Treatment Of Nasopharyngeal Carcinoma Research Articles

Long-term outcomes of anlotinib and penpulimab combined with chemotherapy in the treatment of patients with metastatic nasopharyngeal carcinoma that failed definitive platinum-based chemoradiotherapy.

6040 Background: The median progression-free survival (mPFS) of anti-PD-1 monoclonal antibody (mAb) plus gemcitabine (G) and cisplatin (C) in the first-line treatment of metastatic nasopharyngeal carcinoma (M NPC) is still limited in about 10 ~12 months. The tolerance is also unfavorable, especially for patients (pts) who had undergone platinum-based chemoradiotherapy (CRT) previously. We performed a phase 2 study to explore the potency of replacing cisplatin with anloinib (A), a multi-kinase inhibitor in combined with penpulimab (P), a novel anti-PD-1 mAb as the first-line treatment of M NPC for pts with prior explosure of platinum-based CRT. Here we report the updated long term outcomes of this study. Methods: This is a prospective, three cohorts, single-arm study. Eligible pts were aged 18 ~ 75 years old, diagnosed with NPC and developed metastasis after platinum-based CRT. Pts who were diagnosed as having M NPC at the first visit or experienced treatment failure within 6 months after definitive CRT or adjuvant therapy were excluded. Pts were randomized to receive G + A + P (cohort GAP), G + C + A + P (cohort GCAP) or G+C+P (cohort GCP). Gemcitabine (1000mg/m2, d1, d8) and cisplatin (80mg/m2, d1) were given intravenously for 4 to 6 cycles, 3 weeks per cycle. Penpulimab (200mg, d1) and anlotinib (10mg, qd, d1-14) were given intravenously and orally respectively until disease progression, or unacceptable toxicities. The primary endpoint was objective response rate (ORR). Results: 21 pts were randomized to three cohorts in lead-in phase while only cohort GAP was selected into expansion phase to enrolled another 7 pts. Finally, totally 28 pts were enrolled and received study treatment. The data cutoff date was December 1, 2023. The median follow-up was 20.2 month (95% CI: 17.0, 23.4). The results were summered in the table below. In cohort GAP, the confirmed ORR was 92.3% (95% CI: 64.0%, 99.8%) and the mPFS was still not reached (95% CI: NE, NE). The most common Grade 3 treatment-related adverse event (TRAE) was neutrophil count decreased (3 pts). Only one patient occurred Grade 4 TRAE (neutrophil count decreased) and no treatment-related death was observed. Conclusions: The long term outcomes of this phase 2 study preliminarily disclosed the advantage of the treatment regimen including gemcitabine, anlotinib and penpulimab as the first-line treatment of M NPC, especially for pts who had exposed to platinum-based chemotherapy. The further study with more sample size is warranted. Clinical trial information: NCT04736810 . [Table: see text]

Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis.

e14612 Background: Treatment options for recurrent or metastatic nasopharyngeal carcinoma (NPC) are limited. Recently, the introduction of Immune Checkpoint Inhibitors (ICIs), either as single agents or combined with other treatment options, has emerged as a potential treatment for NPC. Hence, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICIs compared to standard chemotherapy. Methods: We systematically searched PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing ICIs versus standard chemotherapy in patients with NPC. The main outcomes were progression-free survival (PFS), overall survival (OS) and adverse events rate. All analyses used a random-effects model, with 95% confidence intervals (CIs) and were conducted on Review Manager 5.4. Results: A total of 1,188 patients from 5 RCTs were included, of which 634 (53.3%) received PD-1 inhibitors. In a pooled analysis of all studies, treatment with ICIs demonstrated a statistically significant benefit in OS (HR 0.73; 95% CI 0.61-0.87; p<0.01). In trials evaluating ICI monotherapy versus chemotherapy (617 patients), PFS was not significantly different between groups (p=0.91). However, pooling two studies evaluating ICI combined with chemotherapy vs. chemotherapy (541 patients) demonstrated higher PFS for the ICI group (HR 0.53; 95% CI 0.42-0.67; p<0.01). Overall pooled PFS was non-significant (HR 0.75; 95% CI 0.49-1.16; p=0.20). In all subgroup analyses, patients treated with ICI achieved greater PFS than chemotherapy: low EBV DNA level (HR 0.61; 95% CI 0.42-0.87; p=0.007) or high EBV DNA level (HR 0.44; 95% CI 0.35-0.56; p<0.01), without liver metastasis (HR 0.68; 95% CI 0.47-0.98; p=0.04), and with liver metastasis (HR 0.56; 95% CI 0.38-0.83; p=0.04). Moreover, ICIs were well tolerated and not associated with an increased risk of serious adverse events (HR 0.96; 95% CI 0.82-1.11; p=0.56). The frequency of hypothyroidism increased in the ICI group (HR 2.07; 95% CI 1.63-2.63; p<0.01). Other adverse events had similar rates in both groups, such as AST and ALT levels, diarrhea, pruritus, rash, stomatitis, and vomiting. Conclusions: This meta-analysis demonstrated that immune checkpoint inhibitors significantly enhanced overall survival without substantially increasing serious adverse events in patients with M/R NPC. Further studies are needed to identify the patients who benefit the most from ICI monotherapy or combination therapies. [Table: see text]

