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Intense, mutually coherent beams of multiharmonic extreme ultraviolet light can now be created using seeded free-electron lasers, and the phase difference between harmonics can be tuned with attosecond accuracy. However, the absolute value of the phase is generally not determined. We present a method for determining precisely the absolute phase relationship of a fundamental wavelength and its second harmonic, as well as the amplitude ratio. Only a few easily calculated theoretical parameters are required in addition to the experimental data.
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Chirped pulse amplification in optical lasers is a revolutionary technique, which allows the generation of extremely powerful femtosecond pulses in the infrared and visible spectral ranges. Such pulses are nowadays an indispensable tool for a myriad of applications, both in fundamental and applied research. In recent years, a strong need emerged for light sources producing ultra-short and intense laser-like X-ray pulses, to be used for experiments in a variety of disciplines, ranging from physics and chemistry to biology and material sciences. This demand was satisfied by the advent of short-wavelength free-electron lasers. However, for any given free-electron laser setup, a limit presently exists in the generation of ultra-short pulses carrying substantial energy. Here we present the experimental implementation of chirped pulse amplification on a seeded free-electron laser in the extreme-ultraviolet, paving the way to the generation of fully coherent sub-femtosecond gigawatt pulses in the water window (2.3-4.4 nm).
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PURPOSE: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. METHODS AND MATERIALS: The analysis was conducted in 17 patients with "in-field" recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. RESULTS: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). CONCLUSIONS: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.
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Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Lesões por Radiação/etiologia , Pneumonite por Radiação/etiologia , Radiometria/métodos , Radiocirurgia/efeitos adversos , Reoperação , Estudos Retrospectivos , Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
CONTEXT: Half-body irradiation (HBI) is the fastest and most effective tool against uncontrolled pain from widespread bone metastases but is somewhat toxic. OBJECTIVES: To assess the feasibility of lower HBI with helical tomotherapy in patients with metastatic breast cancer in terms of acute toxicity and delay in chemotherapy administration. METHODS: Thirteen breast cancer patients with multiple painful bone metastases to the lower half of the body were enrolled in this prospective trial. Eight patients were receiving chemotherapy. Target volume included all bones from the L3-L4 interface to the femoral shafts. Radiation consisted of 8 Gy in one fraction, delivered with helical tomotherapy. Patients were premedicated only with oral steroids. Pain intensity was scored using the Numeric Rating Scale from 0 to 10. Toxicity was scored using the Common Terminology Criteria for Adverse Events, version 3.0. Quality of life was scored with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, before and 21 days after the radiation course. This trial was approved by the local review board. RESULTS: Median follow-up was at seven months (range 2-12 months). All but two patients had pain relief in the radiated field. Six patients stopped their analgesic drug consumption. Toxicity was acceptable: two Grade 3 hematologic toxicities were registered (anemia and leukopenia). Grade 1-2 toxicities were hematologic = 13, fever = 3, nausea = 2, and diarrhea = 1. Three of the eight patients had a delay in chemotherapy administration because of leukopenia or anemia. Twelve patients answered to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and an improved quality of life was documented in eight cases. CONCLUSION: Lower HBI delivered with helical tomotherapy resulted in a well-tolerated regimen, without significant delay in chemotherapy schedule.
