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We report here a deallylative ß-acylalkylation reaction of allylbenzene derivatives with allyl alcohols in the presence of Cp*Rh catalysts. Allylbenzenes possessing pyridyl and pyrazolyl directing groups were converted to ß-aryl ketones via the cleavage of C(aryl)-C(allyl) bonds. Synthesis of a quinoline derivative from a ß-aryl ketone product bearing a pyrazolyl group was also achieved.
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High-valent cyclopentadienyl cobalt catalysis is a versatile tool for sustainable C-H bond functionalizations. To harness the full potential of this strategy, control of the stereoselectivity of these processes is necessary. Herein, we report highly enantioselective intermolecular carboaminations of alkenes through C-H activation of N-phenoxyamides catalyzed by CoIII -complexes equipped with chiral cyclopentadienyl (Cpx ) ligands. The method converts widely available acrylates as well as bicyclic olefins into attractive enantioenriched isotyrosine derivatives as well as elaborated amino-substituted bicyclic scaffolds under very mild conditions. The outlined reactivity is unique to the Cpx CoIII complexes and is complementary to the reactivity of 4d- and 5d- precious-metal catalysts.
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A method for catalytic conversion of C(aryl)-C(alkenyl) bonds in styrene derivatives to new C-C bonds is developed. In the presence of a rhodium catalyst, the alkenyl groups of styrenes bearing a pyrazolyl directing group were efficiently converted to other carbon substituents upon reacting with various alkenes including styrenes, aliphatic alkenes, and allyl alcohols. It is also indicated that the C-C bond cleavage proceeded via a hydrometalation/ß-carbon elimination pathway.
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A method for the synthesis of N-arylpyrazoles by palladium-catalyzed coupling of aryl triflates with pyrazole derivatives is described. Using tBuBrettPhos as a ligand, the palladium-catalyzed C-N coupling of a variety of aryl triflates including ortho-substituted ones with pyrazole derivatives proceeded efficiently to give N-arylpyrazole products in high yields. 3-Trimethylsilylpyrazole was found to be an excellent pyrazole substrate for the coupling, and the corresponding product, 1-aryl-3-trimethylsilylpyrazole, also served as a great template for the syntheses of N-arylpyrazole derivatives, as demonstrated by regioselective halogenation at the 3-, 4-, and 5-positions of the pyrazole ring.
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A novel method for direct transformation of allyl groups in allylbenzene derivatives to alkenyl groups via rhodium-catalyzed C-C bond cleavage is reported. The alkenylation with styrenes of allylbenzenes containing pyridyl and pyrazolyl groups as a directing group proceeded efficiently to give alkenylation products. We also developed a new protocol for transformation of an ortho-prenylated phenol to an aniline derivative.
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To investigate whether the neurocognitive function at 4 months could be a relevant primary endpoint in clinical trials dealing with brain metastases, we created a Japanese neurocognitive battery and examined the changes in patients' neurocognitive function for 1 year after their brain radiotherapy. In this prospective pilot study, we enrolled 27 patients (20 patients who received whole-brain radiation therapy [WBRT] and seven who received stereotactic irradiation [STI] alone) between March 2009 and December 2010. The follow-up neurocognitive data at 4, 8 and 12 months were available in 22 (17 WBRT, 5 STI), 19 patients (14 WBRT, 5 STI) and 13 patients (9 WBRT, 4 STI), respectively. Among the patients who received WBRT, significant deterioration in delayed memory compared to the baseline (p = 0.04) was observed at 4 months, and at 8 months, significant improvements were observed in immediate memory compared to the baseline (p = 0.008) and 4-months scores (p = 0.005). At 12 months, however, the immediate memory scores had returned to the baseline. Similar trends were observed in other functions (delayed memory, attention and executive functions). In these patients, the correlations between 4-months scores of neurocognitive functions and 12-months scores were significant in immediate memory (γ = 0.68, p = 0.004), delayed memory (γ = 0.738, p = 0.023) and attention (γ = 0.817, p = 0.007). Among the patients who received STI, no significant changes were observed in any functions. These results suggest that 4-months changes in neurocognitive functions were transient but could also be a premonitory index for predicting the neurocognitive function 1 year or later after brain radiation therapy.
