ABSTRACT
BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.
Subject(s)
Chemoradiotherapy , Cyclobutanes , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Organoplatinum Compounds , Radiotherapy, Intensity-Modulated , Humans , Male , Aged , Female , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Cyclobutanes/therapeutic use , Cyclobutanes/administration & dosage , Cyclobutanes/adverse effects , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/drug therapy , Radiotherapy, Intensity-Modulated/adverse effects , Radiotherapy, Intensity-Modulated/methods , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Retrospective Studies , Survival Rate , Treatment Outcome , Kaplan-Meier EstimateABSTRACT
OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.
Subject(s)
Antibodies, Monoclonal, Humanized , Chemoradiotherapy , Induction Chemotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Female , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/pathology , Chemoradiotherapy/methods , Induction Chemotherapy/methods , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Retrospective Studies , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/drug therapy , Adult , Aged , Neoplasm Staging , Treatment Outcome , Kaplan-Meier Estimate , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease-Free Survival , Young AdultABSTRACT
Background: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.
Subject(s)
Nanoparticles , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Photoacoustic Techniques , Photothermal Therapy , Animals , Photoacoustic Techniques/methods , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/diagnostic imaging , Photothermal Therapy/methods , Mice , Cell Line, Tumor , Humans , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/diagnostic imaging , Nanoparticles/chemistry , Infrared Rays , Mice, Nude , Contrast Media/chemistry , Mice, Inbred BALB C , Polymers/chemistry , FemaleABSTRACT
Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic BRCA1/2 mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03-333.76; p = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43-34.21; p = 0.016) compared with those in the HRD group. In vitro experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.
Subject(s)
BRCA1 Protein , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Tumor Microenvironment , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/immunology , Male , Female , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/immunology , Prognosis , Middle Aged , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Mutation , Adult , Homologous Recombination/genetics , Biomarkers, Tumor/genetics , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/genetics , Genomic InstabilityABSTRACT
Nasopharyngeal carcinoma with bone marrow metastasis presents a rare and challenging clinical scenario associated with exceedingly poor prognosis. While standard treatment regimens offer limited efficacy and tolerability in such cases, individualized approaches are increasingly necessary. We present the case of a 64-year-old male diagnosed with recurrent nonkeratinizing undifferentiated nasopharyngeal carcinoma with extensive bone marrow metastasis (rTxN0M1). Treatment was initiated with immunotherapy-based combination therapy, consisting of pembrolizumab and low-dose cisplatin, which resulted in an initial response. Subsequently, there was a transition to standard-dose nab-paclitaxel-cisplatin chemotherapy in combination with pembrolizumab, followed by maintenance therapy with pembrolizumab plus fruquintinib. The patient achieved a sustained response with renormalization of tumor markers, imaging findings, and bone biopsies, resulting in complete remission. This case highlights the successful management of nasopharyngeal carcinoma with extensive bone marrow metastasis through an individualized treatment approach incorporating immunotherapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bone Marrow Neoplasms , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Bone Marrow Neoplasms/secondary , Bone Marrow Neoplasms/therapy , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Immunotherapy/methods , Remission Induction , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Treatment Outcome , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , AlbuminsABSTRACT
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.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Nutritional Status , Humans , Male , Female , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/therapy , Middle Aged , Adult , China , Exercise Therapy/methods , Exercise/physiology , Carcinoma/radiotherapy , AgedABSTRACT
PURPOSE: To address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups. RESULTS: This retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063). CONCLUSIONS: Our study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.