Influence of intensity-modulated radiation therapy on long-term survival and late injury in patients with nasopharyngeal carcinoma after induction chemotherapy.

e24048 Background: To retrospectively analyze the effect of nasopharyngeal primary tumor (GTVnx) target delineation after induction chemotherapy on the long-term survival and late injury of patients after intensity-modulated radiotherapy, so as to provide a reference for the optimal treatment of nasopharyngeal carcinoma. Methods: Retrospective analysis was performed on 52 patients with nasopharyngeal carcinoma who underwent target delineation and radiotherapy after induction chemotherapy in our department from December 2011 to October 2013. All patients underwent long-term survival follow-up and analysis of late injury. The survival rate was calculated by Kaplan-Meier method and log-rank test, Univariate prognostic analysis was performed. Cox model was used to conduct multivariate prognostic analysis. The late radiation toxicity was Evaluation by RTOG/EORTC. Results: From December 2011 to October 2013,52 patients were enrolled in the study group. The follow-up period was up to December 2020. Among them, 23 patients died and the mortality rate was 44.23%, the recurrence rate was 0.38%. Serious adverse reactions occurred in 7 cases (13.2%). The 1,3,5,8 year survival rates were as follows: OS was 94.2%, 82.7%, 65.4%, 49.6%, LRFS was 96.2%, 82.7%, 63.5%, 46.2%, the survival rates of DMFS were 94.2%, 78.8%, 59.6% and 44.2%. Conclusions: The 5 and 8-years OS, LRFS and DMFS of NPC after induction chemotherapy patients treated with IMRT was relatively high, Distant metastasis was the main cause of treatment failure, The main late injuries include grade Ⅰ / Ⅱ hearing impairment, dysphagia dental, caries, xerostomia, the grade Ⅲ and Ⅳ late radiation injury was lower.

Angiogenesis in nasopharyngeal carcinoma: insights, imaging, and therapeutic strategies.

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in southern China frequently diagnosed at advanced stages owing to subtle early symptoms and associated metastasis. Angiogenesis emerges as a pivotal factor in NPC progression, with numerous angiogenesis-related factors showing aberrant expression and contributing to increased neovascularization within NPC tumors. These abnormal vessels not only nourish tumor growth but also facilitate metastasis, culminating in unfavorable patient outcomes. Multiple studies have demonstrated the applicability of various imaging techniques for assessing angiogenesis in NPC tumors, thus serving as a foundation for personalized treatment strategies and prognostic assessments. Anti-angiogenic therapies have exhibited significant potential for inhibiting NPC angiogenesis and exerting anti-tumor effects. To enhance efficacy, anti-angiogenic drugs are frequently combined with other treatment modalities to synergistically enhance anti-tumor effects while mitigating the side effects associated with single-agent therapies, consequently improving patient prognosis. Identifying the potential mechanisms and key targets underlying NPC angiogenesis and exploring more effective detection and treatment approaches holds promise for shaping the future of NPC diagnosis, treatment, and prognosis, thereby offering new avenues and perspectives for research and clinical practice.

