Recurrent Nasopharyngeal Carcinoma Research Articles

Primary nasopharyngeal carcinoma with Sjögren's syndrome and positive cerebrospinal fluid Epstein-Barr virus: a case report and literature review

The study presents an analysis of the diagnostic and treatment protocol for a patient with a first episode of nasopharyngeal carcinoma who also has Sjogren's syndrome and Epstein-Barr Virus (EBV) positive cerebrospinal fluid, as detected through metagenomic next-generation sequencing (mNGS). It reviews existing literature to examine the connections between EBV and various conditions including Sjogren's syndrome, encephalitis or meningitis, and nasopharyngeal carcinoma, emphasizing the importance of EBV positive cerebrospinal fluid. The study focuses on a case from the Eighth Medical Center of the General Hospital of the People's Liberation Army, where a patient was admitted with headaches as the primary symptom on March 3, 2021. This patient had a history of Sjogren's syndrome and was later diagnosed with nasopharyngeal carcinoma. The research involved reviewing both domestic and international databases for cases related to cerebrospinal fluid EBV positive encephalitis or meningitis, and nasopharyngeal carcinoma. It aimed to aggregate data on demographics, initial symptoms, treatment methods, and patient outcomes. Findings suggest that positive cerebrospinal fluid EBV is linked to autoimmune diseases, viral encephalitis or meningitis, and nasopharyngeal carcinoma, albeit infrequently in the context of Sjogren's syndrome. Notably, EBV positive cerebrospinal fluid is commonly associated with recurrent nasopharyngeal carcinoma rather than initial episodes. The study concludes that for patients with an immune condition, exhibiting symptoms like headaches or cranial nerve issues, or in cases where nasopharyngeal carcinoma is suspected, early testing through cerebrospinal fluid mNGS or EBV DNA is recommended. This approach facilitates risk assessment, prognosis determination, and the creation of individualized treatment plans.

Axillary Metastasis as the Initial Presentation of Recurrent Nasopharyngeal Carcinoma

Axillary Metastasis as the Initial Presentation of Recurrent Nasopharyngeal Carcinoma

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-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 (RNA-seq) analysis. The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-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 significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. An MRI-based radiomic signature predicted OS 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 lrNPC patients.

Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma

BackgroundTo compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment.MethodsWe retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors.ResultsThe median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group.ConclusionsFor NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

Efficacy and Safety of Cell-based Immunotherapy in The Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma – A Systematic Review and Meta-analysis

BackgroundRecurrent/Metastatic Nasopharyngeal Carcinoma (RM-NPC) remains difficult to treat and contributes to considerable mortality. The first-line treatment for RM-NPC is Gemcitabine and Cisplatin and second-line treatment options differ. The endemic variant of NPC is associated with Epstein-Barr Virus (EBV). Therefore, Cell-based Immunotherapy (CBI) targeting EBV-specific RM-NPC may be effective. MethodsWe systematically searched PubMed, Embase and the Cochrane Library for randomised or observational studies investigating the efficacy and safety of CBI in the treatment of RM-NPC. We performed all meta-analyses using the random-effects model. Studies were further stratified by endemicity, nature of disease and drug type to investigate for potential between-study heterogeneity and additional pre-specified tests were employed to assess for publication bias. ResultsWe screened 1,671 studies and included 13 studies with 403 participants in the systematic review, of which nine studies were eligible for meta-analysis. The use of CBI monotherapy as second or subsequent line treatment for EBV-positive RM-NPC revealed an ORR of 10 % (95 %CI = 3 %–29 %), median PFS of 2.37 months (95 %CI = 1.23–3.51) and median OS of 10.16 months (95 %CI = 0.67–19.65). For EBV-specific Cytotoxic T-Lymphocyte monotherapy, the pooled PD rate was 54 % (95 %CI = 9 %–93 %), SD rate was 22 % (95 %CI = 2 %–75 %) and incidence rate of any grade adverse events was 45 %. For Dendritic Cell monotherapy, a PD rate of 80 % (95 % CI = 29 %–98 %), SD rate of 11 % (95 % CI = 0 %–82 %) and incidence rate of any grade adverse events of 29 % was achieved. ConclusionCBI monotherapy demonstrates some activity in pre-treated RM-NPC. More trials are needed to better understand how to integrate CBI into RM-NPC care.

