Metastatic Nasopharyngeal Carcinoma Patients Research Articles

Development of a prognostic model to identify the metastatic nasopharyngeal carcinoma patients who may benefit from chemotherapy combination PD-1 inhibitor.

We aimed to establish a prognostic model to identify suitable candidates for chemotherapy combination PD-1 inhibitor in metastatic nasopharyngeal carcinoma (NPC) patients. In this retrospective study, we included 524 patients (192 patients treated with chemotherapy combination PD-1 inhibitor and 332 received chemotherapy alone as first-line regimen) with metastatic NPC between January 2015 and March 2021. We developed a prognostic model to predict progression-free survival (PFS). A model-based trees approach was applied to estimate stratified treatment effects using prognostic scores and two well-matched risk groups (low-risk and high-risk) were created using propensity score matching. A prognostic nomogram was established with good accuracy for predicting PFS (c-index values of 0.71; 95% confidence interval, 0.66-0.73). The survival curves were significantly different between low-risk and high-risk groups (median PFS: 9.8 vs. 22.8 months, P < 0.001, respectively). After propensity matching analysis, chemotherapy combination PD-1 inhibitor was significantly associated with superior PFS as compared with chemotherapy alone (median PFS, 10.6 versus 9.3 months, P = 0.016) in the high-risk group. However, no significant difference between chemotherapy combination PD-1 inhibitor and chemotherapy was observed (P = 0.840) in the low-risk groups. Our novel prognostic model was able to stratify patients with metastatic NPC into low-risk or high-risk groups and identify candidates for PD-1 inhibitor therapy. These results are expected to be confirmed by a prospective clinical trial.

Clinical characteristics and prognostic factors affecting survival after radical radiotherapy for early and late post-treatment metastatic nasopharyngeal carcinoma

ObjectiveWe compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies.MethodsThis was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan–Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models.ResultsThe cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease.ConclusionsThe time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.

Maintenance therapy improves the survival outcomes of patients with metastatic nasopharyngeal carcinoma responding to first-line chemotherapy: a multicentre, randomized controlled clinical study

PurposeTo explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers.MethodsThis was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety.ResultsThe median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373–0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227–0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350–0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230–0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1–2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions.ConclusionFor metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment.Trial registrationThe study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939).

Plasma Circulating Tumor Epstein-Barr Virus for the Surveillance of Cancer Progression in Bone-Only Metastatic Nasopharyngeal Carcinoma.

BackgroundPlasma Epstein–Barr virus DNA (EBV-DNA) is a sensitive and specific biomarker for nasopharyngeal carcinoma (NPC). We investigated whether longitudinal monitoring of EBV-DNA could accurately detect clinical disease progression in NPC patients with bone-only metastases.MethodsIn this retrospective study, a total of 105 patients with bone-only metastatic NPC who were treated with platinum-based first-line chemotherapy were enrolled. Undetectable EBV-DNA after first-line chemotherapy was defined as a biochemical complete response (BCR). The correlation of the EBV-DNA dynamic status with overall survival (OS) and progression-free survival (PFS) was determined by Cox regression. The correlation between non-normalized EBV-DNA period and PFS period was determined.ResultsAfter a median follow-up time of 53.4 months [Interquartile range (IQR): 42.8–80.6], 64 patients had disease progression. Thirty-nine of 105 patients (37.1%) had a BCR at all follow-up time points, and none of these 39 patients had disease progression, corresponding to a negative predictive value (NPV) of 100%. Sixty-six patients had a detectable EBV-DNA during surveillance, with 64 diagnosed as disease progression at the last follow-up, for a positive predictive value (PPV) of 97.0%. Actuarial 3-year OS rates were 45.0% for patients with detectable EBV-DNA during posttreatment surveillance and 100% for patients with undetectable EBV-DNA. Lastly, median lead time between non-normalized EBV-DNA and clinically proven progression was 5.87 ± 0.67 months.ConclusionsTaken together, EBV-DNA provided predictive value for the bone-only metastatic NPC patients. The results should be validated in prospective randomized studies.

