Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.

Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.

Turning whispering-gallery-mode responses through Fano interferences in coupled all-dielectric block-disk cavities.

Here, we theoretically demonstrate a strategy for efficiently turning whispering-gallery-mode (WGM) responses of a subwavelength dielectric disk through their near-field couplings with common low-order electromagnetic resonances of a dielectric block. Both simulations and an analytical coupled oscillator model show that the couplings are Fano interferences between dark high-quality WGMs and bright modes of the block. The responses of a WGM in the coupled system are highly dependent on the strengths and the relative phases of the block modes, the coupling strength, and the decay rate of the WGM. The WGM responses of coupled systems can exceed that of the individual disk. In addition, such a configuration will also facilitate the excitation of WGMs by a normal incident plane wave in experiments. These results could enable new applications for enhancing light-matter interactions.

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).

Fear of recurrence in elderly patients with coronary heart disease: the current situation and influencing factors according to a questionnaire analysis.

OBJECTIVE: Fear of recurrence is a common psychosocial sequela among patients with heart disease. Analyses of coronary heart disease, particularly in elderly patients, are relatively rare. This study aimed to investigate the current situation in this context, as well as the influencing fear factors concerning recurrence in elderly patients with coronary heart disease. METHODS: A total of 200 elderly outpatients with coronary heart disease were recruited to participate in this survey from a tertiary hospital in Baoding (China). The questionnaires included items from the Disease Progression Simplified Scale, the Simplified Coping Style Questionnaire, and the Social Support Rating Scale (SSRS). Univariate and multivariate regression analyses were adopted to investigate the influencing factors on the fear of recurrence. RESULTS: The fear of recurrence score in elderly patients with coronary heart disease was (38.46 ± 8.13), among which 119 cases (59.5%) scored higher than 34 points. The SSRS total average score was (34.89 ± 9.83) points. Positive coping style and social support were negatively correlated with the total score of recurrence fear (r = - 0.621, - 0.413, both P < 0.001). There was a positive correlation between negative coping style and the total score of recurrence fear (r = 0.232, P < 0.001). Multiple linear regression analysis showed that the course of the disease, the number of disease recurrence cases, active coping, and social support were relevant factors in fear of recurrence (all P < 0.05). CONCLUSION: The detection rate of fear of recurrence in elderly patients with coronary heart disease was relatively high but could be reduced by active interventions and enhancing social support.

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.

Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses.

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.

Strong couplings between magnetic quantum emitters and subwavelength all-dielectric resonators with whispering gallery modes.

Here we theoretically investigate the coherent interactions between the quantum emitters with magnetic dipole transitions and subwavelength all-dielectric resonators of whispering gallery modes (WGMs). We extend a semi-analytical method which can efficiently calculate the far-field spectrum of a general hybrid system. Then, a subwavelength sphere with refractive index around n = 3.5 is chosen as the dielectric resonator. Due to the high magnetic field enhancements of the WGMs of the sphere, strong couplings between magnetic quantum emitters and subwavelength WGMs can occur, where a clear Rabi splitting appears on the extinction spectrum of the hybrid system. The match between the relaxation times of the WGMs and emitters are important to efficiently achieve a strong enough coupling. The other parameters including the order of a WGM, the radius, the refractive index, the transition dipole moment and excitation intensity are also important factors that can affect the couplings. Our results pave the way for strong interactions between light and magnetic emitters mediated by subwavelength all-dielectric resonators.

Proposed modifications and incorporation of plasma Epstein-Barr virus DNA improve the TNM staging system for Epstein-Barr virus-related nasopharyngeal carcinoma.

BACKGROUND: The prognosis of patients who have Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without EBV-related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV-related NPC by incorporating the measurement of plasma EBV DNA. METHODS: In total, 979 patients with NPC who received intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT. RESULTS: The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression-free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2-T3N0 or T1-T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2-T3N0 or T1-T3N1, EBV DNA >2000 copies/mL; T1-T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1-T3N2, EBV DNA >2000 copies/mL; T4N0-N2), and stage RIVA (any T and N3). In the validation cohort, the 5-year progression-free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance. CONCLUSIONS: The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV-related NPC.

