1292.
Martel M, Eisbruch A, Lawrence T.S. et al . (1997). ”Spinal cord dose from standard head and neck
irradiation: implications for three-dimensional treatment planning”, Radiother and Oncol 47: 185-189.
Marucci L., Niemierko A., Liebsch N.J. (2004). “Spinal cord tolerance to high-dose fractionated 3D conformal
proton-photon irradiation as evaluated by equivalent uniform dose and dose volume histogram analysis.” Int Jnl Radiat
Oncol Biol Phys 59: 551-555.
Nieder C et al;, (2005), Proposal of human spinal cord reirradiation dose based on collection of data from 40
patients, Int Jnl Radiat Oncol Biol Phys 61, 851-855
Pieters RS et al, 2006; Cauda equina tolerance to high-dose fractionated irradiation, Int Jnl Radiat Oncol Biol
Phys 64: 251-57
Rades et al, (2006), Spinal reirradiation after short-course RT for metastatic spinal cord compression, Int Jnl
Radiat Oncol Biol Phys 63, 872-875.
Schultheiss T.E., L.E. Kun, K.K. Ang, L.C. Stephens. (1995). “Radiation response of the central nervous
system.“ Int Jnl Radiat Oncol Biol Phys 31: 1093-1112.
van Luijk P, Bijl HP, Konings AWT, et al (2005), “Data on dose-volume effects in the rat spinal cord do not
support existing NTCP models”, Int J Radiat Oncol Biol Phys 61: 892-900.
Rectum:
Akimoto T, Muramatsu H, Takahashi M, et al,(2006), “Rectal bleeding after hypofractionated radiotherapy for
prostate cancer: correlation between clinical and dosimetric parameters and the incidence of grade 2 or worse rectal
bleeding”, Int J Radiat Oncol Biol Phys 60: 1033-1039
Brenner DJ (2004), “Fractionation and late rectal toxicity”, Int J Radiat Oncol Biol Phys 60: 1013-1015
Fenwick JD, Khoo V,S, Nahum AE, (2001), “Correlation between dose-surface histograms and the incidence
of long-term rectal bleeding following conformal or conventional radiotherapy treatment of prostate cancer”, Int J Radiat
Oncol Biol Phys 49: 473-480
Jackson A (2001), “Partial irradiation of the rectum”, Sem Rad Onc 11, 215-223.
Jackson A, Skwarchuk MW, Zelefsky MJ, et al (2001), “Late rectal bleeding after conformal radiotherapy of
prostate cancer (II): volume effects and dose-volume histograms”, Int J Radiat Oncol Biol Phys 49: 685-698.
Lee WR, Hanks GE, Hanlon AL, et al (1996), “Lateral rectal shielding reduces late rectal morbidity following
high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: further evidence for a
significant dose effect”, Int J Radiat Oncol Biol Phys 35: 251-257 O’Brien PC (2001), “Radiation injury of the rectum”,
Radiother Oncol 60: 1-14.
Peeters STH, Lebesque JV, Heemsbergen WD, et al (2006), “Localized volume effects for late rectal and
anal toxicity after radiotherapy for prostate cancer”, Int J Radiat Oncol Biol Phys 64: 1151-1161.
Rancati T, Fiorino C, Gagliardi G et al, (2004), “Fitting late rectal bleeding data using different NTCP models :
results from an Italian multi-centric study (AIROPROS0101)”, Radiother Oncol 73: 21-32.
Skwarchuk MW, Jackson A, Zelefsky MJ et al (2000). “Late rectal toxicity after conformal
radiotherapy of prostate cancer (I). Multivariate analysis and dose-response.” Int J Radiat Oncol Biol Phys
47: 103-113.
Tucker SL, Cheung R, Dong L, et al, (2004), “Dose-volume response analysis of late rectal bleeding after
radiotherapy for prostate cancer”, Int J Radiat Oncol Biol Phys 59: 353-365.