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Neoplasias Ósseas/fisiopatologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Irradiação Hemicorpórea/métodos , Dor/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Irradiação Hemicorpórea/efeitos adversos , Humanos , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/fisiopatologia , Manejo da Dor/métodos , Medição da Dor , Cuidados Paliativos/métodos , Estudos Prospectivos , Qualidade de Vida , Radioterapia de Intensidade Modulada/efeitos adversos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
PURPOSE: We have previously shown the feasibility of delivering high doses of radiotherapy in malignant pleural mesothelioma (MPM) patients who underwent radical pleurectomy/decortication (P/D) or surgical biopsy. In this report, we present the long-term results of MPM patients treated with radical P/D followed by high doses of radiotherapy. METHODS AND MATERIALS: Twenty consecutive MPM patients were enrolled in this prospective study and underwent radical P/D followed by high dose radiotherapy. The clinical target volume was defined as the entire hemithorax excluding the intact lung. The dose prescribed was 50 Gy in 25 fractions. Any FDG-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Nineteen patients received cisplatin/pemetrexed chemotherapy. Kaplan-Meier analysis was used to calculate rates of overall survival (OS), progression-free survival (PFS), and loco-regional control (LRC). RESULTS: The median follow-up was of 27 months. The median OS and PFS were 33 and 29 months, respectively. The median LRC was not reached. The Kaplan-Meier estimates of OS at 2 and 3 years were 70% and 49%, respectively. The estimates of PFS at 2 and 3 years were 65% and 46%, respectively. The estimates of LRC at 2 and 3 years were 68% and 59%, respectively. The predominant pattern of failure was distant: 7 patients developed distant metastases as the first site of relapse, whereas only 3 patients experienced an isolated loco-regional recurrence. No fatal toxicity was reported. Five Grades 2-3 pneumonitis were documented. CONCLUSIONS: High dose radiation therapy following radical P/D led to excellent loco-regional control and survival results in MPM patients. A median OS of 33 months and a 3-year OS rate of 49% are among the best observed in recent studies, supporting the idea that this approach represents a concrete therapeutic option for malignant pleural mesothelioma.
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Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Mesotelioma/radioterapia , Mesotelioma/cirurgia , Pleura/efeitos dos fármacos , Pleura/patologia , Derrame Pleural Maligno/radioterapia , Derrame Pleural Maligno/cirurgia , Procedimentos Cirúrgicos Torácicos , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma Maligno , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pleura/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
We present the experimental demonstration of a method for generating two spectrally and temporally separated pulses by an externally seeded, single-pass free-electron laser operating in the extreme-ultraviolet spectral range. Our results, collected on the FERMI@Elettra facility and confirmed by numerical simulations, demonstrate the possibility of controlling both the spectral and temporal features of the generated pulses. A free-electron laser operated in this mode becomes a suitable light source for jitter-free, two-colour pump-probe experiments.
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PURPOSE: To assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction). METHODS AND MATERIALS: Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1-T2 pN0-N1a) invasive ductal carcinoma. RESULTS: 77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged "good/excellent" and "poor" in 75 (97%) and in 2 (3%) patients, respectively. CONCLUSIONS: 40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI.
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Neoplasias da Mama/radioterapia , Mama/patologia , Mama/efeitos da radiação , Carcinoma Ductal de Mama/radioterapia , Fracionamento da Dose de Radiação , Idoso , Idoso de 80 Anos ou mais , Mama/cirurgia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Eritema/etiologia , Feminino , Fibrose/etiologia , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Dor/etiologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodosRESUMO
INTRODUCTION: This study aimed to assess the safety of high doses of radiation delivered with tomotherapy to the intact lung after radical pleurectomy/decortication or biopsy for malignant pleural mesothelioma (MPM). METHODS: Twenty-eight patients were enrolled in this prospective study and underwent adjuvant or definitive tomotherapy after radical pleurectomy/decortication (n = 20) or pleural biopsy (n = 8) for MPM. The dose prescribed to the planning target volume, defined as the entire hemithorax, including chest-wall incisions and drain sites and excluding the intact lung, was 50 Gy delivered in 25 fractions. All patients underwent fluorodeoxyglucose-positron emission tomography for staging after surgery. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost of radiotherapy to 60 Gy. Specific lung dosimetric parameters were reported. Toxicity was graded using the modified Common Toxicity Criteria version 3.0. RESULTS: The median follow-up was of 19 months (range, 6-29 months). Five patients (17.8%) experienced severe respiratory symptoms corresponding to grade 2 pneumonitis in three cases, and grade 3 pneumonitis in two cases. No fatal respiratory toxicity was reported. Controlateral lung V5 was strongly correlated with the risk of pneumonitis. Patients who developed grade 2 and 3 pneumonitis had a higher controlateral lung V5 (mean V5=32%) than those without pneumonitis (mean V5=17%) (p=0.002). Other two grade 3 toxicities were registered: one severe pain to the chest wall, and one severe thrombocytopenia. CONCLUSIONS: Tomotherapy allows the safe delivery of high dose of radiation to the hemithorax of MPM patients with intact lung.
