Low-Dose Ultra-Fractionated Radiotherapy as a Chemosensitizer of Neoadjuvant Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma: A Preliminary Results of the Phase II Trial

Abstract

The main failure model of locally advanced nasopharyngeal carcinoma (LANPC) is local failure and distant metastasis. N stage is a prognostic factor for NPC. Some characteristics of lymph nodes, such as the size, number, laterality, extra-nodal neoplastic spread and central necrosis, were the high-risk factors for treatment failure. Nowadays, neoadjuvant chemotherapy followed with concurrent chemo radiotherapy was recommended for LANPC patients. Low-dose radiotherapy (LDRT), which is < 100 cGy, induces enhanced cell killing in vitro and in vivo by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. Few studies reported about it. Recently, a single arm study showed it could improve the ORR to 82% for head and neck squamous carcinoma when combined with neoadjuvant chemotherapy. So, we aimed to investigate the efficacy of LDRT combined with neoadjuvant chemotherapy for high-risk LANPC.Squamous III-IVA NPC patients (UICC/AJCC 8th) with high-risk factors of lymph nodes were prospectively enrolled in the study. The high-risk factors should include one of these followings: lymph node with central necrosis, extranodal neoplastic spread, contrast-enhancing rim or the shortest diameter of lymph nodes ≥3cm. 3 cycles of neoadjuvant chemotherapy were given, the regimen was docetaxel (75mg/m2 D1) and cisplatin (75mg/m2 D1). LDRT was delivered as 50 cGy per fraction twice a day for gross nodal disease on D1 and D2 of neoadjuvant chemotherapy. All the patients received MRI scan before and after the neoadjuvant chemotherapy. Propensity score matching was used to select the patients as control group. RECIST criteria was used to evaluate the ORR.From Jun 2020 to Jan 2021, a total of 27 patients were enrolled in the study. Another 27 patients were matched for control group. For the whole patients, the median age were 43 years. III and IVA Clinical stage were 25.9%, 74.1% and 29.6%, 70.4% respectively for LDRT and control group (P = 0.761). As for the lymph nodes, the ORR of LDRT group was significantly higher than control group (100% vs 85.2%, P = 0.038). The average regression rate of lymph nodes was 89.4% in LDRT group, CR and PR was 7.4% and 92.6%. However, the average regression rate of it was only 56.24% in control group. There was no CR, PR and SD were 88.9% and 11.1%. For the primary tumor, there was no significant difference. But we found the ORR of it was higher in LDRT group (96.3% vs 81.5%, P = 0.083). And the average regression rate was 57.5% and 38.3% respectively in LDRT and control group.LDRT combined with neoadjuvant chemotherapy could improve the ORR for primary tumor and lymph nodes in high-risk LANPC patients, especially for lymph nodes. This new treatment model could be a promising strategy to improve local control, and needed to be confirmed in the future practice.