Statistical methods for clinical verification of dose–response parameters related to esophageal stricture and AVM obliteration from radiotherapy

Abstract

The purpose of this work is to provide some statistical methods for evaluating the predictive strength of radiobiological models and the validity of dose-response parameters for tumour control and normal tissue complications. This is accomplished by associating the expected complication rates, which are calculated using different models, with the clinical follow-up records. These methods are applied to 77 patients who received radiation treatment for head and neck cancer and 85 patients who were treated for arteriovenous malformation (AVM). The three-dimensional dose distribution delivered to esophagus and AVM nidus and the clinical follow-up results were available for each patient. Dose-response parameters derived by a maximum likelihood fitting were used as a reference to evaluate their compatibility with the examined treatment methodologies. The impact of the parameter uncertainties on the dose-response curves is demonstrated. The clinical utilization of the radiobiological parameters is illustrated. The radiobiological models (relative seriality and linear Poisson) and the reference parameters are validated to prove their suitability in reproducing the treatment outcome pattern of the patient material studied (through the probability of finding a worse fit, area under the ROC curve and chi2 test). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed, and the total volume of AVM. The estimated confidence intervals of the dose-response curves appear to have a significant supporting role on their clinical implementation and use.

Dose-Response Relations for Anal Sphincter Regarding Fecal Leakage and Blood or Phlegm in Stools after Radiotherapy for Prostate Cancer

“…The linear-quadratic model was used to correct each dose distribution in the anal sphincter to 2 Gy per fraction [19] and the α/ ratio assumed was 3 Gy. The biologically effective uniform dose is the uniform dose that causes exactly the same tumor control or NTCP as the real dose distribution [36][37][38]. The uniform dose that is biologically as effective as the dose distribution, D Ǟ , delivered to each patient is determined using this concept, which was introduced by Mavroidis et al [36].…”

“…Newer and more accurate clinical data about dose-response relations of tumors and normal tissues are reported by many investigators at an increasing rate [2,17,18,25,31,37]. However, the reliability of biological treatment planning evaluation needs to be supported through further clinical verification of these data.…”

“…This kind of studies is usually carried out retrospectively, since the clinical outcome of the treatments must be known, although prospective studies can also be performed. However, the clinical utilization of such parameters and means by which the readers may examine whether certain parameters are applicable to their local organ delineation methods and treatment techniques have been illustrated by only a few studies [28,37].…”

Clinical survey for registering treatment decision criteria in advanced non-small-cell lung cancer radiotherapy and determination of the dose–response relationship for 1-year survival

“…Parameters D 50 and g are specific for every organ and type of clinical endpoint and they are derived from clinical data. 30 …”

Variation in radiation sensitivity and repair kinetics in different parts of the spinal cord

“…In the case of lung and head & neck radiation therapy, radiobiologically optimized treatment planning can be performed using relevant dose-response parameters, which can be estimated from well organized studies of treated patients with long follow-up. Usually prospective studies are performed to verify the validity of published parameter sets, whereas the kind of studies carried out to determine these parameter sets are often retrospective since the prevalence of late complications is usually low [8,10]. Regarding the characterization of the dose-response relation for spinal cord, most models seem to work well and are rather accurate in predicting its response to radiation therapy [17].…”