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Journal of Chromatographic Science Jul 2006Analytical microextractions, defined as nonexhaustive sample preparation with a very small volume of extracting phase (microliter range or smaller) relative to the... (Review)
Review
Analytical microextractions, defined as nonexhaustive sample preparation with a very small volume of extracting phase (microliter range or smaller) relative to the sample volume, represent an important development in the field of analytical chemistry. Analytes are extracted by a small volume of a solid or semi-solid polymeric material, as in solid-phase microextraction (SPME), or alternatively by a small volume of a liquid, as in liquid-phase microextraction (LPME). This paper gives an overview of the SPME and LPME techniques and discusses future trends. This includes a discussion of the different extraction formats available, commercial equipment, method transfer from traditional sample preparation methods to microextraction, and performance as well as robustness for the latter type of systems. In addition, the paper contains a unified approach to the understanding of extraction thermodynamics and kinetics applicable to both SPME and LPME.
Topics: Chemical Fractionation; Forecasting; Microchemistry; Solid Phase Microextraction
PubMed: 16884584
DOI: 10.1093/chromsci/44.6.291 -
Cancer Radiotherapie : Journal de La... Oct 2001Bone is one of the three most favored sites of solid tumor metastasis. Skeletal metastasis may be identified by four clinical imaging methods: plain film radiography,... (Review)
Review
Bone is one of the three most favored sites of solid tumor metastasis. Skeletal metastasis may be identified by four clinical imaging methods: plain film radiography, computed tomography scanning, radioisotope scanning, and magnetic resonance imaging. The dose per fraction, total dose, and anatomic distribution of the radiation (dosimetry) are important factors in determining the efficacy and normal tissue tolerance to radiotherapy. Controversies about fractionation of palliative radiotherapy for bone metastasis are steel ongoing. The most commonly used schedules are a single treatment of 8 Gy, 30 Gy in 10 fractions and 20 Gy in 5 fractions. Treatment volumes and safety margins depend on the location and the extent of the bone metastasis, and are also determined by the symptoms felt by the patient.
Topics: Bone Neoplasms; Dose Fractionation, Radiation; Humans; Palliative Care; Patient Care Planning; Radionuclide Imaging; Radiotherapy Dosage
PubMed: 11715322
DOI: 10.1016/s1278-3218(01)00128-7 -
International Journal of Radiation... Apr 2024In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in... (Review)
Review
PURPOSE
In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate and ultrahypofractionated schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at nonirradiated sites, an "abscopal effect." The amplification of antitumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema, and treated RT volumes with ICIs in patients with BC, especially in the era of ultrahypofractionation.
METHODS AND MATERIALS
We conducted a systematic review to delineate the reported treatment details, safety, and efficacy of combining ICI and RT in patients with BC. PubMed, Embase, and Cochrane CENTRAL were searched between 2014 and 2023. Data were extracted to assess the details of ICIs/RT delivery, safety, and efficacy.
RESULTS
Of the 12 eligible studies, 9 involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range, 8-28), and were heterogenous in patient population and reported outcomes. The combination was reported to be safe. We identified 1 study in the perioperative setting, which did a posthoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT.
CONCLUSIONS
In conclusion, there are limited data on the dose, timing, fractionation, and volumes of RT in both the adjuvant and metastatic setting in BC. Ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.
Topics: Humans; Female; Breast Neoplasms; Immunotherapy; Dose Fractionation, Radiation; Tumor Microenvironment
PubMed: 38195030
DOI: 10.1016/j.ijrobp.2024.01.001 -
Journal of Neurosurgery Dec 2012The goal of this study was to develop a technique for performing submillimeter high-precision volume-staged Gamma Knife surgery and investigate its potential benefits in...
OBJECT
The goal of this study was to develop a technique for performing submillimeter high-precision volume-staged Gamma Knife surgery and investigate its potential benefits in comparison with hypofractionated stereotactic radiotherapy (SRT) for treating large arteriovenous malformations (AVMs).
METHODS
The authors analyzed 7 pediatric AVM cases treated with volume-staged stereotactic radiosurgery (SRS) using the Gamma Knife Perfexion at the University of California, San Francisco. The target and normal tissue contours from each case were exported for hypofractionated treatment planning based on the Gamma Knife Extend system or the CyberKnife SRT. Both the Gamma Knife Extend and CyberKnife treatment plans were matched to yield the same level of target coverage (95%-98%) and conformity indices (1.24-1.46). Finally, hypofractionated treatment plans were compared with volume-staged treatment plans for sparing normal brain by using biologically equivalent 12-Gy normal brain volumes.
RESULTS
Hypofractionated Gamma Knife Extend and CyberKnife treatment plans exhibited practically identical sparing of normal brain for the studied cases. However, when matching such values with volume-staged treatments for the biological effective dose, only conservative dose fractionation schemes, such as 27.3 Gy in 5 fractions and 25 Gy in 4 fractions, were found to be comparable to the volume-staged treatments. On average, this represents a mean 18.7% ± 7.3% reduction in the single-fraction biologically equivalent dose for hypofractionated treatments versus the reference volume-staged treatments (p < 0.001).
CONCLUSIONS
Volume staging remains advantageous over hypofractionation in delivering a higher dose to the target and for better sparing of normal brain tissue in the treatment of large AVMs. More clinical data are needed, however, to justify the clinical superiority of this increased dose when compared with a hypofractionated treatment regimen.
Topics: Brain; Child; Dose Fractionation, Radiation; Humans; Intracranial Arteriovenous Malformations; Magnetic Resonance Imaging; Radiosurgery; Treatment Outcome
PubMed: 23205798
DOI: 10.3171/2012.7.GKS121023 -
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 -
BioMed Research International 2013According to Leksell radiosurgery is defined as "the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the... (Review)
Review
According to Leksell radiosurgery is defined as "the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the intact skull." Before its birth in the early 60s and its introduction in clinical therapeutic protocols in late the 80s dose application in radiation therapy of the brain for benign and malignant lesions was based on the administration of cumulative dose into a variable number of fractions. The rationale of dose fractionation is to lessen the risk of injury of normal tissue surrounding the target volume. Radiobiological studies of cell culture lines of malignant tumors and clinical experience with patients treated with conventional fractionated radiotherapy helped establishing this radiobiological principle. Radiosurgery provides a single high dose of radiation which translates into a specific toxic radiobiological response. Radiobiological investigations to study the effect of high dose focused radiation on the central nervous system began in late the 50s. It is well known currently that radiobiological principles applied for dose fractionation are not reproducible when single high dose of ionizing radiation is delivered. A review of the literature about radiobiology of radiosurgery for the central nervous system is presented.
Topics: Central Nervous System; Dose Fractionation, Radiation; Humans; Models, Theoretical; Radiobiology; Radiosurgery
PubMed: 24490157
DOI: 10.1155/2013/362761 -
Seminars in Radiation Oncology Apr 2016Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we... (Review)
Review
Inconsistencies permeate the literature regarding small bowel dose tolerance limits for stereotactic body radiation therapy (SBRT) treatments. In this review, we organized these diverse published limits with MD Anderson at Cooper data into a unified framework, constructing the dose-volume histogram (DVH) Risk Map, demonstrating low-risk and high-risk SBRT dose tolerance limits for small bowel. Statistical models of clinical data from 2 institutions were used to assess the safety spectrum of doses used in the exposure of the gastrointestinal tract in SBRT; 30% of the analyzed cases had vascular endothelial growth factor inhibitors (VEGFI) or other biological agents within 2 years before or after SBRT. For every dose tolerance limit in the DVH Risk Map, the probit dose-response model was used to estimate the risk level from our clinical data. Using the current literature, 21Gy to 5cc of small bowel in 3 fractions has low toxicity and is reasonably safe, with 6.5% estimated risk of grade 3 or higher complications, per Common Terminology Criteria for Adverse Events version 4.0. In the same fractionation for the same volume, if lower risk is required, 16.2Gy has an estimated risk of only 2.5%. Other volumes and fractionations are also reviewed; for all analyzed high-risk small bowel limits, the risk is 8.2% or less, and the low-risk limits have 4% or lower estimated risk. The results support current clinical practice, with some possibility for dose escalation.
Topics: Dose Fractionation, Radiation; Humans; Intestine, Small; Radiation Injuries; Radiation Tolerance; Radiosurgery
PubMed: 27000513
DOI: 10.1016/j.semradonc.2015.11.009 -
Radiotherapy and Oncology : Journal of... Jul 2018Proton treatment slots are a limited resource. Therefore, we consider combined proton-photon treatments in which most fractions are delivered with photons and only a few...
PURPOSE
Proton treatment slots are a limited resource. Therefore, we consider combined proton-photon treatments in which most fractions are delivered with photons and only a few with protons. We demonstrate how both modalities can be combined to optimally capitalize on the proton's ability to reduce normal tissue dose.
METHODS
An optimal combined treatment must account for fractionation effects. We therefore perform simultaneous optimization of intensity-modulated proton (IMPT) and photon (IMRT) plans based on their cumulative biologically effective dose (BED). We demonstrate the method for a sacral chordoma patient, in whom the gross tumor volume (GTV) abuts bowel and rectum.
