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Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein–Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant–adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. This randomised, single-centre, double-blind, placebo-controlled, phase 2 trial was conducted at Sun Yat-sen University Cancer Centre in Guangzhou, China. Adult patients (aged 18–65 years) with newly diagnosed high-risk stage III–IVa locoregionally advanced nasopharyngeal carcinoma, with a pretreatment plasma EBV DNA concentration of at least 1500 copies per mL and an Eastern Cooperative Oncology Group performance score of 0–1, were eligible. Patients were randomly assigned (2:1) using an interactive web response system (block size of six), stratified by TNM stage (III vs IVa), to neoadjuvant toripalimab (240 mg intravenously) or placebo once every 2 weeks for two cycles, followed by concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy and adjuvant toripalimab (240 mg intravenously) or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival in the intention-to-treat population. This study was registered with ClinicalTrials.gov, NCT03925090, and is closed to enrolment; follow-up is ongoing. Between Dec 6, 2019, and Dec 9, 2021, 150 patients were enrolled and randomly assigned to the toripalimab group (n=100) or placebo group (n=50). 115 (77%) patients were male and 35 (23%) were female. As of data cutoff (May 31, 2024), median follow-up for progression-free survival was 37·8 months (IQR 34·2–46·5) for the intention-to-treat population analyses. 2-year progression-free survival was higher in the toripalimab group (92·0% [95% CI 86·7–97·3]) than in the placebo group (74·0% [61·8–86·2]; stratified hazard ratio 0·40 [95% CI 0·18–0·89]; log-rank p=0·019). The most common grade 3 or worse acute adverse events (occurring within 1 year of randomisation) were leukopenia (40 [40%] of 99 patients in the toripalimab group vs 22 [44%] of 50 patients in the placebo group), mucositis (28 [28%] vs ten [20%]), neutropenia (17 [17%] vs nine [18%]), anaemia (16 [16%] vs five [10%]), and weight loss (12 [12%] vs six [12%]). The most common grade 3 or worse late adverse events (occurring >1 year after randomisation) was auditory or hearing loss (eight [8%] vs four [8%]). Immune-mediated adverse events of grade 3 or worse occurred in ten (10%) patients only in the toripalimab group. One (2%) of 50 patients in the placebo group died due to septic shock caused by bacteraemia considered not treatment related. There were no treatment-related deaths in the toripalimab group. Our findings suggested that a so-called sandwich approach involving toripalimab (in the neoadjuvant and adjuvant phases) combined with concurrent chemoradiotherapy could be a highly promising therapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Phase 3 non-inferiority trials are warranted comparing neoadjuvant and adjuvant toripalimab versus cisplatin plus gemcitabine neoadjuvant chemotherapy combined with concurrent chemoradiotherapy. National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Science and Technology Program of Guangzhou, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Postdoctoral Innovative Talent Support Program, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, and Fundamental Research Funds for the Central Universities. For the Chinese translation of the abstract see Supplementary Materials section.

Adding three cycles of induction chemotherapy with gemcitabine and cisplatin to concurrent chemoradiotherapy improved 3-year recurrence-free survival (85.3%, vs. 76.5% with concurrent chemoradiotherapy alone) and overall survival (94.6% vs. 90.3%). Patients receiving induction chemotherapy were more likely to have grade 3 or 4 myelosuppression, nausea, and vomiting.

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18–65 years with newly diagnosed high-risk non-metastatic stage III–IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3–4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0–44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81–90] vs 76% [70–81]; stratified hazard ratio 0·59 [0·38–0·92]; p=0·019). Grade 3–4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3–4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section.

Radiotherapy-induced oral mucositis (RTOM) is a common side effect of radiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (CCRT). In this phase 3 trial, we aim to evaluate the efficacy and safety of Ulinastatin (UTI) for the prevention and treatment of RTOM in LA-NPC patients (NCT03387774). The primary endpoint is the incidence of grade ≥3 acute RTOM during radiotherapy. Secondary endpoints include cumulative incidence of RTOM, recovery rate, the onset time and duration of grade ≥3 RTOM, oral pain (severe), safety and survival outcomes. 179 eligible patients are randomly assigned to UTI Group ( n  = 89) or Control group ( n  = 90). All UTI group patients complete UTI treatment as planned, and both groups complete scheduled CCRT. The incidence of grade 3 RTOM is significantly lower in UTI group compared with control group (25.8% vs 41.1%, P  = 0.030). The trial meet its prespecified primary endpoint. No Ulinastatin related adverse events are observed during treatment. The 3-year overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) in UTI group and control group are similar between two groups. In this work, Ulinastatin can effectively reduce the severity of RTOM and oral pain without increasing toxicity and compromising survivals. Radiotherapy-induced oral mucositis is a common side effect in nasopharyngeal carcinoma treatment. Here, the authors present a phase 3 randomized clinical trial assessing the safety and efficacy of ulinastatin to prevent the incidence and severity of this condition.

