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BACKGROUND: Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. METHODS: This randomised controlled trial was conducted at Fudan University Shanghai Cancer Center (Shanghai, China). We enrolled patients aged 18-75 years, with previously untreated CUP (histologically confirmed metastatic adenocarcinoma, squamous cell carcinoma, poorly differentiated carcinoma, or poorly differentiated neoplasms) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, who were not amenable to local radical treatment. Patients were randomly assigned (1:1) by the Pocock and Simon minimisation method to receive either site-specific therapy or empirical chemotherapy (taxane [175 mg/m2 by intravenous infusion on day 1] plus platinum [cisplatin 75 mg/m2 or carboplatin area under the curve 5 by intravenous infusion on day 1], or gemcitabine [1000 mg/m2 by intravenous infusion on days 1 and 8] plus platinum [same as above]). The minimisation factors were ECOG performance status and the extent of the disease. Clinicians and patients were not masked to interventions. The tumour origin in the site-specific therapy group was predicted by the 90-gene expression assay and treatments were administered accordingly. The primary endpoint was progression-free survival in the intention-to-treat population. The trial has been completed and the analysis is final. This study is registered with ClinicalTrials.gov (NCT03278600). FINDINGS: Between Sept 18, 2017, and March 18, 2021, 182 patients (105 [58%] male, 77 [42%] female) were randomly assigned to receive site-specific therapy (n=91) or empirical chemotherapy (n=91). The five most commonly predicted tissues of origin in the site-specific therapy group were gastro-oesophagus (14 [15%]), lung (12 [13%]), ovary (11 [12%]), cervix (11 [12%]), and breast (nine [10%]). At the data cutoff date (April 30, 2023), median follow-up was 33·3 months (IQR 30·4-51·0) for the site-specific therapy group and 30·9 months (27·6-35·5) for the empirical chemotherapy group. Median progression-free survival was significantly longer with site-specific therapy than with empirical chemotherapy (9·6 months [95% CI 8·4-11·9] vs 6·6 months [5·5-7·9]; unadjusted hazard ratio 0·68 [95% CI 0·49-0·93]; p=0·017). Among the 167 patients who started planned treatment, 46 (56%) of 82 patients in the site-specific therapy group and 52 (61%) of 85 patients in the empirical chemotherapy group had grade 3 or worse treatment-related adverse events; the most frequent of these in the site-specific therapy and empirical chemotherapy groups were decreased neutrophil count (36 [44%] vs 42 [49%]), decreased white blood cell count (17 [21%] vs 26 [31%]), and anaemia (ten [12%] vs nine [11%]). Treatment-related serious adverse events were reported in five (6%) patients in the site-specific therapy group and two (2%) in the empirical chemotherapy group. No treatment-related deaths were observed. INTERPRETATION: This single-centre randomised trial showed that site-specific therapy guided by the 90-gene expression assay could improve progression-free survival compared with empirical chemotherapy among patients with previously untreated CUP. Site-specific prediction by the 90-gene expression assay might provide more disease information and expand the therapeutic armamentarium in these patients. FUNDING: Clinical Research Plan of Shanghai Hospital Development Center, Program for Shanghai Outstanding Academic Leader, and Shanghai Anticancer Association SOAR PROJECT. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Primarias Desconocidas , Humanos , Persona de Mediana Edad , Masculino , Femenino , Neoplasias Primarias Desconocidas/tratamiento farmacológico , Neoplasias Primarias Desconocidas/genética , Neoplasias Primarias Desconocidas/patología , Neoplasias Primarias Desconocidas/mortalidad , Anciano , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gemcitabina , Perfilación de la Expresión Génica , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Carboplatino/administración & dosificación , China , Taxoides/administración & dosificación , Taxoides/uso terapéutico , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) has shown promise in improving the prognosis of individuals with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the factors influencing tumor response and long-term survival in these patients remain unknown. The optimal timing for surgery after the completion of radiotherapy in LA-ESCC remains controversial. Therefore, this study was designed to identify biomarkers and to determine the optimal post-NCRT time-to-surgery (TTS) for patients with LA-ESCC. METHODS: This retrospective study included patients with resectable LA-ESCC who underwent NCRT between May 2017 and June 2021. The tumor shrinkage rate was calculated as the difference between the pre- and post-primary gross tumor volume (GTVp) divided by the pre-GTVp. Univariate and multivariate Cox regression analyses and Kaplan-Meier curves were used to calculate overall survival (OS) and progression-free survival (PFS). RESULTS: We collected data from 248 patients with resectable LA-ESCC who underwent computed tomography (CT) scans before the initiation of treatment. The median follow-up time was 37.7 months. The optimal cutoff of tumor shrinkage was 45%. In the univariate and multivariate analyses, we found a significant association between the tumor shrinkage rate and PFS (p = 0.001). Among the subgroup of patients who responded to treatment, extending the TTS was associated with improved OS (p = 0.037) and PFS (p = 0.028). CONCLUSIONS: For patients with resectable LA-ESCC, the tumor shrinkage rate is an independent prognostic factor for PFS. Thus, for responders, prolonging TTS is recommended to obtain a better OS.
