1. To compare the effectiveness of different drug forms of silymarin: standardized extract of silymarin (SS), micronized silymarin (MS) and silymarin in the form of phytosome (PS) on dyslipidemia and ...liver fat accumulation in a model of metabolic syndrome, in non-obese hereditary hypertriglyceridemic rats. The second aim of this study was to slightly uncover the silymarin action on enzymes and proteins involved in cholesterol metabolism and excretion.
2. Silymarin administered to hereditary hypertriglyceridemic rats as dietary supplements (1%) for 4 weeks significantly lowered the plasma levels of triglycerides, total cholesterol and markedly increased HDL cholesterol level. Western blot analyses showed significant increase in the protein expression of CYP7A1 and CYP4A and increase in protein expression of selected ABC transporters. Silymarin in the form of phytosome and micronized silymarin were more effective forms of silymarin.
3. These findings suggest that silymarin may favorably affect the metabolism of cholesterol and triglycerides in rats with metabolic syndrome. Raising HDL levels suggests potentially important anti-atherogenic effect of silymarin. The changes in expression of cytochromes P450 and ABC transporters involved in cholesterol metabolism and excretion could be partially responsible for the hypolipidemic effect of silymarin.
•Increasing time from diagnosis of metastases to Stereotactic body radiation therapy is negatively impacting on local control.•In-field progression and increasing number of systemic lines are ...significant negative predictive factors for progression free survival in oligometastatic colorectal cancer.•Median overall survival of patients with ablated metastases is 1.6 fold longer than patients without control of oligometastases.
Colorectal cancer (CRC) represents one of the major leading causes of death from cancer. Aim of the present study was to analyze outcome of oligometastatic CRC patients treated with stereotactic body radiation therapy (SBRT), and to evaluate predictive factors of survival.
We included patients with maximum 5 metastases. Previous/concomitant systemic treatments were allowed. End points of the present study were the outcome in terms of Local control of treated metastases (LC), progression free survival (PFS), and overall survival (OS).
437 metastases were treated in 270 patients. Lung was site of metastases in 48.5% of cases, followed by liver (36.4%). Systemic treatment was administered before SBRT in 199 patients (73.7%). Median follow-up time was 23 months (3–98.7). Rates of LC at 1, 3 and 5 years were 95%, 73% and 73%, respectively. Time from diagnosis of metastases to SBRT was the only factor predictive of LC (HR 1.62, p = 0.023). Median PFS was 8.6 months. Rates of OS at 1, 3 and 5 years were 88.5%, 56.6%, and 37.2%, respectively. Lesion greater than 30 mm (HR 1.82, p = 0.030), presence of non-lung metastases (HR 1.67, p = 0.020), the use of systemic treatment before SBRT (HR 1.82, p = 0.023), and progression of treated metastases (HR 1.80, p = 0.007), were all predictive of worse OS.
Stereotactic body radiation therapy represents an effective approach in the management of oligometastatic CRC. Control of treated oligometastases seems to be a strong positive predictive factor for both PFS and OS.
Purpose
To evaluate the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of colorectal liver metastases.
Methods
Forty-two patients with inoperable colorectal ...liver metastases not amenable to radiofrequency ablation (RFA) were treated with SBRT for a total number of 52 lesions. All patients received a total dose of 75 Gy in 3 consecutive fractions. Mean size of the lesions was 3.5 cm (range 1.1–5.4). Toxicity was classified according to the Common Toxicity Criteria version 3.0.
Results
Median follow-up was 24 (range 4–47) months. The progression in field was observed in 5 lesions. Twenty-four months actuarial local control (LC) rate was 91 %. Median overall survival (OS) was 29.2 ± 3.7 months. Actuarial OS rate at 24 months was 65 %. Median progression-free survival was 12.0 ± 4.2 months; 24 months actuarial rate was 35 %. No patients experienced radiation-induced liver disease or grade ≥3 toxicity.
Conclusions
SBRT represents a feasible alternative for the treatment of colorectal liver metastases not amenable to surgery or other ablative treatments in selected patients, showing optimal LC and promising survival rate.
