Cited by 1,826Advanced Radiotherapy TechniquesRadiation Therapy and DosimetryEffects of Radiation Exposure

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Use of Normal Tissue Complication Probability Models in the Clinic

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Marks, Lawrence B., Yorke, Ellen D., Jackson, Andrew, Ten Haken, Randall K., Constine, Louis S., Eisbruch, Avraham, Bentzen, Søren M., Nam, Jiho, Deasy, Joseph O.·2010·International Journal of Radiation Oncology*Biology*Physics

DOI 10.1016/j.ijrobp.2009.07.1754PMC PMC4041542

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Abstract

The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included.

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Tolerance of normal tissue to therapeutic irradiation
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Proposal of a post-prostatectomy clinical target volume based on pre-operative MRI: volumetric and dosimetric comparison to the RTOG guidelines
Croke, J. M., Maclean, J., Nyiri, B. J., Li, Y., Malone, K., Avruch, L. I., Kayser, C., & Malone, S. C. (2014) · Radiation Oncology · doi:10.1186/s13014-014-0303-6 · Cited by 17
“Rectal DVH: 77% of CTV RTOG cases passed all RADICALS criteria and 37% all QUANTEC criteria; versus 73% and 40% for CTV MRI (p = 1.0 for both).”
MethodInfluential
Volumetric-modulated arc radiotherapy for pancreatic malignancies: Dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy
Nabavizadeh, N., Simeonova, A., Waller, J. G., Romer, J. L., Monaco, D., Elliott, D. A., Tanyi, J. A., Fuß, M., Thomas, C. R., & Holland, J. M. (2014) · Medical dosimetry · doi:10.1016/j.meddos.2014.04.001 · Cited by 17
“Individual isodose constraints were placed to ensure that the maximal tolerated doses to the OARs per published Quantitative Analysis of Normal Tissue Effects in the Clinic guidelines were not exceeded.(17) The summated large-field and boost constraints used during planning included the following: the spinal cord Dmax…”
Background
Early intervention using high-precision radiotherapy preserved visual function for five consecutive patients with optic nerve sheath meningioma
Inoue, T., Mimura, O., Masai, N., Ohashi, A., Ikenaga, K., Okuno, Y., NISHIGUCHI, I., & Oh, R. (2018) · International Journal of Clinical Oncology · doi:10.1007/s10147-018-1284-5 · Cited by 17
“All patients were diagnosed * Toshihiko Inoue toinoue@r6.ucom.ne.jp 1 Ashiya Radiotherapy Clinic Nozomi, 3-84 Yoko-cho, Ashiya 659-0034, Japan 2 Department of Neuro-ophthalmological Therapeutics, Hyogo College of Medicine, Nishinomiya, Japan 3 Miyakojima IGRT Clinic, Osaka, Japan with ONSM by an ophthalmologist (OM).”
BackgroundInfluential
External beam planning module of Eclipse for external beam radiation therapy
Saw, C. B., Li, S.-C., Battin, F., McKeague, J., & Peters, C. A. (2018) · Medical dosimetry · doi:10.1016/j.meddos.2018.03.003 · Cited by 17
Dose-guided patient positioning in proton radiotherapy using multicriteria-optimization
Kurz, C., Süss, P., Arnsmeyer, C., Haehnle, J., Teichert, K., Landry, G., Hofmaier, J., Exner, F., Hille, L., Kamp, F., et al. (2018) · Zeitschrift für Medizinische Physik · doi:10.1016/j.zemedi.2018.10.003 · Cited by 17
Intensity-modulated radiotherapy for prostate cancer with seminal vesicle involvement (T3b): A multicentric retrospective analysis
Goupy, F., Supiot, S., Pasquier, D., Latorzeff, I., Schick, U., Monpetit, E., Martinage, G., Hervé, C., Proust, B. L., Castelli, J., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210514 · Cited by 17
“Vx: Dose–volume threshold recommendations (volume of organ receiving at least x Gy in %) according to the GETUG ( ̊) (21); RTOG (#) [22]; QUANTEC (&) [20] or Fiorino et al.”
Method
Clinical Spectrum and Outcomes of Ocular and Periocular Complications following External-Beam Radiotherapy for Inoperable Malignant Maxillary Sinus Tumors
Ting, D. S. J., Rana-Rahman, R., Ng, J. Y., Wilkinson, D., Ah-Kine, D., & Patel, T. (2020) · Ocular Oncology and Pathology · doi:10.1159/000511011 · Cited by 17
Progress and prospects of flattening filter free beam technology in radiosurgery and stereotactic body radiotherapy
Ghemis, D. M., & Marcu, L. G. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103396 · Cited by 18
Targeted Endoradiotherapy with Lu2O3-iPSMA/-iFAP Nanoparticles Activated by Neutron Irradiation: Preclinical Evaluation and First Patient Image
