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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Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group
Merlotti, A. M., Alterio, D., Vigna‐Taglianti, R., Muraglia, A., Lastrucci, L., Manzo, R., Gambaro, G., Caspiani, O., Miccichè, F., Deodato, F., et al. (2014) · Radiation Oncology · doi:10.1186/s13014-014-0264-9 · Cited by 110
Dosimetric comparison of RapidPlan and manually optimized plans in volumetric modulated arc therapy for prostate cancer
Kubo, K., Monzen, H., Ishii, K., Tamura, M., Kawamorita, R., Sumida, I., Mizuno, H., & Nishimura, Y. (2017) · Physica Medica · doi:10.1016/j.ejmp.2017.06.026 · Cited by 108
Results of a Multicentric In Silico Clinical Trial (ROCOCO): Comparing Radiotherapy with Photons and Protons for Non-small Cell Lung Cancer
Roelofs, E., Engelsman, M., Rasch, C. R. N., Persoon, L. C. G. G., Qamhiyeh, S., Ruysscher, D. D., Verhaegen, F., Pijls-Johannesma, M. C. G., & Lambin, P. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31823529fc · Cited by 107
A comparison of mechanism‐inspired models for particle relative biological effectiveness (RBE)
Stewart, R. D., Carlson, D. J., Butkus, M. P., Hawkins, R. B., Friedrich, T., & Scholz, M. (2018) · Medical Physics · doi:10.1002/mp.13207 · Cited by 107
A voxel-based investigation for MRI-only radiotherapy of the brain using ultra short echo times
Edmund, J., Kjer, H. M., Leemput, K. V., Hansen, R. H., Andersen, J. A. L., & Andreasen, D. (2014) · Physics in Medicine and Biology · doi:10.1088/0031-9155/59/23/7501 · Cited by 99
The REQUITE Project: Validating Predictive Models and Biomarkers of Radiotherapy Toxicity to Reduce Side-effects and Improve Quality of Life in Cancer Survivors
West, C., Azria, D., Chang-Claude, J. C., Davidson, S. E., Lambin, P., Rosenstein, B. S., Ruysscher, D. D., Talbot, C. J., Thierens, H. M., Valdagni, R., et al. (2014) · Clinical Oncology · doi:10.1016/j.clon.2014.09.008 · Cited by 99
MRI-based treatment planning for proton radiotherapy: dosimetric validation of a deep learning-based liver synthetic CT generation method
Liu, Y., Lei, Y., Wang, Y., Wang, T., Ren, L., Lin, L., McDonald, M. W., Curran, W. J., Liu, T., Zhou, J., et al. (2019) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ab25bc · Cited by 99
“OAR constrains were based on QUANTEC (Marks et al., 2010) for conventional fraction of 1.8–2.0 Gy per fraction.”
MethodInfluential
Radiosurgery of multiple brain metastases with single-isocenter dynamic conformal arcs (SIDCA)
Huang, Y., Chin, K., Robbins, J. R., Kim, J., Li, H., Amro, H., Chetty, I. J., Gordon, J., & Ryu, S. (2014) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2014.05.009 · Cited by 99
“The risk of radiation necrosis increases rapidly with volume of normal brain receiving 12 Gy or above [21], therefore a greater volume of metastatic lesions may be treated with VMAT in a single fraction.”
Background
Radiomics in radiooncology – challenging the medical physicist
Peeken, J. C., Bernhofer, M., Wiestler, B., Goldberg, T., Cremers, D., Rost, B., Wilkens, J. J., Combs, S. E., & Nüsslin, F. (2018) · Physica Medica · doi:10.1016/j.ejmp.2018.03.012 · Cited by 98
Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns
Wahl, R. L., Sgouros, G., Iravani, A., Jacene, H., Pryma, D., Saboury, B., Capala, J., & Graves, S. A. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262751 · Cited by 95
“(6) summarized normal-tissue tolerances to external photon irradiation as they were known in 1991, and these data have been gradually updated and expanded through other initiatives such as Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and Hypofractionated Treatment Effects in the Clinic (HyTEC…”
Method
An overlap‐volume‐histogram based method for rectal dose prediction and automated treatment planning in the external beam prostate radiotherapy following hydrogel injection
Yang, Y., Ford, E. C., Wu, B., Pinkawa, M., van Triest, B., Campbell, P. H., Song, D. Y., & McNutt, T. (2012) · Medical Physics · doi:10.1118/1.4769424 · Cited by 96
Patient‐reported outcomes after 3‐dimensional conformal, intensity‐modulated, or proton beam radiotherapy for localized prostate cancer
Gray, P. J., Paly, J. J., Yeap, B. Y., Sanda, M. G., Sandler, H. M., Michalski, J. M., Talcott, J. A., Coen, J. J., Hamstra, D. A., Shipley, W. U., et al. (2013) · Cancer · doi:10.1002/cncr.27956 · Cited by 94
“however, acute bowel toxicity after radiotherapy is less studied.(27,28) We observed that PBT was not associated with a clinically meaningful decrement in bowel QOL in the acute period after radiation.”
