Late rectal bleeding after conformal radiotherapy of prostate cancer (II):Volume effects and dose-volume histograms

Purpose and Objective: Late rectal bleeding is a potentially dose limiting complication of three-dimensional conformal radiotherapy (3D-CRT) for prost ate cancer, The frequency of late rectal bleeding has been shown to increas e as the prescription dose rises above 70 Gy, The purpose of this study is to identify features of the cumulative dose-volume histogram (DVH) for the rectal wall that correlate with late rectal bleeding after 3D-CRT for prost ate cancer. Methods and Materials: Follow-up information on rectal bleeding is availabl e for 261 and 315 patients treated using 3D-CRT at Memorial Sloan-Fettering Cancer Center for Stage T1c-T3 prostate canter with minimum target doses o f 70.2 and 75.6 Gy, respectively, All patients in this study were treated w ith a coplanar 6-field technique (2 lateral and 4 oblique fields), Patients were classified as having rectal bleeding if they bled (greater than or eq ual to Grade 2) before 30 months, and nonbleeding (less than or equal to Gr ade 1) if they were without bleeding at 30 months, using the RTOG morbidity scale. Rectal bleeding was observed in 13 and 38 of the patients treated a t 70.2 and 75.6 Gy, respectively. Treatment plans were analyzed for 39 nonb leeding and 13 bleeding patients receiving 70.2 Gy, and 83 nonbleeding and 36 bleeding patients receiving 75.6 Gy, Dose-volume histograms (DVHs) for t he anatomic rectal wall were calculated. Average DVHs of the bleeding and n onbleeding patients were generated, and a permutation test was used to asse ss the significance of differences between them, for each dose group. The c onfounding effect of total rectal wall volume (V-RW) was removed by calcula ting the average differences in DVHs between all combinations of bleeding a nd nonbleeding patients with similar V(RW)s. Finally, multivariate analysis using logistic regression was performed to test the significance of the DV H variables in the presence of anatomic, geometric, and medical variables p reviously found to correlate with rectal bleeding in a companion analysis o f the same patients. Results: The area under the average percent volume DVH for the rectal wall of patients with bleeding was significantly higher than those of patients w ithout bleeding in both dose groups (p = 0.02, 70.2 Gy; p < 0.0001, 75.6 Gy ), However, small V(RW)s were associated with rectal bleeding (p = 0.06, 70 .2 Gy; p < 0.01, 75.6 Gy), resulting in an increase in average percent volu mes exposed to all doses for patients with rectal bleeding. For patients wi th similar V(RW)s, rectal bleeding was significantly correlated with the vo lumes exposed to 46 Gy in both dose groups (p = 0.02, 70.2 Gy; p = 0.005, 7 5.6 Gy, tolerance in V-RW: 5 ccs), For the 75.6 Gy dose group, the percent volume receiving 77 Gy was significantly correlated with rectal bleeding (p < 0.005). Bivariate analysis using logistic regression, including V-RW tog ether with a single DVH variable, showed good agreement with the above anal ysis, Multivariate analysis revealed a borderline significant correlation o f the percent volume receiving 71 Gy in the 70.2 Gy dose group. It also sho wed that the DVH variables were highly correlated with geometric and dosime tric variables previously found to correlate with rectal bleeding in multiv ariate analysis. Conclusion: Significant volume effects were found in the probability of lat e rectal bleeding for patients undergoing 3D-CRT for prostate cancer with p rescription doses of 70.2 and 75.6 Gy. The percent volumes exposed to 71 an d 77 Gy in the 70.2 and 75.6 Gy dose groups respectively were significantly correlated with rectal bleeding. The independent correlation of small V-RW with rectal bleeding may indicate the existence of a functional reserve fo r the rectum. The independent association with larger percent volumes expos ed to intermediate doses (<similar to> 46 Gy) seen in both dose groups may indicate that a large surrounding region of intermediate dose may interfere with the ability to repair the effects of a central high dose region. (C) 2001 Elsevier Science Inc.