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1.
Anticancer Res ; 41(9): 4571-4575, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475085

RESUMO

BACKGROUND/AIM: The purpose of this study was to compare the dose distribution between scanning carbon-ion radiotherapy (sCIRT) and volumetric-modulated arc therapy with stereotactic body radiation therapy (VMAT-SBRT) for stage I non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifteen patients with early-stage NSCLC who underwent sCIRT at Kanagawa Cancer Center between 2018-2020 were enrolled. Dose-volume histogram parameters of the planned target volume and normal organs for sCIRT and VMAT-SBRT were evaluated. RESULTS: The homogeneity index of the target volume of sCIRT was significantly lower than that of VMAT-SBRT. The dose of sCIRT was significantly lower than that of VMAT-SBRT at low volumes in the lung, heart, spinal cord, and esophagus. CONCLUSION: The dose distribution of sCIRT for early-stage NSCLC was better than that of VMAT-SBRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioterapia com Íons Pesados/métodos , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
2.
Br J Radiol ; 94(1125): 20210176, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34233469

RESUMO

OBJECTIVES: While hypofractionated stereotactic body radiotherapy (SBRT) has been largely adopted in the adult setting, its use remains limited in pediatric patients. This is due, among other factors, to fear of potential toxicities of hypofractionated regimens at a young age. In this context, we report the preliminary acute (<3 months from SBRT) and middle-term (3-24 months) toxicity results of a national prospective study investigating SBRT in pediatric patients. METHODS: Between 2013 and 2019, 61 patients were included. The first 40 patients (median age: 12 y, range: 3-20) who completed a 2-year-follow-up were included in the present analysis. SBRT was used for treating lung, brain or (para)spinal lesions, either as first irradiation (35%) or in the reirradiation setting (65%). RESULTS: Acute and middle-term grade ≥2 toxicities occurred in 12.5 and 7.5% of the patients, respectively. No grade ≥4 toxicities occurred. Almost all toxicities occurred in the reirradiation setting. CONCLUSION: SBRT showed a favorable safety profile in young patients treated for lung, brain, and (para)spinal lesions. ADVANCES IN KNOWLEDGE: SBRT appeared to be safe in pediatric patients treated for multiple oncology indications. These results support further evaluation of SBRT, which may have a role to play in this patient population in the future.


Assuntos
Neoplasias Encefálicas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Neoplasias da Coluna Vertebral/radioterapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , França , Humanos , Masculino , Pediatria/métodos , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Reirradiação/métodos , Resultado do Tratamento , Adulto Jovem
3.
Cochrane Database Syst Rev ; 7: CD013224, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196007

