Whether PD-L1/PD-1 expression plays a significant role in the prognosis of NPC is still controversial. The present study mainly aimed to investigate the prognostic significance of PD-L1/PD-1 expression in patients with NPC. A systematical research was performed in the PubMed, Web of Science, EMBASE, and the Cochrane Library databases up to January 06, 2019. Eighteen studies met eligible criteria were included in the meta-analysis. Quality assessment of included articles was evaluated by Newcastle–Ottawa quality assessment scale (NOS). Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were used to elucidated the primary endpoint, overall survival (OS), and the secondary endpoints. Furthermore, the relationship between clinicopathological features of NPC and PD-L1/PD-1 expression was estimated by relative ratios (RRs) and 95% CIs. A total of 1836 patients from 15 included studies concerning PD-L1 and 678 patients from six studies regarding PD-1 were included in the meta-analysis. Pooled results revealed that PD-L1 expression in NPC did not correlate with OS (HR 1.34 95% CI 0.93–1.93, p = 0.11), DFS (HR 1.82, 95% CI 0.86–3.85, p = 0.12), PFS (HR 1.19, 95% CI 0.46–3.08, p = 0.72), and DMFS (HR 2.26, 95% CI 0.60–8.56, p = 0.23). Meanwhile, no statistically significant differences existed between the expression level of PD-1 in tumor infiltrating lymphocytes (TILs) and the OS in NPC, with the pooled HR 1.29 (95% CI 0.68–2.42, p = 0.44). In subgroup analysis, higher expression of PD-L1 in immune cells correlated with better OS in patients with NPC, with a pooled HR 0.68 (95% CI 0.47–0.99, p = 0.04). Among the clinicopathological features included in our study, we found that the positive expression of PD-L1 in NPC associated with the higher expression of PD-1 (RR 1.25, 95% CI 1.02–1.52, p = 0.03). Our meta-analysis indicated that higher/positive expression of PD-L1/PD-1 may not serve as suitable biomarkers for the prognosis of NPC, which was not in consistent with some previous studies about the prognostic value of PD-L1/PD-1 in other types of tumors. Despite the positive results in subgroup analysis and study about clinicopathological features, it may still need corroboration of prospective and large-scale studies.

Background: PLEK2 (pleckstrin) could bind to membrane‐bound phosphatidylinositols and further promote cell spread. Recently, several studies have noted the importance of PLEK2 in tumor metastasis. However, the role of PLEK2 in head and neck squamous cell carcinoma (HNSCC) remains to be elucidated.Methods: The PLEK2 expression in HNSCC was identified using Oncomine, Gene Expression Omnibus (GEO), UALCAN databases, and western blot analysis. Prognosis analysis was performed using Kaplan–Meier plotter, DriverDBv3, UALCAN, UCSC Xena, and GEO databases. Single‐cell functional analysis was further performed using the cancerSEA database. The PLEK2‐related co‑expressed genes were identified, and gene set enrichment analysis was performed using LinkedOmics. Furthermore, the top 10 hub genes were identified using the cytoHubba plug‐in of Cytoscape. Then, gene enrichment analysis, pathway activity, and drug sensitivity analyses of the hub genes were performed using the R package “clusterProfiler” and GSCAlite. Finally, the UCSC Xena browser was utilized to explore the hub gene most likely to play a synergic role with PLEK2 in HNSCC.Results: Elevated expression of PLEK2 was observed in HNSCC and even in HNSCC subgroups based on diverse clinicopathological features, portending a poor prognosis in HNSCC. PLEK2 was correlated with metastasis and hypoxia in HNSCC, and the PLEK2‐related co‐expressed genes were mainly involved in the focal adhesion pathway. The top 10 hub genes were primarily enriched in focal adhesion, HPV infection, ECM‐receptor interaction, and PI3K‐AKT signaling pathway, and epithelial–mesenchymal transition pathway was activated. Furthermore, the expression levels of the hub genes were associated with sensitivity and resistance to various small molecules and anti‐cancer drugs. Further study suggested that ITGA3 and PLEK2 might be viewed as inextricably linked in facilitating HNSCC metastasis.Conclusions: In general, PLEK2 might serve as a potential biomarker for the diagnosis of HNSCC and guide the development of targeted therapies for HNSCC.

Background: The management of locally advanced recurrent nasopharyngeal carcinoma (rNPC) is challenging. The objective of our study was to compare salvage endoscopic nasopharyngectomy (ENPG) with intensity-modulated radiotherapy (IMRT) in clinical outcomes and complications of locally advanced rNPC. Methods: Patients with histologically confirmed rNPC in rT_3-4N_0-3M₀ stages were retrospectively enrolled between January 2013 and December 2019 in this multicenter, case-matched study. The baseline clinicopathological characteristics of patients were balanced by propensity score matching between the ENPG and IMRT groups. ENPG was performed in patients with easily or potentially resectable tumors. The oncological outcomes as well as treatment-related complications were compared between two groups. Results: A total of 176 patients were enrolled and 106 patients were matched. The ENPG group (n = 53) and the IMRT group (n = 53) showed comparable outcomes in the 3-year overall survival rate (68.4% vs. 65.4%, P = 0.401), cancer-specific survival rate (80.9% vs. 74.4%, P = 0.076), locoregional failure-free survival rate (36.6% vs. 45.3%, P = 0.076), and progression-free survival rate (27.5% vs. 32.3%, P = 0.216). The incidence of severe treatment-related complications of patients in the ENPG group was lower than that in the IMRT group (37.7% vs. 67.9%, P = 0.002). The most common complications were post perioperative hemorrhage (13.2%) in ENPG group and temporal lobe necrosis (47.2%) in IMRT group, respectively. Conclusion: Salvage ENPG exhibits comparable efficacy but less toxicities than IMRT in carefully screened patients with locally advanced rNPC, which may be a new choice of local treatment. Graphical

