Low-dose fractionated radiotherapy combined with induction chemotherapy in high-risk nasopharyngeal carcinoma: An open-label, randomized phase 2 trial.

BACKGROUND

Outcomes for locally advanced nasopharyngeal carcinoma (LANPC) remain suboptimal despite comprehensive therapy. Preclinical studies demonstrated that low-dose fractionated radiotherapy (LDFRT) could potentiate chemotherapy, warranting further investigation.

METHODS

This open-label, randomized phase 2 trial enrolled LANPC patients with advanced nodal stage (N2-N3 with necrosis, extranodal extension, or short axis ≥ 3 cm). Eligible patients were randomized to the LDFRT or control group. All patients received three cycles of induction chemotherapy (IC) followed by concurrent chemoradiotherapy. The LDFRT group received 50 cGy radiation twice daily for 2 days targeting positive lymph nodes during each cycle of IC. The primary endpoint was the overall (nasopharynx and lymph nodes) objective response rate (ORR) after IC, with the secondary endpoints including 2-year survival outcomes and safety.

RESULTS

Eighty-two patients (41 per group) were included in the intention-to-treat analysis. After IC, the LDFRT group demonstrated a significantly higher overall ORR (100% vs. 85.4%, p = 0.03) and numerically higher CR rate (14.6% vs. 2.4%, p = 0.11). The LDFRT group achieved greater median lymph node and total tumor volume regression compared to the control group (90.1% vs 53.91%; 77.1% vs 55.1%, respectively; p < 0.001). After a median follow-up of 26.2 months, the 2-year progression-free survival (PFS) and distant metastasis-free survival (DMFS) showed trends favored LDFRT (87.6% vs. 71.9%, p = 0.17; 90.1% vs. 77.1%, p = 0.23, respectively). Acute toxicities were comparable between groups.

CONCLUSIONS

In high-risk LANPC, LDFRT with IC improved ORR and tumor volume reduction, and was associated with a potential benefit in PFS and DMFS.