The SUV(max)-based RI calculated after the first 2 weeks of RCT provided the best predictor of pathological treatment response, reaching AUCs of 0.87 and 0.84 for the TRG and the ypT stage, respectively. However, a few patients presented with peritumoral inflammatory reactions, which led to mispredictions. Exclusion of these patients further enhanced the predictive accuracy of PET imaging to AUCs of 0.97 and 0.89 for TRG and ypT, respectively.

For rectal cancer, an accurate PET-based prediction of the pathological treatment response is feasible already after 2 weeks of CRT. The presented predictive model could be used to select patients to be considered for less invasive surgical interventions or even a "wait and see" policy. Also, based on the predicted response, early modifications of the treatment protocol are possible, which might result in an improved clinical outcome.

PET-CT increases the interobserver agreement in the GTV definition in rectal cancer, helps to avoid geographical misses and allows tailoring the caudal border of the treatment volume.

This study presents areas in rectal tumors with an initially high FDG uptake to be most likely to show residual disease after CRT. This could indicate a higher (C)RT-resistance for tumor regions with a high FDG uptake prior to treatment.

Automatically generated PET-CT based contours show the best correlation with the surgical specimen and thus provide a useful and powerful tool to accurately determine the largest tumor dimension in rectal cancer. This could be used as a quick and reliable tool for target delineation in radiotherapy. However, a 3D volume analysis is needed to confirm these results.

Radiochemotherapy of rectal cancer leads to significant early changes in the metabolic activity of the tumor, which was not the case early after hypofractionated radiotherapy alone, despite the higher radiotherapy dose given. Thus, the chemotherapeutic agent Capecitabine might be responsible for the early metabolic treatment responses during radiochemotherapy in rectal cancer.

The combination of short-course radiotherapy and rapamycin turned out to be feasible, provided that the interval between neo-adjuvant treatment and surgical resection is at least 6 weeks. Although from this cohort no clear increase in pCR could be observed, a clear metabolic response after rapamycin run-in was observed, indicating a biological activity of this drug in rectal cancer.

This study strongly underlines the necessity of BGL-normalization of PET-data and a precise time-management between FDG injection and the start of PET acquisition when using sequential FDG-PET-CT imaging for the prediction of pathological treatment response.