Integrated transcriptomic analysis reveals hub genes involved in diagnosis and prognosis of pancreatic cancer.

BACKGROUND: The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. METHODS: Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. RESULTS: Based on integrated transcriptomic analysis, we identified a 19 gene module (SYCN, PNLIPRP1, CAP2, GNMT, MAT1A, ABAT, GPT2, ADHFE1, PHGDH, PSAT1, ERP27, PDIA2, MT1H, COMP, COL5A2, FN1, COL1A2, FAP and POSTN) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log2(MAT1A)-0.1526*log2(MT1H) + 0.4645*log2(FN1) -0.2244*log2(FAP), log2(gene count). Besides, a four-hub gene module was also identified as prognostic model = - 1.400*log2(CEL) + 1.321*log2(CPA1) + 0.454*log2(POSTN) + 1.011*log2(PM20D1), log2(gene count). CONCLUSION: Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.

10-Year Results of Therapeutic Ratio by Intensity-Modulated Radiotherapy Versus Two-Dimensional Radiotherapy in Patients with Nasopharyngeal Carcinoma.

BACKGROUND: The purpose of this study was to verify 10-year results of survival and late toxicities and assess the ultimate therapeutic ratio of intensity-modulated radiotherapy (IMRT) versus two-dimensional radiotherapy (2DRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We retrospectively reviewed the data from 1,276 patients with nonmetastatic NPC who received IMRT or 2DRT from January 2003 to December 2006. RESULTS: Of the 1,276 patients, 512 were treated with IMRT and 764 with 2DRT. Median follow-up was 115 months. At 10 years, the IMRT group demonstrated significantly better results than the 2DRT group in local failure-free survival (L-FFS; 90% vs. 84%; hazard ratio [HR], 0.57, 95% confidence interval [CI], 0.40-0.81; p = .001), failure-free survival (FFS; 69% vs. 58%; HR, 0.69, 95% CI, 0.57-0.83; p < .001), and overall survival (OS; 75% vs. 63%; HR, 0.62, 95% CI, 0.51-0.77; p < .001). Subgroup multivariate analyses showed that radiotherapeutic technique (IMRT vs. 2DRT) remained an independent prognostic factor for L-FFS in the T1 subgroup (HR, 0.30; 95% CI, 0.11-0.80; p = .02); for FFS in the stage II subgroup (HR, 0.42; 95% CI, 0.24-0.73; p = .002); and for OS in the stage I (HR, 0.20; 95% CI, 0.04-0.96; p = .04), stage II (HR, 0.39; 95% CI, 0.21-0.75; p = .004), and stage IVA-B (HR, 0.74, 95% CI, 0.56-0.98; p = .04) subgroups. The incidence of grade 3-4 temporal lobe necrosis, cranial neuropathy, eye damage, ear damage, neck soft tissue damage, trismus, and dry mouth was significantly lower in the IMRT group than in the 2DRT group. CONCLUSION: IMRT demonstrated an improved ultimate therapeutic ratio compared with 2DRT in patients with NPC after a 10-year follow-up, with significant improvement of L-FFS, FFS, and OS and decrease in most late toxicities. IMPLICATIONS FOR PRACTICE: The ultimate therapeutic ratio of intensity-modulated radiotherapy versus two-dimensional radiotherapy in patients with nasopharyngeal carcinoma is unclear. In this retrospective study of 1,276 patients with nonmetastatic nasopharyngeal carcinoma with a follow-up of 115 months, intensity-modulated radiotherapy demonstrated an improved ultimate therapeutic ratio compared with two-dimensional radiotherapy, with significant improvement of local failure-free survival, failure-free survival, and overall survival and decrease in most late toxicities and noncancer deaths. However, distant control remains insufficient with this treatment modality.

