Low-dose fractionated radiotherapy combined with neoadjuvant chemotherapy for T3-4 nasopharyngeal carcinoma patients: Preliminary results of a phase II randomized controlled trial.

6049 Background: Over 70% of NPC patients were local advanced NPC (LANPC). The 5-year local recurrence-free survival rate is only 70% in T3-4 patients. Neoadjuvant chemotherapy (NACT) followed with concurrent chemoradiotherapy (CCRT) was recommended for LANPC patients. Low-dose fractionated radiotherapy (LDFRT), which is < 100cGy, induces enhanced cell killing by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. The synergy of LDFRT and NACT has not been used in the clinical practice and few studies focused on it. A single arm study found the ORR of primary site was improved to 90% for head and neck squamous carcinoma patients treated with LDFRT and NACT. Our previous study found the ORR of lymph nodes was higher in LDFRT group for high-risk LANPC patients. However, another study showed there was no significant difference between LDFRT and control group for LANPC patients. So, we aimed to investigate the potential efficacy of this novel neoadjuvant therapy for T3-4 NPC patients. Methods: 60 pathological confirmed T3-4 (UICC/AJCC8 th ) NPC patients were prospectively enrolled in our study. They were randomly assigned to two groups. For the LDFRT group, the patients received 3 cycles of NACT (docetaxel 75mg/m 2 D1, cisplatin 80mg/m 2 D1) with LDFRT, and followed with CCRT. LDFRT was delivered as 50cGy per fraction twice a day to primary site on D1,2 for each cycle of NACT. The patients in the control group only received NACT and followed with CCRT. All the patients underwent IGRT. RECIST criteria and CTCAE 5.0 was used to evaluate the ORR and toxicity at post-NACT and the completion of CCRT. Results: from Feb 2022 to Dec 2022, 60 T3-4 NPC patients were included, and 30 patients for each group. For the primary site, the median volume reduction rate and the ORR after NACT was significantly improved in LDFRT group (69.27% vs 40.10%, p< 0.001;93.33% vs 73.33%, p= 0.038). For the median volume reduction rate of primary site and lymph node, it was also obviously improved in LDFRT group (86.59% vs 55.43%, p< 0.001). Though there was a tendency of ORR improvement in LDFRT group, but no significant difference (96.67% vs 83.33%, p= 0.195). After the completion of CCRT, the median volume reduction rate of primary site had an increased tendency in LDFRT group (96.16% vs 88.3%, p= 0.065), but the ORR had no statistical significance (LDFRT group: CR 45.8%, PR 54.2%; control group: CR 37.5%, PR 62.5%). For the toxicity, the incidence of grade 3-4 adverse events had no difference between two groups ( p= 0.786). No grade 5 adverse events occurred. Conclusions: LDFRT combined with NACT could obviously improve the median volume reduction rate and ORR of primary tumor for T3-4 NPC patients, and the toxicity was similar and tolerable. The novel treatment could be a promising strategy to improve treatment response, and needed to be confirmed further. Clinical trial information: NCT05503914 .