RESUMEN
Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.
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Linfocitos T CD8-positivos , Quimiocina CXCL13 , Inmunoterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Análisis de la Célula Individual , Estructuras Linfoides Terciarias , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/metabolismo , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/genética , Quimiocina CXCL13/metabolismo , Quimiocina CXCL13/genética , Inmunoterapia/métodos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Perfilación de la Expresión Génica , Progresión de la Enfermedad , Transcriptoma , Linfocitos B/inmunología , Linfocitos B/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Pronóstico , Fibroblastos/metabolismo , Fibroblastos/inmunologíaRESUMEN
PURPOSE: To evaluate the long-term efficacy and safety of GP and TPF sequential chemotherapy regimens in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: From 2005 to 2016, a total of 408 LA-NPC patients treated with GP or TPF sequential chemoradiotherapy were retrospectively included. Propensity Score Matching (PSM) was employed to balance the baseline variables. Survival outcomes and acute toxicities were compared between both groups. RESULTS: A total of 230 patients were selected by 1:1 PSM. At a median follow-up of 91 months, no significant differences were observed between the matched GP and TPF groups regarding 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregionally relapse-free survival (83.4% vs. 83.4%, P = 0.796; 75.6% vs. 68.6%, P = 0.301; 86.7% vs. 81.1%, P = 0.096; and 87.4% vs. 87.2%, P = 0.721). Notable disparities in adverse effects were identified, with higher incidences of grade 3/4 thrombocytopenia in the GP group while grade 3/4 leukopenia and neutropenia in the TPF group. Though not recorded in our cohort, combined with the FAERS database, thrombotic adverse reactions are a concern for the GP regimen, while the TPF regimen requires vigilance for life-threatening adverse reactions such as septic shock, acute respiratory distress syndrome, and laryngeal edema. CONCLUSION: No significant difference in long-term outcomes was observed between the GP and TPF sequential chemotherapy regimens for LA-NPC. Differences in adverse effects should be noted when choosing the regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Puntaje de Propensión , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano , Resultado del Tratamiento , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Gemcitabina , Estudios de Seguimiento , Compuestos OrganoplatinosRESUMEN
The objective of this study was to construct a concise prediction model for serious adverse events (SAEs) in order to assess the likelihood of SAE occurrence among hospitalized patients undergoing concurrent chemoradiotherapy. An electronic database of a Cancer Centre was utilized to conduct a cross-sectional review survey. Our research involved the recruitment of 239 patients who were undergoing concurrent chemoradiotherapy in the Department of Nasopharynx and Radiotherapy. The clinical prediction rule was derived using logistic regression analysis, with SAE serving as the primary outcome. Internal verification was conducted. The occurrence rate of SAE in the derivation cohort was 59.4%. The ultimate model used had 3 variables, namely cystatin C, C-reactive protein, and serum amyloid A. The model exhibited an area under the curve of 0.626 (95% CI: 0.555-0.696; Pâ <â .001). The model accurately predicts the occurrence of SAE, and the variable data can be easily obtained, and the assessment technique is straightforward.
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Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Carcinoma Nasofaríngeo/terapia , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Persona de Mediana Edad , Neoplasias Nasofaríngeas/terapia , Estudios Transversales , Adulto , Medición de Riesgo , Anciano , Modelos Logísticos , Estudios Retrospectivos , Proteína C-Reactiva/análisisRESUMEN
BACKGROUND AND AIM: The German NPC-GPOH trials introduced treatment including neoadjuvant chemotherapy, radiochemotherapy (RCT) and antiviral treatment in patients aged 25 years or younger with nasopharyngeal cancer (NPC). We conducted a retrospective study on outcomes of patients at the age of ≥26 years treated accordingly at our institution. METHODS: Consecutive patients who received primary RCT for NPC were included. The Kaplan-Meier method was used to calculate survival probabilities, and the Cox regression analysis was used to test for an influence of the variables on outcomes. Acute and late toxicity were evaluated via CTCAE criteria and LENT/SOMA criteria, respectively. RESULTS: In total, 30 patients were included. Diagnosis was made from 09/1994 to 11/2016. The median 5 year overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS) and locoregional recurrence-free survival (LRC) were 75%, 56%, 83%, and 85%, respectively. We found a negative impact on outcomes (p < .05) in case of older age (OS), history of smoking (OS), and T4 stage/ UICC stage IV (DFS). WHO histologic type significantly influenced outcomes, with best outcomes for type III and worst outcomes for type I. The rates of acute and late toxicities were acceptable. CONCLUSION: We found excellent outcomes and good feasibility of the NPC-GPOH trials regimen in adult patients. Additionally, we identified patients with outcomes which need to be improved (smokers, histologic type I tumors) and with particularly excellent outcomes (histologic type III tumors). This stimulates further studies on treatment intensification or de-escalation aiming at reduced side effects with optimal tumor control in NPC.