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Neoplasias Esofágicas , Esofagectomía , Terapia Neoadyuvante , Tiempo de Tratamiento , Carga Tumoral , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Masculino , Estudios Retrospectivos , Femenino , Terapia Neoadyuvante/mortalidad , Persona de Mediana Edad , Tasa de Supervivencia , Anciano , Estudios de Seguimiento , Pronóstico , Quimioradioterapia/mortalidad , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Adulto , Quimioradioterapia AdyuvanteRESUMEN
BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.
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Neoplasias Esofágicas , Ganglios Linfáticos , Metástasis Linfática , Humanos , Masculino , Femenino , Tasa de Supervivencia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Estudios de Seguimiento , Pronóstico , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Anciano , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/secundario , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía/mortalidad , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Many patients undergo dose reduction or early termination of chemotherapy to reduce chemoradiotherapy-related toxicity, which may increase their risk of survival. However, this strategy may result in underdosing patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). This study aimed to analyze the relationship between the relative dose intensity (RDI) and survival outcomes in patients with LA-ESCC. METHODS: This retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4NanyM0) receiving neoadjuvant chemoradiotherapy (NCRT) with curative-intent esophagectomy. The patients received 2 courses of paclitaxel plus carboplatin (TC) combination radiotherapy prior to undergoing surgery. During NCRT, RDI was computed, defined as the received dose as a percentage of the standard dose, and the incidence of dose delays was estimated (≥ 7 days in any course cycle). The best RDI cutoff value (0.7) was obtained using ROC curve. The Kaplan-Meier survival curves were compared using the log-rank test, the treatment effect was measured using hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: We included 132 patients in this study, divided into RDI < 0.7 and RDI ≥ 0.7 groups using cut-off value of 0.7. RDI grade was an independent prognostic factor for OS. Baseline demographic and clinical characteristics were well balanced between the groups. There was no evidence that patients with RDI < 0.7 experienced less toxicity or those with RDI ≥ 0.7 resulted in more toxicity. However, patients with RDI < 0.7 who were given reduced doses had a worse overall survival [HR 0.49, 95% CI 0.27-0.88, P = 0.015]. The risk of a lower RDI increased with a longer dose delay time (P < 0.001). CONCLUSION: The RDI below 0.7 for avoiding chemoradiotherapy toxicity administration led to a reduction in the dose intensity of treatment and decreased overall survival.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Humanos , Femenino , Masculino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Paclitaxel/administración & dosificación , Quimioradioterapia/métodos , Carboplatino/administración & dosificación , Esofagectomía , Adulto , Estimación de Kaplan-Meier , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
