Nasopharyngeal carcinoma (NPC) is sensitive to chemotherapy and radiotherapy, with current treatment recommendations largely based on TNM-stage. Radiotherapy remains the backbone of treatment for NPC. Over the past decades, the addition of concurrent chemotherapy to radiotherapy for early-stage disease, and the combination of induction chemotherapy (IC) or adjuvant chemotherapy (AC) with chemoradiotherapy vs chemoradiotherapy alone for advanced disease have led to substantial improvements in survival of patients with NPC. Nonetheless, in the era of precision oncology, there is growing recognition that patients with NPC are clinically heterogeneous even within the same stage-group, and future advances must focus on individualisation of systemic therapy and radiotherapy. In this review, we summarised the published evidence on EBV DNA as a biomarker for clinical stratification and treatment response in NPC, and discussed some of the ongoing clinical trials of EBV DNA-directed personalisation of systemic therapy in locoregionally-advanced disease. Next, we assessed the evidence concerning individualised radiotherapy strategies for target volume delineation of the primary tumour and cervical nodes that ought to be based on individual tumour extent and IC response (for locoregionally-advanced NPC) as opposed to the historical one-size fits all approach. In the same vein, radiotherapy dose de-escalation may be considered in good responders to IC, whereas for the poor responders, altered fractionation or dose escalation may be required to target resistant disease. These concepts are particularly relevant in the era of combinatorial immune checkpoint blockade therapy with radiotherapy, where preservation of circulating immune cells is crucial to evoke immune-mediated antitumour cytotoxicity.

Although the 5-year relative survival rates for resectable solid tumors have improved over the past few years, the risk of postoperative recurrence necessitates effective monitoring strategies. Recent advancements in molecular residual disease (MRD) testing based on circulating tumor DNA (ctDNA) analysis have shown considerable promise in the context of predicting recurrence; however, significant barriers to widespread clinical implementation remain-mainly, low awareness among healthcare professionals, high costs, and lack of standardized assays and comprehensive evidence. This position paper, led by the Japan Society of Clinical Oncology, aims to establish a common framework for the appropriate clinical use of MRD testing in a tumor type-agnostic manner. It synthesizes currently available evidence, reviews region-specific clinical trends, addresses critical clinical questions related to MRD testing, and offers recommendations to guide healthcare professionals, biotechnology and pharmaceutical companies, and regulatory authorities. These recommendations were developed based on a voting process involving 15 expert members, ensuring a consensus-driven approach. These findings underscore the importance of collaborative efforts among various stakeholders in enhancing the clinical utility of MRD testing. This project aimed to foster consensus and provide clear guidelines to support the advancement of precision medicine in oncology and improve patient outcomes in the context of perioperative care.

The optimal treatment strategy (radiotherapy with induction, concurrent or adjuvant chemotherapy) for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains to be addressed. Identifying biomarkers related to precise prognostic risk stratification and treatment benefits gained have been explored in recent years.

We carried out a systematic review of the published literature covering these topics. Of 3732 references screened, 26 articles were found eligible for inclusion.

Regarding the issue of treatment pathway in LA-NPC, induction chemotherapy is usually preferred over adjuvant chemotherapy. It is paramount to stress patient selection to identify those cases at high risk of relapse requiring systemic intensification. Concerning a role for Epstein-Barr virus (EBV) DNA-based personalized therapy, EBV DNA and its kinetics in plasma potentially represents a robust prognostic marker after (chemo)radiotherapy, but it is necessary to standardize test and cut-off levels.

This systematic review provides an overview of biomarker-guided systemic treatment designed to improve prognosis, including key aspects of current guidelines, biomolecular signature aspects and potential limitations between applicability to cancer treatment in endemic regions versus non-endemic regions.