Association of Epstein–Barr virus DNA and SAA with S1 maintenance therapy outcomes in patients with metastatic nasopharyngeal carcinoma

Objectives: The relevant biomarkers in predicting maintenance therapy (MT) outcomes in metastatic nasopharyngeal carcinoma (NPC) are yet unclear. Patients & methods: Metastatic NPC patients were randomly divided intoMT (S1-MT) and non-MT groups. The association of Epstein-Barr virus DNA (EBV-DNA) and SAA with survival was assessed. Results: A total of 183 patients were included. S1-MT significantly increased the progression-free survival (PFS) and overall survival (OS) of the metastatic NPC patients (both p<0.001). For patients who were EBV-DNA positive or had decreased SAA, the PFS and OS increased significantly after S1-MT (both p<0.001), while patients with stable SAA did not benefit from S1-MT. Conclusion: S1-MT improved the PFS and OS of metastatic NPC patients. EBV-DNA and SAA status were closely associated with the outcomes of S1-MT. Clinical trial registration number: ChiCTR-IOR-16007939.

Camrelizumab plus famitinib in patients with recurrent or metastatic nasopharyngeal carcinoma: Data from an open-label, multicenter phase II basket study.

e18031 Background: Immune-checkpoint inhibitor (ICI) in combination with antiangiogenic therapy have the potential for synergistic activity. We report the results of camrelizumab plus famitinib for the treatment of recurrent or metastatic, ICI-resistant nasopharyngeal carcinoma (NPC) from an open-label, multicenter, phase II basket trial. Methods: Patients (pts) with histologically confirmed recurrent or metastatic NPC (nonkeratinizing carcinoma, WHO type II-III), who had been treated with platinum-based chemotherapy and ICIs (≤2 lines of systemic treatment), were enrolled to receive camrelizumab (200 mg intravenously every 3 weeks) and famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per RECIST version 1.1, and secondary endpoints included duration of response (DoR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Results: Between Oct 23, 2020, and Sep 24, 2021, 15 recurrent or metastatic NPC pts were enrolled. Among them, 12 (80.0%) and 3 (20.0%) pts had received their prior 1st-line and 2nd-line treatment, respectively. All pts were pretreated with anti-PD-1/PD-L1 immunotherapy (toripalimab, n = 9; tislelizumab, n = 4; sintilimab, n = 1; pembrolizumab, n = 1). As of Nov 30, 2021, median time from enrollment to data cutoff was 6.3 months (range, 2.2-13.3). No pt had a complete response, 5 (33.3%) pts had a confirmed partial response, 7 (46.7%) pts had stable disease, 2 (13.3%) pts had progressive disease and 1 (6.7%) pt was not evaluable. The ORR was 33.3% (95% confidence interval [CI], 11.8-61.6), the DCR was 80.0% (95% CI, 51.9-95.7). Most pts (73.3%) experienced reduction in target lesion size from baseline, with a median change of -36.0%. The median DoR was 4.2 months (95% CI, 2.1-not reached [NR]), median PFS was 6.3 months (95% CI, 4.1-NR), and median OS has not been reached. Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 7 (46.7%) pts, mainly decreased platelet count (13.3%), decreased neutrophil count (13.3%) and palmar-plantar erythrodysaesthesia syndrome (13.3%). Treatment interruption and discontinuation due to TRAEs occurred in 11 (73.3%) and 1 (6.7%) pts, respectively. Five (33.3%) pts had serious TRAEs (grade 2 platelet count decreased, grade 2 pharyngeal necrosis, grade 2 pulmonary tuberculosis, grade 3 left ventricular dysfunction, grade 3 pharyngeal hemorrhage; n = 1 for each), and no treatment-related death was reported. Conclusions: Camrelizumab plus famitinib showed encouraging antitumor activity in recurrent or metastatic NPC patients who were resistant to ICI treatment, with an acceptable and manageable safety profile. This combination might provide a novel alternative treatment strategy in this challenging disease setting and support further investigation. Clinical trial information: NCT04346381.