Tucker SL, Zhang M, Dong L, et al (2006), “Cluster model analysis of late rectal bleeding after imrt of
prostate cancer: a case-control study”, Int J Radiat Oncol Biol Phys 64: 1255-1264
Zapatero A, Garcia-Vicente F, Modolell I, et al, (2004) “Impact of mean rectal dose on late rectal bleeding
after conformal radiotherapy for prostate cancer: dose-volume effect”, Int J Radiat Oncol Biol Phys 59: 1343-1351
Lung
Bradley J, Graham MV, Winter K, et al (2005), “Toxicity and outcome results of RTOG 9311: a phase I - II
dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung
carcinoma”, Int J Radiat Oncol Biol Phys 61: 318-328
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Graham MV, Purdy JA, Emami B, et al (1999), “Clinical dose-volume histogram analysis for pneumonitis
after 3D treatment for non-small cell lung cancer (NSCLC)”, Int J Radiat Oncol Biol Phys 45: 323-329.
Hernando M.L., L.B. Marks, G.C.Bentel, et al. (2001). “Radiation-induced pulmonary toxicity: a dose-volume
histogram analysis in 201 patients with lung cancer.” Int J Radiat Oncol Biol Phys 51: 650-659.
Kelsey CR et al, (2006), Radiation-induced narrowing of the tracheobronchial tree: an in-depth analysis,
Lung Cancer 52: 111Khan MA, Van Dyk J, Yeung IWT, Hill RP (2003), “Partial volume rat lung irradiation: assessment of early
DNA damage in different lung regions and effects of radical scavengers”, Radiother and Oncol 66: 95-102.
Kwa S.L.S., Lebesque J.V., Theuws J.C. et al (1998). “Radiation pneumonitis as a function of mean lung
dose: an analysis of pooled data or 540 patients.” Int J Radiat Oncol Biol Phys 42: 1-9.
Kwa S.L.S., Theuws J.C.M., Wagenaar A. et al. (1998). “Evaluation of two dose-volume histrogram reduction
models for the prediction of radiation pneumonitis” Radiother and Oncol 48: 61-69.
Marks LB, Munley MT, Bentel GC, et al (1997), “Physical and biological predictors of changes in whole-lung
function following throacic irradiation”, Int Jnl Radiat Oncol Biol Phys 39: 563-570.
Marks L.B.(2002).“Dosimetric predictors of radiation-induced lung injury.” Int J Radiat Oncol Biol Phys
54:313-316.
Martel M.K., R.K.Ten Haken, M.B.Hazuk, A.T.Turrisi, B.A.Fraass, A.S.Lichter . (1994). “Dose-volume
histogram and 3-D treatment planning evaluation of patients with pneumonitis.” Int J Radiat Oncol Biol Phys 28: 575581.
Mehta V (2005). “Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer:
pulmonary function, prediction and prevention.” Int J Radiat Oncol Biol Phys 63: 5-24
Miller KL, et al (2005) , Bronchial stenosis: an underreported complication of high-dose external beam RT for
lung cancer, Int J Radiat Oncol Biol Phys 61: 64-69
Morgan GW and Breit SN (1995), “Radiation and the lung: a reevaluation of the mechanisms mediating
pulmonary injury”, Int Jnl Radiat Oncol Biol Phys 31: 361-369
Rodriques G., Lock M., D’Souza D. et al. (2004). ”Prediction of radiation pneumonitis by dose-volume
histogram parameters in lung cancer – a systematic review.” Radiother and Oncol 71: 127-138.
Seppenwoolde Y and Lebesque JV (2001), “Partial irradiation of the lung”, Sem Rad Onc 11, 247-258.
Seppenwoolde Y., Lebesque J.V., De Jaeger K., et al. (2003). ”Comparing different NTCP models that
predict the incidence of radiation pneumonitis.” Int J Radiat Oncol Biol Phys 55: 724-735.
Seppenwoolde Y, DeJaeger K, Boersma LJ, et al (2004), “Regional differences in lung radiosensitivity after
radiotherapy for non-small-cell lung cancer”, Int J Radiat Oncol Biol Phys 60: 748-758.
