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Karen Krueger

Conformal Terminology
March 28, 2015

Quantitative Analysis of Normal Tissue Effects in the Clinic

In the past radiation oncologists relied on experience and observation to determine the
fields and doses used for radiation therapy. In 1991 a group of investigators, realizing the clinical
need for the knowledge of normal tissue tolerance doses and side effects, compiled their clinical
information regarding partial or organ tolerance doses.1 The investigators used their experience
and judgement along with the information to produce the Enami Paper.1 Computed
tomography simulation based treatment planning revolutionized target visualization and enabled
three-dimensional (3D) conformal treatment planning.2 The new technology improved dose
uniformity of the target volume and allowed better visualization of the dose distribution to the
surrounding normal tissues. Improved visualization of the patient and dose distribution,
increased flexibility in determining which regions of normal tissue would be incidentally
irradiated during the course of treatment. However, the increase in combined modality therapy
increased the significance of early and late toxicities.2 Treatment planners need information to
predict the risk of normal tissue injury in order to design a plan that optimizes the therapeutic
ratio (do significantly more good than harm).
Since the advent of 3D planning, there have been numerous studies evaluating
associations between dosimetric parameters and normal tissue outcomes.1 A large committee of
57 experts, was formed by the American Association of Physicists in Medicine (AAPM) to
produce the quantitative analysis of normal tissue effects in the clinic (QUANTEC).1,3 In 2010,
the QUANTEC review was published.3 The goal of the QUANTEC review was to summarize the
current three dimensional data in order to update and refine the normal tissue tolerance dose and
volume tolerance guidelines outlined in the paper by Enami et al.1 The primary goal of
QUANTEC was to summarize the information and present it so that it was clinically useful. In
order to achieve this goal, the committee defined three aims for QUANTEC:

1) To provide critical overview of the current state of knowledge on quantitative doseresponse and dose-volume relationships for clinically relevant normal-tissue
2) To produce practical guidance allowing the clinician to reasonable (though not
necessarily precisely) categorize toxicity risk based on dose-volume parameters or
model results2
3) To identify future research avenues that would help improve risk estimation or
mitigation of early and late side effects of radiation therapy2
The review was published in The International Journal of Radiation Oncology Biology *
Physics and included 16 organ specific papers and several general rule papers.3 The
information presented in the review was primarily information extracted from publications.1
Summary tables were included so that the data was accessible and easily understood. Data used
for models and dose/volume recommendations are typically based on dose-volume histograms
(DVHs). Dose volume histograms are not ideal representations of 3D dose distributions because
spatial information is not considered and therefore all regions are considered to be of equal
functional importance.1 Models that consider a larger fraction of the DVH are more reliable than
the threshold models that only consider one point on the DVH. Nonetheless, reports correlating
single DVH point thresholds to toxicity are common and are often included in the QUANTEC
The QUANTEC papers are a good review of the currently available organ-specific
dose/volume/outcome data. A summary table of data that is generally considered clinically
acceptable is included in the QUANTEC review.1 The information presented in QUANTEC is
not perfect. Physicians and treatment planners are encouraged to read individual papers so that
they might understand the origin, certainty, and differences in treatment, that apply to the data
provided in the table. Many details are covered within each paper, including explication of
available data and how structures should be contoured.3 Information in the QUANTEC papers is
meant to inform physicians and treatment planners of normal tissue complication probabilities as
best determined by the currently available data. The review is intended to inform and guide,
however, every patient is unique and certain clinical situations require treatments that exceed the
recommended dose/volume values presented. QUANTEC is updated as new research is

16 Organ-Specific Papers & 5 Vision Papers

1. Brain
2. Optic Nerve/Chiasm
3. Brain Stem
4. Spinal Cord
5. Ear
6. Parotid
7. Larynx/Pharynx
8. Lung
9. Heart
10. Esophagus
11. Liver
12. Stomach/Small Bowel
13. Kidney
14. Bladder
15. Rectum
16. Penile Bulb

1. True Dose
2. Imaging
3. Bio Markers
4. Data Sharing
5. Lessons of QUANTEC

Figure 1. Image showing three-dimensional dose distribution reduced to a twodimensional DVH by discarding all spatial, anatomic, and physiologic data. The DVH is then
reduced to a single value of interest, such as the mean dose, the percent of the organ receiving a
specific volume, or a model-based normal tissue complication probability.

Figure 2.4

1. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability
models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):S10-S19.
2. Bentzen SM, Constine LS, Deasy JO, et al. Int J Radiat Oncol Biol Phys. Quantitative
analyses of normal tissue effects in the clinic (QUANTEC): an introduction to the
scientific issues. 2010;76(3):S3-S9. doi:10.1016/j.ijrobp.2009.09.040
3. Demarco M, Dilling TJ. A review of QUANTEC normal tissue tolerances. [PowerPoint].
Tampa,FL: Moffitt Cancer Center.
4. DesRosiers C. Calculation algorithms in radiation therapy treatment planning systems.
[PowerPoint]. Indianapolis, IN: Indiana University School of Medicine, 2013.