Platinum-based chemotherapy plus PD-1 inhibitors (chemoimmunotherapy) was the standard systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, biomarkers to predict the survival outcomes remained unsatisfying. This study aimed to establish a simple but easily applicable model to predict the survival outcomes of R/M NPC receiving chemoimmunotherapy. A total of 319 R/M NPC patients treated by chemoimmunotherapy with or without local therapy at our hospital were randomly divided into training (n=223) and validation (n=96) cohorts at a ratio of 7:3. An easily applicable prognostic risk grouping model was created using common independent predictors of progression-free survival (PFS) and overall survival (OS) in the training set. Model performance was assessed in the validation set. Pretreatment IL-6 and EBV DNA levels were identified as independent prognostic factors (scored on 0-4 points), and used to develop a prognostic risk grouping model with distinct survivals: 0-1 point (low risk), 2-3 points (intermediate risk), and 4 points (high risk). In the training set, the median PFS were not reached (NR), 18.90, and 7.73 months (P<0.001) respectively in the low-, intermediate-, and high-risk groups, while the median OS were NR, NR and 13.6 months (P<0.001). Results were further confirmed in the validation set. This model predicted both PFS and OS in R/M NPC patients undergoing chemoimmunotherapy. This finding may help clinicians with an initial prognostic estimation but warrants further prospective investigation for the value of IL-6 and EBV DNA.

While immunotherapy has demonstrated encouraging efficacy in locally advanced nasopharyngeal carcinoma (LANPC), the optimal combination modalities and treatment duration remain undetermined. In the present study, we developed a clinical trial protocol to evaluate shortened period of immunotherapy could enhance the efficacy of LANPC. This open-label, randomized, single-blind, multicenter phase II trial (Tori-013) investigates the efficacy and safety of toripalimab (anti-PD-1 monoclonal antibody) combined with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in patients with stage III/IVa nasopharyngeal carcinoma (NPC). Eligible participants (estimated n=154) are randomized 1:1 to receive either IC (gemcitabine + cisplatin) plus CCRT (cisplatin + radiotherapy ≥ 70 Gy) with toripalimab (240 mg, Q3W) or placebo. Toripalimab/placebo is administered during IC and CCRT phases, followed by two additional cycles post-radiotherapy. The primary endpoint is 3-year progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), Epstein-Barr virus (EBV) DNA dynamics, lymphocyte subset changes, and safety. Safety assessments focus on immune-related adverse events (irAEs) graded by CTCAE v5.0. Approved by the Ethics Committee of Sichuan Cancer Hospital (KY-2021-113) and registered (ChiCTR2200055494), this trial aims to establish a novel, streamlined immunochemoradiotherapy strategy for locally advanced NPC, potentially enhancing efficacy while maintaining tolerability

