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

Abstract

155 Background: The paradigm of locally advanced (T3/4; T1-4N1-2) rectal cancers (LARC) requires an intensified treatment for better pathological outcomes. Treatment intensification may be done by radiation dose escalation of long course neoadjuvant chemoradiation therapy (NACRT) by image guided Intensity Modulated Radiation Therapy (IG-IMRT) to increase downstaging with potentially higher local control rates. We aimed to analyze the efficacy and safety of NACRT with dose escalated IG-IMRT in LARC. Methods: 20 patients of LARC were recruited in this prospective interventional phase-II study treated by IG-IMRT with 45 Gray/25 fractions to elective nodal volumes and concomitant boost of 55 Gray/25 fractions to gross primary and nodal disease with concurrent capecitabine (825 mg/m2 twice a day on radiation days). All were planned to undergo definitive surgery 6-8 weeks post completion of NACRT with Total mesorectal excision by Low anterior resection (LAR) or Abdominoperineal resection (APR) followed by 6-8 cycles of adjuvant chemotherapy. Post operative response assessment was assessed by Modified Ryan’s scheme for regression and by tumor downstaging. Primary end point was acute toxicity assessment and secondary end points were pathological complete response (pCR) and loco-regional control (LRC). Results: Of 20 patients, 18 underwent definitive surgery and received full course adjuvant chemotherapy (90%). Median follow up was 15.1 months. 2 patients refused surgery, had complete clinical response (cCR) on assessment and were on follow up. Tumor downstaging was achieved in 14 (77.7%) patients and nodal downstaging was achieved in 15/18 (83.3%) patients. In 4 patients (22.2%) pCR was achieved and overall complete response (OCR defined as pCR and nearCR, including 2 patients with cCR) in 10 patients (50%). 4 patients planned for APR underwent LAR achieving a sphincter preservation rate of 22%. Grade 3 toxicities were observed in 2 patients which resolved on first follow up. No Grade 4 acute toxicities were reported. No loco-regional relapses were found and all patients are disease free at the time of last follow up. Conclusions: Dose escalation with IG-IMRT offers higher rates of pCR and OCR with acceptable toxicity profile and excellent short term locoregional control. [Table: see text]