PURPOSE:Therapeutic options beyond platinum, gemcitabine, and immunotherapy in recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC) remain limited. Median overall survival (OS) for R/M disease is 20 months. This study evaluated the efficacy and safety of trifluridine/tipiracil (FTD/TPI) in platinum-resistant R/M NPC. PATIENTS AND METHODS:In this single-arm, phase II study, patients received oral FTD/TPI at 35 mg/m2 twice daily on days 1 to 5 and 8 to 12 of each 28-day cycle. The primary endpoint was disease control rate (DCR) at 12 weeks. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS:Thirty-five patients were enrolled. The median age was 56 years with a median of 2 prior lines of systemic therapy (range, 1-7). Forty five percent patients had prior fluoropyrimidine. The DCR at 12 weeks was 57.1% [95% confidence interval (CI), 39.4%-73.7%], and the ORR was 22.9% (95% CI, 10.4-40.1). The DCR was comparable with and without fluoropyrimidine exposure (55.6% vs. 58.8%). The median PFS was 6.5 months, and the median OS was 13.1 months. Treatment-emergent adverse events were predominantly hematologic, including ≥ grade 3 neutropenia (43%), anemia (26%), and thrombocytopenia (9%), with grade ≥3 events largely hematologic. Dose modifications were required in 60%, most commonly due to neutropenia, manageable with dose reduction. One patient discontinued treatment because of symptomatic anemia. Grades 3 to 4 neutropenia was significantly associated with improved ORR (P < 0.001). Exploratory plasma proteomic analyses suggested potential differences in baseline and on-treatment protein expression between responders and nonresponders, warranting further validation in larger cohorts. CONCLUSIONS:FTD/TPI demonstrated a manageable safety profile and encouraging antitumor activity. It is a convenient oral alternative to intravenous chemotherapy.

PURPOSE:Locoregionally advanced oral cavity squamous cell carcinoma (LA-OCSCC) has marked physical, psychological, and functional burden. Patients remain at high risk of relapse, often experiencing psychosocial distress. This study examined lived experiences of LA-OCSCC patients in the Asia-Pacific region to identify opportunities to reduce anxiety and improve coping strategies. METHODS:115 participants were interviewed across Australia, Hong Kong, South Korea, Taiwan, and Vietnam, including LA-OCSCC patients who underwent surgery and adjuvant chemoradiotherapy, their caregivers, and multidisciplinary care teams (clinical radiation and medical oncologists, supportive care specialists, nurse/case managers, psychologists, dietitians, speech therapists, and dentists). The Psycho-Onco Emotional Anxiety (POEM) framework informed research materials and analysis. RESULTS:Physical and functional impairments from tri-modality treatment led to profound psychosocial distress, negative psychosexual well-being, and social withdrawal, diminishing quality of life. Patients also faced stigma associated with OCSCC and social constraints, including gender norms discouraging men from showing vulnerability or seeking support. Fear of recurrence driven by awareness of the aggressive and recurrent nature of OCSCC further exacerbates anxiety. Limited access to psychosocial care, coupled with a lack of recognition among patients and caregivers of its benefits, further restricted the implementation of patient-centered care. CONCLUSION:Defining the psychological and emotional burden of LA-OCSCC is a crucial step toward enabling HCPs to recognize distress early and apply targeted screening strategies that strengthen patient support, engagement, and adherence to care. IMPLICATIONS FOR CANCER SURVIVORS:Timely and integrated psychosocial and rehabilitative care is crucial to restoring function and reducing anxiety, addressing the long-term effects of treatment and ultimately improving cancer survivorship.

To investigate change in diffusion weighted imaging (DWI) between pre-treatment (pre-) and after induction chemotherapy (post-IC) for long-term outcome prediction in advanced nasopharyngeal carcinoma (adNPC). Mean apparent diffusion coefficients (ADCs) of two DWIs (ADCpre and ADCpost−IC) and changes in ADC between two scans (ΔADC

Fragmentomics analysis of plasma autosomal DNA has shown promise in cancer diagnostics. Here we evaluated the clinical utility of plasma Epstein-Barr virus (EBV) DNA fragmentomics analysis for nasopharyngeal carcinoma (NPC) screening. Among our prospective cohort of approximately 20,000 subjects that underwent two rounds of screening, we analyzed the first-round blood samples of subjects who tested positive for EBV DNA via polymerase chain reaction (PCR) (n = 558). We found that those who subsequently developed NPC in the second round exhibited a distinctive mononucleosomal size pattern, an NPC-associated end motif (specifically, a depletion of CC-motif) and aberrations in methylation identified through fragmentomics-based methylation analysis (FRAGMA). Subjects with these aberrant fragmentomics features and higher quantity of EBV DNA had a relative risk of 87.1 times greater for developing NPC in the second round compared to subjects tested negative for EBV DNA on PCR. These results demonstrate plasma DNA fragmentomics could predict future cancer risk.

