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1.
Tumour Biol ; 36(11): 8349-57, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26014515

RESUMEN

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.


Asunto(s)
Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Pronóstico , Radioterapia de Intensidad Modulada , Adolescente , Adulto , Anciano , Carcinoma , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patología , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Factores de Riesgo
2.
Cancer ; 120(22): 3502-9, 2014 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-25056602

RESUMEN

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.


Asunto(s)
Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Radioterapia de Intensidad Modulada , Adulto , Anciano , Carcinoma , Causas de Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/mortalidad , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Insuficiencia del Tratamiento , Carga Tumoral
3.
Head Neck ; 41(5): 1246-1252, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30593728

RESUMEN

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.


Asunto(s)
Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidad Modulada , Adolescente , Adulto , Anciano , Análisis de Varianza , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/secundario , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Análisis de Supervivencia , Insuficiencia del Tratamiento , Resultado del Tratamiento , Adulto Joven
4.
Int J Radiat Oncol Biol Phys ; 104(4): 836-844, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-30954521

RESUMEN

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.


Asunto(s)
Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/efectos adversos , Femenino , Humanos , Quimioterapia de Inducción/efectos adversos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia , Estudios Prospectivos , Dosificación Radioterapéutica , Tamaño de la Muestra , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral , Adulto Joven
5.
J Med Radiat Sci ; 64(2): 106-113, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27741377

RESUMEN

INTRODUCTION: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, an effective immobilisation system is important to minimise set up deviation. This study evaluated the effectiveness of three immobilisation systems by assessing their set up deviations. METHODS: Patients were randomly assigned to one of the three immobilisation systems: (1) supine on head rest and base plate (HB); (2) supine with alpha cradle supporting the head and shoulder (AC); (3) supine with vacuum bag supporting the head and shoulder (VB). CBCT was conducted weekly for each patient on the linear accelerator. Image registration was conducted at the nasopharynx (NP) and cervical regions. The translational displacements (latero-medial, antero-posterior and cranio-caudal), rotational displacements (pitch, yaw and roll) and 3D vectors obtained at the NP and cervical regions were recorded and compared among the three systems. RESULTS: The mean translational and rotational deviations were within 3 mm and 2°, respectively, and the range of 3D vector was 1.53-3.47 mm. At the NP region, the AC system demonstrated the smallest translational and rotational deviations and 3D vector. The differences were significant except for the latero-medial, yaw and roll directions. Similarly, at the cervical region, the AC system showed smaller translational and rotational deviations and 3D vector, with only the cranio-caudal and yaw deviations that did not reach statistical significance. CONCLUSIONS: Set up deviation was greater in the neck than the NP region. The set up accuracy of the AC system was better than the other two systems, and it is recommended for IMRT of NPC patients in our institution.


Asunto(s)
Carcinoma/radioterapia , Inmovilización/instrumentación , Neoplasias Nasofaríngeas/radioterapia , Planificación de la Radioterapia Asistida por Computador/instrumentación , Errores de Configuración en Radioterapia , Radioterapia de Intensidad Modulada/instrumentación , Adulto , Anciano , Carcinoma/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagen , Resultado del Tratamiento , Adulto Joven
6.
Oncotarget ; 6(27): 24511-21, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-26087194

RESUMEN

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.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/secundario , Quimioradioterapia/métodos , Neoplasias Nasofaríngeas/patología , Radioterapia de Intensidad Modulada/métodos , Adolescente , Adulto , Anciano , Carcinoma , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Pronóstico , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto Joven
7.
Int J Radiat Oncol Biol Phys ; 58(3): 682-7, 2004 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-14967420

RESUMEN

PURPOSE: To report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9-78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68-70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT. RESULTS: The treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V(95-GTV)) was 98.5%, and the dose encompassing 95% of GTV (D(95-GTV)) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3-13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%). CONCLUSION: The improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome.


