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BACKGROUND: Compared with the conventional work-up (CWU) including computed tomography (CT) of the chest and abdomen, MRI of the head and neck, and skeletal scintigraphy, positron emission tomography (PET)/MRI might improve diagnostic accuracy, shorten the work-up time, and reduce false-positive (FP) findings in patients with nasopharyngeal carcinoma (NPC). However, evidence of cost-effectiveness is needed for the adoption of PET/MRI for the initial staging in NPC. PURPOSE: To evaluate the cost-effectiveness and clinical value of PET/MRI as an initial staging procedure for NPC. STUDY TYPE: Retrospective cohort cost effectiveness study. SUBJECTS: Three hundred forty-three patients with a median age of 51 (13-81) years underwent PET/MRI before treatment (the PET/MRI group) and the remaining 677 patients with a median age of 55 (15-95) years only underwent CWU (the CWU group). There were 80 (23.3%) females and 193 (28.5%) females in the PET/MRI and CWU groups, respectively. FIELD STRENGTH/SEQUENCE: 3-T integrated PET/MRI system, diffusion-weighted echo-planar imaging (b = 0 and 1000 s/mm2 ) and [18F] fluorodeoxyglucose PET. ASSESSMENT: The primary end point was the FP rate. Costs were determined as issued in 2021 by the Medical Insurance Administration Bureau of Zhejiang, China. STATISTICAL TESTS: Incremental cost effectiveness ratio (ICER) measured cost of using PET/MRI per percent of patients who avoided a FP. A P-value <0.05 was considered statistically significant. RESULTS: For the whole group, the de novo metastatic disease rate was 5.2% (53/1020). A total of 187 patients with FP results were observed. Significantly more patients with FP results were observed in the CWU group compared to the PET/MRI group (25.6% vs. 4.1%). The ICER was $54 for each percent of patients avoiding a FP finding. DATA CONCLUSION: Compared with CWU, PET/MRI may reduce the FP risk. Furthermore, PET/MRI may be cost-effective as an initial staging procedure for NPC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.
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Fluordesoxiglucose F18 , Neoplasias Nasofaríngeas , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Carcinoma Nasofaríngeo , Estudos Retrospectivos , Compostos Radiofarmacêuticos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/patologiaRESUMO
PURPOSE: Accurately segmenting the hippocampus is an essential step in brain tumor radiotherapy planning. Some patients undergo brain tumor resection beforehand, which can significantly alter the postoperative regions' appearances and intensity of the 3D MR images. However, there are limited tumor resection patient images for deep neural networks to be effective. METHODS: We propose a novel automatic hippocampus segmentation framework via postoperative image synthesis. The variational generative adversarial network consists of intensity alignment and a weight-map-guided feature fusion module, which transfers the postoperative regions to the preoperative images. In addition, to further boost the performance of hippocampus segmentation, We design a joint training strategy to optimize the image synthesis network and the segmentation task simultaneously. RESULTS: Comprehensive experiments demonstrate that our proposed method on the dataset with 48 nasopharyngeal carcinoma patients and 67 brain tumor patients observes consistent improvements over state-of-the-art methods. CONCLUSION: The proposed postoperative image synthesis method act as a novel and powerful scheme to generate additional training data. Compared with existing deep learning methods, it achieves better accuracy for hippocampus segmentation of brain tumor patients who have undergone brain tumor resection. It can be used as an automatic contouring tool for hippocampus delineation in hippocampus-sparing radiotherapy.
