Here we report long-term outcomes of adjuvant metronomic capecitabine in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicenter, open-label, parallel-group, randomized, controlled, phase 3 trial, 406 patients who had completed definitive chemoradiotherapy were randomly assigned (1:1) to receive either adjuvant metronomic capecitabine (650 mg m-2 twice daily for 1 year) or observation. The primary endpoint was failure-free survival; secondary endpoints included overall survival (OS), distant failure-free survival, locoregional failure-free survival, and safety, as reported in this analysis. The trial met its primary endpoint. With a median follow-up of 71.3 months, metronomic capecitabine significantly improved OS (hazard ratio = 0.53, 95% confidence interval, 0.31-0.91, P = 0.019). Grade 3 adverse events occurred in 35 (17%) of 201 patients in the metronomic capecitabine group and 11 (6%) of 200 in the observation group; one (<1%) grade 4 neutropenia was reported. In a post hoc analysis, completion of the 1 year course was associated with improved OS, whereas dose reductions and relative dose intensity showed no association with OS. Patients with a higher post-radiotherapy neutrophil-to-lymphocyte ratio derived greater benefit from metronomic capecitabine. These findings support the long-term therapeutic benefit of adjuvant metronomic capecitabine in locoregionally advanced nasopharyngeal carcinoma. ClinicalTrials.gov identifier: NCT02958111 .

Radioresistance challenges the clinical outcomes of nasopharyngeal carcinoma (NPC). The 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) is a crucial kinase of PI3K/AKT signaling pathway which has been implicated in the process of radioresistance. However, the role of PDK1 in NPC remains largely unclear.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically on the based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported significantly improved failure-free survival using gemcitabine plus cisplatin induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized trial, patients were assigned to be treated with concurrent chemoradiotherapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiotherapy (n = 242). With a median follow-up of 69.8 months, the induction chemotherapy group had a significantly higher 5-year OS (87.9% v 78.8%, hazard ratio, 0.51 [95% CI 0.34 to 0.78]; P = .001) and a comparable risk of late toxicities (≥ grade 3, 11.3% v 11.4%). Notably, the depth of the tumor response to induction chemotherapy correlated significantly and positively with survival (complete response v partial response v stable/progressive disease, 5-year OS, 100% v 88.4% v 61.5%, P = .005). Besides, patients with a low pretreatment cell-free Epstein-Barr virus DNA load (< 4,000 copies/mL) might not benefit from induction chemotherapy (5-year OS, 90.6% v 91.4%, P = .77). In conclusion, induction chemotherapy before concurrent chemoradiotherapy improved OS significantly in patients with locally advanced nasopharyngeal carcinoma, without increasing the risk of late toxicities. Tumor response to induction chemotherapy and pretreatment cell-free Epstein-Barr virus DNA might be useful to guide individualized treatment.

Egl-9 Family Hypoxia Inducible Factor 1 (EGLN1) is a proline hydroxylase mediating degradation of hypoxia-inducible factor α (HIFα) through the ubiquitination system. Studies have indicated an essential role for EGLN1 in angiogenesis and tumorigenesis. However, there is no consensus on the regulation of EGLN1 and its mechanism of action on nasopharyngeal carcinoma (NPC). This study explored the association of the expression of EGLN1 with characteristics of NPC tumors and its underlying mechanism. We found that the expression of EGLN1 showed a positive correlation with tumor T classification and clinical staging of patients with NPC. EGLN1 could promote cell proliferation, invasion and migration, and even enhance the cancer stem cells (CSCs) prosperity and radioresistance of NPC cells. Mechanistically, EGLN1 facilitated degradation of tumor protein p53 through the ubiquitination system. This effect could be weakened in the presence of dimethyloxalylglycine (DMOG), suggesting that EGLN1 down-regulated p53 based on its hydroxylase activity. In conclusion, overexpression of EGLN1 promoted oncogenesis and induced a CSC-like phenotype in NPC cells, then enhancing the ability for radioresistance by interacting with p53 in a hydroxylase-dependent manner. Thus, EGLN1 might serve as a potential therapeutic target for NPC.