Asunto(s)
Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Radioterapia Conformacional/métodos , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador
8.
Zhonghua Zhong Liu Za Zhi ; 25(4): 386-9, 2003 Jul.
Artículo en Zh | MEDLINE | ID: mdl-12921573

RESUMEN

OBJECTIVE: To evaluate the feasibility, toxicity and tumor control of intensity modulated radiation therapy (IMRT) for recurrent nasopharyngeal carcinoma. METHODS: Fourty-nine patients (Karnofsky performance status (KPS) >or= 80) with local-regional recurrence in the nasopharynx were treated with full course IMRT. Three patients with cervical lymph node metastasis (N1 2 and N3 1) were further supplemented with 5 to 6 courses of chemotherapy (Cisplatin + 5-Fu) after IMRT. RESULTS: The results of treatment plan showed that the mean dose of covering gross tumor volume (GTV) (D(95)) in the nasopharynx was 68.09 Gy and the mean volume of GTV (V(95)) receiving the 95% dose was 98.46%. The mean dose of GTV, clinical target volume CTV1 and CTV2 in the targets were 71.40 Gy, 63.63 Gy and 59.81 Gy. The median follow-up time was 9 months (range 3 to 16 months). The local-regional progression-free survival was 100% with local-regional residual disease in 3 (6.1%) cases but was complicated with nasopharyngeal mucosa necrosis in 14 (28.6%) cases after IMRT. CONCLUSION: Intensity modulated radiation therapy, as a re-treatment option for recurrent nasopharyngeal carcinoma, is able to improve the tumor target coverage and spare the adjacent critical structures. As high dose IMRT can result in radio-necrosis of nasopharyngeal mucosa, the prescription dose of GTV should be suitably decreased to 60 - 65 Gy.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Radioterapia Conformacional/métodos , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Traumatismos por Radiación/patología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador
9.
Int J Radiat Oncol Biol Phys ; 85(4): 929-34, 2013 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-22975606

RESUMEN

PURPOSE: To evaluate the patterns of nodal failure and toxicity in clinically negative necks of N0-1 nasopharyngeal carcinoma (NPC) patients who were treated with intensity modulated radiation therapy (IMRT) but did not receive elective neck irradiation (ENI) to level IV and Vb nodes. METHODS AND MATERIALS: We conducted a phase 2 prospective study in N0-1 NPC patients treated with IMRT. ENI included the retropharyngeal nodes and levels II to Va but omitted levels IV and Vb in clinically negative necks. Patterns of nodal failure, regional control (RC), and late toxicity were evaluated. RESULTS: Between 2001 and 2008, a total of 212 patients (128 N0 and 84 N1) were enrolled in the study. Seven patients (4 in-field and 3 out-of-field) developed nodal failure. One patient (0.5%) developed nodal failure at level Vb, but no patients developed nodal failure at level IV. The 5-year RC rates of the entire group, N0 patients and N1 patients were 95.6%, 98.2%, and 91.3%, respectively. Fifteen patients (7.1%) developed distant metastases. The 5-year distant failure-free survival (DFFS) and overall survival (OS) rates were 91.4% and 89.8%, respectively. The rates of grade 2 or greater skin dystrophy, subcutaneous fibrosis and xerostomia were 6.2%, 16.6%, and 17.9%, respectively. CONCLUSIONS: The rate of out-of-field nodal failure when omitting ENI to levels IV and Vb in clinically negative necks of patients with N0-1 NPC was extremely low; therefore, a further phase 3 study is warranted.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Irradiación Linfática , Metástasis Linfática , Neoplasias Nasofaríngeas/radioterapia , Tratamientos Conservadores del Órgano/métodos , Adolescente , Adulto , Anciano , Braquiterapia , Carcinoma , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/secundario , Cuello , Estadificación de Neoplasias/métodos , Estudios Prospectivos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Tasa de Supervivencia , Xerostomía , Adulto Joven
10.
Eur J Radiol ; 81(11): 3496-503, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22483601