Luna‐Gutiérrez, M., Ocampo‐García, B., Jiménez‐Mancilla, N., Ancira-Cortez, A., Trujillo-Benítez, D., Hernández-Jiménez, T., Ramírez-Nava, G., Hernández-Ramírez, R., Santos‐Cuevas, C., & Ferro‐Flores, G. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14040720 · Cited by 17
Intramedullary Spinal Cord Lesions: A Single-Center Experience
Jecko, V., Roblot, P., Mongardi, L., Ollivier, M., Piccoli, N. D., Charleux, T., Wavasseur, T., Gimbert, É., Liguoro, D., Chotard, G., et al. (2022) · Neurospine · doi:10.14245/ns.2143190.595 · Cited by 17
Dynamic conformal arc cranial stereotactic radiosurgery: implications of multileaf collimator margin on dose–volume metrics
Tanyi, J. A., Doss, E. J., Kato, C. M., Monaco, D., ZMeng, L., Chen, Y., Kubicky, C. D., Marquez, C., & Fuß, M. (2012) · British Journal of Radiology · doi:10.1259/bjr/79414773 · Cited by 17
Preliminary results of radiotherapy for primary intraocular non-Hodgkin lymphoma
Mikami, R., Nakayama, H., Gotô, H., Kimura, K., Usui, Y., Nogi, S., Tajima, Y., Okubo, M., Kanesaka, N., Sugahara, S., et al. (2013) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2013.769216 · Cited by 17
The benefit of using bladder sub-volume equivalent uniform dose constraints in prostate intensity-modulated radiotherapy planning
Zhu, J., Simon, A., Haigron, P., Lafond, C., Acosta, O., Shu, H., Castelli, J., Li, B., & de Crevoisier, R. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s116508 · Cited by 17
The impact of continuous positive airway pressure on radiation dose to heart and lung during left-sided postmastectomy radiotherapy when deep inspiration breath hold technique is not applicable: a case report
Kil, W. J., Pham, T., Hossain, S., Casaigne, J., Jones, K. R., & Khalil, M. (2018) · Radiation Oncology Journal · doi:10.3857/roj.2018.00017 · Cited by 17
“, hypercholesterolemia, hypertension, and cigarette smoking) are also closely related with cardiac and pulmonary events, it has been emphasized to lower radiation dose to the heart and lung as low as reasonably achievable during radiotherapy (RT) for breast cancer to reduce RT-related cardiac and pulmonary toxicities…”
BackgroundInfluential
Sensorineural Hearing Loss in Nasopharyngeal Carcinoma Survivors in the Modern Treatment Era — The Early and Late Effects of Radiation and Cisplatin
Yip, P. L., Mok, K. C. J., Ho, H., Lee, W. Y. V., Wong, A. C. L., Lau, C. T., Wong, F. C. S., Yeung, K. W. A., & Lee, S. F. (2021) · Clinical Oncology · doi:10.1016/j.clon.2021.10.013 · Cited by 16
Parameters of the Lyman Model for Calculation of Normal-Tissue Complication Probability: A Systematic Literature Review
Dennstädt, F., Medová, M., Putora, P. M., & Glatzer, M. (2022) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2022.08.039 · Cited by 16
“Whereas the latter ones are estimating complication probability under uniform irradiation, the mechanistic models ascribe the volume dependence of the so-called ‘serial’ or ‘parallel’ complications to radiotherapy-mediated disruption of the organ’s functional architecture 22 .”
Background
A Dosimetric and Radiobiological Comparison of Intensity Modulated Radiotherapy, Volumetric Modulated Arc Therapy and Helical Tomotherapy Planning Techniques in Synchronous Bilateral Breast Cancer
Balasubramanian, S., & Shobana, M. K. (2022) · Asian Pacific Journal of Cancer Prevention · doi:10.31557/apjcp.2022.23.12.4233 · Cited by 16
“OARs’ tolerance dose for producing 50% of complications (if irradiated uniformly) is TD50 (Marks et al., 2010; Niemierko et al., 1991) Table 1. summarises the parameters utilized for the calculations of Niemierko’s EUD model (Emami et al., 1991).”
BackgroundMethod
Factors associated with acute esophagitis during radiation therapy for lung cancer
Herr, D. J., Yin, H., Bergsma, D. P., Dragovic, A. F., Matuszak, M. M., Grubb, M., Dominello, M. M., Movsas, B., Kestin, L. L., Boike, T. P., et al. (2024) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2024.110349 · Cited by 16
“…Effects (QUANTEC) analysis summarized the available literature and recommended a mean esophagus dose (MED) 34 Gy for limiting the rate of grade 3 esophagitis to 5 – 20 %, as well as suggesting additional volumetric constraints for limiting the rate of grade 2 esophagitis to less than 30 %[13].”
Method
Clinical benefits of deep inspiration breath-hold in postoperative radiotherapy for right-sided breast cancer: a meta-analysis
Zhuo-cheng, L., Jian, C., Li, Y., Pan, Z., Yang, G., & Sun, X. (2024) · BMC Cancer · doi:10.1186/s12885-024-12992-2 · Cited by 16