OBJECTIVE: The SGLT2 inhibitor, canagliflozin, not only reduces glycemia in patients with type 2 diabetes but also exerts cardioprotective effects in individuals without diabetes. However, its potential beneficial effects in cardiac arrest have not been characterized. The purpose of this study was to examine the protective effect of canagliflozin pretreatment on postresuscitation-induced cardiac dysfunction in vivo. METHODS: Male C57/BL6 mice were randomized to vehicle (sham and control) or canagliflozin treatment groups. All mice except for the sham-operated mice were subjected to potassium chloride-induced cardiac arrest followed by chest compressions and intravenous epinephrine for resuscitation. Canagliflozin therapy efficacies were evaluated by electrocardiogram, echocardiography, histological analysis, inflammatory response, serum markers of myocardial injury, protein phosphorylation analysis, and immunohistological assessment. RESULTS: Canagliflozin-pretreated mice exhibited a higher survival rate (P < 0.05), a shorter return of spontaneous circulation (ROSC) time (P < 0.01) and a higher neurological score (P < 0.01 or P < 0.001) than control mice after resuscitation. Canagliflozin was effective at improving cardiac arrest and resuscitation-associated cardiac dysfunction, indicated by increased left ventricular ejection fraction and fractional shortening (P < 0.001). Canagliflozin reduced serum levels of LDH, CK-MB and α-HBDH, ameliorated systemic inflammatory response, and diminished the incidence of early resuscitation-induced arrhythmia. Notably, canagliflozin promoted phosphorylation of cardiac STAT-3 postresuscitation. Furthermore, pharmacological inhibition of STAT-3 by Ag490 blunted STAT-3 phosphorylation and abolished the cardioprotective actions of canagliflozin. CONCLUSIONS: Canagliflozin offered a strong cardioprotective effect against cardiac arrest and resuscitation-induced cardiac dysfunction. This canagliflozin-induced cardioprotection is mediated by the STAT-3-dependent cell-survival signaling pathway.
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Cardiomiopatías , Reanimación Cardiopulmonar , Diabetes Mellitus Tipo 2 , Paro Cardíaco , Animales , Humanos , Masculino , Ratones , Canagliflozina/farmacología , Modelos Animales de Enfermedad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
Torsion of the spermatic cord is a urological emergency that must be treated immediately with surgery, yet detorsion of the testis can cause testicular tissue damage because of ischemia-reperfusion (I/R) injury. I/R injury is a complex pathophysiological process that may affect the functions of distant organs. Here, we examined whether testicular torsion/detorsion (TT) causes myocardial dysfunction. We next investigated the potential beneficial effect and underlying mechanisms of remote ischemic postconditioning (RIPost) on cardiac function after testicular torsion/detorsion. Male Sprague-Dawley rats were assigned to three different sets of experimental groups. Testicular I/R was induced by rotating the right testis to 1080° clockwise for 3 h followed by 3 h of detorsion. RIPost was induced at the onset of testicular detorsion by four cycles of 5-min bilateral femoral artery occlusion with 5-min reperfusion. Cardiac function was determined postdetorsion, and the cardioprotective effect of RIPost was examined. Testicular torsion/detorsion-treated rats had reduced serum testosterone levels, impaired systemic hemodynamics, elevated systemic inflammatory responses, and increased serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), α-hydroxybutyrate dehydrogenase (α-HBDH), and cardiac troponin I (cTnI). However, RIPost attenuated remote heart dysfunction induced by testicular torsion/detorsion. Furthermore, RIPost enhanced the phosphorylation of ventricular signal transducer and activator of transcription (STAT)-3, which is a key component of the survivor activating factor enhancement (SAFE) signaling pathways. Inhibition of STAT-3 with Ag490 abolished the RIPost-induced cardioprotection and STAT-3 phosphorylation. Testicular torsion followed by detorsion may cause impaired cardiac function in rats. RIPost effectively attenuates this remote cardiac dysfunction. RIPost-induced protective effects may be mediated by the STAT-3 signaling pathway.