To compare the performance of magnetic bead (MB) and the concentrated precipitation (CP) based RT-qPCR to qualify cell free EBV DNA (cfEBV DNA) for nasopharyngeal carcinoma (NPC) in non-endemic area of China. From January 2014 to June 2024, a retrospective analysis of 2 cohort studies on cfEBV DNA in NPC patients was conducted to assess the diagnostic value, positive detection rate and clinical application. cfEBV DNA detection with CP based RT-qPCR in cohort 1 and MB based RT-qPCR method in cohort 2. The MB based RT-qPCR for the quantitative measurement of cfEBV DNA load was higher than the CP based RT-qPCR in the same plasma samples from NPC patients (P < 0.001). CP based RT-qPCR measured cfEBV DNA in 1405 NPC and 244 healthy controls in cohort 1 with 40.8% sensitivity (AUC = 0.704, 95% CI: 0.676-0.731). In cohort 2(683 naive NPC and 303 controls), cfEBV DNA had a sensitivity of 75.84% (AUC = 0.879, 95% CI: 0.86-0.90). There were no significant differences in TNM stage among NPC between the two cohorts (P > 0.05). The MB method considerably increased the positive detection rate of cfEBV DNA in NPCs at stages III-IV, T2-T4, N1-N3, and M0 (P < 0.001). At the end of treatment, 97.51% of patients had no detectable EBV and just 2.49% had detectable cfEBV DNA. Those who received ≤ 2 or ≥ 3 cycles of NAC had a median t1/2 clearance rate of 9.8 days and 12.6 days, respectively. MB based RT-qPCR increased the quantity of cfEBV DNA. MB based RT-qPCR demonstrated superior sensitivity and positive detection rates for cfEBV DNA. cfEBV DNA can be more positively noticed, with a higher diagnostic value and a broader variety of clinical applications among NPC in non-endemic areas.

Approximately 20% to 30% of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) experience disease relapse despite definitive chemoradiotherapy. The programmed cell death 1 (PD-1) blockade camrelizumab has demonstrated considerable value in recurrent or metastatic NPC, while its role in locoregionally advanced NPC is unclear.

To evaluate the efficacy and safety of adjuvant camrelizumab for patients with locoregionally advanced NPC.

Randomized, open-label, multicenter, phase 3 clinical trial conducted from August 2018 to November 2021 at 11 centers in China and enrolling 450 patients with T4N1M0 or T1-4N2-3M0 NPC who had completed induction-concurrent chemoradiotherapy. The final date of follow-up was March 20, 2024.

Patients were randomized (1:1) to receive adjuvant camrelizumab (200 mg intravenously once every 3 weeks for 12 cycles; n = 226) or observation (standard therapy group; n = 224).

The primary end point was event-free survival (freedom from distant metastasis, locoregional relapse, or death due to any cause). Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, safety, and health-related quality of life.

Among the 450 participants (mean age, 45 [SD, 10] years; 24% women), after a median follow-up of 39 (IQR, 33-50) months, the camrelizumab group had a 3-year event-free survival rate of 86.9%, whereas the standard therapy group had a rate of 77.3% (stratified hazard ratio, 0.56; 95% CI, 0.36-0.89; P = .01). Grade 3 or 4 adverse events were reported in 23 patients (11.2%) in the camrelizumab and 7 (3.2%) in the standard therapy group. Reactive capillary endothelial proliferation was the most common adverse event related to camrelizumab, occurring in 85.8% of patients at grade 1 or 2, while 2% of patients had grade 3 or 4 events. There was no significant deterioration in quality of life associated with camrelizumab treatment.

Adjuvant PD-1 blockade with camrelizumab significantly improved event-free survival with manageable toxicities, highlighting its potential role in the management of locoregionally advanced NPC.

ClinicalTrials.gov Identifier: NCT03427827.

Difficulties in microbiologically confirming childhood tuberculosis (TB) can result in delayed treatment and increased disease severity.

In this study, we for the first time used whole genome next-generation sequencing (NGS) to detect cell-free DNA (cfDNA) from Mycobacterium tuberculosis (MTB) in plasma from children.

We enrolled 94 children with active TB and 32 children with other respiratory infections. Combining NGS with probe capture enrichment (targeted cfNGS) showed higher coverage and detecting capability than did NGS alone. The targeted cfNGS showed slightly lower sensitivity (31.9% vs. 44.7%, P = 0.072) and specificity (96.9% vs. 100.0%, P = 0.236) to those of sputum tested using Xpert. Agreement between cfNGS-plasma and Xpert-sputum was weak (κ = 0.217). Concordant results were obtained for only 85 children (67.5%; 16 cases positive by both tests and 69 cases negative by both tests). A total of 40 children with MTB culture negative results were tested to have positive cfNGS-plasma or Xpert-sputum outcomes, yielding a significantly increased percentage of children with bacteriological evidence (20.2% [19/94] for MTB culture-positive only vs. 62.8% [59/94] for cfNGS-plasma, Xpert-sputum or culture positive).

These data suggest that cfNGS performed well for diagnosing TB using plasma from children. cfNGS may be a new method for diagnosing patients with paucibacillary TB.

Plasma circulating tumor HPV DNA (ctHPVDNA) persistence after curative-intent treatment may identify patients with HPV-positive cancers at risk for recurrence. Technical validation is required for use as an integral biomarker in a prospective clinical trial.