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Neoplasias Encefálicas/radioterapia , Cognição/efeitos da radiação , Irradiação Craniana , Memória/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Testes Neuropsicológicos , Projetos Piloto , Prognóstico , Estudos Prospectivos , Radiocirurgia , Adulto JovemRESUMO
BACKGROUND: The aim of our study was to analyze changes over time in the characteristics, treatment, and outcome of patients with primary central nervous system lymphoma (PCNSL). METHODS: Data on 315 patients with histologically proven PCNSL undergoing radiotherapy between 2005 and 2009 were collected from 20 Japanese institutions using a questionnaire. These data were then compared with data on 273 patients treated during the period 1995-2004 and those on 466 patients treated during the period 1985-1994. RESULTS: In terms of patient and tumor characteristics, we found a significant increase in mean patient age in the 2005-2009 period compared to the 1985-2004 period (63 vs. 58-59 years, respectively) and in the percentage of patients with better performance status (PS) during the 2005-2009 period compared with the 1995-2004 period (World Health Organization PS 0-2: 73 vs. 65 %, respectively). Regarding treatment, relative to the 1995-2004 period, significant changes in the 2005-2009 period were (1) decreased rate of attempting tumor resection (23 vs. 44 %); (2) increased use of chemotherapy (78 vs. 68 %), and (3) increased use of methotrexate (MTX)-containing regimens (84 vs. 53 %). The 5-year overall survival rates were 15.3, 30.1, and 36.5 % for patients seen during the 1985-1994, 1995-2004, and 2005-2009 periods, respectively, but relapse-free survival did not improve between the 1995-2004 and 2005-2009 periods (26.7 vs. 25.7 % at 5 years, respectively). Patients receiving MTX-containing chemotherapy had 5-year survival rates of 19, 50, and 44 % during these three periods, respectively. CONCLUSIONS: Although patient backgrounds differed among the study periods, recent trends were a high patient age, better PS, avoidance of extensive tumor resection, more frequent use of chemotherapy, and improved survival. The recent improvement in survival may be due to improvements in second-line treatment and supportive care.
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Neoplasias do Sistema Nervoso Central/radioterapia , Sistema Nervoso Central/patologia , Linfoma/radioterapia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Sistema Nervoso Central/efeitos da radiação , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Japão , Linfoma/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Inquéritos e Questionários , Taxa de SobrevidaRESUMO
OBJECTIVE: This study aimed to compare the diagnostic performance in the detection of brain metastases between contrast-enhanced T1-weighted volume isotropic turbo spin echo acquisition (T1-VISTA) and 3-dimensional T1-weighted fluid-attenuated inversion recovery (3D-T1-FLAIR) imaging at 3 T. METHODS: Two neuroradiologists selected 129 true (metastases) and 70 false (vessels and artifacts) lesions on the contrast-enhanced T1-VISTA and 3D-T1-FLAIR images of 14 cancer patients with hyperintense brain lesions. Four blinded neuroradiologists distinguished between the true and false lesions, using a 5-point confidence rating scale. The receiver operating characteristic analysis was performed to compare the diagnostic performance. Contrast-to-noise ratio of the true lesions was also compared between the 2 sequences by using paired t tests. RESULTS: For lesions less than 3 mm, the area under curve and sensitivity achieved by T1-VISTA imaging were significantly greater than 3D-T1-FLAIR imaging. The contrast-to-noise ratio was also significantly greater with T1-VISTA imaging. CONCLUSIONS: The contrast-enhanced T1-VISTA imaging is better suited than 3D-T1-FLAIR imaging, for detection of small metastases.
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Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Área Sob a Curva , Artefatos , Neoplasias Encefálicas/secundário , Meios de Contraste , Feminino , Gadolínio , Gadolínio DTPA , Compostos Heterocíclicos , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
Two glioblastoma multiforme patients underwent (18)F-FMISO (fluoromisonidazole) positron emission tomography study to access the tumor oxygenation status before and immediately after fractionated radiotherapy concomitant with temozolomide chemotherapy. In both cases, a prominent (18)F-FMISO tumor accumulation observed in the first study was notably decreased in the second study, which was supposed to be a reoxygenation of the tumor. As far as we investigated, this is the first report of the changes of oxygenation status in glioblastoma multiforme treated through radiation therapy with temozolomide.