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Poscondicionamiento Isquémico , Daño por Reperfusión , Torsión del Cordón Espermático , Humanos , Ratas , Masculino , Animales , Torsión del Cordón Espermático/complicaciones , Torsión del Cordón Espermático/metabolismo , Torsión del Cordón Espermático/prevención & control , Ratas Sprague-Dawley , Poscondicionamiento Isquémico/efectos adversos , Testículo/metabolismo , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismoRESUMEN
PURPOSE: The aim of this study was to evaluate the impact of the spatial heterogeneity of prostate-specific membrane antigen (PSMA) uptake on circulating tumor DNA (ctDNA) characteristics and the response rate to new hormonal agent (NHA) treatment. METHODS: This retrospective study included 153 patients with metastatic castration-resistant prostate cancer (mCRPC) who underwent gallium-68 [68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and ctDNA sequencing with a less than 2-week interval. SUVhetero was defined as the variance of SUVmean for each PSMA-positive lesion. SUVmax-mean was obtained by subtracting the SUVmax by the SUVmean. Patients receiving abiraterone treatment after [68 Ga]Ga-PSMA-11 PET/CT and ctDNA sequencing and with complete follow-up record were included into prostate-specific antigen (PSA) response rate analysis. PSA response was defined as a reduction of greater than 50% from baseline. RESULTS: The ctDNA detection rate was 65% (100/153). Higher SUVhetero value contributed to higher ctDNA% (Spearman's rho = 0.278, p < 0.002). A total of 60 patients were included in PSA response rate analysis. The median follow-up was 19.3 (IQR 16.2-23.2) months. Compare to patients with higher SUVhetero value, patients with NA SUVhetero had a higher PSA response rate (52% vs. 90%, p = 0.036). A higher SUVmax-mean value was strongly correlated with higher SUVhetero (Spearman's rho = 0.833, p < 0.0001). Patients with higher SUVmax-mean value also had a higher PSA response rate compared to patients with lower SUVmax-mean value (83.3% vs. 53.3%, p = 0.024). An external cohort confirmed baseline SUVmax-mean value was associated with enzalutamide treatment response rate. Patients with alterations in AR, DNA damage repair pathway, TP53, AR-associated pathway, cell cycle pathway, or WNT pathway had higher SUVmax-mean value compared to those without (p < 0.05). CONCLUSION: Spatial heterogeneity of the PSMA uptake was associated with ctDNA characteristics and response rate to NHA treatment.
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Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Radioisótopos de Galio , Antígeno Prostático Específico/metabolismo , Estudios Retrospectivos , Neoplasias de la Próstata/patología , GenómicaRESUMEN
BACKGROUND: Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. METHODS AND RESULTS: Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. CONCLUSIONS: We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.
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Adenocarcinoma , Neoplasias Primarias Desconocidas , Infecciones por Papillomavirus , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Neoplasias Primarias Desconocidas/patología , Estudios Retrospectivos , Biomarcadores de Tumor/metabolismo , Proteínas RepresorasRESUMEN
BACKGROUND: While the Oncotype DX 21-gene recurrence score (RS) has been recommended for guiding ER+/HER2- breast cancer treatment decisions, it is limited by cost and availability. PURPOSE: To develop a multiparametric MRI-based radiomics model for assessing ER+/HER2- breast cancer patients' 21-gene RS. STUDY TYPE: Retrospective. SUBJECTS: A total of 151 patients with pathologically confirmed ER+/HER2- breast cancers, who underwent preoperative breast MR examinations and 21-gene expression assays, divided into training (n = 106) and validation (n = 45) cohorts. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhancement (DCE) sequence at 1.5 T or 3 T. ASSESSMENT: A total of 1046 radiomics features were extracted from each MRI sequence with a manual lesion segmentation method. After feature dimension reduction by the recursive feature elimination method and dataset balance by the synthetic minority oversampling technique, linear support vector machine classifier models were built to distinguish high RS (RS ≥ 26) from low RS (RS < 26) from T2WI, DWI apparent diffusion coefficient (ADC) maps, DCE and their combination (multiparametric). A model based on clinical characteristics and a fusion model combining clinical characteristics and multiparametric MRI were also built. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve analysis and De Long's test with Bonferroni correction were used. A P value <0.01 was considered statistically significant. RESULTS: The area under the ROC curve (AUC) value of multiparametric radiomics model was 0.92, significantly higher than DCE (0.83), T2WI (0.78), and ADC (0.77) models in the training cohort. The radiomics model also achieved good performance in the validation cohort (AUC = 0.77). The fusion model had significantly higher performance than the clinical model in both the training (AUC = 0.92 and 0.64, respectively) and validation cohorts (AUC = 0.78 and 0.62, respectively). DATA CONCLUSION: The proposed multiparametric MRI-based radiomics models may have potential to help distinguish ER+/HER2- breast cancer patients' recurrence risk. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.