Background
Radiation Therapy Definitions and Reporting Guidelines for Thymic Malignancies
Gomez, D. R., Komaki, R. U., Yu, J. B., Ikushima, H., & Bezjak, A. (2011) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31821ea60c · Cited by 93
Deep inspiration breath-hold technique in left-sided breast cancer radiation therapy: Evaluating cardiac contact distance as a predictor of cardiac exposure for patient selection
Rochet, N., Drake, J. I., Harrington, K., Wolfgang, J. A., Napolitano, B. N., Sadek, B. T., Shenouda, M. N., Keruakous, A. R., Niemierko, A., & Taghian, A. G. (2014) · Practical Radiation Oncology · doi:10.1016/j.prro.2014.08.003 · Cited by 94
Trial Watch
Vacchelli, E., Vitale, I., Tartour, É., Eggermont, A. M. M., Sautès‐Fridman, C., Galon, J., Zitvogel, L., Kroemer, G., & Galluzzi, L. (2013) · OncoImmunology · doi:10.4161/onci.25595 · Cited by 95
The clinical manifestations and molecular pathogenesis of radiation fibrosis
Fijardo, M., Kwan, J. Y. Y., Bissey, P.-A., Citrin, D. E., Yip, K. W., & Liu, F. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105089 · Cited by 97
“11 Subsequent clinical data and reports were compiled in the quantitative analyses of normal tissue effects in the clinic (QUANTEC) studies to summarize the dose, volume, and outcomes in the scope of irradiated organ-speci ﬁ c risks.”
BackgroundInfluential
Implementation of deep learning-based auto-segmentation for radiotherapy planning structures: a workflow study at two cancer centers
Wong, J., Huang, V., Wells, D., Giambattista, J., Giambattista, J., Kolbeck, C., Otto, K. F., Saibishkumar, E. P., & Alexander, A. (2021) · Radiation Oncology · doi:10.1186/s13014-021-01831-4 · Cited by 89
“4e, f ) suggesting a weaker association; this structure more likely will have DC inaccuracies that are felt to be more clinically impactful since the relevant dose constraint considers the mean dose to the whole parotid volume [13].”
Background
Machine learning applications in radiation oncology
Field, M., Hardcastle, N., Jameson, M., Aherne, N. J., & Holloway, L. C. (2021) · Physics and Imaging in Radiation Oncology · doi:10.1016/j.phro.2021.05.007 · Cited by 95
“Achieving this is challenging due to the wide number of influencing factors and the variation in radiation dose distributions [41].”
Background
Organs at risk radiation dose constraints
Noël, G., & Antoni, D. (2021) · Cancer/Radiothérapie · doi:10.1016/j.canrad.2021.11.001 · Cited by 93
Standardizing Naming Conventions in Radiation Oncology
Santanam, L., Hurkmans, C., Mutic, S., van Vliet-Vroegindeweij, C., Brame, S., Straube, W. L., Galvin, J. M., Tripuraneni, P., Michalski, J. M., & Bosch, W. R. (2012) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2011.09.054 · Cited by 89
Diagnostic and therapeutic management of hepatocellular carcinoma
Bellissimo, F. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i42.12003 · Cited by 87
Adaptations to a Generalized Radiation Dose Reconstruction Methodology for Use in Epidemiologic Studies: An Update from the MD Anderson Late Effect Group
Howell, R. M., Smith, S. A., Weathers, R. E., Kry, S. F., & Stovall, M. A. (2019) · Radiation Research · doi:10.1667/rr15201.1 · Cited by 86
“Such data are summarized for adult radiotherapy practice in the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review (57) mostly based on short-term follow-up.”