Development and analytical validation of a digital droplet PCR assay for detection and quantification of 13 high-risk HPV types (i.e., Cell-Free 13) was performed with oligonucleotides/plasmids encoding type-specific E6/E7 coding regions. Clinical performance, determinants of detection/quantification, and associations of pre-treatment ctHPVDNA with progression-free survival (PFS) were also evaluated in a prospective cohort of 272 head and neck cancer patients.

Limit of detection, limit of quantification, and linear range of quantification were 5, 16 and 16-200,000 virus copies for all 13 high-risk HPV types. No cross-reactivity was detected across all 13 HPV types. At 10,000 copies, inter-assay coefficients of variation ranged from 0.3 to 4.6%. Multiplexing, DNA purification method, input plasma volume, total input cell-free (< 1800 ng) or genomic (< 700 ng) DNA did not affect HPV detection or quantification. The assay had a sensitivity of 91.7% (95%CI 87.3-94.9%) and specificity of 97.7% (95%CI 87.7-99.9%) for ctHPVDNA detection in the setting of newly diagnosed HPV-positive oropharyngeal cancer. Tumor and nodal stage categories, tumor viral load (ρ = 0.41, p < 0.05), and HPV integration status were associated with ctHPVDNA quantitative level. Pre-treatment ctHPVDNA greater than the median (231 copies/ml) was associated with worse PFS (HR = 2.14, 95%CI 1.16-3.97, p = 0.0156) in univariate analysis. However, this was no longer significant after adjustment for clinical covariates (HRadj = 1.81, 95%CI 0.97-3.37, p = 0.0635).

Cell-Free 13 demonstrated excellent analytical performance and clinical sensitivity/specificity in HPV-positive oropharyngeal cancer. Pre-treatment ctHPVDNA may be associated with oncologic outcomes.

Neutrophil-to-lymphocyte ratio (NLR) can be treated as a simple indicator of patients' immune status by representing the state of the systemic inflammatory response. Immunotherapy now is the accepted second-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the significance of NLR in patients with R/M NPC undergoing treatment with PD-L1 (programmed cell death-ligand 1) inhibitors is still uncertain.

We analyzed the relationship between baseline NLR with 153 patients' efficacy and survival from a multicenter, prospective, Phase 2 study. We employed restricted cubic spline plots to get the nonlinear relationship between NLR and progression-free survival (PFS) or overall survival (OS). We identified the ideal cut-off value through the analysis of the receiver operating characteristic curve (ROC curve). We used Logistic regression, Cox regression, Log-rank test, and Kaplan-Meier method to analyze the association between NLR and patients' disease control rate (DCR) and PFS or OS.

The ideal threshold value for NLR was 2.826. NLR was identified as a significant independent predictor of DCR (OR = 0.17, 95% CI = 0.05-0.48, p = 0.001), indicating that a higher NLR is associated with worse DCR. NLR (AUC = 0.634) showed superior predictive capability for DCR in comparison to lymphocytes (AUC = 0.602) and neutrophils (AUC = 0.593). High NLR values were risk factors both for poor PFS (HR = 2.53, 95% CI = 1.58-4.06, p < 0.001) and OS (HR = 3.89, 95% CI = 2.09-7.24, p < 0.001).

Elevated NLR is strongly associated with lower response to treatment and reduced survival rates in patients with R/M NPC being treated with PD-L1 inhibitors. Patients with high NLR values have poor efficacy and survival.

Rapid and sensitive detection of Epstein-Barr virus cell-free DNA (EBV cfDNA) is crucial for early diagnosis and monitoring of nasopharyngeal carcinoma (NPC), but accessibility to screening is limited by complicated and costly conventional DNA isolation and purification approaches. Here, a fully integrated ion concentration polarization (ICP)-enriched and nanozyme-catalyzed lateral flow assay (ICP-cLFA) is developed, enabling total analysis of EBV cfDNA in whole blood samples, with DNA isolation, pre-concentration, and amplification performed on a microfluidic chip, consequently providing the signal readout within 75 min. Specifically, ICP preconcentration and amplification steps, together with target recognition catalyzed by a platinum-decorated mesoporous gold nanosphere (MGNS@Pt) nanozyme, result in an ultralow detection limit of 4 aM in standard cfDNA samples and 100 aM in whole blood from NPC-bearing rats. The high sensitivity and specificity of the ICP-cLFA suggest strong potential for cfDNA screening in resource-limited clinical and field applications.

