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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Kraus, K. M., Winter, J., Yating, Z., Ahmed, M., Combs, S. E., Wilkens, J. J., & Bartzsch, S. H. (2022) · Cancers · doi:10.3390/cancers14030685 · Cited by 13
Dose comparison of robustly optimized intensity modulated proton therapy (IMPT) vs IMRT and VMAT photon plans for testicular seminoma
Rønde, H. S., Kronborg, C. J. S., Høyer, M., Hansen, J., Bak, M. E., Agergaard, S. N., Als, A. B., Agerbæk, M., Lauritsen, J., Petersen, P. M., et al. (2023) · Acta Oncologica · doi:10.1080/0284186x.2023.2254925 · Cited by 13
Optically stimulated luminescence dosimeters for simultaneous measurement of point dose and dose-weighted LET in an adaptive proton therapy workflow
Bobić, M., Christensen, J. B., Lee, H., Choulilitsa, E., Czerska, K., Togno, M., Safai, S., Yukihara, E. G., Winey, B. A., Lomax, A., et al. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2023.1333039 · Cited by 13
Influence of monte carlo variance with fluence smoothing in VMAT treatment planning with Monaco TPS
Sarkar, B., Manikandan, A., Nandy, M., Munshi, A., Sayan, P., & Sujatha, N. (2016) · Indian Journal of Cancer · doi:10.4103/0019-509x.180820 · Cited by 13
A treatment planning study of prone vs. supine positions for locally advanced rectal carcinoma
Scobioala, S., Kittel, C., Niermann, P., Wolters, H., Susek, K. H., Haverkamp, U., & Eich, H. T. (2018) · Strahlentherapie und Onkologie · doi:10.1007/s00066-018-1324-0 · Cited by 13
Dosimetric benefits of adaptive radiation therapy for patients with stage III non-small cell lung cancer
Hoppen, L., Sarria, G. R., Kwok, C. S., Boda‐Heggemann, J., Buergy, D., Ehmann, M., Giordano, F. A., & Fleckenstein, J. (2023) · Radiation Oncology · doi:10.1186/s13014-023-02222-7 · Cited by 13
“Since the known OAR tolerances are today solely based on the initial treatment plans [44], OAR tolerances are likely to change for ART.”
Background
Stereotactic Body Radiotherapy: Volumetric Modulated Arc Therapy versus 3D Non-Coplanar Conformal Radiotherapy for the Treatment of Early Stage Lung Cancer
Herbert, C., Kwa, W., Nakano, S., James, K., Moiseenko, V., Wu, J., Schellenberg, D. D., & Liu, M. (2013) · Technology in Cancer Research & Treatment · doi:10.7785/tcrt.2012.500338 · Cited by 13
“The introduction and adoption of new treatment techniques is dependent upon one or both of two factors: improved dosimetry and faster delivery time (7).”
BackgroundResult
Contraintes de doses aux organes à risque en radiothérapie conformationnelle et stéréotaxique : intestin grêle et duodénum
Goupy, F., Chajon, É., Castelli, J., Prisé, É. L., Duvergé, L., Jaksic, N., Vogin, G., Monpetit, E., Klein, V. A., de Bosschère, L., et al. (2017) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2017.07.036 · Cited by 13
Volumetric modulated arc therapy applied to synchronous bilateral breast cancer radiotherapy: dosimetric study on deep inspiration breath hold versus free breathing set up
Gaudino, D., Cima, S., Frapolli, M., Daniele, D., Muoio, B., Pesce, G., Martucci, F., Azinwi, N. C., Bosetti, D. G., Bellesi, L., et al. (2018) · Biomedical Physics & Engineering Express · doi:10.1088/2057-1976/aac19b · Cited by 13
Role of Germline Genetics in Identifying Survivors at Risk for Adverse Effects of Cancer Treatment
Morton, L. M., Kerns, S. L., & Dolan, M. E. (2018) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_201391 · Cited by 13
Central Nervous System Cancers
Nath, S. K., Trifiletti, D. M., Zaorsky, N. G., & Rusthoven, C. G. (2019) · Springer eBooks · doi:10.1007/978-3-319-96809-4_3 · Cited by 14
Evolving Role of Stereotactic Body Radiation Therapy in the Management of Spine Metastases
de Moraes, F. Y., Chen, X., Yan, M., Spratt, D. E., Redmond, K., Jackson, W., & Yamada, Y. J. (2020) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2019.12.001 · Cited by 13
Construction des modèles radiobiologiques de type TCP (tumor control probability) et NTCP (normal tissue complication probability) : de la dose à la prédiction des effets cliniques
Chaikh, A., Thariat, J., Thureau, S., Tessonnier, T., Kammerer, E., Fontbonne, C., Dubray, B. M., Balosso, J., & Fontbonne, J. M. (2020) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2019.12.004 · Cited by 13
Dosimetric comparison of 3-dimensional conformal and field-in-field radiotherapy techniques for the adjuvant treatment of early stage endometrial cancer
