Paradoxical regression.

Top Line: With a rise in the use of total neoadjuvant therapy and “watch-and-wait” approaches for rectal cancer, should we use a higher than normal dose for the boost?

The Study: RECTAL-BOOST was a pragmatic, randomized phase 2 trial where patients with locally advanced rectal cancer received standard neoadjuvant chemoradiation +/- a 3 Gy x 5 = 15 Gy boost prior to the start of treatment. It sought to determine if dose escalation improved the rates of pathologic complete response (pCR) and sustained clinical response (no surgery nor evidence of tumor for 2 years) compared to standard treatment. Patients had tumors within 10 cm of the anorectal junction with cT4, cT3 within 1mm of mesorectal fascia, cN2, or extra-mesorectal lymph node metastasis present. Everyone received standard 2 Gy x 25 = 50 Gy with concurrent capecitabine +/- boost to the MRI-delineated primary tumor plus a 7-13 mm asymmetric margin. Finally, a 12-week interval between radiation completion and surgery was standardly used. Among over 120 patients enrolled, the combined rate of either pCR or 2-year sustained clinical response was the same in both arms (36-37%). Despite a significantly higher rate of near-complete tumor regression with dose escalation (45 → 69%), again there was no increase in pCR rate. A similar finding was seen in INTERACT.

TBL: Adding a dose-escalated boost to standard chemoradiation for locally-advanced rectal cancer results in greater (partial) tumor regression but no increase in the rate of pathologic complete response. | Couwenberg, Int J Radiat Oncol Biol Phys 2020