Epstein-Barr virus (EBV), the first human oncovirus discovered in 1964, has become a focal point in virology, immunology, and oncology because of its unique biological characteristics and significant role in human diseases. As we commemorate the 60th anniversary of EBV's discovery, it is an opportune moment to reflect on the major advancements in our understanding of this complex virus. In this review, we highlight key milestones in EBV research, including its virion structure and life cycle, interactions with the host immune system, association with EBV-associated diseases, and targeted intervention strategies.

Recent advancements in wearable electrochemical biosensors have opened new avenues for on-body and continuous detection of biomarkers, enabling personalized, real-time, and preventive healthcare. While glucose monitoring has set a precedent for wearable biosensors, the field is rapidly expanding to include a wider range of analytes crucial for disease diagnosis, treatment, and management. In this review, recent key innovations are examined in the design and manufacturing underpinning these biosensing platforms including biorecognition elements, signal transduction methods, electrode and substrate materials, and fabrication techniques. The applications of these biosensors are then highlighted in detecting a variety of biochemical markers, such as small molecules, hormones, drugs, and macromolecules, in biofluids including interstitial fluid, sweat, wound exudate, saliva, and tears. Additionally, the review also covers recent advances in wearable electrochemical biosensing platforms, such as multi-sensory integration, closed-loop control, and power supply. Furthermore, the challenges associated with critical issues are discussed, such as biocompatibility, biofouling, and sensor degradation, and the opportunities in materials science, nanotechnology, and artificial intelligence to overcome these limitations.

Cancer has consistently been the leading cause of death worldwide, with head and neck cancer (HNC) being one of the top ten causes of cancer-related death. Nasopharyngeal carcinoma (NPC), in particular, is a cancer that is unique to East Asia. Numerous studies have shown that the Epstein-Barr virus (EBV) DNA load and the systemic immune inflammation (SII) index can serve as prognostic indicators for NPC patients. However, no studies have compared different predictive models of inflammatory factors. This study combines the SII and the EBV virus load in patients with stage I to IV NPC and compares different inflammatory factor models to determine the best predictive model.

We reviewed 240 patients with stage I to IV NPC who were diagnosed between January 2016 and July 2023. We collected data from adult patients who were diagnosed with NPC and included those who completed the definitive staging workup and treatment in this analysis. We tested various inflammatory markers and the EBV DNA load via Cox regression for survival analysis.

We found that the EBV viral load, the SII, and the SIRI are related to the severity of nasopharyngeal cancer. In the univariate Cox regression analysis, clinical stage, EBV virus load (HR: 2.15, 95 % CI: 1.19-3.90), NLR (2.37, 1.29-4.34), PLR (2.7, 1.06-6.87), SIRI (2.02, 1.11-3.68), and SII (2.45, 1.251-4.89) were prognostic factors for overall survival. In the multivariate analysis, after adjusting for sex, age and clinical stage, a higher EBV virus load and SII were associated with a worse prognosis (HR: 4.71, 1.95-11.41).

The combination of the EBV viral load and the SII was a better predictor of NPC prognosis.

To investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention.

950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures.

Tumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation.

The earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein-Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant-adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

This randomised, single-centre, double-blind, placebo-controlled, phase 2 trial was conducted at Sun Yat-sen University Cancer Centre in Guangzhou, China. Adult patients (aged 18-65 years) with newly diagnosed high-risk stage III-IVa locoregionally advanced nasopharyngeal carcinoma, with a pretreatment plasma EBV DNA concentration of at least 1500 copies per mL and an Eastern Cooperative Oncology Group performance score of 0-1, were eligible. Patients were randomly assigned (2:1) using an interactive web response system (block size of six), stratified by TNM stage (III vs IVa), to neoadjuvant toripalimab (240 mg intravenously) or placebo once every 2 weeks for two cycles, followed by concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy and adjuvant toripalimab (240 mg intravenously) or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival in the intention-to-treat population. This study was registered with ClinicalTrials.gov, NCT03925090, and is closed to enrolment; follow-up is ongoing.