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Quimioradioterapia , Neoplasias Nasofaríngeas , Terapia Neoadyuvante , Humanos , Masculino , Femenino , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Adulto Joven , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Anciano , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Supervivencia sin Enfermedad , Terapia Combinada/métodos , Tasa de SupervivenciaRESUMEN
Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular, benign and locally aggressive tumour that predominantly affects adolescent males. Recognised for its persistence and propensity to recur, patients usually present with gradual development of symptoms such as epistaxis and nasal obstruction over several months to years. Diagnosis typically combines clinical assessments and radiographic studies, often involving preoperative angiography to identify feeder vessels and facilitate embolisation, reducing intraoperative bleeding during surgical interventions. A comprehensive approach to treatment, considering both tumour characteristics and patient well-being, is crucial, particularly when dealing with cases involving intracranial extension. Surgical excision remains the primary treatment for angiofibroma, though radiotherapy is considered for cases with intracranial extension. This case report outlines a case involving a young man in his 20s with a large bilateral JNA extending into the intracranial area. The patient underwent preoperative embolisation followed by surgical resection using a nasofrontomaxillary swing approach with a bifrontal craniotomy window. This alternative approach provided enhanced exposure to address the involvement of the infratemporal fossa, anterior and middle skull base. Postoperatively, residual intracranial tumour was managed with radiation therapy. Over a 2-year follow-up, the patient remains asymptomatic, with a minor postradiation reduction in the intracranial component's size.
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Angiofibroma , Embolización Terapéutica , Neoplasias Nasofaríngeas , Humanos , Angiofibroma/cirugía , Angiofibroma/terapia , Angiofibroma/diagnóstico , Masculino , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/cirugía , Embolización Terapéutica/métodos , Neoplasias Encefálicas/terapia , Craneotomía/métodos , Adulto , Adulto Joven , Imagen por Resonancia MagnéticaRESUMEN
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.
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Proteína BRCA1 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Microambiente Tumoral , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/inmunología , Masculino , Femenino , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/inmunología , Pronóstico , Persona de Mediana Edad , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutación , Adulto , Recombinación Homóloga/genética , Biomarcadores de Tumor/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/genética , Inestabilidad GenómicaRESUMEN
RATIONALE: Hyalinizing clear cell carcinoma (HCCC) arising from a minor salivary gland is a rare malignant neoplasm. Most HCCC has been reported in the palate and tongue base, and only rarely in the nasopharynx. Here, we report a rare case of nasopharyngeal HCCC. PATIENT CONCERNS: A 44-year-old male who complained of otorrhea and aural fullness for 5 years was found to have a nasopharyngeal mass. DIAGNOSES: HCCC by fluorescence in situ hybridization analysis. INTERVENTIONS: Surgical resection plus concurrent chemotherapy and radiation therapy were administered. OUTCOMES: The patient recovered well with symptoms improved at postoperative follow-up. LESSONS: HCCC should be included in the differential diagnosis of nasopharyngeal mass. Overall, the prognosis of HCCC is positive after tumor resection and adequate management.
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Adenocarcinoma de Células Claras , Neoplasias Nasofaríngeas , Humanos , Masculino , Adulto , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirugía , Neoplasias Nasofaríngeas/patología , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/cirugía , Diagnóstico DiferencialRESUMEN
This study elucidates the intricate relationship between nasopharyngeal carcinoma (NPC), a significant malignancy predominant in Asia with notable global incidence and mortality rates, and the host microbiota, including those of tumour, nasal, nasopharyngeal, oral, oropharyngeal, and gut communities. It underscores how the composition and diversity of microbiota are altered in NPC, delving into their implications for disease pathogenesis, treatment response, and the side effects of therapies. A consistent reduction in alpha diversity across oral, nasal, and gut microbiomes in NPC patients compared to healthy individuals signals a distinct microbial signature indicative of the diseased state. The study also shows unique microbial changes tied to different NPC stages, indicating a dynamic interplay between disease progression and microbiota composition. Patients with specific microbial profiles exhibit varied responses to chemotherapy and immunotherapy, underscoring the potential for treatment personalisation based on microbiota analysis. Furthermore, the side effects of NPC treatments, such as oral mucositis, are intensified by shifts in microbial communities, suggesting a direct link between microbiota composition and treatment tolerance. This nexus offers opportunities for interventions aimed at modulating the microbiota to alleviate side effects, improve quality of life, and potentially enhance treatment efficacy. Highlighting the dual potential of microbiota as both a therapeutic target and a biomarker for NPC, this review emphasises its significance in influencing treatment outcomes and side effects, heralding a new era in NPC management through personalised treatment strategies and innovative approaches.