Subject(s)
Chemoradiotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Staging , Humans , Female , Male , Retrospective Studies , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Survival Rate , Chemoradiotherapy/methods , Chemoradiotherapy/mortality , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Follow-Up Studies , Prognosis , Adult , SEER Program/statistics & numerical data , Aged , Young AdultABSTRACT
OBJECTIVES: This study aimed to evaluate the efficacy of adjuvant chemotherapy (AC) in patients with different midpoint-radiotherapy (mid-RT) Epstein-Barr virus (EBV) DNA plasma loads for locoregionally advanced nasopharyngeal carcinoma (NPC), and to provide decision-making regarding the use of AC. MATERIALS AND METHODS: A total of 675 consecutive patients diagnosed with stage III-IVa NPC were enrolled in this study. All patients underwent concurrent chemoradiotherapy (CCRT), either with or without induction chemotherapy or AC, or a combination of both. The primary endpoint of this study was progression-free survival (PFS). RESULTS: Among the 675 enrolled patients, 248 (36.7 %) received AC and 427 (63.3 %) were only observed after CCRT. In total, 149 (22.1 %) patients had detectable mid-RT EBV DNA levels, whereas 526 (77.9 %) had undetectable mid-RT EBV DNA levels. Patients with detectable mid-RT EBV DNA had worse 5-year PFS than those with undetectable mid-RT EBV DNA (74.8 % vs. 81.9 %, P = 0.045). AC group showed significantly better 5-year PFS than observation in patients with detectable mid-RT EBV DNA (82.8 % vs. 66.8 %; HR, 0.480; 95 % CI 0.250-0.919, P = 0.027). Multivariate analyses demonstrated that the treatment methods (AC vs. observation) were independent prognostic factors for PFS (HR, 0.37; 95 % CI 0.19-0.74, P = 0.005). However, in patients with undetectable mid-RT EBV DNA (5-year PFS: HR 0.873, 95 % CI 0.565-1.349, P = 0.52), AC group showed no survival benefit for observation. CONCLUSION: AC could reduce the risk of disease progression compared to observation in patients with detectable mid-RT EBV DNA. Our findings suggest that AC is effective in patients at a high risk of treatment failure.
Subject(s)
DNA, Viral , Herpesvirus 4, Human , Humans , Male , Female , Middle Aged , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/isolation & purification , DNA, Viral/blood , Chemotherapy, Adjuvant/methods , Adult , Aged , Viral Load , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/drug therapy , Chemoradiotherapy/methods , Epstein-Barr Virus Infections , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/drug therapy , Young Adult , AdolescentSubject(s)
Immunotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/therapy , Immunotherapy/methods , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/drug therapy , Neoplasm Metastasis , Combined Modality TherapyABSTRACT
OBJECTIVE: To analyze the efficacy and adverse effects of anti-PD-1 immune checkpoint inhibitors aimed at nasopharyngeal carcinoma (NPC). METHODS: During the first stage of the study, using 40 patients with stage III/IVa NPC treated with anti-PD-1 immune checkpoint inhibitors in combination with chemoradiotherapy as a first-line treatment (observation group) and 70 patients with NPC treated with chemoradiotherapy alone (control group). In the second stage of the study, 88 patients with NPC treated with immune checkpoint inhibitors were grouped according to the number of lines of immunotherapy, the number of times, and the types of application. RESULTS: Observation of the short-term effects in the first stage indicated that the objective response rate (ORR) of the observation group and the control group against primary foci of NPC was 75.0% versus 40.0%; the mortality rate of the observation group was much lower than that of the control group. The overall first-line treatment evaluation of the observation vs. control groups were as follows: ORR (67.5% vs. 38.6%); median PFS (17.52 vs. 17.21 months); and median OS (18.68 vs. 18.14 months), respectively (p < 0.05). The second stage of the study had an ORR of 53.4%, and the efficacy of immunotherapy was related to staging, timing, and frequency. CONCLUSION: Anti-PD-1 immune checkpoint inhibitors combined with chemoradiotherapy as the first-line treatment for nasopharyngeal carcinoma may improve patient outcomes significantly. Timing, frequency, and the type of immunotherapy exerted an effect on the efficacy of immunotherapy. Adverse effects that occurred during treatment were tolerable and controllable.
