Reduced-dose radiotherapy for Epstein-Barr virus DNA selected staged III nasopharyngeal carcinoma: A single-arm, phase 2 trial

Eur J Cancer. 2023 Nov:194:113336. doi: 10.1016/j.ejca.2023.113336. Epub 2023 Sep 9.

Abstract

Background: Radiotherapy-related toxicities of nasopharyngeal carcinoma (NPC) caused by a standard dose of 70 Gy remain a critical issue. Therefore, we assessed whether a radiotherapy dose of 60 Gy was non-inferior to the standard dose in patients with low-risk stage III NPC with a favourable response to induction chemotherapy (IC).

Patients and methods: We did a single-arm, single-centre, phase II clinical trial in China. Patients with low-risk (Epstein-Barr virus [EBV] DNA level <4000 copies/ml) stage III NPC were treated with two cycles IC. Patients with complete/partial response and undetectable EBV DNA level were assigned 60 Gy intensity-modulated radiotherapy concurrently with three cycles of cisplatin. The primary end-point was 2-year progression-free survival (PFS). This trial is registered with ClinicalTrials.gov, number NCT03668730.

Results: One patient quit because of withdrawal of informed consent after IC. In total, 215 patients completed two cycles of IC, after which 116 (54.0%) and 99 (46.0%) patients were assigned 60 and 70 Gy radiotherapy, respectively. For 215 patients, the 2-year PFS was 90.7% (95% CI, 86.8%-94.6%) with a median follow-up of 43.9 months (interquartile range [IQR], 39.8-46.2). For patients treated with 60 Gy radiotherapy, the 2-year PFS rate was 94.8% (95%CI 90.7%-98.9%) with a median follow-up of 43.9 months (IQR 40.2-46.2). The most common late toxicity was grade 1-2 dry mouth (incidence rate: 54.3%). No grade 3+ long-term adverse event was observed, and most quality-of-life items, domains, and symptom scores returned to baseline by 6 months.

Conclusion: Reduced-dose radiation (60 Gy) is associated with favourable survival outcomes and limited treatment-related toxicities in patients with low-risk stage III NPC sensitive to IC.

Keywords: De-escalation; Epstein-Barr virus DNA; Induction chemotherapy; Intensity-modulated radiotherapy; Nasopharyngeal carcinoma.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemoradiotherapy / adverse effects
  • DNA, Viral
  • Disease-Free Survival
  • Epstein-Barr Virus Infections* / complications
  • Herpesvirus 4, Human / genetics
  • Humans
  • Nasopharyngeal Carcinoma / drug therapy
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms* / drug therapy
  • Radiotherapy, Intensity-Modulated* / adverse effects

Substances

  • DNA, Viral

Associated data

  • ClinicalTrials.gov/NCT03668730