Between Dec 6, 2019, and Dec 9, 2021, 150 patients were enrolled and randomly assigned to the toripalimab group (n=100) or placebo group (n=50). 115 (77%) patients were male and 35 (23%) were female. As of data cutoff (May 31, 2024), median follow-up for progression-free survival was 37·8 months (IQR 34·2-46·5) for the intention-to-treat population analyses. 2-year progression-free survival was higher in the toripalimab group (92·0% [95% CI 86·7-97·3]) than in the placebo group (74·0% [61·8-86·2]; stratified hazard ratio 0·40 [95% CI 0·18-0·89]; log-rank p=0·019). The most common grade 3 or worse acute adverse events (occurring within 1 year of randomisation) were leukopenia (40 [40%] of 99 patients in the toripalimab group vs 22 [44%] of 50 patients in the placebo group), mucositis (28 [28%] vs ten [20%]), neutropenia (17 [17%] vs nine [18%]), anaemia (16 [16%] vs five [10%]), and weight loss (12 [12%] vs six [12%]). The most common grade 3 or worse late adverse events (occurring >1 year after randomisation) was auditory or hearing loss (eight [8%] vs four [8%]). Immune-mediated adverse events of grade 3 or worse occurred in ten (10%) patients only in the toripalimab group. One (2%) of 50 patients in the placebo group died due to septic shock caused by bacteraemia considered not treatment related. There were no treatment-related deaths in the toripalimab group.

Our findings suggested that a so-called sandwich approach involving toripalimab (in the neoadjuvant and adjuvant phases) combined with concurrent chemoradiotherapy could be a highly promising therapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Phase 3 non-inferiority trials are warranted comparing neoadjuvant and adjuvant toripalimab versus cisplatin plus gemcitabine neoadjuvant chemotherapy combined with concurrent chemoradiotherapy.

National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Science and Technology Program of Guangzhou, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Postdoctoral Innovative Talent Support Program, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, and Fundamental Research Funds for the Central Universities.

For the Chinese translation of the abstract see Supplementary Materials section.

Induction chemotherapy (IC) before concurrent chemoradiotherapy does not universally improve long-term overall survival (OS) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Conventional risk stratification often yields suboptimal IC decisions. Our study introduces a ternary classification of predicted individual treatment effect (PITE) to guide personalized IC decisions.

A two-center retrospective analysis of 1,213 patients with LANPC was conducted to develop and validate prognostic models integrating magnetic resonance imaging and clinical data to estimate individual 5-year OS probabilities for IC and non-IC treatments. Differences in these probabilities defined PITE, facilitating patient stratification into three IC recommendation categories. Model effectiveness was validated using Kaplan-Meier estimators, decision curve-like analysis, and evaluations of variable importance and distribution.

The models exhibited strong predictive performance in both treatments across training and cross-validation sets, enabling accurate PITE calculations and patient classification. Compared with non-IC treatment, IC markedly improved OS in the IC-preferred group (HR = 0.62, p = 0.02), had no effect in the IC-neutral group (HR = 1.00, p = 0.70), and worsened OS in the IC-opposed group (HR = 2.00, p = 0.03). The ternary PITE classification effectively identified 41.7 % of high-risk patients not benefiting from IC, and yielded a 2.68 % higher mean 5-year OS probability over risk-based decisions. Significantly increasing distributions of key prognostic indicators, such as metastatic lymph node number and plasma Epstein-Barr virus DNA level from IC-opposed to IC-preferred groups, further validated the clinical relevance of PITE classification.

The ternary PITE classification offers an accurate and clinically advantageous approach to guide personalized IC decision-making in patients with LANPC.

Circulating tumour DNA (ctDNA) has emerged as a valuable liquid biopsy biomarker in the field of oncology, including head and neck squamous cell carcinomas (HNSCCs), offering potential insights into cancer diagnosis, progression, and prognosis. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in HNSCC.

PubMed and Ovid were searched as part of our review. Studies that investigated the relationship between ctDNA and prognosis in HNSCC patients were included. Outcomes extracted included basic characteristics, ctDNA details and survival data. Meta-analysis was performed on eligible studies to determine pooled progression-free/recurrence-free survival (RFS/PFS) and overall survival (OS).

Twenty-two studies were included, involving 5062 HNSCC patients from 11 countries. The meta-analysis demonstrated that the positive ctDNA/methylation detection was associated with worse OS (HR = 2.00, 95% CI 1.35-2.96) and worse PFS/RFS (HR = 3.54, 95% CI 1.05-11.85). Positive ctEBV DNA was associated with poorer OS (HR = 2.86, 95% CI 1.84-4.45) and poorer PFS/RFS (HR = 1.93, 95% CI 1.74-2.13). Positive ctHPV DNA was associated with poorer OS (HR = 1.38, 95% CI 1.07-1.38) but not PFS/PFS (HR = 1.33, 95% CI 0.96-1.85).

Meta-analysis indicates that the status of ctDNA is significantly associated with the prognosis of HNSCC patients, with ctDNA/methylation-negative patients demonstrating better PFS/RFS and OS.

