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Radiation Oncology (London, England) Dec 2011Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and... (Review)
Review
Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques.
Topics: Acromegaly; Adenoma; Dose Fractionation, Radiation; Humans; Hypopituitarism; Pituitary Neoplasms; Radiotherapy
PubMed: 22136376
DOI: 10.1186/1748-717X-6-167 -
International Journal of Radiation... Jul 2018Radiation therapy is a core modality of cancer treatment; however, concerns have been expressed regarding its underutilization and its lack of prioritization as a... (Review)
Review
Radiation therapy is a core modality of cancer treatment; however, concerns have been expressed regarding its underutilization and its lack of prioritization as a research domain relative to other cancer treatment modalities, despite its rapid technical evolution. It is therefore important to understand, from a public policy perspective, the evolution of global radiation therapy research, to identify strengths, weaknesses, and opportunities. This study used a bibliometric approach to undertake a quantitative analysis of global radiation therapy research published between 2001 and 2015 and available in the Web of Science (Wos) database, with particular focus on the 25 leading research-active countries. A total of 62,550 radiation therapy research articles from 127 countries, published in 2531 international journals, were analyzed. The United States was responsible for 32.3% of these outputs, followed by Japan (8.0%) and Germany (7.7%). Nearly half of all publications related to preparation and delivery of radiation therapy, combined-modality regimens, and dose fractionation studies. Health services research, palliative care, and quality of life studies represented only 2%, 5%, and 4% of all research outputs, respectively. Countries varied significantly in their commitment to different research domains, and trial-related publications represented only 5.1% of total output. Research impact was analyzed according to 3 different citation scores, with research outputs from Denmark, The Netherlands, and the United States consistently the highest ranked. Globally, radiation therapy publication outputs continue to increase but lag behind other spheres of cancer management. The types of radiation therapy research undertaken appear to be regionally patterned, and there is a clear disconcordance between the volume of research output from individual countries and its citation impact. Greater support for radiation therapy research in low- and middle-income countries is required, including international collaboration. The study findings are expected to provide the requisite knowledge to guide future radiation therapy research programs.
Topics: Bibliometrics; Biomedical Research; Clinical Trials as Topic; Combined Modality Therapy; Developed Countries; Developing Countries; Dose Fractionation, Radiation; Humans; Neoplasms
PubMed: 29976487
DOI: 10.1016/j.ijrobp.2018.03.009 -
Radiation Oncology (London, England) Aug 2021Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological...
BACKGROUND
Multifocal manifestation of high-grade glioma is a rare disease with very unfavourable prognosis. The pathogenesis of multifocal glioma and pathophysiological differences to unifocal glioma are not fully understood. The optimal treatment of patients suffering from multifocal high-grade glioma is not defined in the current guidelines, therefore individual case series may be helpful as guidance for clinical decision-making.
METHODS
Patients with multifocal high-grade glioma treated with conventionally fractionated radiation therapy (RT) in our institution with or without concomitant chemotherapy between April 2011 and April 2019 were retrospectively analysed. Multifocality was neuroradiologically assessed and defined as at least two independent contrast-enhancing foci in the MRI T1 contrast-enhanced sequence. IDH mutational status and MGMT methylation status were assessed from histopathology records. GTV, PTV as well as the V30Gy, V45Gy and D2% volumes of the brain were analysed. Overall and progression-free survival were calculated from the diagnosis until death and from start of radiation therapy until diagnosis of progression of disease in MRI for all patients.
