Activation Of The Hypothalamic Serotonin/Corticotropin-Releasing Factor Pathway Induces Ghrelin Insufficiency And Resistance In Cancer Cachexia Syndrome

than cN). Multivariable logistic regression analysis was done to identify independent predictors for pCR. Results: A total number of 1593 patients were included, with a median interval of 14 weeks between radiotherapy and surgery (range 6-85 weeks; interquartile range 1216 weeks). Outcome measures were calculated for intervals up to week 13 (N=312), in week 13/14 (N=511), in week 15/16 (N=406) and after week 16 (N=364). Age, tumor localization and R0 resection rate were equally distributed between the four groups; significant differences were found for cT stage (cT4 17.3%, 18.4%, 24.5%, 26.6% respectively; P= 0.010), and cM stage (cM1 4.4%, 4.8%, 8.9%, 14.9% respectively; P=0.000). Resection in week 15/16 resulted in the highest percentage of pCR (18.0%; P=0.013). Results for secondary endpoints in week 15/16 were: T downstaging 55.2% (P=0.165), N downstaging 58.6% (P=0.036) and (near) complete response 23.2% (P=0.124). Resection in week 15/16 was independently associated with pCR in a multivariable logistic regression analysis (HR 1.6; 95%CI 1.1-2.2). Conclusion: Based on differences in clinical practice regarding timing of TME surgery among 92 Dutch hospitals, we were able to demonstrate that the pCR rate after neoadjuvant CRT for rectal cancer is related to the time interval between radiotherapy and surgery. Delaying surgery until the 15th or 16th week after start of CRT seems to result in the highest chance of pCR, both in univariable and multivariable analysis. This corresponds with a time interval of approximately 10 to 11 weeks between end of CRT and surgery, based on a conventional five weeks treatment period.