Yavaş, G., Yavaş, Ç., Acar, H., Buyukyoruk, A., Çobanoğlu, G., Kerimoğlu, Ö. S., Yavas, O., & Çelık, Ç. (2012) · Physica Medica · doi:10.1016/j.ejmp.2012.11.002 · Cited by 13
Development and validation of a heart atlas to study cardiac exposure to radiation following treatment for breast cancer
Koay, E. J., & Smith, B. D. (2011) · Breast Diseases A Year Book Quarterly · doi:10.1016/j.breastdis.2011.03.016 · Cited by 13
Radiothérapie conformationnelle avec modulation d’intensité des cancers des voies aérodigestives supérieures. Dose de tolérance des tissus sains : moelle épinière et plexus brachial
Boisselier, P., Racadot, S., Thariat, J., Graff-Cailleaud, P., & Pointreau, Y. (2016) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2016.08.124 · Cited by 13
A Trans-Agency Workshop on the Pathophysiology of Radiation-Induced Lung Injury
Cassatt, D. R., Gorovets, A., Karimi-Shah, B. A., Roberts, R., Price, P. W., Satyamitra, M. M., Todd, N. F., Wang, S., & Marzella, L. (2021) · Radiation Research · doi:10.1667/rade-21-00127.1 · Cited by 12
“In another study, Marks and colleagues (49) studied the probability of RP developing in cancer patients treated with partial-lung irradiation.”
Background
Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose
Ong, A. L. K., Knight, K. A., Panettieri, V., Dimmock, M., Tuan, J. K. L., Tan, H. Q., & Wright, C. A. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1084311 · Cited by 12
“According to the QUANTEC publication on GU toxicity (36), in view of the extensive volumetric changes of the bladder due to variable bladder filling, it was concluded that both the maximum dose and a relatively large irradiation bladder volume (50%) may be associated with Grade ≥3 late GU toxicity.”
Background
Obtaining organ-specific radiobiological parameters from clinical data for radiation therapy planning of head and neck cancers
Quashie, E. E., Li, X. A., Prior, P., Awan, M. J., Schultz, C. J., & Tai, A. (2023) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ad07f5 · Cited by 12
A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy
Masuo, M., Shinohara, E., Kitano, M., Maruta, R., Chonabayashi, S., Endo, S., Matumoto, S., Nishiyama, N., Machitori, Y., & Kobayashi, M. (2023) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyad158 · Cited by 12
Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial
Rades, D., Lomidze, D., Jankarashvili, N., López‐Campos, F., Navarro-Martín, A., Šegedin, B., Grošelj, B., Staackmann, C., Kristiansen, C., Dennis, K. E. B., et al. (2024) · Cancers · doi:10.3390/cancers16061149 · Cited by 12
“Gy without exceeding the tolerance dose of the spinal cord of 45–50 Gy [19,20].”
Background
Modelling radiobiology
Gardner, L. L., Thompson, S. J., O’Connor, J. D., & McMahon, S. J. (2024) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ad70f0 · Cited by 12
Reirradiation dose constraints in clinical practice: Results of an international survey
Stroom, J. C., Ayadi, M., Aarberg, A. E., Batel, V., Ceylan, C., Cleary, S., Greco, C., Hoffmann, L., Jackson, A., Kelly, C., et al. (2025) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2025.111030 · Cited by 12
Self-citation
Comparative dosimetric analysis of IMRT and VMAT (RapidArc) in brain, head and neck, breast and prostate malignancies
Ali, M. A., Babaiah, M., Nagaraju, M., & George, G. (2014) · International Journal of Cancer Therapy and Oncology · doi:10.14319/ijcto.0301.9 · Cited by 12
Mechanistic modelling of radiotherapy-induced lung toxicity
Rutkowska, E., Syndikus, I., Baker, C. R., & Nahum, A. E. (2012) · British Journal of Radiology · doi:10.1259/bjr/28365782 · Cited by 12
“To make this possible more quantitative end pointspecific data need to be collected [40–42].”
Background
Primary angiosarcoma of the breast: a radiation oncologist’s perspective with a concise review of the literature
Singh, R., Chufal, K. S., Pahuja, A. K., Tamilarasu, S., Chowdhary, R. L., & Ahmad, I. (2019) · BMJ Case Reports · doi:10.1136/bcr-2018-227036 · Cited by 12
Radiation protraction schedules for low-grade gliomas: a comparison between different mathematical models
Budia, I., Álvarez-Arenas, A., Woolley, T. E., Calvo, G. F., & Belmonte-Beitia, J. (2019) · Journal of The Royal Society Interface · doi:10.1098/rsif.2019.0665 · Cited by 12
“Specifically, for the brain, a maximum dose below 60 Gy implies a probability of 3% necrosis [10].”