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Pulmão/efeitos da radiação , Mesotelioma/radioterapia , Neoplasias Pleurais/radioterapia , Pneumonectomia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Pulmão/cirurgia , Masculino , Mesotelioma/patologia , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pleurais/patologia , Neoplasias Pleurais/cirurgia , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
PURPOSE: To assess the locoregional failure in patients with Stage I-II breast cancer treated with radical mastectomy and to evaluate whether a subset of these patients might be at sufficiently high risk of locoregional recurrence (LRR) to benefit from postmastectomy irradiation (PMRT). METHODS AND MATERIALS: Stage I-II breast cancer patients (n = 150) treated with radical mastectomy without adjuvant irradiation between 1999 and 2005 were analyzed. The pattern of LRR was reported. Kaplan-Meier analysis was used to calculate rates of LRR, and Cox proportional hazards methods were used to evaluate potential risk factors. RESULTS: Median follow-up was 75 months. Mean patient age was 56 years. One-hundred forty-three (95%) patients received adjuvant systemic therapy: 85 (57%) hormonal therapy alone, 14 (9%) chemotherapy alone, and 44 (29%) both chemotherapy and hormonal therapy. Statistically significant factors associated with increased risk of LRR were premenopausal status (p = 0.004), estrogen receptor negative cancer (p = 0.02), pathologic grade 3 (p = 0.02), and lymphovascular invasion (p = 0.001). T and N stage were not associated with increased risk of regional recurrence. The 5-year LRR rate for patients with zero or one, two, three, and four risk factors was 1%, 10.3%, 24.2%, and 75%, respectively. CONCLUSIONS: A subset of patients with early-stage breast cancer is at high risk of LRR, and therefore PMRT might be beneficial.
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Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Radical , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Modelos de Riscos Proporcionais , Receptores de Estrogênio/análise , Estudos Retrospectivos , Fatores de Risco , Falha de TratamentoRESUMO
PURPOSE: To extend the application of current radiation therapy (RT) based normal tissue complication probability (NTCP) models of radiation-induced fibrosis (RIF) of the breast to include the effects of fractionation, inhomogeneous dose, incomplete recovery, and time after the end of radiotherapy in partial breast irradiation (PBI). MATERIALS AND METHODS: An NTCP Lyman model with biologically effective uniform dose (BEUD) with and without a correction for the effect of incomplete repair was used. The time to occurrence of RIF was also taken into account. The radiobiological parameters were determined by fitting incidences of moderate/severe RIF in published randomized studies on RT of the breast. The NTCP model was used to calculate the risk of toxicity in 35 patients treated with intensity modulated, non-accelerated PBI and the result was compared with observed incidence of RIF. RESULTS: With α/ß fixed at 3Gy the parameters of the model without correction for incomplete repair extracted from fitting were: 50% complication probability biologically effective dose BEUD(50) = 107.2 Gy (95%CI = 95.9-118.6 Gy), volume parameter n = 0.06 (95%CI = 0-0.23), and slope of dose response m = 0.22, (95%CI = 0.20-0.23). After including the correction for incomplete repair with repair halftime for subcutaneous tissue of τ = 4.4 h we obtained BEUD(50) = 105.8 Gy (95%CI = 96.9-114.6Gy), n = 0.15 (95%CI = 0-0.33), m = 0.22 (95%CI = 0.20-0.23). Average NTCP predicted by these models, 4.3% and 2.0% respectively, offered a good agreement with RIF incidence in our patients, 5.7%, after an average follow-up of 12 months. CONCLUSION: The NTCP models of RIF, incorporating the effects of fractionation, volume effect, and latency of toxicity look promising to model PBI. Clinical validation from a prospective PBI treatment study is under development and will help test this preliminary result.