Taxane/gemcitabine-containing chemotherapy plus locoregional IMRT for patients with de novo metastatic nasopharyngeal carcinoma: the treatment outcomes and prognostic factors analysis

PurposeTo evaluate treatment outcomes of de novo metastatic nasopharyngeal carcinoma (mNPC) patients receiving taxane/gemcitabine-containing chemotherapy followed by locoregional intensity-modulated radiotherapy (IMRT) and analyze potential prognostic factors.MethodsA total of 118 patients between March 2008 and November 2018 were retrospectively analyzed. All the patients were treated with taxane/gemcitabine-containing systemic chemotherapy followed by definitive locoregional IMRT. Potential prognostic factors including baseline absolute lymphocyte count (ALC) and the subdivision of metastasis were analyzed.ResultsThe median follow-up time for the whole group was 31.5 months (range 5–138 months). Of the 118 patients, 9 (7.6%) patients experienced local regional failure and 60 (50.8%) patients had progression of distant metastasis. At the time of the last follow-up, 61 (51.7%) patients were dead. The 5-year actuarial progression free survival (PFS), overall survival (OS),distant metastasis relapse free survival (DMFS) and local regional recurrence free survival (LRFS) were 34.2%, 44%, 41.1% and 82.6%, respectively. Baseline lymphocyte count ≥ 1600/μl prior to the treatment conferred better locoregional control (5y-LRFS 96% vs. 64.7%, p < 0.001) and distant metastasis control (5y-MFS 50.4% vs. 32.4%, p = 0.023). The multivariate analysis showed that high lymphocyte count was the most relevant predictor of superior PFS (HR = 0.236, p < 0.001) and OS (HR = 0.518, p = 0.04). M subdivision was found as another independent prognostic factor for OS but not for PFS.ConclusionTaxane/gemcitabine-containing chemotherapy combined with IMRT represents an effective treatment modality for mNPC. Baseline ALC is an independent significant prognostic factor for PFS and OS.

M1 stage subdivisions based on 18F-FDG PET-CT parameters to identify locoregional radiotherapy for metastatic nasopharyngeal carcinoma.

Purpose:To establish a risk classification of de novo metastatic nasopharyngeal carcinoma (mNPC) patients based on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) radiomics parameters to identify suitable candidates for locoregional radiotherapy (LRRT).Methods:In all, 586 de novo mNPC patients who underwent 18F-FDG PET-CT prior to palliative chemotherapy (PCT) were involved. A Cox regression model was performed to identify prognostic factors for overall survival (OS). Candidate PET-CT parameters were incorporated into the PET-CT parameter score (PPS). Recursive partitioning analysis (RPA) was applied to construct a risk stratification system.Results:Multivariate Cox regression analyses revealed that total lesion glycolysis of locoregional lesions (LRL-TLG), the number of bone metastases (BMs), metabolic tumor volume of distant soft tissue metastases (DSTM-MTV), pretreatment Epstein–Barr virus DNA (EBV DNA), and liver involvement were independent prognosticators for OS. The number of BMs, LRL-TLG, and DSTM-MTV were incorporated as the PPS. Eligible patients were divided into three stages by the RPA-risk stratification model: M1a (low risk, PPSlow + no liver involvement), M1b (intermediate risk, PPSlow + liver involvement, PPShigh + low EBV DNA), and M1c (high risk, PPShigh + high EBV DNA). PCT followed by LRRT displayed favorable OS rates compared to PCT alone in M1a patients (p < 0.001). No significant survival difference was observed between PCT plus LRRT and PCT alone in M1b and M1c patients (p > 0.05).Conclusions:The PPS-based RPA stratification model could identify suitable candidates for LRRT. Patients with stage M1a disease could benefit from LRRT.

Nasopharyngeal Carcinoma: Clinical Achievements and Considerations Among Treatment Options.

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.

Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein-Barr Virus Infection.

