Quantum squeezing-induced quantum entanglement and EPR steering in a coupled optomechanical system.

We propose a theoretical project in which quantum squeezing induces quantum entanglement and Einstein-Podolsky-Rosen steering in a coupled whispering-gallery-mode optomechanical system. Through pumping the χ(2)-nonlinear resonator with the phase matching condition, the generated squeezed resonator mode and the mechanical mode of the optomechanical resonator can generate strong quantum entanglement and EPR steering, where the squeezing of the nonlinear resonator plays the vital role. The transitions from zero entanglement to strong entanglement and one-way steering to two-way steering can be realized by adjusting the system parameters appropriately. The photon-photon entanglement and steering between the two resonators can also be obtained by deducing the amplitude of the driving laser. Our project does not need an extraordinarily squeezed field, and it is convenient to manipulate and provides a novel and flexible avenue for diverse applications in quantum technology dependent on both optomechanical and photon-photon entanglement and steering.

Photon blockade with a trapped Λ-type three-level atom in asymmetrical cavity.

We propose a scheme to manipulate strong and nonreciprocal photon blockades in asymmetrical Fabry-Perot cavity with a Λ-type three-level atom. Utilizing the mechanisms of both conventional and unconventional blockade, the strong photon blockade is achieved by the anharmonic eigenenergy spectrum brought by Λ-type atom and the destructive quantum interference effect induced by a microwave field. By optimizing the system parameters, the manipulation of strong photon blockade over a wide range of cavity detuning can be realized. Using spatial symmetry breaking introduced by the asymmetry of cavity, the direction-dependent nonreciprocal photon blockade can be achieved, and the nonreciprocity can reach the maximum at optimal cavity detuning. In particular, manipulating the occurring position of nonreciprocal photon blockade can be implemented by simply adjusting the cavity detuning. Our scheme provides feasible access for generating high-quality nonreciprocal single-photon sources.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Melatonin attenuates nicotine-induced autophagy and neurological changes by decreasing the production of reactive oxygen species.

Purpose: The aim of this study was to explore the mechanism of neurological changes underlying the toxicity of nicotine.Materials and methods: Rat pheochromocytoma 12 (PC12) cells and human neuroglia (HM) cells were used. The ROS levels of the cells were detected by the FACScan. Autophagy flux was monitored by a tandem monomeric RFP-GFP-tagged LC3 lentivirus. The autophagic proteins LC3, SQSTM1/p62 and Beclin1 were detected by western blot assay. In order to evaluate the effects of nicotine and melatonin on the morphological changes of neurons, primary cortical neurons were obtained and immunocytochemistry of TUBB3 tubulin were conducted.Results: Nicotine increased the levels of reactive oxygen species (ROS) in PC12 and HM cells in a concentration-dependent manner. Microscopy showed increased autophagic flux in nicotine-treated PC12 cells. Subsequent western blotting results showed that nicotine induced increase in the levels of LC3B-II and Beclin1, and decreased SQSTM1/p62 in a concentration-dependent manner. Finally, nicotine treatment reduced the length of TUBB3-positive axons and dendrites. Melatonin, a mitochondrially targeted antioxidant, reduced the ROS level, and blocked autophagy activation and the morphologic structural changes induced by nicotine.Conclusions: Our results suggested that the role of nicotine in neuronal toxicity maybe through the induction of ROS and the subsequent activation of autophagy. These effects could be restored by melatonin.

Prognostic Value of Cervical Nodal Necrosis in Nasopharyngeal Carcinoma: Analysis of 1800 Patients with Positive Cervical Nodal Metastasis at MR Imaging.

