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Journal of Cutaneous and Aesthetic... 2021Keloids are dermal tumors that are due to increased production of collagen caused by abnormal and prolonged wound healing. The incidence of recurrence is extremely high...
BACKGROUND
Keloids are dermal tumors that are due to increased production of collagen caused by abnormal and prolonged wound healing. The incidence of recurrence is extremely high if only conservative measures are used. This study was conducted to evaluate the feasibility and efficacy surgery and high dose rate brachytherapy as an adjuvant therapy for treatment of keloids.
MATERIALS AND METHODS
50 patients with clinically diagnosed 71 keloids were treated with excision of keloid and post-operative high-dose rate brachytherapy were studied. Complete excision of the keloid till the healthy skin margin was excised. The wound were closed in 2 layers. Subcutaneous tissue closed using absorbable suture, over which a 6F flexible polyethylene tube was placed. High dose rate cobalt-60 brachytherapy was administered. Total of 15 Gy in divided dose, 5 Gy in 3 fractions were administered.
RESULTS
50 patients with 71 keloids were studied. Out of the 50 patients, 12 were male (24%) and 38 were females (76%). Age of the patients ranged between 14 and 71 years. Recurrence rate was 2% with 2 keloids recurring at 5 months interval. 4 patients scored the results as unacceptable, remaining 45 patients rated their results as excellent during their follow up at 10 days, 3 months and 6 months.
CONCLUSION
Treatment of keloids in the plastic surgeon's practice even today is still challenging. Many therapies have been described, but recurrence rate is high with mono-therapy. Combination therapy especially surgical excision with postoperative radiotherapy is best in preventing recurrence.
PubMed: 34908777
DOI: 10.4103/JCAS.JCAS_120_16 -
World Neurosurgery Aug 2021To evaluate the relationships between calibration dose rate, calculated biologically effective dose (BED), and clinical factors and tumor control after stereotactic...
OBJECTIVE
To evaluate the relationships between calibration dose rate, calculated biologically effective dose (BED), and clinical factors and tumor control after stereotactic radiosurgery (SRS) for acoustic neuroma.
METHODS
We performed a retrospective study of all patients with acoustic neuromas treated with frame-based cobalt-60 SRS at a single institution between 2005 and 2019. The calibration dose rate and cobalt-60 half-life were used to calculate the nominal dose rate during treatment. An SRS-specific monoexponential model accounting for treatment time per lesion was used to estimate BED.
RESULTS
The study included 607 patients with 612 acoustic neuromas. Median follow-up was 5.0 years. There was no association between dose rate or BED with local failure (LF), radiologic edema, or symptomatic edema. Cystic tumors (adjusted hazard ratio 0.26, P = 0.028) were associated with lower LF, while use of SRS as salvage treatment for growing tumors (adjusted hazard ratio 4.9, P < 0.0001) was associated with higher LF. LF occurred more frequently in larger-diameter tumors, while radiologic or symptomatic edema occurred more frequently in larger-volume tumors.
CONCLUSIONS
Radiosurgery dose rate and BED were not associated with tumor control or radiologic or symptomatic edema. Salvage SRS and larger tumors were associated with a higher LF rate, while cystic tumors were associated with a lower LF rate. Patients with larger tumors should be counseled appropriately about potential side effects and when to seek follow-up care.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calibration; Cobalt Radioisotopes; Cranial Nerve Neoplasms; Cysts; Dose-Response Relationship, Radiation; Edema; Female; Half-Life; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroma, Acoustic; Postoperative Complications; Radiation Dosage; Radiosurgery; Retrospective Studies; Treatment Outcome; Tumor Burden; Young Adult
PubMed: 34098139
DOI: 10.1016/j.wneu.2021.05.122 -
Neurosurgery Jan 2022Radiosurgery dose rate and biologically effective dose (BED) are associated with outcomes after stereotactic radiosurgery (SRS) for functional neurosurgical conditions...
BACKGROUND
Radiosurgery dose rate and biologically effective dose (BED) are associated with outcomes after stereotactic radiosurgery (SRS) for functional neurosurgical conditions and some benign tumors. It is not known if these factors affect the efficacy of SRS for meningioma.
OBJECTIVE
To determine the association between cobalt-60 dose rate and BED on outcomes in patients with meningioma treated with SRS.
