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1.
Cancer Res Treat ; 52(1): 31-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31048664

RESUMO

PURPOSE: The purpose of this study was to compare the survival and toxicities in cervical esophageal squamous cell carcinoma (CESCC) treated by concurrent chemoradiothrapy with either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) techniques. Materials and Methods: A total of 112 consecutive CESCC patients were retrospectively reviewed. 3D-CRT and IMRT groups had been analyzed by propensity score matching method, with sex, age, Karnofsky performance status, induction chemotherapy, and tumor stage well matched. The Kaplan-Meier method and Cox proportional hazards model were used for overall survival (OS) and progression-free survival (PFS). Toxicities were compared between two groups by Fisher exact test. RESULTS: With a median follow-up time of 34.9 months, the 3-year OS (p=0.927) and PFS (p=0.859) rate was 49.6% and 45.8% in 3D-CRT group, compared with 54.4% and 42.8% in IMRT group. The rates of grade ≥ 3 esophagitis, grade ≥ 2 pneumonitis, esophageal stricture, and hemorrhage were comparable between two groups, while the rate of tracheostomy dependence was much higher in IMRT group than 3D-CRT group (14.3% vs.1.8%, p=0.032). Radiotherapy technique (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.01 to 0.79) and pretreatment hoarseness (HR, 0.12; 95% CI 0.02 to 0.70) were independently prognostic of tracheostomy dependence. CONCLUSION: No survival benefits had been observed while comparing IMRT versus 3D-CRT in CESCC patients. IMRT with fraction dose escalation and pretreatment hoarseness were considered to be associated with a higher risk for tracheostomy dependence. Radiation dose escalation beyond 60 Gy should be taken into account carefully when using IMRT with hypofractionated regimen.

2.
Int J Radiat Oncol Biol Phys ; 104(4): 836-844, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30954521

RESUMO

PURPOSE: To evaluate the long-term locoregional control, failure patterns, and late toxicity after reducing the target volume and radiation dose in patients with locoregionally advanced nasopharyngeal carcinoma patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Previously untreated patients with locoregionally advanced nasopharyngeal carcinoma were recruited into this prospective study. All patients received 2 cycles of IC followed by CCRT. The gross tumor volumes of the nasopharynx (GTVnx) and the neck lymph nodes (GTVnd) were delineated according to the post-IC tumor extension and received full therapeutic doses (68 Gy and 62-66 Gy, respectively). The primary tumor shrinkage after IC was included in the high-risk clinical target volume (CTV1) with a reduced dose of 60 Gy. The locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were calculated using the Kaplan-Meier method. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. RESULTS: There were 112 patients enrolled in this study. The average mean dose of post-GTVnx, post-GTVnd (left), post-GTVnd (right), post-CTV1, and post-low-risk clinical target volume (CTV2) was 75.24, 68.97, 69.16, 70.49, and 63.37 Gy, respectively. With a median follow-up of 125.95 months, the 10-year LRRFS, DMFS and OS were 89.0%, 83.3%, and 75.9%, respectively. There were 8 local recurrences and 6 regional recurrences in 12 patients. All 8 of the local recurrences were in-field; among the 6 regional recurrences, 4 were in-field, 1 was marginal, and 1 was out-field. The most common late toxicities were grade 1 to 2 subcutaneous fibrosis, hearing loss, and xerostomia. No grade 4 late toxicities were observed. CONCLUSIONS: Reduction of the target volumes according to the post-IC tumor extension and radiation dose to the post-IC tumor shrinkage could yield excellent long-term locoregional control with limited marginal and out-field recurrences and mild late toxicities.


