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trial rectal chemoradiotherapy dose-escalation

Dose-escalated chemoradiotherapy improved nine-year survival in locally advanced rectal cancer

A 56 Gy simultaneous integrated boost improved nine-year survival and disease control compared with standard 50 Gy chemoradiotherapy.

RadOncToday · ·1 min read

KEY POINTS

  • This open-label randomized phase 2 trial enrolled 106 patients with stage II–III rectal adenocarcinoma between 2013 and 2015. Almost all had cT3–4 disease, 86.8% were node-positive, 66.4% had mesorectal-fascia involvement and 54.7% had extramural venous invasion.
  • Patients received pelvic intensity-modulated radiotherapy of 50 Gy in 25 fractions with concurrent capecitabine. The experimental arm received a simultaneous integrated boost to 56 Gy to the primary tumour region and 60 Gy to clinically involved lateral pelvic nodes.
  • The primary endpoint was negative: pathological complete response occurred in 15.2% versus 18.4% with dose escalation and standard chemoradiotherapy, respectively (p = 0.695). Overall complete response, including watch-and-wait patients, was 18.2% versus 17.6%.
  • After a median follow-up of 116.6 months, nine-year disease-free survival was 70.8% versus 47.4% (hazard ratio 0.46, p = 0.013), and overall survival was 74.3% versus 48.9% (hazard ratio 0.43, p = 0.008).
  • Nine-year metastasis-free survival was 70.8% versus 47.2% (hazard ratio 0.48, p = 0.017), local control was 87.1% versus 70.1% (hazard ratio 0.40, p = 0.038), and cancer-specific survival was 77.4% versus 57.2% (p = 0.027).
  • Among the 89 patients receiving curative-intent surgery or watch-and-wait management, nine-year disease-free survival was 79.5% versus 60.4%, overall survival was 83.4% versus 62.4%, and locoregional recurrence was 4.2% versus 10.7%.
  • Acute grade 3 toxicity occurred in 14.5% versus 19.6%, with no grade 3 or higher postoperative complications. Exploratory analysis suggested a benefit among patients who did not receive perioperative chemotherapy, but not among those who did.

CLINICAL TAKEAWAY

These results suggest that a 56 Gy simultaneous integrated boost can improve long-term disease control without materially increasing toxicity. The finding is not sufficient to redefine contemporary practice: this was a small phase 2 trial, its primary endpoint was negative, treatment predated routine total neoadjuvant therapy, and imbalances in receipt of curative treatment may have influenced long-term outcomes.

SOURCE

International Journal of Radiation Oncology, Biology, Physics