PURPOSE: To evaluate the prognostic value of cervical nodal necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance (MR) imaging. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of 1800 patients with newly diagnosed stage T1, 4N1, 3M0 NPC who were treated with definitive radiation therapy, with or without chemotherapy, between January 2007 and December 2009; the requirement to obtain informed consent was waived. MR images were reviewed to assess lymph node status, and patients were divided into CNN and non-CNN groups. The overall survival, disease-free survival, regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. RESULTS: The incidence of CNN was 44.0% (792 of 1800). After the median follow-up period of 53 months, the 5-year overall survival, disease-free survival, RRFS, and DMFS rates of the CNN and non-CNN groups were 78.8% and 91.8%, 78.2% and 91.2%, 78.6% and 91.8%, and 78.4% and 91.6%, respectively (for all rates, P < .001). The distant metastasis rate was 18.7% (148 of 792) for the CNN group versus 4.6% (46 of 1008) for the non-CNN group (P < .01). Subgroup analysis revealed similar survival outcomes between stage N1 disease with CNN and stage N2 disease without CNN, stage N2 disease with CNN, and stage N3 disease regardless of CNN. CNN, T stage, N stage, age older than 44 years, and male sex were significant independent negative prognostic factors for overall survival, disease-free survival, RRFS, and DMFS. CONCLUSION: CNN is an independent negative prognostic factor in patients with NPC, and it may be appropriate to investigate whether N stage should be upgraded by one level in patients with CNN.

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors.

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4.

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.

Retrieving soil moisture using cosmic-ray neutron technology based on COSMIC model in the desert-oasis region.

Cosmic-ray neutron technology could estimate average soil moisture on scale of hectometers by monitoring the neutron intensity near the ground, which has been successfully applied in forest, grassland, farmland, and other ecosystems. To verify the reliability of Cosmic-ray Soil Moisture Interaction Code (COSMIC) model for retrieving mesoscale soil moisture in arid regions, we carried out soil moisture observation experiment by using the cosmic-ray neutron rover in the desert-oasis region of the middle reaches of Heihe River. The results showed that the fast neutron intensity in the desert-oasis region were 350-715 counts·(30 s)-1, and the calibrated high energy neutron intensity (Ncosmic) were (38.5±2.2) counts·(30 s)-1, which was affected by land surface characteristics. Both COSMIC model (root mean square error=0.019 g·g-1) and N0 equation (root mean square error=0.018 g·g-1) could well assess the mesoscale soil moisture, with the accuracy of soil moisture being higher considering soil lattice water. The average penetration depth was 19 cm in the oasis region and 36 cm in the desert region during the experiment. COSMIC model could be used to retrieve soil moisture by cosmic ray neutron in the desert-oasis regions, which had great potential to realize data assimilation of surface meteorological-hydrological-ecological variables by combining with land surface models.

Intraparenchymal papillary meningioma of brainstem: case report and literature review.

Both intraparenchymal papillary meningioma and papillary meningioma with cyst formation of brainstem have never been reported. The authors present an extremely rare case of patient with intraparenchymal papillary meningioma of brainstem. A 23-year-old Chinese male presented with a 4-month history of progressive left upper limb and facial nerve palsy. Magnetic resonance imaging revealed a cystic-solid, heterogeneously enhancing mass in pons and right cerebral peduncle with no dural attachment. The tumor was totally removed via subtemporal approach. During surgery, the lesion was found to be completely intraparenchymal. Histological and immunohistochemical examinations were compatible with the diagnosis of papillary meningioma. The lesion recurred nine months after primary surgery, a second surgery followed by radiotherapy was performed. Till to now (nearly 2 years after the treatment), the patient is tumor free survival. Intraparenchymal meningioma of brainstem with cystic formation is very rare, however, it should be considered as a differential diagnosis of a brainstem neoplasm. The present case strongly recommended that postoperative radiotherapy was essential for the patients with papillary meningiomas.

Potential Therapeutic Application of Local Anesthetics in Cancer Treatment.

Local anesthetics are voltage-gated sodium channel blockers primarily administered locally or to the innervating nerves for anesthetic or analgesic purposes. In vitro studies have found direct effects of local anesthetics on cancer cells, such as impact on cancer cell proliferation, apoptosis, migration, invasion, and chemosensitivity, by multiple mechanisms. So far, in vivo evidence regarding the effect of local anesthetics on cancer cell lines is relatively lacking. Local and regional anesthesia administration has been reported to reduce postoperative pain and opioid use in cancer treatment. Additionally, regional anesthesia may reduce the perioperative stress response. However, the clinical therapeutic application of local anesthetics in cancer remains exploratory. In this review, we will discuss the direct and indirect effects of local anesthetics on cancer cells, and discuss the current evidence related to the use of local anesthetics in the treatment of cancer.

Apatinib for recurrent/progressive glioblastoma multiforme: A salvage option.