To study the efficacy and safety of Polyethylene glycolated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prevention of neutropenia during concurrent chemoradiotherapy for nasopharyngeal carcinoma (NPC). This is a single-center, prospective, randomized controlled study conducted from June 1, 2021, to October 31, 2022 on patients diagnosed with locally advanced NPC. Participants were divided into an experimental group and a control group. The experimental group received PEG-rhG-CSF injections post-chemotherapy cycles, whereas the control group received standard care without additional intervention. Outcomes assessed included grade 3/4 neutropenia incidence, blood cell count changes, febrile neutropenia rates, delays or interruptions in chemotherapy/radiotherapy due to hematological toxicity, oral mucositis incidents, and bone pain occurrences, comparing these between both groups. 1. 88 patients with locally advanced NPC were included, the incidence of grade 3 neutropenia in the experimental group was lower than that in the control group (P = 0.026); 2. The white blood cell count and neutrophil count in D7, D10, D14, and D21 in the experimental group were higher than those in the control group (P<0.01); 3. The rate of delayed chemotherapy in the experimental group was lower than that in the control group (2.3% vs. 29.5%), P = 0.001; the rate of interruption of radiotherapy in the experimental group was lower than that in the control group (2.3% vs.27.3%), P = 0.003; 4. The incidence of bone pain in the experimental group was 34.1%, of which most were mild bone pain, and no severe bone pain occurred. The leukocyte and neutrophil counts of the patients in the bone pain group were significantly higher than those of the patients in the no bone pain group, P(WBC) = 0.001, P(ANC) = 0.002. The preventive use of PEG-rhG-CSF decreases the incidence of neutropenia in patients undergoing concurrent chemoradiotherapy for NPC, thereby reducing rates of chemotherapy delays and radiotherapy interruptions, with mild adverse reactions that are tolerable by patients.

The aim of this trial was to address whether elective ipsilateral upper-neck irradiation (UNI) sparing the uninvolved lower neck provides similar regional relapse-free survival compared with standard whole-neck irradiation (WNI) in patients with nasopharyngeal carcinoma. This open-label, non-inferiority, randomised, controlled, phase 3 trial was done at three Chinese medical centres. Patients aged 18–65 years with untreated, non-keratinising, non-distant metastatic (M0) nasopharyngeal carcinoma; with N0–N1 disease (according to International Union Against Cancer–American Joint Committee on Cancer TNM classification, seventh edition); and a Karnofsky performance status score of 70 or higher were randomly assigned (1:1) to receive elective UNI or WNI of the uninvolved neck. Total radiation doses of 70 Gy (for the primary tumour volume and the enlarged retropharyngeal nodes), 66–70 Gy (for the involved cervical lymph nodes), 60–62 Gy (for the high-risk target volume), and 54–56 Gy (for the low-risk target volume) were administered in 30–33 fractions, five fractions per week. Patients with stage II–IVA disease were recommended to receive combined intravenous cisplatin-based chemotherapy (either induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy alone). Randomisation was done centrally by the Clinical Trials Centre of Sun Yat-sen University Cancer Centre by means of a computer-generated random number code with a block size of four. Patients were stratified according to treatment centre and nodal status. Investigators and patients were not masked to treatment allocation. The primary endpoint was regional relapse-free survival in the intention-to-treat population. Non-inferiority was indicated if the upper limit of the 95% CI of the difference in 3-year regional relapse-free survival between the UNI and WNI groups was within 8%. Adverse events were analysed in the safety population (defined as all patients who commenced the randomly assigned treatment). This study is registered with ClinicalTrials.gov, NCT02642107, and is closed. Between Jan 22, 2016, and May 23, 2018, 446 patients from 469 screened were randomly assigned to receive UNI (n=224) or WNI (n=222). Median follow-up was 53 months (IQR 46–59). 3-year regional relapse-free survival was similar in the UNI and WNI groups (97·7% [95% CI 95·7–99·7] in the UNI group vs 96·3% [93·8–98·8] in the WNI group; difference −1·4% [95% CI −4·6 to 1·8]; pnon-inferiority<0·0001). Although acute radiation-related toxic effects were similar between the groups, the incidence of late toxicity was lower in the UNI group than in the WNI group, including any-grade hypothyroidism (66 [30%] of 222 patients vs 87 [39%] of 221), skin toxicity (32 [14%] vs 55 [25%]), dysphagia (38 [17%] vs 71 [32%]), and neck tissue damage (50 [23%] vs 88 [40%]). No patients died during treatment. After treatment, one patient in the WNI group died from a non-cancer-related cause (dermatomyositis). Elective UNI of the uninvolved neck provides similar regional control and results in less radiation toxicity compared with standard WNI in patients with N0–N1 nasopharyngeal carcinoma. Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province, and the Overseas Expertise Introduction Project for Discipline Innovation. For the Chinese translation of the abstract see Supplementary Materials section.