Novel prognostic biomarkers in nasopharyngeal carcinoma unveiled by mega-data bioinformatics analysis

Nasopharyngeal carcinoma (NPC) is commonly diagnosed at an advanced stage with a high incidence rate in Southeast Asia and Southeast China. However, the limited availability of NPC patient survival data in public databases has resulted in less rigorous studies examining the prediction of NPC survival through construction of Kaplan-Meier curves. These studies have primarily relied on small samples of NPC patients with progression-free survival (PFS) information or data from head and neck squamous cell carcinoma (HNSCC) studies almost without NPC patients. Thus, we coanalyzed RNA expression profiles in eleven datasets (46 normal (control) vs 160 tumor (NPC)) downloaded from the Gene Expression Omnibus (GEO) database and survival data provided by Jun Ma from Sun Yat-sen University. Then, differential analysis, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and network analysis were performed using STRING database. After that, 2142 upregulated differentially expressed genes (DEGs) and 3857 downregulated DEGs were screened. Twenty-five of them were identified as hub genes, which were enriched in several pathways (cilium movement, extracellular matrix structural constituent, homologous recombination and cell cycle). Utilizing the comprehensive dataset we amassed from GEO database, we conducted a survival analysis of DEGs and subsequently constructed survival models. Seven DEGs (RASGRP2, MOCOS, TTC9, ARHGAP4, DPM3, CD37, and CD72) were identified and closely related to the survival prognosis of NPC. Finally, qRT-PCR, WB and IHC were performed to confirm the elevated expression of RASGRP2 and the decreased expression of TTC9, CD37, DPM3 and ARHGAP4, consistent with the DEG analysis. Conclusively, our findings provide insights into the novel prognostic biomarkers of NPC by mega-data bioinformatics analysis, which suggests that they may serve special targets in the treatment of NPC.

Combining Mefloquine with an Mcl-1 Inhibitor as a Novel Therapeutic Strategy for the Treatment of Nasopharyngeal Carcinoma

Considering the established pharmacokinetics and toxicity profiles, drug repurposing has emerged as an alternative therapeutic approach for treating cancer. Mefloquine has previously demonstrated inhibitory effects on multiple cancer types. This study aims to explore the impact of mefloquine on nasopharyngeal carcinoma (NPC). We found that mefloquine, at pharmacologically achievable concentrations, displayed anti-NPC activity while sparing normal counterparts. Mefloquine inhibits proliferation and induces death by reducing the levels of Cyclin A2, Bcl-2, and Bcl-xL. Intriguingly, we observed an increase in the levels of the anti-apoptotic protein Mcl-1. Mefloquine exerts its effects on NPC cells by inducing lysosomal-mediated ROS production, and the heightened expression of Mcl-1 is a consequence of ROS generation in mefloquine-treated NPC cells. The combination of an Mcl-1 inhibitor with mefloquine synergistically inhibits NPC growth in mice without causing substantial toxicity. These findings demonstrate the effectiveness and limited toxicity of mefloquine as a monotherapy and in combination with an Mcl-1 inhibitor. Our research underscores the promise of the mefloquine and Mcl-1 inhibitor combination as a potential treatment for NPC. Additionally, the elevation of Mcl-1 is a compensatory response in cells exposed to oxidative stress, offering a potential target to overcome resistance induced by pro-oxidant therapies.

Isogarcinol inhibits nasopharyngeal carcinoma growth through mitochondria-mediated autophagic cell death

Background and aimsIsogarcinol, a natural compound extracted from the fruits of Garcinia oblongifolia, has potential chemopreventive activity. This study aimed to elucidate the anti-tumor effects and mechanism of action of isogarcinol on nasopharyngeal carcinoma (NPC). MethodsIsogarcinol was isolated from Garcinia oblongifolia by using chromatographic separation. The anti-tumor effects of isogarcinol in NPC cells were tested by MTT assay, flow cytometry, wound healing assay, western blotting, transwell assay, colony formation assay, immunofluorescence, and transmission electron microscopy (TEM). The anti-tumor efficacy in vivo was evaluated in NPC cells xenograft models. ResultsFunctional studies revealed that isogarcinol inhibited the proliferation, colony formation, migration and invasion abilities of NPC cells in vitro. Isogarcinol caused mitochondrial damage to overproduce reactive oxygen species through reducing the mitochondrial membrane potential and ΔΨm. Isogarcinol also substantially inhibited NPC cells growth in a xenograft tumor model without any obvious toxicity when compared with paclitaxel (PTX). Mechanistic studies have illustrated that isogarcinol increased the Bax/Bcl-2 ratio, cleaved caspase-3, and cytoplasmic cytochrome C levels to induce mitochondrial apoptosis. The ROS overproduction by isogarcinol could suppress EMT pathway via decreasing the levels of p-Akt and Snail. Furthermore, isogarcinol promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, but increased p62 level to block autophagic flux, resulting in the accumulation of damaged mitochondria to promote autophagic cell death in NPC cells. ConclusionThis study provides a new theoretical foundation for the anti-tumor application of Garcinia oblongifolia and confirms that isogarcinol could be developed as a candidate drug for NPC treatment with low toxicity.