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Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Redes Neurais de Computação , Imageamento Tridimensional , Hipocampo/diagnóstico por imagem , Hipocampo/cirurgiaRESUMO
Wilms' tumor 1-associated protein (WTAP), a component of the m6A methyltransferase complex, recruits the m6A methyltransferases METTL3 and METTL14 to the corresponding mRNA targets to participate in the formation of N6-methyladenosine. However, the molecular mechanism of WTAP in the tumorigenesis and progression of nasopharyngeal carcinoma (NPC) remains unclear. This study aimed to explore the prognostic value and biological function of WTAP in NPC. We assessed WTAP expression and its prognostic significance using microarray datasets from the Gene Expression Omnibus (GSE12452) database and 100 NPC tissues via bioinformatics analysis and immunohistochemistry (IHC), respectively. Moreover, gene ontology (GO) and gene set enrichment analysis (GSEA) were performed. In addition, the correlation of WTAP expression with the expression of immune cell biomarkers was analyzed. The results showed that WTAP expression was significantly overexpressed in NPC tissues in GSE12452. The overexpression of WTAP was validated by the external datasets including NPC tissues (GSE150430) and NPC cell lines (GSE39826). GO analysis suggested enrichment in the nucleoplasm (cellular component) and cell cycle (biological process). The GSEA revealed that differentially expressed genes were enriched in E2F-targets, Myc_targets_v1, G2M checkpoint, Myc_targets_v2, and Interferon-alpha-response. In IHC analysis, WTAP was upregulated in NPC tissues, and high levels of WTAP expression were significantly correlated with the advanced T stage (p=0.047) and advanced N stage (p=0.018). Cox regression demonstrated that WTAP overexpression was an independent biomarker of poor prognosis for overall survival (hazard ratio [HR], 4.747; 95% confidence interval [CI], 1.671-13.482; p=0.003). In IHC analysis, the expression of WTAP was positively correlated with CD206 (biomarker for M2 macrophages) (p=0.018) but negatively correlated with CD8a (biomarker for cytotoxic T cells) (p=0.001). In conclusion, WTAP is a promising prognostic biomarker and may participate in the regulation of immune cell infiltration in NPC.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Linhagem Celular Tumoral , Prognóstico , Ciclo Celular/genética , Neoplasias Nasofaríngeas/genética , Metiltransferases/genética , Metiltransferases/metabolismo , Fatores de Processamento de RNA , Proteínas de Ciclo Celular/metabolismoRESUMO
Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC. Materials and Methods In this retrospective study, MRI data sets covering the nasopharynx from 1021 patients (median age, 47 years; 751 male, 270 female) with NPC between September 2016 and September 2017 were collected and divided into training, validation, and testing cohorts of 715, 103, and 203 patients, respectively. GTV contours were delineated for 1021 patients and were defined by consensus of two experts. A three-dimensional convolutional neural network was applied to 818 training and validation MRI data sets to construct the AI tool, which was tested in 203 independent MRI data sets. Next, the AI tool was compared against eight qualified radiation oncologists in a multicenter evaluation by using a random sample of 20 test MRI examinations. The Wilcoxon matched-pairs signed rank test was used to compare the difference of Dice similarity coefficient (DSC) of pre- versus post-AI assistance. Results The AI-generated contours demonstrated a high level of accuracy when compared with ground truth contours at testing in 203 patients (DSC, 0.79; 2.0-mm difference in average surface distance). In multicenter evaluation, AI assistance improved contouring accuracy (five of eight oncologists had a higher median DSC after AI assistance; average median DSC, 0.74 vs 0.78; P < .001), reduced intra- and interobserver variation (by 36.4% and 54.5%, respectively), and reduced contouring time (by 39.4%). Conclusion The AI contouring tool improved primary gross tumor contouring accuracy of nasopharyngeal carcinoma, which could have a positive impact on tumor control and patient survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Chang in this issue.
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Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Adolescente , Adulto , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Induction chemotherapy of docetaxel plus cisplatin (TP) is myelosuppressive, leading to severe neutropenia and febrile neutropenia (FN). Herein, we aimed to investigate the efficacy and safety of mecapegfilgrastim in the prevention of neutropenia in patients with locally advanced nasopharyngeal carcinoma who received the TP regimen. METHODS: A total of 30 treatment-naive patients with locally advanced nasopharyngeal carcinoma were included in this study. Mecapegfilgrastim 6 mg was injected 24-48 h after the completion of induction chemotherapy with the TP regimen. RESULTS: The incidence of grade ≥3 neutropenia during the three induction chemotherapy cycles was 6.7% (95% CI, 0.8%-22.1%). In the first cycle of chemotherapy, the incidence of grade ≥3 neutropenia was 3.3% (95% CI, 0.1%-17.2%). No FN or antibiotic usage was reported. All 30 patients completed the induction chemotherapy cycles. CONCLUSION: Mecapegfilgrastim effectively reduced the incidence of chemotherapy-induced neutropenia and FN in patients with locally advanced nasopharyngeal carcinoma.