RESUMO

BACKGROUND: Chordoma is a rare primary bone tumour with a high propensity for local recurrence. Surgical resection is the mainstay of treatment, but complete resection is often morbid due to tumour location. Similarly, the dose of radiotherapy (RT) that surrounding healthy organs can tolerate is frequently below that required to provide effective tumour control. Therefore, clinicians have investigated different radiation delivery techniques, often in combination with surgery, aimed to improve the therapeutic ratio. OBJECTIVES: To assess the effects and toxicity of proton and photon adjuvant radiotherapy (RT) in people with biopsy-confirmed chordoma. SEARCH METHODS: We searched CENTRAL (2021, Issue 4); MEDLINE Ovid (1946 to April 2021); Embase Ovid (1980 to April 2021) and online registers of clinical trials, and abstracts of scientific meetings up until April 2021. SELECTION CRITERIA: We included adults with pathologically confirmed primary chordoma, who were irradiated with curative intent, with protons or photons in the form of fractionated RT, SRS (stereotactic radiosurgery), SBRT (stereotactic body radiotherapy), or IMRT (intensity modulated radiation therapy). We limited analysis to studies that included outcomes of participants treated with both protons and photons. DATA COLLECTION AND ANALYSIS: The primary outcomes were local control, mortality, recurrence, and treatment-related toxicity. We followed current standard Cochrane methodological procedures for data extraction, management, and analysis. We used the ROBINS-I tool to assess risk of bias, and GRADE to assess the certainty of the evidence. MAIN RESULTS: We included six observational studies with 187 adult participants. We judged all studies to be at high risk of bias. Four studies were included in meta-analysis. We are uncertain if proton compared to photon therapy worsens or has no effect on local control (hazard ratio (HR) 5.34, 95% confidence interval (CI) 0.66 to 43.43; 2 observational studies, 39 participants; very low-certainty evidence). Median survival time ranged between 45.5 months and 66 months. We are uncertain if proton compared to photon therapy reduces or has no effect on mortality (HR 0.44, 95% CI 0.13 to 1.57; 4 observational studies, 65 participants; very low-certainty evidence). Median recurrence-free survival ranged between 3 and 10 years. We are uncertain whether proton compared to photon therapy reduces or has no effect on recurrence (HR 0.34, 95% CI 0.10 to 1.17; 4 observational studies, 94 participants; very low-certainty evidence). One study assessed treatment-related toxicity and reported that four participants on proton therapy developed radiation-induced necrosis in the temporal bone, radiation-induced damage to the brainstem, and chronic mastoiditis; one participant on photon therapy developed hearing loss, worsening of the seventh cranial nerve paresis, and ulcerative keratitis (risk ratio (RR) 1.28, 95% CI 0.17 to 9.86; 1 observational study, 33 participants; very low-certainty evidence). There is no evidence that protons led to reduced toxicity. There is very low-certainty evidence to show an advantage for proton therapy in comparison to photon therapy with respect to local control, mortality, recurrence, and treatment related toxicity. AUTHORS' CONCLUSIONS: There is a lack of published evidence to confirm a clinical difference in effect with either proton or photon therapy for the treatment of chordoma. As radiation techniques evolve, multi-institutional data should be collected prospectively and published, to help identify persons that would most benefit from the available radiation treatment techniques.


Assuntos
Neoplasias Ósseas/radioterapia , Cordoma/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/métodos , Adulto , Viés , Neoplasias Ósseas/mortalidade , Cordoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Observacionais como Assunto , Fótons/efeitos adversos , Intervalo Livre de Progressão , Terapia com Prótons/efeitos adversos , Radiocirurgia/métodos , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada/métodos , Fatores de Tempo
4.
Lancet Oncol ; 22(8): 1093-1102, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237249

RESUMO

BACKGROUND: There is paucity of investigations into immunotherapy or targeted therapy for postoperative locally recurrent pancreatic cancer. We aimed to assess the efficacy of stereotactic body radiotherapy (SBRT) plus pembrolizumab and trametinib in these patients. METHODS: In this open-label, randomised, controlled, phase 2 study, participants were recruited from Changhai Hospital affiliated to Naval Medical University, Shanghai, China. Eligible patients were aged 18 years or older with histologically confirmed pancreatic ductal adenocarcinoma characterised by mutant KRAS and positive immunohistochemical staining of PD-L1, Eastern Cooperative Oncology Group performance status of 0 or 1, and documented local recurrence after surgery followed by chemotherapy (mFOLFIRINOX or 5-fluorouracil). Eligible participants were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive SBRT with doses ranging from 35-40 Gy in five fractions, intravenous pembrolizumab 200 mg once every 3 weeks, and oral trametinib 2 mg once daily or SBRT (same regimen) and intravenous gemcitabine (1000 mg/m2) on day 1 and 8 of a 21-day cycle for eight cycles until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in the as-treated population in all participants who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02704156, and is now complete. FINDINGS: Between Oct 10, 2016, and Oct 28, 2017, 198 patients were screen, of whom 170 patients were enrolled and randomly assigned to receive SBRT plus pembrolizumab and trametinib (n=85) or SBRT plus gemcitabine (n=85). As of the clinical cutoff date (Nov 30, 2020), median follow-up was 23·3 months (IQR 20·5-27·4). Median overall survival was 24·9 months (23·3-26·5) with SBRT plus pembrolizumab and trametinib and 22·4 months (95% CI 21·2-23·6) with SBRT plus gemcitabine (hazard ratio [HR] 0·60 [95% CI 0·44-0·82]; p=0·0012). The most common grade 3 or 4 adverse effects were increased alanine aminotransferase or aspartate aminotransferase (ten [12%] of 85 in SBRT plus pembrolizumab and trametinib group vs six [7%] of 85 in SBRT plus gemcitabine group), increased blood bilirubin (four [5%] vs none), neutropenia (one [1%] vs nine [11%]), and thrombocytopenia (one [1%] vs four [5%]). Serious adverse events were reported by 19 (22%) participants in the SBRT plus pembrolizumab and trametinib group and 12 (14%) in the SBRT plus gemcitabine group. No treatment-related deaths occurred. INTERPRETATION: The combination of SBRT plus pembrolizumab and trametinib could be a novel treatment option for patients with locally recurrent pancreatic cancer after surgery. Phase 3 trials are needed to confirm our findings. FUNDING: Shanghai Shenkang Center and Changhai Hospital. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Terapia Combinada/métodos , Neoplasias Pancreáticas/terapia , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Idoso , China , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiocirurgia/métodos
6.
Medicine (Baltimore) ; 100(22): e26203, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087891