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Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Fracionamento da Dose de Radiação , Glioblastoma/metabolismo , Glioblastoma/terapia , Misonidazol/análogos & derivados , Oxigênio/metabolismo , Tomografia por Emissão de Pósitrons , Idoso , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/efeitos da radiação , Quimiorradioterapia Adjuvante , Dacarbazina/uso terapêutico , Progressão da Doença , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Radiossensibilizantes , Temozolomida , Resultado do TratamentoRESUMO
Background and purpose: To minimize cognitive decline without increasing brain tumor recurrence (BTR) by reduced-dose whole-brain radiotherapy (RD-WBRT) (25 Gy, 10 fractions) + stereotactic radiosurgery (SRS) in patients with ≤ 4 brain metastases. Materials and methods: Eligible patients with ≤ 4 brain metastases on contrast-enhanced MRI and Karnofsky Performance Status ≥ 70. The primary endpoint was the non-inferiority of BTR at distant sites in the brain (BTR-distant)-free survival at 6 months compared to that of the standard dose (SD)-WBRT (30 Gy, 10 fractions) + SRS arm in a randomized clinical trial (JROSG99-1) of SRS with/without SD-WBRT. Secondary endpoints included BTR at any brain sites (BTR-all) and neurocognitive function assessed by a six-test standardized battery. Results: Forty patients from seven institutions were enrolled (median age 69 years). The primary tumor site was a lung in 28 patients; 20 patients had a solitary brain metastasis. The median survival time was 19.0 months (95 %CI: 13.8 %-27.5 %). The BTR-distant-free survival at 6 months was 76.9 % (59.5 %-87.7 %), which is comparable to that of historical control although predetermined non-inferiority (>71 %) could not be confirmed (p = 0.16). The cumulative incidence of BTR-all at 6 months accounting for the competing risk of death was 23.0 % (11.4-37.1), which was not worse than that of historical control (p = 0.774). The frequency of the cumulative incidence of persistent cognitive decline at 6 months was 48.6 % under the [>2.0 SD in ≥ 1 test] definition. Conclusions: RD-WBRT may yield comparable intracranial tumor control when combined with SRS, and may reduce the risk of neurocognitive decline compared to that after SD-WBRT.
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OBJECTIVE: To investigate the outcome of linac-based fractionated stereotactic radiotherapy over the last 10 years for intracranial skull base benign meningiomas in patients who were inoperable, who had residual tumors with some components of high mitotic index after surgery and who experienced relapse of the tumor. METHODS: Twenty-seven patients with intracranial skull base benign meningiomas treated with fractionated stereotactic radiotherapy were retrospectively reviewed. Twenty-seven cases were diagnosed as benign meningiomas on pathological (17 cases) or radiological (10 cases) examination. The median follow-up time was 90 months after initial treatment and 63 months after fractionated stereotactic radiotherapy. The median biological equivalent dose calculated using an α/ß ratio of 2.0 Gy was 82.0 Gy (range, 60-106 Gy). RESULTS: The 5-year overall survival was 95.7 (95% confidence interval: 87.3-100)% after initial treatment and 96.2 (88.8-100)% after fractionated stereotactic radiotherapy. The 5-year overall survival and local control rate of patients who received fractionated stereotactic radiotherapy alone were both 100%. The 5-year progression-free survival and local control rate after fractionated stereotactic radiotherapy were all 100% with a tumor volume of <9.1 cc and 68.2 (37.2-99.2) and 75.8 (45.2-100)% for the tumors 9.1 cc, respectively. The difference was significant in progression-free survival (P = 0.022) and local control rate (P = 0.044). The local control rate was significantly worse in patients who received fractionated stereotactic radiotherapy for relapsed tumors (P = 0.01). No late radiation damage was observed in the follow-up period. CONCLUSIONS: The long-term outcome suggests that fractionated stereotactic radiotherapy is a safe and effective treatment for intracranial skull base benign meningioma, especially for those who have tumors <9.1 cc or would receive fractionated stereotactic radiotherapy with or without surgery as the initial treatment.
