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Current Pharmaceutical Design 2017This review aims to present the relevant background information and current research status in concentration of polyphenols using membrane technologies. The potential... (Review)
Review
BACKGROUND
This review aims to present the relevant background information and current research status in concentration of polyphenols using membrane technologies. The potential implementation of membrane separation to bioactive compounds like soluble phenolics from aqueous and organic solvent solutions is gaining increasing interest in the recent years. This review does not pretend to cover the abundant published literature on the subject, but to be representative for the observed tendencies in membrane processes applications for concentration of polyphenols derived from natural products. The first part of the article includes general information regarding the polyphenols and the traditional methods for their separation (such as: thin layer chromatography; paper chromatography; gas chromatography; high performance liquid chromatography; capillary electrophoresis), while the second part presents a review of different membrane processes applied for concentration of polyphenols. Three main sources for such implementations are discussed: (1) aqueous or organic solvent extracts from plant material, (2) fruits, and (3) recovery of polyphenols from industrial waste liquids. A diversity of membrane processes are considered in a large scope of implementations ranging from lab-scale studies to pilot and semiindustrial scale operations.
CONCLUSION
Membrane technology is an excellent candidate to make a paradigm shift in biological active compounds fractionation/separation processes. Presented results clearly demonstrate that membrane processes are of great advantages over traditionally used methods; however, characterization of separated polyphenols has to be improved. Most of citied authors concentrated their investigation only on the total amount of polyphenols determination. Exhaustive studies including: antioxidant activities, retention index, total soluble solids, or volume reduction factor, have been only carried out by a few authors.
Topics: Chemical Fractionation; Chromatography, Gas; Chromatography, High Pressure Liquid; Chromatography, Paper; Chromatography, Thin Layer; Electrophoresis, Capillary; Membranes, Artificial; Polyphenols
PubMed: 27774906
DOI: 10.2174/1381612822666161021124358 -
International Journal of Radiation... May 2019Spatially fractionated radiation therapy represents a significant departure from canonical thinking in radiation oncology despite having origins in the early 1900s. The... (Review)
Review
Spatially fractionated radiation therapy represents a significant departure from canonical thinking in radiation oncology despite having origins in the early 1900s. The original and most common implementation of spatially fractionated radiation therapy uses commercially available blocks or multileaf collimators to deliver a nonconfluent, sieve-like pattern of radiation to the target volume in a nonuniform dose distribution. Dosimetrically, this is parameterized by the ratio of the valley dose in cold spots to the peak dose in hot spots, or the valley-to-peak dose ratio. The radiobiologic mechanisms are postulated to involve radiation-induced bystander effects, microvascular alterations, and/or immunomodulation. Current indications include bulky or locally advanced disease that would not be amenable to conventional radiation or that has proved refractory to chemoradiation. Early-phase clinical trials have shown remarkable success, with some response rates >90% and minimal toxicity. This has promoted technological developments in 3-dimensional formats (LATTICE), micron-size beams (microbeam), and proton arrays. Nevertheless, more clinical and biological data are needed to specify ideal dosimetry parameters and to formulate robust clinical indications and guidelines for optimal standardized care.
Topics: Animals; Bystander Effect; Clinical Trials as Topic; Dose Fractionation, Radiation; Humans; Immunomodulation; Mice; Microvessels; Neoplasms; Radiation Oncology
PubMed: 30684666
DOI: 10.1016/j.ijrobp.2019.01.073 -
Physics in Medicine and Biology Aug 2023Radiation-induced cell death is a complex process influenced by physical, chemical and biological phenomena. Although consensus on the nature and the mechanism of the...
Radiation-induced cell death is a complex process influenced by physical, chemical and biological phenomena. Although consensus on the nature and the mechanism of the bystander effect were not yet made, the immune process presumably plays an important role in many aspects of the radiotherapy including the bystander effect. A mathematical model of immune response during and after radiation therapy is presented.Immune response of host body and immune suppression of tumor cells are modelled with four compartments in this study; viable tumor cells, T cell lymphocytes, immune triggering cells, and doomed cells. The growth of tumor was analyzed in two distinctive modes of tumor status (immune limited and immune escape) and its bifurcation condition.Tumors in the immune limited mode can grow only up to a finite size, named as terminal tumor volume analytically calculated from the model. The dynamics of the tumor growth in the immune escape mode is much more complex than the tumors in the immune limited mode especially when the status of tumor is close to the bifurcation condition. Radiation can kill tumor cells not only by radiation damage but also by boosting immune reaction.The model demonstrated that the highly heterogeneous dose distribution in spatially fractionated radiotherapy (SFRT) can make a drastic difference in tumor cell killing compared to the homogeneous dose distribution. SFRT cannot only enhance but also moderate the cell killing depending on the immune response triggered by many factors such as dose prescription parameters, tumor volume at the time of treatment and tumor characteristics. The model was applied to the lifted data of 67NR tumors on mice and a sarcoma patient treated multiple times over 1200 days for the treatment of tumor recurrence as a demonstration.