Synthesis and Evaluation of [64Cu]Cu-NOTA-HFn for PET Imaging of Transferrin Receptor 1 Expression in Nasopharyngeal Carcinoma.

As recurrent and metastatic nasopharyngeal carcinoma (NPC) is the most common cause of death among patients with NPC, there is an urgent clinical need for the development of precision diagnosis to guide personalized treatment. Recent emerging evidence substantiates the increased expression of transferrin receptor 1 (also known as cluster of differentiation 71, CD71) within tumor tissues and the inherent targeting capability of natural heavy-chain ferritin (HFn) toward CD71. This study aimed to synthesize and assess a radiotracer ([64Cu]Cu-NOTA-HFn) designed to target CD71 for positron emission tomography (PET) imaging in an NPC tumor-bearing mouse model. The entire radiolabeling process of [64Cu]Cu-NOTA-HFn was completed within 15 min with high yield (>98.5%) and high molar activity (72.96 ± 21.33 GBq/μmol). The in vitro solubility and stability experiments indicated that [64Cu]Cu-NOTA-HFn had a high water solubility (log P = -2.42 ± 0.52, n = 6) and good stability in phosphate-buffered saline (PBS) for up to 48 h. The cell saturation binding assay indicated that [64Cu]Cu-NOTA-HFn had a nanomolar affinity (Kd = 10.9 ± 6.1 nM) for CD71-overexpressing C666-1 cells. To test the target engagement in vivo, prolonged-time PET imaging was performed at 1, 6, 12, 24, and 36 h postinjection (p.i.) of [64Cu]Cu-NOTA-HFn to C666-1 NPC tumor-bearing mice. The C666-1 tumors could be visualized by [64Cu]Cu-NOTA-HFn and blocked by nonradiolabeled HFn. PET imaging quantitative analysis demonstrated that the uptake of [64Cu]Cu-NOTA-HFn in C666-1 tumors peaked at 6 h p.i. and the best radioactive tumor-to-muscle ratio was 10.53 ± 3.11 (n = 3). Ex vivo biodistribution assay at 6 h p.i. showed that the tumor uptakes were 1.43 ± 0.23%ID/g in the nonblock group and 0.92 ± 0.2%ID/g in the block group (n = 3, p < 0.05). Immunohistochemistry and immunofluorescence staining confirmed positive expression of CD71 and the uptake of HFn in C666-1 tumor tissues. In conclusion, our experiments demonstrated that [64Cu]Cu-NOTA-HFn possesses a very high target engagement for CD71-positive NPC tumors and provided a fundamental basis for further clinical translation.

Abstract CT113: A dose-exploring, randomized, open-label, Phase I study for toripalimab subcutaneous injection in patients with advanced nasopharyngeal carcinoma

