Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.

Passive magnetic-free broadband optical isolator based on unidirectional self-induced transparency.

Achieving a broadband nonreciprocal device without gain and any external bias is very challenging and highly desirable for modern photonic technologies and quantum networks. Here we theoretically propose a passive and magnetic-free all-optical isolator for a femtosecond laser pulse by exploiting a new mechanism of unidirectional self-induced transparency, obtained with a nonlinear medium followed by a normal absorbing medium at one side. The transmission contrast between the forward and backward directions can reach 14.3 dB for a 2π - 5 fs laser pulse. The 20 dB bandwidth is about 56 nm, already comparable with a magneto-optical isolator. This work provides a new mechanism which may benefit non-magnetic isolation of ultrashort laser pulses.

Quantum ghost imaging of a vector field.

Quantum ghost image technique utilizing position or momentum correlations between entangled photons can realize nonlocal reconstruction of the image of an object. In this work, based on polarization entanglement, we experimentally demonstrate quantum ghost imaging of vector images by using a geometric phase object. We also provide a corresponding theoretical analysis. Additionally, we offer a geometrical optics path explanation of ghost imaging for vector fields. The proposed strategy offers new insights into the fundamental development of ghost imaging and also holds great promise for developing complex structured ghost imaging techniques. Our work expanding the principle of ghost imaging to spatially varying vector beams will lead to interesting developments of this field.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

FOXA2 suppresses gallbladder carcinoma cell migration, invasion, and epithelial-mesenchymal transition by targeting SERPINB5.

BACKGROUND: Gallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial-mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC. METHODS: FOXA2 expression in GBC tissues was first detected using immunohistochemistry (IHC), followed by correlation analysis with clinicopathological characteristics and survival prognosis. Subsequently, the effects of FOXA2 on GBC cell migration and invasion, as well as EMT induction, were evaluated by scratch, Transwell, RT-PCR, and Western blot assays, together with animal experimentation. Ultimately, mRNA sequencing was carried out to identify the key downstream target genes of FOXA2 in controlling the EMT process in GBC cells, and dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine its regulatory mechanism. RESULTS: FOXA2 was underexpressed in GBC tissues and inversely correlated with tumor node metastasis stage, lymph node metastasis, and poor patient prognosis. FOXA2 exerts suppressive effects on EMT and metastasis of GBC in vivo and in vitro. FOXA2 can impede GBC cell migratory and invasive functions and EMT by positively mediating serine protein kinase inhibitor B5 (SERPINB5) expression. CONCLUSION: FOXA2 directly binds to the SERPINB5 promoter region to stimulate its transcription, thereby modulating the migration and invasion behaviors of GBC cells as well as the EMT process, which might be an effective therapeutic target against GBC.

Role of chemotherapy in patients with nasopharynx carcinoma treated with radiotherapy (MAC-NPC): an updated individual patient data network meta-analysis.

BACKGROUND: The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis. METHODS: For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524. FINDINGS: The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2-13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59-0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69-0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75-1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%). INTERPRETATION: The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma. FUNDING: Institut National du Cancer and Ligue Nationale Contre le Cancer.

Cerebellar Continuous Theta Burst Stimulation Facilitates Auditory-Vocal Integration in Spinocerebellar Ataxia.

Clinical studies have shown the efficacy of transcranial magnetic stimulation in treating movement disorders in patients with spinocerebellar ataxia (SCA). However, whether similar effects occur for their speech motor disorders remains largely unknown. The present event-related potential study investigated whether and how abnormalities in auditory-vocal integration associated with SCA can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the right cerebellum. After receiving active or sham cerebellar c-TBS, 19 patients with SCA were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted by ±200 cents. Behaviorally, active cerebellar c-TBS led to smaller magnitudes of vocal compensations for pitch perturbations than sham stimulation. Parallel modulatory effects were also observed at the cortical level, as reflected by increased P1 and P2 responses but decreased N1 responses elicited by active cerebellar c-TBS. Moreover, smaller magnitudes of vocal compensations were predicted by larger amplitudes of cortical P1 and P2 responses. These findings provide the first neurobehavioral evidence that c-TBS over the right cerebellum produces modulatory effects on abnormal auditory-motor integration for vocal pitch regulation in patients with SCA, offering a starting point for the treatment of speech motor disorders associated with SCA with cerebellar c-TBS.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Photonic bandgap engineering in hybrid one-dimensional photonic crystals containing all-dielectric elliptical metamaterials.