Epstein-Barr virus (EBV)+ve nasopharyngeal carcinoma (NPC) is prevalent in Southern China where patients with recurrent/ metastatic disease can be treated with chemotherapy and/or immune-checkpoint inhibitors. Claudin 1 (CLDN1) is a member of the tight junction (TJ) family of proteins that is overexpressed in some cancers with their non-junctional (NJ) epitopes exposed at the epithelium. This study investigated CLDN1 as a novel therapeutic target in NPC and evaluated the preclinical activity of ALE.C04 - a first-in-class, highly specific monoclonal antibody targeting NJ-CLDN1, in NPC models. Expression of NJ-CLDN1 was assessed in three EBV+ve NPC cell lines (C666-1, NPC43 and C17C), four patient-derived- xenografts (PDXs) and NPC biopsies (n=44). The anti-proliferative effect of ALE.C04 was evaluated in NJ-CLDN1+ve NPC cell lines by clonogenic and invasion assay, co-cultured with or without human-derived natural killer (NK) cells. Results are validated in PDX models (C15, C17). ALE.C04 was administrated either as a single agent or in combination with chemotherapy or bevacizumab. NJ-CLDN1 were overexpressed in two NPC cell line (NPC43 and C17C), three PDXs (C15, C17 and X2117) and biopsies (80%). Interestingly, NJ-CLDN1 was not detected in PDX Xeno-666 and its derived cell line, C666-1. A non-significant correlation trend was found between h-score with overall survival. Treatment with ALE.C04 suppressed colony formation of NJ-CLDN1+ve cell lines, with more significant effect observed in C17C. Effect of ALE.C04 as a single agent is modest on the growth of NJ-CLDN1+ve positive cell lines and C17 PDX model. Whilst in combinatorial approach, ALE.C04 showed synergism with gemcitabine as tumor growth was suppressed in C17 PDX. In contrast, ALE.C04 monotherapy significantly suppressed growth in C15 PDX, resulting in substantial changes in gene expression profile (via RNA-Sequencing) compared to the control group. The results of the in vitro coculture assay and in vivo combination with gemcitabine and bevacizumab will be presented. The results generated to date provide a proof-of-concept of targeting NJ-CLDN1 signaling in NPC using ALE.C04, especially in combination with chemotherapy or anti-vascular agent. ALE.C04 is now being evaluated in patients with NPC and other head and neck cancers in a phase 1 clinical trial (NCT06054477). Kar Wei Chin, Connie Wun Chun Hui, Chi-Hang Wong, Grace T. Y. Chung, Winky Lai, Alberto Toso, Luigi Manenti, Li Lili, Chi Man Tsang, Qian Tao, Edwin Pun Hui, Anthony T. C Chan, Kwok Wai Lo, Brigette B. Y. Ma. Evaluation of a novel target Claudin1 in preclinical models of nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7338.

INTRODUCTION:This study explored liver- and tumour-specific indicators predictive of suboptimal survival outcomes following repeat transarterial chemoembolisation (TACE) in intermediate-stage hepatocellular carcinoma (HCC) patients after an initial TACE. METHODS:This study included 300 HCC patients who underwent TACE treatment. Based on whether persistent albumin-bilirubin (ALBI) grade deterioration (PABD) occurred after the initial TACE, defining as a shift in ALBI grade to a higher grade from baseline without recovery within 90 days, patients were divided into PABD and non-PABD groups. Overall survival of non-PABD and PABD groups according to subgroups stratified by baseline ALBI grade and tumour burden was compared with that of patients receiving only sorafenib or supportive care during the same period. RESULTS:Repeat TACE provided a survival benefit over systemic therapy or supportive care for patients in all post-TACE non-PABD or most PABD subgroups, regardless of baseline liver condition (ie, modified albumin-bilirubin [mALBI] grade and tumour burden). This benefit was absent in two subgroups among patients who developed PABD after the initial TACE, namely, (1) those with a baseline liver condition of mALBI grade 1 or 2a and tumour burden exceeding the up-to-11 criteria, and (2) those with a baseline liver condition of mALBI grade 2b, regardless of tumour burden. CONCLUSION:Repeat TACE is not recommended for patients with persistent liver function deterioration after the initial TACE, particularly those exhibiting suboptimal baseline liver function or excessive tumour burden. Understanding the liver condition and tumour burden in HCC patients may assist clinicians in planning optimal treatment strategies, leading to better prognosis.