Introduction Involved site radiation therapy (ISRT) is a widely used treatment for primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma with control rates over 85%; however, its complications could reach 30%–50%. Intralesional rituximab injection has shown promising results with remission rates between 65% and 100% and minimal complications. This study aimed to conduct a multicentre randomised controlled clinical trial to compare the safety and efficacy of intralesional rituximab injection versus ISRT on primary ocular adnexal MALT lymphoma. Methods and analysis This is a multicentre randomised controlled trial and will be conducted at eight ophthalmic departments and institutes in China. 108 patients with primary ocular adnexal MALT lymphoma will be enrolled and randomised to undergo intralesional rituximab injection or ISRT. Comprehensive examinations will be performed before and after the treatment. The primary outcome is the cumulative occurrence rate of complications of grade ≥2 within 5 years after treatment commencement. The main secondary outcome is overall response rate, and progression-free survival, time to next treatment and overall survival will also be compared between the groups. Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of the Zhongshan Ophthalmic Center (ID: 2023KYPJ125-3; V.20240818) and the ‘5010 Plan’ evaluation committee at Sun Yat-sen University, Guangzhou, China, and all subcentres. All the participants will be required to provide written informed consent. The results will be disseminated through scientific meetings and published in peer-reviewed journals. Trial registration number NCT06190301.

Background/Objectives: To compare diagnostic performance and cost-effectiveness of [¹⁸F]FDG PET/CT versus MRI for cervical lymph node assessment in nasopharyngeal carcinoma (NPC) and to evaluate their impact on N-staging and upper-neck-only irradiation planning. Materials and Methods: We retrospectively identified treatment-naïve NPC patients who underwent both MRI and FDG PET/CT within 14 days prior to ultrasound-guided biopsy of specific cervical lymph nodes with rigorous one-to-one multimodal matching. Using histopathology as the reference standard (Cohort A, node level), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were compared between PET/CT and MRI. In a staging cohort (Cohort B, patient level), we compared imaging-based N-staging accuracy and the pathology-concordant classification of treatment recommendations assuming upper-neck-only irradiation for N0 to N1 disease. In discordant cases (Cohort C), three experienced radiation oncologists designed dose prescriptions and neck irradiation volumes, first using MRI alone and then after reviewing PET/CT to quantify decision impact. A decision tree/Markov model (10-year horizon) evaluated cost-effectiveness of MRI- versus PET/CT-initiated strategies. Results: In total, 694 biopsy-verified lymph nodes from 649 patients were analyzed. PET/CT demonstrated higher sensitivity (96.0% vs. 92.6%, p = 0.001) and NPV (80.2% vs. 66.7%, p < 0.001) than MRI, with comparable specificity (64.0% vs. 59.0%, p = 0.317) and PPV (91.4% vs. 90.0%, p = 0.203); AUCs were 0.864 and 0.841, respectively (p = 0.298). In Cohort B (N = 503), PET/CT provided accurate N-staging for a significantly higher proportion of patients compared to MRI (8.0% vs. 4.2%, p = 0.021) and yielded more accurate recommendations for upper-neck-only irradiation when restricted to N0 to N1 disease (93.8% vs. 88.9%, p = 0.003). In discordant cases (Cohort C, N = 62), PET/CT substantially improved accuracy compared with MRI and prompted clinically meaningful plan adjustments, including dose escalation for metastatic nodes (up to 16.7%) and expansion from upper-neck-only to whole-neck irradiation with rates of 6.4%, 8.0%, and 11.3% for the three radiation oncologists, respectively. In the base case economic analysis, PET/CT achieved higher effectiveness (5.329 vs. 5.305 quality-adjusted life years [QALYs]) at higher cost (US$27,228 vs. US$25,596), with an incremental cost–effectiveness ratio (ICER) of approximately US$68,000 per QALY, remaining below a willingness-to-pay threshold of US$100,000 per QALY; probabilistic sensitivity analysis favored PET/CT in 79.6% of iterations. Conclusions: FDG PET/CT provided superior sensitivity and negative predictive value versus MRI for detecting nodal metastases in NPC, improving pathology-adjudicated N-staging and the accuracy of upper-neck-only irradiation recommendations. PET/CT was cost-effective in the modeled setting, although treatment de-escalation for benign nodes remained conservative in clinical decision-making.