RESUMO

ABSTRACT: The brainstem arteriovenous malformations (BS-AVMs) have a high morbidity and mortality and stereotactic radiosurgery (SRS) has been widely used to treat BS-AVMs. However, no consensus is reached in the explicit predictors of obliteration for BS-AVMs after SRS.To identify the predictors of clinical outcomes for BS-AVMs treated by SRS, we performed a retrospective observational study of BS-AVMs patients treated by SRS at our institution from 2006 to 2016. The primary outcomes were obliteration of nidus and favorable outcomes (AVM nidus obliteration with mRS score ≤2). For getting the outcomes more accurate, we also pooled the results of previous studies as well as our study by meta-analysis.A total of 26 patients diagnosed with BS-AVMs, with mean volume of 2.6 ml, were treated with SRS. Hemorrhage presentation accounted for 69% of these patients. Overall obliteration rate was 42% with mean follow-up of more than five years and two patients (8%) had a post-SRS hemorrhage. Favorable outcomes were observed in 8 patients (31%). Higher margin dose (>15Gy) was associated with higher obliteration (P = .042) and small volume of nidus was associated with favorable outcomes (P = .036). After pooling the results of 7 studies and present study, non-prior embolization (P = .049) and higher margin dose (P = .04) were associated with higher obliteration rate, in addition, the lower Virginia Radiosurgery AVM Scale (VRAS) was associated with favorable outcomes (P = .02) of BS-AVMs after SRS.In the BS-AVMs patients treated by SRS, higher margin dose (19-24Gy) and non-prior embolization were the independent predictors of higher obliteration rate. In addition, smaller volume of nidus and lower VRAS were the potential predictors of long-term favorable outcomes for these patients.


Assuntos
Tronco Encefálico/irrigação sanguínea , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/radioterapia , Radiocirurgia/efeitos adversos , Adolescente , Adulto , Idoso , Tronco Encefálico/patologia , Regras de Decisão Clínica , Embolização Terapêutica/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/mortalidade , Hemorragias Intracranianas/epidemiologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
J Clin Neurosci ; 89: 91-96, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119301

RESUMO

The visualization of intracranial epidermoid tumors is often limited by difficulties associated with distinguishing the tumor from the surrounding cerebrospinal fluid using traditional computed tomography (CT) or magnetic resonance imaging (MRI) modalities. This report describes our experience using CT cisternography to visualize intracranial epidermoid tumors in three illustrative cases. CT cisternography of the epidermoid tumor provides more clarity and precision compared to traditional neuroimaging modalities. We demonstrate the feasibility of using CT cisternography to produce high-resolution images with well-defined tumor margins that can be used effectively for precise SRS treatment planning.