Abstract Background Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, in combination with gemcitabine and cisplatin (GP) has been approved as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) by the US FDA in October 2023. This is the first-in-human clinical trial (NCT05751486) to investigate the pharmacokinetics of toripalimab subcutaneous (SC) formulation in RM-NPC and determine the appropriate subcutaneous administration regimen for subsequent clinical trials. Methods Patients with histologically confirmed RM-NPC and without previously systemic therapy for RM disease were enrolled. Eligible patients were assigned to receive toripalimab SC 240 mg every 3 weeks (Q3W), 360 mg Q3W or 480 mg Q6W, in combination with GP for up to 6 cycles, followed by toripalimab SC monotherapy until disease progression, intolerable toxicity, or completion of 2 years of treatment. Tumor response was assessed per RECIST v1.1. The primary endpoint was pharmacokinetic (PK) profile. Secondary endpoints included safety, efficacy, and immunogenicity. Results From November 24, 2022 to November 20, 2023, a total of 38 patients (240 mg cohort, n=12; 360 mg cohort, n=13; 480 mg cohort, n=13) were enrolled, the median follow-up time was 6.8 months. The median age was 49 years, and 28 (73.7%) patients were males. PK analysis showed that in the first cycle, the exposure (AUC0-21days and Ctrough) of toripalimab 360 mg Q3W SC regimen was comparable to that of 240 mg Q3W intravenous (IV) regimen (table 1). Objective Response Rates (ORR) in 240 mg, 360 mg and 480 mg cohorts were 100%, 92.3% and 92.3%, respectively. By November 20, 2023, 71.1% (27/38) patients have ongoing responses. No new safety signal was identified. The incidence of Grade ≥3 adverse events (AEs) was 76.3% with no fatal AEs. The incidence of investigator-determined immune-related AEs was 36.8% with 1 (2.6%) Grade ≥3. Conclusions Toripalimab SC formulation showed similar safety and clinical efficacy with toripalimab IV formulation when combined with GP in patients with RM-NPC. The exposure of toripalimab 360 mg Q3W SC was comparable to that of 240 mg Q3W IV. Toripalimab SC formulation is planned for phase III clinical development. Table 1. PK parameters of each dose cohort. Parameters JS001sc Cohorts (N = 36) IV ref-model based 240 mg SC Q3W, n=12 480 mg SC Q6W, n=12 360 mg SC Q3W, n=12 240 mg IV Q3W, n=1014 Cycle 1 Ctrough, μg/mL GM (% CV) 10.2 (57.1) 8.4 (43.5) 18.6 (50.1) 10.2 (61.8) Cycle 1 AUC (0-Xd), μg•d/mL GM (% CV) 8376 (0-21 d) (39.3) 25316 (0-42 d) (35.4) 14229 (0-21 d) (58.2) 13386 (27.0) Bioavailability 62.6% (25.3%-100.0%) Citation Format: Hai-Qiang Mai, Ya-Qian Han, Guo-Wu Wu, Kun-Yu Yang, Chuan-Ben Chen, Mo Wang, Xian-Ming Luo, Shuang-Hui Wei, Xi Tan, Peng Xue, Rui-Hua Xu. A dose-exploring, randomized, open-label, Phase I study for toripalimab subcutaneous injection in patients with advanced nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT113.

Abstract 4025: A phase II trial of neoadjuvant gemcitabine, cisplatin plus tislelizumab followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Clinical efficacy, safety and the biomarker analysis

Abstract Immune checkpoint inhibitors (ICIs) have been widely used in recurrent or metastatic nasopharyngeal carcinoma (NPC), but the addition of ICIs to chemoradiotherapy in locoregionally advanced (LA) NPC requires further investigation. We conducted a phase II, single-arm trial to evaluate the efficacy and safety of neoadjuvant gemcitabine, cisplatin (GP) plus tislelizumab followed by concurrent chemoradiotherapy (CCRT) in LA-NPC. All participants received 3 cycles of GP chemotherapy plus tislelizumab (200 mg) followed by 3 cycles of cisplatin-based CCRT. The primary endpoint was the clinical complete response rate (CR) after neoadjuvant chemoimmunotherapy (NAT). The secondary endpoints include pathological CR rate, progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), etc. Pretreatment blood samples and paired (pre-/post-NAT) tissue biopsies were collected to perform full-spectrum peripheral T-cell profiling, PD-L1 and tertiary lymphoid structures (TLS) staining. Among all 63 participants, the CR rate after NAT reached 41.3% (95% CI, 28.8%-53.8%), far exceeding our hypothesized CR rate of 22%. The objective response rate (ORR) and pCR rate after NAT were 88.9% (95% CI, 80.9% to 96.9%) and 74.6% (95% CI, 62.1% to 84.7%), respectively. As of July 15th, 2023, after the median follow-up of 25 months, the 2-year PFS and OS were 98.4% and 100%. The incidence of grade 3-4 immunotherapy-related adverse events was 1.6%. The compliance of CCRT was not compromised. Patients who achieved CR had significantly more circulating CD4+ and CD8+ effector memory T cells (Tem), regulatory T cells (Treg) and follicular helper T cells (Tfh). The peripheral abundance of LAG3+ Tem and Tfh were independently predictive of NAT response. The number and maturation of TLS significantly increased after NAT in the CR group, but not in the Non-CR group. GP chemotherapy plus tislelizumab followed by CCRT was highly therapeutic and safe in treating LA-NPC, further randomized phase III studies are awaited. Citation Format: Xiao-Yun Li, Si-Yi Xie, Qiu-Yan Chen, Hai-Qiang Mai, Lin-Quan Tang. A phase II trial of neoadjuvant gemcitabine, cisplatin plus tislelizumab followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Clinical efficacy, safety and the biomarker analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4025.