Metamaterials with negative permittivities or/and permeabilities greatly enrich photonic bandgap (PBG) engineering in one-dimensional (1-D) photonic crystals (PhCs). Nevertheless, their inevitable optical losses strongly destroy the crucial prohibition characteristic of PBGs, which makes such engineered PBGs not utilizable in some relevant physical processes and optical/optoelectronic devices. Herein, we bridge a link between 1-D PhCs and all-dielectric loss-free metamaterials and propose a hybrid 1-D PhC containing all-dielectric elliptical metamaterials to engineer angle-dependence of PBGs. Associating the Bragg scattering theory with the iso-frequency curve analysis, an analytical model is established to precisely describe the angle-dependence of PBG. Based on the analytical model, two types of special PBGs, i.e., angle-insensitive and angle-sensitive PBGs, are designed. By further introducing defects into the designed 1-D PhCs, angle-dependence of defect modes can also be flexibly controlled. Our protocol opens a viable route to precisely engineering PBGs and promotes the development of PBG-based physics and applications.

Wide-angle polarization selectivity based on anomalous defect mode in photonic crystal containing hyperbolic metamaterials.

Conventional defect modes in all-dielectric 1D photonic crystals (PCs) are polarization-insensitive. This poses a great challenge in achieving high-performance polarization selectivity. In this Letter, we introduce a defect layer into a 1D PC containing hyperbolic metamaterials to achieve an anomalous defect mode with polarization-sensitive characteristics. As the incident angle increases, such a defect mode remains almost unshifted under transverse magnetic polarization, while strongly shifting toward shorter wavelengths under transverse electric polarization. The polarization-sensitive characteristics of the defect mode can be well explained by the Fabry-Perot resonance condition. Assisted by the polarization-sensitive defect mode, wide-angle polarization selectivity with an operating angle width up to 54.8° can be realized. Our work provides a route to designing wide-angle linear polarizers using simple 1D structures, which would be useful in liquid crystal display and Q-switched lasers.

Quantum Squeezing Induced Optical Nonreciprocity.

We propose an all-optical approach to achieve optical nonreciprocity on a chip by quantum squeezing one of two coupled resonator modes. By parametric pumping a χ^{(2)}-nonlinear resonator unidirectionally with a classical coherent field, we squeeze the resonator mode in a selective direction due to the phase-matching condition, and induce a chiral photon interaction between two resonators. Based on this chiral interresonator coupling, we achieve an all-optical diode and a three-port quasicirculator. By applying a second squeezed-vacuum field to the squeezed resonator mode, our nonreciprocal device also works for single-photon pulses. We obtain an isolation ratio of >40 dB for the diode and fidelity of >98% for the quasicirculator, and insertion loss of <1 dB for both. We also show that nonreciprocal transmission of strong light can be switched on and off by a relative weak pump light. This achievement implies a nonreciprocal optical transistor. Our protocol opens up a new route to achieve integrable all-optical nonreciprocal devices permitting chip-compatible optical isolation and nonreciporcal quantum information processing.

Nonreciprocal Single-Photon Band Structure.

We study a single-photon band structure in a one-dimensional coupled-resonator optical waveguide that chirally couples to an array of two-level quantum emitters (QEs). The chiral interaction between the resonator mode and the QE can break the time-reversal symmetry without the magneto-optical effect and an external or synthetic magnetic field. As a result, nonreciprocal single-photon edge states, band gaps, and flat bands appear. By using such a chiral QE coupled-resonator optical waveguide system, including a finite number of unit cells and working in the nonreciprocal band gap, we achieve frequency-multiplexed single-photon circulators with high fidelity and low insertion loss. The chiral QE-light interaction can also protect one-way propagation of single photons against backscattering. Our work opens a new door for studying unconventional photonic band structures without electronic counterparts in condensed matter and exploring its applications in the quantum regime.

Opioid-sparing effects of ultrasound-guided erector spinae plane block for adult patients undergoing surgery: A systematic review and meta-analysis.

BACKGROUND: Erector spinae plane block (ESPB) is a new method of administering analgesics to patients perioperatively. The aim of this meta-analysis was to evaluate the opioid-sparing effects of erector spinae plane block in patients during the perioperative period compared to conventional analgesia and identify its role in the development of opioid-free anesthesia. METHODS: Relevant study articles were retrieved from PubMed, the Web of Science, Medline via Ovid, Embase via Ovid, and the Cochrane Central Register of Controlled Trials (CENTRAL) on June 11, 2020. We included randomized controlled trials (RCTs) comparing the use of ESPB with control (no/sham block). The primary outcome was opioid consumption at 24 h after surgery and intraoperative opioid consumption. A random-effects model was used to calculate the standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) if there was significant heterogeneity in the data; otherwise, the fixed-effect model was used. RESULTS: A total of 25 randomized controlled trials involving 1461 patients were included. The use of ultrasound-guided ESPB was associated with reduced opioid consumption at 24 h after surgery [SMD: -2.14, 95% CI: -2.61 to -1.67, p < 0.001] and during the intraoperative period [SMD: -2.30, 95% CI: -3.21 to -1.40, p < 0.001]. In addition, it took a longer time to administer the first rescue analgesia in the ESPB group [SMD: 3.60, 95% CI: 2.23-4.97, p < 0.001] and the group was associated with lower incidences of postoperative nausea or vomiting (PONV) [OR: 0.50, 95% CI: 0.34-0.72, p < 0.001]. CONCLUSIONS: Ultrasound-guided ESPB could provide an opioid-sparing effect and effective analgesia in adults undergoing surgeries with general anesthesia, and then promote opioid-free anesthesia development.

Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: The role of surgery compared with reirradiation in the primary treatment of patients with resectable, locally recurrent nasopharyngeal carcinoma (NPC) who have previously received radiotherapy is a matter of debate. In this trial, we compared the efficacy and safety outcomes of salvage endoscopic surgery versus intensity-modulated radiotherapy (IMRT) in patients with resectable locally recurrent NPC. METHODS: This multicentre, open-label, randomised, controlled, phase 3 trial was done in three hospitals in southern China. We included patients aged 18-70 years with a Karnofsky Performance Status score of at least 70 who were histopathologically diagnosed with undifferentiated or differentiated, non-keratinising, locally recurrent NPC with tumours confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Eligible patients were randomly assigned (1:1) to receive either endoscopic nasopharyngectomy (ENPG group) or IMRT (IMRT group). Randomisation was done manually using a computer-generated random number code and patients were stratified by treatment centre. Treatment group assignment was not masked. The primary endpoint was overall survival, compared between the groups at 3 years. Efficacy analyses were done by intention to treat. Safety analysis was done in patients who received treatment according to the treatment they actually received. This trial was prospectively registered at the Chinese Clinical Trial Registry, ChiCTR-TRC-11001573, and is currently in follow-up. FINDINGS: Between Sept 30, 2011, and Jan 16, 2017, 200 eligible patients were randomly assigned to receive either ENPG (n=100) or IMRT (n=100). At a median follow-up of 56·0 months (IQR 42·0-69·0), 74 patients had died (29 [29%] of 100 patients in the ENPG group and 45 [45%] of 100 patients in the IMRT group). The 3-year overall survival was 85·8% (95% CI 78·9-92·7) in the ENPG group and 68·0% (58·6-77·4) in the IMRT group (hazard ratio 0·47, 95% CI 0·29-0·76; p=0·0015). The most common grade 3 or worse radiation-related late adverse event was pharyngeal mucositis (in five [5%] of 99 patients who underwent ENPG and 26 [26%] of 101 patients who underwent IMRT). Five [5%] of the 99 patients who underwent ENPG and 20 [20%] of the 101 patients who underwent IMRT died due to late toxic effects specific to radiotherapy; attribution to previous radiotherapy or trial radiotherapy is unclear due to the long-term nature of radiation-related toxicity. INTERPRETATION: Endoscopic surgery significantly improved overall survival compared with IMRT in patients with resectable locally recurrent NPC. These results suggest that ENPG could be considered as the standard treatment option for this patient population, although long-term follow-up is needed to further determine the efficacy and toxicity of this strategy. FUNDING: Sun Yat-sen University Clinical Research 5010 Program.

Configurable phonon polaritons in twisted α-MoO3.

Moiré engineering is being intensively investigated as a method to tune the electronic, magnetic and optical properties of twisted van der Waals materials. Advances in moiré engineering stem from the formation of peculiar moiré superlattices at small, specific twist angles. Here we report configurable nanoscale light-matter waves-phonon polaritons-by twisting stacked α-phase molybdenum trioxide (α-MoO3) slabs over a broad range of twist angles from 0° to 90°. Our combined experimental and theoretical results reveal a variety of polariton wavefront geometries and topological transitions as a function of the twist angle. In contrast to the origin of the modified electronic band structure in moiré superlattices, the polariton twisting configuration is attributed to the electromagnetic interaction of highly anisotropic hyperbolic polaritons in stacked α-MoO3 slabs. These results indicate twisted α-MoO3 to be a promising platform for nanophotonic devices with tunable functionalities.

Author Correction: Configurable phonon polaritons in twisted α-MoO3.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The role of the bacterial microbiome in the treatment of cancer.

The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.

Effect of Yb3+ concentration on upconversion luminescence and optical thermometry sensitivity of La2MoO6: Yb3+, Er3+ phosphors.

La2MoO6:Yb3+,Er3+ upconversion (UC) micro-crystals with a tetragonal structure were fabricated through a modified sol-gel method. The samples are found to be spherical in shape with a diameter of about 300 nm. Upon excitation of 980 nm light, the UC emission spectra of the phosphors exhibit green and red bands corresponding to the characteristic transitions of Er3+ ions. As Yb3+ concentration rises, the green emission intensity increases and reaches the maximum at 2.0% Yb3+ content, while the ratio of green/red emission intensities (IG/IR) declines monotonically. Temperature sensing capability was studied employing the fluorescent intensity ratio technique from the thermally coupled levels 2H11/2 and 4S3/2 of Er3+ in temperature range of 293∼533 K. It is interesting to find that Yb3+ concentration has influence on the absolute sensitivity SA, while the relative sensitivity SR is almost independent of Yb3+ content. Furthermore, excellent thermal stability and high temperature sensitivity is also demonstrated in the 2.0% Yb3+-doped sample with the obtained maximum SA and SR as high as 0.008K-1 and 1.093%K-1, respectively. The experimental results indicate that Yb3+/Er3+ co-doped La2MoO6 phosphors can be excellent candidates for temperature sensing applications.

Clinical outcomes of carbon-ion radiotherapy for patients with locoregionally recurrent nasopharyngeal carcinoma.

BACKGROUND: Reirradiation for locoregionally recurrent nasopharyngeal carcinoma (LR-NPC) after high-dose radiotherapy (RT) is challenging and usually is associated with poor survival and severe toxicities. Because of its physical and biological advantages over photon-beam RT, carbon-ion RT (CIRT) could be a potential treatment option for patients with LR-NPC. METHODS: Patients with LR-NPC who underwent salvage therapy using CIRT at the Shanghai Proton and Heavy Ion Center between May 2015 and June 2019 were analyzed. CIRT doses were 50 to 69 gray equivalent (GyE) (2.0-3.0 GyE per fraction). Overall survival (OS), local control, regional control, distant control, and acute and late toxicities were analyzed. Univariable and multivariable analyses of OS and local control were performed using the Cox regression model. RESULTS: Among the 206 patients included, 139 patients (67.5%) had recurrent American Joint Committee on Cancer stage III or stage IV disease. With a median follow-up of 22.8 months, the 2-year OS, local control, regional control, and distant control rates were 83.7%, 58.0%, 87.3%, and 94.7%, respectively. Multivariable analysis revealed that older age (P = .017) was predictive of worse OS, whereas a larger tumor volume (P = .049) and a lower biological equivalent dose (P = .029) were associated with inferior local control. No patient developed an acute toxicity of ≥grade 3 during CIRT. Severe (≥grade 3) late toxicities included temporal lobe necrosis (0.97%), cranial neuropathy (0.49%), hearing loss (1.46%), xerostomia (0.49%), and mucosal necrosis (16.02%) (toxicities were graded using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer criteria). CONCLUSIONS: Salvage treatment using CIRT is efficacious for patients with LR-NPC and its toxicities are acceptable. CIRT may improve the survival and toxicity profiles substantially for patients with LR-NPC compared with the reported results after photon-based intensity-modulated RT.

Genome-wide association study identifies genetic susceptibility loci and pathways of radiation-induced acute oral mucositis.

BACKGROUND: Radiation-induced oral mucositis (OM) is one of the most common acute complications for head and neck cancer. Severe OM is associated with radiation treatment breaks, which harms successful tumor management. Radiogenomics studies have indicated that genetic variants are associated with adverse effects of radiotherapy. METHODS: A large-scale genome-wide scan was performed in 1467 nasopharyngeal carcinoma patients, including 753 treated with 2D-CRT from Genetic Architecture of the Radiotherapy Toxicity and Prognosis (GARTP) cohort and 714 treated with IMRT (192 from the GARTP and 522 newly recruited). Subgroup analysis by radiotherapy technique was further performed in the top associations. We also performed physical and regulatory mapping of the risk loci and gene set enrichment analysis of the candidate target genes. RESULTS: We identified 50 associated genomic loci and 64 genes via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping and gene-based analysis, and 36 of these loci were replicated in subgroup analysis. Interestingly, one of the top loci located in TNKS, a gene relevant to radiation toxicity, was associated with increased OM risk with OR = 3.72 of the lead SNP rs117157809 (95% CI 2.10-6.57; P = 6.33 × 10-6). Gene set analyses showed that the 64 candidate target genes were enriched in the biological processes of regulating telomere capping and maintenance and telomerase activity (Top P = 7.73 × 10-7). CONCLUSIONS: These results enhance the biological understanding of radiotherapy toxicity. The association signals enriched in telomere function regulation implicate the potential underlying mechanism and warrant further functional investigation and potential individual radiotherapy applications.