RESUMEN

PURPOSE: To investigate the correlation between the alterations of single-voxel (1)H MRS and the histopathological characteristics of radiation brain injury following radiation. MATERIALS AND METHODS: Twenty-seven rabbits were randomized into nine groups to receive radiation with a single dose of 25 Gy. The observation time points included a pre-radiation and 1, 2, 3, 4, 5, 6, 7, and 8 wk following radiation. Each treatment group underwent conventional MRI and single-voxel 1H MRS, N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were observed over the region of interest, and the presence or absence of lactate (Lac) and lipid (Lip) was detected. Histological specimens of each group were obtained after image acquisition. RESULTS: The values of Cho were significantly increased in the first 3 wk, and decreased over the following 5 wk after radiation. Levels of NAA showed a trend toward a decrease 5 wk after radiation. The levels of Cr were not changed between before and after radiation. The Cho/NAA metabolic ratio was significantly increased in weeks 6, 7, and 8 following irradiation, compared to pre-radiation values. Vascular and glial injury appeared on 2 wk after RT in the histology samples, until 4 wk after RT, necrosis of the oligodendrocytes, neuronal degeneration and demyelination could be observed. CONCLUSIONS: MRS is sensitive to detect metabolic changes following radiation, and can be used in the early diagnosis of radiation brain injury.


Asunto(s)
Ácido Aspártico/análogos & derivados , Lesiones Encefálicas/metabolismo , Colina/análisis , Espectroscopía de Resonancia Magnética/métodos , Traumatismos Experimentales por Radiación/metabolismo , Animales , Ácido Aspártico/análisis , Protones , Conejos , Estadística como Asunto
11.
J Neurol Sci ; 313(1-2): 64-74, 2012 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-21996274

RESUMEN

Multiple sclerosis (MS) is a debilitating neurodegenerative disease characterized by axonal/neuronal damage that may be caused by defective remyelination. Current therapies aim to slow the rate of degeneration, however there are no treatment options that can stop or reverse the myelin sheath damage. Bone marrow mesenchymal stem cells (MSCs) are a potential candidate for the cell implantation-targeted therapeutic strategies, but the pro-remyelination effects of MSCs when directly injected into a demyelinated cord lesion have been questioned. Neurotrophin-3 (NT-3) has been shown to serve a crucial role in the proliferation, differentiation and maturation of oligodendrocyte lineages. Here, we showed that implantation of NT-3 gene-modified MSCs via a recombinant adenoviral vector (Adv) into a region of ethidium bromide (EB)-induced demyelination in the spinal cord resulted in significant improvement of locomotor function and restoration of electrophysiological properties in rats. The morphological basis of this recovery was evidenced by robust myelin basic protein (MBP) expression and the extensive remyelination. AdvNT-3-MSC implants promote the endogenous remyelinating cells to participate directly in myelination, which was confirmed under light and electron microscopy. Our study suggested that genetically modified MSCs could be a potential therapeutic avenue for improving the efficacy of stem cell treatment for neurodegenerative diseases such as MS.


Asunto(s)
Enfermedades Desmielinizantes/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Vaina de Mielina/fisiología , Neurotrofina 3/administración & dosificación , Neurotrofina 3/genética , Recuperación de la Función/genética , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/cirugía , Animales , Enfermedades Desmielinizantes/genética , Enfermedades Desmielinizantes/cirugía , Femenino , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Actividad Motora/genética , Proteína Básica de Mielina/biosíntesis , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Ratas , Ratas Sprague-Dawley , Vértebras Torácicas
12.
Cancer ; 117(9): 1874-83, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-21509764

RESUMEN

BACKGROUND: The aim of this phase 2 study was to determine the long-term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy. METHODS: Eighty-one patients with pathologically diagnosed locally advanced NPC were enrolled in this study. IMRT was delivered with the SMART boost technique at prescribed doses of 68 grays (Gy)/30 fraction to the nasopharynx gross target volume. Concurrent cisplatin chemotherapy (80 mg/m(2) /d on Days 1 and 22) was administered. RESULTS: The mean actual physical dose delivered to the nasopharynx gross target volume was 73.8 Gy, and the mean biologically effective dose (BED) for the nasopharynx gross target volume was 84.8 Gy. With a median follow-up of 54 months, 4 (4.9%) patients experienced local recurrence. The 5-year local control rate was 94.9%. Eighteen patients died. Among them, 66.7% died of distant metastasis. The 5-year disease-free and overall survivals were 76.7% and 74.5%, respectively. The most common late toxicities among 68 patients with ≥4 years follow-up were grade 1-2 xerostomia, hearing loss, skin dystrophy, and subcutaneous fibrosis. No grade 4 late toxicities were noted. CONCLUSIONS: IMRT with SMART to enhance BED and concurrent chemotherapy is feasible in patients with locally advanced NPC. Long-term results showed excellent local control with fewer late toxicities, although no further improvement was noted in overall survival, and the major cause of death was distant metastasis. Exploration of more effective combined chemoradiation strategies is warranted.


