Impact of biological clearance on tumor radioresponsiveness

To determine the capacity of biological clearance in tumor regression following radiotherapy by using metastatic brain tumors as a clinical model in which mechanical clearance is negligible.

Thirty-eight tumors (19 nonsmall cell lung cancer, 11 small cell lung cancer, and 8 nonlung cancer) in 23 patients were followed with computed tomography (CT) scans over 3 months or more following initiation of radiotherapy, with doses ranging between 34 and 66 Gy. The tumor regression rate (RR; mm3/day), which represented the capacity of biological clearance, was calculated for each CT observation period. The complete response (CR) rate was calculated. The relationship between RR and tumor diameter was determined with regression analysis in conjunction with the pattern of contrast enhancement and the type of primary disease. The change of the RR also was examined.

The CR rate was 60.5% for the total group; it was lower for ring-enhanced tumors (41.7%) than diffusely enhanced tumors (69.2%), which included mostly small cell lung cancer metastases. The RR correlated significantly with the tumor diameter (D), with a regression curve of exponential function (RR = 0.035 *D2.5). The RR varied widely and was rather large until 40 days following initiation of radiotherapy, especially for the subgroups of diffusely enhanced tumors and the small cell lung cancer tumors, and became rather constant thereafter.

A tumor diameter exponent in the regression curve of smaller than 3.0 indicates that the larger the tumor volume is, the smaller the capacity of biological clearance. The capacity of biological clearance also is dependent on vascularity and cellularity of the tumor components expressed by the pattern of contrast enhancement.