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Neoplasias de la Mama , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Imagen de Difusión por Resonancia MagnéticaRESUMEN
We investigate the usage of polyelectrolyte complex materials for water remediation purposes, specifically their ability to remove nanoplastics from water, on which there is currently little to no prior research. We demonstrate that oppositely charged random copolymers are effective at quantitatively removing nanoplastic contamination from aqueous solution. The mechanisms underlying this remediation ability are explored through computational simulations, with corroborating quartz crystal microbalance adsorption experiments. We find that hydrophobic nanostructures and interactions likely play an important role.
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Soy sauce is a popular fermented seasoning due to its distinct flavor and rich umami taste. Its traditional production involves two stages: solid-state fermentation and moromi (brine fermentation). During moromi, the dominant microbial population in the soy sauce mash changes, which is called microbial succession and is essential for the formation of soy sauce flavor compounds. Research has identified the sequence of succession, starting with Tetragenococcus halophilus, then Zygosaccharomyces rouxii, and lastly, Starmerella etchellsii. Factors such as the environment, microbial diversity, and interspecies relationships drive this process. Salt and ethanol tolerance influence microbial survival, while nutrients in the soy sauce mash support the cells in resisting external stress. Different microbial strains have varying abilities to survive and respond to external factors during fermentation, which impacts soy sauce quality. In this review, we would examine the factors behind the succession of common microbial populations in the soy sauce mash and explore how microbial succession affects soy sauce quality. The insights gained can help better manage the dynamic changes in microbes during fermentation, leading to improved production efficiency.
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Photonic devices based on a lithium-niobate-on-insulator (LNOI) are current research hotspots; however, owing to the high refractive index contrast of the LNOI platform and inherent birefringence of lithium niobate itself, such photonic devices are generally polarization sensitive, affecting their further wide application. This paper proposes a simple, compact, and efficient polarization rotator (PR) based on a laterally asymmetric rib waveguide by depositing a layer of semi-infinite silicon nitride dielectric material on one side of the rib waveguide. The results show that a PR with a polarization rotation region length of 15.77 µm is achieved, and the polarization extinction ratio (PER), insertion loss (IL), and polarization conversion efficiency (PCE) are 38.57/68.95 and 0.2/0.22 dB, and 99.99%/almost 100%, respectively, for the fundamental transverse electric mode (T E 0) and transverse magnetic mode (T M 0) at a 1.55 µm wavelength. The operation bandwidth is around 120 nm for the T E 0 mode and T M 0 mode when the PER, IL, and PCE are greater than 20 dB, less than 0.32 dB, and more than 99%, respectively. Fabrication tolerances to the key structural parameters are investigated in detail. In addition, the evolution fields of the T E 0 mode and T M 0 mode along the propagation direction through the proposed device are presented.
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BACKGROUND: Once malignancy tumors were diagnosed, the determination of tissue origin and tumor type is critical for clinical management. Although the significant advance in imaging techniques and histopathological approaches, the diagnosis remains challenging in patients with metastatic and poorly differentiated or undifferentiated tumors. Gene expression profiling has been demonstrated the ability to classify multiple tumor types. The present study aims to assess the performance of a 90-gene expression test for tumor classification (i.e. the determination of tumor tissue of origin) in real clinical settings. METHODS: Formalin-fixed paraffin-embedded samples and associated clinicopathologic information were collected from three cancer centers between January 2016 and January 2021. A total of 1417 specimens that met quality control criteria (RNA quality, tumor cell content ≥ 60% and so on) were analyzed by the 90-gene expression test to identify the tumor tissue of origin. The performance was evaluated by comparing the test results with histopathological diagnosis. RESULTS: The 1417 samples represent 21 main tumor types classified by common tissue origins and anatomic sites. Overall, the 90-gene expression test reached an accuracy of 94.4% (1338/1417, 95% CI: 0.93 to 0.96). Among different tumor types, sensitivities were ranged from 74.2% (head&neck tumor) to 100% (adrenal carcinoma, mesothelioma, and prostate cancer). Sensitivities for the most prevalent cancers of lung, breast, colorectum, and gastroesophagus are 95.0%, 98.4%, 93.9%, and 90.6%, respectively. Moreover, specificities for all 21 tumor types are greater than 99%. CONCLUSIONS: These findings showed robust performance of the 90-gene expression test for identifying the tumor tissue of origin and support the use of molecular testing as an adjunct to tumor classification, especially to those poorly differentiated or undifferentiated tumors in clinical practice.