Background As a traditional Chinese fitness technique, Baduanjin is a low- to medium-intensity aerobic exercise that has a common regulatory effect on both body and mind and is also an important means of disease prevention and treatment. However, the role of Baduanjin in improving patients’ nutritional status and promoting tumor recovery remains to be confirmed. Objective This study aims to investigate the effectiveness of the modified Baduanjin exercise on the nutritional status of patients with nasopharyngeal carcinoma. Design This is a randomized controlled trial. Setting(s) The participants were recruited from patients in the Radiotherapy Department of the First Affiliated Hospital of Guangxi Medical University in China. Participants A total of 121 patients with nasopharyngeal carcinoma were randomly divided into the control group and the Baduanjin group. Finally, 106 patients completed the study (53 cases each in the control group and the Baduanjin group) with the intervention time from the beginning to the end of radiotherapy. Methods The control group received conventional care (health education and regular conventional exercise), and the Baduanjin exercise group received health education and regularly improved Baduanjin exercise, with the intervention time from the beginning to the end of the radiotherapy. Patient-generated subjective global assessment (PG-SGA) was evaluated before, during (15 times), and at the end of radiotherapy as the main evaluation index to compare nutritional status between the two groups. Results From August 2022 to December 2022, 121 patients with nasopharyngeal carcinoma were randomly divided into the control group and the Baduanjin group. During the intervention, 15 patients withdrew from the study, leading to 53 of 59 patients in the control group and 53 of 62 patients in the Baduanjin group. After the intervention, the PG-SGA score, radioactive oral mucositis, and oropharyngeal pain score were lower ( P  < 0.05), whereas anorexia scores, the levels of hemoglobin, albumin, prealbumin, and total protein were higher than those in the control group ( P  < 0.05). Conclusions Modified Baduanjin exercise can improve the nutritional status of patients with nasopharyngeal carcinoma and deserves further clinical application. Trial registration This study was registered in the Chinese Clinical Trial Registry under the registration number ChiCTR2200064519, registered on August 27, 2022. The public research topic is the construction and intervention research based on Internet + nasopharyngeal carcinoma.

Objective: To observe the clinical efficacy of Dendrobium officinale in the treatment of radiotherapy-induced oral mucositis in nasopharyngeal carcinoma patients, and to explore its regulating effect on immune function and oral microbiota by comparing immune-related factors and oral microbiota before and after the intervention. Methods: We conducted a randomized double-blinded controlled trial in Zhejiang Cancer Hospital. Sixty patients with nasopharyngeal cancer combined with radiotherapy-induced oral mucositis were randomly divided into a study group and control group, with 30 cases in each group The study group used compound vitamin B12 solution and Dendrobium tea drink, and the control group simply used compound vitamin B12 solution rinse. When the patients developed radiotherapy-induced oral mucositis (at the time of 10F radiotherapy), and after 1 month of Dendrobium treatment (at the end of radiotherapy), the salivary flow rate was measured without stimulation to evaluate the degree of oral mucositis and the clinical efficacy. We also detected the content of EGF in saliva and the content of IL-10 and IL-11 in serum, and analyzed the differences in microbial community structure. All patients consented before enrollment. Results: The salivary flow rate and oral mucosal fraction of the study group after treatment were significantly improved, which was better than that of the control group(P < .05). The content of IL-10 in the study group after treatment increased significantly compared with that before treatment(P < .05). There was a significant difference between the oral flora of the study group before and after treatment (Unique OTU counts: 5390 vs 3906), and there was also a difference between the oral flora of the study group and control group after treatment (Unique OTU counts: 5671 vs 5439). After treatment, Erysipelotrichales (Phylum Firmicutes, LDA score = 2.80, P = .034), Leptotrichiaceae (Fusobacteria,LDA score = 3.38, P = .030) and Campylobacteraceae (Proteobacteria, LDA score = 3.35, P = .026) were significantly enriched in the study group. The use of Dendrobium officinale in nasopharyngeal carcinoma patients with radiotherapy-induced oral mucositis showed little difference in microbial diversity and abundance, but there were significant differences among oral bacteria genera. Conclusions: Dendrobium officinale is effective in the treatment of radiotherapy-induced oral mucositis, which may be related to the improvement of salivary gland function and regulation of the oral microenvironment. Dendrobium officinale may reduce the symptoms of radiotherapy-induced oral mucositis by affecting the systemic cellular immune function. It may reduce the secretion of pro-inflammatory factors of the relevant flora by directly changing the oral flora and regulating the oral micro-ecology.