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Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia , Adulto , Idoso , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Pessoa de Meia-Idade , Índice Mitótico , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Radiografia , Radiocirurgia/métodos , Estudos Retrospectivos , Base do Crânio , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Several recent studies have shown that oligometastatic disease has curative potential, although it was previously considered to signal a patient's last stage of life. Stereotactic body radiotherapy has been available for extra-cranial metastases in addition to stereotactic cranial radiotherapy for brain metastases. The aim of the present study was to retrospectively evaluate the clinical outcomes of stereotactic radiotherapy for patients with oligometastatic lesions. METHODS: Between 1999 and 2008, 41 patients with five or fewer detectable metastases were treated with stereotactic radiotherapy at our institution. The treated oligometastatic lesions were in the brain, lung and adrenal glands. RESULTS: With a median follow-up period of 20 months, the 3-year overall survival, progression-free survival, local control and distant control rates were 39%, 20%, 80% and 35%, respectively, and the respective 5-year rates were 28%, 20%, 80% and 35%. The median survival time was 24 months. According to interval to recurrence, the 3- and 5-year overall survival rates were 19% and 10%, respectively, for patients with <12 months (n = 18), compared with 53% and 40% for those with > or =12 months (n = 23) (P = 0.006). CONCLUSIONS: Precise stereotactic radiotherapy was effective in controlling oligometastatic lesions for patients with a median survival time of 24 months. Interval to recurrence may impact the overall survival rate and should be included in the stratification criteria in a prospective randomized trial to investigate the benefits of stereotactic radiotherapy for patients with oligometastases.
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Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Radiocirurgia , Neoplasias das Glândulas Suprarrenais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Necrose/etiologia , Recidiva Local de Neoplasia/mortalidade , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This is a report of a single-institution prospective study evaluating the safety of a spot-scanning dedicated, small 360-degree gantry, synchrotron-based proton beam therapy (PBT) system. Data collection was performed for 56 patients with 59 treatment sites who received proton beam therapy at Hokkaido University Hospital between March 2014 and July 2015. Forty-one patients were male and 15 were female. The median age was 66 years. The primary lesion sites were prostate (n = 17), bone/soft tissue (n = 10), liver (n = 7), lung (n = 6), central nervous system (n = 5), colon (n = 2), pancreas (n = 2), kidney (n = 2) and others (n = 5). Chemotherapy was administered in 11 patients. The prescribed total dose was from 20 to 76 GyE (Radiobiological equivalent dose, RBE = 1.1), with the median dose of 65 GyE in 4 to 35 fractions. No PBT-related Common Terminology Criteria for Adverse Events Grade 4 or 5 toxicities were observed; the incidence of early PBT-related Grade 4 adverse events was 0% (95% confidence interval 0 to 6.38%). The most common Grade 3 toxicities were hematologic toxicity (12.5%) unlikely to be related to the PBT. One patient developed a left femoral neck fracture (Grade 3) at 14.5 months after PBT for chondrosarcoma of the left pelvis. The pathological findings showed no other malignancies, suggesting that it was possibly related to the PBT. In conclusion, the spot-scanning dedicated, synchrotron-based PBT system is feasible, but further studies on its long-term safety and efficacy are warranted.
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Terapia com Prótons/efeitos adversos , Síncrotrons , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. METHODS AND MATERIALS: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. RESULTS: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. CONCLUSION: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology.
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Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Movimento , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Tomografia Computadorizada por Raios X/métodos , Fracionamento da Dose de Radiação , Humanos , Próteses e Implantes , Sistemas de Informação em RadiologiaRESUMO
PURPOSE: This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade ⩾3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). METHODS AND MATERIALS: The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45Gy(RBE) in 1.8Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. RESULTS: The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP=0.04±0.01 and 0.19±0.03, p=0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI=0.97±0.01 and 0.96±0.02, p=0.3177, and HI=1.24±0.11 and 1.27±0.05, p=0.8473, respectively). CONCLUSION: The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT.
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Neoplasias dos Genitais Femininos/radioterapia , Doenças Hematológicas/etiologia , Pelve/efeitos da radiação , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Medula Óssea/efeitos da radiação , Feminino , Cabeça do Fêmur/efeitos da radiação , Neoplasias dos Genitais Femininos/complicações , Humanos , Modelos Teóricos , Recidiva Local de Neoplasia , Órgãos em Risco , Probabilidade , Lesões por Radiação , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios XRESUMO
We report here a method for direct catalytic introduction of simple α-acylalkyl groups via rhodium-catalyzed C-H functionalization with cyclic alkenyl carbonates, synthetic equivalents to enolates bearing leaving groups. The reaction proceeded smoothly without using bases to give α-aryl ketones in high yields. Various nitrogen-containing aromatic rings and amide groups serve as directing groups. 3-Substituted isocoumarins can also be prepared by one-pot C-H functionalization/cyclization.