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Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1-DXd) is elucidated. DAC treatment significantly enhanced anti-tumor efficacy of I1-DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1-DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.
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Decitabina , Modelos Animais de Doenças , Epigênese Genética , Imunoconjugados , Molécula 1 de Adesão Intercelular , Melanoma , Animais , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Camundongos , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/genética , Decitabina/farmacologia , Decitabina/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , HumanosRESUMO
The prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma (NPC) has decreased with the extensive use of intensity-modulated radiotherapy (IMRT). We aimed to develop a prognostic scoring system (PSS) that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT. The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed. Age, pathologic classification, primary tumor extension, primary gross tumor volume (GTV-p), T and N categories, and baseline lactate dehydrogenase (LDH) level were analyzed. Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS. Independent prognostic factors for locoregional relapse included N2-3 stage, GTV-p ≥26.8 mL, and involvement of one or more structures within cluster 3. We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups: low risk (score 0), intermediate risk (score >0 and ≤1), high risk (score >1 and ≤2), and extremely high risk (score >2). The 5-year locoregional control rates for these groups were 97.4%, 93.6%, 85.2%, and 78.6%, respectively (P < 0.001). We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.
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Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Idoso , Carcinoma , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia , Feminino , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Dosagem Radioterapêutica , Medição de Risco/métodos , Carga Tumoral , Adulto JovemRESUMO
The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9-111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.
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Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma , Criança , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucopenia/etiologia , Neoplasias Pulmonares/secundário , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neutropenia/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Estomatite/etiologia , Taxa de Sobrevida , Xerostomia/etiologia , Adulto JovemRESUMO
BACKGROUND: To evaluate the impact of coronavirus disease 2019 (COVID-19) pandemic on disease extent in patients with nasopharyngeal carcinoma (NPC) using 18 fuorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: This retrospective cohort study included biopsy-proven, newly diagnosed NPC patients using whole-body FDG PET/MR staging in two selected intervals: 1 May 2017 to 31 January 2020 (Group A, the pre-COVID-19 period), and 1 February 2020 to 30 June 2021 (Group B, the COVID-19 period). RESULTS: Three-hundred and ninety patients were included. No significant difference was observed in terms of T classification, N classification, overall stage, N stations, and M stations between the two groups (p > 0.05). For the involved neck node levels, more patients had developed level Vc metastasis in the group B (p = 0.044). CONCLUSION: Although the overall stage was not affected, more patients with NPC had developed level Vc metastasis in the era of COVID-19.
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COVID-19 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Pandemias , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: The purpose of this study is to evaluate the role of 18 fluorodeoxyglucose ( 18 F) PET/MRI ( 18 F-FDG PET/MRI) for detecting bone metastasis in nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Between May 2017 and May 2021, 58 histologically proven NPC patients who underwent both 18 F-FDG PET/MRI and 99m Tc-MDP planar bone scintigraphy (PBS) for tumor staging were included. With the exception of the head, the skeletal system was classified into four groups: the spine, the pelvis, the thorax and the appendix. RESULTS: Nine (15.5 %) of 58 patients were confirmed to have bone metastasis. There was no statistical difference between PET/MRI and PBS in patient-based analysis ( P = 0.125). One patient with a super scan was confirmed to have extensive and diffuse bone metastases and excluded for lesion-based analysis. Of the 57 patients, all 48 true metastatic lesions were positive in PET/MRI whereas only 24 true metastatic lesions were positive in PBS (spine: 8, thorax: 0, pelvis: 11 and appendix: 5). PET/MRI was observed to be more sensitive than PBS in lesion-based analysis (sensitivity 100.0% versus 50.0 %; P < 0.001). CONCLUSIONS: Compared with PBS for tumor staging of NPC, PET/MRI was observed to be more sensitive in the lesion-based analysis of bone metastasis.