METHODS
A single-institution cohort of 336 patients treated between 2005 and 2018 with cobalt-based SRS for 414 separate meningioma lesions was assembled. BED was calculated using an SRS-specific monoexponential model accounting for treatment time per lesion, assuming α/β = 2.47 Gy. Cumulative incidences of local failure (LF) were reported after considering the competing risk of death, on a per-lesion basis. Multivariable analysis of LF was performed using a proportional hazards model.
RESULTS
The most common SRS dose was 12 Gy (n = 227); 140 lesions received 14 Gy. Five-year LF was 15.6% (95% confidence interval 10.4-21.9) and 4.3% (1.4-9.8) in patients who had a dose rate of <2.95 and ≥2.95 Gy/min, respectively (P = .0375). Among 354 grade I or unresected lesions treated with SRS, BED >50 Gy2.47 was associated with a lower incidence of LF (P = .0030). Each 1 Gy/min increase in dose rate was associated with an adjusted hazard ratio of 0.53 (95% confidence interval, 0.29-0.97, P = .041) for LF. Prescription dose >12 Gy was not associated with a lower incidence of LF.
CONCLUSION
Patients with meningiomas treated with lower dose rates experienced a higher incidence of LF than those treated with higher dose rates.
Topics: Cobalt Radioisotopes; Follow-Up Studies; Humans; Meningeal Neoplasms; Meningioma; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 34982881
DOI: 10.1227/NEU.0000000000001755 -
Physics in Medicine and Biology Aug 2023. The objective of this study was to investigate the impact of mean and instantaneous dose rates on the production of reactive oxygen species (ROS) during ultra-high...
. The objective of this study was to investigate the impact of mean and instantaneous dose rates on the production of reactive oxygen species (ROS) during ultra-high dose rate (UHDR) radiotherapy. The study aimed to determine whether either dose rate type plays a role in driving the FLASH effect, a phenomenon where UHDR radiotherapy reduces damage to normal tissues while maintaining tumor control.. Assays of hydrogen peroxide (HO) production and oxygen consumption (ΔpO) were conducted using UHDR electron irradiation. Aqueous solutions of 4% albumin were utilized as the experimental medium. The study compared the effects of varying mean dose rates and instantaneous dose rates on ROS yields. Instantaneous dose rate was varied by changing the source-to-surface distance (SSD), resulting in instantaneous dose rates ranging from 10to 10Gy s. Mean dose rate was manipulated by altering the pulse frequency of the linear accelerator (linac) and by changing the SSD, ranging from 0.14 to 1500 Gy s.. The study found that both ΔHOand ΔpOdecreased as the mean dose rate increased. Multivariate analysis indicated that instantaneous dose rates also contributed to this effect. The variation in ΔpOwas dependent on the initial oxygen concentration in the solution. Based on the analysis of dose rate variation, the study estimated that 7.51 moles of HOwere produced for every mole of Oconsumed.. The results highlight the significance of mean dose rate as a predictor of ROS production during UHDR radiotherapy. As the mean dose rate increased, there was a decrease in oxygen consumption and in HOproduction. These findings have implications for understanding the FLASH effect and its potential optimization. The study sheds light on the role of dose rate parameters and their impact on radiochemical outcomes, contributing to the advancement of UHDR radiotherapy techniques.
Topics: Reactive Oxygen Species; Electrons; Hydrogen Peroxide; Oxygen; Heart Rate; Radiotherapy Dosage
PubMed: 37463588
DOI: 10.1088/1361-6560/ace877 -
Scientific Reports Dec 2022The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver ultra-high dose rates: operating in 9 MeV electron mode (FLASH...
The Radiological Research Accelerator Facility has modified a decommissioned Varian Clinac to deliver ultra-high dose rates: operating in 9 MeV electron mode (FLASH mode), samples can be irradiated at a Source-Surface Distance (SSD) of 20 cm at average dose rates of up to 600 Gy/s (3.3 Gy per 0.13 µs pulse, 180 pulses per second). In this mode multiple pulses are required for most irradiations. By modulating pulse repetition rate and irradiating at SSD = 171 cm, dose rates below 1 Gy/min can be achieved, allowing comparison of FLASH and conventional irradiations with the same beam. Operating in 6 MV photon mode, with the conversion target removed (SuperFLASH mode), samples are irradiated at higher dose rates (0.2-150 Gy per 5 µs pulse, 360 pulses per second) and most irradiations can be performed with a single very high dose rate pulse. In both modes we have seen the expected inverse relation between dose rate and irradiated area, with the highest dose rates obtained for beams with a FWHM of about 2 cm and ± 10% uniformity over 1 cm diameter. As an example of operation of the ultra-high dose rate FLASH irradiator, we present dose rate dependence of dicentric chromosome yields.