Ten haken RK, Martel MK, Kessler ML, et al (1993), “Use of Veff and iso-NTCP in the implementation of
dose escalation protocols“ , Int J Radiat Oncol Biol Phys 27: 689-695
Travis EL, Liao ZX, Tucker SL (1997), “Spatial heterogeneity of the volume effect for radiation pneumonitis in
mouse lung”, Int J Radiat Oncol Biol Phys 38: 1045-1054
Tsougos I, Mavroidis P, Rajala J, et al (2005), “Evaluation of dose-response models and parameters
predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy”, PMB 50: 3535-3554.
Yorke ED, Jackson A, Rosenzweig K et al (2000), “The Lyman and a current parallel model: are they
equivalent in predicting radiation induced lung toxicity”, CD-ROM Proceedings of the World Congress on Medical
Physics and Biomedical Engineering, July 23-28, Chicago IL.
Yorke E.D., Jackson A., Rosenzweig K.E. et al. (2002). “Dose-volume factors contributing to the incidence of
radiation pneumonitis in non-small-cell lung cancer patients treated with three-dimensional conformal radiation
therapy.” Int J Radiat Oncol Biol Phys 54:329-339.
Yorke ED, Jackson A, Rosenzweig KE, et al, (2005), “Correlation of dosimetric factors and radiation
pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study”, Int J Radiat Oncol
Biol Phys 63: 672-682.
Liver
Cheng J C-H, Wu J-K, Huang C-M, et al (2002). “Radiation-induced liver disease after threedimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric analysis and
implication.” Int J Radiat Oncol Biol Phys 54: 156-162.
Cheng JC-H, Liu H-S, Wu J-K, et al, (2005), “Inclusion of biological factors in parallel-architecture normaltissue complication probability model for radiation-induced liver disease”, Int J Radiat Oncol Biol Phys 62: 1150-1156
Dawson LA, Ten Haken RK, Lawrence TS (2001), “Partial irradiation of the Liver”, Sem Rad Onc 11, 240246.
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Dawson LA, Normolle D, Balter JM, et al, (2002), “Analysis of radiation-induced liver disease using the
Lyman NTCP model”, Int J Radiat Oncol Biol Phys 53: 810-821.
Jackson A, Ten Haken RK, Robertson J, et al (1995), “Analysis of clinical complication data for radiation
hepatitis using a parallel architecture model”, Int J Radiat Oncol Biol Phys 31: 883-891
Heart
Eriksson F, Gagliardi G, Liedberg A, Et al (2000), “Long-term cardiac mortality following radiation therapy for
Hodgkins‘s disease: Analysis with the relative seriality model”, Radiother and ONcol 55: 153-162.
Gagliardi G, Lax I, Rutqvist LE (2001), “Partial irradiation of the heart”, Sem Rad ONc 11: 224-233.
Gagliardi G, Lax I, Ottolenghi A, et al (1996), “Long term cardiac mortality after radiotherapy of breast cancer:
Application of the relative seriality model”, BJR 69: 839-846.
Martel MK, Sahudak WM, Ten Haken RK, et al, (1998), “Fraction size and dose parameters related to the
incidence of pericardial effusions”, Int J Radiat Oncol Biol Phys 40:155-161.
Parotids:
Blanco AI, Chao KSC, El Naqa IE et al, (2005) Dose-volume modeling of salivary function in patients with
head-and-neck cancer receiving radiotherapy, Int J Radiat Oncol Biol Phys 62: 1055-1069.
Chao C.K.S., J.O.Deasy, J. Markman, et al. (2001). “A prospective study of salivary function sparing in
patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial
results.” Int J Radiat Oncol Biol Phys 49:907-916.
Eisbruch A., ten Haken R.K., Kim H.M. et al. (1999). ”Dose, volume, and function relationships in parotid
salivary glands following conformal and intensity-modulated irradiation of head and neck cancer.” Int J Radiat Oncol
Biol Phys 45: 577-587.
Eisbruch A, Ship JA, Kim HM, Ten Haken RK, (2001) “Partial irradiation of the parotid gland”, Sem Rad Onc
11, 234-239.
Jellema AP, Doornaert P, Slotman BJ et al (2005). “Does radiation dose to the salivary glands and
oral cavity predict patient-rated xerostomia and sticky saliva in head and neck cancer patients treated with
curative radiotherapy?” Radiother and Oncol 77: 164-171
Roesink J.M., M.A.Moerland , J.J. Battermann, et al. (2001). “Quantitative dose-volume response analysis of
changes in parotid gland function after radiotherapy in the head-and-neck region.“ Int J Radiat Oncol Biol Phys 51:
938-946.