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Neoplasias Ósseas , Neoplasias Nasofaríngeas , Humanos , Fluordesoxiglucose F18 , Carcinoma Nasofaríngeo/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Tomografia por Emissão de Pósitrons , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias Nasofaríngeas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Sensibilidade e EspecificidadeRESUMO
Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells in vitro. Furthermore, I1-MMAE and I1-DXd mediated a potent tumor regression in ATC and PTC xenograft models. To develop a precision medicine, we also explored magnetic resonance imaging (MRI) as a non-invasive biomarker detection method to quantitatively map ICAM1 antigen expression in heterogeneous thyroid tumors. Taken together, this study provides a strong rationale for the further development of I1-MMAE and I1-DXd as promising therapeutic candidates to treat advanced PTC and ATC.
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BACKGROUND: It is controversial and unclear how N-stage would increase the risk of incidence of hypothyroidism (HT) for patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Our study aimed to explore the correlation between cervical lymph node metastasis and the incidence of HT in NPC. MATERIALS AND METHODS: A total of 206 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences, and their clinical information were retrospectively collected. A series of univariate logistic regression models were performed to explore the association of clinical and lymph node indices with the development of HT. Significant features in univariate analysis were then used to construct three prediction models, for HT prediction using multivariate logistic regression based on Bayesian information criterion. Prediction performance of those models was measured by area under the receiver operating characteristic curve (AUC) using 10-fold cross-validation. RESULTS: A total of 111 patients developed HT, and the incidence of HT in N 2-3 and N 0-1 patients was 58.82% and 44.29%, respectively. Compared to Model 1 (consisted of pretreatment TSH concentration, thyroid volume, and N-stage) whose AUCs were 0.801 and 0.766 in training and validation sets, with N-stage be replaced by shortest distance from thyroid, Model 2 achieved more stable AUCs of 0.824 and 0.801. While with numbers of positive lymph nodes in Level IIb additionally added, Model 3 improved its AUCs to 0.841 and 0.813. CONCLUSION: The shortest distance between the lymph nodes and thyroid gland and the number of lymph nodes in IIb are better predictors of radiation-induced HT than the N-stage.
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This paper reviews the factors related to hypothyroidism after radiotherapy in patients with head and neck cancer to facilitate the prevention of radiation-induced hypothyroidism and reduce its incidence. Hypothyroidism is a common complication after radiotherapy in patients with head and neck cancer, wherein the higher the radiation dose to the thyroid and pituitary gland, the higher the incidence of hypothyroidism. With prolonged follow-up time, the incidence of hypothyroidism gradually increases. Intensity modulated radiotherapy should limit the dose to the thyroid, which would reduce the incidence of hypothyroidism. In addition, the risk factors for hypothyroidism include small thyroid volume size, female sex, and previous neck surgery. The incidence of radiation-induced hypothyroidism in head and neck cancer is related to the radiation dose, radiotherapy technique, thyroid volume, sex, and age. A prospective, large sample and long-term follow-up study should be carried out to establish a model of normal tissue complications that are likely to be related to radiation-induced hypothyroidism.
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Radiotherapy is a treatment where radiation is used to eliminate cancer cells. The delineation of organs-at-risk (OARs) is a vital step in radiotherapy treatment planning to avoid damage to healthy organs. For nasopharyngeal cancer, more than 20 OARs are needed to be precisely segmented in advance. The challenge of this task lies in complex anatomical structure, low-contrast organ contours, and the extremely imbalanced size between large and small organs. Common segmentation methods that treat them equally would generally lead to inaccurate small-organ labeling. We propose a novel two-stage deep neural network, FocusNetv2, to solve this challenging problem by automatically locating, ROI-pooling, and segmenting small organs with specifically designed small-organ localization and segmentation sub-networks while maintaining the accuracy of large organ segmentation. In addition to our original FocusNet, we employ a novel adversarial shape constraint on small organs to ensure the consistency between estimated small-organ shapes and organ shape prior knowledge. Our proposed framework is extensively tested on both self-collected dataset of 1,164 CT scans and the MICCAI Head and Neck Auto Segmentation Challenge 2015 dataset, which shows superior performance compared with state-of-the-art head and neck OAR segmentation methods.