Assuntos
Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia , Estudos Prospectivos , Dosagem Radioterapêutica , Tamanho da Amostra , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
3.
Radiology ; 291(3): 677-686, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30912722

RESUMO

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.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Assistida por Computador/métodos , Imagem 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 Jovem
4.
Head Neck ; 41(5): 1246-1252, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30593728

RESUMO

PURPOSE: To analyze the long-term outcome and pattern of failure for patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Patients with NPC after IMRT from 2001 to 2008 were recruited (n = 865). Clinical features, laboratory data, and treatments were collected. RESULTS: The 10-year local recurrence-free survival, distant metastasis-free survival, and disease-specific survival (DSS) were 92.0%, 83.4%, and 78.6%, respectively. A total of 209 patients died: 59% of whom died from distant metastasis. The 10-year DSS was higher in patients who received chemoradiotherapy than those who received IMRT alone for patients with high-risk stage III disease, while there was no survival difference for patients with stage II and low-risk stage III disease. CONCLUSIONS: IMRT provides satisfactory long-term survival for patients with NPC. Distant metastasis has been the most common reason for failure. Adding chemotherapy did not improve survival in patients with stage II and low-risk stage III disease.

5.
Oncol Lett ; 15(5): 7993-7998, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731910

RESUMO

Resistance to apoptosis is an characteristic of cancer cells that serves a critical function in tumor development and represents a target for antitumor therapy. Isoimperatorin (ISOIM), a coumarin compound, exhibits antitumor functions in multiple types of tumor cells. However, its antitumor effects and molecular mechanisms with respect to gastric cancer have not been elucidated. The present study assessed the anti-proliferative and apoptotic effects of ISOIM on human BGC-823 gastric cancer cells and elucidated its underlying molecular mechanisms. Cell proliferation was evaluated using MTT assays. Analysis of cell morphology was performed by hematoxylin and eosin, Hoechst 33258 and acridine orange/ethidium bromide staining. In addition, cell cycle and apoptosis was evaluated using flow cytometry analysis; expression of apoptosis-associated proteins was studied by western blotting. The results of the present study revealed that ISOIM significantly inhibited cell proliferation by arresting the cell cycle at the G2/M phase and induced apoptosis by increasing Bcl-2-associated X (Bax) expression with a concomitant decrease in Bcl-2 expression, resulting in a decreased Bcl-2/Bax ratio compared with the control. In addition, ISOIM treatment also resulted in cytochrome c translocating from the mitochondria to the cytosol. Furthermore, caspase-3 was significantly activated in response to treatment with ISOIM, suggesting that apoptosis in BGC-823 cells is induced in the mitochondrial pathway. Taken together, the results of the present study indicate that ISOIM may significantly induce apoptosis in BGC-823 cells and that the pro-apoptotic mechanisms of ISOIM could be associated with the mitochondrial pathway.

6.
J Cancer ; 9(6): 978-986, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29581777

RESUMO

Background: The purpose of this study is to assess the feasibility of volumetric-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients by comparing the physical dosimetry, delivery efficiency and clinical outcomes with intensity-modulated radiotherapy (IMRT). Methods: A prospective matched study was performed for patients with newly diagnosed NPC who underwent VMAT or IMRT. The patients in two groups were equally matched in terms of gender, age, tumor stage and chemotherapy. The target coverage, homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV), organs at risk (OARs) sparing, average treatment time and clinical outcomes were analyzed. Results: From June 2013 to August 2015, a total of 80 patients were enrolled in this study, with 40 patients in each group. The coverage of PTV was similar for both groups. D2 was observed slight difference only in early stage disease (T1-2) (VMAT vs. IMRT, 7494±109 cGy vs. 7564±92 cGy; p=0.06). The HI of VMAT group was better than that of IMRT group (p=0.001), whereas CI was slightly worse (p=0.061). The maximum doses received by the brain stem, spinal cord, and optic nerve of VMAT were higher than those of IMRT (p<0.05). But the irradiation volumes in healthy tissue were generally lower for VMAT group, with significant differences in V20, V25 and V45 (p<0.05). With regard to the delivery efficiency compared with IMRT (1160 ± 204s), a 69% reduction in treatment time was achieved by VMAT (363 ± 162s). Both groups had 5 cases of nasopharyngeal residual lesions after radiotherapy. The 2-year estimated local relapse-free survival, regional relapse-free survival and locoregional relapse-free survival, distant metastasis-free survival, disease-free survival and overall survival were similar between two groups, with the corresponding rates of 100%, 97.4%, 97.4%, 90.0%, 90.0% and 92.4% in VMAT group, and 100%, 100%, 100%, 95.0%, 95.0% and 97.5% in IMRT group, respectively. Conclusions: Both VMAT and IMRT can meet the clinical requirements for the treatment of NPC. The short-term tumor regression rates and 2-year survival rates with the two techniques are comparable. The faster treatment time benefits of VMAT will enable more patients to receive precision radiotherapy.