Background Fermitin family member 1 (FERMT1) is significantly overexpressed in human cancers and associated with poor prognosis, but its contributions to tumorigenesis and nasopharyngeal carcinoma (NPC) progression remain unclear. Methods The public GEO database was examined to investigate the role of FERMT1. Immunohistochemistry (IHC) staining of FERMT1 was performed in NPC tissues to corroborate the results. Western blotting and qRT-PCR were performed to test the expression of related proteins and mRNAs. Cell counting kit-8 assay (CCK8 assay) and colony formation assays were carried out to investigate the association of FERMT1 expression with NPC cell proliferation. The wound healing assay and Transwell assay were used to detect the migration and invasion of NPC cells. Flow cytometric analysis was conducted to detect the cell cycle transition of NPC cells. Co-immunoprecipitation (Co-IP) was employed to identify the correlation of FEMRT1 and Nod-like receptor family protein 3 (NLRP3). Xenograft tumors were generated to investigate the effect of FERMT1 on the growth of NPC cells in vivo. Results Here, we found that FERMT1 was upregulated in NPC tissues and correlated with the clinicopathological characteristics of NPC patients. Moreover, knockdown of FERMT1 significantly decreased cell proliferation, migration and invasion by mediating epithelial-mesenchymal transition (EMT) and cell cycle arrest of NPC cells both in vitro and in vivo. Knockdown FERMT1 inhibited EMT through directly binding to the NLRP3 and inhibited NF-kB signaling pathway. Conclusion These data indicated that FERMT1 could be a good potential therapeutic target for NPC treatment.

目的 观察培美曲塞+奈达铂联合贝伐珠单抗治疗后培美曲塞联合贝伐珠单抗维持治疗方案在晚期非鳞非小细胞肺癌患者中的疗效和安全性,并探讨影响该化疗方案疗效的相关因素.方法 收集2015年6月—2018年6月经病理确诊的50例晚期非鳞非小细胞肺癌患者,所有患者均接受培美曲塞+奈达铂联合贝伐珠单抗治疗,并对治疗后疾病未进展的患者给予培美曲塞联合贝伐珠单抗维持治疗,直至疾病进展或出现不可耐受的不良反应.对患者的近期疗效和不良反应进行分析.结果 50例患者的客观缓解率(ORR)和疾病控制率(DCR)分别为42％(21/50)和86％(43/50),中位无进展生存期(PFS)为11个月(95％CI:8.1～13.9).治疗相关不良反应主要为骨髓抑制,但均可耐受,无不良反应相关性死亡.结论 培美曲塞+奈达铂联合贝伐珠单抗治疗后培美曲塞联合贝伐珠单抗维持化疗方案在晚期非鳞非小细胞肺癌患者中有较好的疗效和安全性.

6003 Background: Patients suffering from locoregionally advanced nasopharyngeal carcinoma (NPC) commonly develop disease recurrence, despite a high rate of complete clinical remission after standard of care (concurrent cisplatin-radiotherapy, with or without induction chemotherapy). The benefit of additional adjuvant chemotherapy remains unclear. Methods: Patients with high-risk locoregionally advanced NPC (stage III to IVA, excluding T3-4N0 and T3N1), and with no locoregional disease or distant metastasis after definitive chemoradiotherapy, were eligible. They were randomly assigned (1:1) within 12 to 16 weeks after the last radiation dose to receive either capecitabine at a dose of 650 mg/m 2 twice daily for 1 year (metronomic capecitabine group) or observation (standard-therapy group). The primary end point was recurrence-free survival (RFS). The calculated sample size was 201 per group, with an 80% power (two-sided α 0.05) to detect a target hazard ratio (HR) of 0.52. Results: A total of 406 patients underwent randomization, comprising 204 in the metronomic capecitabine group and 202 in the standard-therapy group. After a median follow-up of 36 months (corresponding to 43 months when calculated from the start of standard therapy), the estimated 3-year RFS was 85.9% in the metronomic capecitabine group, as compared with 76.5% in the standard-therapy group (intention-to-treat population; HR 0.51, 95% confidence interval 0.32–0.81; P = 0.003). The incidence of grade 3 adverse events was 17.4% in the metronomic capecitabine group and 5.5% in the standard-therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (9.0%). One grade 4 neutropenia occurred in the metronomic capecitabine group. Neither group sufferd from treatment-related deaths. During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of metronomic adjuvant capecitabine. Conclusions: The addition of metronomic capecitabine as adjuvant therapy to chemoradiotherapy significantly improved RFS in locoregionally advanced NPC, with a manageable safety profile and no compromise to quality of life. Clinical trial information: NCT02958111. [Table: see text]