Purpose: The recurrent/progressive glioblastoma multiforme (GBM) carries a dismal prognosis and the definitive treatment strategy has not yet been established. This study aimed to assess the efficacy and safety of apatinib in recurrent/progressive GBM patients. Materials and methods: The clinical data of 19 recurrent/progressive GBM patients who received apatinib treatment from November 2015 to December 2019 at Sun Yat-sen University Cancer Center were collected retrospectively in this study. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and assessed. Results: The overall ORR was 52.6%, and the DCR was 73.7%. Median PFS and OS were 5.1 and 10.4 months, respectively. The 6-month PFS and OS rates were 38.9% and 68.4%, respectively. The 12-month PFS and OS rates were 16.7% and 36.8%, respectively. The treatment-related toxicities were generally well-tolerated. The most common grade 3/4 AEs were hand-foot syndrome (36.8%) and hypertension (21.1%). Conclusion: Our study showed that apatinib therapy provided a better salvaging option for recurrent/progressive GBM patients and the toxicity was manageable.

Exploring the genes involved in biosynthesis of dihydroquercetin and dihydromyricetin in Ampelopsis grossedentata.

Dihydroquercetin (DHQ), an extremely low content compound (less than 3%) in plants, is an important component of dietary supplements and used as functional food for its antioxidant activity. Moreover, as downstream metabolites of DHQ, an extremely high content of dihydromyricetin (DHM) is up to 38.5% in Ampelopsis grossedentata. However, the mechanisms involved in the biosynthesis and regulation from DHQ to DHM in A. grossedentata remain unclear. In this study, a comparative transcriptome analysis of A. grossedentata containing extreme amounts of DHM was performed on the Illumina HiSeq 2000 sequencing platform. A total of 167,415,597 high-quality clean reads were obtained and assembled into 100,584 unigenes having an N50 value of 1489. Among these contigs, 57,016 (56.68%) were successfully annotated in seven public protein databases. From the differentially expressed gene (DEG) analysis, 926 DEGs were identified between the B group (low DHM: 210.31 mg/g) and D group (high DHM: 359.12 mg/g) libraries, including 446 up-regulated genes and 480 down-regulated genes (B vs. D). Flavonoids (DHQ, DHM)-related DEGs of ten structural enzyme genes, three myeloblastosis transcription factors (MYB TFs), one basic helix-loop-helix (bHLH) TF, and one WD40 domain-containing protein were obtained. The enzyme genes comprised three PALs, two CLs, two CHSs, one F3'H, one F3'5'H (directly converts DHQ to DHM), and one ANS. The expression profiles of randomly selected genes were consistent with the RNA-seq results. Our findings thus provide comprehensive gene expression resources for revealing the molecular mechanism from DHQ to DHM in A. grossedentata. Importantly, this work will spur further genetic studies about A. grossedentata and may eventually lead to genetic improvements of the DHQ content in this plant.

Efficacy of X-ray stereotactic radiotherapy on brain metastases and prognostic analysis.

BACKGROUND AND OBJECTIVE: X-ray stereotactic radiotherapy (SRT) is one of the effective treatments for brain metastases (BM). This study was to evaluate the efficacy of SRT on BM, and investigate prognostic factors. METHODS: Between July 1999 and December 2004, a total of 122 intracranial lesions in 78 patients with BM were treated using SRT in our Center. Forty-nine patients had a solitary lesion and 29 had multiple (2-6) lesions. The median SRT dose was 15 Gy (11-24 Gy) in single fraction for 38 lesions, and 24 Gy (11-40 Gy) in 2-6 fractions for 84 lesions. SRT was combined with whole brain radiotherapy (WBRT) of 30-40 Gy for 39 patients. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed by the log-rank test and Cox model, respectively. RESULTS: The median survival time was 12.9 months (1.7-77.4 months). The 1-year intracranial PFS rate was 87.4%. The 1-and 2-year OS rates were 53.9% and 25.8%, respectively. Univariate analysis showed that the 1-year OS rates were higher in the patients with pretreatment KPS of >/= 70, extracranial lesions controlled, or SRT combined with WBRT than in those with KPS of < 70 (60.7% vs. 29.4%, P = 0.002), extracranial lesions uncontrolled (69% vs. 44.9%, P = 0.005), or SRT alone (64.1% vs. 43.4%, P = 0.03). The benefit of treating with WBRT in combination was mainly achieved in the patients with extracranial lesions controlled or with more than one intracranial lesion. Multivariate analysis showed that KPS score and status of extracranial lesions were independent prognostic factors for OS. CONCLUSIONS: SRT is an effective and safe modality for BM. SRT combined with WBRT may prolong the survival time of the patients with extracranial lesions controlled or multiple intracranial lesions. Independent prognostic factors for OS are KPS score and status of extracranial lesions.

