Prospective evaluation of dose-escalated preoperative concurrent chemo-radiation with image guided-IMRT in locally advanced rectal cancers.

ABSTRACT

Purpose: To analyse the safety and efficacy of neoadjuvant chemoradiation (NACRT) with dose-escalated image-guided intensity modulated radiation therapy (IG-IMRT) in locally advanced (T3/4; T1-4N1-2) rectal cancers (LARCs). Materials and methods: Twenty patients with the diagnosis of LARC were recruited in this prospective interventional single-arm study treated by IG-IMRT with 45 Gray (Gy) in 25 fractions to elective nodal volumes and 55 Gy in 25 fractions to the gross primary and nodal disease with concurrent capecitabine 825 mg/m2 twice daily on radiotherapy days. Patients underwent total mesorectal excision 6-8 weeks post completion of NACRT followed by adjuvant chemotherapy (Capecitabine and oxaliplatin every 3 weekly for 6-8 cycles). Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Clinical T stage was T3T4 in 191 and clinical N0N1 N2 in 2711 patients, respectively. With a median follow up of 21.2 months (13.8-25.6 months), 18 of 20 (90%) patients received the full course of treatment. Tumour and nodal downstaging was achieved in 78% and 84% of patients, respectively. pCR and overall complete response (defined as pCR and near CR) was achieved in 22.2% and 44.4% of patients, respectively. 2 (10%) patients completed NACRT, and achieved complete clinical response but refused surgery. Adjuvant chemotherapy course was completed by 17/18 (94.5%) patients. Grade 3 toxicities were observed in 2 (10%) patients during NACRT. All patients were disease-free at the time of the last follow up. Conclusion: Dose-escalation of NACRT therapy with IG-IMRT in LARC patients offers decent rates of pCR and overall response with excellent LRC and acceptable toxicities.