{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T03:57:36Z","timestamp":1774497456069,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Radiat Oncol"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Biological models are used to relate the outcome of radiation therapy to dose distribution. As use of biological models in treatment planning expands, uncertainties associated with the use of specific models for predicting outcomes should be understood and quantified. In particular, the question to what extent model predictions are data-driven or dependent on the choice of the model has to be explored.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Four dose-response models--logistic, log-logistic, Poisson-based and probit--were tested for their ability and consistency in describing dose-response data for radiation-induced optic neuropathy (RION) and retinopathy (RIRP). Dose to the optic nerves was specified as the minimum dose, <jats:italic>D<\/jats:italic>\n              <jats:sub>\n                <jats:italic>min<\/jats:italic>\n              <\/jats:sub> , received by any segment of the organ to which the damage was diagnosed by ophthalmologic evaluation. For retinopathy, the dose to the retina was specified as the highest isodose covering at least 1\/3 of the retinal surface (<jats:italic>D<\/jats:italic>\n              <jats:sub>\n                <jats:italic>33%<\/jats:italic>\n              <\/jats:sub> ) that geometrically covered the observed retinal damage. Data on both complications were modeled separately for patients treated once daily and twice daily. Model parameters <jats:italic>D<\/jats:italic>\n              <jats:sub>\n                <jats:italic>50<\/jats:italic>\n              <\/jats:sub> and <jats:italic>\u03b3<\/jats:italic> and corresponding confidence intervals were obtained using maximum-likelihood method.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Model parameters were reasonably consistent for RION data for patients treated once daily, <jats:italic>D<\/jats:italic>\n              <jats:sub>\n                <jats:italic>50<\/jats:italic>\n              <\/jats:sub> ranging from 94.2 to 104.7 Gy and <jats:italic>\u03b3<\/jats:italic> from 0.88 to 1.41. Similar consistency was seen for RIRP data which span a broad range of complication incidence, with <jats:italic>D<\/jats:italic>\n              <jats:sub>\n                <jats:italic>50<\/jats:italic>\n              <\/jats:sub> from 72.2 to 75.0 Gy and <jats:italic>\u03b3<\/jats:italic> from 1.51 to 2.16 for patients treated twice daily; 72.2-74.0 Gy and 0.84-1.20 for patients treated once daily. However, large variations were observed for RION in patients treated twice daily, D<jats:sub>50<\/jats:sub> from 96.3 to 125.2 Gy and <jats:italic>\u03b3<\/jats:italic> from 0.80 to 1.56. Complication incidence in this dataset in any dose group did not exceed 20%.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>For the considered data sets, the log-logistic model tends to lead to larger <jats:italic>D<\/jats:italic>\n              <jats:sub>\n                <jats:italic>50<\/jats:italic>\n              <\/jats:sub> and lower <jats:italic>\u03b3<\/jats:italic> compared to other models for all datasets. Statements regarding normal tissue radiosensitivity and steepness of dose-response, based on model parameters, should be made with caution as the latter are not only model-dependent but also sensitive to the range of complication incidence exhibited by clinical data.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1748-717x-6-61","type":"journal-article","created":{"date-parts":[[2011,6,7]],"date-time":"2011-06-07T06:35:37Z","timestamp":1307428537000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A comparison of dose-response characteristics of four NTCP models using outcomes of radiation-induced optic neuropathy and retinopathy"],"prefix":"10.1186","volume":"6","author":[{"given":"Vitali","family":"Moiseenko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William Y","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loren K","family":"Mell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niranjan","family":"Bhandare","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,6,6]]},"reference":[{"key":"389_CR1","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/0360-3016(92)90548-V","volume":"23","author":"A Niemierko","year":"1992","unstructured":"Niemierko A, Urie M, Goitein M: Optimization of 3D radiation therapy with both physical and biological end points and constraints. Int J Radiat Oncol Biol Phys 1992, 23: 99-108. 