LBA12 - 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-Inferio

J. Ma¹, L. Tang¹, L. Chen¹, G. Xu², C. Huang¹, R. Guo¹, W. F. Li¹, Y. P. Mao¹, G. Zhou¹, L. Lu¹, L. Chen¹, Y. Zhang¹, L. Lin¹, L. Liu³, J. B. Li⁴, X. Liu¹, C. Xu¹, F. Y. Xie¹, N. Zhang⁵, and Y. Sun¹; ¹Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China, ²Department of Radiotherapy, Cancer Center, The Peoples Hospital of Zhongshan, Zhongshan, China, ³Imaging Diagnosis and Interventional Center, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China, ⁴Clinical Trials Centre, Sun Yat-sen University Cancer Centre, Guangzhou, China, ⁵Department of Radiation Oncology, First Peoples Hospital of Foshan, Foshan, China

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). This study is registered with ClinicalTrials.gov, NCT04384627.
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 40.4 months till August 20, 2024, intention-to-treat analysis showed that the post-IC GTV group and pre-IC GTV group had similar 3-year LRRFS (91.5 % [95% CI 87.9 to 95.4] v 91.2% [95%CI 87.5 to 95.1], difference 0.3% [lower limit of the one-sided 95% CI -4.9], P<sub>non-inferiority 0.004), 3-year OS (96.8% v 96.7%, P=0.67) and DMFS (91.7% v 93.3%, P=0.50). 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 (13.5% v 27.3%) 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.

LBA 12 – Table 1

	post-IC group (%)	pre-IC group (%)	P value
Intention-to-treat population	n = 225	n = 220
3-yr overall survival	96.8	96.7	0.67
3-yr distant metastasis-free survival	91.7	93.3	0.67
3-yr failure-free survival	85.1	85.9	0.87
Safety population	n = 222	n = 220
Acute grade 3-4 adverse events	37.4	55.5
Late grade 3-4 adverse events	13.5	27.3