BACKGROUND:The novel coronavirus infectious disease (COVID-19) is an international concern as it spreads through human populations and across national and international borders.METHODS:In this retrospective study, we consecutively included all cancer patients who had been identified as having a nucleic acid-confirmed COVID-19 from two designated hospitals in Wuhan, China. COVID-19 patients without cancer were also enrolled for comparison. The clinical data were gathered from the medical records from Jan 14 to March 12, 2020.RESULTS:Among the 117 cancer patients diagnosed with COVID-19, the median age was 63 years and 48.7% were male. Male sex, hematologic cancer, dyspnea on admission, and anti-cancer therapies were associated with an increased risk of mortality in cancer patients with COVID-19. We found that elevated levels of TNF-α, IL-2R, IL-6, and IL-8 were associated with a poorer prognosis in cancer patients with COVID-19, but no statistically significant association was found in patients without cancer. In addition, IL-2R and IL-6 markedly decreased in cancer patients who recovered from COVID-19. However, lymphocyte subsets were diminished in cancer patients who died from COVID-19, including total T cells, total B cells, helper T (Th) cells and suppressor T (Ts) cells.CONCLUSIONS:Cancer patients with COVID-19 were associated with high mortality (23.9%). A decrease in lymphocyte subsets and higher levels of cytokines were associated with a higher risk of severe outcome and could be utilized as the reference index to predict the survival outcome of cancer patients with COVID-19.

Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with high mortality and morbidity worldwide, but the underlying biological mechanisms of molecules and tumor infiltrating-immune cells (TIICs) are still unknown. Methods and Results: We obtained mRNAs, lncRNAs, and miRNAs expression profiles of 546 HNSCC from The Cancer Genome Atlas (TCGA) database to develop a ceRNA network. CIBERSORT was employed to estimate the fraction of 22 types of TIICs in HNSCC. Univariate and multivariate Cox regression and lasso regression analyses were used to develop prognostic signatures. Then, two novel risk signatures were constructed respectively based on six ceRNAs (ANLN, KIT, PRKAA2, NFIA, PTX3 and has-miR-148a-3p) and three immune cells (naïve B cells, regulatory T cells and Neutrophils). Kaplan-Meier (K-M) analysis and Cox regression analysis further proved that these two signatures were significant prognostic factors independent of multiple clinicopathological characteristics. Two nomograms were built based on ceRNAs-riskScore and TIICs-riskScore that could be used to predict the prognosis of HNSCC. Co-expression analysis showed significant correlations between miR-148a-3p and naive B cells, naive B cells and plasmas cells. Conclusion: Through construction of the ceRNA network and estimation of TIICs, we established two risk signatures and their nomograms with excellent utility, which indicated the potential molecular and cellular mechanisms, and predicted the prognosis of HNSCC.

