A novel ratiometric sensor for fluorimetric and visual dual-mode detection of Al3+ in environmental water based on the target-regulated formation of Eu MOFs.

Herein, a novel ratiometric sensor for fluorimetric and smartphone-assisted visual detection of Al3+ in environmental water was developed based on the target-regulated formation of Eu metal-organic frameworks (Eu MOFs). By employing 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid (Hepes), Eu3+ and tetracycline (TC) as raw materials, Eu MOFs with red emission were facilely synthesized through the coordination of Eu3+ with Hepes and TC. However, upon the introduction of Al3+, a higher affinity of TC towards Al3+ resulted in the formation of a TC-Al3+ complex with green fluorescence and inhibited the generation of Eu MOFs. This led to an increase in green fluorescence and a decrease in red fluorescence accompanied by the fluorescence color of the solution changing from red to green under the illumination of the UV lamp. Thus, a ratiometric sensor for fluorimetric and the smartphone-assisted visual detection of Al3+ was established. The ratiometric sensor exhibited high sensitivity for Al3+ detection with a detection limit of 0.14 µM for fluorescence detection and 1.21 µM for visual detection. Additionally, the proposed strategy was successfully applied to detect Al3+ in the environmental water samples with satisfactory results, indicating great application prospects for environmental monitoring.

Prognostic value of lymph node-to-primary tumor ratio of PET standardized uptake value for nasopharyngeal carcinoma: a recursive partitioning risk stratification analysis.

Background: Induction chemotherapy (IC) combined with concurrent chemoradiotherapy has become the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Data on the prognostic value of the lymph node-to-primary tumor ratio (NTR) of positron emission tomography (PET) standardized uptake value (SUV) for patients treated with IC were limited. Objectives: To evaluate the prognostic value of the SUV NTR for patients with LA-NPC treated with IC. Design: In all, 467 patients with pretreatment 18F-fluorodeoxyglucose PET/computed tomography (CT) scans between September 2017 and November 2020 were retrospectively reviewed. Methods: The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value of SUV NTR. Kaplan-Meier method was used to evaluate survival rates. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. Results: The optimal cutoff value of SUV NTR was 0.74. Multivariate analyses showed that SUV NTR and overall stage were independent predictors for distant metastasis-free survival (DMFS) and regional recurrent-free survival (RRFS). Therefore, an RPA model based on the endpoint of DMFS was generated and categorized the patients into three distinct risk groups: RPA I (low risk: SUV NTR < 0.74 and stage III), RPA II (medium risk: SUV NTR < 0.74 and stage IVa, or SUV NTR ⩾ 0.74 and stage III), and RPA III (high risk: SUV NTR ⩾ 0.74 and stage IVa), with a 3-year DMFS of 98.9%, 93.4%, and 84.2%, respectively. ROC analysis showed that the RPA model had superior predictive efficacy than the SUV NTR or overall stage alone. Conclusion: SUV NTR was an independent prognosticator for distant metastasis and regional recurrence in locoregionally advanced NPC. The RPA risk stratification model based on SUV NTR provides improved DMFS and RRFS prediction over the eighth edition of the TNM (Tumor Node Metastasis) staging system.

A facile fluorescence Eu MOF sensor for ascorbic acid and ascorbate oxidase detection.

In this work, a facile fluorescence Eu3+-based metal-organic framework (Eu MOF) sensor for ascorbic acid (AA) and ascorbate oxidase (AAO) detection was developed. The fluorescence of the Eu MOF could be effectively quenched by Ce3+ but not by Ce4+ at an appropriate concentration, and thus, when the reductant AA was added into the solution containing Ce4+, Ce4+ was chemically reduced to Ce3+, which induced the decreased fluorescence signal of the Eu MOF. However, when AAO was introduced, AA was effectively oxidized to dehydroascorbic acid (DHAA) under the catalysis of AAO, and thus, Ce4+ could not be reduced, resulting in the fluorescence restoration of the Eu MOF. Hence, the concentration of AA and AAO could be determined by the fluorescence decrease and restoration of the Eu MOF. The fluorescent platform showed high sensitivity with a limit of detection of 0.32 µM for AA and 1.18 U L-1 for AAO, respectively. Moreover, the proposed method was successfully applied for AA and AAO determination in real samples, indicating great potential for biomedical application in complex matrices.

Radiation-induced nasopharyngeal ulcers after re-irradiation with intensity-modulated radiotherapy in locoregional recurrent nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.

