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The future of radiation oncology is exceptionally strong as we are increasingly involved in nearly all oncology disease sites due to extraordinary advances in radiation oncology treatment management platforms and improvements in treatment execution. Due to our technology and consistent accuracy, compressed radiation oncology treatment strategies are becoming more commonplace secondary to our ability to successfully treat tumor targets with increased normal tissue avoidance. In many disease sites including the central nervous system, pulmonary parenchyma, liver, and other areas, our service is redefining the standards of care. Targeting of disease has improved due to advances in tumor imaging and application of integrated imaging datasets into sophisticated planning systems which can optimize volume driven plans created by talented personnel. Treatment times have significantly decreased due to volume driven arc therapy and positioning is secured by real time imaging and optical tracking. Normal tissue exclusion has permitted compressed treatment schedules making treatment more convenient for the patient. These changes require additional study to further optimize care. Because data exchange worldwide have evolved through digital platforms and prisms, images and radiation datasets worldwide can be shared/reviewed on a same day basis using established de-identification and anonymization methods. Data storage post-trial completion can co-exist with digital pathomic and radiomic information in a single database coupled with patient specific outcome information and serve to move our translational science forward with nimble query elements and artificial intelligence to ask better questions of the data we collect and collate. This will be important moving forward to validate our process improvements at an enterprise level and support our science. We have to be thorough and complete in our data acquisition processes, however if we remain disciplined in our data management plan, our field can grow further and become more successful generating new standards of care from validated datasets.
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BACKGROUND: Radiation exposure can lead to detrimental effects in skin microcirculation. The precise relationship between radiation dose received and its effect on cutaneous perfusion still remains controversial. Previously, we have shown that hyperspectral imaging (HSI) is able to demonstrate long-term reductions in cutaneous perfusion secondary to chronic microvascular injury. This study characterizes the changes in skin microcirculation in response to varying doses of ionizing radiation and investigates these microcirculatory changes as a possible early non-invasive biomarker that may correlate with the extent of long-term microvascular damage. METHODS: Immunocompetent hairless mice (n = 66) were exposed to single fractions of superficial beta-irradiation in doses of 0, 5, 10, 20, 35, or 50 Gy. A HSI device was utilized to measure deoxygenated hemoglobin levels in irradiated and control areas. HSI measurements were performed at baseline before radiation exposure and for the first 3 days post-irradiation. Maximum macroscopic skin reactions were graded, and histological assessment of cutaneous microvascular densities at 4 weeks post-irradiation was performed in harvested tissue by CD31 immunohistochemistry. RESULTS: CD31 immunohistochemistry demonstrated a significant correlation (r = 0.90, p < 0.0001) between dose and vessel density reduction at 4 weeks. Using HSI analysis, early changes in deoxygenated hemoglobin levels were observed during the first 3 days post-irradiation in all groups. These deoxygenated hemoglobin changes varied proportionally with dose (r = 0.98, p < 0.0001) and skin reactions (r = 0.98, p < 0.0001). There was a highly significant correlation (r = 0.91, p < 0.0001) between these early changes in deoxygenated hemoglobin and late vascular injury severity assessed at the end of 4 weeks. CONCLUSION: Radiation dose is directly correlated with cutaneous microvascular injury severity at 4 weeks in our model. Early post-exposure measurement of cutaneous deoxygenated hemoglobin levels may be a useful biomarker for radiation dose reconstruction and predictor for chronic microvascular injury.