DNA damage repair plays an important role in cancer’s initiation and progression, and in therapeutic resistance. The prognostic potential of damage repair indicators was studied in the case of clear cell renal cell carcinoma (ccRCC). Gene expression profiles of the disease were downloaded from cancer genome databases and gene ontology was applied to the DNA repair-related genes. Twenty-six differentially expressed DNA repair genes were identified, and regression analysis was used to identify those with prognostic potential and to construct a risk model. The model accurately predicted patient outcomes and distinguished among patients with different expression levels of immune evasion genes. The data indicate that DNA repair genes can be valuable for predicting the progression of clear cell renal cell carcinoma and the clinical benefits of immunotherapy.

Riluzole is approved by the FDA as an amyotrophic lateral sclerosis (ALS) drug. Previous studies showed that treatment with riluzole suppressed the proliferation of many cancer cells. However, little is known about its effects on nasopharyngeal carcinoma (NPC) and its molecular mode of action. In this study, we determined the effect of riluzole on apoptosis, cell cycle, migration, and invasion in NPC cell lines and investigated its mechanism at the molecular level. By using the human NPC cell lines CNE1, CNE2, and HNE1, we revealed that riluzole effectively inhibited viability of the NPC cell lines in dose- and time-dependent manners. Furthermore, riluzole dose-dependently induced apoptosis and G2/M cell cycle arrest in the NPC cell lines. After combination with radiotherapy (RT), greater cytotoxicity was achieved than with riluzole or RT alone in vitro and vivo. This was associated with the activation of ataxia telangiectasia mutated (ATM) and phosphoinositide p53 pathways. P53 silencing reduced cell reactiveness to riluzole therapy. These observations demonstrate that the riluzole-activated ATM/P53 pathway is directly involved in radiation-induced apoptosis of NPC cells. Given the acceptable side effect, combining of riluzole and radiotherapy is promising in NPC treatment.

Objective:To investigate the impact of connexin 43(CX43) on the connection of S24 glioblastoma multiforme (S24-GBM) cellular network and to explore its role on radio-resistance.Methods:Specific lentiviral vectors were used to knockout CX43 in S24-GBM stem cells (S24-GBMSCs). Alternatively, carbenoxolone (CBX) was used to block transmission of CX43. Subsequently, the animal subjects grafted with S24-GBMSCs were monitored under a multiphoton laser scanning microscope (MPLSM). Dynamic changes of tumor microtubes (TMs) and transmission of Ca 2+ and SR101 in the cellular network were recorded. To study the radiosenstivity of S24-GBM before and after CX43 inhibition, MRI scanning of the brains was taken before and after radiation to assess the tumor sizes. Survival time of each subject was also recorded. Results:In comparison with control group, knockout of CX43 in S24-GBMSCs led to shorter TMs, less TM connected cells, lower Ca 2+ synchronicity and SR101 fluorescence, as well as decreased tumor sizes and prolonged survival time (all P<0.01), which were independent from radiation. However, CBX only demonstrated inhibition on the growth of tumors and the diffussion of Ca 2+ and SR101, without affecting TMs formation. These above-mentioned alterations could be enhanced by the combination of gap43 knockout in S24-GBMSCs with blockage of CX43 by CBX (all P<0.05). Conclusion:CX43 plays a critical role in the radioresistance of S24-GBM by influencing the formation of S24-GBM cellular network and the transmission of important signaling molecules including Ca 2+ and SR101.

Lung adenocarcinoma (LUAD) is a major pathological type of lung cancer. Understanding the mechanism of LUAD at the molecular level is important for a clinical decision. In this study, we use bioinformatic analysis to explore the prognostic value of P4HA1 in lung adenocarcinoma (LUAD) and the relationship with prognosis and tumor-infiltrating immune cells (TIICs). The results showed that the expression of P4HA1 was significantly higher in tumor tissues than in normal tissues for LUAD patients. Upregulated P4HA1 was related to stage and T classification. Kaplan-Meier analysis indicated that upregulation of P4HA1 was significantly related to worse overall survival (OS). Univariate and multivariate Cox analysis indicated P4HA1 remained to be an independent prognostic factor. GSEA showed that several cancer-related and immune-related signaling pathways exhibited prominently differential enrichment in P4HA1-high expression phenotype. In addition, the expression of P4HA1 was significantly correlated with proportion of several TIICs, particularly B cells and CD4+ T cells. In conclusion, our study confirmed that P4HA1 is a promising biomarker of poor prognosis and relates to immune infiltrates in LUAD.