Asunto(s)
Cisplatino/administración & dosificación , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidad Modulada/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/efectos adversos , Terapia Combinada/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Radioterapia de Intensidad Modulada/efectos adversos
13.
Ai Zheng ; 27(3): 327-30, 2008 Mar.
Artículo en Zh | MEDLINE | ID: mdl-18334128

RESUMEN

BACKGROUND & OBJECTIVE: Determination of planning risk volumes (PRVs) for an organ at risk greatly affects dose optimization in designing the intensity-modulated radiation therapy (IMRT) regimen. Patient setup errors have been found to closely correlate to the definition of PRVs. This study was to investigate the safety margin for the organ at risk during IMRT planning for nasopharyngeal carcinoma (NPC) patients. METHODS: Nineteen NPC patients (stage T1-2N0M0) who received IMRT for the first time were studied. Repeated computed tomography (CT) scans were performed for the patients once a week during the whole treatment course. A total of 85 CT scan reports were obtained. Differences between patient positioning of each time and first treatment setup were caluculated by comparing the anatomical landmarks (that is, optical nerve, pituitary, spine, and parotid) on each CT scan image using Osiris software. RESULTS: The displacement of optical nerve and pituitary in X, Y, and Z directions were, in absolute values, (0.86+/-0.53) mm, (0.84+/-0.68) mm, and (0.93+/-1.02)mm, respectively. The standard deviations (SDs) of systematic errors for the axial vector displacement were 0.83 mm, 1.08 mm, and 1.21 mm, while the SDs of random errors were 0.85 mm, 0.83 mm and 1.14 mm. The displacement of spine and parotid in X, Y, and Z directions were, in absolute values, (0.98+/-0.74) mm, (1.25+/-0.88) mm, and (1.43+/-1.02) mm, respectively. The SDs of systematic errors for axial vector displacement were 0.98 mm, 1.35 mm, and 1.87 mm, while the SDs of random errors were 1.02 mm, 1.46 mm, and 1.54 mm. CONCLUSION: It is feasible to determine the size of a safety margin of IMRT for organs at risk using repeated CT scans for NPC patients.


Asunto(s)
Neoplasias Nasofaríngeas/radioterapia , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
14.
Ai Zheng ; 26(2): 200-3, 2007 Feb.
Artículo en Zh | MEDLINE | ID: mdl-17298753

RESUMEN

BACKGROUND & OBJECTIVE: Intensity-modulated radiotherapy (IMRT) may help to diminish radiation-induced normal tissue damage and improve quality of life of nasopharyngeal carcinoma (NPC) patients. However, highly conformal treatment techniques commonly establish steep dose gradients between tumor and normal tissues, therefore, daily setup variations can significantly compromise the ultimate precision of idealized IMRT delivery. This study was to investigate the setup accuracy of thermoplastic masks used for immobilizing NPC patients treated by simultaneous integrated boost IMRT, and to determine adequate margins to account for those uncertainties. METHODS: Nineteen patients with early stage (T1-2N0M0) NPC received CT scan weekly during their 6-week treatment course of fractionated IMRT. A total of 85 scanning parameters were obtained. The differences in anatomic landmark coordinates in 3-dimensional directions between daily setup and the first day setup were calculated through comparing the CT images with Osiris software. RESULTS: Mean target isocenter translation was (0.89+/-0.69) mm in x-direction, (0.82+/-0.79) mm in y-direction, and (0.95+/-1.24) mm in z-direction. The systematic errors were 0.94 mm, 1.00 mm, and 1.32 mm. The random errors were 0.87 mm, 0.80 mm, and 1.04 mm. The mean total magnitude vector of isocenter motion was 1.87 mm; the 95% confidence interval (CI) was 2.03-7.24 mm. CONCLUSION: During IMRT for early stage nasopharyngeal carcinoma, setting appropriate margin of planning target volume (PTV) by widening 3 mm from clinical target volume (CTV) in x, y, z directions will be sufficient to compensate for the dosimetric uncertainty of target areas due to patient setup error. The measured data in the present study should enable the user of this kind of thermoplastic mask to assign appropriate margins for the generation of planning target volumes (PTVs).