RESULTS
20 multifocal glioma cases (18 IDH wild-type glioblastoma cases, one diffuse astrocytic glioma, IDH wild-type case with molecular features of glioblastoma and one anaplastic astrocytoma, IDH wild-type case) were included into the analysis. Resection was performed in two cases and stereotactic biopsy only in 18 cases before the start of radiation therapy. At the start of radiation therapy patients were 61 years old in median (range 42-84 years). Histopathological examination showed IDH wild-type in all cases and MGMT promotor methylation in 11 cases (55%). Prescription schedules were 60 Gy (2 Gy × 30), 59.4 Gy (1.8 Gy × 33), 55 Gy (2.2 Gy × 25) and 50 Gy (2.5 Gy × 20) in 15, three, one and one cases, respectively. Concomitant temozolomide chemotherapy was applied in 16 cases, combined temozolomide/lomustine chemotherapy was applied in one case and concomitant bevacizumab therapy in one case. Median number of GTVs was three. Median volume of the sum of the GTVs was 26 cm. Median volume of the PTV was 425.7 cm and median PTV to brain ratio 32.8 percent. Median D2% of the brain was 61.5 Gy (range 51.2-62.7) and median V30Gy and V45 of the brain were 59.9 percent (range 33-79.7) and 40.7 percent (range 14.9-64.1), respectively. Median survival was eight months (95% KI 3.6-12.4 months) and median progression free survival after initiation of RT five months (95% CI 2.8-7.2 months). Grade 2 toxicities were detected in eight cases and grade 3 toxicities in four cases consisting of increasing edema in three cases and one new-onset seizure. One grade 4 toxicity was detected, which was febrile neutropenia related to concomitant chemotherapy.
CONCLUSION
Conventionally fractionated RT with concomitant chemotherapy could safely be applied in multifocal high-grade glioma in this case series despite large irradiation treatment fields.
Topics: Adult; Aged; Aged, 80 and over; Brain Neoplasms; Chemoradiotherapy; Dose Fractionation, Radiation; Female; Glioma; Humans; Male; Middle Aged; Radiotherapy; Retrospective Studies
PubMed: 34454558
DOI: 10.1186/s13014-021-01886-3 -
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 -
Clinical Cancer Research : An Official... Feb 2019Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume (RTV),...
PURPOSE
Spatial and temporal patterns of response of human glioblastoma to fractionated chemoradiation are described by changes in the bioscales of residual tumor volume (RTV), tumor cell volume fraction (CVF), and tumor cell kill (TCK), as derived from tissue sodium concentration (TSC) measured by quantitative sodium MRI at 3 Tesla. These near real-time patterns during treatment are compared with overall survival.
EXPERIMENTAL DESIGN
Bioscales were mapped during fractionated chemoradiation therapy in patients with glioblastomas ( = 20) using TSC obtained from serial quantitative sodium MRI at 3 Tesla and a two-compartment model of tissue sodium distribution. The responses of these parameters in newly diagnosed human glioblastomas undergoing treatment were compared with time-to-disease progression and survival.
RESULTS
RTV following tumor resection showed decreased CVF due to disruption of normal cell packing by edema and infiltrating tumor cells. CVF showed either increases back toward normal as infiltrating tumor cells were killed, or decreases as cancer cells continued to infiltrate and extend tumor margins. These highly variable tumor responses showed no correlation with time-to-progression or overall survival.
CONCLUSIONS
These bioscales indicate that fractionated chemoradiotherapy of glioblastomas produces variable responses with low cell killing efficiency. These parameters are sensitive to real-time changes within the treatment volume while remaining stable elsewhere, highlighting the potential to individualize therapy earlier in management, should alternative strategies be available.
Topics: Adult; Aged; Cell Size; Chemoradiotherapy; Disease Progression; Dose Fractionation, Radiation; Female; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm, Residual; Sodium; Tumor Burden
PubMed: 30487127
DOI: 10.1158/1078-0432.CCR-18-2079 -
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 -
Radiotherapy and Oncology : Journal of... Jul 2012The concept of radiation dose-volume effect has been exploited in breast cancer as boost treatment for high risk patients and more recently in trials of Partial Breast... (Review)
Review
The concept of radiation dose-volume effect has been exploited in breast cancer as boost treatment for high risk patients and more recently in trials of Partial Breast Irradiation for low risk patients. However, there appears to be paucity of published data on the dose-volume effect of irradiation on breast tissue including the recently published report on Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). This systematic review looks at the current literature for relationship between irradiated breast volume and normal tissue complications and introduces the concept of dose modulation.
Topics: Brachytherapy; Breast; Breast Neoplasms; Dose Fractionation, Radiation; Female; Humans; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant
PubMed: 22682540
DOI: 10.1016/j.radonc.2012.04.025 -
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 -
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