Background Despite transarterial chemoembolization (TACE) serving as the first-line treatment for patients with intermediate stage B hepatocellular carcinoma (HCC), complete response rates are generally below 27%. Purpose To compare the efficacy and safety of an anhydrous cisplatin suspension in ethiodized oil-based TACE versus a conventional aqueous cisplatin emulsion in the treatment of participants with HCC. Materials and Methods In this prospective, multicenter, randomized controlled trial conducted from September 2016 to February 2023, participants from three hospitals in Hong Kong were randomized to an experimental or control group in a 1:1 ratio. The experimental group received an anhydrous cisplatin suspension (4 mL of ethiodized oil with 20 mg of cisplatin powder). The control group received a conventional aqueous cisplatin emulsion. TACE was performed within 4 weeks after randomization in two to three treatments, 2 months apart. Response was assessed with CT and digital subtraction angiography during subsequent TACE. Primary end points were complete tumor response and severe adverse events. Secondary end points included progression-free survival and overall survival (OS). Survival outcomes were compared using the log-rank test and hazard ratios with 95% CIs. Results A total of 77 participants were included (median age, 68 years; IQR, 64-75 years; 59 men). At 6 months, the complete tumor response rate was higher in the suspension group (90% [35 of 39 participants]) compared with the emulsion group (47% [18 of 38 participants]; P < .001). Serious adverse events were similar in the suspension group (2.3% [three of 128 procedures]) and emulsion group (5.2% [eight of 153 procedures]; P = .21). Median progression-free survival was higher in the suspension group (21.1 months; 95% CI:14.3, 38.9) compared with the emulsion group (10.4 months; 95% CI: 7.3, 13.4) (hazard ratio, 0.35; P < .001). Median OS was higher in the suspension group (53.3 months; 95% CI: 40.5, not reached) than in the emulsion group (36.0 months; 95% CI: 25.7, 46.6) (hazard ratio, 0.32; P = .004). Conclusion Ethiodized oil-based TACE using an anhydrous cisplatin suspension resulted in better complete tumor response, progression-free survival, and OS rates compared with the conventional aqueous cisplatin emulsion. ClinicalTrials.gov identifier NCT03268499 © RSNA, 2025 Supplemental material is available for this article.

AIM:Locoregionally advanced oral cavity squamous cell carcinoma (LA-OCSCC) imposes a high disease burden, significantly affecting patients' quality of life. We aimed to identify unmet needs and challenges faced by patients, caregivers, and healthcare professionals (HCPs) in diagnosis and managing LA-OCSCC. METHODS:In-depth interviews were conducted across Australia, Hong Kong, South Korea, Taiwan, and Vietnam with LA-OCSCC patients (n = 28), caregivers (n = 27), and HCPs (surgeons, clinical, radiation, and medical oncologists [n = 30]; nurses, case managers/coordinators, psychologists, speech therapists, dieticians, and dentists [n = 30]). Patients who received post-operative chemoradiotherapy for Stage III-IVB LA-OCSCC, their caregivers, and HCPs were eligible. The interview guide, design, and analysis were based on the Capability, Opportunity, Motivation, Behavior (COM-B) model. RESULTS:Major service gaps in timely diagnosis, treatment, patient-centered care, and therapeutic alliance were identified. Limited awareness of LA-OCSCC led to overlooked symptoms, delaying medical attention. General practitioners were perceived as less experienced in identifying LA-OCSCC symptoms accurately and promptly, with dentists being more informed. A shortage of nurses to support integrated multidisciplinary team discussions, patient education, and to relay patients' needs to specialists, compromised patient-centric care. Psychotherapeutic services were scarce, with supportive care professionals overextending to bridge the gap. CONCLUSION:This study examined LA-OCSCC care management in five Asia-Pacific countries/territories with varying healthcare systems and infrastructure. Given LA-OCSCC's aggressive nature and high burden from disease and treatment, patients and caregivers require support beyond medical interventions. A multi-stakeholder approach with clinical and community care is essential to ensure a comprehensive and sustainable approach to patient-centered care within the different health systems.