Asunto(s)
Neoplasias Nasofaríngeas/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Adulto , Intervalos de Confianza , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Inmovilización , Masculino , Máscaras , Persona de Mediana Edad , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos X
15.
Ai Zheng ; 23(11 Suppl): 1532-7, 2004 Nov.
Artículo en Zh | MEDLINE | ID: mdl-15566674

RESUMEN

BACKGROUND & OBJECTIVE: Local-regional uncontrolled is an important reason of treatment failure for advanced nasopharyngeal carcinoma (NPC) after radiotherapy. Local-regional control rate increased with dose to tumor target volumes. Because of the complex anatomy features, dose escalation using conventional two-dimensional radiotherapy planning is limited by the tolerance of adjacent critical organs. In order to enhance doses to target volumes and local-regional control rates, this study explored application of intensity modulated radiation therapy (IMRT) in local-regional advanced NPC. METHODS: Sixty patients with naive primary NPC, 49 in stage III, and 11 in stage IVa, received IMRT alone with an inverse planning system (CORVUS 3.0, Peacock plan). Treatment was delivered with the Multi-leaf Intensity Modulating Collimator (MIMiC) using a slice-by-slice arc rotation approach. The prescription dose was 68 Gy to nasopharynx gross tumor volume (GTVnx), 60-64 Gy to positive neck lymph nodes (GTVnd), 60 Gy to clinical target volume I (Target I), and 54 Gy to clinical target volume II (Target II), delivered by 30 fractions. Acute normal tissue effects were graded according to RTOG/EORTC radiation morbidity scoring criteria. Local control rate, regional control rate, distant metastasis-free rate, and overall survival rate were calculated using Kaplan-Meier method. RESULTS: Analysis of dose-volume histograms (DVH) showed that the average mean dose delivered were 71.21 Gy to GTVnx, 65.85 Gy to GTVnd(L), 66.26 Gy to GTVnd(R), 67.59 Gy to Target I, and 61.42 Gy to Target II. The mean fractional dosage delivered were 2.37 Gy to GTVnx, 2.20 Gy to GTVnd(L), and 2.21 Gy to GTVnd(R). The average volumes of all target volumes covered by 95% isodose were more than 99%, and the average volume of GTVnx covered by 105% isodose was 43.87%; 5% of brainstem volume, and 1cc of spinal cord volume received average dosage were 46.96 Gy, and 39.99 Gy; 33% of volume of bilateral parotids, and T-M Joints received average dose was less than 38 Gy. There was no Grade 4 acute toxicity in all patients, and incidences of acute grade 3 toxicity of skin, mucous membrane, and salivary glands were 1.7%, 15.0%, and 1.7%, respectively. With the median follow-up of 15.5 months (6-37 months), no patient failed at the primary site, 2 patients relapsed at neck, 7 patients developed distant metastases, 9 patients died. The 3-year local control rate, regional control rate, and distant metastasis-free rate were 96.67%, 94.06%, and 84.98% respectively, 3-year overall survival rate was 74.97%. CONCLUSIONS: IMRT could escalate the total dose and fractional dosage to target volumes, and decrease the irradiation dose of surrounding critical organs. The acute toxicities were slight and tolerable. The local-regional control rates were satisfied. Distant metastasis is the main cause of failure.


Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia Conformacional/métodos , Adulto , Anciano , Neoplasias Óseas/secundario , Carcinoma de Células Escamosas/secundario , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Dosis de Radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Tasa de Supervivencia
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