7.
Oncotarget ; 6(27): 24511-21, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26087194

RESUMO

PURPOSE: To report the distant metastasis (DM) risk and patterns for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to analyze the benefits of chemotherapy based on DM risk. MATERIALS AND METHODS: 576 NPC patients were analyzed. The DM rates were calculated using the Kaplan-Meier method, and the log-rank test was used to compare differences. The patients were divided into different risk subclassifications according to DM hazard ratios. RESULTS: 91 patients developed DM after treatment, with bone as the most common metastatic sites. 82.4% of DMs occurred within 3 years of treatment. Patients were classified as low-risk, intermediate-risk and high-risk, and the corresponding 5-year DM rates were 5.1%, 13.1% and 32.4%, respectively (P < 0.001). Chemotherapy failed to decrease the DM rate in the low-risk subclassification, but decreased the DM risk in the intermediate-risk subclassification (P = 0.025). In the high-risk subclassification, the DM rate was 31.9% though chemotherapy was used, which was significantly higher than that of other two subclassifications. CONCLUSIONS: DM is the dominant treatment failure in NPC treated by IMRT, with similar occurrence times and distributions to those that occurred in the era of conventional radiotherapy. Further studies on treatment optimization are needed in high-risk patients.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/secundário , Quimiorradioterapia/métodos , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Idoso , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
8.
Tumour Biol ; 36(11): 8349-57, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26014515

RESUMO

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4 months. The 5-year DM rate was 15.1%. N2-3, primary tumour volume of nasopharynx (GTVnx) >24.56 cm(3), haemoglobin change after treatment (ΔHGB) >25.8 g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245 U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0-2), intermediate risk (3-4) and high risk (5-8). The 5-year DM rates were 4.6, 21.8 and 50.8%, respectively (P < 0.001). The areas under the curve for DM in the prediction-score model and the UICC/AJCC staging system seventh edition were 0.748 and 0.627, respectively (P < 0.001). The scoring model is useful in evaluating the risk of DM in IMRT-treated NPC patients and guiding future therapeutic trials. Further prospective study is needed.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Radioterapia de Intensidade Modulada , Adolescente , Adulto , Idoso , Carcinoma , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Fatores de Risco
9.
PLoS One ; 10(4): e0125351, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25927527

RESUMO

INTRODUCTION: To evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma. METHODS: Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell's concordance index (c-index) were utilized to test the prognostic value. RESULTS: The median TV significantly increased with advancing recurrent T classification (P<0.001). The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003), overall survival (hazard ratio = 1.015, P<0.001) and toxicity-related death (hazard ratio = 1.014, P<0.001). The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm3 and TV ≥22 cm3, respectively (P < 0.001). In patient with TV <22 cm3, locoregional failure is the leading cause of death. In patients with TV≥22 cm3, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV. CONCLUSIONS: Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.