Topics: Mice; Animals; Neoplasms; Dose Fractionation, Radiation; Immunity; Radiotherapy
PubMed: 37459862
DOI: 10.1088/1361-6560/ace819 -
Chinese Clinical Oncology Apr 2022Our objective was to identify contemporary management options for large brain metastases reported in literature, specifically evaluating local control and risk of... (Review)
Review
OBJECTIVE
Our objective was to identify contemporary management options for large brain metastases reported in literature, specifically evaluating local control and risk of toxicity.
BACKGROUND
Large brain metastases are typically defined as lesions >2 cm in diameter, and historically conferred poor outcomes due to the high rates of radiation necrosis and less local control in comparison to smaller brain metastases.
METHODS
A literature search examining modern management of large brain metastases was performed using ovid-MEDLINE. A total of 18 articles met criteria for review, evaluating single fraction radiosurgery [stereotactic radiosurgery (SRS)] and multi-fraction stereotactic radiation therapy (MFSRT) in both the definitive and post-operative cavity setting, as well as targeted therapies.
CONCLUSIONS
Multi-fractionated radiosurgery represents a modern and attractive treatment approach in the definitive management of patients with large brain metastases, with equivalent local control and reduced rates of radionecrosis less than 13% in comparison to single fraction SRS. In cases where surgery is indicated, fractionated cavity radiation should be considered for large tumor bed volumes. More research is needed for the optimal dose and fractionation regimen for optimal tumor control with reduced risk of radiation toxicity, but common regimens include 3-5 fractions while meeting appropriate biologically effective dose (BED) goals. Future areas of interest include targeted therapies in the initial management of brain metastases as well as pre-operative radiation therapy to reduce risk of leptomeningeal disease (LMD).
Topics: Brain Neoplasms; Dose Fractionation, Radiation; Humans; Meningeal Neoplasms; Radiation Injuries; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 35534794
DOI: 10.21037/cco-21-136 -
Future Oncology (London, England) Aug 2014During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect... (Review)
Review
During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.
Topics: Dose Fractionation, Radiation; Humans; Neoplasms; Organ Sparing Treatments; Radiation Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 23987920
DOI: 10.2217/fon.13.172 -
Radiotherapy and Oncology : Journal of... Nov 2017To perform a systematic review regarding the use of stereotactic ablative radiotherapy (SABR) for the re-irradiation of recurrent malignant disease within the pelvis, to... (Review)
Review
BACKGROUND AND PURPOSE
To perform a systematic review regarding the use of stereotactic ablative radiotherapy (SABR) for the re-irradiation of recurrent malignant disease within the pelvis, to guide the clinical implementation of this technique.
MATERIAL AND METHODS
A systematic search strategy was adopted using the MEDLINE, EMBASE and Cochrane Library databases.
RESULTS
195 articles were identified, of which 17 were appropriate for inclusion. Studies were small and data largely retrospective. In total, 205 patients are reported to have received pelvic SABR re-irradiation. Dose and fractionation schedules and re-irradiated volumes are highly variable. Little information is provided regarding organ at risk constraints adopted in the re-irradiation setting. Treatment appears well-tolerated overall, with nine grade 3 and six grade 4 toxicities amongst thirteen re-irradiated patients. Local control at one year ranged from 51% to 100%. Symptomatic improvements were also noted.
CONCLUSIONS
For previously irradiated patients with recurrent pelvic disease, SABR re-irradiation could be a feasible intervention for those who otherwise have limited options. Evidence to support this technique is limited but shows initial promise. Based on the available literature, suggestions for a more formal SABR re-irradiation pathway are proposed. Prospective studies and a multidisciplinary approach are required to optimise future treatment.
