Neoadjuvant ‘Full Dose’ oxaliplatin/capecitabine/radiotherapy for MRI selected ‘very’ high risk rectal cancers with gross circumferential resection margin (CRM) involvement.

Background Several international randomised trials have reported no additional benefit for adding weekly, low dose (50-60mg/m2), oxaliplatin to capecitabine/5-FU/radiotherapy for locally advanced rectal cancer. The ‘SOCRATES’ phase II study used ‘full dose’ oxaliplatin (130mg/m2) d1 & 29, with acceptable toxicity & increased efficacy. Thus only for MRI defined ‘very’ high risk – gross CRM involvement by tumour/EMVI/multiple lymph nodes – the ‘SOCRATES’ regimen has remained in use in ARI since 2005. Methods Prospective database of all MRI defined ‘high risk’ rectal cancers from NE Scotland, about 700 patients, used to identify oxaliCRT treated patients. Data analysed using SSPS. Results 145 patients identified, with FU up to 13 years. M 98:F 47, age range 29 to 80 years. 126 patients had neoadjuvant oxaliCRT, 12 XELOX before oxaliCRT, & 4 XELOX after oxaliCRT, trying for a clear CRM. 3 patients had raltitrexed instead of capecitabine, 1 on treatment, due to significant IHD. 2 patients did not receive 2nd cycle of oxaliplatin, & no patient died during CRT or within 30 days of surgery. Surgery: 14 patients no surgery, as CRM still involved, 1 ‘open & close’, 86 an anterior resection, 32 an APER, & 8 ‘other’ surgery, such as exenteration. Adjuvant chemotherapy in 50 patients, being XELOX in 33. 127 patients had complete FU from date of diagnosis. For whole cohort 3Y OS 76%, 5Y OS 55%, & no statistical difference in OS for M:F, or N +ve:N -ve. Of those who had surgery, 2 R1 resections, 9% had minimal, 30% partial, 38% good partial & 23% complete pathological responses. Difference in OS between the 4 groups was significant (p<0.0005) Conclusion For ‘very’ high risk patients full dose oxaliplatin CRT may still be of value, with over 80% achieving a R0 resection, & overall 5y OS of 55%. Path response is significant & prognostic.