Assuntos
Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Carcinoma , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Retratamento , Terapia de Salvação , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
10.
Radiology ; 276(1): 243-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25658039

RESUMO

PURPOSE: To identify predictors for the development of temporal lobe injury (TLI) after intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Data in 351 patients with nasopharyngeal carcinoma treated with IMRT were reviewed retrospectively according to institutional ethics committee approval. Clinical factors associated with TLI were analyzed. Dose-volume histograms for 550 evaluable temporal lobes were analyzed, and the predictive value of therapy-associated and patient-associated factors for the occurrence of TLI was evaluated. Survival curves were depicted by using the Kaplan-Meier method and compared by using the log-rank test. Logistic regression analysis was used for multivariate analyses. RESULTS: Median follow-up was 76 months (range, 6-100 months). Twenty-nine of 351 patients (8.3%) developed TLI; 21 patients had unilateral TLI, and eight had bilateral TLI. Median latency from IMRT until first TLI was 33 months (range, 12-83 months) among patients with TLI. The actuarial TLI-free survival rates were 94.4% and 91.3% at 3 and 5 years after radiation therapy, respectively. Logistic regression analysis demonstrated that dose delivered to a 1-cm(3) volume of the temporal lobe (D1cc) was the only independent predictor for TLI. The biologically equivalent tolerance doses at 2 Gy for a 5% and 50% probability of developing TLI were 62.83-Gy equivalents (95% confidence interval: 59.68, 65.97) and 77.58-Gy equivalents (95% confidence interval: 74.85, 80.32), respectively. CONCLUSION: D1cc is predictive for radiation-induced TLI, suggesting that delivery of a high dose of radiation to a small volume of the temporal lobe is unsafe. A D1cc of 62.83 Gy by using a correction formula for varying fraction size may be the dose tolerance of the temporal lobe.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Lobo Temporal/lesões , Adulto , Carcinoma , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Carcinoma Nasofaríngeo , Estudos Retrospectivos
11.
Oral Oncol ; 51(4): 363-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25655559

RESUMO

OBJECTIVES: The utility of [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the prediction of distant metastasis after definitive treatment for non-disseminated NPC patients is not clear. We prospectively investigated the prognostic significance of (18)F-FDG PET-CT performed before treatment for the distant metastasis-free survival (DMFS) of NPC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy. MATERIALS AND METHODS: The results of PET-CT scans performed at initial diagnosis were recorded and analyzed prospectively. Patients then received standard treatment per protocol independent of the PET-CT result. IMRT was administered to the nasopharynx and neck. Early stage patients received IMRT alone, whereas loco-regionally advanced patients received concurrent chemoradiation. Patient outcomes were evaluated. RESULTS: One hundred and seventy-nine patients were analyzable. DM occurred in 33 patients and the 3-year DMFS rate of the whole cohort was 84.1%. The cut-off of the SUVmax at the primary site (SUVmax-P) for DMFS was 10.22 by ROC curve. The 3-year DMFS rates of the higher and lower SUVmax-P groups (SUVmax-P⩽or>10.22) were 93.2% and 75.1%, respectively, with an 18.1% difference (P=0.003). Multivariate analysis indicated that SUVmax-P was a risk factor independently associated with DMFS (HR, 2.672; 95%CI, 1.236-5.776; P=0.012) and OS (HR, 2.417; 95%CI, 1.313-4.448; P=0.005). Subgroup analysis indicated that the 5-year DMFS and OS in loco-regionally advanced patients with SUVmax-P⩽10.22 were similar to those of early stage patients, whereas those of loco-regionally advanced patients with SUVmax-P>10.22 patients predicted worse outcome. CONCLUSION: SUVmax-P is a useful biomarker to predict distant metastasis of NPC patients treated with IMRT. Combining SUVmax-P with tumor overall stage, a more precise picture could be obtained to predict treatment outcome.


Assuntos
Imagem Multimodal , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Prospectivos , Radioterapia de Intensidade Modulada , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Biomed Res Int ; 2014: 326532, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25197637