Assuntos
Neoplasias Encefálicas/cirurgia , Neuroimagem/métodos , Radiocirurgia/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Neuroimagem/normas , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/normas
8.
Anticancer Res ; 41(6): 3179-3185, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083313

RESUMO

BACKGROUND/AIM: The aim of this study was to identify prognostic factors for brain metastases treated with Gamma knife radiosurgery. PATIENTS AND METHODS: Multivariate Cox proportional hazards regression analyses were conducted for patients who received treatment between June 2013 and March 2018. RESULTS: A total of 131 consecutive patients were included. The median follow-up period was 16.0 months (range=1.5-61.5 months). Brain metastases [hazard ratio (HR)=0.42, 95%CI=0.27-0.67, p<0.001], history of systemic therapy (HR=2.23, 95%CI=1.28-3.89, p=0.005), and active extracranial disease (HR=2.49, 95%CI=1.30-4.76, p=0.006) were independent predictors of overall survival. Number of brain metastases (HR=0.39, 95%CI=0.26-0.59, p<0.001) and history of systemic therapy (HR=1.90, 95%CI=1.17-3.08, p=0.005) were independent predictors of intracranial progression-free survival. CONCLUSION: The number of brain metastases and the history of systemic therapy are associated with patient overall survival and intracranial progression-free survival.


Assuntos
Neoplasias Encefálicas/secundário , Metástase Neoplásica/radioterapia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 100(19): e25752, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106604

RESUMO

ABSTRACT: This study was conducted to report long-term outcomes of the frameless robotic stereotactic radiosurgery (SRS) for brain arteriovenous malformation (AVM) at Ramathibodi Hospital.Retrospective data of patients with brain AVM (bAVM), who underwent CyberKnife SRS (CKSRS) at Ramathibodi Hospital from 2009 to 2014, were examined. Exclusion criteria were insufficient follow-up time (<36 months) or incomplete information. Patients' demographics, clinical presentation, treatment parameters, and results were analyzed. Excellent outcome was defined as AVM obliteration without a new neurological deficit. Risk factors for achieving excellent outcome were assessed.From a total of 277 CKSRS treatments for bAVM during the 6 years, 170 AVMs in 166 patients met the inclusion criteria. One hundred and thirty-nine cases (81.76%) presented with hemorrhages from ruptured bAVMs. Almost two-thirds underwent embolization before radiosurgery. With the median AVM volume of 4.17 mL, three-quarters of the cohort had single-fraction CKSRS, utilizing the median prescribed dose of 15 Gray (Gy). In the multisession group (25.29%), the median prescribed dose and the AVM volume were 27.5 Gy and 22.3 mL, respectively. An overall excellent outcome, at a median follow-up period of 72.45 months, was observed in 99 cases (58.24%). Seven AVMs (4.12%) ruptured after CKSRS but 1 patient suffered a new neurological deficit. Two patients (1.18%) were classified into the poor outcome category but there were no deaths. Negative factors for excellent outcome, by multivariate regression analysis, were the male sex and multisession SRS delivery, but not age, history of AVM rupture, previous embolization, or AVM volume.Despite relatively larger bAVM and utilizing a lower prescribed radiation dose, the excellent outcome was within the reported range from previous literature. This study offers one of the longest follow-ups and the largest cohorts from the frameless image-guided robotic SRS community.


Assuntos
Fístula Arteriovenosa/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Assistida por Computador/métodos , Adolescente , Adulto , Feminino , Seguimentos , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
World Neurosurg ; 151: 163-171, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34044166

RESUMO

Stereotactic neurosurgery involves a targeted intervention based on congruence of image guidance to a reference fiducial system. This discipline has widespread applications in radiosurgery, tumor therapy, drug delivery, functional lesioning, and neuromodulation. In this article, we focused on convection-enhanced delivery to deliver therapeutic agents to the brain addressing areas of research and clinical development. We performed a robust literature review of all relevant articles highlighting current efforts and challenges of making this delivery technique more widely understood. We further described key biophysical properties of molecular transport in the extracellular space that may impact the efficacy and control of drug delivery using stereotactic methods. Understanding these principles is critical for further refinement of predictive models that can inform advances in stereotactic techniques for convection-enhanced delivery of therapeutic agents to the brain.