10.1016\/0360-3016(92)90548-V","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR2","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1118\/1.596971","volume":"20","author":"S Sodertrom","year":"1993","unstructured":"Sodertrom S, Brahme A: Optimization of the dose delivery in a few field techniques using radiobiological objective functions. Med Phys 1993, 20: 1201-1210. 10.1118\/1.596971","journal-title":"Med Phys"},{"key":"389_CR3","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1088\/0031-9155\/44\/2\/014","volume":"44","author":"M Alber","year":"1999","unstructured":"Alber M, Nusslin F: An objective function for radiation treatment optimization based on local biological measures. Phys Med Biol 1999, 44: 479-493. 10.1088\/0031-9155\/44\/2\/014","journal-title":"Phys Med Biol"},{"key":"389_CR4","doi-asserted-by":"publisher","first-page":"5851","DOI":"10.1118\/1.3013556","volume":"35","author":"VA Semenenko","year":"2008","unstructured":"Semenenko VA, Reitz B, Day E, Qi XS, Miften M, Li XA: Evaluation of a commercial biologically based IMRT treatment planning system. Med Phys 2008, 35: 5851-5860. 10.1118\/1.3013556","journal-title":"Med Phys"},{"key":"389_CR5","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1118\/1.1924312","volume":"32","author":"Y Yang","year":"2005","unstructured":"Yang Y, Xing L: Towards biologically conformal radiation therapy (BCRT): selective IMRT dose escalation under the guidance of spatial biology distribution. Med Phys 2005, 32: 1473-1484. 10.1118\/1.1924312","journal-title":"Med Phys"},{"key":"389_CR6","first-page":"257","volume":"139","author":"Y Kim","year":"2008","unstructured":"Kim Y, Tome W: Optimization of radiotherapy using biological parameters. Cancer Treat Res 2008, 139: 257-278.","journal-title":"Cancer Treat Res"},{"key":"389_CR7","doi-asserted-by":"publisher","first-page":"4599","DOI":"10.1118\/1.2975229","volume":"35","author":"CP South","year":"2008","unstructured":"South CP, Partridge M, Evans PM: A theoretical framework for prescribing radiotherapy dose distributions using patient-specific biological information. Med Phys 2008, 35: 4599-4611. 10.1118\/1.2975229","journal-title":"Med Phys"},{"key":"389_CR8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1053\/srao.2001.23478","volume":"11","author":"ED Yorke","year":"2001","unstructured":"Yorke ED: Modeling the effects of inhomogeneous dose distributions in normal tissues. Semin Radiat Oncol 2001, 11: 197-209. 10.1053\/srao.2001.23478","journal-title":"Semin Radiat Oncol"},{"key":"389_CR9","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1080\/09553009214552071","volume":"62","author":"P Kallman","year":"1992","unstructured":"Kallman P, Agren A, Brahme A: Tumour and normal tissue responses to fractionated non-uniform dose delivery. Int J Radiat Biol 1992, 62: 249-262. 10.1080\/09553009214552071","journal-title":"Int J Radiat Biol"},{"key":"389_CR10","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/0360-3016(89)90462-8","volume":"17","author":"JT Lyman","year":"1989","unstructured":"Lyman JT, Wolbarst AB: Optimization of radiation therapy, IV: A dose-volume histogram reduction algorithm. Int J Radiat Oncol Biol Phys 1989, 17: 433-436. 10.1016\/0360-3016(89)90462-8","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR11","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/0360-3016(94)00475-Z","volume":"32","author":"P Okunieff","year":"1995","unstructured":"Okunieff P, Morgan D, Niemierko A, Suit HD: Radiation dose-response of human tumors. Int J Radiat Oncol Biol Phys 1995, 32: 1227-1237. 10.1016\/0360-3016(94)00475-Z","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR12","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1118\/1.595312","volume":"10","author":"TE Schultheiss","year":"1983","unstructured":"Schultheiss TE, Orton CG, Peck RA: Models in radiotherapy: volume effects. Med Phys 1983, 10: 410-415. 10.1118\/1.595312","journal-title":"Med Phys"},{"key":"389_CR13","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/S0360-3016(01)02585-8","volume":"52","author":"Q Wu","year":"2002","unstructured":"Wu Q, Mohan R, Niemierko A, Schmidt-Ullrich R: Optimization of intensity-modulated radiotherapy plans based on the equivalent uniform dose. Int J Radiat Oncol Biol Phys 2002, 52: 224-235. 10.1016\/S0360-3016(01)02585-8","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR14","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/S0360-3016(02)03986-X","volume":"55","author":"Y Seppenwoolde","year":"2003","unstructured":"Seppenwoolde Y, Lebesque JV, de Jaeger K, Belderbos JS, Boersma LJ, Schilstra C, et al.: Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys 2003, 55: 724-735. 