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Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Cabeça/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Órgãos em Risco , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for recurrent/metastatic nasopharyngeal carcinoma (NPC); however, there is no standard regimen for those who failed first-line treatment. This study aimed to evaluate the efficacy and safety of apatinib in treating patients with recurrent/metastatic NPC who failed prior platinum-based chemotherapy. METHODS: Patients aged 18-65 years with recurrent/metastatic NPC were treated with apatinib at an initial dose of 500 mg once daily and continued until disease progression, patient withdrawal, or unacceptable toxic effects. The primary endpoints were clinical benefit rate (CBR) and toxicity. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: Nineteen patients were enrolled in this study. At the final follow-up, the CBR was 52.6% (95% CI: 29.8-76.2%) in the intention-to-treat population. The median PFS and OS were 3.7 (95% CI: 0.6-6.8) months and 12.9 (95% CI: 9.3-16.5) months, respectively. The most common grade 3-4 adverse events (AEs) were hand-foot syndrome [3 (15.8%)], neutropenia [2 (10.5%)], proteinuria [2 (10.5%)], oral mucosal pain [2 (10.5%)], hypertension [1 (5.3%)], hyponatremia [1 (5.3%)], artery dissection [1 (5.3%)], and nasopharyngeal hemorrhage [1 (5.3%)]. A serious AEs was reported in one patient who died of nasopharyngeal hemorrhage. Treatment with apatinib did not significantly influence patient-reported quality-of-life, except for nausea/vomiting and pain (P<0.05). CONCLUSIONS: Apatinib achieved modest disease control with acceptable toxicity in recurrent/metastatic NPC patients pretreated with platinum-based chemotherapy.
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BACKGROUND: This study explored the relationship between thyroid-associated antibodies, immune cells, and hypothyroidism to establish a predictive model for the incidence of hypothyroidism in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: A total of 170 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences between January 2015 and August 2018 were included. The complete blood count, biochemical, coagulation function, immune cells, and thyroid-associated antibodies tested before radiotherapy were evaluated. A logistic regression model was performed to elucidate which hematological indexes were related to hypothyroidism development. A predictive model for the incidence of hypothyroidism was established. Internal verification of the multifactor model was performed using the tenfold cross-validation method. RESULTS: The univariate analysis showed that immune cells had no statistically significant differences among the patients with and without hypothyroidism. Sex, N-stage, antithyroid peroxidase antibody (TPO-Ab), antithyroglobulin antibody (TG-Ab), thyroglobulin (TG), and fibrinogen (Fb) were associated with hypothyroidism. Males and early N-stage were protective factors of thyroid function, whereas increases in TPO-Ab, TG-Ab, TG, and Fb counts were associated with an increased rate of hypothyroidism incidence. The multivariate analysis showed that TPO-Ab, TG-Ab, TG, and Fb were independent predictors of hypothyroidism. The comprehensive effect of the significant model, including TPO-Ab, TG-Ab, TG, and Fb counts, represented the optimal method of predicting the incidence of radiation-induced hypothyroidism (AUC = 0.796). Tenfold cross-validation methods were applied for internal validation. The AUCs of the training and testing sets were 0.792 and 0.798, respectively. CONCLUSION: A model combining TPO-Ab, TG-Ab, TG, and Fb can be used to screen populations at a high risk of developing hypothyroidism after radiotherapy.