Capsaicin enhances cisplatin-induced anti-metastasis of nasopharyngeal carcinoma by inhibiting EMT and ERK signaling via SERPINB2.

Cisplatin (DDP)-based combined chemotherapy or concurrent chemoradiotherapy is the mainstay treatment for advanced-stage nasopharyngeal carcinoma (NPC), but needs improvement due to its severe side effects. Capsaicin (CAP) can enhance the anti-tumor activity of cytotoxic drugs. The aim of this study was to investigate the anti-metastasis activity of CAP in combination with DDP in NPC. Herein, CAP and DDP showed synergistic cytotoxic effects on NPC cells. CAP alone and DDP alone inhibited NPC migration and invasion in vitro and in vivo, and the combination of CAP and DDP had the greatest effect. Moreover, CAP upregulated the mRNA and protein expressions of SERPINB2. Further results showed that both SERPINB2 mRNA and protein expressions were downregulated in NPC cell lines and tissues and SERPINB2 overexpression inhibited NPC migration and invasion in vitro and in vivo, while silencing SERPINB2 acted oppositely. In addition, SERPINB2 was abnormally expressed in head and neck squamous cell carcinoma (HNSC) and other multiple cancers and downregulation of SERPINB2 predicted poor prognosis in HNSC according to the Cancer Genome Atlas (TCGA) database. We further found that SERPINB2 overexpression inhibited epithelial-mesenchymal transition (EMT) and the phosphorylated ERK (p-ERK), and the inhibitory effect was enhanced by CAP and DDP. Altogether, our results suggest that the combined inhibition of CAP and DDP on NPC metastasis may be related to the inhibition of EMT and ERK signals mediated by SERPINB2, and CAP may help to improve the efficacy of DDP in the treatment of NPC and develop new therapeutic approaches.

Progress of Angiogenesis Signal Pathway and Antiangiogenic Drugs in Nasopharyngeal Carcinoma.

Nasopharyngeal cancer is a rare cancer with unique ethnic and geographic distribution. Since nasopharyngeal cancer often originates from the pharyngeal crypt, early symptoms are not obvious. They are difficult to detect in time, and the disease is usually diagnosed and treated only when it has progressed to an advanced-stage. Since angiogenesis is essential for the growth and invasion of solid tumors, antiangiogenic therapy has become a common treatment strategy for many solid tumors, and it has also achieved remarkable results in the treatment of nasopharyngeal carcinoma, which is prone to recurrence and distant metastasis. In this paper, we review the latest research progress of antiangiogenic drugs for nasopharyngeal carcinoma and their antiangiogenic mechanism of action and further propose some promising antiangiogenic therapeutic targets.

Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma.

Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.

The Role of PTEN in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.

Plasma Metabolic Profiles-Based Prediction of Induction Chemotherapy Efficacy in Nasopharyngeal Carcinoma: Results of a Bidirectional Clinical Trial.

The efficacy of induction chemotherapy (IC) as a primary treatment for advanced nasopharyngeal carcinoma (NPC) remains a topic of debate, with a lack of dependable biomarkers for predicting its efficacy. This study seeks to establish a predictive classifier utilizing plasma metabolomics profiling. A total of 166 NPC patients enrolled in the clinical trial NCT05682703 and undergoing IC were included in the study. Plasma lipoprotein profiles were obtained using 1H-NMR before and after IC treatment. An AI-assisted radiomics method was developed to effectively evaluate the efficacy. Metabolic biomarkers were identified through a machine learning approach based on a discovery cohort and subsequently validated in a validation cohort that mimicked the most unfavorable scenario in real-world. Our research findings indicate that the effectiveness of IC varies among individual patients, with a correlation observed between efficacy and changes in metabolite profiles. Utilizing machine learning techniques, it was determined that the XGB model exhibited notable efficacy, attaining an Area Under the Curve (AUC) value of 0.792 (95% CI, 0.668-0.913). In the validation cohort, the model exhibited strong stability and generalizability with an AUC of 0.786 (95%CI, 0.533-0.922). In this study, we found that dysregulation of plasma lipoprotein may result in resistance to IC in NPC patients. The prediction model constructed based on the plasma metabolites' profile as good predictive capabilities and potential for real-world generalization. This discovery has implications for the development of treatment strategies and may offer insight into potential targets for enhancing the effectiveness of IC.