10.1016\/S0360-3016(02)03986-X","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR15","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.ijrobp.2006.10.014","volume":"67","author":"M Sohn","year":"2007","unstructured":"Sohn M, Yan D, Liang J, Meldolesi E, Vargas C, Alber M: Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models. Int J Radiat Oncol Biol Phys 2007, 67: 1066-1073. 10.1016\/j.ijrobp.2006.10.014","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR16","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1080\/095530097143860","volume":"71","author":"SM Bentzen","year":"1997","unstructured":"Bentzen SM, Tucker SL: Quantifying the position and steepness of radiation dose-response curves. Int J Radiat Biol 1997, 71: 531-542. 10.1080\/095530097143860","journal-title":"Int J Radiat Biol"},{"key":"389_CR17","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1016\/j.ijrobp.2009.07.1754","volume":"76","author":"LB Marks","year":"2010","unstructured":"Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, et al.: Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010, 76: S10-S19. 10.1016\/j.ijrobp.2009.07.1754","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR18","doi-asserted-by":"publisher","first-page":"S58","DOI":"10.1016\/j.ijrobp.2009.06.090","volume":"76","author":"JO Deasy","year":"2010","unstructured":"Deasy JO, Moiseenko V, Marks L, Chao KS, Nam J, Eisbruch A: Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys 2010, 76: S58-S63. 10.1016\/j.ijrobp.2009.06.090","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR19","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0360-3016(03)01437-8","volume":"58","author":"MW Munter","year":"2004","unstructured":"Munter MW, Karger CP, Hoffner SG, Hof H, Thilmann C, Rudat V, et al.: Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy. Int J Radiat Oncol Biol Phys 2004, 58: 175-184. 10.1016\/S0360-3016(03)01437-8","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR20","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/j.ijrobp.2006.09.035","volume":"67","author":"MW Munter","year":"2007","unstructured":"Munter MW, Hoffner S, Hof H, Herfarth KK, Haberkorn U, Rudat V, et al.: Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine. Int J Radiat Oncol Biol Phys 2007, 67: 651-659. 10.1016\/j.ijrobp.2006.09.035","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR21","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.ijrobp.2004.12.009","volume":"62","author":"N Bhandare","year":"2005","unstructured":"Bhandare N, Monroe AT, Morris CG, Bhatti MT, Mendenhall WM: Does altered fractionation influence the risk of radiation-induced optic neuropathy? Int J Radiat Oncol Biol Phys 2005, 62: 1070-1077. 10.1016\/j.ijrobp.2004.12.009","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR22","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.ijrobp.2004.07.664","volume":"61","author":"AT Monroe","year":"2005","unstructured":"Monroe AT, Bhandare N, Morris CG, Mendenhall WM: Preventing radiation retinopathy with hyperfractionation. Int J Radiat Oncol Biol Phys 2005, 61: 856-864. 10.1016\/j.ijrobp.2004.07.664","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"389_CR23","doi-asserted-by":"publisher","first-page":"S396","DOI":"10.1016\/j.ijrobp.2008.06.1274","volume":"72","author":"N Bhandare","year":"2008","unstructured":"Bhandare N, Song W, Moiseenko V, Malyapa R, Morris CG, Mendenhall WM: Radiation-induced optic neuropothy: dose response and modeling total dose and fractionation. International Journal of Radiation Oncology Biology Physics 2008,72(1):S396. Ref Type: Abstract","journal-title":"International Journal of Radiation Oncology Biology Physics"},{"issue":"6","key":"389_CR24","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1118\/1.2962693","volume":"35","author":"W Song","year":"2008","unstructured":"Song W, Bhandare N, Moiseenko V: Dose Response Analysis of Radiation-Induced Retinopathy (RIRP) Single-Institution Data Using the Lyman NTCP Model. Med Phys 2008,35(6):2934. Ref Type: Abstract","journal-title":"Med Phys"},{"key":"389_CR25","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1080\/09553008514553221","volume":"49","author":"HD Thames","year":"1986","unstructured":"Thames HD, Rozell ME, Tucker SL, Ang KK, Fisher DR, Travis EL: Direct analysis of quantal radiation response data. Int J Radiat Biol Relat Stud Phys Chem Med 1986, 49: 999-1009. 