Radiotherapy with or without concurrent chemotherapy is the standard treatment for nasopharyngeal carcinoma (NPC) patients, whose efficacy is limited partly by intrinsic and acquired radioresistance. DNA methyltransferase 3B (DNMT3B) has been reported to participate in tumorigenesis via DNA methylation, but its role in mediating progression and radioresistance of NPC remains unclear. Therefore, we conducted the following studies to explore the relationship between DNMT3B and NPC. Here, we found that DNMT3B was elevated in NPC tissues and predicted the poor prognosis of NPC patients. We demonstrated for the first time that ionizing radiation could induce DNMT3B, which might be one of the reasons for radioresistance. Silencing of DNMT3B inhibited migration and invasion via suppressing epithelial-mesenchymal transition (EMT) in NPC cells. Furthermore, silencing DNMT3B restored and activated p53 and p21 via DNA demethylation, which led to cell cycle arrest and apoptosis, resulting in increased radiosensitivity of NPC both in vitro and in vivo. DNMT3B functions as a novel oncogene in the radioresistance of NPC through regulating EMT, cell cycle, and apoptosis. Therefore, DNMT3B could be a potential target for NPC treatment.

Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma (NPC), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC. SALL4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL4 expression with radioresistance of NPC. It was revealed that SALL4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL4 silencing increased radiation-induced DNA damage, apoptosis, and G2/M arrest in CNE2 and CNE2R cells. Moreover, knockdown of SALL4 impaired the expression of p-ATM, p-Chk2, p-p53, and anti-apoptosis protein Bcl-2, while pro-apoptosis protein was upregulated. These findings indicate that SALL4 could induce radioresistance via ATM/Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients.

Abstract Background Studies are trying to add immunotherapy to gemcitabine and cisplatin (GP) induction chemotherapy, the standard therapy, in nasopharyngeal carcinoma (NPC) patients with locoregionally advanced disease. However, how the immune system responds to GP remains unknown. Method We examined the dynamic changes of circulating immune cells and plasma cytokines in NPC patients administered with GP. Result After GP administration, immunosuppressive myeloid cells, including CD11b+CD14+ monocytes, CD33+ myeloid cells, CD33+CD11+ myeloid cells, total MDSCs (CD33+CD11+HLA‐DR−/low), monocytic MDSCs, and granulocytic MDSCs decreased significantly. The regulatory T cells and B cells, two important suppressive lymphocyte subpopulations, also decreased. On the other hand, the levels of CD3+ T cells, total B cells, central memory CD4+ T cells, and pro‐inflammatory cytokines (including Interleukin [IL]‐1β, IL‐6, IL‐2, IL‐5, and IL‐8) increased significantly after GP administration. Besides, GP chemotherapy did not weaken the cytotoxic activity and proliferative capacity of T cells. Conclusion Our results showed the immune modulation effect of GP induction chemotherapy in locoregionally advanced NPC, providing a solid basis for its combination with immunotherapy.

Metal-organic frameworks (MOFs) are promising adsorbents for adsorption-driven heat pumps (AHPs) due to their outstanding adsorption performance. However, the role of functionality in tuning the AHP performance has not been elucidated. In this work, the ethanol adsorption behaviors and AHP performance of Zr-based MOFs in three topologies (i.e. csq, ftw and scu) functionalized by -NH2 and -CF3 exhibiting different affinities towards ethanol working fluid were investigated by grand canonical Monte Carlo simulations (GCMC). It was revealed that functionalization not only affected the adsorption capacity but also shifted the steps of isotherms to the low pressure upon functionalization by -NH2. scu-MOFs exhibited the higher coefficient of performance for cooling (COPC) than csq-MOFs and ftw-MOFs. Moreover, functionalization reduced the COPC of ftw-MOFs and scu-MOFs due to the lower working capacity resulting from the reduced pore volumes. On the contrary, the COPC of csq-MOFs can be improved upon functionalization by -NH2. (C) 2019 Elsevier Ltd. All rights reserved.