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Microbiota , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/microbiología , Microbiota/efectos de los fármacos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/microbiología , Resultado del Tratamiento , Microbioma Gastrointestinal/efectos de los fármacos , Inmunoterapia/métodos , Inmunoterapia/efectos adversosRESUMEN
OBJECTIVE: The early response to concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) is closely correlated with prognosis. In this study, we aimed to predict early response using a combined model that combines sub-regional radiomics features from multi-sequence MRI with clinically relevant factors. METHODS: A total of 104 patients with LA-NPC were randomly divided into training and test cohorts at a ratio of 3:1. Radiomic features were extracted from subregions within the tumor area using the K-means clustering method, and feature selection was performed using LASSO regression. Four models were established: a radiomics model, a clinical model, an Intratumor Heterogeneity (ITH) score-based model and a combined model that integrates the ITH score with clinical factors. The predictive performance of these models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Among the models, the combined model incorporating the ITH score and clinical factors exhibited the highest predictive performance in the test cohort (AUC=0.838). Additionally, the models based on ITH score showed superior prognostic value in both the training cohort (AUC=0.888) and the test cohort (AUC=0.833). CONCLUSION: The combined model that integrates the ITH score with clinical factors exhibited superior performance in predicting early response following concurrent chemoradiotherapy in patients with LA-NPC.
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Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patología , Adulto , Quimioradioterapia/métodos , Anciano , Pronóstico , Resultado del Tratamiento , Curva ROCRESUMEN
Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.
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Biomarcadores de Tumor , Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/diagnóstico , Quimioradioterapia/métodos , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Masculino , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Femenino , Cromatografía Líquida de Alta Presión/métodos , Adulto , Metabolómica/métodos , AncianoRESUMEN
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.
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Anticuerpos Monoclonales Humanizados , Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Quimioterapia de Inducción/métodos , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Estudios Retrospectivos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Adulto , Anciano , Estadificación de Neoplasias , Resultado del Tratamiento , Estimación de Kaplan-Meier , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Adulto JovenRESUMEN
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.
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Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Técnicas Fotoacústicas , Terapia Fototérmica , Animales , Técnicas Fotoacústicas/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Terapia Fototérmica/métodos , Ratones , Línea Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico por imagen , Nanopartículas/química , Rayos Infrarrojos , Ratones Desnudos , Medios de Contraste/química , Ratones Endogámicos BALB C , Polímeros/química , FemeninoRESUMEN
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.
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Quimioradioterapia , Ciclobutanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Compuestos Organoplatinos , Radioterapia de Intensidad Modulada , Humanos , Masculino , Anciano , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Ciclobutanos/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Estimación de Kaplan-MeierRESUMEN
BACKGROUND: Recently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed. RESULTS: In both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679-0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448-0.770]. CONCLUSION: The HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.
Asunto(s)
Quimioradioterapia , Hemoglobinas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/sangre , Hemoglobinas/análisis , Pronóstico , Estudios Retrospectivos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/sangre , Adulto , Estadificación de Neoplasias , Anciano , Albúmina Sérica/análisisAsunto(s)
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagen , Fluoroscopía , Constricción Patológica , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico por imagen , Masculino , Radiografía Intervencional , Persona de Mediana Edad , Carcinoma/radioterapia , Carcinoma/terapia , Dilatación/métodos , Traumatismos por Radiación/terapia , Traumatismos por Radiación/etiología , Traumatismos por Radiación/diagnóstico por imagenRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Médula Ósea , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patología , Neoplasias de la Médula Ósea/secundario , Neoplasias de la Médula Ósea/terapia , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Inmunoterapia/métodos , Inducción de Remisión , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , AlbúminasRESUMEN
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.
Asunto(s)
ADN Viral , Herpesvirus Humano 4 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , ADN Viral/sangre , Quimioterapia Adyuvante/métodos , Adulto , Anciano , Carga Viral , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/tratamiento farmacológico , Quimioradioterapia/métodos , Infecciones por Virus de Epstein-Barr , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Adulto Joven , AdolescenteAsunto(s)
Inmunoterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/terapia , Inmunoterapia/métodos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/tratamiento farmacológico , Metástasis de la Neoplasia , Terapia CombinadaRESUMEN
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.