Description: Publication date: Available online 29 June 2018 Source: Radiotherapy and Oncology Author(s): Claudio Fiorino, Calogero Gumina, Paolo Passoni, Anna Palmisano, Sara Broggi, Giovanni M. Cattaneo, Alessandra Di Chiara, Antonio Esposito, Martina Mori, Roberta Raso, Monica Ronzoni, Riccardo Rosati, Najla Slim, Francesco De Cobelli, Riccardo Calandrino, Nadia G. Di Muzio Purpose Introducing a radiobiological index based on early tumor regression during neo-adjuvant radio-chemotherapy (RCT, including oxaliplatin) of rectal adenocarcinoma and testing its discriminative power in predicting the tumor response. Methods Seventy-four patients were treated with Helical Tomotherapy following an adaptive (ART) protocol (41.4 Gy/18 fr, 2.3 Gy/fr) delivering a simultaneous integrated boost on the residual tumor in the last 6 fractions up to 45.6 Gy. T2-weighted MRI were taken before (MRI pre ) and at mid (MRI mid ) therapy and the corresponding tumor volumes were considered ( V pre , V mid ). The “Early Regression Index” ( ER I TCP = - ln [ ( 1 - ( V mid / V pre ) ) V pre ] ) was introduced and its discriminative power was assessed in terms of AUC, sensitivity/specificity, positive/negative predictive value (PPV/NPV). Two end-points were considered: (a) pathological complete response (pCR) or clinical complete response followed by watch-and-wait, (cCR); (b) limited response (residual vital cells (RVC) in the surgical specimen >10%). Results Complete data were available for 65 patients: pCR, cCR and RVC >10% were 20, 2 and 19 respectively. The discriminative power of ERI TCP was moderately high (AUC = 0.81/0.75 for /pCRorcCR/RVC >10% respectively, p  〈 0.0005). ERI TCP was highly sensitive (86–89%) with very high NPV (90–94%). The discriminative power of ERI TCP was confirmed on a subgroup of 44/65 patients when considering tumor volumes delineated by a skilled radiologist. Conclusion A radiobiologically consistent index based on early regression showed high performances in predicting the pathological response after neo-adjuvant RCT for rectal cancer with relevant potentialities for ART/treatment customization.