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Neoplasias da Mama/radioterapia , Mama/efeitos da radiação , Modelos Estatísticos , Órgãos em Risco/efeitos da radiação , Lesões por Radiação/patologia , Tela Subcutânea/patologia , Tela Subcutânea/efeitos da radiação , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Fracionamento da Dose de Radiação , Fibrose , Seguimentos , Humanos , Pessoa de Meia-Idade , RadiometriaRESUMO
AIMS AND BACKGROUND: The present study evaluated toxicity, local control, and survival in patients with relapsed high-grade glioma after surgery and external beam radiation therapy and treated with re-operation and GliaSite brachytherapy. METHODS: Between 2006 and 2008, 15 patients with recurrent high-grade glioma underwent re-operation and GliaSite brachytherapy. Ten patients were males and 5 females. Median age was 40 years (range, 20-71). Karnofsky performance status was ≥70. All patients but one received GliaSite irradiation of the surgical cavity wall at the dose of 4500 cGy at a depth of 1 cm. RESULTS: No severe acute side effects were observed during GliaSite brachytherapy. Pathologically documented, symptomatic late radiation necrosis was observed in 3 patients (20%); 2 subsequently died of further complications. Two patients were alive at a median follow-up 13 months (range, 1-30). Median overall survival after GliaSite brachytherapy was 13 months. CONCLUSIONS: Patients with recurrent high-grade glioma can be treated with additional surgery and GliaSite brachytherapy, delivering 4500 cGy at 1 cm depth without significant acute side effects but with a significant rate (20%) of late radiation necrosis, resulting in 13% of treatment-related deaths. Compared with the literature, survival results in our study appear to be satisfactory, but they may be related to patient selection criteria. Re-intervention followed by GliaSite brachytherapy should not be offered as a standard treatment for recurrent high-grade glioma, because of the high rate of late complications, treatment-related deaths, and high treatment costs.
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Antineoplásicos/uso terapêutico , Braquiterapia , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Braquiterapia/efeitos adversos , Braquiterapia/economia , Braquiterapia/mortalidade , Neoplasias Encefálicas/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Glioma/patologia , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Gradação de Tumores , Estudos Prospectivos , Radioterapia Adjuvante , Resultado do TratamentoRESUMO
To evaluate the outcome of Undifferentiated Nasopharyngeal Carcinomas (UCNT) treated with intensity-modulated radiation therapy with Simultaneous Integrated Boost (SIB), following induction chemotherapy. Between January 2006 and June 2009, 52 patients with stage II B-IVA/B UCNT were treated either with linac-IMRT or Tomotherapy. All patients were scheduled to receive three cycles of cisplatin based neoadjuvant chemotherapy. With a median follow-up of 38.5 months (range 12.3-64.1), 3 year overall survival (OS), disease-free survival (DFS), and DFS by T2a-2b and T3-T4-stage were 95.0%, 84.6%, 89.0%, and 78.0%, respectively. At multivariate analysis, none of the examined prognostic factors reported statistical significance. N-classification was not a significant predictive factor for either OS or development of distant metastases. T-stage alone had a borderline effect on DFS and development of metastases. No difference between Tomotherapy and linac-IMRT emerged in terms of loco-regional control and development of severe, acute, and late toxicities. The most significant severe, acute toxicities were grade 3 (32.7%) and grade 4 (7.7%) mucositis. No grades 3 and 4 late toxicities were observed. The most commonly observed late effect was xerostomia, 11.5% patients complained grade 2 xerostomia. The severity of grade 2 xerostomia diminished over time with only four patients not improving salivation. IMRT-SIB following neoadjuvant chemotherapy was very satisfactory in terms of local control, regional control, DFS and OS rates in patients with stage IIB to IVB UCNT. In our experience, adding concurrent chemotherapy to IMRT after neoadjuvant chemotherapy in loco-regional widespread disease resulted to be the indicated approach.