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Alcenos/química , Carbonatos/química , Isocumarinas/síntese química , Cetonas/síntese química , Ródio/química , Catálise , Ciclização , Isocumarinas/química , Cetonas/química , Estrutura Molecular , NitrogênioRESUMO
INTRODUCTION: We retrospectively evaluated the efficacy of three-dimensional conformal radiotherapy (3D-CRT) for spinal schwannoma. METHODS: Nine patients with spinal schwannoma were treated with 3D-CRT. All patients had a paravertebral or intraosseous component. Tumor sizes ranged from 0.8 to 8.7 cm, with a median of 3.5 cm. The prescribed dose was 50 Gy in 25 fractions at the isocenter, except for 1 patient who received 66 Gy in 33 fractions for a large sacral tumor. The follow-up period ranged from 20 to 137 months, with a median of 72 months. RESULTS: Tumor shrinkage within 3 mm occurred in 4 patients and tumor expansion within 3 mm occurred in 3. One tumor showed neither expansion nor shrinkage at the last follow-up. One patient experienced transient expansion by 8 mm in diameter at 12 months after the completion of radiotherapy (35-43 mm), and then the tumor size remained unchanged for 7 years. No severe late toxicity ≥ grade 3 was observed. CONCLUSIONS: Only 1 of 9 tumors showed transit expansion over 3 mm after 3D-CRT, and severe late radiation toxicity was not observed. Use of 3D-CRT should be considered a treatment option for spinal schwannoma.
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Fracionamento da Dose de Radiação , Imageamento Tridimensional , Neurilemoma/radioterapia , Radioterapia Conformacional/métodos , Neoplasias da Coluna Vertebral/radioterapia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Olfactory neuroblastoma (ONB) is a rare tumor originating from olfactory epithelium. Here we retrospectively analyzed the long-term treatment outcomes and toxicity of radiotherapy for ONB patients for whom computed tomography (CT) and three-dimensional treatment planning was conducted to reappraise the role of radiotherapy in the light of recent advanced technology and chemotherapy. METHODS: Seventeen patients with ONB treated between July 1992 and June 2013 were included. Three patients were Kadish stage B and 14 were stage C. All patients were treated with radiotherapy with or without surgery or chemotherapy. The radiation dose was distributed from 50 Gy to 66 Gy except for one patient who received 40 Gy preoperatively. RESULTS: The median follow-up time was 95 months (range 8-173 months). The 5-year overall survival (OS) and relapse-free survival (RFS) rates were estimated at 88% and 74%, respectively. Five patients with stage C disease had recurrence with the median time to recurrence of 59 months (range 7-115 months). Late adverse events equal to or above Grade 2 in CTCAE v4.03 were observed in three patients. CONCLUSION: Multimodal therapy including radiotherapy with precise treatment planning based on CT simulation achieved an excellent local control rate with acceptable toxicity and reasonable overall survival for patients with ONB.
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Terapia Combinada/efeitos adversos , Estesioneuroblastoma Olfatório/terapia , Cavidade Nasal , Recidiva Local de Neoplasia/terapia , Neoplasias Nasais/terapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estesioneuroblastoma Olfatório/mortalidade , Estesioneuroblastoma Olfatório/secundário , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Nasais/mortalidade , Neoplasias Nasais/patologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
A 55-year-old woman underwent radiosurgery for a left cerebral hemisphere arteriovenous malformation (AVM) and developed radiation-induced necrosis causing a massive edema in the surrounding brain tissues. Despite various therapies, the edema expanded to the ipsilateral hemisphere and induced neurological symptoms. The radiation-induced necrotic lesion was surgically removed 4 years after radiosurgery. While the preoperative FDG PET revealed severe hypometabolism in the left cerebrum, the necrotomy significantly ameliorated the brain edema, glucose metabolism (postoperative FDG PET), and symptoms. This case indicates that radiation necrosis-induced neurological deficits may be associated with brain edema and hypometabolism, which could be reversed by appropriate necrotomy.
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PURPOSE: The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known. METHODS AND MATERIALS: This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months. RESULTS: The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P<.0001) and trigeminal nerve (P<.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients. CONCLUSIONS: Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.