Development and validation of a nomogram to predicting the efficacy of PD-1/PD-L1 inhibitors in patients with nasopharyngeal carcinoma.

With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed to develop a nomogram to evaluate the efficacy of anti-PD-1/PD-L1 in NPC patients. Totally 160 NPC patients were enrolled in the study. Patients were measured before the first PD-1/PD-L1 inhibitors treatment and after 8-12weeks of immunotherapy by radiological examinations to estimate the effect. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to screen hematological markers and establish a predictive model. The nomogram was internally validated by bootstrap resampling and externally validated. Performance of the model was evaluated using concordance index, calibration curve, decision curve analysis and receiver operation characteristic curve. Patients involved were randomly split into training cohort ang validation cohort. Based on Lasso logistic regression, systemic immune-inflammation index (SII) and ALT to AST ratio (LSR) were selected to establish a predictive model. The C-index of training cohort and validating cohort was 0.745 and 0.760. The calibration curves and decision curves showed the precise predictive ability of this nomogram. The benefit of the model showed in decision curve was better than TNM stage. The area under the curve (AUC) value of training cohort and validation cohort was 0.745 and 0.878, respectively. The predictive model helped evaluating efficacy with high accuracy in NPC patients treated with PD-1/PD-L1 inhibitors.

Targeted blocking of EGFR and GLUT1 by compound H reveals a new strategy for treatment of triple-negative breast cancer and nasopharyngeal carcinoma

BackgroundCytoplasmic epidermal growth factor receptor (EGFR) is overexpressed in both nasopharyngeal carcinoma (NPC) and triple-negative breast cancer (TNBC), while clinical outcome and prognosis vary greatly among patients treated with gefitinib, and all patients eventually develop resistance to this agent. Therefore, we propose a new concept for synthesizing multitarget compounds and reveal new therapeutic strategies for NPC and TNBC expressing EGFR. MethodsCompound H was synthesized in our previous study. Molecular docking, and cell thermal shift assays (CETSAs) and drug affinity responsive target stability(DARTS) were used to confirm the binding of compound H to EGFR and GLUT1. Methylthiazolyldiphenyl-tetrazolium bromide(MTT), annexin V-PE assays, mitochondrial membrane potential (MMP) assays, and animal models were used to evaluate the inhibitory effect of compound H on TNBC cell lines. Energy metabolism tests, Western blotting, and immunofluorescence staining were performed to evaluate the synergistic effects on EGFR- and glucose transporter type 1(GLUT1)-mediated energy metabolism. ResultsCompound H can simultaneously act on the EGFR tyrosine kinase ATP-binding site and inhibit GLUT1-mediated energy metabolism, resulting in reductions in ATP, MMP, intra-cellular lactic acid, and EGFR nuclear transfer. The anti-tumor activity of compound H is significantly superior to the combination of GLUT1 inhibitor BAY876 and EGFR inhibitor gefitinib. Compound H has remarkable anti-proliferative effects on TNBC MDA-MB231 cells, and importantly, no obvious toxicity effects of compound H were found in vivo. ConclusionsSynergistic effects of inhibition of EGFR- and GLUT1-mediated energy metabolism by compound H may present a new strategy for the treatment of TNBC and NPC.

MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a tumor that occurs in the nasopharynx. Although advances in detection and treatment have improved the prognosis of NPC the treatment of advanced NPC remains challenging. Here, we explored the effect of microRNA (miR)-122-5p on erastin-induced ferroptosis in NPC cells and the role of ferroptosis in the development of NPC. The effect of miR-122-5p silencing and overexpression and the effect of citrate synthase on erastin-induced lipid peroxidation in NPC cells was analyzed by measuring the amounts of malondialdehyde, Fe2+, glutathione, and reactive oxygen species and the morphological alterations of mitochondria. The malignant biological behavior of NPC cells was examined by cell counting kit-8, EDU, colony formation, Transwell, and wound healing assays. The effects of miR-122-5p on cell proliferation and migration associated with ferroptosis were examined in vivo in a mouse model of NPC generated by subcutaneous injection of NPC cells. We found that erastin induced ferroptosis in NPC cells. miR-122-5p overexpression inhibited CS, thereby promoting erastin-induced ferroptosis in NPC cells and decreasing NPC cell proliferation, migration, and invasion.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section.