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Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/métodos , Adolescente , Adulto , Idoso , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Prognóstico , Radiossensibilizantes/administração & dosagem , Radioterapia de Intensidade Modulada/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Helical Tomotherapy (HT) is a highly conformal image-guided radiation technique, introduced into clinical routine in 2006 at the Centro di Riferimento Oncologico Aviano (Italy). With this new technology, intensity-modulated radiotherapy (IMRT) is delivered using a helicoidal method. Here we present our dosimetric experiences using HT in 100 children, adolescents and young adults treated from May 2006 to February 2011. The median age of the patients was 13 years (range 1-24). The most common treated site was the central nervous system (50; of these, 24 were craniospinal irradiations), followed by thorax (22), head and neck (10), abdomen and pelvis (11), and limbs (7). The use of HT was calculated in accordance to the target dose conformation, the target size and shape, the dose to critical organs adjacent to the target, simultaneous treatment of multiple targets, and re-irradiation. HT has demonstrated to improve target volume dose homogeneity and the sparing of critical structures, when compared to 3D Linac-based radiotherapy (RT). In standard cases this technique represented a comparable alternative to IMRT delivered with conventional linear accelerator. In certain cases (e.g., craniospinal and pleural treatments) only HT generated adequate treatment plans with good target volume coverage. However, the gain in target conformality should be balanced with the spread of low-doses to distant areas. This remains an open issue for the potential risk of secondary malignancies (SMNs) and longer follow-up is mandatory.
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New advances in radiation therapy for children allow increased conformability and reduced doses to non-target tissues. We report our experience in treating a 4-year-old child with craniospinal tomotherapy after surgery of the primary tumor, a supratentorial primitive neuroectodermal tumor. The tomotherapy plan was compared with conventional craniospinal irradiation, 3D conformal radiation therapy, and intensity-modulated radiation therapy plans. The possible disadvantages of tomotherapy related to the radiation dose to organs at risk, treatment planning, and anesthesia should be carefully considered as the use of the technique is not suggested in a general manner, but selectively, in critical pediatric radiotherapy cases.
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Irradiação Craniana , Tumores Neuroectodérmicos Primitivos/radioterapia , Medula Espinal/efeitos da radiação , Neoplasias Supratentoriais/radioterapia , Pré-Escolar , Humanos , Radioterapia Conformacional , Radioterapia de Intensidade ModuladaRESUMO
The present prospective study seeks to evaluate overall and disease free survival, response and organ preservation rate, and toxicity of an intensive chemotherapy regimen (CT) followed by unconventional radiotherapy (RT) in patients with locally advanced operable head and neck cancer. Between January 1998 and December 2006 (June 2005), 115 patients with locally advanced, operable head and neck cancer were evaluated. A total of 333 cycles of neoadjuvant CT (cisplatin-5FU, days 1, 14, 28) followed by hyperfractionated/accelerated radiotherapy were given to 108 patients. A total of 108 patients were evaluable and received the planned CT-RT treatment. Two months after the end of RT, 97.2% of patients had a clinical complete remission of the primary and 67.5% of the neck node site. The overall survival was 55% and cause-specific survival was 73% at 5 years. Of the 33 relapsed patients, 12 recurred only at the primary site and 10 patients had distant metastases. The overall organ preservation rate was 73.5%. The chemotherapy regimen reported an overall cardiotoxicity from 5FU in 14% of patients, with severe toxicity in 3%. The radiotherapy schedule developed 84% of Grade 3-4 mucositis in the observed patients. The accelerated CT-RT regimen is able to achieve a high rate of larynx preservation, a good tolerability, and a satisfactory cause-specific overall survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Terapia de Salvação , Adulto , Idoso , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
PURPOSE: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated. The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment. EXPERIMENTAL DESIGN: We studied how normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted Intraoperative radioTherapy (TARGIT), immediately after the surgical excision. The proteomic profile of the WF and their effects on the activation of intracellular signal transduction pathways of breast cancer cells were also analyzed. RESULTS: WF stimulated proliferation, migration, and invasion of breast cancer cell lines. The stimulatory effect was almost completely abrogated when fluids from TARGIT-treated patients were used. These fluids displayed altered expression of several cytokines and failed to properly stimulate the activation of some intracellular signal transduction pathways, when compared with fluids harvested from untreated patients. CONCLUSIONS: Delivery of TARGIT to the tumor bed alters the molecular composition and biological activity of surgical WF. This novel antitumoral effect could, at least partially, explain the very low recurrence rates found in a large pilot study using TARGIT. It also opens a novel avenue for identifying new molecular targets and testing novel therapeutic agents.
