Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial.

Importance: Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). Objective: To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. Design, Setting, and Participants: This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Interventions: Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). Main Outcomes and Measures: The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Results: Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Conclusions and Relevance: Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02633202.

Variations in cadmium and nitrate co-accumulation among water spinach genotypes and implications for screening safe genotypes for human consumption.

Vegetables are important constituents of the human diet. Heavy metals and nitrate are among the major contaminants of vegetables. Consumption of vegetables and fruits with accumulated heavy metals and nitrate has the potential to damage different body organs leading to unwanted effects. Breeding vegetables with low heavy metal and nitrate contaminants is a cost-effective approach. We investigated 38 water spinach genotypes for low Cd and nitrate co-accumulation. Four genotypes, i.e. JXDY, GZQL, XGDB, and B888, were found to have low co-accumulation of Cd (<0.71 mg/kg dry weight) and nitrate (<3100 mg/kg fresh weight) in the edible parts when grown in soils with moderate contamination of both Cd (1.10 mg/kg) and nitrate (235.2 mg/kg). These genotypes should be appropriate with minimized risk to humans who consume them. The Cd levels in the edible parts of water spinach were positively correlated with the concentration of Pb or Zn, but Cd, Pb, or Zn was negatively correlated with P concentration. These results indicate that these three heavy metals may be absorbed into the plant in similar proportions or in combination, minimizing the influx to aerial parts. Increasing P fertilizer application rates appears to prevent heavy metal and nitrate translocation to shoot tissues and the edible parts of water spinach on co-contaminated soils.

Distribution and health risk assessment of dissolved heavy metals in the Three Gorges Reservoir, China (section in the main urban area of Chongqing).

The Three Gorges Project (TGP) is the largest hydropower station ever built in the world. A better understanding of the concentrations of heavy metals in the aquatic environment of the Three Gorges Reservoir (TGR) is crucial for national drinking water security and sustainable ecosystem development. To thoroughly investigate the impact of heavy metals on water quality after the impoundment to the maximum level of 175 m in the TGR, the concentrations of the dissolved heavy metals (Cr, Cu, Zn, Cd, Pb, As) were measured in April and August 2015, by inductively coupled plasma mass spectrometry (ICP-MS). (1) Except Zn and Pb, most of the heavy metal concentrations in the water of the TGR reached the level of the National Surface Water Environmental Quality Standards (GB3838-2002) I of China, revealing that the water quality of the TGR was good overall. (2) There were significant positive correlations among the concentrations of Cu, As, and Cd, revealing that they may exhibit similar geochemical behaviors. (3) The spatial distribution of the heavy metal concentrations was diverse and complex. The Zn concentration obviously increased in the rainy season from upstream to downstream in the Yangtze River, while the other heavy metals exhibited no significant changes in their concentrations. The distribution characteristics of the heavy metal concentrations on both sides and the middle of the river were different at different sites. (4) The health risk of the six elements was assessed through a human health risk assessment (HHRA), and the assessment results were lower than the maximum acceptable risk level designed by the US EPA and International Commission on Radiological Protection (ICRP). The HHRA model in the aquatic environment revealed that the risk of non-carcinogenic heavy metals (Cu, Zn, and Pb) was at a negligible risk level of 10-11∼10-9 a-1. At all the study sites, the risk of carcinogenic heavy metals (Cr, Cd, and As) was higher than the risk of non-carcinogenic heavy metals. As was the most important risk factor, followed by Cr. The results of this study hold great significance for a timely understanding of the changing water quality for affected departments to ensure the health of the residents in the TGR area.

[Application of 99mTc-DTPA in evaluation of blood-brain barrier permeability in patients receiving whole brain irradiation].

OBJECTIVE: To study the pattern of blood-brain barrier (BBB) permeability changes during whole brain radiotherapy (WBRT) for metastatic brain tumor. METHODS: Twenty patients with metastatic brain tumors receiving WBRT by 6 MV X-ray underwent (99)mTc-DTPA brain SPECT before and during WBRT (20, 40 Gy) and at 2 weeks after the end of irradiation. A frame of transverse (99)mTc-DTPA brain SPECT image that best displayed the brain metastasis was chosen, and the regions of interest (ROI) were defined in the tumor foci (T), the contralateral normal brain tissue (N) and the background outside the soft tissues around the cranium (B). The radioactive counts of every ROI were measured and the ratios of the total counts (T/B and N/B) before and during WBRT (20 Gy, 40 Gy) and at 2 weeks after the irradiation were calculated. RESULTS: The average T/B and N/B in the 20 patients with 30 brain metastases was 142.2-/+51.1 and 82.6-/+42.3 before WBRT, 260.3-/+121.5 and 150.7-/+72.5 during 20 Gy WBRT, 251.6-/+118.3 and 161.8-/+68.4 during 40 Gy WBRT, and 250.3-/+117.2 and 158.6-/+73.5 at 2 weeks after the irradiation, respectively. The measurements during WBRT (20 and 40 Gy) and at 2 weeks after the irradiation group underwent no significant variations (P>0.05), but showed significant differences from those before WBRT (P<0.05). CONCLUSIONS: Irradiation causes direct damage of the BBB function, and the permeability of the BBB increases significantly during and within 2 weeks following 20 and 40 Gy WBRT, which provides the optimal time window for interventions with chemotherapy.