Background
Radiotherapeutic treatment options for oligotopic malignant liver lesions
Wust, P., Beck, M., Dabrowski, R., Neumann, O., Zschaeck, S., Kaul, D., Modest, D. P., Stromberger, C., Gebauer, B., & Ghadjar, P. (2021) · Radiation Oncology · doi:10.1186/s13014-021-01779-5 · Cited by 12
Delineation of organs at risk
Noël, G., Fèvre, C. L., & Antoni, D. (2021) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2021.08.001 · Cited by 12
Radiotherapy of benign intracranial tumours
Dissaux, G., Josset, S., Thillays, F., Lucia, F., Bourbonne, V., Pradier, O., Pasquier, D., & Biau, J. (2021) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2021.08.005 · Cited by 12
Analysis of dose to the macula, optic disc, and lens in relation to vision toxicities – A retrospective study using COMS eye plaques
Oare, C. C., Sun, S. Y., Dusenbery, K. E., Reynolds, M. A., Koozekanani, D. D., Gerbi, B., & Ferreira, C. (2022) · Physica Medica · doi:10.1016/j.ejmp.2022.08.001 · Cited by 12
“Additionally, incidence rates were provided for doses above and below each structure’s median dose to align with reported QUANTEC dose and incidence rates commonly used in external beam therapy [31].”
Method
Reassessing dose constraints of organs at risk in children with abdominal neuroblastoma treated with definitive radiation therapy: A correlation with late toxicity
Kandula, S., Sutter, A. L., Prabhu, R. S., Jegadeesh, N., & Esiashvili, N. (2014) · Pediatric Blood & Cancer · doi:10.1002/pbc.25372 · Cited by 12
“In the case of adults, many well-defined dose-volume parameters for various tissues and organs have materialized [12,13]; however, extrapolation of this data to children is unsatisfactory.”
Background
Application of organ tolerance dose-constraints in clinical studies in radiation oncology
Dörr, W., Herrmann, T., & Baumann, M. A. (2014) · Strahlentherapie und Onkologie · doi:10.1007/s00066-014-0613-5 · Cited by 12
Implementation of a software for REmote COMparison of PARticlE and photon treatment plans: ReCompare
Löck, S., Roth, K., Skripcak, T., Worbs, M., Helmbrecht, S., Jakobi, A., Just, U., Krause, M., Baumann, M. A., Enghardt, W., et al. (2015) · Zeitschrift für Medizinische Physik · doi:10.1016/j.zemedi.2015.02.001 · Cited by 12
Head and neck intensity modulated radiotherapy parotid glands: time of re-planning
Fiorentino, A., Cozzolino, M., Caivano, R., Pedicini, P., Oliviero, C., Chiumento, C., Clemente, S., & Fusco, V. (2013) · La radiologia medica · doi:10.1007/s11547-013-0326-3 · Cited by 12
“The Quantec guidelines were used to evaluate OAR [23].”
Method
The role of stereotactic body radiotherapy and stereotactic radiosurgery in the re-irradiation of metastatic spinal tumors
Jain, A. K., & Yamada, Y. J. (2014) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.2014.940326 · Cited by 12
“2% incidence of myelopathy at a 50 Gy maximum dose level using conventionally fractionated radiotherapy [29].”
Background
Differences in rates of radiation-induced true and false rib fractures after stereotactic body radiation therapy for Stage I primary lung cancer
Miura, H., Inoue, T., Shiomi, H., & Oh, R. (2014) · Journal of Radiation Research · doi:10.1093/jrr/rru107 · Cited by 12
“proposed a new Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) model [16] to help predict clinical outcomes.”
Method
Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer
Ming, X. G., Feng, Y., Liu, H., Zhang, Y., Zhou, L., & Deng, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144211 · Cited by 12
“Earlier investigations also suggested that the irradiated heart volume and the distance between the heart and the field edge can be used to predict the dose to the heart in the radiotherapy of breast cancer [17, 18, 36].”
Background
Accelerated fraction radiotherapy with capecitabine as neoadjuvant therapy for borderline resectable pancreatic cancer.
Chakraborty, S., Morris, M. M., Bauer, T. W., Adams, R. B., Stelow, E. B., Petroni, G. R., & Sanoff, H. K. (2014) · Europe PMC (PubMed Central) · Cited by 12

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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