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PURPOSE: To evaluate the effect of the AeroForm (AirXpanders Inc, Palo Alto, CA) tissue expander on the dose distribution in a phantom from a simulated postmastectomy radiation treatment for breast cancer. METHODS AND MATERIALS: Experiments were conducted to determine the effect on the dose distribution with the metallic reservoir irradiated independently and with the entire AeroForm tissue expander placed on a RANDO phantom (The Phantom Laboratory, Salem, NY). The metallic reservoir was irradiated on a block of solid water with film at various depths ranging from 0 to 8.2 cm from the surface. The intact 400 cc AeroForm was inflated to full capacity and irradiated while positioned on a RANDO phantom, with 12 optically stimulated luminescent dosimeters (OSLDs) placed at clinically relevant expander-tissue interface points. RESULTS: Film dosimetry with the reservoir perpendicular to film reveals 40% transmission at a depth of 0.7 cm, which increases to 60% at a depth of 8.2 cm. In the parallel position, the results vary depending on which area under the reservoir is examined, indicating that the reservoir is not a uniformly dense object. Testing of the intact expander on the phantom revealed that the average percent difference (measured vs expected dose) was 2.7%, σ = 6.2% with heterogeneity correction and 3.7%, σ = 2.4% without heterogeneity correction. The only position where the OSLD readings were consistently higher than the calculated dose by >5% was at position 1, just deep to the canister at the expander-phantom interface. At this position, the readings varied from 5.2% to 14.5%, regardless of heterogeneity correction. CONCLUSIONS: Film dosimetry demonstrated beam attenuation in the shadow of the metallic reservoir in the expander. This decrease in dose was not reproduced on the intact expander on the phantom designed to replicate a clinical setup.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Dosimetría por Película/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Dispositivos de Expansión Tisular , Femenino , Dosimetría por Película/instrumentación , Humanos , Mamoplastia/métodos , Mastectomía/métodos , Fantasmas de Imagen , Dosificación RadioterapéuticaRESUMEN
BACKGROUND: Ionizing radiation is known to have deleterious chronic effects on skin, including fibrosis and poor wound healing, hypothesized as mediated by ischemia and hypoxia. Past studies have been unable to simultaneously investigate changes in perfusion and oxygenation as separate parameters. Hyperspectral imaging has emerged as a tool with which to concurrently measure skin perfusion and oxygenation. The authors investigated the use of hyperspectral imaging in a novel murine model of chronic radiation injury. METHODS: Areas of flank skin (n = 20) on hairless mice were exposed to a 50-Gy dose of beta-radiation. Hyperspectral imaging acquisition was performed at select points through 8 weeks. Immunohistochemical staining and gene expression analysis were performed to evaluate cutaneous vascular density, epidermal cell hypoxia, and angiogenic factors. RESULTS: All irradiated areas developed a chronic-phase wound by day 28. Hyperspectral imaging demonstrated a 21 percent decline in perfusion on day 56 (p < 0.001), whereas oxygenation levels were unchanged. A 1.7-fold reduction in blood vessel density was measured in irradiated skin compared with control tissue (p < 0.001), but no difference in epidermal cell hypoxia was observed. Vascular endothelial growth factor and related receptor expression were significantly lower in irradiated tissue. CONCLUSIONS: The authors' analysis does not support the presence of hypoxia in chronic-phase irradiated skin but suggests that hypoperfusion may be a predominant characteristic. The concurrent states of hypoperfusion and normoxia may be explained by the lower metabolic demands of fibrosed tissue.
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Oxígeno/metabolismo , Traumatismos por Radiación/metabolismo , Traumatismos por Radiación/fisiopatología , Flujo Sanguíneo Regional , Piel/efectos de la radiación , Animales , Fibrosis/etiología , Fibrosis/metabolismo , Fibrosis/fisiopatología , Masculino , Ratones , Ratones Pelados , Piel/irrigación sanguínea , Piel/metabolismo , Piel/patología , Piel/fisiopatologíaRESUMEN
Studies examining acute oxygenation and perfusion changes in irradiated skin are limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance spectroscopy, provides noninvasive, quantified measurements of cutaneous oxygenation and perfusion. This study examines whether HSI can assess acute changes in oxygenation and perfusion following irradiation. Skin on both flanks of nude mice (n=20) was exposed to 50 Gy of beta radiation from a strontium-90 source. Hyperspectral images were obtained before irradiation and on selected days for three weeks. Skin reaction assessment was performed concurrently with HSI. Desquamative injury formed in all irradiated areas. Skin reactions were first seen on day 7, with peak formation on day 14, and resolution beginning by day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous changes were observed (p<0.001). Further increases over baseline were seen on day 14, but returned to baseline levels by day 21. For perfusion, similar increases were seen on days 1 and 14. Unlike tissue oxygenation, perfusion was decreased below baseline on day 21 (p<0.002). HSI allows for complete visualization and quantification of tissue oxygenation and perfusion changes in irradiated skin, and may also allow prediction of acute skin reactions based on early changes seen after irradiation.