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A highly sensitive method based on MBs-cDNA@Apt-AuNCs519 was developed for deoxynivalenol (DON) detection in wheat. The MBs-cDNA@Apt-AuNCs519 was established using green emission gold nanoclusters (AuNCs519) with aggregation-induced emission properties as signal probes and combining amino-modified DON-aptamer (Apt), biotin-modified DNA strand (the partially complementary to Apt (cDNA)), and streptavidin-modified magnetic beads (MBs). The Apt-AuNCs519 were well connected with MBs-cDNA without DON but dissociated from MBs-cDNA@Apt-AuNCs519 with the addition of DON, leading to a noticeable reduction in the fluorescent intensity of the aptasensor. Moreover, this fluorescence aptasensor showed two linear relationships in the concentration range of 0.1-50â¯ng/mL and 50-5000â¯ng/mL with a limit of detection of 3.73â¯pg/mL with good stability, reproducibility and specificity. The results were consistent with high-performance liquid chromatography and enzyme-linked immunosorbent assay methods, further indicating the potential of this method for accurate trace detection of DON in wheat.
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An emerging fluorescent ratiometric aptasensor based on gold nanoclusters (AuNCs) with aggregation-induced emission (AIE) properties was prepared and studied for deoxynivalenol (DON) detection. The ratiometric aptasensor used red fluorescent AuNCs620 labelled with DON aptamer (Apt-AuNCs620) as an indicator and green fluorescent AuNCs519 modified by complementary DNA (cDNA) and magnetic beads (MBs) as internal reference, namely MBs-cDNA-AuNCs519. Under the optimal conditions, the aptasensor exhibited two good linear ranges of 0.1-50 and 50-5000 pg/mL for DON detection with coefficient of determination (R2) of 0.9937 and 0.9928, respectively, and the low detection limit (LOD) of 4.09 pg/mL was achieved. Furthermore, this aptasensor was feasible to detect DON in positive wheat samples, and the results were in line with those from HPLC and ELISA, thus providing a promising route to detect DON with high sensitivity in cereals, even for other mycotoxins by replacing the suitable aptamer and cDNA.
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Background: We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy. Patients and Methods: We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR). Results: A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1-28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3-14.0] vs 5.0 months [95% CI 2.8-7.2], P = 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, P = 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, P = 0.025). Conclusion: mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.
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OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.
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Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gemcitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/uso terapéutico , Capecitabina/administración & dosificación , Adulto , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Paclitaxel/efectos adversos , Albúminas/administración & dosificación , Albúminas/efectos adversos , Albúminas/uso terapéutico , Anciano , Supervivencia sin Progresión , China , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: This retrospective study aimed to determine the optimal metronomic chemotherapy duration (MTCD) as adjuvant therapy for patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: This study involved LANPC patients treated with metronomic chemotherapy (MTC) using a 5-FU prodrug (S1, capecitabine, or tegafur) from May 2013 to September 2020. The optimal MTCD threshold was established using X-tile Bioinformatics software. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were compared between short-term and long-term groups using propensity score matching (PSM). RESULTS: A total of 546 patients were analyzed. MTCD was an independent prognostic factor for OS, PFS, and DMFS (all P < 0.05). Patients were categorized into long-term (>3 months) and short-term (≤3 months) MTCD groups. After a median follow-up of 48 months, significant differences were observed in 4-year OS (97.0 % vs. 87.1 %; P < 0.01), PFS (84.6 % vs. 70.9 %; P < 0.01), DMFS (87.3 % vs. 78.8 %; P < 0.01), and LRRFS (95.3 % vs. 87.4 %; P < 0.01) between the long-term and short-term groups. In the PSM-matched cohort of 196 patients per group, the long-term group demonstrated superior 4-year OS and LRRFS (97.3 % vs. 87.1 %, P < 0.01; 95.2 % vs. 90.0 %, P < 0.05). No significant differences in acute toxicities were observed between the groups (P > 0.05). CONCLUSION: Extended MTC with a 5-FU prodrug (>3 months) may benefit NPC patients. Further prospective studies are needed to validate these findings.
