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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 -
Lung Cancer (Amsterdam, Netherlands) Jun 2002Large radiation fractions are an effective way of killing tumour cells but have generally been avoided in curative treatment of patients because of concerns of a... (Review)
Review
Large radiation fractions are an effective way of killing tumour cells but have generally been avoided in curative treatment of patients because of concerns of a disproportionate increase in late normal tissue toxicity. Radiobiological modelling of the effect of radiation on lung tumours and late-reacting normal tissues, which are more sensitive to large radiation fractions, has been undertaken. The biological effect of radiation on tumours is increased as the overall treatment time is shortened but this is not true for late-reacting normal tissue. Sample data are shown in which the relative increases in radiation effect on the tumour and late-reacting normal tissues are similar after hypofractionation. A favourable therapeutic ratio can be achieved because the bulk of normal tissue will receive a lower dose of radiation at a lower dose per fraction than the tumour, especially with current techniques where the volume of normal tissue irradiated can be sharply reduced. The clinical evidence confirms that lung toxicity is volume-dependent. It is the small Stage I and II tumours which are most likely to benefit from hypofractionated regimens, as the volumes to be treated are smaller and they have a lower incidence of distant metastases. Patients with Stage III tumours with favourable prognostic factors are nowadays treated with combined chemotherapy and radiotherapy and so for this group more conservative hypofractionation regimens are being explored. However, more advanced tumours may be treated with hypofractionation to lower total doses to achieve palliation and a modest degree of survival benefit.
Topics: Carcinoma, Non-Small-Cell Lung; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Humans; Lung Neoplasms; Radiotherapy Dosage; Radiotherapy, High-Energy; Relative Biological Effectiveness
PubMed: 12009230
DOI: 10.1016/s0169-5002(02)00020-x -
Journal of Chromatography. A Jun 2007Stir bar sorptive extraction (SBSE) was introduced in 1999 as a solventless sample preparation method for the extraction and enrichment of organic compounds from aqueous... (Review)
Review
Stir bar sorptive extraction (SBSE) was introduced in 1999 as a solventless sample preparation method for the extraction and enrichment of organic compounds from aqueous matrices. The method is based on sorptive extraction, whereby the solutes are extracted into a polymer coating on a magnetic stirring rod. The extraction is controlled by the partitioning coefficient of the solutes between the polymer coating and the sample matrix and by the phase ratio between the polymer coating and the sample volume. For a polydimethylsiloxane coating and aqueous samples, this partitioning coefficient resembles the octanol-water partitioning coefficient. In comparison to solid phase micro-extraction, a larger amount of sorptive extraction phase is used and consequently extremely high sensitivities can be obtained as illustrated by several successful applications in trace analysis in environmental, food and biomedical fields. Initially SBSE was mostly used for the extraction of compounds from aqueous matrices. The technique has also been applied in headspace mode for liquid and solid samples and in passive air sampling mode. In this review article, the principles of stir bar sorptive extraction are described and an overview of SBSE applications is given.
Topics: Adsorption; Chemical Fractionation; Chlorophenols; Dimethylpolysiloxanes; Environmental Pollutants; Food Analysis; Silicones; Solid Phase Microextraction; Water Pollutants, Chemical
PubMed: 17239895
DOI: 10.1016/j.chroma.2007.01.032 -
Seminars in Radiation Oncology Jan 2020Fundamentals in radiobiology commonly known as the '4R's' concept (ie, reoxygenation, repair, redistribution, and repopulation) have mostly been investigated for... (Review)
Review
Fundamentals in radiobiology commonly known as the '4R's' concept (ie, reoxygenation, repair, redistribution, and repopulation) have mostly been investigated for external beam radiotherapy. However, these fundamentals can be applied to brachytherapy (BT) by accounting for differences in dose rate, fractionation, and response to immunologic agents for this treatment modality. Many improvements have been achieved in the era of dosimetric optimization but still limited data are available regarding radiobiological opportunities for BT. As BT is characterized by a large degree of dose heterogeneity, a wide range of dose rates and fractionations exist within the implanted volume. Calculations based on the linear quadratic model can be used to estimate the dose-response equivalence between various BT modalities. Such models are helpful in daily practice and open possibilities in terms of radiobiological optimization. However, some limitations should be highlighted in terms of the applicability of the linear quadratic model. Furthermore, in vitro models do not account for the complex interplay between the tumor and its microenvironment, including vascularization and/or immune response. Recently, an improved understanding of the tumor's microenvironment has led to investigations of immunomodulatory agents in combination with radiotherapy. BT is a promising candidate to enhance the immunogenic response with concomitant immunotherapy. This review summarizes some of the main mechanisms involved in tissue response to BT. Preclinical data, clinical evidence, as well as novel approaches to radiobiology are highlighted.