Assuntos
Transporte Biológico/fisiologia , Encéfalo/cirurgia , Sistemas de Liberação de Medicamentos , Técnicas Estereotáxicas , Convecção , Sistemas de Liberação de Medicamentos/métodos , Humanos , Radiocirurgia/métodos
11.
BMC Cancer ; 21(1): 494, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941111

RESUMO

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Movimentos dos Órgãos , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/métodos , Austrália , Carcinoma Hepatocelular/secundário , Dinamarca , Marcadores Fiduciais , Humanos , Neoplasias Hepáticas/secundário , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radiocirurgia/instrumentação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Respiração , Resultado do Tratamento
12.
World Neurosurg ; 151: 209-217, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33940266

RESUMO

BACKGROUND: Although cases of trigeminal neuralgia (TN) induced by brainstem infarct have been reported, the neurosurgical literature lacks a comprehensive review for this subpopulation of patients. We present the first systematic review of the literature to discuss pathology, surgical management, and future directions for therapeutic innovation in this population. METHODS: Our systematic review was conducted according to PRISMA guidelines. Resulting articles were screened for those that presented cases of TN associated with brainstem infarct. RESULTS: A review of the literature identified 18 case reports of 21 patients with TN induced by brainstem infarct: 14 pontine infarcts and 7 medullary infarcts. Although many cases of ischemic brainstem lesions are caused by acute stroke, cerebral small vessel disease also plays a role in certain cases, and the relationship between these chronic lesions and TN is more likely to be overlooked. Furthermore, we found that reports of self-resolving TN pain after brainstem infarct is disproportionately biased, as most case reports published their data within the first few months after initial presentation. Reports with follow-up periods >13 months reported eventual pain recurrence that necessitated surgical intervention. Microvascular decompression was not sufficient to treat TN pain associated with concurrent neurovascular compression and brainstem infarct. CONCLUSIONS: Brainstem infarcts affecting the trigeminal pathway represent an understudied pathologic cause of TN. Although the neurosurgical literature lacks a clear picture of the most efficacious interventions in this population, we are optimistic that this review will encourage further investigation into the best treatment for these patients.


Assuntos
Infartos do Tronco Encefálico/cirurgia , Tronco Encefálico/cirurgia , Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo/cirurgia , Humanos , Cirurgia de Descompressão Microvascular/métodos , Radiocirurgia/métodos , Recidiva , Resultado do Tratamento
13.
Lancet Oncol ; 22(6): 824-835, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34015311

