Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study.

PURPOSE: To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers. METHODS: This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety. RESULTS: The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373-0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227-0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350-0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230-0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1-2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions. CONCLUSION: For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment. TRIAL REGISTRATION: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939).

High-Dose Static and Dynamic Intensity-Modulated Radiotherapy Combined with Chemotherapy for Patients with Locally Advanced Nasopharyngeal Carcinoma Improves Survival and Reduces Brainstem Toxicity.

BACKGROUND Intensity-modulated radiotherapy (IMRT) is the standard treatment for patients with nasopharyngeal cancer (NPC). However, the dose-volume criteria for adjacent anatomically normal organs at risk (OARs) remain controversial. The aim of this study was to evaluate the effects of higher than conventional doses of static and dynamic IMRT on the locoregional control of NPC, patient survival, and brainstem radiation toxicity. MATERIAL AND METHODS Patients (n=186) with stage III and stage IVa NPC underwent high-dose static and dynamic IMRT treatment (68-76.96 Gy) with or without chemotherapy for 34-57 days. Overall survival (OS), the presence of distant metastases, and brainstem toxicity were assessed. One-year, three-year, and five-year follow-up was performed. RESULTS High-dose IMRT alone or in combination with chemotherapy resulted in a 100% objective response rate and significantly improved OS rates, with one-year, three-year, and five-year OS rates of 94.1%, 89.8%, and 88.2%, respectively. The local recurrence rate (17.6%), and distant metastasis to the lung, liver, and bone (17.2%), and mortality (n=22) were reduced. Chemotherapy was the only factor that was significantly correlated with patient survival. Brainstem toxicity was reduced in patients treated with static IMRT (0.07%) and dynamic IMRT (0.08%). There were 26 additional factors that were not found to significantly affect brainstem toxicity. CONCLUSIONS High-dose static or dynamic IMRT combined with chemotherapy improved survival and reduces distal metastasis with a very low occurrence of brainstem toxicity in patients with locally advanced NPC. These findings might provide therapeutic guidance for clinicians when planning optimal dose-volume IMRT parameters.

[Habitat suitability index model and minimum habitat area estimation of young Procypris rabaudi (Tchang): a simulation experiment in laboratory].

Under the conditions of simulated micro-habitat in laboratory, and by using experimental ecological methods, this paper evaluated the suitability index (HSI) of young Procypris rabaudi for habitat factors (substrate, light intensity and water depth). The habitat suitability models of the young P. rabaudi were established, and the minimum habitat area of the young P. rabaudi was estimated. The young P. rabaudi preferred the habitats with the gravel diameter from 10 to 15 cm, light intensity from 0.2 to 1.8 lx, and water depth from 0 to 15 cm (distance from the bottom of the tank). The three suitability index models of the substrate, light intensity and water depth for the young P. rabaudi were SI(s) = 1.7338e(-0.997x)(SI(S) is the suitability index of substrate, and x is the gravel diameter; R2 = 0.89, P < 0.01), SI(L) = 3.0121e(-1.339x)(SI(L) is the suitability index of light intensity, and x is the light intensity; R2 = 0.93, P < 0.01), and SI(W) = 2.4055e(-1.245x)(SI(W) is the suitability index of water depth, and x is the water depth; R2 = 0.97, P < 0.01), respectively. Arithmetic mean model HSI = (SI(S)+SI(L)+SI(W))/3 was most available for the estimation of the habitat suitability of young P. rabaudi. A total of seven groups of young P. rabaudi which established and maintained a relatively stable habitat area range were found. This habitat area ranged from 628 to 2015 cm2, with an average of 1114 cm2.

[Cold resistance of Pistacia chinensis and Koelreuteria integrifoliola].

Taking one-year-old dormant shoots of Pistacia chinensis and Koelreuteria integrifoliola as test materials and the shoots of northern indigenous tree species K. paniculata as the control, the changes of their membrane-lipid peroxidation, antioxidative enzyme activity, and organic osmoregulatory substance content under artificial cooling were studied, aimed to analyze the differences of the three tree species in cold resistance. With the decrease of temperature, the ion leakage percentage of the three tree species increased in S-shape, and the SOD and POD activities decreased after an initial increase. The MDA, soluble protein, and soluble sugar contents of K. integrifoliola and K. paniculata under decreasing temperature decreased after an initial increase, while those of P. chinensis had an increasing trend. The semi-lethal temperature (LT50 ) of K. paniculata, K. integrifoliola, and P. chinensis calculated by the Logistic equation of ion leakage percentage was -27.2 degrees C, -23.7 degrees C, and -27.0 degrees C, respectively. Among the three tree species, K. paniculata had the strongest cold resistance, followed by P. chinensis, and K. integrifoliola.