Subject(s)
Chemoradiotherapy , Immune Checkpoint Inhibitors , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Programmed Cell Death 1 Receptor , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Male , Female , Middle Aged , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Adult , Aged , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/immunology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Neoplasm Staging , Treatment Outcome , Young AdultABSTRACT
Immunotherapy is a promising strategy for nasopharyngeal carcinoma (NPC), a common and aggressive malignancy with poor prognosis. However, the literature lacks a comprehensive and objective overview of the current research status and trends of immunotherapy-related fields in NPC. We performed a bibliometric analysis of 513 original articles and reviews in English on immunotherapy for NPC from the Web of Science Core Collection database, using CiteSpace and Bibliometrix software tools. We visualized the development trend of publications, the distribution of countries/regions, the co-occurrence of keywords, the collaboration and citation of authors, the citation of journals, the evolution of topics, and the thematic map. We found that the publication volume increased sharply after 2017, with China as the main contributor and leader, the US as an important partner, and the Netherlands as a potential innovator. The research focused on immune checkpoint inhibitors and cell therapy, which were also the hotspots of clinical trials. Tumor microenvironment, immune infiltration, multicenter studies, and novel immunotherapy were the frontier topics and the key challenges for future research. CD137l-DC, lymphoma, and chimeric antigen receptor were emerging topics with good prospects. Our study provides a valuable insight into the research status and trends of immunotherapy for NPC, which may guide future research directions and clinical applications.
Subject(s)
Bibliometrics , Immunotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Tumor Microenvironment , Humans , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/immunology , Immunotherapy/methods , Immunotherapy/trends , Nasopharyngeal Neoplasms/therapy , Tumor Microenvironment/immunology , Immune Checkpoint Inhibitors/therapeutic use , China/epidemiology , Cell- and Tissue-Based Therapy/methods , Cell- and Tissue-Based Therapy/trendsABSTRACT
Objective:To investigate the differences in the therapeutic effects of endoscopic surgery combined with chemotherapy and endoscopic surgery combined with radiotherapy in the treatment of early nasopharyngeal carcinoma, and to select individualized treatment strategy for early nasopharyngeal carcinoma. Methods:The clinical data of 68 patients with early nasopharyngeal carcinomaï¼Tî1-2N0M0ï¼ who received surgical treatment in a high-incidence area were retrospectively analyzed. According to different treatment methods, they were divided into the surgery + chemotherapy groupï¼n=34, treated with endoscopic surgery combined with chemotherapyï¼ and the surgery + radiotherapy groupï¼n=34, treated with endoscopic surgery combined with radiotherapyï¼. Propensity score matching was used to match the patient data between the two groups at a 1â¶1 ratio. Patients were followed up, and the survival rates and hematological toxicities were compared between the two groups. Results:Twenty-four cases in the surgery + chemotherapy group and 24 cases in the surgery + radiotherapy group were successfully matched. After matching, there was no statistically significant difference in T stage, and clinical stage between the two groupsï¼all P>0.05ï¼. The 3-year OS and DFS in the surgery + chemotherapy group were 100.0% and 95.8%, respectively, while the 3-year OS and DFS in the surgery + radiotherapy group were 100.0% and 100.0%, respectively, with no significant difference in survival rates between the two groupsï¼both P>0.05ï¼. After treatment, there was no statistically significant difference in bone marrow suppression between the surgery + chemotherapy group and the surgery + radiotherapy group ï¼all P> 0.05ï¼ Conclusion:Endoscopic surgery combined with chemotherapy and surgery combined with radiotherapy have comparable clinical efficacy in the treatment of early nasopharyngeal carcinoma, but without radiotherapy-related complications, which is worth further investigation.