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Administración Metronómica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Puntaje de Propensión , Humanos , Masculino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Femenino , Persona de Mediana Edad , Quimioterapia Adyuvante/métodos , Estudios Retrospectivos , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Adulto , Anciano , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Objective: To explore the prognostic outcomes associated with different types of septic cardiomyopathy and analyze the factors that exert an influence on these outcomes. Methods: The data collected within 24 hours of ICU admission included cardiac troponin I (cTnI), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP); SOFA (sequential organ failure assessment) scores, and the proportion of vasopressor use. Based on echocardiographic outcomes, septic cardiomyopathy was categorized into left ventricular (LV) systolic dysfunction, LV diastolic dysfunction, and right ventricular (RV) systolic dysfunction. Differences between the mortality and survival groups, as well as between each cardiomyopathy subgroup and the non-cardiomyopathy group were compared, to explore the influencing factors of cardiomyopathy. Results: A cohort of 184 patients were included in this study, with LV diastolic dysfunction having the highest incidence rate (43.5%). The mortality group had significantly higher SOFA scores, vasopressor use, and cTnI levels compared to the survival group; the survival group had better LV diastolic function than the mortality group (p < 0.05 for all). In contrast to the non-cardiomyopathy group, each subgroup within the cardiomyopathy category exhibited elevated levels of cTnI. The subgroup with left ventricular diastolic dysfunction demonstrated a higher prevalence of advanced age, hypertension, diabetes mellitus, coronary artery disease, and an increased mortality rate; the RV systolic dysfunction subgroup had higher SOFA scores and NT-proBNP levels, and a higher mortality rate (P < 0.05 for all); the LV systolic dysfunction subgroup had a similar mortality rate (P > 0.05). Conclusion: Patients with advanced age, hypertension, diabetes mellitus, or coronary artery disease are more prone to develop LV diastolic dysfunction type of cardiomyopathy; cardiomyopathy subgroups had higher levels of cTnI. The RV systolic dysfunction cardiomyopathy subgroup had higher SOFA scores and NT-proBNP levels. The occurrence of RV systolic dysfunction in patients with sepsis significantly increased the mortality rate.
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The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.
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Anticuerpos Monoclonales Humanizados , Quimioterapia de Inducción , Neoplasias Nasofaríngeas , Piridinas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Quimioterapia de Inducción/efectos adversos , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Quimioradioterapia/efectos adversosRESUMEN
BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.
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MicroARNs , Neoplasias Ováricas , Humanos , Femenino , Cisplatino/farmacología , Regulación hacia Arriba , ARN Circular/genética , Recurrencia Local de Neoplasia , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , MicroARNs/genética , Adenosina , Fosfatidilinositol 3-Quinasa Clase Ia/genéticaRESUMEN
To assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p < 0.05). The ITC regimen also conferred a significant improvement in OS when comparing to C alone (HR 0.336, 95%CI 0.123-0.915, p = 0.033). The IT and IC regimens achieved a nearly identical PFS (HR 0.955, 95%CI 0.515-1.77, p = 0.884), although the IT regimen was associated with a lower occurrence of SAEs in contrast to the IC regimen (p < 0.05). In addition, the IT regimen demonstrated superior PFS (HR 0.583, 95%CI 0.345-0.985, p = 0.044) and fewer SAEs when compared to C alone (p < 0.05). These findings collectively support the notion that the combination of ICIs, target and chemotherapy exhibits robust antitumor activity in previously treated R/M NPC patients, without a significant increase in adverse events.