Quantum speed limit based on the bound of Bures angle.

In this paper, we investigate the unified bound of quantum speed limit time in open systems based on the modified Bures angle. This bound is applied to the damped Jaynes-Cummings model and the dephasing model, and the analytical quantum speed limit time is obtained for both models. As an example, the maximum coherent qubit state with white noise is chosen as the initial states for the damped Jaynes-Cummings model. It is found that the quantum speed limit time in both the non-Markovian and the Markovian regimes can be decreased by the white noise compared with the pure state. In addition, for the dephasing model, we find that the quantum speed limit time is not only related to the coherence of initial state and non-Markovianity, but also dependent on the population of initial excited state.

Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial.

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods: Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results: A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions: Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

Upfront Cranial Radiotherapy vs. EGFR Tyrosine Kinase Inhibitors Alone for the Treatment of Brain Metastases From Non-small-cell Lung Cancer: A Meta-Analysis of 1465 Patients.

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is revolutionizing the management of brain metastases (BMs). This study was to explore the value of upfront cranial radiotherapy (RT) in EGFR-mutated non-small cell lung cancer (NSCLC) with BMs compared with EGFR-TKIs alone. Methods: We searched all topic-related comparative articles in public databases (MEDLINE, EMBASE, Cochrane Library, and Web of Science) and conference proceedings. Outcomes of interest were intracranial objective response rate (ORR), overall survival (OS), and intracranial progression-free survival (PFS). Statistical analyses were calculated using Review Manager 5.3 software. Results: Thirteen comparative studies that included a total of 1,456 patients were eligible. Upfront brain RT had significantly higher OS (HR = 0.78, 95% CI = 0.65-0.93, P = 0.005) than EGFR-TKI alone. Upfront RT plus TKI had superior OS (HR = 0.71, 95% CI = 0.58-0.86, P = 0.0005) and intracranial PFS (HR = 0.69, 95% CI = 0.49-0.99, P = 0.04). The pooled data favored upfront whole brain RT (WBRT) plus TKI in terms of intracranial PFS (HR = 0.64, 95% CI = 0.48-0.85, P = 0.002) and OS (HR = 0.75, 95% CI = 0.57-1, P = 0.05). Upfront stereotactic radiosurgery (SRS) was associated with better OS (HR = 0.37, 95% CI = 0.26-0.54, P < 0.00001). Similar results were observed when analysis was restricted to the use of erlotinib or geftinib. Conclusions: The upfront use of brain RT seemed critical, especially for SRS. Upfront administration of upfront WBRT plus EGFR-TKI had better survival outcomes and seemed superior to EGFR-TKI alone.

Outcome of fractionated stereotactic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma.

PURPOSE: Local recurrence remains one of the major causes of failure in nasopharyngeal carcinoma (NPC). Stereotactic radiosurgery and fractionated stereotactic radiation therapy (FSRT) have recently evolved as a salvage option of NPC. This study was conducted to review the treatment outcome after FSRT for NPC. METHODS AND MATERIALS: Between September 1999 and December 2005, 90 patients with persistent (Group 1: n = 34, relapse within 6 months of RT) or recurrent (Group 2: n = 56, relapse beyond 6 months) NPC received FSRT using multiple noncoplanar arcs of 8-MV photon to the target. Median FSRT dose was 18 Gy in three fractions (Group 1) or 48 Gy in six fractions (Group 2). Median follow-up was 20.3 months. RESULTS: Complete response rate after FSRT was 66% for Group 1 and 63% for Group 2. One-, 2-, and 3-year disease-specific survival (DSS) and progression-free survival (PFS) rates for all patients were 82.6%, 74.8%, 57.5%, and 72.9%, 60.4%, 54.5%, respectively. Three-year local failure-free survival, DSS, and PFS rates were 89.4%, 80.7%, and 72.3% for Group 1, and 75.1%, 45.9%, and 42.9% for Group 2, respectively. Multivariate analysis showed that recurrent disease and large tumor volume were independent factors that predicted poorer DSS and PFS. Seventeen patients developed late complications, including 2 with fatal hemorrhage. CONCLUSIONS: Our results indicate that FSRT is effective for patients with persistent and recurrent NPC. Compared with reported results of radiosurgery, FSRT provides satisfactory tumor control and survival with a lower risk of complications and it may be a better treatment for local failures of NPC.

