Neoadjuvant Conformal Chemoradiation with Induction Chemotherapy for Rectal Adenocarcinoma. A Prospective Observational Study

Abstract

Background & Aims: The purpose of this prospective observational study was to evaluate the rate and
the prognostic factors for down-staging and complete response for rectal adenocarcinoma after induction
chemotherapy and neoadjuvant chemoradiation followed by surgery, and to analyze the rate of sphinctersaving surgery.

Methods: We included from March 2011 to October 2013 a number of 88 patients hospitalized with locally advanced rectal adenocarcinoma in the Prof. Dr. Ion Chiricuta Institute of Oncology, Cluj. The treatment schedule included 2-4 cycles of Oxaliplatin plus a fluoropyrimidine followed by concomitant chemoradiation with a dose of 50 Gy in 25 fractions combined with a fluoropyrimidine monotherapy.

Results:The rate of T down-staging was 49.4% (40/81 evaluable patients). Independent prognostic factors for T down-staging were: age >57 years (p<0.01), cN0 (p<0.01), distance from anal verge >5 cm (p<0.01), initial CEA <6.2 ng/ml (p<0.01), higher number of chemotherapy cycles with Oxaliplatin (pROC=0.05) and protraction of radiotherapy of >35 days (p<0.01). Nine patients from 81 (11.1%) presented complete response (7 pathological and 2 clinical); the independent prognostic factors were stage cT2 versus cT3-4 (p<0.01), initial tumor size ≤3.5 cm and distance from anal verge >5 cm (p=0.03). Sixty-eight patients (79.1%) underwent radical surgery and among them 35 patients (51.5 %) had a sphincter saving procedure.

Conclusions: Induction chemotherapy with neoadjuvant chemoradiation produced important down-staging in rectal adenocarcinoma. Independent prognostic factors for T down-staging were: age, cN0, distance from anal verge, initial CEA, the number of Oxaliplatin cycles and duration of radiotherapy; for complete response: cT2, initial tumor size and distance from the anal verge.
 
Abbreviations: 5FU: 5-fluorouracil; AJCC: American Joint Committee on Cancer; AV: anal verge; CAPOX: Capecitabine plus Oxaliplatin; CCR: clinical complete response; CRT: chemoradiation; CTC4.0: Common Terminology Criteria for Adverse Events, version 4.0; ECOG: Eastern Collaborative Oncology Group; EUS: endorectal ultrasound; FOLFOX: 5-fluorouracil plus Oxaliplatin; LARC: locally advanced rectal cancer; PCR: pathological complete response; PS: performance status; PTV: planning target volume; R0: Resection, 0 (microscopically clear resection margin); ROC curve: receiver operating characteristic curve; TME: total mesorectal excision; TRG: tumor regression grade.