RESUMO

BACKGROUND: Previous phase 2 trials of neoadjuvant anti-PD-1 or anti-PD-L1 monotherapy in patients with early-stage non-small-cell lung cancer have reported major pathological response rates in the range of 15-45%. Evidence suggests that stereotactic body radiotherapy might be a potent immunomodulator in advanced non-small-cell lung cancer (NSCLC). In this trial, we aimed to evaluate the use of stereotactic body radiotherapy in patients with early-stage NSCLC as an immunomodulator to enhance the anti-tumour immune response associated with the anti-PD-L1 antibody durvalumab. METHODS: We did a single-centre, open-label, randomised, controlled, phase 2 trial, comparing neoadjuvant durvalumab alone with neoadjuvant durvalumab plus stereotactic radiotherapy in patients with early-stage NSCLC, at NewYork-Presbyterian and Weill Cornell Medical Center (New York, NY, USA). We enrolled patients with potentially resectable early-stage NSCLC (clinical stages I-IIIA as per the 7th edition of the American Joint Committee on Cancer) who were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients were randomly assigned (1:1) to either neoadjuvant durvalumab monotherapy or neoadjuvant durvalumab plus stereotactic body radiotherapy (8 Gy × 3 fractions), using permuted blocks with varied sizes and no stratification for clinical or molecular variables. Patients, treating physicians, and all study personnel were unmasked to treatment assignment after all patients were randomly assigned. All patients received two cycles of durvalumab 3 weeks apart at a dose of 1·12 g by intravenous infusion over 60 min. Those in the durvalumab plus radiotherapy group also received three consecutive daily fractions of 8 Gy stereotactic body radiotherapy delivered to the primary tumour immediately before the first cycle of durvalumab. Patients without systemic disease progression proceeded to surgical resection. The primary endpoint was major pathological response in the primary tumour. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrial.gov, NCT02904954, and is ongoing but closed to accrual. FINDINGS: Between Jan 25, 2017, and Sept 15, 2020, 96 patients were screened and 60 were enrolled and randomly assigned to either the durvalumab monotherapy group (n=30) or the durvalumab plus radiotherapy group (n=30). 26 (87%) of 30 patients in each group had their tumours surgically resected. Major pathological response was observed in two (6·7% [95% CI 0·8-22·1]) of 30 patients in the durvalumab monotherapy group and 16 (53·3% [34·3-71·7]) of 30 patients in the durvalumab plus radiotherapy group. The difference in the major pathological response rates between both groups was significant (crude odds ratio 16·0 [95% CI 3·2-79·6]; p<0·0001). In the 16 patients in the dual therapy group with a major pathological response, eight (50%) had a complete pathological response. The second cycle of durvalumab was withheld in three (10%) of 30 patients in the dual therapy group due to immune-related adverse events (grade 3 hepatitis, grade 2 pancreatitis, and grade 3 fatigue and thrombocytopaenia). Grade 3-4 adverse events occurred in five (17%) of 30 patients in the durvalumab monotherapy group and six (20%) of 30 patients in the durvalumab plus radiotherapy group. The most frequent grade 3-4 events were hyponatraemia (three [10%] patients in the durvalumab monotherapy group) and hyperlipasaemia (three [10%] patients in the durvalumab plus radiotherapy group). Two patients in each group had serious adverse events (pulmonary embolism [n=1] and stroke [n=1] in the durvalumab monotherapy group, and pancreatitis [n=1] and fatigue [n=1] in the durvalumab plus radiotherapy group). No treatment-related deaths or deaths within 30 days of surgery were reported. INTERPRETATION: Neoadjuvant durvalumab combined with stereotactic body radiotherapy is well tolerated, safe, and associated with a high major pathological response rate. This neoadjuvant strategy should be validated in a larger trial. FUNDING: AstraZeneca.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Radiocirurgia/métodos , Adulto Jovem
14.
World Neurosurg ; 151: e899-e910, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33989823

RESUMO

OBJECTIVE: Gamma Knife surgery (GKS) is an established treatment option for trigeminal neuralgia (TN). However, the long-term efficacy of GKS for patients with TN has not been well studied. The aim of the study is to evaluate the sequential course of pain control after GKS and analyze the factors associated with the long-term analgesic effect, focusing on radiation dosimetry and neurovascular conflict (NVC) factors. METHODS: We analyzed 83 patients undergoing GKS for TN in our institution between 2005 and 2013 with a follow-up duration >7 years. Tolerable pain with increased medication, persistent-intractable pain, and recurrence were classified as poor outcomes, and any other outcome was classified as a favorable outcome. The dosimetry factors and locational relationship between NVC and the target were analyzed in terms of their correlation with a favorable outcome. RESULTS: Adequate pain relief was achieved in 93% of patients a month and a half after GKS, but the pain recurred in 41.5% of patients on average 36 months after treatment. A larger V40Gy (P = 0.002) and higher homogeneity index (P = 0.027) were significantly associated with the long-term favorable outcomes. About 40% of patients had multiple NVC sites, and insufficient inclusion of the NVC in the target was significantly correlated with long-term poor outcomes (P = 0.002). CONCLUSIONS: Targeting the center of the trigeminal nerve in the area of NVC with GKS is associated with favorable long-term pain control.


