Recent randomized studies have shown low compliance to adjuvant chemotherapy in stage III rectal cancer pts who received preoperative combined chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision (TME surgery). We examined whether giving part of the chemotherapy prior to radiotherapy (delivered by brachytherapy (HDRBT)) and surgery (instead of chemotherapy after RT and surgery, which is the current standard of care) for pts with node positive operable rectal cancer, would result in higher pt compliance to chemotherapy.
Between 2010-2017, 180 eligible pts were randomly assigned (2:1) to two arms, 6 cycles of FOLFOX prior to radiotherapy and surgery following by 6 cycles of FOLFOX in adjuvant (Arm A, (AA)), or 12 cycles of FOLFOX in adjuvant (Arm B, (AB)). The primary end point was compliance to chemotherapy (pts receiving at least 85% of full-dose CT prescribed at each cycle (x 12 cycles), 1 yr post-diagnosis); secondary end points were disease free survival rate (DFS), pT0N0, local recurrence rate and overall survival (OS), 5 yrs post-surgery.
All pts were randomly assigned to either AA (n = 120; 84 pts were male (M), median age (MA) was 65 years) or AB (n = 60; 35 pts were M, MA was 63.5 years). Compliance on AA was 78% and 51.9% on AB. Levels of G3/G4 toxicity were 30.8% in AA and 28.3% in AB respectively. 174 of 178 pts completed HDRBT as planned (97.7%). In AA, 3 pts progressed locally under CT. 1 pt refused HDRBT after randomization in AB. pT0N0 for AA and AB were 35pts (30.1%) and 15 pts (25%). The 3-year DFS was 80% with AA and 76% with AB (p = 0.6511). The 3-year OS for AA and AB were 94% and 85%, respectively (p = 0.8219).
The safety and improved compliance to neoadjuvant CT is confirmed in this study using HDRBT as a neoadjuvant modality for rectal cancer. There is no statistical difference in pT0N0 rate, local recurrence, and DFS between the two arms in the early result analysis, but favorable oncological outcomes are observed. At the time of this reporting, pelvic nodal recurrence is seldom isolated, asymptomatic and preceded by systemic failure.
Clinical trial identification
Legal entity responsible for the study
Jewish General Hospital-McGill.
All authors have declared no conflicts of interest.