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Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Irinotecán , Inmunoterapia , Neoplasias Nasofaríngeas/tratamiento farmacológicoRESUMEN
BACKGROUND: Several studies have indicated that magnetic resonance imaging radiomics can predict survival in patients with breast cancer, but the potential biological underpinning remains indistinct. Herein, we aim to develop an interpretable deep-learning-based network for classifying recurrence risk and revealing the potential biological mechanisms. METHODS: In this multicenter study, 1113 nonmetastatic invasive breast cancer patients were included, and were divided into the training cohort (n = 698), the validation cohort (n = 171), and the testing cohort (n = 244). The Radiomic DeepSurv Net (RDeepNet) model was constructed using the Cox proportional hazards deep neural network DeepSurv for predicting individual recurrence risk. RNA-sequencing was performed to explore the association between radiomics and tumor microenvironment. Correlation and variance analyses were conducted to examine changes of radiomics among patients with different therapeutic responses and after neoadjuvant chemotherapy. The association and quantitative relation of radiomics and epigenetic molecular characteristics were further analyzed to reveal the mechanisms of radiomics. RESULTS: The RDeepNet model showed a significant association with recurrence-free survival (RFS) (HR 0.03, 95% CI 0.02-0.06, P < 0.001) and achieved AUCs of 0.98, 0.94, and 0.92 for 1-, 2-, and 3-year RFS, respectively. In the validation and testing cohorts, the RDeepNet model could also clarify patients into high- and low-risk groups, and demonstrated AUCs of 0.91 and 0.94 for 3-year RFS, respectively. Radiomic features displayed differential expression between the two risk groups. Furthermore, the generalizability of RDeepNet model was confirmed across different molecular subtypes and patient populations with different therapy regimens (All P < 0.001). The study also identified variations in radiomic features among patients with diverse therapeutic responses and after neoadjuvant chemotherapy. Importantly, a significant correlation between radiomics and long non-coding RNAs (lncRNAs) was discovered. A key lncRNA was found to be noninvasively quantified by a deep learning-based radiomics prediction model with AUCs of 0.79 in the training cohort and 0.77 in the testing cohort. CONCLUSIONS: This study demonstrates that machine learning radiomics of MRI can effectively predict RFS after surgery in patients with breast cancer, and highlights the feasibility of non-invasive quantification of lncRNAs using radiomics, which indicates the potential of radiomics in guiding treatment decisions.
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Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , ARN Largo no Codificante/genética , Aprendizaje Automático , Imagen por Resonancia Magnética , Proteínas Tirosina Quinasas Receptoras , Estudios de Cohortes , Estudios Retrospectivos , Microambiente TumoralRESUMEN
We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR treatment in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients who progressed to previous anti-PD1 therapy. Enrolled patients were divided into a combination group and a chemotherapy only group. A total of 145 patients were enrolled. The median progress-free survival (mPFS) was 7.9 months and 4.4 months, respectively for the two groups. The combination group exhibited significantly longer PFS (HR=0.363, p < 0.001), and better disease control ratio (DCR, p = 0.022) compared with the chemotherapy group. Among the combination group, longer PFS was found in those patients who received different PD1 inhibitor from prior therapy, reached object response rate (ORR) from prior anti-PD1 therapy, and EBV DNA ≤ 1500 copy/ml before therapy, comparing to the corresponding other patients. R/M NPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR agents.
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Inmunoterapia , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico , Neoplasias Nasofaríngeas/tratamiento farmacológicoRESUMEN
Background: There are limited treatment options for patients with metastatic nasopharyngeal carcinoma (mNPC) after failure of platinum-based chemotherapy. In this trial, we assessed the efficacy and safety of sintilimab plus bevacizumab in patients with mNPC where platinum-based chemotherapy has been ineffective. Methods: This was a single-centre, open-label, single-arm, phase 2 trial in Guangzhou, China for patients with mNPC progressed after at least one line of systemic therapy. Eligible patients were between 18 and 75 years old, were histologically confirmed differentiated or undifferentiated non-keratinized NPC, were ineffective after platinum-based chemotherapy, and they had at least one measurable metastatic lesion assessed with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V.1.1) by investigators and unsuitable for local surgery or radiotherapy. Key exclusion criterion was previous treatment with anti-PD-1/PD-L1 antibodies plus anti-VEGF antibodies and high risk of hemorrhage or nasopharyngeal necrosis. Patients were enrolled and received sintilimab (200 mg) plus bevacizumab (7.5 mg/kg) intravenously every 3 weeks. Intention-to-treat population was included in primary endpoint analyses and safety analyses. The primary endpoint was objective response rate (ORR) assessed by investigators following the guidelines of RECIST V1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. This trial is registered with ClinicalTrials.gov (NCT04872582). Findings: Between July 29, 2021 and August 16, 2022, 33 patients were enrolled. Median age was 46 years (range, 18-64 years), and 63.6% of patients had previously received two or more lines of chemotherapy for metastatic disease. Median follow-up was 7.6 months (range, 4.1-17.5 months). ORR was 54.5% (95% CI, 36.4-71.9%) with 3 complete responses (9.1%) and 15 partial responses (45.5%). Median PFS was 6.8 months (95% CI, 5.2 months to not estimable). Median DOR was 7.2 months (95% CI, 4.4 months to not estimable). Median OS was not reached. The most common potential immune-related adverse event (AE) was Grade 1-2 hypothyroidism (42.4%). Treatment-related grade 3 or 4 AEs occurred in 7 patients (21.2%), including nasal necrosis (3/33), hypertension (1/33), pruritus (1/33), total bilirubin increased (1/33) and anaphylactic shock (1/33). No treatment-related deaths and severe epistaxis occurred. Interpretation: This phase 2 trial showed that sintilimab plus bevacizumab demonstrated promising antitumour activity and manageable toxicities in patients with mNPC after failure of platinum-based chemotherapy. Further trials are warranted, and the detailed mechanisms need to be elucidated. Funding: The Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, and the Science and Technology Planning Project of International Cooperation of Guangdong Province.