This study aimed to explore the selection of induction chemotherapy (IC) cycles for stage N3 nasopharyngeal carcinoma (NPC). We employed propensity score matching (PSM) to categorize patients into 3-cycle and 4-cycle IC groups (IC = 3 and IC = 4). The log-rank and chi-squared tests were used respectively to evaluate the differences in survival and acute toxicities. Survival outcomes including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were evaluated among the two groups. After PSM, each group comprised 99 patients. The IC = 4 group exhibited markedly improved survival outcomes compared with the IC = 3 group. Multivariate analysis revealed that pre-EBV DNA was an independent risk factor affecting PFS and DMFS. For high-risk patients with pre-EBV DNA ≥ 7800 copies/ml, the IC = 4 group demonstrated greater survival compared to the IC = 3 group. Among low-risk patients with pre-EBV DNA < 7800 copies/ml, both groups showed comparable survival outcomes. In terms of acute adverse reactions, the IC = 4 group experienced higher incidences, particularly with grade 2-4 alanine transaminase elevation and thrombocytopenia. For stage N3 NPC, pre-EBV DNA could be a powerful predictor for guiding the selection of IC cycles. The IC = 4 regimen is probably more beneficial to high-risk patients due to superior survival, while for low-risk patients, the IC = 3 regimen may be sufficient.

This study aimed to investigate the clinical benefit of adding concurrent chemotherapy to intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients with an intermediate risk (stage II and T3N0M0).

A multicenter phase II randomized trial was conducted in intermediate-risk NPC patients. Enrolled patients were previously untreated and aged ranged from 18 to 70 years without severe coexisting diseases. Patients were randomly assigned to receive IMRT alone or IMRT+concurrent chemotherapy (CC; three cycles of 80 mg/m2 cisplatin every 3 weeks). Primary endpoint was defined as 3‑year progression-free survival (PFS). The secondary endpoints were distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRRFS), overall survival (OS), and treatment-associated toxicity. We registered this study with Chinese Clinical Trial Registry (CliCTR1800017132; registered July 13, 2018, study start July 13, 2018).

From November 2015 to July 2019, 42 patients with stage II and T3N0M0 NPC were enrolled; 20 patients received IMRT alone while 22 patients received IMRT+CC. After a median of 58 months of follow-up, we estimated the 3‑year PFS rates as 90% (IMRT group) and 86.4% (IMRT+CC group; hazard ratio 1.387, 95% confidence interval 0.240-8.014; P = 0.719). The 3‑year PFS, OS, and cumulative DMFS and LRRFS showed no significant differences between the two groups (P > 0.05). However, the IMRT group displayed a lower incidence of nausea/vomiting, leucopenia, and dry mouth than the IMRT+CC group.

Adding CC to IMRT provided no survival benefit but increased treatment-associated toxicities in patients with intermediate-risk NPC.

Serum biomarkers have a significant impact on the prediction of treatment outcomes in patients diagnosed with nasopharyngeal carcinoma (NPC). The primary aim of this study was to develop and validate a nomogram that incorporates hemoglobin, albumin, and globulin ratio (HAGR) and clinical data to accurately forecast treatment outcomes in patients with NPC.

A total of 796 patients diagnosed with NPC were included in the study.

The results of the multivariate Cox analysis revealed that TNM stage and HAGR were found to be significant independent prognostic factors for OS and PFS. Furthermore, the utilization of the nomogram demonstrated a significant improvement in the evaluation of OS, PFS compared with the eighth TNM staging system. Additionally, the implementation of Kaplan-Meier curves and decision curve analysis curves further confirmed the discriminability and clinical effectiveness of the nomogram.

The HAGR, an innovative prognostic factor grounded in the realm of immunonutrition, has emerged as a promising prognostic marker for both OS and PFS in individuals afflicted with NPC.

Modern cancer research depends heavily on the identification and validation of biomarkers because they provide important information about the diagnosis, prognosis, and response to treatment of the cancer. This review will provide a comprehensive overview of cancer biomarkers, including their development phases and recent breakthroughs in transcriptomics and computational techniques for detecting these biomarkers. Blood-based biomarkers have great potential for non-invasive tumor dynamics and treatment response monitoring. These include circulating tumor DNA, exosomes, and microRNAs. Comprehensive molecular profiles are provided by multi-omic technologies, which combine proteomics, metabolomics, and genomes to support the identification of biomarkers and the targeting of therapeutic interventions. Genetic changes are detected by next-generation sequencing, and patterns of protein expression are found by protein arrays and mass spectrometry. Tumor heterogeneity and clonal evolution can be understood using metabolic profiling and single-cell studies. It is projected that the use of several biomarkers-genetic, protein, mRNA, microRNA, and DNA profiles, among others-will rise, enabling multi-biomarker analysis and improving individualised treatment plans. Biomarker identification and patient outcome prediction are further improved by developments in AI algorithms and imaging techniques. Robust biomarker validation and reproducibility require cooperation between industry, academia, and doctors. Biomarkers can provide individualized care, meet unmet clinical needs, and enhance patient outcomes despite some obstacles. Precision medicine will continue to take shape as scientific research advances and the integration of biomarkers with cutting-edge technologies continues to offer a more promising future for personalized cancer care.

