Primary and Secondary Endpoint Analysis of N08C9 (Alliance): A Phase 3 Randomized Trial of Sulfasalazine Versus Placebo in the Prevention of Acute Radiation Enteritis

5 fractions) or no additional treatment (NAT). In the PORTEC trials patients with endometrial cancer underwent hysterectomy with bilateral salpingo-oophorectomy and were randomly assigned to postoperative EBRT (46 Gy in 2 Gy fractions) vs NAT (PORTEC-1, n Z 714), or EBRT vs vaginal brachytherapy (VBT, PORTEC-2, n Z 427). The Dutch Pathology Registry of histoand cytopathology was used to verify second cancers in TME and PORTEC-1 patients. Second cancers of PORTEC-2 trial patients were collected from the trial database. A competing risk model was used to estimate the cumulative probability of developing a second cancer. Standardized incidence ratios (SIR) were estimated as the ratio of the observed trial patients’ second cancers to those expected in the Dutch general population stratified by age, sex and calendar time. Results: A total of 2671 patients were analyzed, and 785 second cancers occurred. The most common second cancers were basal cell carcinomas of the skin (BCC, n Z 277), followed by gastrointestinal (n Z 117) and breast cancers (n Z 76). No difference was found in second cancer probability between NAT (10-year and 15-year rates 13.1% and 21.5%, respectively), EBRT (12.6% and 20.7%), and VBT (10-year rate 13.4%). In the individual trials no difference was found between treatment arms either. Also after exclusion of BCC from the analysis, no significant differences were found. Moreover, there was no difference between the second cancer types between treatment groups. Although patients 60, there was no difference between treatment arms for patients < 60 years. SIR based on all included patients for all types of second cancers were 2.98 (95% CI Z 2.82-3.14), for men 3.23 (95% CI Z 2.98-3.50) and women 2.78 (95% CI Z 2.58-3.00). Conclusions: There was no increased probability of developing second cancers in irradiated patients in these 3 randomized trials. However, patients treated for rectal or endometrial cancer had a higher probability of developing second cancers compared to the general population stratified by age, sex and calendar time. Author Disclosure: L.M. Wiltink: None. R.A. Nout: None. M. Fiocco: None. E. Meershoek-Klein Kranenbarg: None. I.M. JurgenliemkSchulz: None. J.J. Jobsen: None. I.D. Nagtegaal: None. C.J.H. van de Velde: None. C.L. Creutzberg: None. C.A.M. Marijnen: None.