RESUMO

An approximate correction method for the CT value-electron density curve of CBCT was established, through comparison and fitting with FBCT images, and applied to evaluate the therapeutic dose of IMRT. The precision of using CBCT for plan calculation was validated by comparing the dose distribution between CBCT- and FBCT-based IMRT plans. Also setup deviations were simulated to evaluate the ability of the CBCT-based calculation for detecting the dose errors caused by positioning deviation. The gamma comparison between CBCT- and FBCT-based dose computations showed that the pass rates of (2%, 2 mm) criteria were better than 97.60 ± 0.83% and 97.74 ± 2.08% in the phantom and 10 NPC cases. When setup deviation was introduced into CBCT-based dose calculation, the gamma pass rate significantly decreased while the volumetric doses of the targets and some normal organs exhibited different changes compared to the original plan. Our results validated the above CT value-electron density correction which reduced the difference between CBCT- and FBCT-based IMRT plan calculation for NPC to less than 2%. Online CBCT-based dose calculation can be used to reflect and evaluate the dose distribution discrepancy caused by setup deviation and structure changes during the treatment, ensuring more effective quality control of IMRT treatment.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Cabeça/efeitos da radiação , Pescoço/efeitos da radiação , Radioterapia de Intensidade Modulada , Simulação por Computador , Relação Dose-Resposta à Radiação , Elétrons , Humanos , Reprodutibilidade dos Testes
13.
Cancer ; 120(22): 3502-9, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25056602

RESUMO

BACKGROUND: The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model. METHODS: Between January 2003 and December 2007, a total of 117 patients with locally recurrent nonmetastatic nasopharyngeal carcinoma were randomized to 2 different models of total dose and fraction size: group A (59 patients) received 60 gray in 27 fractions and group B (58 patients) received 68 gray in 34 fractions. Both groups received 5 daily fractions per week. All patients received IMRT alone. RESULTS: The median follow-up was 25.0 months. The 5-year overall survival in group A was higher than that in group B (44.2% vs 30.3%; P =.06), and the local failure-free survival in group A was slightly lower than that in group B (63.7% vs 71.0%; P =.41). Severe late complications were the main cause of death. The incidences of mucosal necrosis and massive hemorrhage in patients in group B were significantly higher than those among patients in group A at 50.8% versus 28.8% (P =.02) and 31.0% versus 18.6% (P =.12), respectively. Tumor volume (P<.01) and model of total dose and fraction size (P =.03) were found to be significant factors for mucosal necrosis and massive hemorrhage. CONCLUSIONS: Appropriately decreasing the total dose and increasing the fraction size can achieve local control similar to that achieved with a higher dose after IMRT; furthermore, it can improve overall survival by significantly reducing the incidence of severe late complications including mucosal necrosis and massive hemorrhage.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Carcinoma , Causas de Morte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/mortalidade , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Falha de Tratamento , Carga Tumoral
14.
Asian Pac J Cancer Prev ; 15(7): 3169-73, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24815465

RESUMO

BACKGROUND: To investigate factors associated with overall survival in patients with newly diagnosed metastatic nasopharyngeal carcinoma. MATERIALS AND METHODS: Two hundred and two consecutive patients with pathologically confirmed nasopharyngeal carcinoma with distant metastasis at diagnosis seen between December 2007 and May 2011 were reviewed. Patient, tumor and treatment factors were analyzed for their significance regarding overall survival. RESULTS: The median follow-up time was 22 months. At the time of this report, 116 patients had died. For 112 patients, cause of death was nasopharyngeal carcinoma. The 1, 2, 3, and 4-year overall survival rates were 75.6%, 50.2%, 39.2%, and 28.2%, respectively. Cox regression multivariate analysis showed that T-stage (p=0.045), N-stage (p=0.014), metastasis number (p<0.001) and radiotherapy for nasopharynx and neck (p<0.001) were significant factors for overall survival. CONCLUSIONS: Early T-stage and N-stage, solitary metastasis in a single organ were good prognostic factors for patients with newly diagnosed metastatic nasopharyngeal carcinoma. Radiotherapy should be strongly recommended in systemic treatment.


