Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model

Abstract

Purpose/background: Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic).

Material and methods: One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model.

Results: Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44).

Conclusions: Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.

Figure 1

Kaplan-Meier actuarial estimate of late rectal bleeding >= grade 2. Ninety percent of cases are observed within two years of the end of radiotherapy.

Figure 2

Freedom from >= grade 2 rectal bleeding in patients aged over (or under) 77 years when commencing RT (p=0.007; log-rank test).

Figure 3

Incidence of late rectal bleeding as a function of gEUD. Data was binned in 1 Gy intervals according to computed gEUD values with the best fit n parameter value of 0.068. Error bars are binomial 68% confidence intervals. Only three plans fell outside the gEUD range 62 to 68, and were not included. The estimated 95% confidence interval for the best-fit model is shown by thin solid lines. The QUANTEC-recommended LKB model is shown as the dashed line (ignoring a small error due to the slightly different n values). Observed rates are smaller than QUANTEC predicted rates at all gEUD levels.