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Critical Reviews in Oncology/hematology Feb 2010The simultaneous integrated boost (SIB)-IMRT technique allows the simultaneous delivery of different dose levels to different target volumes within a single treatment... (Review)
Review
The simultaneous integrated boost (SIB)-IMRT technique allows the simultaneous delivery of different dose levels to different target volumes within a single treatment fraction. The most significant aspect associated with SIB-IMRT is related to the fractionation strategy, concerning two time-dose parameters: (1) the shortening of the overall treatment time (OTT); (2) the increase of fraction size (FS) to the boost volume. The SIB-IMRT technique represents, therefore, a new way to investigate the accelerated fractionation in definitive treatment of head and neck (H&N) cancers. The aims of this paper are the following: (1) to briefly review the influence of OTT and FS on H&N tumors and on acutely and late responding normal tissues; (2) to review the results of clinical studies of accelerated radiotherapy not employing IMRT in H&N cancer; (3) to review the clinical experiences of the SIB-IMRT technique and to compare the different SIB regimes in terms of radiobiological efficacy.
Topics: Animals; Carcinoma; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Head and Neck Neoplasms; Humans; Radiobiology; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Relative Biological Effectiveness; Time Factors
PubMed: 19409808
DOI: 10.1016/j.critrevonc.2009.03.003 -
Journal of Neuro-oncology Sep 2022Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the...
OBJECTIVE
Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the GKI stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control and adverse radiation effect (ARE) outcomes following 5 fraction GKI-HSRS for intact brain metastases.
METHODS
Patients with intact brain metastases treated with 5-fraction GKI-HSRS were retrospectively reviewed. Survival, local control, and adverse radiation effect rates were determined. Univariable and multivariable regression (MVA) were performed on potential predictive factors.
RESULTS
Two hundred and ninety-nine metastases in 146 patients were identified. The median clinical follow-up was 10.7 months (range 0.5-47.6). The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5) in 5 daily fractions and 52% (range, 45-93), respectively. The median overall survival (OS) was 12.7 months, and the 1-year local failure rate was 15.2%. MVA identified a total dose of 27.5 Gy vs. ≤ 25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥ 4.5 cc (HR 7.29, p < 0.001) as a significant predictor of symptomatic ARE.
CONCLUSION
Moderate total doses in 5 daily fractions of GKI-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE.
Topics: Biological Products; Brain Neoplasms; Dose Fractionation, Radiation; Humans; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 35999435
DOI: 10.1007/s11060-022-04115-3 -
International Journal of Radiation... Jan 1998The influence of treatment parameters, such as (a) fraction size and (b) average and maximum dose (as derived from three-dimensional (3D) distributions), on the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
PURPOSE
The influence of treatment parameters, such as (a) fraction size and (b) average and maximum dose (as derived from three-dimensional (3D) distributions), on the incidence of pericarditis was analyzed. To understand and predict the dose and volume effect on the pericardium, a normal tissue-complication probability model was tested with these complication data.
METHODS AND MATERIALS
Patients (n = 57) entered in 3 consecutive University of Michigan protocols of combined modality for treatment of localized esophageal carcinoma, and having 3D treatment planning for radiation therapy were the subject of this study. Univariate and multivariate analyses were performed to determine the significance of the effect of fraction size and dose parameters on the development of any grade of pericarditis. Dose distributions were corrected for the biological effect of fraction size using the linear-quadratic method. Normal tissue complication probability (NTCP) was calculated with the Lyman model.
RESULTS
Nonmalignant pericardial effusions occurred in 5 of the 57 patients; all effusions were in patients who received treatment with 3.5 Gy daily fractions. On multivariate analysis, no dose factor except fraction size predicted pericarditis, until the dose distributions were corrected for the effect of fraction size ("bio"-dose). Then, both "bio-average" and "bio-maximum" dose were significant predictive factors (p = 0.014). NTCPs for the patients with pericarditis range from 62% to 99% for the calculations with the "bio"-dose distributions vs. 0.5% to 27% for the uncorrected distributions.