Method
Comparison of Deep Learning-Based and Patch-Based Methods for Pseudo-CT Generation in MRI-Based Prostate Dose Planning
Largent, A., Barateau, A., Nunes, J., Mylona, E., Castelli, J., Lafond, C., Greer, P. B., Dowling, J., Baxter, J. S. H., Saint‐Jalmes, H., et al. (2019) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2019.08.049 · Cited by 88
Dose–Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An “All-in-One” Multicenter–Multidisciplinary Practical Summary
Bisello, S., Cilla, S., Benini, A., Cardano, R., Nguyen, N. P., Deodato, F., Macchia, G., Buwenge, M., Cammelli, S., Wondemagegnehu, T., et al. (2022) · Current Oncology · doi:10.3390/curroncol29100552 · Cited by 87
“4 Gy < 15 cm3 [8] (A) Dose to bladder-wall: DMAX(0.1 cm3 ) < 28.2 Gy [6] (A); D15 cm3 < 16.8 Gy; [7] (A) Dose to bladder-wall: DMAX(0.1 cm3 ) < 38 Gy [6] (A); D15 cm3 < 18.3 Gy; [7] (A) For primary prostate SBRT only: V18.”
BackgroundInfluential
Organ-sparing radiation therapy for head and neck cancer
Wang, X., Hu, C., & Eisbruch, A. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.106 · Cited by 86
“Most available data about the tolerated dose to normal tissues are based on retrospective analyses or expert opinions”
BackgroundSelf-citation
Comparing Unet training with three different datasets to correct CBCT images for prostate radiotherapy dose calculations
Landry, G., Hansen, D. C., Kamp, F., Li, M., Hoyle, B., Weller, J., Parodi, K., Belka, C., & Kurz, C. (2018) · Physics in Medicine and Biology · doi:10.1088/1361-6560/aaf496 · Cited by 85
“For the OARs, in particular the bladder and the rectum, plans aimed at respecting the upper dose thresholds given in the QUANTEC report (Marks et al 2010).”
Background
Head and Neck Cancer Adaptive Radiation Therapy (ART): Conceptual Considerations for the Informed Clinician
Heukelom, J., & Fuller, C. D. (2019) · Seminars in Radiation Oncology · doi:10.1016/j.semradonc.2019.02.008 · Cited by 84
Minimally invasive local therapies for liver cancer.
Li, D., Kang, J., Golas, B. J., Yeung, V. W., & Madoff, D. C. (2014) · PubMed Central · doi:10.7497/j.issn.2095-3941.2014.04.001 · Cited by 81
COSMIC: A Regimen of Intensity Modulated Radiation Therapy Plus Dose-Escalated, Raster-Scanned Carbon Ion Boost for Malignant Salivary Gland Tumors: Results of the Prospective Phase 2 Trial
Jensen, A. D., Nikoghosyan, A. V., Lossner, K., Haberer, T., Jäkel, O., Münter, M., & Debus, J. (2015) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2015.05.013 · Cited by 81
Practical Considerations in the Re-Irradiation of Recurrent and Second Primary Head-and-Neck Cancer: Who, Why, How, and How Much?
Chen, A. M., Phillips, T. L., & Lee, N. Y. (2011) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2011.06.1998 · Cited by 81
Optimize and refine therapeutic index in radiation therapy: Overview of a century
Chargari, C., Magné, N., Guy, J., Rancoule, C., Lévy, A., Goodman, K. A., & Deutsch, É. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.03.001 · Cited by 90
New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy
Khalil, A. A., Hoffmann, L., Møller, D. S., Farr, K. P., & Knap, M. M. (2015) · Acta Oncologica · doi:10.3109/0284186x.2015.1061216 · Cited by 80
“showed that only mlD, V20 and V30 were predictive of the severe rP [21].”
Assessing the Role of Artificial Intelligence (AI) in Clinical Oncology: Utility of Machine Learning in Radiotherapy Target Volume Delineation
Boon, I. S., Yong, T. P. T. A., & Boon, C. S. (2018) · Medicines · doi:10.3390/medicines5040131 · Cited by 83
Electronic Patient-Reported Outcome Measures in Radiation Oncology: Initial Experience After Workflow Implementation
Hauth, F., Bizu, V., App, R., Lautenbacher, H., Tenev, A., Bitzer, M., Malek, N. P., Zips, D., & Gani, C. (2019) · JMIR mhealth and uhealth · doi:10.2196/12345 · Cited by 84
“Normal Tissue Complication Probability models have been established to estimate the likelihood of a specific toxicity [29].”