BackgroundAn increasing number of immuno-therapeutic agents have proven efficacy in hepatocellular carcinoma (HCC). Inflammatory markers (c-reactive protein, interleukin-8 and inflammatory score) have been found to be prognostic factors in HCC patients. These inflammatory markers have demonstrated correlations with quality of life (QOL) disturbances in fatigue, appetite loss and nutritional concern. Type I interferon response triggered by HCC could be responsible for an inflammatory state and anorexia-cachexia syndrome leading to these specific QOL impairment. Peripheral blood Interferon Stimulated Gene 15 (ISG15) messenger ribonucleic acid (mRNA) transcript level, a biomarker for type I interferon response, was evaluated for its prognostic significance for overall survival (OS) in a prospective cohort of HCC patients. QOL measurement was employed to systemically capture and quantify patients’ clinical manifestations for correlations with ISG15 mRNA transcript level.MethodsClinical, QOL and laboratory data of 340 treatment naïve HCC patients were collected at study entry. ISG15 mRNA transcript levels in circulating leucocytes were quantified. Independent prognostic factors for OS were identified. Correlation analyses between ISG15 mRNA transcript level and scores of QOL factors were performed.ResultsHigh ISG15 mRNA transcript level in circulating leucocytes was an independent prognostic factor for poor OS (hazard ratio 1.62 [1.23-2.15]; p-value<0.01). The median OS of patients with high ISG15 gene expression was significantly shorter than those with low expression, 4.7 versus 14.3 months respectively (p-value<0.03). There were significant correlations between high ISG15 mRNA transcript level and worse scores in QLQ-C30 fatigue, appetite loss and QLQ-HCC18 nutritional disturbances (p-values <0.05).ConclusionsElevated ISG15 mRNA transcript level in peripheral blood leucocytes was an independent poor prognostic factor for OS in HCC patients. Patients with higher ISG15 gene expression, suggesting more intense type I interferon response, had significantly worse OS. High ISG15 gene expression demonstrated significant correlations with QOL disturbances in fatigue, appetite loss and nutritional concern. These QOL factors could be capturing the anorexia-cachexia manifestations from interferon response induced by HCC.

BACKGROUND AND PURPOSE:Quantification of deep invasion of the primary tumor is a predictor of outcome in oral cancer, but its predictive value in nasopharyngeal carcinoma (NPC) is unknown. This study aimed to investigate deep invasion of the primary NPC by using volumetric measurements on MRI for the prediction of outcome. MATERIALS AND METHODS:Retrospective review was conducted of 822 MRIs from patients with newly diagnosed nonmetastatic NPC with volumetric analysis of the primary tumor to obtain total primary tumor volume (PTV), deep invasion volume (DIV), and ratio of deep to the total primary tumor volume (DIVr). Optimal predictors were identified by the multivariable Cox regression and c-index correlating with disease-free survival (DFS), distant metastases-free survival (DMFS), and overall survival (OS). RESULTS:High DIVr, DIV, and PTV significantly correlated with poor DFS, DMFS, and OS (all P < .01); DIVr being the optimal measurement (hazard ratio = 3.234 for DFS, 3.409 for DMFS, and 3.184 for OS). Compared with the eighth edition American Joint Committee on Cancer (AJCC) T-category, DIVr showed modest improvement in c-indexes for predicting DFS (0.602 versus 0.620, P = .03) and DMFS (0.597 versus 0.626, P < .01), but not OS (P = .15). The use of a DIVr-based T-category had similar survival prognostication to the eighth edition AJCC T-category although there was improved prediction in DMFS. CONCLUSIONS:DIVr is a better predictor of outcome in NPC than PTV or DIV, with slightly superior performance to the eighth edition AJCC T-category especially for DMFS.