OBJECTIVE: To analyze the interrelation between radiation dose and radiation-induced nasopharyngeal ulcer (RINU) in locoregional recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: Clinical data were collected from 363 patients with locoregional recurrent NPC who received re-irradiated with definitive IMRT from 2009 to 2017. Twenty-nine patients were diagnosed with RINU. Univariate and multivariate analyses were used to re-evaluate the first and second radiotherapy plans and to identify predictive dosimetric factors. RESULTS: All dosimetric parameters were notably associated with the progression to RINU (p < 0.01) using paired samples Wilcoxon signed rank tests. Multivariate analysis showed that EQD2_ [Formula: see text]D80 (dose for 80 percent volume of the unilateral nasopharynx lesion) was an independent prognostic factor for RINU (p = 0.001). The area under the ROC curve for EQD2_ [Formula: see text]D80 was 0.846 (p < 0.001), and the cutoff point of 137.035 Gy could potentially be the dose tolerance of the nasopharyngeal mucosa. CONCLUSIONS: The sum of equivalent dose in 2 Gy fractions (EQD2) in the overlapping volumes between initial and re-irradiated nasopharyngeal mucosal tissue can be effective in predicting the hazard of developing RINU in NPC patients undergoing radical re­irradiation with IMRT and we propose a EQD2_ [Formula: see text]D80 threshold of 137.035 Gy for the nasopharynx.

Prognostic value of circulating Epstein-Barr virus DNA level post-induction chemotherapy for patients with nasopharyngeal carcinoma: A recursive partitioning risk stratification analysis.

BACKGROUND: To evaluate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level post-induction chemotherapy (IC) for patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 893 newly diagnosed NPC patients treated with IC were retrospectively reviewed. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off value of post-IC EBV DNA. RESULTS: Post-IC EBV DNA levels and overall stage were independent predictors for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). The RPA model base on post-IC EBV DNA and overall stage categorized the patients into three distinct risk groups: RPA I (low-risk: stage II-III and post-IC EBV DNA < 200 copies/mL), RPA II (median-risk: stage II-III and post-IC EBV DNA ≥ 200 copies/mL, or stage IVA and post-IC EBV DNA < 200 copies/mL), and RPA III (high-risk: stage IVA and post-IC EBV DNA ≥ 200 copies/mL), with 3-year PFS of 91.1%, 82.6%, and 60.2%, respectively (p < 0.001). The DMFS and OS rates in different RPA groups were also distinct. The RPA model showed better risk discrimination than either the overall stage or post-RT EBV DNA alone. CONCLUSIONS: Plasma EBV DNA level post-IC was a robust prognostic biomarker for NPC. We developed an RPA model that provides improved risk discrimination over the 8th edition of the TNM staging system by integrating the post-IC EBV DNA level and the overall stage.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Local control and failure patterns after intensity modulated radiotherapy with reduced target volume delineation after induction chemotherapy for patients with T4 nasopharyngeal carcinoma.

BACKGROUND: The delineation of target volume after induction chemotherapy(IC) for nasopharyngeal carcinoma(NPC) is currently controversial. In this study, we aimed to analyze the long-term local control(LC) and failure patterns of T4 NPC treated with reduced target volume radiotherapy after IC. METHODS: From September 2007 to January 2013, 145 patients with T4 NPC were retrospectively reviewed. All patients received at least 1 cycle of IC followed by intensity modulated radiotherapy(IMRT). The gross tumor volume(GTV) was delineated according to the post-IC images for intracavity tumors and lymph nodes. The LC and overall survival (OS) rates were calculated using the Kaplan-Meier method. The location and extent of local failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. RESULTS: With a median follow-up time of 95 months (range, 16-142 months), 23 local failures were found. The estimated 10-year LC and OS rates were 81.1%and 54.8% respectively. Among the 20 local failures with available diagnostic images, 18(90%) occurred within the 95% isodose lines and were considered in-field failures and 2(10%) were marginal. There was no outside-field failure. CONCLUSIONS: In-field failure was the major pattern of local failure for T4 NPC. IMRT with reduced target volume after IC seems to be feasible. Further researches exploring optimal volume and radiation dose for local advanced NPC in the era of IC are warranted.

Dosimetric predictors of temporal lobe injury after intensity-modulated radiotherapy for T4 nasopharyngeal carcinoma: a competing risk study.