“The current guidelines for treatment planning in right-sided breast cancer suggest maintaining a mean liver dose (Dmean) within the range of 28–32 Gy to minimize the risk of radiation-induced liver injury [40].”
Background
Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis
Kim, E. S., & Yeo, S. (2014) · Oncology Letters · doi:10.3892/ol.2014.2039 · Cited by 16
Development of a small-animal focal brain irradiation model to study radiation injury and radiation-injury modifiers
Hidéghety, K., Plangár, I., Mán, I., Fekete, G., Nagy, Z., Volford, G., Tőkés, T., Szabó, E. R., Szabó, Z., Brinyiczki, K., et al. (2013) · International Journal of Radiation Biology · doi:10.3109/09553002.2013.784424 · Cited by 16
Comp Plan: A computer program to generate dose and radiobiological metrics from dose-volume histogram files
Holloway, L. C., Miller, J.-A., Kumar, S., Whelan, B., & Vinod, S. K. (2012) · Medical dosimetry · doi:10.1016/j.meddos.2011.11.004 · Cited by 16
Comparison of once daily radiotherapy to 60 G y and twice daily radiotherapy to 45 G y for limited stage small‐cell lung cancer
Han, D., Hao, S., Tao, C., Zhao, Q., Wei, Y., Song, Z., & Li, B. (2015) · Thoracic Cancer · doi:10.1111/1759-7714.12262 · Cited by 16
A theoretical stochastic control framework for adapting radiotherapy to hypoxia
Saberian, F., Ghate, A., & Kim, M. (2016) · Physics in Medicine and Biology · doi:10.1088/0031-9155/61/19/7136 · Cited by 16
“The tolerance dose values for various normal tissues were similar to [3, 23, 33, 34] and are listed in Table 2 below.”
Background
Normal tissue complication probability modeling of radiation-induced sensorineural hearing loss after head-and-neck radiation therapy
Cheraghi, S., Nikoofar, A., Bakhshandeh, M., Khoei, S., Farahani, S., Abdollahi, H., & Mahdavi, S. R. (2017) · International Journal of Radiation Biology · doi:10.1080/09553002.2017.1385872 · Cited by 16
“It has been suggested that the mean and prescribed dose to the cochlea should be limited to below 45Gy and 12–14Gy for conventionally fractionated and stereotactic radiosurgery, respectively (Marks et al. 2010).”
Background
Identifying optimal clinical scenarios for synchrotron microbeam radiation therapy: A treatment planning study
Smyth, L. M. L., Day, L. R. J., Woodford, K., Rogers, P. A. W., Crosbie, J. C., & Senthi, S. (2019) · Physica Medica · doi:10.1016/j.ejmp.2019.03.019 · Cited by 16
Liver-directed combined radiotherapy as a bridge to curative surgery in locally advanced hepatocellular carcinoma beyond the Milan criteria
Lee, W. H., Byun, H. K., Choi, J. S., Choi, G. H., Han, D. H., Joo, D. J., Kim, D. Y., Han, K.-H., & Seong, J. (2020) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2020.07.046 · Cited by 16
Carbon ion reirradiation compared to intensity-modulated re-radiotherapy for recurrent head and neck cancer (CARE): a randomized controlled trial
Held, T., Lang, K., Regnery, S., Weusthof, K., Hommertgen, A., Jäkel, C., Tonndorf‐Martini, E., Krisam, J., Plinkert, P. K., Zaoui, K., et al. (2020) · Radiation Oncology · doi:10.1186/s13014-020-01625-0 · Cited by 16
A predictive model to guide management of the overlap region between target volume and organs at risk in prostate cancer volumetric modulated arc therapy
Mattes, M. D., Lee, J. C., Elnaiem, S., Guirguis, A., Ikoro, N. C., & Ashamalla, H. L. (2014) · Radiation Oncology Journal · doi:10.3857/roj.2014.32.1.23 · Cited by 16
“23 boost plans were chosen to be consistent with the clinical dose-volume constraints for a full course of prostate IMRT represented in the QUANTEC guidelines [21].”
Method
Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols
Liu, F., Yorke, E. D., Belderbos, J. S. A., Borst, G. R., Rosenzweig, K. E., Lebesque, J. V., & Jackson, A. (2012) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2012.03.024 · Cited by 16
Self-citation
DOSIMETRIC COMPARISON OF WHOLE BREAST RADIOTHERAPY USING FIELD IN FIELD AND CONFORMAL RADIOTHERAPY TECHNIQUES IN EARLY STAGE BREAST CANCER
Yavaş, G., Yavaş, Ç., & Acar, H. (2012) · Iranian Journal of radiation research/Iranian journal of radiation research · Cited by 16
Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms
Yang, J., Zhang, P., Zhang, L., Shu, H., Li, B., & Gui, Z. (2017) · Physica Medica · doi:10.1016/j.ejmp.2016.12.021 · Cited by 16
Uncomplicated and Cancer-Free Control Probability (UCFCP): A new integral approach to treatment plan optimization in photon radiation therapy