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Autoanticorpos/sangue , Fibrinogênio/análise , Hipotireoidismo/epidemiologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Tireoglobulina/sangue , Adulto , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: We investigated the risk factors of radiation-induced thyroid dysfunction, then combined the clinical factors and optimum thyroid dosimetric parameters to predict the incidence rate of hypothyroidism (HT) and to guide individualized treatment. METHODS: A total of 206 patients with histologically proven nasopharyngeal carcinoma (NPC) treated at the Cancer Hospital of the University of Chinese Academy of Sciences between January 2015 and August 2018 were included. Dose-volume histogram (DVH) data, including mean dose, absolute volume, V20, V25, V30, V35, V40, V45, V50, V55, and V60 were extracted and used as dosimetric parameters. A logistic regression analysis model was built to identify predictors related to HT occurring within 2 years. RESULTS: Sex, N stage, thyroid volume, mean thyroid dose, and thyroid V20 and V50 were significantly different between patients with and without HT. Logistic regression analysis showed that N stage, thyroid volume, and thyroid V50 were independent predictors of HT. The radiosensitivity of the thyroid decreased as the thyroid volume increased. Patients with N stage > 1 had significantly higher HT incidence (37.38%) than patients with N stage ≤1 (13.11%). The incidence of HT was 54.55% in patients with thyroid V50 > 24% and was 34.15% in patients with thyroid V50 ≤ 24%. CONCLUSIONS: The incidence of HT is significantly associated with N stage, thyroid volume, and thyroid V50. More attention should be paid to patients with NPC with thyroid volume ≤ 12.82 cm3 and advanced N stage disease.
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Hipotireoidismo/etiologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Glândula Tireoide/efeitos da radiação , Adulto , Feminino , Humanos , Hipotireoidismo/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Radiometria , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Glândula Tireoide/patologiaRESUMO
BACKGROUND AND AIMS: Malnutrition is a concern in patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy (CRT)/radiotherapy (RT), which is considered to be related with radiation-induced oral mucositis (ROM). The study aimed to evaluate the nutritional status of NPC patients during RT and investigate its association with ROM. METHODS: A prospective study was conducted in NPC patients. Patients were divided into three subgroups (mild, moderate, and severe groups) based on the duration of severe ROM (≥ grade 3). Body weight, body mass index (BMI), albumin, prealbumin, NRS2002, and ROM grade were assessed on a weekly basis before and during CRT/RT. The statistical analysis was performed in the overall group and between three subgroups. RESULTS: A total of 176 patients were included. In the overall group, body weight and BMI kept decreasing since week 1 of RT, and NRS2002 score and ROM grade increased (p < 0.001). NRS2002 score and prealbumin levels were significantly different between each subgroup (p ≤ 0.046). Significant differences were observed in the proportion of patients receiving enteral nutrition, duration of parenteral nutrition, and total calories provided by nutritional support among three subgroups (p = 0.045-0.001). CONCLUSIONS: Malnutrition occurred early in NPC patients and worsened continuously during RT. ROM was strongly associated with nutritional status. Nutritional support should be provided at the start of RT, especially in patients at high-risk of severe ROM.
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BACKGROUND: This study investigated lymph node distribution in patients with lateralized cancer of the nasopharynx to identify areas suitable for clinical target volume (CTV) reduction. METHODS: A total of 1680 patients with nasopharyngeal carcinoma (NPC) whose tumor involvement was assessed by MRI were reviewed retrospectively. RESULTS: One hundred and twelve patients (7%) had a lateralized primary lesion. Of these, 9 patients (8%) had contralateral lymph nodes including 4 (4%) who had contralateral cervical lymph nodes (CLNs). The rates of contralateral level III/Va metastasis were <1% (1 of 104) and 12.5% (1 of 8) in patients without and with contralateral retropharynx/level II involvement, respectively. No known risk factors were significantly associated with contralateral lymph node metastasis. CONCLUSION: Reduced cervical CTV coverage, including the contralateral level II, is feasible in patients with lateralized primary NPC, which may help to better protect the cervical OAR, including the thyroid, larynx, and esophagus. © 2015 Wiley Periodicals, Inc. Head Neck 38: E468-E472, 2016.
Assuntos
Metástase Linfática/patologia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Carga TumoralRESUMO
This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases.