The clinical target volume in lung, head-and-neck, and esophageal cancer: Lessons from pathological measurement and recurrence analysis

Abstract

Radiotherapy research has achieved remarkable progress in target volume definition. Advances in medical imaging facilitate more precise localization of the gross tumor volume, alongside a more detailed understanding of the geometric uncertainties associated with treatment delivery that has enabled robust safety margins to be customized to the specific treatment scenario at hand. By contrast, the clinical target volume, meant to encompass gross tumor, as well as, adjacent sub-clinical disease, has evolved very little. It is more often defined by clinician experience and institutional convention than on a patient-specific basis. This disparity arises from the inherent invisibility of sub-clinical disease in current medical imaging. Its incidence and expanse can only be ascertained via indirect means. This article reviews two such strategies: histopathological measurements on resection specimen and analyses of locoregional recurrences after radiotherapy.

Keywords: Adaptive radiotherapy; Clinical target volume; Microscopic tumor extension; Particle beam irradiation.

Fig. 1

Graphical overview of microscopic extension summary statistics meant to encourage a broad assessment of compatibility between the various studies. Values for each sample are marked as colored lines (yellow: mean and standard deviation; green: named percentile) on a 50 mm scale with 5 mm sub-divisions. Green numbers above lines indicate the percentile whose value is reported. Values were taken directly from the source texts if available (solid lines). Otherwise values were estimated from tables and graphs (dotted lines). If extension data was grouped into bins, their upper edges were used for calculation in the latter case, e.g. if five instances of infiltration were observed at distances of 10–15 mm, an extension distance of 15 mm was assigned to all five cases. Tumor sites are demarcated by colored panels and labeled at the top of each panel. More lightly tinted panels of the same primary color indicate stratification by attributes listed on the sides, while the stratum each sample belongs to is given directly above its scale. Darker shades of the primary color signify results for un-stratified samples. Individual studies are identified by tabs on the upper (first author) and lower (reference number) edge of a lighter shape surrounding the scales and linking them across different stratifications. Measurements are generally reported for the entire cohort (i.e. including extension-negative samples) and the sample size is given underneath each scale. Abbreviations: ADC, adenocarcinoma; SCC, squamous cell carcinoma; NSCLC, non-small cell lung cancer; HNSCC, head-and-neck SCC; SUP, superior; INF, inferior; MED, medial; LAT, lateral; G, histological grade. Notes: *Results are plotted for extension positive samples only and the positive ratio is given underneath; §Excludes measurements from one outlying patient. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)