Sánchez-Nieto, B., Romero‐Expósito, M., Terrón, J. A., & Sánchez-Doblado, F. (2017) · Physica Medica · doi:10.1016/j.ejmp.2017.03.025 · Cited by 16
Salvage reirradiation for local failure of prostate cancer after curative radiation therapy: Association of rectal toxicity with dose distribution and normal-tissue complication probability models
Dipasquale, G., Zilli, T., Fiorino, C., Rouzaud, M., & Miralbell, R. (2018) · Advances in Radiation Oncology · doi:10.1016/j.adro.2018.06.001 · Cited by 16
Contemporary Radiation Treatment of Prostate Cancer in Africa: A Ghanaian Experience
Asamoah, F. A., Yarney, J., Awasthi, S., Vanderpuye, V. D. N. K., Venkat, P. S., Fink, A., Naghavi, A. O., Abrahams, A. O. D., Mensah, J. E., Sasu, E., et al. (2018) · Journal of Global Oncology · doi:10.1200/jgo.17.00234 · Cited by 16
“Multiple fields (four to six), wedges, and customized cerrobend blocks were used to optimize dose distribution to the planning target volume and to meet constraints for organs at risk using quantitative analysis of normal tissue effects in the clinic for the bladder, small bowel, rectum, and femoral heads.(11) All tre…”
Method
A Phase I/II Study of Stereotactic Hypofractionated Once-weekly Radiation Therapy (SHORT) for Prostate Cancer
Mallick, I., Arunsingh, M. A., Chakraborty, S., Arun, B., Prasath, S., Roy, P., Dabkara, D., Achari, R. B., Chatterjee, S., & Gupta, S. (2019) · Clinical Oncology · doi:10.1016/j.clon.2019.09.046 · Cited by 16
Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer
Chung, J.-H., Kang, S. Y., Wu, H.-G., Seo, Y. S., Kim, D., Kang, K. W., Kim, H. J., & Cheon, G. J. (2020) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2020.01.009 · Cited by 16
Radiochemotherapy with Paclitaxel for Recurrent Previously Irradiated Squamous Cell Carcinoma of the Head and Neck
Rades, D., Seidl, D., Wollenberg, B., Schild, S. E., & Hakim, S. G. (2016) · Anticancer Research · doi:10.21873/anticanres.11126 · Cited by 15
Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO
Spatola, C., Privitera, G., Milazzotto, R., Tocco, A., Acquaviva, G., Marletta, F., Marino, L., Grazia, A. D., Salvo, R., Cartia, G., et al. (2019) · La radiologia medica · doi:10.1007/s11547-019-01007-x · Cited by 16
A randomized prospective study comparing acute toxicity, compliance and objective response rate between simultaneous integrated boost and sequential intensity-modulated radiotherapy for locally advanced head and neck cancer
Grover, A., Soni, T. P., Patni, N., Singh, D. K., Jakhotia, N., Gupta, A. K., Sharma, L. M., Sharma, S., & Gothwal, R. S. (2021) · Radiation Oncology Journal · doi:10.3857/roj.2020.01018 · Cited by 15
“as per the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) guidelines [10].”
Method
Predicting acute severe toxicity for head and neck squamous cell carcinomas by combining dosimetry with a radiosensitivity biomarker: a pilot study
Deneuve, S., Bastogne, T., Duclos, M., Mirjolet, C., Bois, P., Bachmann, P., Nokovitch, L., Roux, P., Girodet, D., Poupart, M., et al. (2022) · Tumori Journal · doi:10.1177/03008916221078061 · Cited by 15
A Patient Selection Approach Based on NTCP Models and DVH Parameters for Definitive Proton Therapy in Locally Advanced Sinonasal Cancer Patients
Mirandola, A., Russo, S., Bonora, M., Vischioni, B., Camarda, A. M., Ingargiola, R., Molinelli, S., Ronchi, S., Rossi, E., Vai, A., et al. (2022) · Cancers · doi:10.3390/cancers14112678 · Cited by 15
“The volume of optic nerves and chiasm receiving doses higher than 55 Gy(RBE) was also estimated, being related to the risk of radiation-induced optic neuropathy (RION), as reported in QUANTEC series [14,18,29,30].”
Background
A New Approach to Quantify and Grade Radiation Dermatitis Using Deep-Learning Segmentation in Skin Photographs
Park, Y. I., Choi, S. H., Hong, C., Cho, M. S., Son, J., Han, M. C., Kim, J., Kim, H., Kim, D. W., & Kim, J. S. (2022) · Clinical Oncology · doi:10.1016/j.clon.2022.07.001 · Cited by 15
Personalized mid-course FDG-PET based adaptive treatment planning for non-small cell lung cancer using machine learning and optimization
Ajdari, A., Liao, Z. X., Mohan, R., Wei, X., & Bortfeld, T. R. (2022) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ac88b3 · Cited by 15
“Additionally, in linewith the accepted level of toxicity for grade 2RP, as reported in QUANTEC2013 (Marks et al 2010), an upper bound q = 20%was set for the RPNTCP constraint (2.12).”
BackgroundInfluential