This study elucidates the intricate relationship between nasopharyngeal carcinoma (NPC), a significant malignancy predominant in Asia with notable global incidence and mortality rates, and the host microbiota, including those of tumour, nasal, nasopharyngeal, oral, oropharyngeal, and gut communities. It underscores how the composition and diversity of microbiota are altered in NPC, delving into their implications for disease pathogenesis, treatment response, and the side effects of therapies. A consistent reduction in alpha diversity across oral, nasal, and gut microbiomes in NPC patients compared to healthy individuals signals a distinct microbial signature indicative of the diseased state. The study also shows unique microbial changes tied to different NPC stages, indicating a dynamic interplay between disease progression and microbiota composition. Patients with specific microbial profiles exhibit varied responses to chemotherapy and immunotherapy, underscoring the potential for treatment personalisation based on microbiota analysis. Furthermore, the side effects of NPC treatments, such as oral mucositis, are intensified by shifts in microbial communities, suggesting a direct link between microbiota composition and treatment tolerance. This nexus offers opportunities for interventions aimed at modulating the microbiota to alleviate side effects, improve quality of life, and potentially enhance treatment efficacy. Highlighting the dual potential of microbiota as both a therapeutic target and a biomarker for NPC, this review emphasises its significance in influencing treatment outcomes and side effects, heralding a new era in NPC management through personalised treatment strategies and innovative approaches.

To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC).

A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve.

Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort.

The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.

Nasopharyngeal carcinoma (NPC), a rare form of squamous cell carcinoma originating from the nasopharynx epithelium, exhibits a higher prevalence in southern China, Southeast Asia, the Arctic, North Africa, and the Middle East, with significant incidence in northeastern India, particularly Nagaland. Commonly presenting with nasal and otological symptoms, NPC diagnosis is challenging due to its diverse clinical manifestations. This case report highlights two atypical NPC cases: a 32-year-old female presenting with chronic headache and giddiness and a 22-year-old male with severe right-sided facial pain and trismus. Both cases underwent extensive diagnostic procedures, including imaging and biopsies, ultimately confirming NPC. Treatment involved radiotherapy and chemotherapy, resulting in significant symptom improvement. These cases underscore the importance of recognizing unusual NPC presentations to facilitate early diagnosis and treatment, improving patient outcomes.

Nasopharyngeal carcinoma (NPC), arising from nasopharyngeal epithelium is caused by Epstein-Barr virus (EBV). It is common in South China, South East Asia and North East India. The aim and objectives of this study were to determine the prevalence of EBV in formalin-fixed paraffin-embedded (FFPE) tissue sections of clinically suspected NPC patients, correlate the results of polymerase chain reaction (PCR) with histopathology findings, and to determine the utility of tissue EBV DNA as a diagnostic bio-marker.

31 FFPE tissue samples were collected from clinically suspected NPC patients from April 2018-December 2019. Histopathological diagnosis was done by examination of Hematoxylin and Eosin stained slides. Presence of EBV was detected by EBNA-1 PCR. IHC was performed using EBV Latent Membrane Protein 1.

Of the 31 clinically suspected NPC cases, 15 (48.4 %) were histopathological confirmed NPC. Of these15, 13 (86.6 %) were non-keratinising undifferentiated NPC, and one each were keratinising NPC and non-keratinising differentiated NPC respectively. EBV EBNA1 PCR was positive in 35.5 % (11/31) of clinically suspected NPC cases. Of the 11 PCR positive cases, 9 (81.8 %) were histopathological confirmed NPC. Of the 31 clinically suspected NPC cases, IHC was indicated in 23 biopsies. Of which, 12 (52.2 %) were positive for LMP1 in the abnormal cells. Of the 12 IHC positive samples, 10 were NPC cases.

EBV DNA as an indicator towards NPC among clinically suspected cases had a sensitivity of 60 % and specificity of 87.5 %. In this study, addition of EBV DNA detection by PCR from FFPE tissue sections could confirm EBV association in 20 % of cases where it was not detected by EBV LMP1 IHC, thus helped in increasing the detection of EBV positivity in NPC cases. Early diagnosis of NPC will improve the cure rate and hence reduce the morbidity and mortality rates.