Assuntos
Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Nasofaringe/efeitos da radiação , Pescoço/efeitos da radiação , Adolescente , Adulto , Idoso , Carcinoma , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Nasofaringe/patologia , Pescoço/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Radioterapia Conformacional , Taxa de Sobrevida , Taxoides/uso terapêutico , Adulto Jovem
15.
Radiat Oncol ; 9: 87, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24674015

RESUMO

BACKGROUND: To investigate the clinical feature and the local failure patterns after intensity-modulated radiotherapy for nasopharyngeal carcinoma. METHODS: Between March 2007 and July 2009, 710 patients with nasopharyngeal carcinoma were treated with intensity-modulated radiotherapy. The magnetic resonance imagings obtained at recurrence were registered with the original planning computed tomography for dosimetry analysis. RESULTS: With a median follow-up of 38 months, 34 patients have developed local recurrence (32 cases valid). The incidence of invasion to nasopharynx, parapharyngeal space and the retropharyngeal space by the primary tumors was 100%, 75.0% and 62.5%, respectively, but 78.1%, 34.4% and 21.9% at recurrence, respectively. The rate of invasion to ethmoid sinus was 3.1% by the primary tumors but 28.1% at recurrence (p=0.005). The topographic analysis of the local failure patterns showed "central" in 16 patients; "marginal" in 9; and "outside" in 7. The median volumes of primary gross tumor were 45.84 cm(3) in the central failure group, 29.44 cm(3) in the marginal failure group, and 21.52 cm(3) in the outside failure group, respectively (p=0.012), and the median volumes of primary clinical target1 were 87.28 cm(3), 61.90 cm(3) and 58.74 cm(3) in the three groups, respectively (p=0.033). CONCLUSIONS: In patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy, the recurrent tumors had their unique characteristic and regularity of invasion to adjacent structures. "Central" failure was the major local failure pattern. The volumes of primary gross tumor and clinical target1 were significantly correlated with recurrent patterns. Employ more aggressive approaches to tumor cells which will be insensitive to radiotherapy may be an effective way to reduce the central failure.


Assuntos
Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia/diagnóstico , Radioterapia de Intensidade Modulada , Adulto , Idoso , Carcinoma , Feminino , Seguimentos , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Dosagem Radioterapêutica , Falha de Tratamento , Carga Tumoral , Adulto Jovem
16.
J Cancer Res Clin Oncol ; 140(1): 69-76, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24173695

RESUMO

PURPOSE: We aimed to analyze prognostic factors in patients with nasopharyngeal carcinoma (NPC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT); in addition, we aimed to elucidate the value of primary gross tumor volume (GTVp) in predicting prognosis of patients. METHODS: Between February 2001 and December 2008, 321 patients with NPC treated with concurrent chemotherapy and IMRT were analyzed retrospectively. GTVp was calculated from treatment planning computed tomography scans. A receiver operating characteristics (ROC) curve was used to determine the best cutoff point of GTVp. RESULTS: The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) for NPC patients were 93.8, 80.1, 73.0, and 83.7 %, respectively. Univariate and multivariate analyses indicated that GTVp had exhibited a statistically significant correlation with LFFS, DMFS, DFS, and OS (P < 0.05, all), whereas T classification was not an independent prognostic factor. According to ROC curve analysis, 49 and 19 mL were determined as the cutoff points of GTVp for local control and distant metastasis, respectively. Based on this, 321 patients were divided into three volume subgroups. LFFS, DMFS, DFS, and OS demonstrated significant differences among patients in different volume subgroups (P < 0.001, all) and were superior to T classification for predicting prognosis of NPC patients. CONCLUSIONS: Primary gross tumor volume is an independent prognostic factor in local control, distant metastasis, disease-free survival, and overall survival in NPC. An adjusted TNM staging system that includes GTVp as a quantitative indicator to evaluate prognosis is warranted.