Abstract Purpose To assess the impact of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams for stereotactic body radiotherapy (SBRT) in inoperable stage I NSCLC. Current ...data were compared against a cohort of patients previously treated with advanced conformal techniques (3DCRT) based on conformal arcs. Methods and materials From July 2006 to December 2011 132 patients underwent SBRT, 86 by 3DCRT with flattened beams (FF), while the last 46 with VMAT RapidArc and unflattened beams (FFF). All patients were treated with 48 Gy in four fractions of 12 Gy each. Patients underwent follow-up. Clinical outcome was evaluated with thoracic and abdominal CT scan and 18FDG-CTPET before and after treatment. Results Both techniques achieved adequate dose conformity to the target but with a statistically significant reduction of ipsilateral lung doses in RapidArc plans and also of Beam-on-Time (BOT) with FFF mode. The median follow up was 16 months (range 2–24 months). At 1 year, local control rate was 100% with FFF beams compared with 92.5% with FF beams ( p = 0.03). Conclusions SBRT with FFF beams permitted us a safe delivery of high dose per fraction in a short treatment time and resulted in an earlier radiological response compared with FF beams.
To compare advanced treatment techniques with photons and protons as a stereotactic body radiation therapy (SBRT) for adrenal glands metastases. Planning computer tomographic (CT) scans of 10 ...patients were selected. A total dose of 45 Gy in 7.5 Gy fractions was prescribed. Organs at risk (OAR) were liver and kidneys. Dose-volume metrics were defined to quantify quality of plans assessing target coverage and sparing of organs at risk. Plans for RapidArc, intensity-modulated radiotherapy (IMRT), dynamic conformal arcs, 3D conformal static fields, and intensity modulated protons were compared. The main planning objective for the clinical target volume (CTV) was to cover 100% of the volume with 95% (V^sub 95%^ = 100%) and to keep the maximum dose below 107% of the prescribed dose (V^sub 107%^ = 0%). Planning objective for planning target volume (PTV) was V^sub 95%^ > 80%. For kidneys, the general planning objective was V^sub 15Gy^ < 35% and for liver V^sub 15Gy^ < (liver volume-700 cm^sup 3^). All techniques achieved the minimum and maximum dose objective for CTV and PTV, D^sub 5-95%^ ranged from 1 Gy (protons) to 1.6 Gy (conformal static fields) on CTV. Maximal organ at risk sparing was achieved by protons. RapidArc presented the second lowest dose bath (V^sub 10Gy^ and integral dose) after protons and the best conformality together with IMRT. Stereotactic body radiation therapy (SBRT) to adrenal glands metastases is achievable with several advanced techniques with either photons or protons. The intensity modulated approaches using either static fields, dynamic arcs or protons are superior to the other conformal solutions. For their simplicity, IMRT or RapidArc should be considered as the first option radiation treatment for those patients not eligible for proton treatment.PUBLICATION ABSTRACT
Liver metastases and SBRT: A new paradigm? Comito, Tiziana; Clerici, Elena; Tozzi, Angelo ...
Reports of Practical Oncology and Radiotherapy,
11/2015, Letnik:
20, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract Background The outstanding innovations made by early diagnosis, novel surgical techniques, effective chemotherapy regimens and conformal radiotherapy, have significantly improved patients ...overall survival and quality of life. Multidisciplinary approach to cancer has also led to an increased prevalence of patients with few, organ-confined metastases, who can experience long-term survival even if their disease is no longer localized. Liver is one of the most common site for metastatic disease from several cancers, and when metastatic disease is confined to liver, given the ability of this organ to regenerate almost to its optimal volume, surgical resection represents the standard of care because is associated with a better prognosis. Approximately 70–90% of liver metastases, however, are unresectable and a safe, effective alternative therapeutic option is necessary for these patients. Materials and methods A review of the current literature was performed to analyze the role of SBRT in treating liver metastases from different cancers. A literature search using the terms “SBRT” and “liver metastases” was carried out in PUBMED. Results Stereotactic body radiation therapy has shown to provide promising results in the treatment of liver metastases, thanks to the ability of this procedure to deliver a conformal high dose of radiation to the target lesion and a minimal dose to surrounding critical tissues. Conclusion Stereotactic body radiation therapy is a non-invasive, well-tolerated and effective treatment for patients with liver metastases not suitable for surgical resection.
Purpose
The aim of the present study was to provide predictive factors for survival outcomes of oligometastatic prostate cancer (PC) patients treated with stereotactic body radiation therapy (SBRT) ...as a metastases-directed therapy (MDT).