Subject(s)
Carcinoma , Endoscopy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/radiotherapy , Retrospective Studies , Male , Prognosis , Female , Combined Modality Therapy , Carcinoma/therapy , Survival Rate , Middle Aged , Neoplasm Staging , Incidence , Treatment Outcome , AdultABSTRACT
RATIONALE: Nasopharyngeal carcinoma has a high incidence in East and Southeast Asia, often with distant metastasis. However, leptomeningeal metastasis (LM) is extremely rare and usually has a poor prognosis. This paper reports the clinical treatment of a patient with meningeal metastasis of nasopharyngeal carcinoma (NPC) in order to improve the clinician's understanding of the disease. Early diagnosis of the disease can alleviate the pain of patients and prolong their survival time. PATIENT CONCERNS: We report the case of a 55-year-old female with a history of NPC with LM. Brain magnetic resonance imaging showed temporal lobe enhancement, peripheral edema, and enhancement of the adjacent meninges. Cerebrospinal fluid cytology suggests the presence of malignant tumor cells. DIAGNOSES: The patient was diagnosed with LM from NPC. INTERVENTIONS: The patients were regularly given targeted therapy with nimotuzumab, immunotherapy with karyolizumab, and lumbar intrathecal methotrexate chemotherapy and supportive treatment. OUTCOMES: The patient had survived for 3 years since the diagnosis of LM and was in good condition and still under active antitumor treatment. LESSONS: Leptomeningeal metastasis of NPC is a rare disease. Although there is currently no unified treatment plan, the neurological symptoms can still be controlled and the quality of life can be improved through active treatment.
Subject(s)
Meningeal Neoplasms , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Female , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/drug therapy , Meningeal Neoplasms/secondary , Meningeal Neoplasms/therapy , Meningeal Carcinomatosis/secondary , Meningeal Carcinomatosis/drug therapy , Magnetic Resonance ImagingABSTRACT
BACKGROUND: The sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal carcinoma (NPC), and the specific biomarker determining the response to immunotherapy in NPC remains uncertain. METHODS: We assessed the associations between pre-immunotherapy and post-immunotherapy serum lipoproteins and survival in a training cohort (N=160) and corroborated these findings in a validation cohort (N=100). Animal studies were performed to explore the underlying mechanisms. Additionally, the relationship between high-density lipoprotein-cholesterol (HDL-C) levels and M1/M2-like macrophages, as well as activated CD8+T cells in tumor tissues from patients with NPC who received immunotherapy, was investigated. RESULTS: The lipoproteins cholesterol, HDL-C, low-density lipoprotein-cholesterol, triglycerides, apolipoprotein A-1 (ApoA1), and apolipoprotein B, were significantly altered after immunotherapy. Patients with higher baseline HDL-C or ApoA1, or those with increased HDL-C or ApoA1 after immunotherapy had longer progression-free survival, a finding verified in the validation cohort (p<0.05). Multivariate analysis revealed that baseline HDL-C and elevated HDL-C post-immunotherapy were independent predictors of superior PFS (p<0.05). Furthermore, we discovered that L-4F, an ApoA1 mimetic, could inhibit tumor growth in NPC xenografts. This effect was associated with L-4F's ability to polarize M2-like macrophages towards an M1-like phenotype via the activation of mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) p65, thereby alleviating immunosuppression in the tumor microenvironment. Importantly, in patients with NPC with high plasma HDL-C levels, the number of M2-like macrophages was significantly decreased, while M1-like macrophages and activated CD8+T cells were notably increased in those with high HDL-C levels. CONCLUSION: Higher baseline HDL-C levels or an increase in HDL-C post-immunotherapy can enhance immunotherapeutic responses in patients with NPC by reprogramming M2-like macrophages towards the M1 phenotype. This suggests a potential role for prospectively exploring ApoA1 mimetics as adjuvant agents in combination with immunotherapy.