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Perfilación de la Expresión Génica , Neoplasias de Cabeza y Cuello , Biomarcadores de Tumor/genética , Expresión Génica , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodosRESUMEN
OBJECTIVE: To investigate the clinical significance of the expression of the stemness marker CD133 in circulating tumor cells of newly diagnosed metastatic castration-sensitive prostate cancer patients. METHODS: For this study, 104 metastatic castration-sensitive prostate cancer patients treated at the Fudan University Shanghai Cancer Center from September 2015 to February 2017 were considered. After enrollment, the patients received androgen deprivation therapy (bicalutamide + goserelin). Circulating tumor cells were isolated and identified using the CanPatrol system, which can identify not only traditional epithelial markers but also mesenchymal markers in cells that have undergone epithelial mesenchymal transition. CD133 was used to characterize the circulating tumor cells. The primary endpoint of this research was to evaluate progression to castration resistance. RESULTS: Among the 104 patients enrolled, 89 patients were circulating tumor cell positive at baseline, and the median circulating tumor cell count was four. The median follow-up was 24 months, and at the end of follow-up, the proportion of patients who progressed to castration-resistant prostate cancer in the CTC+CD133+ group was 93.3%, which was significantly higher than that of the circulating tumor cell negative group (73.3%) and the CTC+CD133- group (75.0%), with P = 0.043. After follow-up, progression-free survival for CTC+CD133+, CTC+CD133-, and circulating tumor cell patients was 10.0, 13.0, and 14.0 months, respectively, with P = 0.022. Univariate and multivariate analyses also confirmed that the characterization of circulating tumor cells using CD133 can independently predict progression-free survival in metastatic castration-sensitive prostate cancer patients after receiving androgen deprivation therapy (P = 0.042; hazard ratio 1.396). CONCLUSION: Baseline CTC+CD133+ was a poor independent prognostic factor for metastatic castration-sensitive prostate cancer patients to progress to castration-resistant prostate cancer after receiving androgen deprivation therapy.
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Células Neoplásicas Circulantes , Neoplasias de la Próstata Resistentes a la Castración , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , Biomarcadores de Tumor , Castración , China , Humanos , Masculino , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Pronóstico , Supervivencia sin ProgresiónRESUMEN
Objective: This study aimed to evaluate the prognostic value of preoperative radiomics and establish an integrated model for esophageal squamous cell cancer (ESCC). Methods: A total of 931 patients were retrospectively enrolled in this study (training cohort, n=624; validation cohort, n=307). Radiomics features were obtained by contrast-enhanced computed tomography (CT) before esophagectomy. A radiomics index was set based on features of tumor and reginal lymph nodes by using the least absolute shrinkage and selection operator (LASSO) Cox regression. Prognostic nomogram was built based on radiomics index and other independent risk factors. The prognostic value was assessed by using Harrell's concordance index, time-dependent receiver operating characteristics and Kaplan-Meier curves. Results: Twelve radiomic features from tumor and lymph node regions were identified to build a radiomics index, which was significantly associated with overall survival (OS) in both training cohort and validation cohort. The radiomics index was highly correlated with clinical tumor-node-metastasis (cTNM) and pathologic TNM (pTNM) stages, but it demonstrated a better prognostic value compared with cTNM stage and was almost comparable with pTNM stage. Multivariable Cox regression showed that the radiomics index was an independent prognostic factor. An integrated model was constructed based on gender, preoperative serum sodium concentration, pTNM and the radiomics index for clinical usefulness. The integrated model demonstrated discriminatory ability better compared with the traditional clinical-pathologic model and pTNM alone, indicating incremental value for prognosis. Conclusions: CT-based radiomics for primary tumor and reginal lymph nodes was sufficient in predicting OS for patients with ESCC. The integrated model demonstrated incremental value for prognosis and was robust for clinical applications.