[Multi-center phase II clinical trial of humanized anti-epidermal factor receptor monoclonal antibody h-R3 combined with radiotherapy for locoregionally advanced nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the efficacy and safty of the humanized anti-epidermal factor receptor monoclonal antibody h-R3 in combination with radiotherapy for locoregionally advanced nasopharyngeal carcinoma. METHODS: Totally, 137 patients from 7 medical center around China were randomly divided into combined therapy group or control group. There was no difference in Karnofsky performance score between two groups. All patients in both groups received radical conventionally fractionated radiotherapy to the total dose of D(T) 70-76 Gy. For the combined therapy group, h-R3 was added at a dose of 100 mg i.v. weekly for 8 weeks started at the beginning of radiotherapy. RESULTS: Of the 137 eligilbe patients, 70 were in the combined therapy group treated by h-R3 plus radiotherapy and 67 in the control group by radiotherapy alone. The intent-to-treat (ITT) population consisted of 130 patients, while the per-protocol (PP) population was composed of 126 patients. The efficacy was assessed respectively at three point of time: the end of treatment, the 5th- and 17th-week after treatment. The complete response (CR) of the combined therapy group was significantly higher than that of the control group in both ITT and PP (ITT: 65.63%, 87.50%, 90.63% versus 27.27%, 42.42%, 51.52%; PP: 67.21%, 90.16%, 93.44% versus 27.69%, 43.08%, 52.31%; P < 0.05, respectively). The most common h-R3-related adverse reactions were fever (4.3%), hypotension (2.9%), nausea (1.4%), dizziness (2.9%) and rash (1.4%), which could be reversible if treated properly. Radiotherapy combined with 100 mg h-R3 i. v. weekly was tolerable and did not aggravate the side effects of radiation. The quality of life in the combined therapy group was comparable to that in the control group. CONCLUSION: This phase 1 multicenter clinical trial shows that h-R3 in combination with radiotherapy is effective and well-tolerated for the treatment of locoregionally advanced nasopharyngeal carcinoma.

Low serum level of miR-485-3p predicts poor survival in patients with glioblastoma.

MicroRNAs (miRNAs) are short noncoding RNAs that play critical roles in human malignancies and can be used as biomarkers for cancer. Until now, a number of biomarkers for prognosis of glioblastoma (GBM) have been reported in tumor tissues but only a few biomarkers in circulating fluid. Using a custom microarray, we previously identified 19 differentially expressed miRNAs in serum of patients with GBM. In this study, we investigated whether 3 of the 19 miRNAs in serum could be used as prognostic biomarkers for patients with GBM. We first validated the serum levels of 3 candidate miRNAs in an independent cohort of 24 GBM patients and 12 healthy volunteers by real-time quantitative reverse transcription PCR (qRT-PCR), and then evaluated the prognostic value of these miRNAs in a total of 36 GBM patients. The results show that the serum levels of the 3 miRNAs (miR-451a, miR-485-3p and miR-4298) determined by qRT-PCR are significantly different between 24 GBM patients and 12 healthy volunteers (all P <0.05) and are in concordance with the results of microarray analysis. High serum level of miR-451a is correlated with positive tumor O(6)-methylguanine-DNA methyltransferase (MGMT) expression (P = 0.040). Survival analysis showed that low serum miR-485-3p level is associated with poor progression-free survival (PFS) (P < 0.004) and overall survival (OS) (P < 0.023). Furthermore, univariate and multivariate Cox analyses demonstrated that that serum miR-485-3p expression is a significant independent prognostic factor for PFS and OS in GBM patients. In conclusion, serum miR-485-3p level is reduced and might be a potential prognostic biomarker in GBM patients.