Epstein–Barr virus (EBV), a type 4 γ herpes virus, is recognized as a causative agent in nasopharyngeal carcinoma (NPC). Incidence of EBV-positive NPC have grown in recent decades along with worse outcomes compared with their EBV-negative counterparts. Latent membrane protein 1 (LMP1), encoded by EBV, induces NPC progression. The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases (RTK), is a driver of tumorigenesis, including for NPC. Little data exist on the relationship between EGFR and EBV-induced NPC. In our initial review, we found that LMP1 promoted the expression of EGFR in NPC in two main ways: the NF-κB pathway and STAT3 activation. On the other hand, EGFR also enhances EBV infection in NPC cells. Moreover, activation of EGFR signalling affects NPC cell proliferation, cell cycle progression, angiogenesis, invasion, and metastasis. Since EGFR promotes tumorigenesis and progression by downstream signalling pathways, causing poor outcomes in NPC patients, EGFR-targeted drugs could be considered a newly developed anti-tumor drug. Here, we summarize the major studies on EBV, EGFR, and LMP1-regulatory EGFR expression and nucleus location in NPC and discuss the clinical efficacy of EGFR-targeted agents in locally advanced NPC (LA NPC) and recurrent or metastatic NPC (R/M NPC) patients.

Capecitabine maintenance therapy after induction chemotherapy in newly diagnosed metastatic nasopharyngeal carcinoma: An open-label, randomized, controlled, phase trial.

6044 Background: Capecitabine maintenance therapy improves outcomes in various tumor types, but minimal data are available on the effect of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC). We aimed to investigate whether capecitabine maintenance therapy would prolong the progression-free survival (PFS) of newly diagnosed metastatic NPC, in comparison to best supportive care (BSC). Methods: This was an open-label, randomized, controlled, phase trial. Eligible patients for maintenance randomisation were aged 18-65 years old with newly diagnosed metastatic NPC at the Sun Yat-Sun University Cancer Center (SYSUCC), had completed 4 to 6 cycles of induction chemotherapy as per protocol and had achieved disease control to protocol treatment, including capecitabine. Patients were randomly assigned 1:1 to capecitabine maintenance (oral 1,250 mg/m2/day on days 1-14 every 21 days) for up to 24 months with BSC or BSC alone. The primary endpoint was PFS. The secondary endpoints included overall survival, duration of response, objective response rate and adverse effects. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02460419 and is ongoing and no longer recruiting new patients. Results: Between May 16th, 2015, and January 9th, 2020, 140 metastatic NPC patients were screened, and 104 eligible patients were randomly assigned to capecitabine maintenance plus BSC (n = 52) or BSC alone (n = 52). After a median follow-up of 33.1 months (IQR, 21.5-50.7 months), median PFS was 35.2 months in the capecitabine maintenance group and 9.1 months in the BSC group (HR: 0.426; 95%CI: 0.248-0.731, P = 0.001). The most commongrade 3 or 4 adverse events during maintenance therapy were hand-foot syndrome (10.0%), nausea/vomiting (6.0%), fatigue (4.0%), and mucositis (4.0%). Totally 37 deaths occurred during follow-up, 14 (26.9%) in the capecitabine maintenance group and 23 (44.2%) in the BSC group. Overall survival data was immature. No deaths in the capecitabine maintenance group were deemed treatment related. Conclusions: Capecitabine maintenance significantly improved PFS in patients with newly diagnosed metastatic NPC who achieved disease control after induction chemotherapy compared to BSC and exhibited low grade and manageable toxicities. Clinical trial information: NCT02460419.

The efficacy of locoregional radiotherapy plus chemotherapy vs. chemotherapy alone in metastatic nasopharyngeal carcinoma: a meta-analysis.

The role of locoregional radiotherapy (LRT) of the nasopharynx and neck in patients with metastatic nasopharyngeal carcinoma (M-NPC) remains unclear. The present meta-analysis aimed to compare the efficacy of chemotherapy (CT) plus LRT with CT alone in M-NPC patients. Eligible manuscripts were searched in the following electronic databases: Cochrane Library, Embase, and PubMed. The hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS), and the risk ratio (RR) of the objective response rate (ORR) and disease control rate (DCR) were pooled and expressed with the 95% confidence intervals (CIs). The analysis was conducted using Review Manager and Stata software. In total 15 retrospective studies and 1 randomized controlled trial were identified comparing 3,402 M-NPC patients of whom 1,387 received CT alone and 2,015 were treated with CT plus LRT. The adjusted HR of OS for CT plus LRT compared with CT alone was 0.45 (95% CI: 0.40-0.52), while the pooled HR of PFS was 0.37 (95% CI: 0.29-0.49). The pooled RR of ORR and DCR for CT plus LRT compared with CT alone was 0.60 (95% CI: 0.46-0.79) and 0.77 (95% CI: 0.71-0.85), respectively. Heterogeneity or publication bias in the studies was not found to have altered the conclusion. For patients with M-NPC, CT + LRT is superior to CT alone providing the higher OS, PFS, ORR, and DCR compared with CT alone. CT combined with LRT should be recommended as a more suitable choice for M-NPC patients.

