The QUANTEC (quantitative analysis of normal tissue effects in the clinic) 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” paper (IJROBP 21:109, 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.

The three dimensional dose/volume/outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold “tolerance dose/volume” levels. There are strong volume and fractionation effects.

Radiation therapy has curative or palliative potential in roughly half of all incident solid tumours, and offers organ and function preservation in most cases. Unfortunately, early and late toxicity limits the deliverable intensity of radiotherapy, and might affect the long-term health-related quality of life of the patient. Recent progress in molecular pathology and normal-tissue radiobiology has improved the mechanistic understanding of late normal-tissue effects and shifted the focus from initial-damage induction to damage recognition and tissue remodelling. This stimulates research into new pharmacological strategies for preventing or reducing the side effects of radiation therapy.

Advances in dose/volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible due to sub-optimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge-base includes the need for more data on the effect of patient-related co-factors, interactions between dose-distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to non-uniform dose distributions. Research priorities for the next 5 to 10 years are proposed.

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