RESULTS
In an optimal combination, proton and photon fractions deliver similar doses to bowel and rectum to protect these dose-limiting normal tissues through fractionation. However, proton fractions deliver, on average, higher doses to the GTV. Thereby, the photon dose bath is reduced. An optimized 30-fraction treatment with 10 IMPT fractions achieved more than 50% of the integral dose reduction in the gastrointestinal tract that is possible with 30 IMPT fractions (compared to 33% for a simple proton-photon combination in which both modalities deliver the same target dose).
CONCLUSIONS
A limited number of proton fractions can best be used if protons hypofractionate parts of the GTV while maintaining near-uniform fractionation in dose-limiting normal tissues.
Topics: Bone Neoplasms; Chordoma; Combined Modality Therapy; Dose Fractionation, Radiation; Humans; Neoplasms; Photons; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Rectum; Sacrum
PubMed: 29370987
DOI: 10.1016/j.radonc.2017.12.031 -
Acta Oncologica (Stockholm, Sweden) 2000Both conformal and intensity-modulated radiation therapy have great potential to further increase tumor control rates and decrease morbidity. A homogeneous escalation of... (Review)
Review
Both conformal and intensity-modulated radiation therapy have great potential to further increase tumor control rates and decrease morbidity. A homogeneous escalation of 'biological' dose within a tumor should increase the likelihood of local cure, especially within the mid-range (e.g. 15% to 80%) of tumor control rates, and conversely, a lower control rate should follow a homogeneously reduced dose. However, when the dose to critical normal tissues is tightly constrained, the dose distributions within the treatment volume may necessarily be heterogeneous, and the effect on tumor control probability will depend upon the magnitude of over- or underdosage, and on the proportions of the tumor clonogen population receiving higher or lower than the nominal dose. Dose-volume histograms provide a measure of heterogeneity of dose within the planned treatment volume, but tumor control probability is also influenced by other variables, e.g. inherent tumor clonogen radiosensitivity and growth rates during a course of treatment, alpha/beta ratios, oxygenation and clonogen density throughout the target volume. Heterogeneity in these factors introduces heterogeneity in tumor responses and a less steep change in tumor control probability with change in dose, reducing the gains or losses that would be predicted to result from heterogeneity of dose. Similarly, modeling the effect of inhomogeneous dose distributions on estimates of probability of complications in normal tissues is hindered by uncertainty of estimates for alpha/beta ratios, especially for late-responding tissues, and lack of data on volume effects. Although the effects of dose inhomogeneity cannot be presented with sufficiently reliable quantitation to be directly applicable to dose prescriptions in radiation therapy, the relative influences of heterogeneities in dose and volume can be modeled to provide a framework for clinical decision-making. The magnitude of a dose reduction is the major determinant of decline in tumor control probability. A large dose reduction to even a small volume of tumor can profoundly decrease tumor control probability. Conversely, the most rapid improvement in tumor control probability occurs the closer to 100% the amount of tumor exposed to an increased dose. Escalation of dose is of little value unless it is distributed through most of the tumor: even very large increases in dose to small volumes are of little benefit.
Topics: Dose Fractionation, Radiation; Humans; Neoplasms; Oxygen; Radiotherapy, Conformal
PubMed: 11093365
DOI: 10.1080/028418600750013258 -
Radiotherapy and Oncology : Journal of... Jan 2020To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI...
OBJECTIVE
To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI guidance.
MATERIAL AND METHODS
For 15 patients (18 lesions) receiving fSRS only (fSRS) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRS), a treatment planning MRI (MR0) and repeated MRI during treatment (MR1) were acquired. The impact of target volume changes on the target coverage was analyzed by evaluating the planned dose distribution (based on MR0) on the planning target volume (PTV) during treatment as defined on MR1. The predictive value of target volume changes before treatment (using the diagnostic MRI (MRD)) was studied to identify patients that experienced the largest changes during treatment.
RESULTS
Target volume changes during fSRS did result in large declines of the PTV dose coverage up to -34.8% (median = 3.2%) for fSRS patients. For fSRS the variation and declines were smaller (median PTV dose coverage change = -0.5% (-4.5% to 1.9%)). Target volumes changes did also impact the minimum dose in the PTV (fSRS; -2.7 Gy (-16.5 to 2.3 Gy), fSRS; -0.4 Gy (-4.2 to 2.5 Gy)). Changes in target volume before treatment (i.e. seen between the MRD and MR0) predicted which patients experienced the largest dose coverage declines during treatment.
CONCLUSION
Target volume changes in brain metastases during fSRS can result in worsening of the target dose coverage. Patients benefiting the most from a repeated MRI during treatment could be identified before treatment.
Topics: Aged; Aged, 80 and over; Brain Neoplasms; Dose Fractionation, Radiation; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Radiosurgery; Radiotherapy Planning, Computer-Assisted
PubMed: 31431379
DOI: 10.1016/j.radonc.2019.07.011