Esophagus
Belderbos J, Heemsbergen W, Hoogeman M, et al (2005), “Acute esophageal toxicity in non-small cell lung
cancer patients after high-dose conformal radiotherapy”, Radiother and Oncol 75: 157-164
Bradley J, Deasy JO, Bentzen S, El Naqa I (2004), “Dosimetric correlates for acute esophagitis in patients
treated with radiotherapy for lung carcinoma”, Int J Radiat Oncol Biol Phys 58: 1106-1113
Chapet O, Kong F-M, Lee JS, et al, (2005), “Normal tissue complication probability modeling for acute
esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer”, Radiother and Oncol
77, 176-181.
Maguire PD, Sibley GS, Zhou S-M, et al (1999), “Clinical and dosimetric predictors of radiation-induced
esophageal toxicity”, Int Jnl Radiat Oncol Biol Phys 45: 97-103.
Poltinnikov IM, Fallon K, Xiao Y, et al, (2005), “Combination of longitudinal and circumferential threedimensional esophageal dose distribution predicts acute esophagitis in hypofractionated reirradiation of patients with
non-small-cell lung cancer treated in stereotactic body frame”, Int J Radiat Oncol Biol Phys 62: 652-658.
Hypofractionation
Herfarth K, Debus J, Wannenmacher M, (2004), “Stereotactic Radiation Therapy of liver metastases: update
of the initial phase-I/II trial”, Front Radiat Ther Oncol 38, 100-105,
Fowler JF, Ritter ZMA, Chappell RJ, Brenner DJ, (2003), “What hypofractionated protocols should be tested
for prostate cancer?” Int J Radiat Oncol Biol Phys 56: 1093-1104
Milker-Zabel S, et al, ( 2003), Clinical results of retreatment of vertebral bone metastases by stereotactic
conformal radiotherapy and intensity-modulated RT, Int Jnl Radiat Oncol Biol Phys 55, 162-67.
Onimaru R, Shirato H, Shimizu S, et al (2003), “Tolerance of organs at risk in small-volume hypofractionated,
image-guided radiotherapy for primary and metastatic lung cancers”, Int J Radiat Oncol Biol Phys 56: 126-135
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Ricke J, Seidensticker MS, Ludemann L, et al (2005), “In vivo assessment of the tolerance dose of small liver
volumes after single-fraction HDR irradiation”, Int J Radiat Oncol Biol Phys 62: 776-784
Sampson MC, Katz A, Constine LS (2006), “Stereotactic body radiation therapy for extracranial
oligometastasis: does the sword have a double edge?”, Sem Rad Onc 16: 67-76.
Schefter TE, Kavanagh BD, Timmerman RD, et al (2005),” A phase I trial of stereotactic body radiation
therapy (SBRT) for liver metastases”, Int J Radiat Oncol Biol Phys 62, 1371-1378
Wersäll PJ, Blomgren H, Lax I, et al (2005), “Extracranial stereotactic radiotherapy for primary and metastatic
renal cell carcinoma”, Radiother and Oncol 77: 88-95
Other complications
Debus J., Hug E.B., Liebsch N.J., et al. (1997). “Brainstem tolerance to conformal radiotherapy of skull base
tumors”. Int Jnl Radiat Oncol Biol Phys 39. 967-975.
Levegrun S, Ton L, Debus J (2001), “Partial irradiation of the brain”, Sem Rad Onc 11:259-267
Meeks S.L., Buatti J.M., Foote K.D. et al. (2000) “Calculation of cranial nerve complication probability for
acoustic neuroma radiosurgery”. Int Jnl Radiat Oncol Biol Phys 47: 597-602.
Yeh S-A, Tang Y, Lui C-C, et al (2005), “Treatment outcomes and late complications of 849 patients with
nasopharyngeal carcinoma treated with radiotherapy alone”, Int J Radiat Oncol Biol Phys 62: 672-679
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