Parameters for the Lyman Kutcher Burman (LKB) model of Normal Tissue Complication Probability (NTCP) for specific rectal complications observed in clinical practise

Background and purpose The Normal Tissue Complication Probability (NTCP) for rectum is usually defined for late rectal bleeding. This study calculates NTCP parameter values for additional rectal toxicity endpoints observed in clinical practise. Materials and methods 388 patients from the multicentre MRC-RT01 prostate conformal radiotherapy trial (ISRCTN 47772397) were used to derive independent Lyman Kutcher Burman model (LKB) parameters for five late rectal toxicity endpoints: rectal bleeding, proctitis, stool frequency, loose stools and rectal urgency. The parameters were derived using maximum likelihood estimation. Bootstrap and leave-one-out methods were employed to test the generalisability of the results for use in a general population. Results A consistent pattern of increasing value of TD50(1) for Grade 2 toxicity only compared to Grades 1 and 2 toxicity was observed for all endpoints. Parameter values varied between endpoints (particularly for the volume parameter n). TD50(1), m and n were 68.5 Gy (95% CI)(66.8–70.8), 0.15 (0.13–0.17) and 0.13 (0.10–0.17), respectively, for G2 rectal bleeding. Bootstrap and leave-one-out results showed that the rectal bleeding and proctitis parameter fits were extremely robust. Conclusions The variation between the values derived for different endpoints may indicate different patho-physiological responses of the rectum to radiation. Therefore different parameter sets would be required to predict specific rectal toxicity endpoints.