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.

The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma.

This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis.

The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups.

A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients.

To evaluate the prognostic significance of platelet distribution width-to-lymphocyte ratio (PDWLR) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Moreover, a nomogram based on PDWLR was built and validated to predict the overall survival (OS) of this population.

All LA-NPC patients who were diagnosed and treated between January 2015 and December 2017 at Guangxi Medical University Cancer Hospital were included. Cox regression analyses were performed to assess PDWLR and clinical features that might affect OS to screen for independent predictors. The independent predictors and important clinical variables were used to build and validate a nomogram for predicting OS. Then, the capability of the model was estimated by discrimination, calibration and clinical usefulness. Risk stratification was conducted using the nomogram-calculated risk score, and the comparison of survival in the high-risk group and the low-risk group was through Kaplan-Meier method.

This study included 746 LA-NPC patients. Multivariate Cox analysis suggested that age (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.18-2.78, P = 0.007), gender (HR: 2.03, 95% CI: 1.12-3.68, P = 0.019), pre-treatment plasma Epstein-Barr virus (EBV) DNA (HR: 1.55, 95% CI: 1.01-2.39, P = 0.047), PDWLR (HR: 2.61, 95% CI: 1.67-4.09, P < 0.001) were independent predictors of OS. Compared to the 8th edition TNM staging system, the nomogram based on the above four factors and important clinical variables (T stage and N stage) demonstrated better predictive performance. Moreover, the model had the ability to identify individuals at high risk.

PDWLR was a promising negative predictor for patients with LA-NPC. The nomogram based on PDWLR demonstrated better predictive performance than the current staging system.

This study aims to assess the current research status, focus areas, and developmental trends in nasopharyngeal carcinoma (NPC) through a bibliometric analysis.

Articles focusing on NPC published from 2000 to 2023 were retrieved from the Web of Science database. VOSviewer and CiteSpace were used for bibliometric and visual analysis.

A total of 14516 related publications were retrieved. There has been a steady increase in the number of NPC-related publications from 2000 to 2023. China was the dominant country in this field with 8948 papers (61.64%), followed by the USA (2234, 15.39%). Sun Yat-sen University was the most influential institution, while Ma J was the most prolific author. Furthermore, Head And Neck-journal For The Sciences And Specialties Of The Head And Neck was the most prolific journal. International Journal of Radiation Oncology Biology Physics had the highest total citation counts. "Introduction chemotherapy", "Concurrent chemotherapy", "Epithelial-mesenchymal transition", "Cancer stem cells", "MicroRNAs", "LncRNA", "Exosomes", and "Biomarker" were the most common keywords. The reference "Chen YP, 2019, Lancet" had the highest citations and strong outbreak value.

The past two decades have witnessed a significant increase in research on NPC. The optimization of treatment mode is the most widely studied aspect at present. The mechanism of occurrence and development and the most favorable diagnostic and therapeutic targets are the research hotspots in the future.

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.

Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an inborn error of immunity that manifests as immune deficiency and dysregulation; symptoms include frequent infections and lymphoproliferation. In our dose-finding and phase 3 placebo-controlled trials, treatment with the selective PI3Kδ inhibitor leniolisib reduced lymphoproliferation and normalized lymphocyte subsets. Here, we present 6 years of follow-up from the 6 adult patients in the original dose-finding trial receiving leniolisib. We used data from the ongoing open-label extension study, which was supplemented at later time points by investigators, including health-related quality of life (HRQoL) assessed through a clinician-reported questionnaire. We observed improvements in HRQoL: 5 of 6 patients experienced an increase in physical capabilities and socialization, and a decrease in prescribed medications. Immune subsets improved in all patients: mean transitional B-cell levels decreased from 38.17% to 2.47% and the CD4:CD8 T-cell ratio normalized to 1.11. Manifestations seen before and within the first year of leniolisib exposure, such as infections and gastrointestinal conditions, attenuated after year 2, with few new conditions emerging out to year 6. Thrombocytopenia or lymphopenia remained present in half of patients at year 6. Of 83 adverse events through year 5, 90.36% were grade 1; none were grade 4/5 nor deemed leniolisib related. Collectively, we saw an enhancement in HRQoL as well as durable changes in lymphocyte subsets and clinical manifestations, further supporting the use of leniolisib as a long-term therapeutic option for the treatment of APDS. This trial was registered at www.ClinicalTrials.gov as #NCT02859727.