gms | German Medical Science

Purpose: The correlation between complication probability and dose-volume histograms (DVHs) can be described with the linear-quadratic (LQ) model. The HD8 trial of the German Hodgkin Lymphoma Study Group (GHSG) for early-stage unfavourable Hodgkin’s lymphoma (HL) was designed to test whether radiotherapy (RT) can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after two cycles of COPP alternating with two cycles of ABVD chemotherapy. Considering the number of side-effects that were found in the HD8 trial, we wanted to prove in this analysis, if biophysical parameters for the LQ-model could be determined. Additionally the results of HD8 will be presented.

Material and Methods: Between 1993 and 1998, 1204 patients with newly diagnosed histology-proven HL in clinical stages I/IIA/IIB with defined risk factors and stage IIIA without risk factor were enrolled into the multicenter HD8 study. Patients were randomized to receive two cycles of COPP alternating with two cycles of ABVD followed by RT of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B).

Of 913 patients the rates of acute gastrointestinal side-effects during and after the end of RT could be determined. The arm comparison showed differences between arm A and arm B (grade 1-2: 16,6 vs. 3,9; grade 3-4: 0,9 vs. 0,2; p<0.001). Out of the DVHs for a “standard patient“ (volume intestine 2300 cm3) we determined for the normal tissue complication probability (NTCP) (V,D,m,n,TD50) the biophysical parameter TD50 and n (volume dependent) in that manner, that the observed NTCPs both in arm A and in arm B correlated with the calculated values.

Results: According to the gastrointestinal toxicity the different radiation treatment volumes resulted in different NTCPs. Based on these findings the derived calculations showed values of n = 0.09 and TD50 = 32 Gy, for the parameter m we used a literature value. However, this biophysical model is sensitive towards variations of the parameters. A deviation of 1% of TD50 in the steepest part of the dose-response curve results in a deviation of 10% of the NTCP.

Conclusion: RT volume size reduction from EF to IF after two cycles of COPP alternating with two cycles of ABVD chemotherapy gives similar results and less toxicity in patients with early-stage unfavourable HL. Biophysical parameter for the LQ-model could be determined out of the complication probability data after RT of HL. Due to the exponential dependence this biophysical model is instable. It represents a “start model” until further data will be incorporated.