This chapter is devoted to discussing organ radiation safety and sensitivity. Emami's 1991 paper discussing normal tissue tolerance was a good beginning to understanding the absolute safety of radiation to uninvolved tissue. As radiation treatment delivery techniques have become ever more sophisticated, the questions concerning radiation safety, dose, fractionation and disease control have become ever more complex.
Bentzen's introduction to the Quantec scientific issues states, "NTCP (normal tissue complication probability) 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 because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions." IJROBP 2010:76(3) Supplememnt S1-S160)
Organ toxicity to radiation has always been a key consideration. Initially, the key limiting organ was skin, with the Skin Erythema Dose being the dose limiting toxicity. With the advent of megavoltage radiation, with its skin sparing dosimetry skin dose was no longer the dose limiting toxicity. The focus began to shift to internal organ dose limiting toxicities.
A second sea change in radiation therapy delivery came about with the advent of sophisticated imaging based radiation therapy and a rapid migration from plane films and boney anatomic treatment delivery to 3d-conformal radiation therapy using CT, MRI, PET and other 3d imaging modalities. This was further refined with the advent of intensity modulated radiation therapy, and the advent of proton dose distributions. There is a need to understand the toxicities to uninvolved tissues with inhomogenous dosimetry, non-standard dose-fractionation schemes, partial organ irradiation tolerances, and the general toxicities associated with radiation treatment.
The compilation here attempts to examine the available data (which is disparate), and organize it in such a way so as to provide a reasonable clinical reference guide. Please note that the data here may be controversial, particularly when non-conventional dose/fractionation schemes are used. For example, a debate recently took place on spinal cord dose constraints. The original study author used a dose of 36 Gy as a dose limiting constraint. Conventional wisdom uses 45 Gy, while the NCCN guidelines recommended 41 Gy (NCCN slcl v2.2014, v2.2015 citing CALGB 30610, A. Turrisi, personal communication). I used 39 Gy as a reasonable (so I thought) compromise, and was castigated for it by a well known and established radiation oncologist, who repeated the act at a national conference from the floor microphone. It seems to me that a better approach is to dilligently study the data, accepting the fact that we do not know enough about the subject, and to systematically acquire new data to insure that future patients will benefit from greater understanding and application of that understanding to improve disease control and to minimize adverse impact on the lives of cancer patients.