Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial

Purpose To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG-PET/CT).Methods The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of (18) F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed (18) F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m(2) twice daily orally) was prescribed for the entire treatment duration.Results Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. (18) F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT.Conclusions Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.