Role of differentially expressed genes and long non-coding RNAs in papillary thyroid carcinoma diagnosis, progression, and prognosis.

Currently, the combination of ultrasonography and fine-needle aspiration biopsy (FNAB) can not discriminate between benign and malignant tumor of thyroid in some cases. The main issue in assessing the patients with thyroid nodules is to distinguish thyroid cancer from benign nodules, and reduce diagnostic surgery. To identify potential molecular biomarkers for patients with indeterminate FNAB, we explored the differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) in TCGA database between 318 papillary thyroid carcinoma (PTC) tissues and 35 normal thyroid gland tissues by DESeq R. Furthermore, DEGs were verified by gene expression profile GSE33630. Ten top DEGs and DElncRNAs were identified as candidate biomarkers for diagnosis and Lasso (Least Absolute Shrinkage and Selection Operator) logistic regression analysis were performed to improve the diagnostic accuracy of them. Besides, partial molecular biomarkers of top DEGs and DElncRNAs were closely related to the tumor stage (T), lymph node metastasis (N), metastasis (M) and pathological stage of PTC, which could reflect behavior of tumor progression. According to multivariate Cox analysis, the combination of two DEGs (METTL7B and KCTD16) and two DElncRNAs (LINC02454 and LINC02471) could predict the outcome in a more exact way. In conclusion, top DEGs and DElncRNAs could raise diagnosis of PTC in indeterminate FNAB specimens, and some could function as molecule biomarkers for tumor progression and prognosis.

The 50 Most-cited Articles in Gastroenterology and Hepatology from Mainland China.

OBJECTIVE: To identify and analyze the 50 most-cited gastroenterology and hepatology articles originating from mainland China. METHODS: We utilized the 2015 edition of Journal Citation Reports and PubMed to determine the 50 most-cited gastroenterology and hepatology articles from 75 professional journals and four leading journals in clinical medicine, which are The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The British Medical Journal. Then we excluded the articles written outside mainland China and collected the basic information, including the title, authors, year of publication, source journal, city, institution, number of citations, and topic of the research. RESULTS: The number of citations for the top 50 papers ranged from 279 to 89 (mean, 129). These articles were published between 2005 and 2012, in which 2009 was the year with the largest number of highly cited papers(13). All articles were published in 15 journals. The journal Hepatology published the largest number of articles(21), followed by Journal of Gastroenterology and Hepatology(4), Journal of Hepatology(4) and World Journal of Gastroenterology(4). The top 50 articles originated mainly from Shanghai(20), Guangzhou(13) and Beijing(6). Sun Yat-sen University produced most highly cited papers(10). The number of basic research was far more than clinical research, of which the ratio was about 1.78(32:18). In all these articles, hepatocellular carcinoma was the most-discussed topic(19), followed by hepatitis B virus(8) and endoscopic(5). CONCLUSIONS: Although a large gap remains between mainland China and the global community, the gastroenterology and hepatology research from China is gradually recognized by the world.

Value of the prognostic nutritional index and weight loss in predicting metastasis and long-term mortality in nasopharyngeal carcinoma.

BACKGROUND: To evaluate the influence of the progonistic nutritional index (PNI) and weight loss on metastasis and long-term mortality in nasopharyngeal carcinoma (NPC). METHODS: We retrospectively reviewed 694 newly diagnosed patients with non-disseminated, biopsy-proven NPC. Survival analysis was used to evaluate the predictive value of PNI and weight loss. RESULTS: Multivariate analysis demonstrated that a low pre-therapy PNI (< 55.0) was an independent predictor of poor overall survival (OS) (P = 0.012), distant metastasis-free survival (DMFS) (P = 0.011) and progression-free survival (P = 0.012). High weight loss (HWL, weight loss during treatment ≥10 %) was an independent predictor of poor OS (P = 0.001) and DMFS (P = 0.014). Advanced stage disease, female gender, chemotherapy, high white blood cell count, high serum globulin concentration and pre-therapy body-mass index were predictors of HWL. CONCLUSION: Pre-therapy PNI and weight loss have significant predictive value for metastasis and mortality in patients with NPC.