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PURPOSE: No specific irradiation guidelines have been proposed for parotid lymph node (PLN) metastasis in patients with nasopharyngeal carcinoma (NPC). This study aimed to explore the dose prescription and target delineation for PLN metastasis in patients with NPC. METHODS: With the NPC database from a big-data platform, 10,685 patients with primarily diagnosed, non-distant metastatic, histologically proven NPC and treated with intensity modulated radiotherapy (IMRT) at our center from 2008 to 2019 were reviewed and those with PLN metastasis were enrolled in this study. Dosimetry parameters were collected from the dose-volume histograms (DVH). The primary endpoint was overall survival (OS). Least absolute shrinkage and selection operator regression (LASSO) was operated for variable selection. Multivariate Cox regression analysis was applied to identify the independent prognostic factors. RESULTS: PLN metastases were identified in 275/10685 (2.5%) patients. Of 367 positive PLN, 199 were in superficial intra-parotid, followed by 70 in deep intra-parotid, 54 in subparotid and 44 in subcutaneous pre-auricular. Better survival outcome was observed in PLN-radical IMRT group, compared with PLN-sparing group. In 190 patients received PLN-radical IMRT, multivariate analysis revealed that D95% of level VIII > 55 Gy was an independent beneficial prognostic factor for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and parotid relapse-free survival (PRFS). CONCLUSION: Based on the distribution pattern of PLN metastasis in NPC and the result of dose-finding study, involving the ipsilateral level VIII into low-risk clinical target volume (CTV2) is recommended for NPC with PLN metastasis.
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Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Metástasis Linfática/radioterapia , Metástasis Linfática/patología , Carcinoma/radioterapia , Carcinoma/patología , Recurrencia Local de Neoplasia/patología , Ganglios Linfáticos/patología , Estudios Retrospectivos , Pronóstico , Estadificación de NeoplasiasRESUMEN
Binary ruthenium dioxide (RuO2) has gradually attracted much attention in condensed matter physics and material sciences due to its various intriguing physical properties, such as strain-induced superconductivity, anomalous Hall effect, collinear anti-ferromagnetism, etc. However, its complex emergent electronic states and the corresponding phase diagram over a wide temperature range remain unexplored, which is critically important to understanding the underlying physics and exploring its final physical properties and functionalities. Here, through optimizing the growth conditions by using versatile pulsed laser deposition, high-quality epitaxial RuO2thin films with clear lattice structure are obtained, upon which the electronic transport is investigated, and emergent electronic states and the relevant physical properties are unveiled. Firstly, at a high-temperature range, it is the Bloch-Grüneisen state, instead of the common Fermi liquid metallic state, that dominates the electrical transport behavior. Moreover, the recently reported anomalous Hall effect is also revealed, which confirms the presence of the Berry phase in the energy band structure. More excitingly, we find that above the superconductivity transition temperature, a new positive magnetic resistance quantum coherent state with an unusual dip as well as an angel-dependent critical magnetic field emerges, which can be attributed to the weak antilocalization effect. Lastly, the complex phase diagram with multiple intriguing emergent electronic states over a wide temperature range is mapped. The results greatly promote the fundamental physics understanding of the binary oxide RuO2and provide guidelines for its practical applications and functionalities.