Assuntos
Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiometria/métodos , Recidiva , Estudos Retrospectivos , Tempo , Resultado do Tratamento
15.
BMC Cancer ; 21(1): 482, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931014

RESUMO

BACKGROUND: This retrospective study aimed to evaluate the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with stereotactic body radiation therapy (SBRT) and to elucidate potential mechanisms of acquired resistance. METHODS: Patients with advanced NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016 and August 2019. Eligible patients were treated with thoracic SBRT, and TKI was continued after SBRT until it was considered ineffective. The control group was treated with TKIs monotherapy. Propensity score matching (PSM, ratio of 1:2) was used to account for differences in baseline characteristics. Overall survival (OS), progression-free survival (PFS), treatment safety and resistance mechanisms were evaluated. RESULTS: Three hundred eight patients were included in the study population. Among them, 262 patients received TKIs alone, and 46 patients received TKIs with SBRT. Baseline characteristics were not significantly different between the two cohorts after PSM. The median PFS was 19.4 months in the TKIs +SBRT group compared to 13.7 months in the TKIs group (p = 0.034). An influence on OS has not yet been shown (p = 0.557). Of the 135 patients evaluated after PSM, 28 and 71 patients in the TKIs and TKIs +SBRT cohorts, respectively, had plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) performed at baseline and disease progression. In the TKIs +SBRT cohort, the NGS results showed that T790M mutations were detected in 64.3% (18/28) of patients. Patients in the TKIs cohort exhibited fewer T790M-positive mutations (40.8%, p = 0.035) compared to patients in the TKIs +SBRT cohort. CONCLUSION: Real world data prove that TKIs plus thoracic SBRT significantly extend PFS with tolerable toxicity. The mutation ratio of T790M was increased in the TKIs +SBRT group compared to the TKIs only group. Further randomized studies are warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/métodos , DNA/sangue , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Pontuação de Propensão , Inibidores de Proteínas Quinases/efeitos adversos , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Adulto Jovem
16.
Turk Neurosurg ; 31(4): 519-529, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33978200

RESUMO

AIM: To analyze the results of stereotactic radiosurgery in 295 patients with residual Grade I meningiomas located at parasellar region, petroclival region, cerebellopontine angle and parasagittal region. MATERIAL AND METHODS: A total of 295 patients with Grade 1 residual Meningiomas (197 women, 98 men), who were treated by adjuvant radiosurgery in Gazi University Gamma Knife Center between 2004-2015 were analyzed. WHO Grade 2 and 3 meningiomas were not included in our study. Minimum radiological follow-up was 24 months. The median follow-up was 54 months. The tumor volume, location, treatment dose, morbidity, progression free survival and tumor control rate were analyzed. RESULTS: The median tumor volume was 5.2 cm3 (0.04-39.7), median age was 50 (20-80), median dose was 14 Gy and tumor control rate was 94.5% (stationary in 85.0%, volume reduction in 9.5%). Increase in tumor volume was seen in 16 patients (5.5%) and re-operation was performed in 5 of them (1.6%). Stereotactic radiosurgery was performed again for 8 patients (2.7%).The location of the tumors was as follows: 39.3% parasellar region, 20% cerebellopontine angle, 13.6% petroclival and 27.1% was parasagittal, falcine or convexity. Major morbidities were detected in 6 (2%) patients. Minor morbidities were detected in 18 (6.1%) patients. CONCLUSION: Stereotactic radiosurgery is an effective and safe treatment modality for residual Grade I meningiomas.


Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Estado Terminal/epidemiologia , Estado Terminal/terapia , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/epidemiologia , Meningioma/patologia , Meningioma/cirurgia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Radiocirurgia/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
17.
Cancer Treat Rev ; 98: 102206, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33965893

RESUMO

BACKGROUND AND PURPOSE: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT. MATERIALS AND METHODS: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation. RESULTS: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure). CONCLUSION: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Guias de Prática Clínica como Assunto/normas , Neoplasias da Próstata/cirurgia , Radiocirurgia/métodos , Terapia de Salvação/métodos , Consenso , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia
18.
BMC Neurol ; 21(1): 207, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022822