DISCUSSION
A normal tissue complication probability (NTCP) model predicts a trend towards a high incidence of radiation pericarditis for patients who have high complication probabilities. It is important to correct the dose distribution for the effects of fractionation, particularly when the fraction size deviates greatly from standard (2.0 Gy) fractionation.
Topics: Adenocarcinoma; Analysis of Variance; Clinical Protocols; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Esophageal Neoplasms; Humans; Incidence; Pericardial Effusion; Probability
PubMed: 9422572
DOI: 10.1016/s0360-3016(97)00584-1 -
Cancer Radiotherapie : Journal de La... Jun 2005Gliomas are the most frequent tumors of the central nervous system of the adult. These intraparenchymal tumors are infiltrative and the most important criterion for... (Review)
Review
Gliomas are the most frequent tumors of the central nervous system of the adult. These intraparenchymal tumors are infiltrative and the most important criterion for definition of GTV and CTV is the extent of infiltration. Delineation of GTV and CTV for untreated and resected glioma remains a controversial and difficult issue because of the discrepancy between real tumor invasion and that estimated by CT or MRI. Is particularly helpful a joint analysis of the four different methods as histopathological correlations with CT and MRI, use of new modality imaging, pattern of relapses after treatment and interobserver studies. The presence of isolated tumor cells in intact brain, oedema or adjacent structures requires the definition of two different options for CTV: i) a geometrical option with GTV defined as the tumor mass revealed by the contrast-enhanced zone on CT or MRI and a CTV with an expanded margin of 2 or 3 cm; ii) an anatomic option including the entire zone of oedema or isolated tumor cell infiltration extending at least as far as the limits of the hyperintense zone on T2-weighted MRI. Inclusion of adjacent structures (such as white matter, corpus callosum, subarachnoid spaces) in the CTV mainly depends on the site of the tumor and size of the volume is generally enlarged.
Topics: Brain Neoplasms; Dose Fractionation, Radiation; Glioma; Humans; Magnetic Resonance Imaging; Patient Care Planning; Tomography, X-Ray Computed
PubMed: 15975842
DOI: 10.1016/j.canrad.2005.04.002 -
Medical Physics Nov 2015Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the...
PURPOSE
Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose-volume histograms for tumor and normal tissues of organs around the tumor.
METHODS
Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose-volume histogram.
RESULTS
It was found that the optimization of fractionation scheme incorporating the dose-volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8-32 fractions with a daily dose of 2.2-6.3 Gy.
CONCLUSIONS
It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose-volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.
Topics: Algorithms; Computer Simulation; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Humans; Models, Biological; Models, Statistical; Neoplasms; Organ Sparing Treatments; Organs at Risk; Radiotherapy Planning, Computer-Assisted; Reproducibility of Results; Sensitivity and Specificity
PubMed: 26520713
DOI: 10.1118/1.4931969 -
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 -
Harefuah May 2016The article by Dr. Cohen-Inbar published in this issue of Harefuah is a timely review that brings to the general medical community the recent important developments in...
The article by Dr. Cohen-Inbar published in this issue of Harefuah is a timely review that brings to the general medical community the recent important developments in the field of radiosurgery--the evolution of multi-session radiosurgery [or "FSR", standing for Fractionated Stereotactic Radiation]. Radiosurgery and FSR continue to have a tremendous impact on modern neurosurgery. Sharing sub-millimetric accuracy in radiation delivery made possible by real-time-imaging positioning, frameless single and multisession radiosurgery have become two faces of a therapeutic technique with wide application in the field of intracranial pathology. Blending dose fractionation with delivery precision, FSR is a hybrid tool that can be implemented safely and effectively for practically any intra-cranial pathology without restrictions of volume or location. Dr. Cohen Inbar reviews the available data regarding doses, fractionation schemes, and results for the different pathologies in which FSR is being increasingly applied. FSR, as single-dose radiosurgery since the late 1980s, has changed the practice of neurosurgery. Radical microsorgical tumor removal at any cost in demanding intracranial locations has been replaced by upfront conservative volume-reduction surgery, leaving the more complicated part of those tumors to safer elimination by precise irradiation in single or multiple sessions. In Israel, further to the first unit operative since 1993 at the Sheba Medical Center, 3 new active LINAC based treatment sites have been added in recent years, with facilities either planned or under construction in the remaining major medical centers with neurosurgical and radiotherapy resources. They are evidence of the central role this modality has captured in the management of intracranial pathology.