Topics: Particle Accelerators; Photons; Electrons; Radiotherapy Dosage; Radiometry
PubMed: 36550150
DOI: 10.1038/s41598-022-19211-7 -
Genome Integrity 2019Nontargeted effects include radiation-induced genomic instability (RIGI) which is observed in the progeny of cells exposed to ionizing radiation and can be manifested in...
Nontargeted effects include radiation-induced genomic instability (RIGI) which is observed in the progeny of cells exposed to ionizing radiation and can be manifested in different ways, including chromosomal instability and micronucleus (MN) formation. Since genomic instability is commonly observed in tumors and has a role in tumor progression, RIGI has the potential of being an important mechanism for radiation-induced cancer. The work presented explores the role of dose and dose rate on RIGI, determined using a MN assay, in normal primary human fibroblast (HF19) cells exposed to either 0.1 Gy or 1 Gy of X-rays delivered either as an acute (0.42 Gy/min) or protracted (0.0031 Gy/min) exposure. While the expected increase in MN was observed following the first mitosis of the irradiated cells compared to unirradiated controls, the results also demonstrate a significant increase in MN yields in the progeny of these cells at 10 and 20 population doublings following irradiation. Minimal difference was observed between the two doses used (0.1 and 1 Gy) and the dose rates (acute and protracted). Therefore, these nontargeted effects have the potential to be important for the low-dose and dose-rate exposure. The results also show an enhancement of the cellular levels of reactive oxygen species after 20 population doublings, which suggests that ionising radiation (IR) could potentially perturb the homeostasis of oxidative stress and so modify the background rate of endogenous DNA damage induction. In conclusion, the investigations have demonstrated that normal primary human fibroblast (HF19) cells are susceptible to the induction of early DNA damage and RIGI, not only after a high dose and high dose rate exposure to low linear energy transfer, but also following low dose, low dose rate exposures. The results suggest that the mechanism of radiation induced RIGI in HF19 cells can be correlated with the induction of reactive oxygen species levels following exposure to 0.1 and 1 Gy low-dose rate and high-dose rate x-ray irradiation.
PubMed: 31897286
DOI: 10.4103/genint.genint_5_19 -
International Journal of Radiation... 2023Increasing epidemiological and biological evidence suggests that radiation exposure enhances cancer risk in a dose-dependent manner. This can be attributed to the... (Review)
Review
PURPOSE
Increasing epidemiological and biological evidence suggests that radiation exposure enhances cancer risk in a dose-dependent manner. This can be attributed to the 'dose-rate effect,' where the biological effect of low dose-rate radiation is lower than that of the same dose at a high dose-rate. This effect has been reported in epidemiological studies and experimental biology, although the underlying biological mechanisms are not completely understood. In this review, we aim to propose a suitable model for radiation carcinogenesis based on the dose-rate effect in tissue stem cells.
METHODS
We surveyed and summarized the latest studies on the mechanisms of carcinogenesis. Next, we summarized the radiosensitivity of intestinal stem cells and the role of dose-rate in the modulation of stem-cell dynamics after irradiation.
RESULTS
Consistently, driver mutations can be detected in most cancers from past to present, supporting the hypothesis that cancer progression is initiated by the accumulation of driver mutations. Recent reports demonstrated that driver mutations can be observed even in normal tissues, which suggests that the accumulation of mutations is a necessary condition for cancer progression. In addition, driver mutations in tissue stem cells can cause tumors, whereas they are not sufficient when they occur in non-stem cells. For non-stem cells, tissue remodeling induced by marked inflammation after the loss of tissue cells is important in addition to the accumulation of mutations. Therefore, the mechanism of carcinogenesis differs according to the cell type and magnitude of stress. In addition, our results indicated that non-irradiated stem cells tend to be eliminated from three-dimensional cultures of intestinal stem cells (organoids) composed of irradiated and non-irradiated stem cells, supporting the stem-cell competition.