6003 Background: GP regimen has been established as the standard first-line treatment option for patients with recurrent/metastatic NPC. However, its efficacy in locoregionally advanced disease remains unclear. Methods: Patients with previously untreated, non-metastatic stage III-IVB (except T3-4N0M0, AJCC 7th) NPC, aged 18–64 years without severe comorbidities were eligible. They were randomly assigned (1:1) to receive GP IC (gemcitabine 1 g/m2on days 1 & 8, cisplatin 80 mg/m2 on day 1, q3w for 3 cycles) plus CCRT (cisplatin 100 mg/m2, q3w for 3 cycles, concurrently with intensity-modulated radiotherapy) or CCRT alone. The primary endpoint was failure-free survival (FFS). The calculated sample size was 238 per group, with an 80% power (two-sided α 0.05) to detect a treatment failure hazard ratio (HR) of 0.52. Results: From Dec 2013 to Sep 2016, 480 patients from 12 centers were randomly assigned to IC+CCRT (n = 242) or CCRT alone (n = 238) group. Baseline characteristics were well balanced. After a median follow-up of 39 months, 3-year FFS was 85.8% in the IC+CCRT group and 77.2% in the CCRT alone group (intention-to-treat population; HR 0.53, 95% confidence interval 0.34–0.81; P = 0.003). In GP+CCRT group, 239 patients started GP IC and 231 (96.7%) completed all three cycles. The most common ≥grade 3 adverse events (AE) in IC+CCRT and CCRT group were mucositis (28.9% vs. 32.1%), neutropenia (28.0% vs. 10.5%) and leukopenia (26.4% vs. 20.3%). Conclusions: Adding GP IC to CCRT significantly improved FFS in locoregionally advanced NPC and is well tolerated with favorable toxicity profile. Clinical trial information: NCT01872962. [Table: see text]

Reduced CO, uptake of ionic liquid/metal-organic framework (IL/MOF) composites has been observed in many experiments. However, simulation study gives rise to the opposite tendency. To understand such a phenomenon, both experiment and simulation were performed in this work. Two amino acid ionic liquids (AAILs) (i.e., [Emim] [Gly] and [Emim][Phe]) and two Zr-based MOFs (i.e., UiO-66 and NU-1000) were used to prepare a variety of IL/MOF composites. The reduced CO2 uptake observed in all IL/MOF composites upon ILs loading regardless of the amount of ILs is consistent with previous experimental reports. According to pore size distribution, similar pore sizes of the composites to those of pristine MOFs revealed that the blocking of channels by loaded AAILs into MOFs occurred, leading to decreased uptakes. Moreover, molecular simulation demonstrated that the blockage in channels significantly decreased CO2 uptake compared with the model consisting of randomly distributed ILs, which approximates experimental observations. This study provides experimental and theoretical evidence for the existing blockage in MOF channels upon ILs introduction, which contributed to the reduced CO2 uptakes of IL/MOF composites.

To report long‐term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III–IVB (except T3–4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m 2 d1), cisplatin (60 mg/m 2 d1), and fluorouracil (600 mg/m 2 /d civ d1–5) every 3 weeks. Patients from both groups received intensity‐modulated radiotherapy concurrently with three cycles of 100 mg/m 2 cisplatin every 3 weeks. After a median follow‐up of 71.5 months, the IC plus CCRT group showed significantly better 5‐year failure‐free survival (FFS, 77.4% vs . 66.4%, p = 0.019), overall survival (OS, 85.6% vs . 77.7%, p = 0.042), distant failure‐free survival (88% vs . 79.8%, p = 0.030), and locoregional failure‐free survival (90.7% vs . 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein–Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long‐term follow‐up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.