Evaluation of a novel model incorporating serological indicators into the conventional TNM staging system for nasopharyngeal carcinoma.

BACKGROUND: Non-anatomical factors significantly affect treatment guidance and prognostic prediction in nasopharyngeal carcinoma (NPC) patients. Here, we developed a novel survival model by combining conventional TNM staging and serological indicators. METHODS: We retrospectively enrolled 10,914 eligible patients with nonmetastatic NPC over 2009-2017 and randomly divided them into training (n = 7672) and validation (n = 3242) cohorts. The new staging system was constructed based on T category, N category, and pretreatment serological markers by using recursive partitioning analysis (RPA). RESULTS: In multivariate Cox analysis, pretreatment cell-free Epstein-Barr virus (cfEBV) DNA levels of >2000 copies/mL [HROS (95 % CI) = 1.78 (1.57-2.02)], elevated lactate dehydrogenase (LDH) levels [HROS (95 % CI) = 1.64 (1.41-1.92)], and C-reactive protein-to-albumin ratio (CAR) of >0.04 [HROS (95 % CI) = 1.20 (1.07-1.34)] were associated with negative prognosis (all P < 0.05). Through RPA, we stratified patients into four risk groups: RPA I (n = 3209), RPA II (n = 2063), RPA III (n = 1263), and RPA IV (n = 1137), with 5-year overall survival (OS) rates of 93.2 %, 86.0 %, 80.6 %, and 71.9 % (all P < 0.001), respectively. Compared with the TNM staging system (eighth edition), RPA risk grouping demonstrated higher prognostic prediction efficacy in the training [area under the curve (AUC) = 0.661 vs. 0.631, P < 0.001] and validation (AUC = 0.687 vs. 0.654, P = 0.001) cohorts. Furthermore, our model could distinguish sensitive patients suitable for induction chemotherapy well. CONCLUSION: Our novel RPA staging model outperformed the current TNM staging system in prognostic prediction and clinical decision-making. We recommend incorporating cfEBV DNA, LDH, and CAR into the TNM staging system.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Dextran-based self-healing hydrogels formed by reversible diels-alder reaction under physiological conditions.

A dextran-based self-healing hydrogel is prepared by reversible Diels-Alder reaction under physiological conditions. Cytocompatible fulvene-modified dextran as main polymer chains and dichloromaleic-acid-modified poly(ethylene glycol) as cross-linkers are used. Both macro- and microscopic observation as well as the rheological recovery test confirm the self-healing property of the dextran-l-poly(ethylene glycol) hydrogels ("l" means "linked-by"). In addition, scanning electrochemical microscopy is used to qualitatively and quantitatively in situ track the self-healing process of the hydrogel for the first time. It is found that the longitudinal depth of scratch on hydrogel surface almost completely healed at 37 °C after 7 h. This work represents a facile approach for fabrication of polysaccharide self-healing hydrogel, which can be potentially used in several biomedical fields.

[Value of postoperative adjuvant chemotherapy in locally advanced rectal cancer patients with ypT1-4N0 after neo-adjuvant chemoradiotherapy].