Metastatic characteristics associated with survival of synchronous metastatic nasopharyngeal carcinoma in non-epidemic areas

IntroductionThe current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a “catch-all” category, we previously successfully established a M1 subdivision system based on prognostic metastatic characteristics in epidemic areas. We aimed to figure out metastatic characteristics associated with survival outcomes of NPC in non-epidemic areas. MethodsA total of 428 newly diagnosed de novo metastatic NPC patients from 2010 to 2016 were analyzed from the population-based Surveillance, Epidemiology, and End Results program. Cox proportional hazard ratios (HRs) were used to identify independent prognostic factors for survival. ResultsThe most frequently involved metastatic locations were the bones (53.04%), the lungs (36.68%), the livers (29.21%) and the distant lymph nodes (24.07%). Univariate analysis indicated that bone involvement (HR = 1.39, 95% CI = 1.09–1.77), liver involvement (HR = 1.44, 95% CI = 1.12–1.85) and multiple metastatic locations (HR = 1.32, 95% CI = 1.04–1.67) were negative prognostic factors of overall survival (OS) for patients with synchronous metastasis. We established a new M1 subdivision system based on metastatic characteristics: M1a, without bone and liver involvement; M1b, single bone or liver involvement; M1c, multiple metastatic locations including bone and/or liver. Multivariate analysis confirmed that our new subcategories were associated with significantly different OS (M1b vs M1a: HR = 1.54, 95% CI = 1.11–2.16; M1c vs M1a: HR = 2.03, 95% CI = 1.47–2.78). ConclusionsSynchronous metastatic NPC patients with multiple metastatic locations involved bone and/or liver were prone to suffer from dismal OS and might need more attentions for selection of treatment modality.

Prognostic model for risk stratification of de novo metastatic nasopharyngeal carcinoma patients treated with chemotherapy followed by locoregional radiotherapy

BackgroundThere is no clinically applicable prognostic model designed for patients with de novo metastatic nasopharyngeal carcinoma (mNPC) treated with chemotherapy followed by locoregional radiotherapy (LRRT). We sought to develop a predictive tool of overall survival for individualized prediction and risk stratification in this heterogeneous patient population.Patients and methodsA total of 244 eligible patients with de novo mNPC, who were treated with platinum-based first-line chemotherapy followed by LRRT, were included in this retrospective study. We divided patients into the training and validation sets based on the date of initial treatment, with 152 patients treated between 2008 and 2013 comprising the training set for model development and 92 patients treated at a later time (2014 to 2015) forming the validation set. We applied Cox proportional hazards model to examine factors associated with overall survival (OS). We developed and subsequently validated a prognostic model to predict OS. We assessed the performance of this prognostic model and stratified patients based on prognostic scores obtained from this proposed model.ResultsThe median OS of the entire cohort was 60.9 months. C-creative protein, number of metastatic sites, liver metastasis, post-treatment Epstein–Barr virus DNA, and response of metastasis were significantly associated with OS. A prognostic model for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.759), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.800], and calibration, and was further validated in an independent dataset. A risk stratification derived from the model can stratify these patients into three prognostic subgroups with significantly different survival.ConclusionWe developed and validated a prognostic model that exhibited adequate performance in individualized prediction and risk stratification for patients with de novo mNPC treated with chemotherapy followed by LRRT.

Optimizing the Treatment Pattern for De Novo Metastatic Nasopharyngeal Carcinoma Patients: A Large-Scale Retrospective Cohort Study.