Assuntos
Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Metástase Neoplásica , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Prognóstico , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Adulto Jovem
17.
BMC Cancer ; 13: 397, 2013 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-23978128

RESUMO

BACKGROUND: To identify the radiation volume effect and significant dosimetric parameters for temporal lobe injury (TLI) and determine the radiation dose tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT). METHODS: Twenty NPC patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were reviewed. Dose-volume data was retrospectively analyzed. RESULTS: Paired samples t-tests showed all dosimetric parameters significantly correlated with TLI, except the TL volume (TLV) and V75 (the TLV that received ≥75 Gy, P = 0.73 and 0.22, respectively). Receiver operating characteristic (ROC) curves showed V10 and V20 (P = 0.552 and 0.11, respectively) were the only non-significant predictors from V10 to V70 for TLI. D(0.5cc) (dose to 0.5 ml of the TLV) was an independent predictor for TLI (P < 0.001) in multivariate analysis; the area under the ROC curve for D(0.5cc) was 0.843 (P < 0.001), and the cutoff point 69 Gy was deemed as the radiation dose limit. The distribution of high dose 'hot spot' regions and the location of TLI were consistent. CONCLUSIONS: A D0.5cc of 69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent on high dose 'hot spots' in the TL; physicians should be cautious of such 'hot spots' in the TL during IMRT treatment plan optimization, review and approval.


Assuntos
Neoplasias Nasofaríngeas/complicações , Lesões por Radiação/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Lobo Temporal/patologia , Lobo Temporal/efeitos da radiação , Adulto , Carcinoma , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/radioterapia , Estadiamento de Neoplasias , Curva ROC , Doses de Radiação , Tolerância a Radiação , Radiometria , Dosagem Radioterapêutica , Resultado do Tratamento , Adulto Jovem
18.
Biomed Res Int ; 2013: 872739, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23862160

RESUMO

This study presented the analysis of free-breathing lung tumor motion characteristics using GE 4DCT and Varian RPM systems. Tumor respiratory movement was found to be associated with GTV size, the superior-inferior tumor location in the lung, and the attachment degree to rigid structure (e.g., chest wall, vertebrae, or mediastinum), with tumor location being the most important factor among the other two. Improved outcomes in survival and local control of 43 lung cancer patients were also reported. Consideration of respiration-induced motion based on 4DCT for lung cancer yields individualized margin and more accurate and safe target coverage and thus can potentially improve treatment outcome.


Assuntos
Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Movimento , Respiração , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Intervalo Livre de Doença , Feminino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Falha de Tratamento , Resultado do Tratamento
19.
Radiat Oncol ; 8: 87, 2013 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-23578324

RESUMO

BACKGROUND: The correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system. METHODS: Between February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann-Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis. RESULTS: Median primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 - 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis. CONCLUSION: Tumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system.


Assuntos
Neoplasias Nasofaríngeas/classificação , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias/métodos , Adolescente , Adulto , Idoso , Carcinoma , Criança , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Metástase Neoplásica/patologia , Radioterapia de Intensidade Modulada , Carga Tumoral , Adulto Jovem
20.
Mol Biosyst ; 9(6): 1372-80, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23475132

RESUMO

Zebrafish embryogenesis is a rapid process driven by a myriad of gene products and small molecules. As previous studies have detailed the relevant transcriptional and proteomics changes, here we assess the metabolomic changes that occur at different stages of embryogenesis (4, 8, 12, 24 and 48 hours post fertilization). Metabolite levels were detected using GC-MS and LC-MS, following which multivariate analysis (OPLS-DA) was applied to identify metabolites that were differentially regulated throughout embryogenesis. From the two robust OPLS-DA models that were generated (Q(2)(cum) = 0.940 and Q(2)(cum) = 0.894), a total of 60 detected metabolites (20 from GC-MS, 40 from LC-MS) were identified and found to be important in discriminating between developmental stages. Hierarchical clustering analysis was applied to the dataset and metabolite classes such as amino acids and lipids were shown to be differentially regulated. Biologically relevant transcriptomic and proteomic data were associated with metabolites to provide a more holistic systems perspective of embryogenesis. In summary, the metabolic profiles of different developmental stages highlight the dynamic changes occurring during embryogenesis. These data could serve as a basis for future toxicological or developmental studies.


Assuntos
Metaboloma , Metabolômica , Peixe-Zebra/embriologia , Animais , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Regulação da Expressão Gênica no Desenvolvimento , Espectrometria de Massas , Proteômica , Transcriptoma
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