OBJECTIVE: The purpose of this study was to investigate the value of postoperative chemotherapy for locally advanced rectal cancer patients who reached pathological ypT1-4N0 after neo-adjuvant chemoradiotherapy. METHODS: We performed a retrospective study of 104 patients treated with preoperative chemoradiotherapy followed by radical resection, who achieved pathological ypT1-4N0, between Mar 2003 and Dec 2010. There were 73 patients who received postoperative adjuvant chemotherapy, and the other 31 patients did not. The distribution of final pathologic stages for these patients was ypT1-2N0 in 39 cases and ypT3-4N0 in 65 cases. RESULTS: The median follow-up was 41 months. The 3-year overall survival rate (OS) and recurrence-free survival rate (RFS) for the whole group (ypT1-4N0) were 93.4% and 85.3%, respectively. The 3-year OS and RFS in the adjuvant chemotherapy group and non-adjuvant chemotherapy group were 95.5%, 88.6% and 88.6%, 77.2%, respectively. There were no significant differences in 3-year RFS (P = 0.108) and OS (P = 0.106) between the two groups. The 3-year local recurrence and distant metastasis rates in the adjuvant chemotherapy group were 4.1% (3/73) and 5.5% (4/73), while for the non-adjuvant chemotherapy group, the 3-year local recurrence rate and distant metastasis rate were 3.2% (1/31) and 16.1% (5/31), respectively. Significant difference was found in distant metastasis rates (P = 0.030) between the two groups, but not in local recurrence rates (P = 0.676).Further subgroup analysis indicated that for the ypT1-2N0 patients, there were no significant differences in 3-year OS (P = 0.296) and RFS (P = 0.939) between the adjuvant and non-adjuvant chemotherapy groups, while negative results displayed in 3-year local recurrence rates (P = 0.676) and distant metastasis rates (P = 0.414). However, for patients with ypT3-4N0, significant differences were showed in both the 3-year OS (P = 0.034) and RFS (P = 0.025), and further analysis revealed that the 3-year distant metastasis rate was significantly higher in the non-adjuvant chemotherapy group than in the adjuvant chemotherapy group (P = 0.010) , but with non-significant difference in the 3-year local recurrence (P = 0.548). CONCLUSIONS: Adjuvant chemotherapy may not improve survival for ypT1-2N0 patients. However, it may be clinically meaningful for ypT3-4N0 patients by decreasing distant metastasis rate. Further randomized controlled clinical trials are needed to confirm our results.

Upper-Neck Versus Whole-Neck Irradiation at the Contralateral Uninvolved Neck in Patients With Unilateral N3 Nasopharyngeal Carcinoma.

PURPOSE: Upper-neck irradiation (UNI) at the uninvolved neck has shown similar regional relapse-free survival as standard whole-neck irradiation (WNI) in patients with N0-1 nasopharyngeal carcinoma. However, whether UNI at the contralateral uninvolved neck is feasible in unilateral N3 disease, defined as >6 cm and/or below the caudal border of the cricoid cartilage, remains unclear. METHODS AND MATERIALS: Data for 291 patients with nasopharyngeal carcinoma with unilateral N3 disease who were treated with intensity modulated radiation therapy from 2009 to 2015 were retrospectively analyzed. Among them, 190 received bilateral WNI (WNI group); the remaining 101 received WNI at the involved neck and UNI at the contralateral uninvolved neck (UNI group). Survival rates were estimated using the Kaplan-Meier method, and differences between groups were compared using the log rank tests. RESULTS: The median follow-up was 79.4 months (interquartile range, 56.0-89.3). Twenty-five patients had regional lymph node relapses (UNI: 10.9%, 11/101 vs WNI: 7.4%, 14/190; P = .31). Of these, 23 patients relapsed within the previously involved neck regions, while only 2 patients had relapses in the contralateral uninvolved neck (1 each in the UNI and WNI groups). Five-year regional relapse-free survival rates were similar between groups (89.7% vs 92.7%, P = .29). Similar between-group findings were also observed for 5-year overall survival (76.1% vs 80.4%, P = .40), distant metastasis-free survival (74.9% vs 79.2%, P = .44), and local relapse-free survival (95.6% vs 94.7%, P = .64). Furthermore, oncologic outcomes in subgroup and multivariable analyses were similar between groups. CONCLUSIONS: Regional control and survival outcomes were comparable in UNI at the contralateral uninvolved neck and standard WNI in patients with nasopharyngeal carcinoma with unilateral N3 disease. Our findings provide evidence for future radiation therapy guidelines of nasopharyngeal carcinoma.