Topics: Brachytherapy; Combined Modality Therapy; Dose Fractionation, Radiation; Humans; Immunomodulation; Models, Biological; Neoplasms; Radiobiology; Radiometry; Radiotherapy Dosage; Tumor Microenvironment
PubMed: 31727299
DOI: 10.1016/j.semradonc.2019.08.009 -
Bioanalysis Apr 2011Bioanalysis usually requires a preparation procedure for sample cleanup or preconcentration. Conventional sample preparation techniques are often time consuming and... (Review)
Review
Bioanalysis usually requires a preparation procedure for sample cleanup or preconcentration. Conventional sample preparation techniques are often time consuming and labor intensive. Among recent progress in sample preparation, single drop microextraction (SDME) is one of the most efficient techniques providing both sample cleanup and preconcentration capabilities. In SDME, analytes are extracted from a sample solution into an acceptor drop and the drop is introduced to subsequent analysis. Since the volume of the acceptor drop is 1-10 µl or less, the consumption of solvents can be minimized and the preconcentration effect is enhanced. In this review, the basic principles of two-phase and three-phase SDME are described briefly and then recently developed modes of SDME, coupling with analytical instruments, and methods to enhance the drop stability are discussed. Recent applications of SDME to biological samples, including urine, blood and saliva, for the analysis of drugs, metal ions and biomarkers are reviewed.
Topics: Analytic Sample Preparation Methods; Biopharmaceutics; Chemical Fractionation; Chromatography, High Pressure Liquid
PubMed: 21452996
DOI: 10.4155/bio.11.3 -
Radiotherapy and Oncology : Journal of... Aug 2022The effects of radiation on the heart are dependent on dose, fractionation, overall treatment time, and pre-existing cardiovascular pathology. Murine models have played... (Review)
Review
BACKGROUND AND PURPOSE
The effects of radiation on the heart are dependent on dose, fractionation, overall treatment time, and pre-existing cardiovascular pathology. Murine models have played a central role in improving our understanding of the radiation response of the heart yet a wide range of exposure parameters have been used. We evaluated the study design of published murine cardiac irradiation experiments to assess gaps in the literature and to suggest guidance for the harmonisation of future study reporting.
METHODS AND MATERIALS
A systematic review of mouse/rat studies published 1981-2021 that examined the effect of radiation on the heart was performed. The protocol was published on PROSPERO (CRD42021238921) and the findings were reported in accordance with the PRISMA guidance. Risk of bias was assessed using the SYRCLE checklist.
RESULTS
159 relevant full-text original articles were reviewed. The heart only was the target volume in 67% of the studies and simulation details were unavailable for 44% studies. Dosimetry methods were reported in 31% studies. The pulmonary effects of whole and partial heart irradiation were reported in 13% studies. Seventy-eight unique dose-fractionation schedules were evaluated. Large heterogeneity was observed in the endpoints measured, and the reporting standards were highly variable.
CONCLUSIONS
Current murine models of radiation cardiotoxicity cover a wide range of irradiation configurations and latency periods. There is a lack of evidence describing clinically relevant dose-fractionations, circulating biomarkers and radioprotectants. Recommendations for the consistent reporting of methods and results of in vivo cardiac irradiation studies are made to increase their suitability for informing the design of clinical studies.
Topics: Animals; Cardiotoxicity; Disease Models, Animal; Dose Fractionation, Radiation; Heart; Mice; Radiometry; Rats
PubMed: 35533784
DOI: 10.1016/j.radonc.2022.04.030 -
Journal of Neuro-oncology Oct 2019The optimal interfraction intervals for fractionated radiosurgery has yet to be established. We investigated the outcome of fractionated gamma knife radiosurgery (FGKRS)... (Clinical Trial)
Clinical Trial
PURPOSE
The optimal interfraction intervals for fractionated radiosurgery has yet to be established. We investigated the outcome of fractionated gamma knife radiosurgery (FGKRS) for large brain metastases (BMs) according to different interfraction intervals.
METHODS
Between September 2016 and May 2018, a total of 45 patients who underwent FGKRS for BMs were enrolled in this study. They were divided into two groups (standard fractionation over 3 consecutive days with a 24-h interfraction interval versus prolonged fractionation over 4 or 5 days with an interfraction interval of at least 48-h). BMs with ≥ 2 cm in maximum diameter or ≥ 5 cm in volume were included in analysis.
RESULTS
Among 52 BMs treated with 3-fraction GKRS, 25 (48.1%) were treated with standard fractionation scheme, and 27 (51.9%) with prolonged fractionation scheme. The median follow-up period was 10.5 months (range 5-25). Local tumor control rates of the standard group were 88.9% at 6 months and 77.8% at 12 months, whereas those of the prolonged group were 100% at 6 and 12 months (p = 0.023, log-rank test). In multivariate analysis, fractionation scheme (hazard ratio [HR] 0.294, 95% CI 0.099-0.873; p = 0.027) and tumor volume (HR 0.200, 95% CI 0.051-0.781; p = 0.021) were revealed as the only significant factors affecting the local tumor control after 3-fraction GKRS.