Abstract 1109: LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis

Abstract Background: Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown. Methods: LINC01770 expression was determined using quantitative real-time reverse transcription PCR, and its prognostic value was evaluated using Kaplan-Meier survival analysis. RNA sequencing and bioinformatic analysis were used to determine the potential function of LINC01770, and its biological effects were investigated using in vitro and in vivo experiments. Mass spectrometry-coupled RNA pull-down assays and western blotting identified LINC01770 interacting proteins, followed by confirmation using RNA immunoprecipitation (RIP) assays. Ferroptosis and lipid peroxidation were detected using flow cytometry. Results: LINC01770 was overexpressed in NPC tissues according to microarray screening. Patients with NPC showing high LINC01770 expression experienced shorter survival and worse prognosis. In vitro and in vivo experiments suggested that knockdown of LINC01770 expression significantly inhibited the proliferation, migration, and invasion of NPC cells. Sequencing and functional complementation experiments showed that LINC01770 regulates the proliferation and metastasis of NPC through TEA domain transcription factor 1 (TEAD1). Meanwhile, RIP and PCR experiments suggested that LINC01770 and TEAD1 were common targets of microRNAs miR-615-5p and miR-1293. Overexpression of LINC01770 promoted ferroptosis in vitro and in vivo through the TEAD1/Acyl-CoA synthetase long chain family member 4 (ACSL4)/transferrin receptor (TFRC) pathway. Conclusions: LINC01770 is a prognostic biomarker for NPC and participates in the regulation of TEAD1 signaling pathway through competitive binding to miRNA-615-5p and miRNA-1293, resulting in NPC metastasis and progression. Radiation resistant cells are in a delicate balance between lipid peroxidation and increased vulnerability to ferroptosis, suggesting that ferroptosis could be used to kill NPC cells and reverse their radiotherapy resistance during the malignant progression of NPC caused by high expression of LINC01770. Thus, inducing ferroptosis could be used to treat recurrent and refractory NPC. Citation Format: Qingqing Xu, Ciming Sun, Suixian Zhang, Xuan Li, Lei Chen, Ming Chen. LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1109.

Cost-efficiency and budget-neutral expanded access modeling of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma

ABSTRACT Aims: To estimate, in the setting of recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) for an assumed 1,207 incident US cases in 2024, (1) the cost-efficiency of a toripalimab-gemcitabine-cisplatin regimen compared to a similar pembrolizumab regimen; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens afforded by the accrued savings. Methods: Simulation modeling utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) and drug administration costs over one and two years of treatment with treatment rates ranging from 45% to 90%. In the absence of trial data for pembrolizumab-gemcitabine-cisplatin in R/M NPC, it is assumed that such regimen would be comparable to toripalimab-gemcitabine-cisplatin in efficacy and safety. Results: In the models utilizing the WAC, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 1,207-patient panel, estimated 1-year savings range from $21,733,702 (45% treatment rate) to $43,467,404 (90% rate). Reallocating these savings permits budget-neutral expanded access to an additional 2,359 (45% rate) to 4,717 (90% rate) toripalimab maintenance cycles or to an additional 126 (45% rate) to 252 (90%) full 1-year toripalimab regimens with all agents. Two-year savings range from $42,259,976 (45% rate) to $84,519,952 (90% rate). Reallocating these efficiencies provides expanded access ranging from an additional 4,586 (45% rate) to 9,172 (90% rate) toripalimab cycles or to an additional 128 to 257 full 2-year toripalimab regimens. The ex ante ASP model showed similar results. Conclusion: This simulation demonstrates that treatment with toripalimab generates savings that enable budget-neutral funding for up to an additional 252 regimens with toripalimab-gemcitabine-cisplatin for one full year, the equivalent of approximately 21% of the 2024 incident cases of R/M NPC in the US.