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Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Proliferação de Células/efeitos da radiação , Animais , Mama/citologia , Mama/efeitos da radiação , Neoplasias da Mama/cirurgia , Movimento Celular , Células Cultivadas , Progressão da Doença , Endotélio Vascular/citologia , Endotélio Vascular/efeitos da radiação , Feminino , Seguimentos , Humanos , Cuidados Intraoperatórios , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/efeitos da radiação , Mastectomia Segmentar , Camundongos , Pessoa de Meia-Idade , Células NIH 3T3 , Invasividade Neoplásica , Recidiva Local de Neoplasia/prevenção & controle , Projetos Piloto , Proteômica , Dosagem Radioterapêutica , Veias Umbilicais/citologia , Veias Umbilicais/efeitos da radiaçãoRESUMO
Research and development are currently trying to run a storage ring free-electron laser down to 150 nm with robust optics. Vacuum-ultraviolet fluoride optics with protected oxide layers and enhanced metallic mirrors are investigated.
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Mirrors for storage ring free-electron lasers in the vacuum ultraviolet must provide adequate reflectivity and resistance against synchrotron radiation. The free-electron laser system at ELETTRA (Trieste, Italy) is targeted to lase in the spectral range between 155 and 200 nm. It was demonstrated that dense oxide multilayer coatings allow lasing down to 189.9 nm. However, pure oxide systems show significant absorption at lower wavelengths and cannot be employed below 189.9 nm. Fluoride stacks can be deposited down to 130 nm with high reflection values above 95%, but their resistance against the harsh synchrotron environment is poor. They rapidly degrade; lasing cannot be realized with this mirror approach. For the range between 170 and 190 nm, hybrid systems--combining fluoride and oxide materials--have been manufactured. With appropriate deposition procedures, mirrors achieve reflectance values up to 99% and an adequate radiation resistance simultaneously. A mirror based on a conventional fluoride stack protected by a dense silicon dioxide protection layer was deposited and successfully employed for free-electron lasing at 176.4 nm.
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PURPOSE: We evaluated the potential of PET/CT and [(18)F]fluoromethylcholine (FCH) in the assessment of suspected recurrence of prostate cancer after treatment. METHODS: One hundred consecutive prostate cancer patients with a persistent increase in serum PSA (>0.1 ng/ml) after radical prostatectomy (58 cases), radiotherapy (21 cases) or hormonal therapy alone (21 cases) were investigated. After injection of 3.7-4.07 MBq/kg of FCH, both early (at <15 min) and delayed (at >60 min) PET/CT scans were performed in 43 patients, delayed PET/CT scans in 53 patients and early PET/CT scans in four patients. RESULTS: Of the 100 patients, 54 (PSA 0.22-511.79 ng/ml) showed positive FCH PET/CT scans. Thirty-seven patients had bone and/or abdominal lymph node uptake, while 17 showed pelvic activity. Malignant disease was confirmed in all but one. Delayed SUV(max) of bone metastases was significantly higher (p<0.0001 by paired t test) than that measured at <15 min, whereas no differences were observed between early and delayed SUVs of malignant lymph nodes or pelvic disease. Forty-six patients (PSA 0.12-14.3 ng/ml) showed negative FCH PET/CT scans. Of the negative PET/CT scans, 89% were obtained in patients with serum PSA <4 ng/ml and 87% in patients with a Gleason score <8. In none of these cases could recurrent tumour be proven clinically during a follow-up of 6 months. CONCLUSION: FCH PET/CT is not likely to have a significant impact on the care of prostate cancer patients with biochemical recurrence until PSA increases to above 4 ng/ml. However, in selected patients, FCH PET/CT helps to exclude distant metastases when salvage local treatment is intended.