ObjectivesTo investigate the optimal treatment pattern in patients with de novo metastatic nasopharyngeal carcinoma (NPC).MethodsWe assessed 502 consecutive and unselected de novo metastatic NPC patients in Sun Yat-sen University Cancer Center (SYSUCC) from November 2006 to October 2016 in our study. All patients were treated with palliative chemotherapy (PCT) and 308 patients received locoregional radiotherapy (LRRT) subsequently. Our primary study endpoint was overall survival (OS).ResultsThe patients treated with LRRT were associated with improved survival on univariate analysis (3-year OS rate 63.7% vs. 31.8%, P < 0.001) and multivariate analysis (HR 0.52, 95%CI 0.40–0.68, P < 0.001). The overall survival benefit of more than 4 PCT cycles was significant in female (HR 0.45, 95% CI 0.24–0.86, P = 0.016) and patients with multiple metastatic sites (HR 0.42, 95% CI 0.26–0.66, P < 0.001). The application of concurrent chemotherapy (CCT) was not associated with better survival among patients receiving LRRT (HR 1.31, 95% CI 0.92–1.86, P = 0.141).ConclusionLRRT prolonged survival in de novo metastatic NPC. For patients treated with multiple metastatic sites, more than 4 cycles of PCT is necessary. CCT does not improve survival in de novo metastatic NPC patients.

Comparison of Gemcitabine Plus Cisplatin vs. Docetaxel Plus Fluorouracil Plus Cisplatin Palliative Chemotherapy for Metastatic Nasopharyngeal Carcinoma.

Objective: Our study aimed to compare the efficacy and toxicity of two chemotherapy regimens, gemcitabine plus cisplatin (GP) vs. docetaxel plus, fluorouracil plus cisplatin (TPF), in metastatic nasopharyngeal carcinoma (NPC) patients.Methods: We retrospectively enrolled metastatic NPC patients between July 2006 and December 2016 who were treated with TPF or GP palliative chemotherapy (PCT). The association between the PCT regimens and survival conditions was evaluated by log-rank tests and the Cox proportional hazards model. A cohort was created using propensity score matching with the ratio of 1:1 to clarify the results of the multivariable Cox regression analyses. Overall survival (OS) was the primary endpoint.Results: Of 266 eligible patients, 186 and 80 patients, respectively, received TPF and GP regimen. No significant difference was demonstrated in the survival rate between the GP and TPF groups (3-year OS: 52.6 vs. 50.3%; P = 0.929). However, multivariable analysis suggested receiving GP as an independent protective factor (hazard ratio, 0.864; 95% confidence interval, 0.753–0.992; P = 0.042). In the matched cohort, treatment with GP was also associated with a significantly higher OS (3-year OS: 52.6 vs. 35.6%, P = 0.042). Subgroup analysis indicated that the superiority of GP reflected in patients with secondary metastases rather than primary metastases. The incidence of grade 3 to 4 treatment-related toxicity was more common in the TPF group than in the GP group.Conclusion: Our study suggested that GP might be superior to TPF for metastatic NPC patients, especially those with secondary distant metastases. Further studies are necessary to validate our results.

Prognostic factors in metastatic nasopharyngeal carcinoma

IntroductionNasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis. ObjectiveThe study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma. MethodsA retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14 years (2003–2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance. ResultsOne hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1–156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1–156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3‒G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1–41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor. ConclusionOligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma.

Clinical response and biomarker analysis of a phase II basket trial of toripalimab, a PD-1 mAb in combination with standard chemotherapy as a first-line treatment for patients with solid tumors.