Authors: Marks, L. B., Yorke, E. D., Jackson, A., Ten Haken, R. K., Constine, L. S., Eisbruch, A., Bentzen, S. M., Nam, J., & Deasy, J. O.
Affiliations: University of North Carolina at Chapel Hill (US)
Memorial Sloan Kettering Cancer Center (US)
University of Rochester Medicine (US)
University of Michigan (US)
University of Wisconsin–Madison (US)
Washington University in St. Louis (US)
Corresponding author: Marks, Lawrence B.
ORCID: Marks, Lawrence B.
Yorke, Ellen D.
Jackson, Andrew
Constine, Louis S.
Eisbruch, Avraham
Bentzen, Søren M.
Nam, Jiho
Deasy, Joseph O.
Venue: International Journal of Radiation Oncology*Biology*Physics
Publisher: Elsevier BV
Published: 2010-03
Volume: 76
Issue: 3
Pages: S10-S19
ISSN: 0360-3016 (ISSN-L)
DOI: 10.1016/j.ijrobp.2009.07.1754
PMC: PMC4041542
OpenAlex: W2046701188
Cited by: 1,826
References: 30
Citations by year: 2026: 92 · 2025: 110 · 2024: 125 · 2023: 132 · 2022: 130 · 2021: 160 · 2020: 138 · 2019: 146 · 2018: 164 · 2017: 122 · 2016: 108 · 2015: 102 · 2014: 112 · 2013: 87 · 2012: 55
FWCI: 56.07
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: International Journal of Radiation Oncology*Biology*Physics (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Lance Armstrong Foundation
Armstrong Foundation
National Institutes of Health
National Cancer Institute (CA69579, R29CA069579, R29CA085181, R01CA069579, R01CA129182, R01CA085181, CA85181)
Topics: Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords: normal tissue complication probability, QUANTEC, normal tissue tolerance, NTCP models
MeSH terms: Adult, Child, Dose-Response Relationship, Radiation, Humans, Models, Biological, Organ Specificity, Radiation Injuries, Radiation Tolerance, Models, Statistical, Practice Guidelines as Topic, Radiation Oncology, Dose Fractionation, Radiation

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Use of Normal Tissue Complication Probability Models in the Clinic

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