Topics: Dose Fractionation, Radiation; Humans; Neoplasm Recurrence, Local; Pelvic Neoplasms; Radiosurgery; Re-Irradiation; Retrospective Studies
PubMed: 29066125
DOI: 10.1016/j.radonc.2017.09.030 -
Seminars in Radiation Oncology Apr 2016Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for... (Review)
Review
Patients with tumors adjacent to the optic nerves and chiasm are frequently not candidates for single-fraction stereotactic radiosurgery (SRS) due to concern for radiation-induced optic neuropathy. However, these patients have been successfully treated with hypofractionated SRS over 2-5 days, though dose constraints have not yet been well defined. We reviewed the literature on optic tolerance to radiation and constructed a dose-response model for visual pathway tolerance to SRS delivered in 1-5 fractions. We analyzed optic nerve and chiasm dose-volume histogram (DVH) data from perioptic tumors, defined as those within 3mm of the optic nerves or chiasm, treated with SRS from 2000-2013 at our institution. Tumors with subsequent local progression were excluded from the primary analysis of vision outcome. A total of 262 evaluable cases (26 with malignant and 236 with benign tumors) with visual field and clinical outcomes were analyzed. Median patient follow-up was 37 months (range: 2-142 months). The median number of fractions was 3 (1 fraction n = 47, 2 fraction n = 28, 3 fraction n = 111, 4 fraction n = 10, and 5 fraction n = 66); doses were converted to 3-fraction equivalent doses with the linear quadratic model using α/β = 2Gy prior to modeling. Optic structure dose parameters analyzed included Dmin, Dmedian, Dmean, Dmax, V30Gy, V25Gy, V20Gy, V15Gy, V10Gy, V5Gy, D50%, D10%, D5%, D1%, D1cc, D0.50cc, D0.25cc, D0.20cc, D0.10cc, D0.05cc, D0.03cc. From the plan DVHs, a maximum-likelihood parameter fitting of the probit dose-response model was performed using DVH Evaluator software. The 68% CIs, corresponding to one standard deviation, were calculated using the profile likelihood method. Of the 262 analyzed, 2 (0.8%) patients experienced common terminology criteria for adverse events grade 4 vision loss in one eye, defined as vision of 20/200 or worse in the affected eye. One of these patients had received 2 previous courses of radiotherapy to the optic structures. Both cases were meningiomas treated with 25Gy in 5 fractions, with a 3-fraction equivalent optic nerve Dmax of 19.2 and 22.2Gy. Fitting these data to a probit dose-response model enabled risk estimates to be made for these previously unvalidated optic pathway constraints: the Dmax limits of 12Gy in 1 fraction from QUANTEC, 19.5Gy in 3 fractions from Timmerman 2008, and 25Gy in 5 fractions from AAPM Task Group 101 all had less than 1% risk. In 262 patients with perioptic tumors treated with SRS, we found a risk of optic complications of less than 1%. These data support previously unvalidated estimates as safe guidelines, which may in fact underestimate the tolerance of the optic structures, particularly in patients without prior radiation. Further investigation would refine the estimated normal tissue complication probability for SRS near the optic apparatus.
Topics: Dose Fractionation, Radiation; Humans; Models, Theoretical; Radiation Dose Hypofractionation; Radiation Injuries; Radiation Tolerance; Radiosurgery; Radiotherapy Dosage; Visual Pathways
PubMed: 27000505
DOI: 10.1016/j.semradonc.2015.11.008 -
Clinical Oncology (Royal College of... Apr 2021Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of...
AIMS
Preoperative (chemo)radiotherapy followed by total mesorectal excision is the current standard of care for patients with locally advanced rectal cancer. The use of intensity-modulated radiotherapy (IMRT) for rectal cancer is increasing in the UK. However, the extent of IMRT implementation and current practice was not previously known. A national survey was commissioned to investigate the landscape of IMRT use for rectal cancer and to inform the development of national rectal cancer IMRT guidance.
MATERIALS AND METHODS
A web-based survey was developed by the National Rectal Cancer IMRT Guidance working group in collaboration with the Royal College of Radiologists and disseminated to all UK radiotherapy centres. The survey enquired about the implementation of IMRT with a focus on the following aspects of the workflow: dose fractionation schedules and use of a boost; pre-treatment preparation and simulation; target volume/organ at risk definition; treatment planning and treatment verification. A descriptive statistical analysis was carried out.
