Radiotherapy Target Volume Delineation Based on Post-Induction Chemotherapy Gross Tumor Volume vs. Pre-Induction Volume for Locoregionally Advanced Nasopharyngeal Carcinoma: An Open-label, Non-Inferiority, Multicenter, Randomized Phase III Trial

Abstract

Purpose/Objective(s)

Radiotherapy target volume delineation based on pre-induction chemotherapy gross tumor volume (pre-IC GTV) is the standard principle in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after IC. However, over 90% patients responded to IC, with a significant volume reduction in GTV. We aimed to address whether radiotherapy target volume delineation based on pre-IC GTV can be safely reduced to post-IC GTV for LANPC patients treated with intensity-modulated radiotherapy.

Materials/Methods

In this open-label, non-inferiority, randomized controlled, phase III trial, patients with newly diagnosed, non-keratinising, non-metastatic NPC were recruited from three Chinese medical centers. Key inclusion criteria were aged 18–70 years, stage III-IVa disease (AJCC 8th edition), and a Karnofsky performance status score of at least 70. Eligible patients were required to have completed 3 cycles of IC and then were randomly assigned (1:1; block size of four) to receive radiotherapy with target volume delineation either based on post-IC or pre-IC GTV. Randomization was centrally performed with a random number code stratified by treatment center and stage. The primary endpoint was locoregional relapse-free survival (LRRFS). Non-inferiority was indicated if the lower limit of the 95% confidence interval (CI) of the difference in 3-year LRRFS between 2 groups was greater than -8%. The secondary endpoints were overall survival (OS), distant metastasis-free survival (DMFS), adverse events (AEs) and quality of life (QoL).

Results

A total of 445 patients were recruited (225 patients in the post-IC GTV group and 220 patients in the pre-IC GTV group). After a median follow-up of 38.7 months till June 30, 2024, intention-to-treat analysis showed that the post-IC GTV group and pre-IC GTV group had similar 3-year LRRFS (89.9% [95% CI 85.6 to 93.8] v 89.6% [95%CI 85.9 to 94.2], difference 0.3% [lower limit of the one-sided 95% CI -5.3], P_{non-inferiority} 0.007), 3-year OS (96.7% v 96.6%, P=0.64) and DMFS (91.2% v 92.7%, P=0.62). In the safety population (n=442), the post-IC GTV group had lower incidence of acute grade 3-4 AEs (37.4% v 55.5%) and late radiation related grade 3-4 AEs (22.5% v 33.6%) to the pre-IC GTV group. During follow up, the post-IC GTV group had significantly better QoL scores for global health (82.1 v 73.4, P<0.001) and emotional functioning (94.4 v 90.3, P=0.25).

Conclusion

Radiotherapy target volume delineation based on post-IC GTV was noninferior to that based on pre-IC GTV in LRRFS with less toxicities and better quality of life in LANPC. This study is registered with ClinicalTrials.gov, NCT04384627.