Topics: Brain Neoplasms; Dose Fractionation, Radiation; Humans; Israel; Neurosurgery; Radiosurgery
PubMed: 27526561
DOI: No ID Found -
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 -
International Journal of Radiation... Apr 2000The treatment of thoracic malignancies is frequently limited by the 'tolerance' of normal lung tissue. In order to learn more about the factors that influence lung... (Review)
Review
PURPOSE
The treatment of thoracic malignancies is frequently limited by the 'tolerance' of normal lung tissue. In order to learn more about the factors that influence lung tolerance an animal model that closely mimics the clinical exposure situation is required. The lungs of pigs are similar to those of man in a variety of ways and the animal's size permits the irradiation of partial tissue volumes comparable with those used clinically; very rarely in man is the whole lung irradiated. In this report, the available data for the effects of irradiation on pig lung are reviewed as they relate to the key issues in radiotherapy.
RESULTS
The dose-effect relationships for exposure to single doses indicate that for a significant impairment in both early and late lung function and for the histological detection of fibrosis, the dose-related changes in pig and man are similar. Studies with dose-fractionation using X-rays indicate a large dependence of the iso-effective dose on fraction number and fraction size, and the parameters obtained were not significantly influenced by the time of assessment after irradiation. A simple power-law function fitted the whole data set better than the linear-quadratic model, with a fraction number exponent (N) of 0.44+/-0.06 for treatments given in 1-30 fractions. The alpha/beta values ranged from 0.6 to 4.86 Gy, tending to increase with the length of the follow-up period; however; the majority of these alpha/beta values were not significantly different from zero at the 5% level. Studies of the effect of changes in the volume of lung tissue irradiated indicated the need for care in the use of the terms 'tolerance' and 'iso-effective' dose. Doses that were iso-effective for the severity of regional damage were not matched by those for total lung function. The same level of damage in a small volume compared with a large volume had less effect, i.e. was better tolerated in terms of changes in total lung function.
CONCLUSION
Iso-effective doses in pig and humans are lower than those for the more common laboratory animal species. This observation may be related to the differences in anatomical structure of the lungs in the different species.
Topics: Animals; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Fast Neutrons; Lung; Radiation Tolerance; Swine; Time Factors
PubMed: 10815623
DOI: 10.1080/095530000138439 -
Radiation Oncology (London, England) Jan 2017Intraoperative radiotherapy differs from conventional, fractionated radiotherapy in several aspects that may influence its biological effect. The radiation quality... (Review)
Review
Intraoperative radiotherapy differs from conventional, fractionated radiotherapy in several aspects that may influence its biological effect. The radiation quality influences the relative biologic effectiveness (RBE), and the role of the five R's of radiotherapy (reassortment, repair, reoxygenation, repopulation, radiosensitivity) is different. Furthermore, putative special biological effects and the small volume receiving a high single dose may be important. The present review focuses on RBE, repair, and repopulation, and gives an overview of the other factors that potentially contribute to the efficacy. The increased RBE should be taken into account for low-energy X-rays while evidence of RBE < 1 for high-energy electrons at higher doses is presented. Various evidence supports a hypothesis that saturation of the primary DNA double-strand break (DSB) repair mechanisms leads to increasing use of an error-prone backup repair system leading to genomic instability that may contribute to inactivate tumour cells at high single doses. Furthermore, the elimination of repopulation of residual tumour cells in the tumour bed implies that some patients are likely to have very few residual tumour cells which may be cured even by low doses to the tumour bed. The highly localised dose distribution of IORT has the potential to inactivate tumour cells while sparing normal tissue by minimising the volume exposed to high doses. Whether special effects of high single doses also contribute to the efficacy will require further experimental and clinical studies.
Topics: Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Humans; Intraoperative Period; Neoplasms; Relative Biological Effectiveness
PubMed: 28107823
DOI: 10.1186/s13014-016-0750-3