Toripalimab plus chemotherapy in American patients with recurrent or metastatic nasopharyngeal carcinoma: A cost-effectiveness analysis.

Toripalimab, combined with gemcitabine and cisplatin, has been approved as the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), representing a significant milestone as the first FDA-approved innovative therapy for this condition. Despite this achievement, there's a lack of data on the cost-effectiveness of toripalimab for RM-NPC patients in the American context. To assess the cost-effectiveness of toripalimab plus chemotherapy versus chemotherapy alone, a 3-state partitioned survival model was constructed. The study involved participants with characteristics matching those in the JUPITER-02 trial. Cost and utility inputs were collected from literature. Main outcomes measured were quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Univariate and probabilistic sensitivity analyses, subgroup analyses, and scenario analyses were conducted to verify the robustness of results. The study found that the toripalimab regimen resulted in 4.390 QALYs at a cost of $361,813, while the chemotherapy-only regimen yielded 1.685 QALYs at a cost of $161,632. This translates to an ICER of $74,004/QALY, below the willingness-to-pay threshold of $150,000/QALY. Sensitivity analyses indicated that utility values, discount rate, and the price of toripalimab significantly impact INMB. With an 87.10% probability of being cost-effective at a $150,000/QALY threshold, the probabilistic sensitivity analysis supports toripalimab plus chemotherapy as a viable option. Scenario analysis showed that toripalimab remains cost-effective unless its price increases by 125%. Additionally, a simulated 15-year study period increases the ICER to $88,026/QALY. Subgroup analysis revealed ICERs of $76,538/QALY for PD-L1 positive and $70,158/QALY for PD-L1 negative groups. Toripalimab in combination with chemotherapy is likely to be a cost-effective alternative to standard chemotherapy for American patients with RM-NPC. This evidence can guide clinical and reimbursement decision-making in treating RM-NPC patients.

Deciphering the Prognostic Efficacy of MRI Radiomics in Nasopharyngeal Carcinoma: A Comprehensive Meta-Analysis.

This meta-analysis investigates the prognostic value of MRI-based radiomics in nasopharyngeal carcinoma treatment outcomes, specifically focusing on overall survival (OS) variability. The study protocol was registered with INPLASY (INPLASY202420101). Initially, a systematic review identified 15 relevant studies involving 6243 patients through a comprehensive search across PubMed, Embase, and Web of Science, adhering to PRISMA guidelines. The methodological quality was assessed using the Quality in Prognosis Studies (QUIPS) tool and the Radiomics Quality Score (RQS), highlighting a low risk of bias in most domains. Our analysis revealed a significant average concordance index (c-index) of 72% across studies, indicating the potential of radiomics in clinical prognostication. However, moderate heterogeneity was observed, particularly in OS predictions. Subgroup analyses and meta-regression identified validation methods and radiomics software as significant heterogeneity moderators. Notably, the number of features in the prognosis model correlated positively with its performance. These findings suggest radiomics' promising role in enhancing cancer treatment strategies, though the observed heterogeneity and potential biases call for cautious interpretation and standardization in future research.

PICK1 inhibits the malignancy of nasopharyngeal carcinoma and serves as a novel prognostic marker

Although many important advances have been made in the treatment of nasopharyngeal carcinoma (NPC) in recent years, local recurrence and distant metastasis remain the main factors affecting NPC prognosis. Biomarkers for predicting the prognosis of NPC need to be urgently identified. Here, we used whole-exon sequencing (WES) to determine whether PICK1 mutations are associated with the prognosis of NPC. Functionally, PICK1 inhibits the proliferation and metastasis of NPC cells both in vivo and in vitro. Mechanistically, PICK1 inhibited the expression of proteins related to the Wnt/β-catenin signaling pathway. PICK1 restrained the nuclear accumulation of β-catenin and accelerated the degradation of β-catenin through the ubiquitin-proteasome pathway. The reduced PICK1 levels were significantly associated with poor patient prognosis. Hence, our study findings reveal the mechanism by which PICK1 inactivates the Wnt/β-catenin signaling pathway, thereby inhibiting the progression of NPC. They support PICK1 as a potential tumor suppressor and prognostic marker for NPC.