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Crizotinib, a multitargeted MET/ALK/ROS1 tyrosine kinase inhibitor, has been approved for the treatment of ROS1 fusion-positive non-small cell lung cancers (NSCLCs). However, "on-target" or "off-target" resistance alterations often emerge that confer the drug resistance. Patients with ROS1-rearranged NSCLC who develop crizotinib resistance, especially those acquiring "off-target" resistance mutations, still lack effective therapeutic options for after crizotinib treatment. Herein, we reported a patient with stage IVb lung adenocarcinoma harboring ROS1 fusion, who acquired a BRAF V600E and lost the ROS1 fusion after progression on crizotinib. It was deduced that the V600E may originate from a subclone with an extremely low fraction that was independent of ROS1 fusion-positive cells. The patient was subsequently treated with dabrafenib and trametinib combination and achieved a partial response lasting for more than 6 months. Our study revealed that BRAF V600E can confer the crizotinib resistance in ROS1 fusion-positive NSCLC and presented the first case showing that the treatment with dabrafenib and trametinib can serve as an effective option for later-line treatment for this molecular-defined subgroup. KEY POINTS: Patients with ROS1-rearranged non-small cell lung cancer (NSCLC) who acquire "off-target" resistance mutations to crizotinib still lack effective therapeutic options for after crizotinib treatment. This report describes the case of a patient with ROS1-rearranged NSCLC who acquired a BRAF V600E and lost the ROS1 fusion after crizotinib failure. The case was subsequently treated with dabrafenib and trametinib combination and achieved a partial response lasting for more than 6 months. This is the first article reporting that treatment with dabrafenib and trametinib may serve as an effective option for later-line treatment for patients harboring resistant BRAF V600E.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Crizotinib/uso terapéutico , Resistencia a Antineoplásicos , Humanos , Imidazoles , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Oximas , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Piridonas , PirimidinonasRESUMEN
BACKGROUND: This study aimed to establish an effective and practical prognostic index for esophageal squamous cell cancer (ESCC) based on the coagulation factors. METHODS: The training cohort of 965 patients with ESCC was retrospectively collected at Sichuan Cancer Hospital from 2012 to 2014, along with clinical characteristics and follow-up information. Risk factors of coagulation status, including 11 blood parameters (platelet [PLT], mean platelet volume [MPV], platelet distribution width [PDW], plateletocrit [PCT], thrombin time [TT], prothrombin time [PT], international normalized ratio [INR], activated partial thromboplastin time [APTT], fibrinogen, D-dimer, and fibrinogen degradation product [FDP]), were studied by least absolute shrinkage and selection operator (LASSO) Cox regression and the Coagulation Index was established. The index was validated in a cohort of 848 patients with ESCC at the same institution, from 2015 to 2016. RESULTS: Three variables of PLT, MPV, and fibrinogen were identified by selecting features with coefficients in the LASSO algorithm, and a Coagulation Index was established as follows: Coagulation Index = 0.0005 × PLT (109/L) - 0.0384 × MPV (fL) + 0.1148 × fibrinogen (g/L). A higher Coagulation Index score was significantly associated with higher pT stage and pN stage (p < 0.05). With this prognostic index, patients could be stratified into three risk groups. The 3-year overall survival (OS) rates of the low-, middle- and high-risk groups in the training cohort were 63.5%, 55.5% and 43.1%, respectively (log-rank p < 0.001). Similarly, in the validation set, the respective 3-year OS for each risk group was significantly different across the three risk groups. Multivariate analysis indicated that the Coagulation Index remained a significant factor for predicting OS, independently of pathological TNM stage. CONCLUSIONS: The Coagulation Index is an independent predictor of survival for patients with ESCC.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Pruebas de Coagulación Sanguínea , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. METHODS: In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. RESULTS: For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84-0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82-0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82-0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47-0.99) for identifying the tumor origins. CONCLUSIONS: The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.
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BACKGROUND: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. METHODS: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. RESULTS: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. CONCLUSION: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.
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Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/terapia , Carga Tumoral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Terapia Combinada/métodos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Esofagitis/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Pronóstico , Supervivencia sin Progresión , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Traumatismos por Radiación/epidemiología , Neumonitis por Radiación/epidemiología , Análisis de Regresión , Estudios RetrospectivosRESUMEN
OBJECTIVE: To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria. METHODS: A total of 1097 school students (610 males and 487 females, ages 12-15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume. RESULTS: The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (ß = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (ß = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria. CONCLUSIONS: Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents.