RESUMEN
As humans, we are constantly exposed to ionizing radiation from natural, man-made and cosmic sources which can damage DNA, leading to deleterious effects including cancer incidence. In this work, we introduce a method to monitor strand breaks resulting from damage due to the direct effect of ionizing radiation and provide evidence for sequence-dependent effects leading to strand breaks. To analyze only DNA strand breaks caused by radiation damage due to the direct effect of ionizing radiation, we combined an established technique to generate dehydrated DNA samples with a technique to analyze single-strand breaks on short oligonucleotide sequences via denaturing gel electrophoresis. We find that direct damage primarily results in a reduced number of strand breaks in guanine triplet regions (GGG) when compared to isolated guanine (G) bases with identical flanking base context. In addition, we observe strand break behavior possibly indicative of protection of guanine bases when flanked by pyrimidines and sensitization of guanine to strand break when flanked by adenine (A) bases in both isolated G and GGG cases. These observations provide insight into the strand break behavior in GGG regions damaged via the direct effect of ionizing radiation. In addition, this could be indicative of DNA sequences that are naturally more susceptible to strand break due to the direct effect of ionizing radiation.
Asunto(s)
Roturas del ADN/efectos de la radiación , Tolerancia a Radiación/genética , Repeticiones de Trinucleótidos/genética , Secuencia de BasesRESUMEN
Electron paramagnetic resonance (EPR) and online UV-visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV-visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5-0.8â MGy, in contrast to the saturating dose of â¼0.2â MGy observed using EPR at much lower dose rates. The observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure.
Asunto(s)
Disulfuros/química , Muramidasa/química , Conformación Proteica/efectos de la radiación , Animales , Pollos , Cristalografía por Rayos X , Espectroscopía de Resonancia por Spin del Electrón , Modelos Moleculares , Rayos XRESUMEN
Background: Re-irradiation for recurrent gliomas is a controversial treatment option with no clear standard dose or concurrent systemic therapy. Methods: This series represents a single-institution retrospective review of patients treated with re-irradiation for recurrent high-grade glioma. After 2012, patients were commonly offered concurrent bevacizumab as a cytoprotective agent against radiation necrosis. Kaplan-Meier method was used to estimate overall survival and progression-free survival. Cox proportional hazards regression was used to identify factors associated with overall survival and progression-free survival. Results: Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P < .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15). Conclusion: High dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma.
RESUMEN
BACKGROUND: To describe intensity-modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose-limiting structures. METHODS: Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease-specific survival were estimated using the Kaplan Meier method. RESULTS: Twenty patients were included. Nineteen patients had T3-4 tumors. Median follow-up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2-year OS was 94.7% (95% CI: 85.2%-100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy-proven. CONCLUSIONS: IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.
Asunto(s)
Neoplasias de Cabeza y Cuello , Radiocirugia , Radioterapia de Intensidad Modulada , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Cherenkov light emission has been shown to correlate with ionizing radiation dose delivery in solid tissue. An important clinical application of Cherenkov light is the real-time verification of radiation treatment delivery in vivo. To test the feasibility of treatment field verification, Cherenkov light images were acquired concurrent with radiation beam delivery to standard and anthropomorphic phantoms. Specifically, we tested two clinical treatment scenarios: (a) Observation of field overlaps or gaps in matched 3D fields and (b) Patient positioning shifts during intensity modulated radiation therapy (IMRT) field delivery. Further development of this technique would allow real-time detection of treatment delivery errors on the order of millimeters so that patient safety and treatment quality can be improved. METHODS: Cherenkov light emission was captured using a PI-MAX4 intensified charge coupled device (ICCD) system (Princeton Instruments). All radiation delivery was performed using a Varian Trilogy linear accelerator (linac) operated at 6 MV or 18 MV for photon and 6 MeV or 16 MeV for electron studies. Field matching studies were conducted with photon and electron beams at gantry angles of 0°, 15°, and 45°. For each modality and gantry angle, a total of three data sets were acquired. Overlap and gap distances of 0, 2, 5, and 10 mm were tested and delivered to solid phantom material of 30 × 30 × 5 cm3 . Phantom materials used were white plastic water and brown solid water. Tests were additionally performed on an anthropomorphic phantom with an irregular surface. Positioning shift studies were performed using IMRT fields delivered to a thoracic anthropomorphic phantom. For thoracic phantom measurements, the camera was placed laterally to observe the entire right side of the phantom. Fields were delivered with known translational patient positioning shifts in four directions. Changes in the Cherenkov fluence were evaluated through the generation of difference maps from unshifted Cherenkov images. All images were evaluated using ImageJ, Python, and MATLAB software packages. RESULTS: For matched fields, Cherenkov images were able to quantitate matched field separations with discrepancies between 2 and 4 mm, depending on gantry angle and beam energy or modality. For all photon and electron beams delivered at a gantry angle of 0°, image analysis indicated average discrepancies of less than 2 mm for all field gaps and overlaps, with 83% of matched fields exhibiting discrepancies less than 1 mm. Beams delivered obliquely to the phantom surface exhibited average discrepancies as high as 4 mm for electron beams delivered at large oblique angles. Finally, for IMRT field delivery, vertical and lateral patient positioning shifts of 2 mm were detected in some cases, indicating the potential detectability threshold of using this technique alone. CONCLUSIONS: Our study indicates that Cherenkov imaging can be used to support and bolster current treatment delivery verification techniques, improving our ability to recognize and rectify millimeter-scale delivery and positioning errors.
Asunto(s)
Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada , Estudios de Factibilidad , Humanos , MasculinoRESUMEN
BACKGROUND: Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored. OBJECTIVE: To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas. METHODS: We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression. RESULTS: The study cohort included 227 patients with available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rates were 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044). CONCLUSION: Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effects may impact post-treatment functional outcomes. Further research remains warranted.
Asunto(s)
Audición/efectos de la radiación , Neuroma Acústico/radioterapia , Dosis de Radiación , Radiocirugia/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Audición/fisiología , Pérdida Auditiva/diagnóstico por imagen , Pérdida Auditiva/etiología , Pérdida Auditiva/prevención & control , Pruebas Auditivas/tendencias , Humanos , Masculino , Persona de Mediana Edad , Neuroma Acústico/diagnóstico por imagen , Radiocirugia/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
In recent years, small animal image-guided irradiators have been widely utilized in preclinical studies involving rodent models. However, the dosimetry commissioning of such equipment involving kilovoltage small-field dosimetry has not received as much interest as the megavoltage small-field dosimetry used clinically. To date, a paucity of measured kilovoltage beam data, especially for field sizes less than 3 mm, can be found in the literature. For improvement of rodent treatments in the future, this work aims to provide comprehensive and accurate beam data for the small animal radiation research platform (SARRP, Xstrahl) using EBT3 Gafchromic films and Monte Carlo calculation, with submillimeter resolution and accuracy. This work includes three primary tasks: (1) establish an optimized film measurement protocol for small field dosimetry of kilovoltage photon beam. (2) Acquire dosimetric data including (a) depth dose curves from the surface to 6 cm depth (b) beam profiles, (c) penumbra, (d) cone factors and (e) 2D dose distribution. These tasks were undertaken for a 220 kVp photon beam with five different small field widths and 33 cm source to surface distance (0.5 mm and 1 mm circular fields, 3 × 3 mm2, 5 × 5 mm2, 10 × 10 mm2 square fields). Beam data was measured with EBT3 films. (3) Provide comparative dosimetry for film measurements, Monte Carlo calculations, and the dose calculations performed with the SARRP treatment planning system, Muriplan. For the majority of parameters, film measurement agreed with Monte Carlo simulation within 1%. There were, however, discrepancies between measured beam data and Muriplan treatment planning data. Specifically, for PDD, Muriplan underestimates the dose for field sizes of 0.5 mm and 1 mm. For beam profiles comparisons, the calculation from Muriplan predicts a smaller lateral distance between the 50% isodose lines compared to film measurement. There is a difference of 0.18, 0.72, 0.6 mm between Muriplan and film for field sizes of 3, 5, 10 mm, respectively. This work demonstrates that accurate and precise kilovoltage small-field dosimetry can be conducted using EBT3 Gafchromic film with an optimized protocol. In addition, discrepancies between measured beam data and Muriplan were identified.
Asunto(s)
Dosimetría por Película/métodos , Método de Montecarlo , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia Guiada por Imagen/instrumentación , Animales , Diseño de EquipoRESUMEN
BACKGROUND: The SpaceOAR hydrogel is employed to limit rectal radiation dose during prostate radiotherapy. We identified a novel parameter - the product of angle θ and hydrogel volume - to quantify hydrogel placement. This parameter predicted rectum dosimetry and acute rectal toxicity in prostate cancer patients treated with stereotactic body radiotherapy to 36.25 Gy in 5 fractions. METHODS: Twenty men with low- and intermediate-risk prostate cancer underwent hydrogel placement from 2015 to 2017. Hydrogel symmetry was assessed on the CT simulation scan in 3 axial slices (midgland, 1 cm above midgland, 1 cm below midgland). Two novel parameters quantifying hydrogel placement - hydrogel volume and angle θ formed by the prostate, hydrogel, and rectum - were measured, and the normalized product of θ and hydrogel volume calculated. These were then correlated with perirectal distance, rectum maximum 1-3 cc point doses (rDmax 1-3 cc), and rectum volumes receiving 80-95% of the prescription dose (rV80-95%). Acute rectal toxicity was recorded per RTOG criteria. RESULTS: In 50% of patients, hydrogel placement was symmetric bilaterally to within 1 cm of midline in all three CT simulation scan axial slices. Lateral hydrogel asymmetry < 2 cm in any one axial slice did not affect rectum dosimetry, but absence of hydrogel in the inferior axial slice resulted in a mean increase of 171 cGy in the rDmax 1 cc (p < 0.005). The perirectal distance measured at prostate midgland, midline (mean 9.1 ± 4.3 mm) correlated strongly with rV95 (R2 0.6, p < 0.001). The mean hydrogel volume and θ were 10.3 ± 4.5 cc and 70 ± 49°, respectively. Perirectal distance, rV95 and rDmax 1 cc correlated with hydrogel angle θ (p < 0.01), and yet more strongly with the novel metric θ*hydrogel volume (p < 0.001). With a median follow up of 14 months, no rectal toxicity >grade 2 was observed. Low grade rectal toxicity was observed in a third of men and resolved within 1 month of SBRT. Men who had these symptoms had higher rDmax 1 cc and smaller θ*hydrogel volume measurements. CONCLUSIONS: Optimal hydrogel placement occurs at prostate midgland, midline. The novel parameter θ*hydrogel volume describes a large proportion of rectum dosimetric benefit derived from hydrogel placement, and can be used to assess the learning curve phenomenon for hydrogel placement.
Asunto(s)
Hidrogeles/química , Modelos Estadísticos , Órganos en Riesgo/efectos de la radiación , Neoplasias de la Próstata/cirugía , Radiocirugia , Planificación de la Radioterapia Asistida por Computador/métodos , Recto/efectos de la radiación , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodosRESUMEN
PURPOSE: The precise dosimetric and geometric characteristics of small animal irradiators are essential to achieving reproducible dose delivery, especially in cases where image-guidance is utilized. Currently, radiochromic film is the established measurement tool used to evaluate beam characteristics for these systems. However, only 2D information can be acquired with film. This study characterized both the dosimetric and geometric properties of the small animal research radiation platform (SARRP, Xstrahl) for commissioning purposes using a 3D radiochromic dosimetry system with a submillimeter resolution optical computed tomography (OCT) scanner. METHODS: Like a modern clinical linear accelerator, the SARRP features both a beam delivery system and a cone beam computed tomography (CBCT) imaging system. Dosimetric and geometric characteristics of the SARRP were studied using EBT3 radiochromic film and 3D PRESAGE dosimeters. Dosimetric measurements included percent depth dose (PDD) curves and beam profiles. For geometric evaluation, the isocenter sizes of the treatment stage and gantry rotations as well as their coincidence were measured using star shot patterns. A commercial Epson Expression 11000XL flatbed scanner was used for readout of irradiated EBT3 films at 300 dpi resolution. Each irradiated PRESAGE dosimeter was scanned using a submillimeter resolution single laser beam OCT scanner. Acquired data were reconstructed with a resolution of 0.3 mm/pixel. RESULTS: PDD data measured from films and 3D dosimeters agree to within ±3% for depths up to 5 cm, for both 3 × 3 and 10 × 10 mm2 fixed collimation. Profiles were analyzed at 10, 20, and 30 mm depth for 3 × 3 mm2 and 10 × 10 mm2 fields. The FWHM measurements for both dosimeters agreed to within 0.01 mm, and the penumbras agreed to within 0.1 mm for 3 × 3 mm2 and 0.5 mm for 10 × 10 mm2 . Gantry and treatment stage isocenter sizes were determined to be 0.21 and 0.43 mm using EBT3 film, and 1.72 and 0.75 mm using PRESAGE dosimeters. Absolute isocenter shifts, evaluated with 3D phantoms, were 0.80 mm for the gantry rotation isocenter (treatment isocenter) with respect to the laser-defined setup isocenter, and 0.71 mm for the gantry rotation isocenter relative to treatment stage rotation isocenter (CBCT isocenter). The difference between CBCT isocenter and laser-defined setup isocenter was 0.68 mm. CONCLUSIONS: This study demonstrated that 3D PRESAGE dosimeters can be used for verification of precise targeting for the SARRP. This 3D dosimetry system can be utilized to obtain information on both geometric and dosimetric properties, as well as acquire beam data parameters for the purpose of commissioning image-guided small animal irradiator systems.
Asunto(s)
Tomografía Computarizada de Haz Cónico/instrumentación , Dosímetros de Radiación , Tomografía Óptica/instrumentación , Animales , Calibración , Diseño de Equipo , Dosimetría por Película , Dosis de RadiaciónRESUMEN
PURPOSE: To implement Velocity-based image fusion and adaptive deformable registration to enable treatment planning for preclinical murine models of fractionated stereotactic radiosurgery (fSRS) using the small animal radiation research platform (SARRP). METHODS AND MATERIALS: C57BL6 mice underwent 3 unique cone beam computed tomography (CBCT) scans: 2 in the prone position and a third supine. A single T1-weighted post-contrast magnetic resonance imaging (MRI) series of a murine metastatic brain tumor model was selected for MRI-to-CBCT registration and gross tumor volume (GTV) identification. Two arms were compared: Arm 1, where we performed 3 individual MRI-to-CBCT fusions using rigid registration, contouring GTVs on each, and Arm 2, where the authors performed MRI-to-CBCT fusion and contoured GTV on the first CBCT followed by Velocity-based adaptive registration. The first CBCT and associated GTV were exported from MuriPlan (Xstrahl Life Sciences) into Velocity (Varian Medical Systems, Inc, Palo Alto, CA). In Arm 1, the second and third CBCTs were exported similarly along with associated GTVs (Arm 1), while in Arm 2, the first (prone) CBCT was fused separately to the second (prone) and third (supine) CBCTs, performing deformable registrations on initial CBCTs and applying resulting matrices to the contoured GTV. Resulting GTVs were compared between Arms 1 and 2. RESULTS: Comparing GTV overlays using repeated MRI fusion and GTV delineation (Arm 1) versus those of Velocity-based CBCT and GTV adaptive fusion (Arm 2), mean deviations ± standard deviation in the axial, sagittal, and coronal planes were 0.46 ± 0.16, 0.46 ± 0.22, and 0.37 ± 0.22 mm for prone-to-prone and 0.52 ± 0.27, 0.52 ± 0.36, and 0.68 ± 0.31 mm for prone-to-supine adaptive fusions, respectively. CONCLUSIONS: Velocity-based adaptive fusion of CBCTs and contoured volumes allows for efficient fSRS planning using a single MRI-to-CBCT fusion. This technique is immediately implementable on current SARRP systems, facilitating advanced preclinical treatment paradigms using existing clinical treatment planning software.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Tomografía Computarizada de Haz Cónico/métodos , Imagen por Resonancia Magnética/métodos , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Animales , Neoplasias Encefálicas/diagnóstico por imagen , Masculino , Ratones , Ratones Endogámicos C57BL , Carga TumoralRESUMEN
PURPOSE: To establish a novel preclinical model for stereotactic radiosurgery (SRS) with combined mouselike phantom quality assurance in the setting of brain metastases. METHODS AND MATERIALS: C57B6 mice underwent intracranial injection of B16-F10 melanoma cells. T1-weighted postcontrast magnetic resonance imaging (MRI) was performed on day 11 after injection. The MRI images were fused with cone beam computed tomography (CBCT) images using the Small Animal Radiation Research Platform (SARRP). The gross tumor volume (GTV) was contoured using the MRI. A single sagittal arc using the 3 × 3 mm2 collimator was used to deliver 18 Gy prescribed to the isocenter. MRI was performed 7 days after radiation treatment, and the dose delivered to the mice was confirmed using 2 mouselike anthropomorphic phantoms: 1 in the axial orientation and the other in the sagittal orientation. The SARRP output was measured using a PTW Farmer type ionization chamber as per the American Association of Physicists in Medicine Task Group report 61, and the H-D curve was generated up to a maximum dose of 30 Gy. Irradiated films were analyzed based on optical density distribution and H-D curve. RESULTS: The tumor volume on day 11, before intervention, was 2.48 ± 1.37 mm3 in the no-SRS arm versus 3.75 ± 1.19 mm3 in the SRS arm (NS). In the SRS arm, GTV maximum dose (Dmax) and mean dose were 2048 ± 207 and 1785 ± 14 cGy. Using the mouselike phantoms, the radiochromic film showed close precision in comparison with projected isodose lines, with a Dmax of 1903.4 and 1972.7 cGy, the axial and sagittal phantoms, respectively. Tumor volume 7 days after treatment was 7.34 ± 8.24 mm3 in the SRS arm and 60.20 ± 40.4 mm3 in the no-SRS arm (P=.009). No mice in the control group survived more than 22 days after implantation, with a median overall survival (mOS) of 19 days; mOS was not reached in the SRS group, with 1 death noted. CONCLUSIONS: Single-fraction SRS of 18 Gy delivered in a single arc can be delivered accurately with MRI T1-weighted postcontrast-based treatment planning. The mouse like phantom allows for verification of dose delivery and accuracy.
Asunto(s)
Neoplasias Encefálicas/radioterapia , Melanoma/radioterapia , Fantasmas de Imagen , Garantía de la Calidad de Atención de Salud , Radiocirugia/normas , Animales , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Tomografía Computarizada de Haz Cónico , Medios de Contraste , Imagen por Resonancia Magnética , Masculino , Melanoma/diagnóstico por imagen , Melanoma/patología , Melanoma/secundario , Ratones , Ratones Endogámicos C57BL , Imagen Multimodal/métodos , Dosificación Radioterapéutica , Factores de Tiempo , Carga TumoralRESUMEN
PURPOSE: We investigate clinical, pathologic, and treatment paradigm-related factors affecting local control of brain metastases after stereotactic radiosurgery (SRS) with or without whole brain radiotherapy (WBRT). METHODS AND MATERIALS: Patients with brain metastases treated with SRS alone, before or after WBRT were considered to determine predictors of local failure (LF), time to failure and survival. RESULTS: Among 137 patients, 411 brain metastases were analyzed. 23% of patients received SRS alone, 51% received WBRT prior to SRS, and 26% received SRS followed by WBRT. LF occurred in 125 metastases: 63% after SRS alone, 20% after WBRT then SRS, and 22% after SRS then WBRT. Median time to local failure was significantly less after SRS alone compared to WBRT then SRS (12.1 v. 22.7 months, p=0.003). Tumor volume was significantly associated with LF (HR:5.2, p<0.001, 95% CI:3.4-7.8). CONCLUSIONS: WBRT+SRS results in reduced LF. Local control was not significantly different after SRS as salvage therapy versus upfront SRS.
RESUMEN
BACKGROUND: Stereotactic radiosurgery for the treatment of brain metastases is commonly delivered without regard to primary cancer histology. This study sought to determine if the primary site of origin for brain metastases affected the propensity for local failure. METHODS: A total of 83 patients with 200 brain metastases were examined retrospectively for predictors of infield failure. Tumor, patient, and treatment characteristics were analyzed including primary tumor histology, radiosurgical dose and age. Cox proportional hazards models, univariate and multivariate analyses were used to identify predictors of local failure. RESULTS: Freedom from local failure for the entire population was 83% and 65% at 6 and 12 months, respectively. Multivariate analysis revealed that breast cancer brain metastases have a significantly lower risk of local failure than melanoma (HR = 0.31, p< 0.001). Additionally, multivariate analysis revealed that increasing dose lowered risk for local failure (HR = 0.87, p<0.001). CONCLUSIONS: Melanoma histology leads to a higher rate of local failure. Higher prescription dose results in higher incidence of local control.
RESUMEN
An understanding of charge transfer (CT) in DNA lies at the root of assessing the risks and benefits of exposure to ionizing radiation. Energy deposition by high-energy photons and fast-charged particles creates holes and excess electrons (EEs) in DNA, and the subsequent reactions determine the complexity of DNA damage and ultimately the risk of disease. Further interest in CT comes from the possibility that hole transfer, excess electron transfer (EET), or both in DNA might be used to develop nanoscale circuits. To study EET in DNA, EPR spectroscopy was used to determine the distribution of EE trapping by oligodeoxynucleotides irradiated and observed at 4 K. Our results indicate that stretches of consecutive adenine bases on the same strand serve as an ideal conduit for intrastrand EET in duplex DNA at 4 K. Specifically, we show that A is an efficient trap for EE at 4 K if, and only if, the A strand of the duplex does not contain one of the other three bases. If there is a T, C, or G on the A strand, then trapping occurs at T or C instead of A. This holds true for stretches up to 32 A's. Whereas T competes effectively against A for the EE, it does not compete effectively against C. Long stretches of T pass the majority of EE to C. Our results show that AT stretches channel EE to cytosine, an end point with significance to both radiation damage and the photochemical repair of pyrimidine dimers.
Asunto(s)
Adenina/química , ADN/química , Daño del ADN , Espectroscopía de Resonancia por Spin del Electrón , Transporte de Electrón , Radicales Libres/química , Radiación IonizanteRESUMEN
Our lab investigated damage of DNA due to ionizing radiation using electron paramagnetic resonance (EPR). Through studies focused on one-electron-reduction of synthetic oligodeoxynucleotides containing only thymine and adenine, we discovered the significant presence of a contaminant in all samples. The contaminant was observed to have a reduction potential greater than that of thymine. In addition, the contaminant yielded a sharp EPR singlet when it was one-electron reduced that interfered with the distinctive doublet of one-electron reduced thymine. We determined that the contaminant contained a benzoyl group, a chemical used in to protect the amine group of adenine during oligodeoxynucleotide synthesis. Derivatives of benzoyl and 16 different oligomer sequences were prepared in a LiCl glass and studied using EPR after X-irradiating at 4K. This treatment selectively creates one-electron reduced radicals. Synthetic derivatives were used to develop an EPR benchmark of the benzoyl radical. Using this, along with the known spectra of one-electron reduced nucleobases, we performed component analysis of the EPR signal from each sample. This analysis revealed that 2-9% of adenines, in the commercially synthesized oligomers delivered to us, were left contaminated with benzoyl. We concluded that the presence of benzoyl is a potential source of error in a variety of experiments utilizing synthesized oligodeoxynucleotides.
Asunto(s)
Electrones , Oligodesoxirribonucleótidos/química , Adenina/química , Daño del ADN , Espectroscopía de Resonancia por Spin del Electrón , Transporte de Electrón , Oligodesoxirribonucleótidos/síntesis química , Oxidación-Reducción , Radiación Ionizante , Timina/químicaRESUMEN
A qualitative and quantitative analysis of the radicals underlying the radiation-induced signal (RIS) in fingernails was conducted in an attempt to identify properties of these radicals that could be used for biodosimetry purposes. A qualitative analysis of RIS showed the presence of at least three components, two of which were observed at low doses (<50 Gy) and the third required higher doses (>500 Gy). The low dose signal, obtained by reconstruction, consists of a 10 gauss singlet at g = 2.0053 and an 18 gauss doublet centered at g = 2.0044. Based on the initial slope of the dose-response curve, the chemical (radical) yields of the radicals giving rise to the singlet and doublet were 327 (+/-113) and 122 (+/-9) nmol J-1 (standard error, SE), respectively. At doses below 50 Gy, the singlet signal is the dominant component. Above this dose range, the signal intensity of the singlet rapidly dose-saturates. At doses <50 Gy, there is a small contribution of the doublet signal that increases in its proportion of the RIS as dose increases. A third component was revealed at high dose with a spectral extent of approximately 100 gauss and displayed peaks due to g anisotropy at g = 2.056, 2.026, and 1.996. The total radical yield calculated from the initial slope of the dose-response curve averaged 458 +/- (116) nmol J-1 (SE) in irradiated nail clippings obtained from six volunteers. Such high yields indicate that nails are a strong candidate for biodosimetry at low doses. In a comparison of relative stabilities of the radicals underlying the singlet and doublet signals, the stability of the doublet signal is more sensitive to the moisture content of the nail than the singlet. This differential in radical stabilities could provide a method for removing the doublet signal under controlled exposures to high humidities (>70% relative humidity). The decay of the singlet signal in RIS varies with exposure of a nail clipping to differing ambient humidities. However, long exposures (>6 h) to relative humidities of 72-94% results in singlet intensities that approach 7.0 +/- (3.2)% (standard deviation) of the original intensities in an irradiated nail. This result suggests the existence of a subpopulation of radicals underlying the singlet signal that is relatively insensitive to decay under exposure of nails even to high humidities. Therefore, exposures of an irradiated nail clipping under controlled humidities may provide a method for estimating the exposure dose of the nail that is based on the intensity of the signal of the humidity insensitive radical population underlying the singlet signal.