Methods
In this cohort study, endpoints included overall survival (OS), progression-free survival (PFS), distant progression-free survival (DFS) and local control of treated metastases (LC). The binary classification tree approach with recursive partitioning analysis (RPA) was applied to stratify the patients into risk groups based on OS, PFS and DPFS; for each endpoint, disease-free interval (DFI) was calculated. We included patients with synchronous or metachronous metastases from prostate adenocarcinoma treated with SBRT.
Results
119 Metastases were treated with SBRT in 92 patients. Median follow-up was 22.2 months. Rates of OS at 1 and 3 years were 96.9% and 88.0%, while DPFS was 51.9% and 20.9%. Recursive partitioning analysis identified three prognostic classes for OS: Class 1: castration-sensitive patients (3 years OS 95%); Class 2: castration-resistant patients with low-intermediate risk NCCN disease (3 years OS 88.8%); Class 3: castration-resistant patients with high-risk NCCN disease (3 years OS 76.9%). Regarding DPFS, RPA divided patients into two classes, according to a cutoff value of DFI of 34 months (3 years PFS of 28.7% vs 5.8%). Three classes were identified for DPFS: Class 1: DFI < 34 months (3 years DPFS 9.1%); Class 2: DFI > 34 months and high-risk NCCN PC (3 years DPFS 21%); Class 3: DFI > 34 months and low-intermediate risk NCCN disease (3 years DPFS 60.2%).
Conclusion
Oligometastatic PC represents nowadays a setting of particular interest in which local ablative therapies play a decisive role. In the present study, we recognized the importance of DFI, together with NCCN class risk, to predict the risk of new metastases after SBRT in oligometastatic PC.
Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. ...The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS).
From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1-3 cm and 32Gy/4 fractions for lesions 3.1-5 cm. Local progression was defined as increase of the enhancing abnormality on MRI, and distant progression as new brain metastases outside the irradiated volume. Toxicity in terms of radio-necrosis was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion- MRI.
The median maximum diameter of BM was 2.9 cm (range 2.1-5 cm), the median gross target volume (GTV) was 16.3 cm(3) and the median planning target volume (PTV) was 33.7 cm(3) The median,1,2-year local control rate was 30 months, 96, 96 %; the median, 1-2-year rate of BDP was 24 months, 12, 24 %; the median,1,2-year OS was 14 months, 69, 33 %. KPS and controlled extracranial disease were associated with significant survival benefit (p <0.01). Brain radio-necrosis occurred in six patients (5.8 %).
In patients with single, large BMs unsuitable for surgical resection, HSRT is a safe and feasible treatment, with good brain local control and limited toxicity.
Abstract Objective To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. Methods A retrospective ...analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Results Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI >18 months. No cases of acute G3 toxicity or greater occurred. Conclusions SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.
Endosonography (EUS) performed prior to endoscopic retrograde cholangiopancreatography (ERCP) or surgery in patients with a low to moderate probability of choledocholithiasis can reduce morbidity, ...mortality and costs.
This study aimed at evaluating the sensitivity and specificity of EUS and transabdominal ultrasonography (TUS) compared to ERCP in a cohort of 100 patients diagnosed with extrahepatic biliary obstruction.
There were four working groups. The first group processed the initial data including history, physical examination and assessment of laboratory markers of cholestasis. The second group examined TUS. The third group examined the pancreas and biliary tree using EUS, always prior to ERCP. The fourth working group carried out ERCP.
The sensitivity and accuracy of EUS in the diagnosis of common bile duct dilatation were 84% and 83%, respectively, i.e. significantly higher (p=0.0001) than TUS (46% and 66%, respectively). The specificities of methods (82%, 91%) were not significantly different (p=0.218). The sensitivity and accuracy of EUS in the diagnosis of pathological content of the common bile duct were 88% and 92%, respectively, i.e. significantly higher (p<0.0001) than TUS (33% and 64%). The specificities of the methods (96%, 94%) were not significantly different (p=0.641). The incidence of choledocholithiasis in the high-risk group was significantly higher than in the moderate-risk group (p=0.012).
Radial EUS is a method with high sensitivity, specificity, positive and negative predictive values. It should therefore be preferred to ERCP in patients with low or moderate risk of choledocholithiasis.
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