10.1080\/09553008514553221","journal-title":"Int J Radiat Biol Relat Stud Phys Chem Med"},{"key":"389_CR26","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/0167-8140(93)90175-8","volume":"29","author":"SA Roberts","year":"1993","unstructured":"Roberts SA, Hendry JH: The delay before onset of accelerated tumour cell repopulation during radiotherapy: a direct maximum-likelihood analysis of a collection of worldwide tumour-control data. Radiother Oncol 1993, 29: 69-74. 10.1016\/0167-8140(93)90175-8","journal-title":"Radiother Oncol"},{"key":"389_CR27","doi-asserted-by":"publisher","first-page":"119","DOI":"10.2307\/2685469","volume":"52","author":"A Agresti","year":"1998","unstructured":"Agresti A, Coull B: Approximate is better than \"exact\" for interval estimation of binomial proportions. The American Statistician 1998, 52: 119-126. 10.2307\/2685469","journal-title":"The American Statistician"},{"key":"389_CR28","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S0360-3016(98)00057-1","volume":"41","author":"M Langer","year":"1998","unstructured":"Langer M, Morrill SS, Lane R: A test of the claim that plan rankings are determined by relative complication and tumor-control probabilities. Int J Radiat Oncol Biol Phys 1998, 41: 451-457. 10.1016\/S0360-3016(98)00057-1","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR29","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/S0360-3016(98)00128-X","volume":"41","author":"M Zaider","year":"1998","unstructured":"Zaider M, Amols HI: A little to a lot or a lot to a little: is NTCP always minimized in multiport therapy? Int J Radiat Oncol Biol Phys 1998, 41: 945-950. 10.1016\/S0360-3016(98)00128-X","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR30","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/S0360-3016(99)00473-3","volume":"46","author":"V Moiseenko","year":"2000","unstructured":"Moiseenko V, Battista J, van Dyk J: Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme. Int J Radiat Oncol Biol Phys 2000, 46: 983-993. 10.1016\/S0360-3016(99)00473-3","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR31","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0167-8140(01)00441-8","volume":"61","author":"F Claus","year":"2001","unstructured":"Claus F, De Gersem W, Vanhoutte I, Duthoy W, Remouchamps V, De Wagter C, et al.: Evaluation of a leaf position optimization tool for intensity modulated radiation therapy of head and neck cancer. Radiother Oncol 2001, 61: 281-286. 10.1016\/S0167-8140(01)00441-8","journal-title":"Radiother Oncol"},{"key":"389_CR32","volume-title":"Applied Radiobiology and Bioeffect Planning","author":"DR Wigg","year":"2001","unstructured":"Wigg DR: Applied Radiobiology and Bioeffect Planning. 1st edition. Madison, Wisconsin: Medical Physics Publishing; 2001.","edition":"1"},{"key":"389_CR33","doi-asserted-by":"publisher","first-page":"3544","DOI":"10.1118\/1.2760027","volume":"34","author":"MG Witte","year":"2007","unstructured":"Witte MG, van der GJ, Schneider C, Lebesque JV, Alber M, van Herk M: IMRT optimization including random and systematic geometric errors based on the expectation of TCP and NTCP. Med Phys 2007, 34: 3544-3555. 10.1118\/1.2760027","journal-title":"Med Phys"},{"key":"389_CR34","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1016\/0360-3016(89)90972-3","volume":"16","author":"GJ Kutcher","year":"1989","unstructured":"Kutcher GJ, Burman C: Calculation of complication probability factors for non-uniform normal tissue irradiation: the effective volume method. Int J Radiat Oncol Biol Phys 1989, 16: 1623-1630. 10.1016\/0360-3016(89)90972-3","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"389_CR35","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1080\/02841860600936369","volume":"45","author":"LA Dawson","year":"2006","unstructured":"Dawson LA, Eccles C, Craig T: Individualized image guided iso-NTCP based liver cancer SBRT. Acta Oncol 2006, 45: 856-864. 10.1080\/02841860600936369","journal-title":"Acta Oncol"}],"container-title":["Radiation Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1748-717X-6-61.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T14:19:44Z","timestamp":1630505984000},"score":1,"resource":{"primary":{"URL":"https:\/\/ro-journal.biomedcentral.com\/articles\/10.1186\/1748-717X-6-61"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,6]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["389"],"URL":"https:\/\/doi.org\/10.1186\/1748-717x-6-61","relation":{},"ISSN":["1748-717X"],"issn-type":[{"value":"1748-717X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,6]]},"assertion":[{"value":"31 January 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"61"}}