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Objective: To analyze the epidemiological data of patients with septic cardiomyopathy and investigate the relationship between ultrasonic parameters and prognosis of patients with sepsis. Methods: In this study, we enrolled patients with sepsis who were treated at the Department of Critical Care Medicine in the Beijing Electric Power Hospital (No.1 Taipingqiao Xili, Fengtai District, Beijing) from January 2020 to June 2022. All patients received standardized treatment. Their general medical status and 28-day prognosis were recorded. Transthoracic echocardiography was performed within 24 hours after admission. We compared the ultrasound indexes between the mortality group and the survival group at the end of 28 days. We included parameters with significant difference in the logistic regression model to identify the independent risk factors for prognosis and evaluated their predictive value using receiver operating characteristic (ROC) curve. Results: We included 100 patients with sepsis in this study; the mortality rate was 33% and the prevalence rate of septic cardiomyopathy was 49%. The peak e' velocity and right ventricular systolic tricuspid annulus velocity (RV-Sm) of the survival group were significantly higher than those of the mortality group (P < 0.05). Results of logistic regression analysis showed that the peak e' velocity and RV-Sm were independent risk factors for prognosis. The area under curve of the peak e' velocity and the RV-Sm was 0.657 and 0.668, respectively (P < 0.05). Conclusion: The prevalence rate of septic cardiomyopathy in septic patients is high. In this study, we found that the peak e' velocity and right ventricular systolic tricuspid annulus velocity were important predictors of short-term prognosis.
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Background: Epstein-Barr virus (EBV) DNA seronegative (Sero-) and seropositive (Sero+) nasopharyngeal carcinoma (NPC) are distinctly different disease subtypes. Patients with higher baseline EBV DNA titers seem to benefit less from anti-PD1 immunotherapy, but underlying mechanisms remain unclear. Tumor microenvironment (TME) characteristics could be the important factor affecting the efficacy of immunotherapy. Here, we illuminated the distinct multicellular ecosystems of EBV DNA Sero- and Sero+ NPCs from cellular compositional and functional perspectives at single-cell resolution. Method: We performed single-cell RNA sequencing analyses of 28,423 cells from ten NPC samples and one non-tumor nasopharyngeal tissue. The markers, function, and dynamics of related cells were analyzed. Results: We found that tumor cells from EBV DNA Sero+ samples exhibit low-differentiation potential, stronger stemness signature, and upregulated signaling pathways associated with cancer hallmarks than that of EBV DNA Sero- samples. Transcriptional heterogeneity and dynamics in T cells were associated with EBV DNA seropositivity status, indicating different immunoinhibitory mechanisms employed by malignant cells depending on EBV DNA seropositivity status. The low expression of classical immune checkpoints, early-triggered cytotoxic T-lymphocyte response, global activation of IFN-mediated signatures, and enhanced cell-cell interplays cooperatively tend to form a specific immune context in EBV DNA Sero+ NPC. Conclusions: Collectively, we illuminated the distinct multicellular ecosystems of EBV DNA Sero- and Sero+ NPCs from single-cell perspective. Our study provides insights into the altered tumor microenvironment of NPC associated with EBV DNA seropositivity, which will help direct the development of rational immunotherapy strategies.