BACKGROUND:Treatment response evaluated by tumour size change is an important indicator for outcome prediction. Advanced nasopharyngeal carcinoma (adNPC) grows irregularly, and so the unidimensional measurement may not be accurately applied to adNPC for outcome prediction. This study aimed to evaluate values of unidimensional and volumetric measurements for treatment response to induction chemotherapy (IC) for outcome prediction in adNPC and compared the values with that of RECIST 1.1 guideline. MATERIALS AND METHODS:Pre-treatment and post-IC magnetic resonance images (MRIs) from 124 patients with stage III-IVA NPC were retrospectively reviewed. Sums of the maximum unidimensional diameters (D) and volumes of the targeted tumours (primary tumour and two largest metastatic lymph nodes) on the pre- (Dpre and Vpre) and post-IC MRIs (Dpost-IC and Vpost-IC) and percentage changes in D (Δ D%) and V (ΔV%) between two scans were calculated and correlated with disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) using Cox regression analysis. Area under the curves (AUCs) of independent measurements and RECIST groups (RECIST response and non-response groups) for predicting disease recurrence, locoregional recurrence, and distant metastases, respectively, were calculated and compared using the DeLong test. RESULTS:Univariable analysis showed correlations between high Dpost-IC with poor DFS and DMFS (P < 0.05), but not with LRRFS (P = 0.07); high Vpost-IC and low ΔV% (less decrease in volume on post-IC) with poor DFS, LRRFS, and DMFS (P < 0.05); and no correlations between Dpre, ΔD%, and Vpre and the outcomes (P > 0.05). Multivariable analysis showed that ΔV% was the only independent measurement for outcomes (P < 0.05). Compared with RECIST groups, ΔV% of 47.9% (median value) showed a higher AUC for disease recurrence (0.682 versus 0.526, P < 0.01) and for locoregional recurrence (0.782 versus 0.585, P < 0.01), but not for distant metastases (0.593 versus 0.518, P = 0.26). CONCLUSIONS:Volumetric measurement to evaluate treatment response to IC outperformed unidimensional measurement and RECIST guideline in outcome prediction in adNPC.

BACKGROUND:Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS:EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS:The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION:A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.

Purpose Extranodal extension (ENE) has the potential to add value to the current nodal staging system (N8th) for predicting outcome in nasopharyngeal carcinoma (NPC). This study aimed to incorporate ENE, as well as cervical nodal necrosis (CNN) to the current stage N3 and evaluated their impact on outcome prediction. The findings were validated on an external cohort. Methods & Materials Pre-treatment MRI of 750 patients from the internal cohort were retrospectively reviewed. Predictive values of six modified nodal staging systems that incorporated four patterns of ENE and two patterns of CNN to the current stage N3 for disease-free survival (DFS) were compared with that of N8th using multivariate cox-regression and concordance statistics in the internal cohort. Performance of stage N3 for predicting disease recurrence was calculated. An external cohort of 179 patients was used to validate the findings. Results Incorporation of advanced ENE, which infiltrates into adjacent muscle/skin/salivary glands outperformed the other five modifications for predicting outcomes (p < 0.01) and achieved a significantly higher c-index for 5-year DFS (0.69 vs 0.72) (p < 0.01) when compared with that of N8th staging system. By adding advanced ENE to the current N3 increased the sensitivity for predicting disease recurrence from 22.4 % to 47.1 %. The finding was validated in the external cohort (5-year DFS 0.65 vs. 0.72, p < 0.01; sensitivity of stage N3 increased from 14.0 % to 41.9 % for disease recurrence). Conclusion Results from two centre cohorts confirmed that the radiological advanced ENE should be considered as a criterion for stage N3 disease in NPC.

To investigate the potential of T1rho, a new quantitative imaging sequence for cancer, for pre and early intra-treatment prediction of treatment response in nasopharyngeal carcinoma (NPC) and compare the results with those of diffusion-weighted imaging (DWI). T1rho and DWI imaging of primary NPCs were performed pre- and early intra-treatment in 41 prospectively recruited patients. The mean preT1rho, preADC, intraT1rho, intraADC, and

6032 Background: Despite effective local treatment, up to 30% of patients with nasopharyngeal carcinoma (NPC) relapse and require systemic treatment. There are limited therapeutic options beyond cisplatin, gemcitabine and immunotherapy and the median survival of r/m disease is about 20 months. Capecitabine, a fluoropyrimidine, has shown some efficacy with a median time to progression of 4.9 months in heavily pretreated r/m NPC but there is a need for alternative treatments. FTD/TPI is an oral drug combination of trifluridine and tipiracil, a thymidine phosphorylase inhibitor preventing rapid degradation of trifluridine, thus increasing its exposure. It has shown activity in colorectal, gastric and breast cancers despite prior fluoropyrimidines. This study explores the efficacy and safety of FTD/TPI in r/m NPC, with or without prior exposure to fluoropyrimidines. Methods: In this single-arm phase II trial, patients were administered oral FTD/TPI twice daily at 35mg/m2 on days 1-5 and 8-12 of a 28-day cycle. The primary endpoint was disease control rate (DCR) at 12 weeks, with secondary endpoints including progression-free survival (PFS), overall response rate (ORR), safety, and tolerability. Results: A total of 33 patients were recruited. Median age was 56 years (range: 34-82), most were males (n=27, 82%), with median of 3 (range: 1-12) prior lines of treatment in the metastatic setting. Approximately half (48.5%) received prior fluoropyrimidines. DCR at 12 weeks was 63.6%, with an ORR of 18.2%. DCR was 68.8% and 58.8% in patients with and without prior fluoropyrimidine exposure respectively. Median PFS was 6.5 months (95% CI 2.8-10.2) and overall survival was 13.1 months (95% CI 7.1-19.2). FTD/TPI demonstrated a manageable safety profile, with most common treatment-related adverse events of neutropenia, anaemia, fatigue, nausea and anorexia. 60% of patients required dose modifications, most commonly due to neutropenia, that could be overcome by dose reduction or prolongation to 5-weekly cycles. 1 patient required discontinuation due to anaemia resulting in syncope. Conclusions: FTD/TPI is well tolerated, compares favorably to Capecitabine and showed promising anti-tumor activity with meaningful clinical benefit regardless of prior exposure to fluoropyrimidines. This oral chemotherapy offers an attractive choice for patients valuing quality of life, minimizing hospital visits and resource utilization such as chemotherapy infusions. Further investigations in randomized studies are warranted. Clinical trial information: NCT04627961 .

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

6010 Background: Stage IVA NPC had the worst prognosis despite the current standard of neoadjuvant chemotherapy and concurrent chemoradiation (CRT). There is no safety and efficacy data combining immune checkpoint inhibitor (ICI) and CRT in NPC. Methods: We conducted an open label, single arm, multi-site, phase 2 clinical trial in AJCC 8th Edition Stage IVA (T4 and/or N3, M0) WHO type 2/3 Epstein Barr virus (EBV) +ve NPC (Clinical trial register NCT03734809). The experimental treatment consisted of neoadjuvant pembrolizumab (200 mg D1), gemcitabine (1000 mg/m2 D1+8) and cisplatin (80 mg/m2 D1) q3w x2 followed by concurrent pembrolizumab (200 mg x3 week 1, 4 and 7) and cisplatin (40 mg/m2 weekly x7) during intensity-modulated radiation (IMRT), and maintenance pembrolizumab 200 mg q3w x12 from 4 weeks post-RT. By Fleming one-stage design (type I error 0.05, power 0.80, 10% drop out), planned sample size is 46. Primary endpoint is 2-year (yr) progression free survival (PFS). Secondary endpoints include safety and tolerability. Plasma EBV DNA (pEBV DNA) was monitored. Results: Accrual was completed with 46 subjects recruited at two study sites from May 2019 to June 2022 in Hong Kong (n=31) and Singapore (n=15). This protocol specified analysis included 37 subjects with >12 months post-treatment follow up (median 26.8 months, 95% CI 21.3-32.9). Patient demographics: mean age 52 (range 27 - 84); M:F 31:6; ECOG 0=23, 1=14; stages: T4N1-2 (16), T1-3N3 (18), T4N3 (3). Overall compliance rate: neoadjuvant cisplatin 98.6%, gemcitabine 97.7%, concurrent cisplatin 73.7%, pembrolizumab 100% (neoadjuvant), 77.5% (concurrent), 77% (maintenance), IMRT 99.7% (69.96 Gy). Treatment related adverse events (≥ grade 3, >10%): dysphagia (32.4%), mucositis (29.7%), neutropenia (29.7%), radiation dermatitis (24.3%), anemia (18.9%), hyponatremia (13.5%), thrombocytopenia (10.8%). No ≥ grade 4 mucositis/dermatitis. The 2-yr PFS was 69.6% (95% CI 53.8 - 88.5%). At the end of neoadjuvant, CRT and maintenance phases, molecular remission (pEBV DNA = 0) was achieved in 24.3%, 70.3% and 70.3% of patients respectively, which strongly correlated with PFS (p=0.0253, 0.0007 and <0.0001 respectively, Table). Conclusions: Pembrolizumab incorporated into neoadjuvant, CRT and maintenance protocol is safe with promising results. This strategy of combining ICI with neoadjuvant chemotherapy and CRT is being tested in several ongoing phase 3 trials in advanced NPC. Clinical trial information: NCT03734809 . [Table: see text]

PDF file - 269K, Additional detail of methodology, adverse events, epitope peptides and epitope-specific T cell responses. Also includes all results obtained using ELIspot assays with overlapping peptides and analysis of regulatory T cells in patients.