RESUMO

BACKGROUND: Treating chordoma through surgery alone is often ineffective. Thus, surgery often performed with irradiation, with a reported 5-year survival rate of 60-75%. The clinical course varies, and disease rarity prevents larger number of clinical investigations. METHODS: In total, 19 patients with clival chordomas were retrospectively extracted from our institutional database. They were initially treated with maximal tumor removal using the extended transsphenoidal approach between March 2006 and January 2021. When total tumor removal was achieved, prophylactic irradiation was not performed. If tumor remnants or recurrence were confirmed, Gamma Knife (GK) radiosurgery was performed. The mean follow-up period was 106.7 months (ranged 27-224 months). The clinical course and prognostic factors were investigated. RESULTS: Total removal was achieved in 10 patients, whereas 4 patients suffered recurrence and required GK. GK was applied to 11 patients with a 50% isodose of 13-18 Gy (mean: 15.4 Gy), and eight patients remained progression free, whereas three patients suffered repeated local recurrence and died of tumor-related complications. The mean overall progression-free interval was 57.2 months (range: 6-169 months). One male patient died of tumor un-related lung cancer 36 months after the initial treatment, and other patients survived throughout the observational periods. The mean overall survival was 106.7 months (range: 27-224 months). Thus, the 5-year survival rate was 94.7%. Statistical analysis indicated that sex (men), > 15 Gy of 50% isodose by GK, and screening brain examinations as prophylactic medicine were significant favorable prognostic factors. CONCLUSIONS: The favorable outcomes in this investigation suggest the importance of early detection and treatment. Surgery may enable better conditions for sufficient GK doses.


Assuntos
Cordoma/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias da Base do Crânio/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Radiocirurgia/métodos , Estudos Retrospectivos , Taxa de Sobrevida
19.
Anticancer Res ; 41(5): 2575-2581, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952486

RESUMO

BACKGROUND/AIM: Few previous studies have evaluated the effectiveness of single-isocenter multitarget (SIMT) stereotactic radiosurgery (SRS) in clinical practice. PATIENTS AND METHODS: Gross tumor volumes of 113 metastases in 13 patients were measured by contrast-enhanced magnetic resonance imaging. Prescribed doses were set at 20-24 Gy. Based on tumor reduction rates (TRRs) measured before and after SIMT SRS, tumor shrinkage effect was categorized into four grades; almost disappeared: TRR=1, decreased: 0.3≤TRR<1, stable: -0.2

Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos
20.
World Neurosurg ; 150: e750-e755, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33812069

RESUMO

BACKGROUND: Arteriovenous malformations (AVMs) are rare vascular congenital lesions that affect mainly patients during their productive years of life. In order to obtain a better quality of life for patients with this disease, a multidisciplinary approach is recommended. Radiosurgery is one of the treatment modalities available for AVMs, but many factors may influence the effectiveness of this strategy. Classically, it has been said that deep-seated lesions have a particular behavior compared with AVMs in other regions, but a differentiation between thalamic lesions and those located in the basal ganglia has not been made. METHODS: Institutional records for central core AVMs treated with radiosurgery between January 2004 and January 2014 were retrospectively analyzed. Brainstem lesions were excluded from the analysis. RESULTS: Forty-nine patients with deep-seated AVMs were included. Forty-three (87.8%) were located in the thalamus and 6 (12.2%) in the area of basal ganglia. The nidus mean volume was 4.1 cm3 (SD: 4.1), the maximum diameter mean was of 19.5 mm (SD: 8.0). The prescription dose was 18.2 Gy (SD: 2.1), and the follow-up time was 75.8 months (SD: 32.5). There was a greater obliteration rate in thalamic AVMs compared with those located in the basal ganglia: 81.4% versus 33.3% (P = 0.026), respectively. There was no association between categorical variables and obliteration rate. CONCLUSIONS: Stereotactic radiosurgery is a good option for patients with thalamic and basal ganglia AVMs, but a multidisciplinary approach to decision-making is mandatory in order to achieve the best results.


Assuntos
Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/cirurgia , Gânglios da Base/patologia , Malformações Arteriovenosas Intracranianas/patologia , Malformações Arteriovenosas Intracranianas/cirurgia , Tálamo/patologia , Adulto , Gânglios da Base/cirurgia , Feminino , Humanos , Masculino , Prognóstico , Radiocirurgia/métodos , Estudos Retrospectivos , Tálamo/cirurgia , Resultado do Tratamento
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