e15083 Background: Platinum based chemotherapy is the standard care for 1st line treatment of metastatic gastric adenocarcinoma (GC), esophageal squamous cell carcinoma (ESSC), nasopharyngeal carcinoma (NPC) and head and neck squamous cell carcinoma (HNSCC). Combinations of PD-1 blockade with chemotherapy have shown promising but mixed results in solid tumors. Predictive biomarkers for chemo-immunotherapy combination as 1st line treatment remain undefined. Methods: Patients (n = 60) included in this analysis were four complete cohorts from a multi-center, phase Ib/II trial (NCT02915432) evaluating the safety and activity of toripalimab, a humanized PD-1 antibody in combination with standard chemotherapy for the 1st line treatment of GC, EC, NPC and HNSCC (excluding NPC). Whole exome sequencing (WES), RNA sequencing and immunohistochemistry were performed on tumor biopsy samples. PD-L1 expression and tumor mutational burden (TMB) were evaluated for correlation with clinical efficacy. Results: From Oct 2016 to Feb 2019, 33 GC, 12 ESSC, 12 NPC and 3 HNSCC patients were enrolled and treated with 240mg or 360 mg toripalimab Q3W via IV infusion in combination with Oxaliplatin/Capecitabine (XELOX), Paclitaxel/Cisplatin (PP), Gemcitabine/Cisplatin (GP) and Docetaxel/Cisplatin/5-FU(TPF) respectively. By the data cutoff date of Nov 15, 2019, all patients experienced treatment related adverse event (TRAE). There was one TRAE (heart failure) leading to death. Grade 3-4 TRAEs occurred in 67% patients, mostly attributed to chemotherapy, including 27% neutropenia, 23% thrombocytopenia, 18% leukopenia and 12% anemia. As assessed by investigators according to RECIST v1.1, the ORR/DCR were 54.5%/84.8%, 66.7%/91.7%, 75.0%/83.3% and 33.3%/100% respectively for GC, EC, NPC and HSNCC cohorts. The median duration of response was 8.3, 6.8, 7.7 and 7.1 months respectively. WES showed distinctive patterns of genomic alterations among different cohorts. The clinical response was not correlated with either PD-L1 expression or tumor mutational burden. Conclusions: Toripalimab in combination with chemotherapy as first-line treatments showed promising results for metastatic GC, EC, NPC and HNSCC patients. Two randomized Phase III trials of toripalimab in combination with Paclitaxel/Cisplatin or Gemcitabine/Cisplatin versus chemotherapy alone are ongoing to further evaluate the combination as first-line treatments in metastatic EC and NPC patients. Clinical trial information: NCT02915432 .

Quality of life and survival outcome for patients with nasopharyngeal carcinoma treated by volumetric-modulated arc therapy versus intensity-modulated radiotherapy

BackgroundTo evaluate the longitudinal changes of quality of life (QoL) and survival in patients with nasopharyngeal carcinoma (NPC) treated by volumetric-modulated arc therapy (VMAT) versus intensity-modulated radiotherapy (IMRT).MethodsOne hundred and forty non-distant metastatic NPC patients treated by VMAT (n = 66) or IMRT (n = 74) with simultaneously integrated boost between March 2013 and December 2015 at a single institute were analyzed. QoL was prospectively assessed by the EORTC QLQ-C30 and HN35 questionnaires at the four time points: before RT, RT 42.4 Gy (20 fractions), and 3, 12 months after RT.ResultsThe 3-year locoregional relapse-free survival, distant metastasis-free survival, failure-free survival, and overall survival rates were 96.6, 89.4, 86.1%, and 87.4 for the VMAT group, respectively, compared with 91.4, 90.0, 79.8, and 91.3% for the IMRT group (p value > 0.05). The pattern of QoL changes was similar between the VMAT and IMRT group. No statistically or clinically significant difference in all the QoL scales was observed between VMAT and IMRT group at each time point. Compared to before RT, we observed statistically (p<0.05) and clinically (difference of mean scores≧10) better outcome in global QoL and social functioning, but worse head and neck symptomatic outcome in swallowing, taste/smell, opening mouth, dry mouth, and sticky saliva at the time point of 1 year after RT for both groups.ConclusionThe study provides the evidence that the tumor control, survival and changes of QoL is compatible for NPC patients treated by VMAT versus IMRT.

Intensive Local Radiotherapy Is Associated With Better Local Control and Prolonged Survival in Bone-Metastatic Nasopharyngeal Carcinoma Patients.

Objective: To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC).Background: The current treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients.Methods: Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model.Results: Patients who received 60–75 Gy/30–35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37–0.78, P = 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46–0.84, P = 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67–0.95, P = 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10–0.75, P = 0.007), PFS (HR, 0.60, 95% CI, 0.42–0.87, P = 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29–1.03, P = 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS.Conclusions: Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor.