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  • 1
    In: Signal Transduction and Targeted Therapy, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2024-06-19)
    Abstract: Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3–36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9–7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.
    Type of Medium: Online Resource
    ISSN: 2059-3635
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
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  • 2
    In: Head & Neck, Wiley, Vol. 43, No. 9 ( 2021-09), p. 2602-2610
    Abstract: To evaluate the value of locoregional radiation therapy (LRRT) in de novo metastatic nasopharyngeal carcinoma (mNPC) and identify suitable candidates for additional LRRT after palliative chemotherapy (PCT). Methods Patients with de novo mNPC received platinum‐based chemotherapy for a minimum of four cycles with or without definitive LRRT via intensity‐modulated radiation therapy (IMRT) were all candidates for this study. Results A total of 168 patients were included for this analysis. Additional LRRT was associated with significantly longer median OS (69.5 vs. 17.8 months, p   〈  0.001) when compared with PCT alone. However, this survival benefit of LRRT was only reflected in patients with oligometastatic diseases (90.8 vs. 17 months, p   〈  0.001), but not for those with polymetastatic disease ( p  = 0.86). Conclusions Additional LRRT after PCT may only improve OS for oligometastatic patients. For patients with polymetastatic disease, intensive systemic treatment such as the combination of immunotherapy and adequate PCT might be necessary.
    Type of Medium: Online Resource
    ISSN: 1043-3074 , 1097-0347
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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  • 3
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 14, No. 2 ( 2023-04), p. 815-825
    Abstract: Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA‐NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in ClinicalTrials.gov (NCT02575547). Methods Patients with biopsy‐proven NPC and planned for IC + CCRT were recruited. IC entailed two cycles of 3‐weekly docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 ; CCRT entailed two to three cycles of 3‐weekly cisplatin 100 mg/m 2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre‐IC, post‐cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL 5.0 ) by the end of treatment (W7‐CCRT). Secondary endpoints included body mass index, NRS2002 and PG‐SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicities and survivals. The associations between primary and secondary endpoints were also evaluated. Results One hundred and seventy‐one patients were enrolled. Median follow‐up was 67.4 (IQR: 64.1–71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4‐CCRT (median of 4.0% [IQR: 0.0–7.0%]) and peaked at W7‐CCRT (median of 8.5% [IQR: 4.1–11.7%] ). 71.9% (123/171) of patients recorded a WL 5.0 by W7‐CCRT, which was associated with a higher malnutrition risk (NRS2002 ≥ 3 points: 87.7% [WL ≥ 5.0%] vs 58.7% [WL  〈  5.0%], P   〈  0.001) and requirement of nutritional intervention (PG‐SGA ≥ 9 points: 82.0% [WL ≥ 5.0%] vs 66.7% [WL 〈  5.0%], P  = 0.038). The median %WL at W7‐CCRT was higher in patients who suffered from ≥ G2 mucositis (9.0% vs 6.6%, P  = 0.025) and xerostomia (9.1% vs 6.3%, P  = 0.003). Besides, patients with cumulative WL 5.0 also reported a higher detriment on QoL at W7‐CCRT compared with patients without, with a difference of −8.3 points (95% CI [−15.1, −1.4], P  = 0.019). Conclusions We observed a high prevalence of WL among LA‐NPC patients who were treated with IC + CCRT, which peaked during CCRT, and had a detriment on patients' QoL. Our data support the need to monitor patient's nutritional status during the later phase of treatment with IC + CCRT and inform on nutritional intervention strategies.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 6036-6036
    Abstract: 6036 Background: We conducted a multicenter prospective study (NCT02575547) to investigate the association between longitudinal nutritional status and survival in locally advanced nasopharynx cancer (LA-NPC) treated with induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT). Methods: All patients with biopsy-proven LA-NPC and planned for IC-CCRT were recruited from ten institutions. IC entailed 2 cycles of docetaxel 75mg/m 2 /3w and cisplatin 75mg/m 2 /3w; CCRT entailed 2-3 cycles cisplatin 100mg/m 2 /3w and IMRT (70-72Gy/30-32fr). Study parameters included weight loss (WL), % of ideal body weight (%IBW), body mass index (BMI), nutrition risk screening 2002 (NRS2002), patient-generated subjective global assessment (PG-SGA), and EORTC QLQ-C30 that were collected at the following time-points: baseline (T1), 1 w pre-2 nd IC (T2), 1 w pre-CCRT (T3), 4 w mid-CCRT (T4), end-CCRT (T5), 3 mo post-CCRT (T6), 1 y post-CCRT (T7), 2 y post-CCRT (T8). Results: 186 patients were recruited; 171 were eligible for analysis. Median follow-up was 35.8 mo (range 12.3-46.1 mo). Compliance rates were 97.7% (167/171) and 87.7% (150/171) for IC and CCRT, respectively; all except one completed RT. Longitudinal assessment indicated the worst nutritional status at T5, followed by recovery at T8: 27.1% with %IBW 〈 90%; 69.2% with WL ≥5%, which was also associated with a worsened QOL (OR = 6.23 for QOL change ≥25.0, P = 0.012). Interestingly, T1 nutritional status was not associated with prognosis (P 〉 0.05 for all). However, nutritional parameters at T5 were significantly associated with survival; %IBW 〈 90% was the strongest predictor for inferior DMFS (HR = 2.669) and OS (HR = 4.661) among all parameters (multivariable-adjusted P 〈 0.05). Subgroup analyses revealed that %IBW 〈 90%, WL ≥10% at T5 represented the most adverse subset of patients (Table). Conclusions: Here, we show that poor nutrition despite systemic intensification leads to inferior QOL and disease control in LA-NPC patients. This is counter-intuitive and highlights the crucial importance of paracrine factors in optimising treatment efficacy. Clinical trial information: NCT02575547. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 5
    In: The Lancet Oncology, Elsevier BV, Vol. 22, No. 8 ( 2021-08), p. 1162-1174
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2049730-1
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  • 6
    In: The Oncologist, Oxford University Press (OUP), Vol. 27, No. 4 ( 2022-04-05), p. e340-e349
    Abstract: Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized. Material and Methods We quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups. Results Plasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P = .001 or HR 2.74, 95% CI 1.27-5.91, P = .010), DMFS (HR 2.82, 95% CI 1.36-5.85, P = .005 or HR 3.27, 95% CI 1.57-6.81, P = .002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P = .018 or HR 2.03, 95% CI 1.14-3.62, P = .016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P = .070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis. Conclusion Plasma BART8-3p is a promising biomarker for the detection and prognosis of NPC.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 7
    In: Angewandte Chemie International Edition, Wiley, Vol. 60, No. 43 ( 2021-10-18), p. 23388-23393
    Abstract: PtSe 2 is a typical noble metal dichalcogenide (NMD) that holds promising possibility for next‐generation electronics and photonics. However, when applied in hydrogen evolution reaction (HER), it exhibits sluggish kinetics due to the insufficient capability of absorbing active species. Here, we construct PtSe 2 /Pt heterointerface to boost the reaction dynamics of PtSe 2 , enabled by an in situ electrochemical method. It is found that Se vacancies are induced around the heterointerface, reducing the coordination environment. Correspondingly, the exposed Pt atoms at the very vicinity of Se vacancies are activated, with enhanced overlap with H 1s orbital. The adsorption of H . intermediate is thus strengthened, achieving near thermoneutral free energy change. Consequently, the as‐prepared PtSe 2 /Pt exhibits extraordinary HER activity even superior to Pt/C, with an overpotential of 42 mV at 10 mA cm −2 and a Tafel slope of 53 mV dec −1 . This work raises attention on NMDs toward HER and provides insights for the rational construction of novel heterointerfaces.
    Type of Medium: Online Resource
    ISSN: 1433-7851 , 1521-3773
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
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    detail.hit.zdb_id: 123227-7
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  BMC Cancer Vol. 22, No. 1 ( 2022-12)
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: No standard radiotherapy regimens have been established for the treatment of de novo metastatic nasopharyngeal carcinoma (mNPC) with bone-only metastasis. The current study aimed to investigate the efficacy of palliative chemotherapy (PCT) plus locoregional radiotherapy (LRRT) with or without local radiotherapy (RT) for metastatic bone lesions in mNPC. Methods We retrospectively analysed 131 de novo patients with mNPC who had bone-only metastasis and received at least two cycles of PCT with LRRT. The difference in survival was evaluated by the log-rank test. Univariable and multivariable analyses were performed by Cox regression. Results The median overall survival (OS) and progression-free survival (PFS) were 33.0 months and 24.0 months, respectively. Patients with five or fewer metastatic bone lesions had significantly longer OS (72.0 months vs. 23.0 months, Hazard ratios (HR) = 0.45, p   〈   0.001) and PFS (48.0 months vs. 15.0 months, HR = 0.52, p  = 0.004) than those who had more than five metastatic bone lesions. Patients who received four or more cycles of chemotherapy were associated with significantly longer OS (unreached vs. 19.0 months, HR = 0.27, p   〈   0.001) and PFS (66 months vs. 16.0 months, HR = 0.32, p   〈   0.001). Multivariate analysis confirmed that fewer bone metastases (≤ 5) and more chemotherapy cycles (≥ 4) were favourable prognostic factors for OS. Subgroup analysis revealed that RT to metastatic bone lesions tended to prolong OS (83.0 months vs. 45.0 months) and PFS (60 months vs. 36.5 months) in patients with five or fewer metastatic bone lesions than in those without RT to metastatic bone lesions ( p   〉  0.05). Patients who received a RT dose 〉  30 Gy had neither better OS (63.5 months vs. 32.0 months, p  = 0.299) nor PFS (48.0 months vs. 28.0 months, p  = 0.615) than those who received a RT dose ≤30 Gy. Conclusions Local RT to bone metastases may not significantly improve survival in patients with de novo mNPC with bone-only metastasis who have already received PCT plus LRRT. Receiving four or more cycles of chemotherapy can significantly prolong survival and is a favourable independent protective factor.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 9
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2024-03-28)
    Abstract: Epstein-Barr virus (EBV) encoded microRNA BART8-3p (miR-BART8-3p) was significantly associated with the metastasis in nasopharyngeal carcinoma (NPC). To explore the clinical values of plasma miR-BART8-3p in patients with early NPC. We retrospectively analyzed 126 patients with stage I and II NPC. A receiver operating characteristic curve was used to examine the diagnostic performance. Kaplan‒Meier analysis was applied to determine survival differences. Cox regression was used for univariate and multivariate analyses. Compared to healthy subjects, plasma EBV miR-BART8-3p was highly expressed in early NPC patients. The sensitivity, specificity, and area under the curve value of plasma miR-BART8-3p combined with plasma EBV DNA was up to 88.9%, 94.4%, and 0.931. Compared to patients with low expression of miR-BART8-3p, patients with high expression of miR-BART8-3p had poorer 5-year overall survival (OS) (98.9% vs. 91.1%, P = 0.025), locoregional recurrence-free survival (LRRFS) (100% vs. 83.9%, P  〈  0.001) and distant metastasis-free survival (DMFS) (98.9% vs. 88.0%, P = 0.006). Risk stratification analysis revealed that high-risk patients (with high levels of EBV DNA and miR-BART8-3p) had inferior OS, LRRFS, and DMFS than low-risk patients (without high levels of EBV DNA and miR-BART8-3p). Multivariate analysis verified that the high-risk group was an unfavorable factor for OS, LRRFS, and DMFS. A combination of plasma EBV miR-BART8-3p and EBV DNA could be a potential biomarker for the diagnosis and prognosis in early NPC.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2615211-3
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  • 10
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2023-04-28)
    Abstract: Head and neck squamous cell carcinoma (HNSCC) are the most common cancers in the head and neck. Therapeutic response-related genes (TRRGs) are closely associated with carcinogenesis and prognosis in HNSCC. However, the clinical value and prognostic significance of TRRGs are still unclear. We aimed to construct a prognostic risk model to predict therapy response and prognosis in TRRGs-defined subgroups of HNSCC. Methods The multiomics data and clinical information of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA). The profile data GSE65858 and GSE67614 chip was downloaded from public functional genomics data Gene Expression Omnibus (GEO). Based on TCGA-HNSC database, patients were divided into a remission group and a non-remission group according to therapy response, and differentially expressed TRRGs between those two groups were screened. Using Cox regression analysis and Least absolute shrinkage and selection operator (LASSO) analysis, candidate TRRGs that can predict the prognosis of HNSCC were identified and used to construct a TRRGs-based signature and a prognostic nomogram. Result A total of 1896 differentially expressed TRRGs were screened, including 1530 upregulated genes and 366 downregulated genes. Then, 206 differently expressed TRRGs that was significantly associated with the survival were chosen using univariate Cox regression analysis. Finally, a total of 20 candidate TRRGs genes were identified by LASSO analysis to establish a signature for risk prediction, and the risk score of each patient was calculated. Patients were divided into a high-risk group (Risk-H) and a low-risk group (Risk-L) based on the risk score. Results showed that the Risk-L patients had better overall survival (OS) than Risk-H patients. Receiver operating characteristic (ROC) curve analysis revealed great predictive performance for 1-, 3-, and 5-year OS in TCGA-HNSC and GEO databases. Moreover, for patients treated with post-operative radiotherapy, Risk-L patients had longer OS and lower recurrence than Risk-H patients. The nomogram involves risk score and other clinical factors had good performance in predicting survival probability. Conclusions The proposed risk prognostic signature and Nomogram based on TRRGs are novel promising tools for predicting therapy response and overall survival in HNSCC patients.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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