Salvage endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a non-endemic area.

To analyze oncological outcomes of endoscopic surgical treatment of locally recurrent EBV-related undifferentiated non-keratinizing nasopharyngeal carcinoma (uNK-NPC) in a non-endemic area. Retrospective review of patients affected by recurrent uNK-NPC treated with nasopharyngeal endoscopic resection (NER) in a tertiary-care referral center from 2003 to 2022, by evaluating survival rates, prognostic factors, and follow-up strategies. The oncological outcomes of 41 patients were analyzed, over a mean follow-up period of 57 months. The 5-year overall, disease-specific, and disease-free survival of the cohort were 60.7% ± 8.9%, 69% ± 9%, and 39.7% ± 9.2%, respectively. The local (rT) and regional (rN) extension of recurrent disease, stage of disease, and status of resection margins appeared to significantly influence survivals. After a mean follow-up period of 21 months, a further recurrence after NER was observed in 36.6% of cases. Skull base osteonecrosis induced by previous irradiation and post-surgical bone remodeling represent the major challenges for early detection of further local relapses during postoperative follow-up. NER appeared as a safe and effective treatment for recurrent uNK-NPC. The adequate selection of patients eligible for NER is essential, to maximize the chances to cure and minimize the risk of local complications.

Remodeling the tumor-immune microenvironment by anti-CTLA4 blockade enhanced subsequent anti-PD-1 efficacy in advanced nasopharyngeal carcinoma

Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells.

53 Reirradiation with Stereotactic Ablative Radiotherapy in Recurrent Nasopharyngeal Carcinoma

53 Reirradiation with Stereotactic Ablative Radiotherapy in Recurrent Nasopharyngeal Carcinoma

A Pilot Study of Anlotinib as a Combination Treatment in Advanced Nasopharyngeal Carcinoma.

To investigate the short-term objective response and treatment toxicity of anlotinib as a combination treatment in patients with Recurrent or Metastatic Nasopharyngeal Carcinoma (RM-NPC). Patients with RM-NPC who received anlotinib as a combination treatment between March 2021 and July 2022 were retrospectively analyzed.The efficacy and safety of anlotinib as a combination treatment were analyzed. A total of 17 patients with RM-NPC were included in this study. Of these patients, 2 (11.8%) had local recurrence, 4 (23.5%) had cervical lymph node recurrence, and 11 (64.9%) had distant failure. The most common metastatic site was the liver (47.1%), followed by the lung (23.5%) and bone (23.5%). Anlotinib was given as first-line treatment in 3 patients (17.6%), second lines treatment in 7 patients (41.2%), and third to six-lines treatment in 7 patients (41.2%). All patients received anlotinib combined with chemotherapy and/or immunotherapy. One patient achieved a complete response (5.9%), 7 patients had a partial response (41.2%), 5 patients had stable disease (29.4%), and 4 patients had progressive disease (23.5%). The overall disease control rate and the overall response rate were 76.5% and 47.1%, respectively. The median progression-free survival was 8.1 months, and the median overall survival was not reached. The incidence of grade 3 adverse events was 30%. No unexpected side effects or treatment-related death were observed. Anlotinib, as a combination treatment, has a promising antitumor activity and a manageable safety profile in patients with RM-NPC. Our results add to the growing evidence that supports the benefits of combining antiangiogenic drugs in RM-NPC. Randomized controlled clinical trials investigating the evaluation of anlotinib are warranted.

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.

Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study

ObjectiveThis study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M−NPC). Patients and MethodsThis multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M−NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. ResultsA total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8–25.2) months. ORR was 26.1 % (95 %CI:10.2–48.4). The ORR were 44.4 % (95 %CI: 13.7–78.8) and 14.3 % (95 %CI:1.8–42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2–73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9–45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84–9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5–91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. ConclusionCadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

Tumor volume instead of recurrent T category predicts clinical outcome of patients with locally recurrent nasopharyngeal carcinoma salvaged by carbon ion radiation therapy

BackgroundAlthough carbon ion radiation therapy (CIRT) substantially improves the overall survival (OS) of patients with LR-NPC, approximately 40% of the patients may develop local recurrence. The purpose of study is to assess the value of tumor volume (TV) as a predictive tool to guide individualized CIRT. MethodsConsecutive patients with LR-NPC treated using CIRT at Shanghai Proton and Heavy Ion Center between April 2015 and May 2019 were included. TV before CIRT was delineated and calculated. The generalized additive Cox model was used to examine the relationship between TV and OS and local progression-free survival (LPFS). A cutoff value of tumor volume was identified to best discriminate patients with different 2-year OS rates, using receiver operating characteristic (ROC) analysis. ResultsA total of 157 patients were enrolled. The median tumor volume was 22.49 (2.52–90.13) ml. In the univariable analyses, tumor volume was significantly associated with OS (p < 0.001) and LPFS (p = 0.01). The relationships with OS (p = 0.009) and LPFS (p = 0.020) remained significant in multivariable analyses. Using ROC analysis, a TV of 26.69 ml was identified to predict the 2-year OS rate. To facilitate potential clinical use, 25 ml was designated as the final cutoff value. The 2-year OS and LPFS rates were 88.6 % vs 62.3 %, and 54.7 % vs 35.5 %, for patients with a TV ≤ 25 ml and > 25 ml, respectively. ConclusionTumor volume could predict the OS and LPFS of patients. We propose that tumor volume should be considered in the risk stratification and CIRT-based treatment for patients with LR-NPC.

Primary nasopharyngeal carcinoma with cerebrospinal fluid EBV positivity: A case report and mini literature review

BackgroundTo summarize the diagnosis and treatment of a patient with nasopharyngeal carcinoma and cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) positivity (determined by next-generation sequencing), review the relevant literature, and explore the significance of EBV presence in the CSF of patients with nasopharyngeal carcinoma. MethodsA patient presenting with headache as the initial symptom was diagnosed with nasopharyngeal carcinoma and admitted to the Eighth Medical Center of Chinese PLA General Hospital on March 3, 2021. Available databases were screened for reports on nasopharyngeal carcinoma with EBV-positive CSF and analyzed. The patients’ general information, initial symptoms, treatment, and prognosis were subsequently evaluated. ResultsEBV-positive CSF is commonly observed in patients with recurrent nasopharyngeal carcinoma. However, no reports of EBV-positive CSF in patients with primary nasopharyngeal carcinoma have been published to date. ConclusionThe presence of EBV in the CSF of patients with recurrent nasopharyngeal carcinoma is indicative of a poor prognosis. Thus, newly diagnosed nasopharyngeal carcinoma patients should undergo a lumbar puncture as soon as possible to have their CSF tested for EBV. Such a measure would promptly predict the prognosis and facilitate the development of a personalized treatment strategy.

Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

Toripalimab (Loqtorzi) for nasopharyngeal carcinoma.

Toripalimab-tpzi (Loqtorzi – Coherus Biosciences), a programmed death receptor-1 (PD-1)-blocking antibody, has been approved by the FDA for use in combination with cisplatin and gemcitabine for first-line treatment of recurrent locally advanced or metastatic nasopharyngeal carcinoma and for use as monotherapy for treatment of recurrent unresectable or metastatic nasopharyngeal carcinoma in adults with disease progression on or after platinum-based chemotherapy. It is the first immune checkpoint inhibitor to be approved in the US for treatment of nasopharyngeal carcinoma.