CONCLUSIONS
We propose a unique scheme in which the dose-rate dependent response of intestinal stem cells incorporates the concept of the threshold of stem-cell competition and context-dependent target shift from stem cells to whole tissue. The concept highlights four key issues that should be considered in radiation carcinogenesis: i.e. accumulation of mutations; tissue reconstitution; stem-cell competition; and environmental factors like epigenetic modifications.
Topics: Humans; Dose-Response Relationship, Radiation; Carcinogenesis; Stem Cells; Radiation Exposure; Mutation
PubMed: 36971595
DOI: 10.1080/09553002.2023.2194398 -
International Journal of Molecular... Oct 2022FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer... (Review)
Review
FLASH radiotherapy, or the delivery of a dose at an ultra-high dose rate (>40 Gy/s), has recently emerged as a promising tool to enhance the therapeutic index in cancer treatment. The remarkable sparing of normal tissues and equivalent tumor control by FLASH irradiation compared to conventional dose rate irradiation—the FLASH effect—has already been demonstrated in several preclinical models and even in a first patient with T-cell cutaneous lymphoma. However, the biological mechanisms responsible for the differential effect produced by FLASH irradiation in normal and cancer cells remain to be elucidated. This is of great importance because a good understanding of the underlying radiobiological mechanisms and characterization of the specific beam parameters is required for a successful clinical translation of FLASH radiotherapy. In this review, we summarize the FLASH investigations performed so far and critically evaluate the current hypotheses explaining the FLASH effect, including oxygen depletion, the production of reactive oxygen species, and an altered immune response. We also propose a new theory that assumes an important role of mitochondria in mediating the normal tissue and tumor response to FLASH dose rates.
Topics: Humans; Radiotherapy Dosage; Reactive Oxygen Species; Neoplasms; Oxygen
PubMed: 36292961
DOI: 10.3390/ijms232012109 -
Radiation Protection Dosimetry Sep 2022To evaluate biological effects triggered by low levels of radiation, we established a uniquely sensitive experimental system to detect somatic mutations. By using the...
To evaluate biological effects triggered by low levels of radiation, we established a uniquely sensitive experimental system to detect somatic mutations. By using the system, we found that mutant frequencies induced by X-rays were statistically significant at doses over 0.15 Gy, and a linear dose relationship with the mutant frequency was observed at doses over 0.15 Gy. The mutation spectra analysis revealed that mutation events generated by X-ray doses below 0.1 Gy were similar to those observed in unirradiated controls. In addition, a significant inflection point for both, the mutant frequency and the mutation spectra, was found at dose-rates around 11 mGy/day when cells were cultured in medium containing tritiated water. Because induced radiation-type events presented a clear dose/dose-rate dependency above the critical dose or the inflection point, these observations suggest that mutation events generated by radiation could change at a threshold dose-rate or a critical dose.
Topics: Beta Particles; DNA Breaks, Double-Stranded; Dose-Response Relationship, Radiation; Mutation; Tritium; X-Rays
PubMed: 36083726
DOI: 10.1093/rpd/ncac036 -
Journal of Radiation Research Mar 2023While epidemiological data are available for the dose and dose-rate effectiveness factor (DDREF) for human populations, animal models have contributed significantly to... (Review)
Review
While epidemiological data are available for the dose and dose-rate effectiveness factor (DDREF) for human populations, animal models have contributed significantly to providing quantitative data with mechanistic insights. The aim of the current review is to compile both the in vitro experiments with reference to the dose-rate effects of DNA damage and repair, and the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. In particular, the review focuses especially on the results pertaining to underlying biological mechanisms and discusses their possible involvement in the process of radiation-induced carcinogenesis. Because the concept of adverse outcome pathway (AOP) together with the key events has been considered as a clue to estimate radiation risks at low doses and low dose-rates, the review scrutinized the dose-rate dependency of the key events related to carcinogenesis, which enables us to unify the underlying critical mechanisms to establish a connection between animal experimental studies with human epidemiological studies.
Topics: Animals; Humans; Dose-Response Relationship, Radiation; Neoplasms, Radiation-Induced; Mammary Glands, Human; Risk Assessment; Radiation Exposure; Carcinogenesis; Models, Animal; Gastrointestinal Tract
PubMed: 36773323
DOI: 10.1093/jrr/rrad002