Dose–volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment
Mazzola, R., Ricchetti, F., Fiorentino, A., Fersino, S., Giaj‐Levra, N., Naccarato, S., Sicignano, G., Albanese, S., Paola, G. D., Alterio, D., et al. (2014) · British Journal of Radiology · doi:10.1259/bjr.20140543 · Cited by 78
Thyroid V40 Predicts Primary Hypothyroidism After Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma
Sommat, K., Ong, W. S., Hussain, A., Soong, Y. L., Tan, T. W. K., Wee, J. T. S., & Fong, K. W. (2017) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2017.03.007 · Cited by 78
Management of Patients with ≥4 Brain Metastases Using Stereotactic Radiosurgery Boost after Whole Brain Irradiation
Dinçoğlan, F., Sager, O., Gamsız, H., Uysal, B., Demiral, S., Oysul, K., Şirin, S., Çağlan, A., & Beyzadeoğlu, M. (2014) · Tumori Journal · doi:10.1177/1578.17210 · Cited by 78
Radiation-induced esophagitis in lung cancer
Baker, S. E., & Fairchild, A. M. (2016) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s96443 · Cited by 78
Revisiting the dose constraints for head and neck OARs in the current era of IMRT
Brodin, N. P., & Tomé, W. A. (2018) · Oral Oncology · doi:10.1016/j.oraloncology.2018.08.018 · Cited by 77
Trial Watch: Immunotherapy plus radiation therapy for oncological indications
Vacchelli, E., Bloy, N., Aranda, F., Buqué, A., Cremer, I., Demaria, S., Eggermont, A. M. M., Formenti, S. C., Fridman, W. H., Fucikova, J. P., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1214790 · Cited by 76
“or by selectively limiting toxicity to normal tissues (radioprotection).(2,56-58) Multiple molecules have been shown to mediate”
Background
Inclusion of clinical risk factors into NTCP modelling of late rectal toxicity after high dose radiotherapy for prostate cancer
Rancati, T., Fiorino, C., Fellin, G., Vavassori, V., Cagna, E., Borca, V. C., Girelli, G. F., Menegotti, L., Monti, A. F., Tortoreto, F., et al. (2011) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2011.06.032 · Cited by 76
“The development of normal tissue complication (NTCP) models is an important step of this process; the basic idea was to pragmatically ‘‘reduce’’ the dose–volume histogram (DVH) of an organ at risk to a number expressing the risk of toxicity, through a simple mathematical model [3].”
Background
Physically constrained voxel‐based penalty adaptation for ultra‐fast IMRT planning
Wahl, N., Bangert, M., Kamerling, C. P., Ziegenhein, P., Bol, G. H., Raaymakers, B. W., & Oelfke, U. (2016) · Journal of Applied Clinical Medical Physics · doi:10.1120/jacmp.v17i4.6117 · Cited by 75
Lymphocyte sparing normal tissue effects in the clinic (LymphoTEC): A systematic review of dose constraint considerations to mitigate radiation-related lymphopenia in the era of immunotherapy
Venkatesulu, B., Giridhar, P., Pujari, L., Chou, B., Lee, J. H., Block, A. M., Upadhyay, R., Welsh, J. S., Harkenrider, M. M., Krishnan, S., et al. (2022) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2022.10.019 · Cited by 75
Intensity Modulated Radiation Therapy Dose Painting for Localized Prostate Cancer Using 11C-choline Positron Emission Tomography Scans
Chang, J. H., Joon, D. L., Lee, S. T., Gong, S. J., Anderson, N., Scott, A. M., Davis, I. D., Clouston, D. R., Bolton, D. M., Hamilton, C. S., et al. (2012) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2012.01.087 · Cited by 74
A multidimensional nomogram combining overall stage, dose volume histogram parameters and radiomics to predict progression-free survival in patients with locoregionally advanced nasopharyngeal carcinoma
Yang, K., Tian, J., Zhang, B., Li, M., Xie, W., Zou, Y., Tan, Q., Liu, L., Zhu, J., Shou, A., et al. (2019) · Oral Oncology · doi:10.1016/j.oraloncology.2019.09.022 · Cited by 72
Tumor Response After Neoadjuvant Magnetic Resonance Guided Single Ablative Dose Partial Breast Irradiation
Vasmel, J. E., Charaghvandi, R. K., Houweling, A. C., Philippens, M. E. P., van Asselen, B., Vreuls, C. P. H., van Diest, P. J., van Leeuwen, A. M. G., van Gorp, J., Witkamp, A. J., et al. (2019) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2019.11.406 · Cited by 72
Results of a Multi-Institutional Phase 2 Clinical Trial for 4DCT-Ventilation Functional Avoidance Thoracic Radiation Therapy
Vinogradskiy, Y. Y., Castillo, R., Castillo, E. M., Schubert, L. K., Jones, B. L., Faught, A. M., Gaspar, L. E., Kwak, J., Bowles, D. W., Waxweiler, T. V., et al. (2021) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2021.10.147 · Cited by 77
Machine Learning and Radiogenomics: Lessons Learned and Future Directions
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“Both the ASTRO and the European Society of Radiation Oncology recognize a need for improved radiation toxicity models—including through ML (218)—and have pushed for utilization of big data toward “precision” radiation oncology (219, 220).”
Background

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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