CONCLUSIONS
Our preliminary tumor control results suggest a promising role of 3-fraction GKRS with an interfraction interval of at least 48-h. This fractionation regimen could be an effective and safe treatment option in the management of large BMs.
Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Dose Fractionation, Radiation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome; Tumor Burden; Young Adult
PubMed: 31446529
DOI: 10.1007/s11060-019-03267-z -
Neurosurgical Review Apr 2009The optimal management of craniopharyngiomas remains controversial. The first-line treatment usually consists of surgical resection. Complete tumor removal provides a... (Review)
Review
The optimal management of craniopharyngiomas remains controversial. The first-line treatment usually consists of surgical resection. Complete tumor removal provides a high rate of long-term control; however, aggressive surgery is associated with significant incidence of complications. Radiotherapy (RT) is currently used in patients after limited surgery and achieves excellent long-term tumor control. Stereotactic radiotherapy, both in the form of radiosurgery (RS) or fractionated stereotactic radiotherapy (FSRT), has been developed as a more accurate technique of irradiation with more precise tumor localization and consequently a reduction in the volume of normal brain irradiated to high radiation doses. We provide a review of published data on outcome of conventional fractionated RT and modern radiation techniques. FSRT is a suitable treatment technique for all sizes of craniopharyngiomas, and efficacy is comparable to conventional RT. Single-fraction stereotactic radiosurgery is usually delivered to small tumors away from critical structures. Longer follow-up is necessary to confirm the excellent tumor control and the potential reduction of long-term radiation toxicity.
Topics: Craniopharyngioma; Dose Fractionation, Radiation; Humans; Pituitary Neoplasms; Radiosurgery; Time Factors; Treatment Outcome
PubMed: 19165514
DOI: 10.1007/s10143-009-0186-4 -
Rays 2005Clinical radiobiology is concerned with the relationship between a given radiation dose and the resulting biological effect on tumors and normal tissues, as well as with... (Review)
Review
Clinical radiobiology is concerned with the relationship between a given radiation dose and the resulting biological effect on tumors and normal tissues, as well as with all confounding factors related to the delivery of radiation (e.g. dose per fraction, overall treatment time, volume of tumor/normal tissue irradiated, concomitant use of chemotherapy) and/or associated with preexisting conditions of the host (e.g. diabetes, hypertension, genetic syndromes) that may influence this relationship. This article briefly reviews few of the concepts associated with the dose-effect relationships in both normal tissues and tumors of the head and neck area and presents an operational way to integrate all these concepts into the routine radiotherapy planning processes.
Topics: Comorbidity; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Head and Neck Neoplasms; Humans; Probability; Radiation Tolerance; Radiotherapy Dosage; Radiotherapy, Conformal
PubMed: 16294902
DOI: No ID Found -
Radiotherapy and Oncology : Journal of... Sep 2023Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause anti-tumour activity. The current study investigates whether CP-506 improves outcome of radiotherapy in vivo.
MATERIALS AND METHODS
Mice bearing FaDu and UT-SCC-5 xenografts were randomized to receive 5 daily injections of CP-506/vehicle followed by single dose (SD) irradiation. In addition, CP-506 was combined once per week with fractionated irradiation (30 fractions/6 weeks). Animals were followed-up to score all recurrences. In parallel, tumours were harvested to evaluate pimonidazole hypoxia, DNA damage (γH2AX), expression of oxidoreductases.
RESULTS
CP-506 treatment significantly increased local control rate after SD in FaDu, 62% vs. 27% (p = 0.024). In UT-SCC-5, this effect was not curative and only marginally significant. CP-506 induced significant DNA damage in FaDu (p = 0.009) but not in UT- SCC-5. Hypoxic volume (HV) was significantly smaller (p = 0.038) after pretreatment with CP-506 as compared to vehicle in FaDu but not in less responsive UT-SCC-5. Adding CP-506 to fractionated radiotherapy in FaDu did not result in significant benefit.
CONCLUSION
The results support the use of CP-506 in combination with radiation in particular using hypofractionation schedules in hypoxic tumours. The magnitude of effect depends on the tumour model, therefore it is expected that applying appropriate patient stratification strategy will further enhance the benefit of CP-506 treatment for cancer patients. A phase I-IIA clinical trial of CP-506 in monotherapy or in combination with carboplatin or a checkpoint inhibitor has been approved (NCT04954599).
Topics: Humans; Animals; Mice; Carcinoma, Squamous Cell; Prodrugs; Dose Fractionation, Radiation; Hypoxia; Probability
PubMed: 37315579
DOI: 10.1016/j.radonc.2023.109738