Subject(s)
Cholesterol, HDL , Immunotherapy , Nasopharyngeal Carcinoma , Tumor-Associated Macrophages , Humans , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/drug therapy , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Immunotherapy/methods , Animals , Female , Male , Cholesterol, HDL/metabolism , Cholesterol, HDL/blood , Mice , Middle Aged , Phenotype , Tumor Microenvironment , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/drug therapy , AdultABSTRACT
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
Subject(s)
Antibodies, Monoclonal, Humanized , Chemoradiotherapy , Induction Chemotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Middle Aged , Male , Female , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/drug therapy , Adult , China/epidemiology , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/therapy , Chemoradiotherapy/methods , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Aged , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gemcitabine , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Deoxycytidine/administration & dosage , Young Adult , Adolescent , Progression-Free SurvivalABSTRACT
OBJECTIVE: The International Union for Cancer Control/American Joint Committee on Cancer (UICC/AJCC) rT staging is not clinically practical for recurrent nasopharyngeal carcinoma (rNPC). The aim of this study was to establish a new rT staging to guide the treatment of rNPC. METHODS: We conducted a retrospective analysis of 175 patients diagnosed with rNPC between January 2012 and December 2020, using ROC curve analysis to evaluate its effectiveness. RESULTS: We analyzed the overall survival (OS) and progression-free survival(PFS) of patients diagnosed with rNPC according to the 8th (UICC/AJCC) rT staging, and found that the overall survival of rT1 and rT2 patients (OS; 29.98% vs. 27.09%, p = 0.8059) and progression-free survival (PFS; 28.48% vs. 26.12%, p = 0.4045) had no significant difference. In rT1 and rT2 patients of this study, overall survival(OS; 30.44% vs. 24.91%, p = 0.0229) and progression-free survival(PFS 29.12% vs. 24.03%, p = 0.0459) had a significant difference. Smoking, family history, and time interval of initial recurrence were independent prognostic factors for OS and PFS. CONCLUSION: The new rT staging of this study has a better predictive value for survival of rNPC patients than the 8th (UICC/AJCC) rT staging.
Subject(s)
Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Humans , Male , Female , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/therapy , Middle Aged , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/therapy , Adult , Aged , Young Adult , Prognosis , Survival RateSubject(s)
Hyperbaric Oxygenation , Kidney Neoplasms , Lung Diseases, Interstitial , Nasopharyngeal Carcinoma , Radiosurgery , Humans , Radiosurgery/methods , Radiosurgery/adverse effects , Hyperbaric Oxygenation/methods , Kidney Neoplasms/radiotherapy , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/therapy , Male , Lung Diseases, Interstitial/etiology , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/therapy , Prostatectomy/methods , Prostatectomy/adverse effects , Radiation Dose HypofractionationABSTRACT
BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.
Subject(s)
Chemoradiotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Nomograms , Humans , Female , Male , Retrospective Studies , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/pathology , Chemoradiotherapy/methods , Prognosis , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/blood , Nasopharyngeal Neoplasms/pathology , Adult , Blood Platelets/pathology , Aged , Serum Albumin/analysis , Neoplasm Staging , Young Adult , Proportional Hazards Models , Platelet Count , Biomarkers, Tumor/bloodABSTRACT
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare disease worldwide; To the best of our knowledge, there is no established standard of care specifically tailored for the adolescent population. The majority of existing research relies on retrospective data analysis. OBJECTIVE: Evaluate clinical features, treatment results, prognostic factors and late toxicities of locally advanced NPC patients treated with tomotherapy. DESIGN: Retrospective. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: Between January 2007 and January 2020, we treated patients with NPC, aged between 14 and 21 years, with concomitant chemoradiotherapy using tomotherapy at our institution. We prospectively collected details of clinical characteristics, treatment modalities, outcomes and prognostic factors of these patients and then analysed them retrospectively. MAIN OUTCOME MEASURES: 3-5 years overall survival (OS), 3-5 years locoregional control rate, 3-5 years disease-free survival (DFS), prognostic factors. SAMPLE SIZE: 51 patients. RESULTS: There were 26 male and 25 female patients included in our study. The mean age was 16.5 years, 5 (9.8%) patients with stage III, and 46 (90.2%) with stage IVa according to the American Joint Committee on Cancer, 8th edition staging system. Most patients (98%) received two or more cycles of induction chemotherapy. All patients received concomitant chemoradiotherapy. The median total dose of radiotherapy delivered was 6600 cGy (range 4800-7000). With a median follow-up of 73 months (range 9-168 months), a 5-year locoregional control rate, 5-year OS and 5-year DFS rates were 100%, 86.8% and 71.7%, respectively. Five years later, disease control was 71.7%. Ten (19.6%) patients had disease recurrence in the form of distant metastases during the follow up. CONCLUSIONS: Helical tomotherapy has an excellent late toxicity profile without compromising clinical outcome for patients with NPC. Radiotherapy remains the mainstay of treatment of nasopharyngeal carcinoma to achieve remarkable local control rates. LIMITATIONS: Single institution experience, small number of patients, and retrospective design.