RESULTS
In total, 44 of 63 centres (70%) responded to the survey; 30/44 (68%) and 36/44 (82%) centres currently use IMRT to treat all patients and selected patients with rectal cancer, respectively. There was general agreement concerning several aspects of the IMRT workflow, including patient positioning, use of intravenous contrast and bladder protocols. Greater variation in practice was identified regarding rectal protocols; use of a boost to primary/nodal disease; target volume delineation; organ at risk delineation and dose constraints and treatment verification. Delineation of individual small bowel loops and daily volumetric treatment verification were considered potentially feasible by most centres.
CONCLUSION
This survey identified that IMRT is already used to treat rectal cancer in many UK radiotherapy centres, but there is heterogeneity between centres in its implementation and practice. These results have been a valuable aid in framing the recommendations within the new National Rectal Cancer IMRT Guidance.
Topics: Dose Fractionation, Radiation; Humans; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; United Kingdom
PubMed: 33423883
DOI: 10.1016/j.clon.2020.12.011 -
Radiotherapy and Oncology : Journal of... Sep 2019The limited radiation tolerance of the small-bowel causes toxicity for patients receiving conventionally-fractionated radiotherapy for rectal cancer. Safe radiotherapy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The limited radiation tolerance of the small-bowel causes toxicity for patients receiving conventionally-fractionated radiotherapy for rectal cancer. Safe radiotherapy dose-escalation will require a better understanding of such toxicity. We conducted a systematic review and meta-analysis using published datasets of small bowel dose-volume and outcomes to analyse the relationship with acute toxicity.
MATERIALS AND METHODS
SCOPUS, EMBASE & MEDLINE were searched to identify twelve publications reporting small-bowel dose-volumes and toxicity data or analysis. Where suitable data were available (mean absolute volume with parametric error measures), fixed-effects inverse-variance meta-analysis was used to compare cohorts of patients according to Grade ≥3 toxicity. For other data, non-parametric examinations of irradiated small-bowel dose-volume and incidence of toxicity were conducted, and a univariate logistic regression model was fitted.
RESULTS
On fixed-effects meta-analysis of three studies (203 patients), each of the dose-volume measures V-V were significantly greater (p < 0.00001) for patients with Grade ≥3 toxicity than for those without. Absolute difference was largest for the lowest dose-volume parameter; however relative difference increases with increasing dose. On logistic regression multiple small-bowel DVH parameters were predictive of toxicity risk (V, V, V - V), with V the strongest (p = 0.004).
CONCLUSIONS
Analysis of published clinical cohort dose-volume data provides evidence for a significant dose-volume-toxicity response effect for a wide range of clinically-relevant doses in the treatment of rectal cancer. Both low dose and high dose are shown to predict toxicity risk, which has important implications for radiotherapy planning and consideration of dose escalation for these patients.
Topics: Dose Fractionation, Radiation; Humans; Intestine, Small; Radiotherapy; Radiotherapy Dosage; Rectal Neoplasms
PubMed: 31136961
DOI: 10.1016/j.radonc.2019.05.001 -
Pediatric Blood & Cancer May 2023Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which... (Review)
Review
BACKGROUND
Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which has led to variations in constraints over the years. In this study, we identify these variations in dose constraints within pediatric trials both in the United States and in Europe used in the past 30 years.
PROCEDURE
All pediatric trials from the Children's Oncology Group website were queried from inception until January 2022 and a sampling of European studies was included. Dose constraints were identified and built into an organ-based interactive web application with filters to display data by organs at risk (OAR), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US and European trials RESULTS: One hundred five closed trials were included-93 US trials and 12 European trials. Thirty-eight separate OAR were found with high-dose constraint variability. Across all trials, nine organs had greater than 10 different constraints (median 16, range 11-26), including serial organs. When comparing US versus European dose tolerances, the United States constraints were higher for seven OAR, lower for one, and identical for five. No OAR had constraints change systematically over the last 30 years.
CONCLUSION
Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OAR. Continued efforts focused on standardization of OAR dose constraints and risk profiles are essential to increase consistency of protocol outcomes and ultimately to reduce radiation toxicities in the pediatric population.
Topics: Humans; Child; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Organs at Risk; Dose Fractionation, Radiation; Radiation Injuries
PubMed: 36880707
DOI: 10.1002/pbc.30270