BACKGROUND: In patients with T4 nasopharyngeal carcinoma (NPC), death may occur prior to the occurrence of temporal lobe injury (TLI). Because such competing risk death precludes the occurrence of TLI and thus the competing risk analysis should be applied to TLI research. The aim was to investigate the incidence and predictive factors of TLI after intensity-modulated radiotherapy (IMRT) among T4 NPC patients. METHODS: From March 2008 to December 2014, T4 NPC patients treated with full-course radical IMRT at our center were reviewed retrospectively. A nested case-control study was designed for this cohort of patients. The cases were patients with TLI diagnosed by MRI during the follow-up period, and the controls were patients without TLI after IMRT matched 1:1 to each case by gender, age at diagnosis, intercranial involvement, and follow-up time. The end point was time to TLI or death without prior TLI. We analyzed the cumulative incidence function (CIF) and performed a competing risk regression model to identify the predictors of TLI. RESULTS: With a median follow-up of 40.1 months, 63 patients (63/506, 12.5%) developed TLI as diagnosed by MRI, and 136 deaths occurred during the period. The cumulative incidence of TLI at 5 years was 13.2%, while 26.7% died without prior TLI. The univariate analysis showed that all selected dosimetric parameters were associated with the occurrence of TLI. On multivariate analysis, D1cc and V20 remained statistically significant. Based on the area-under-the-curve (AUC) values, D1cc was considered the most predictive. The patients with D1cc > 71.14 Gy had a 7.920-fold increased risk of TLI compared with those with D1cc ≤71.14 Gy (P < 0.05). Similarly, V20 > 42.22 cc was found to result in a statistically significant higher risk of TLI (subdistribution hazard ratio [sHR] =3.123, P < 0.05). CONCLUSIONS: TL D1cc and V20 were predictive of TLI after IMRT for T4 NPC. They should be considered as first and second priorities of dose constraints of the TL. D1cc ≤71.14 Gy and V20 ≤ 42.22 cc could be useful dose-volume constraints for reducing the occurrence of TLI during IMRT treatment planning without obviously compromising the tumor coverage.

The prognostic value of tumor depth for cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas.

BACKGROUND: To analyze the prognostic value of the clinicopathological parameters of primary lesions for predicting cervical lymph node metastasis in patients with hypopharyngeal and/or supraglottic carcinoma. METHODS: We enrolled 127 patients with squamous cell carcinomas originating in the hypopharyngeal and/or supraglottic regions. RESULTS: Multivariate analysis identified the tumor depth as an independent predictive factor for lymph node metastasis (odds ratio, 4.959; 95% confidence interval, 2.290-10.739; P < 0.0001) with a predictive value of 0.966. A cutoff value of 4.5 mm was determined. CONCLUSION: The tumor depth of the primary lesion is a potent predictor of cervical lymph node metastasis in hypopharyngeal and supraglottic carcinomas. In cases with clinically negative nodal status, elective neck dissection should be adopted for patients with a tumor depth reaching 4.5 mm. Regular outpatient follow-up is recommended for patients with a tumor depth less than 1.0 mm. Close follow-up or preventative therapy should be considered between 1.0 and 4.5 mm.

The prognostic value of preoperative prognostic nutritional index in patients with hypopharyngeal squamous cell carcinoma: a retrospective study.

BACKGROUND: To analyze the prognostic value of preoperative prognostic nutritional index (PNI) in predicting the survival outcome of hypopharyngeal squamous cell carcinoma (HPSCC) patients receiving radical surgery. METHODS: From March 2006 to August 2016, 123 eligible HPSCC patients were reviewed. The preoperative PNI was calculated as serum albumin (g/dL) × 10 + total lymphocyte count (mm-3) × 0.005. These biomarkers were measured within 2 weeks prior to surgery. The impact of preoperative PNI on overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier method and Cox proportional hazards model. RESULTS: Median value of 52.0 for the PNI was selected as the cutoff point. PNI value was then classified into two groups: high PNI (> 52.0) versus low PNI (≤ 52.0). Multivariate analysis showed that high preoperative PNI was an independent prognostic factor for better OS (P = 0.000), PFS (P = 0.001), LRFS (P = 0.005) and DMFS (P = 0.016). CONCLUSIONS: High PNI predicts superior survival in HPSCC patients treated with radical surgery. As easily accessible biomarkers, preoperative PNI together with the conventional TNM staging system can be utilized to enhance the accuracy in predicting survival and determining therapy strategies in these patients.

Radiation-induced hypothyroidism after IMRT for nasopharyngeal carcinoma: Clinical and dosimetric predictors in a prospective cohort study.

OBJECTIVES: To investigate the rate and risk factors for developing hypothyroidism (HT) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: A total of 135 consecutive patients treated with IMRT for NPC were prospectively evaluated during a median follow up of 34.1months. Serum thyroid function assessments before and after IMRT were periodically monitored. To identify risk factors for HT occurrence, univariate and multivariate Cox regression analyses were performed. RESULTS: Thirty-nine patients (28.9%) developed primary HT. The 2- and 3-year incidences of primary HT were 29.6% and 43.9%, respectively. The median clinical latency for primary HT was 15.1months (3.2-33.8months). No cases of central HT were observed. Univariate and multivariate analyses revealed that the risk increased with younger age and decreased with higher pretreatment thyroid volume. Patients with thyroid mean dose ≥45Gy had a 4.9 times increased risk of HT than those receiving lower mean dose. Alternatively, the thyroid V45 below 0.5 and V50 below 0.35 were found to significantly lower the incidence rate of HT. CONCLUSION: The incidence of primary HT after IMRT for NPC continued to increase with time. The thyroid mean dose constraint was approximately 45Gy. We recommended plan optimization objectives to reduce thyroid V45 to 0.5 and V50 to 0.35.

Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

AIM: To evaluate the efficacy and safety of using nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) in the primary treatment of locoregionally advanced nasopharyngeal carcinoma. METHODS: Between December 2009 and December 2013, 38 newly diagnosed patients with stage III-IV nasopharyngeal carcinoma were treated with IMRT and nimotuzumab concomitantly. The distribution of disease was stage III in 20 (52.6%), stage IV A in 9 (23.7%), and stage IV B in 9 (23.7%). All the patients received at least two cycles of cisplatin-based neoadjuvant chemotherapy followed by nimotuzumab 200 mg/week concurrently with IMRT. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. RESULTS: With a median follow-up of 39.7 months (range, 13.3-66.5 months), the estimated 3-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, progression failure-free survival, and overall survival rates were 92.8%, 92.9%, 89.5%, 78.7%, and 87.5%, respectively. The median cycle for nimotuzumab addition was 6 weeks. Grade 3 radiation-induced mucositis accounted for 36.8% of treated people. No skin rash and infusion reaction were observed, distinctly from what is reported in cetuximab-treated patients. CONCLUSION: Nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities for patients.

Concurrent chemoradiotherapy was associated with a higher severe late toxicity rate in nasopharyngeal carcinoma patients compared with radiotherapy alone: a meta-analysis based on randomized controlled trials.

BACKGROUND: To investigate the incidence and risk of severe late toxicity with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma patients. METHODS: Eligible studies included prospective randomized controlled trials (RCTs) evaluating CCRT versus radiotherapy alone in patients with nasopharyngeal carcinoma and in which data on severe late toxicities were available. Random effects or fixed effect models were applied to obtain the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Five RCTs with 1102 patients with NPC were included in this analysis. The summary incidence of overall severe late toxicities in patients receiving CCRT was 30.7% (95% CI, 18-47.2%) and the incidence of radiotherapy alone group was 21.7% (95% CI, 13.3-33.4%). The use of concurrent chemotherapy was associated with an increased risk of severe late toxicities, with a RR of 1.349 (95% CI, 1.108-1.643; P = 0.005). As for specific late toxicity, CCRT significantly increased the risk of ear deafness/otitis (RR = 1.567; 95% CI, 1.192-2.052), but other late toxicities were not significantly different. Patients receiving concurrent chemotherapy regimens with 3-week high-dose cisplatin (HC) have a higher risk of ear deafness/otitis (RR = 1.672; 95% CI, 1.174-2.382; P = 0.026). However, there was no significant increase in the RR of severe ear complication with the addition of non-3-week high-dose cisplatin (nonHC) regimens (RR = 1.433; 95% CI, 0.946-2.171; P = 0.095). CONCLUSION: With the present evidence, the addition of concurrent chemotherapy seems to increase the risk of severe late toxicities in patients with NPC, especially when using HC regimen for the occurrence of severe ototoxicity.

Effectiveness and toxicities of intensity-modulated radiation therapy for patients with T4 nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the effectiveness and toxicities in T4 nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT) combined with chemotherapy. METHODS: This is a retrospective analysis of 81 patients treated with intensity-modulated radiotherapy (IMRT). All the primary tumors were attributed to T4 stage according to the AJCC2010 staging system. And the distribution of disease by N stage was N0 in 13.6%, N1 in 30.9%, N2 in 37%, and N3 in 18.5%. Cisplatin-based chemotherapy was offered to all patients. Radiotherapy-related toxicities were graded according to the Acute and the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group (RTOG) scoring criteria. Chemotherapy-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3.0. Prognostic factors were assessed by univariate analysis. RESULTS: With a median follow-up of 37 months, 12 patients experienced local regional failure and total distant metastasis occurred in 18 patients, representing the major mode of failure. Ten patients died. Among them, 70% died of distant metastasis. The 3-year actuarial rates of local failure-free survival (LFFS), regional failure-free survival (RFFS), distant failure-free survival (DFFS), overall survival (OS), and progression-free survival (PFS) were 83.8%, 97.4%, 81.3%, 90%, and 69.7%, respectively. Acute and late toxicities were mild or moderate. CONCLUSIONS: IMRT provides excellent local-regional control for T4 NPC. Distant metastasis remains the major cause of treatment failure. Further explorations of the sequence and regimen of systemic therapy are needed in the future.