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Ecosistema , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , ADN , Neoplasias Nasofaríngeas/genética , Microambiente TumoralRESUMEN
Background: We aimed to establish a prognostic model to identify suitable candidates for chemotherapy combination PD-1 inhibitor in metastatic nasopharyngeal carcinoma (NPC) patients. Patients and methods: In this retrospective study, we included 524 patients (192 patients treated with chemotherapy combination PD-1 inhibitor and 332 received chemotherapy alone as first-line regimen) with metastatic NPC between January 2015 and March 2021. We developed a prognostic model to predict progression-free survival (PFS). A model-based trees approach was applied to estimate stratified treatment effects using prognostic scores and two well-matched risk groups (low-risk and high-risk) were created using propensity score matching. Results: A prognostic nomogram was established with good accuracy for predicting PFS (c-index values of 0.71; 95% confidence interval, 0.66-0.73). The survival curves were significantly different between low-risk and high-risk groups (median PFS: 9.8 vs. 22.8 months, P < 0.001, respectively). After propensity matching analysis, chemotherapy combination PD-1 inhibitor was significantly associated with superior PFS as compared with chemotherapy alone (median PFS, 10.6 versus 9.3 months, P = 0.016) in the high-risk group. However, no significant difference between chemotherapy combination PD-1 inhibitor and chemotherapy was observed (P = 0.840) in the low-risk groups. Conclusions: Our novel prognostic model was able to stratify patients with metastatic NPC into low-risk or high-risk groups and identify candidates for PD-1 inhibitor therapy. These results are expected to be confirmed by a prospective clinical trial.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias Nasofaríngeas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVES: To determine the values of quantitative metrics derived from synthetic MRI (SyMRI) and apparent diffusion coefficient (ADC) in evaluating the prognostic factors of cervical carcinoma (CC). METHODS: In this prospective study, 74 patients with pathologically confirmed CC were enrolled. Pretreatment quantitative metrics including T1, T2 and ADC values were obtained from SyMRI and diffusion-weighted imaging (DWI) sequences. The values of all metrics were compared for different prognostic features using Student's t-test or Mann-Whitney U-test. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were utilized to evaluate the diagnostic performance of quantitative variables. RESULTS: T1 and T2 values of parametrial involvement (PMI)-negative were significantly higher than those of PMI-positive (p = 0.002 and < 0.001), while ADC values did not show a significant difference. The area under curve (AUC) of T1 and T2 values for identifying PMI were 0.743 and 0.831. Only the T2 values showed a significant difference between the lymphovascular space involvement (LVSI)-negative and LVSI-positive (p < 0.001), and the AUC of T2 values for discriminating LVSI was 0.814. The differences of T1, T2, and ADC values between the well/moderately and the poorly differentiated CC were significant (all p < 0.001). The AUCs of T1, T2 and ADC values for predicting differentiation grades were 0.762, 0.830, and 0.808. The combined model of all metrics proved to achieve good diagnostic performance with the AUC of 0.866. CONCLUSION: SyMRI may be a potential noninvasive tool for assessing the prognostic factors such as PMI, LVSI, and differentiation grades in CC. Moreover, the overall diagnostic performances of synthetic quantitative metrics were superior to the ADC values, especially in identifying PMI and LVSI. ADVANCES IN KNOWLEDGE: This is the first study to assess the utility of SyMRI-derived parameters and ADC value in evaluating the prognostic factors in CC.
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Carcinoma , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudios Prospectivos , Pronóstico , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patologíaRESUMEN
PURPOSE: This study aimed to identify patients with pathological complete response (pCR) and make better clinical decisions by constructing a preoperative predictive model based on tumoral and peritumoral volumes of multiparametric magnetic resonance imaging (MRI) obtained before neoadjuvant chemotherapy (NAC). METHODS: This study investigated MRI before NAC in 448 patients with nonmetastatic invasive ductal breast cancer (Sun Yat-sen Memorial Hospital, Sun Yat-sen University, n = 362, training cohort; and Sun Yat-sen University Cancer Center, n = 86, validation cohort). The tumoral and peritumoral volumes of interest (VOIs) were segmented and MRI features were extracted. The radiomic features were filtered via a random forest algorithm, and a supporting vector machine was used for modeling. The receiver operator characteristic curve and area under the curve (AUC) were calculated to assess the performance of the radiomics-based classifiers. RESULTS: For each MRI sequence, a total of 863 radiomic features were extracted and the top 30 features were selected for model construction. The radiomic classifiers of tumoral VOI and peritumoral VOI were both promising for predicting pCR, with AUCs of 0.96 and 0.97 in the training cohort and 0.89 and 0.78 in the validation cohort, respectively. The tumoral + peritumoral VOI radiomic model could further improve the predictive accuracy, with AUCs of 0.98 and 0.92 in the training and validation cohorts. CONCLUSIONS: The tumoral and peritumoral multiparametric MRI radiomics model can promisingly predict pCR in breast cancer using MRI images before surgery. Our results highlighted the potential value of the tumoral and peritumoral radiomic model in cancer management.