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1.
Environ Sci Technol ; 56(19): 13644-13653, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36150089

RESUMO

Amines are frequently included in formulations of the herbicides glyphosate, 2,4-D, and dicamba to increase herbicide solubility and reduce herbicide volatilization by producing herbicide-amine salts. Amines, which typically have higher vapor pressures than the corresponding herbicides, could potentially volatilize from these salts and enter the atmosphere, where they may impact atmospheric chemistry, human health, and climate. Amine volatilization from herbicide-amine salts may additionally contribute to volatilization of dicamba and 2,4-D. In this study, we established that amines applied in herbicide-amine salt formulations undergo extensive volatilization. Both dimethylamine and isopropylamine volatilized when aqueous salt solutions were dried to a residue at ∼20 °C, while lower-vapor pressure amines like diglycolamine and n,n-bis-(3-aminopropyl)methylamine did not. However, all four amines volatilized from salt residues at 40-80 °C. Because amine loss typically exceeded herbicide loss, we proposed that neutral amines dominated volatilization and that higher temperatures altered their protonation state and vapor pressure. Due to an estimated 4.0 Gg N/yr applied as amines to major U.S. crops, amine emissions from herbicide-amine salts may be important on regional scales. Further characterization of worldwide herbicide-amine use would enable this contribution to be compared to the 285 Gg N/yr of methylamines emitted globally.


Assuntos
Dicamba , Herbicidas , Ácido 2,4-Diclorofenoxiacético , Aminas , Dicamba/química , Dimetilaminas , Herbicidas/química , Humanos , Metilaminas , Sais , Volatilização
2.
Indoor Air ; 31(4): 1199-1216, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33484190

RESUMO

Reactive oxygen species (ROS) are an important contributor to adverse health effects associated with ambient air pollution. Despite infiltration of ROS from outdoors, and possible indoor sources (eg, combustion), there are limited data available on indoor ROS. In this study, part of the second phase of Air Composition and Reactivity from Outdoor aNd Indoor Mixing campaign (ACRONIM-2), we constructed and deployed an online, continuous, system to measure extracellular gas- and particle-phase ROS during summer in an unoccupied residence in St. Louis, MO, USA. Over a period of one week, we observed that the non-denuded outdoor ROS (representing particle-phase ROS and some gas-phase ROS) concentration ranged from 1 to 4 nmol/m3 (as H2 O2 ). Outdoor concentrations were highest in the afternoon, coincident with peak photochemistry periods. The indoor concentrations of particle-phase ROS were nearly equal to outdoor concentrations, regardless of window-opening status or air exchange rates. The indoor/outdoor ratio of non-denuded ROS (I/OROS ) was significantly less than 1 with windows open and even lower with windows closed. Combined, these observations suggest that gas-phase ROS are efficiently removed by interior building surfaces and that there may be an indoor source of particle-phase ROS.


Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental , Tamanho da Partícula , Material Particulado/análise , Espécies Reativas de Oxigênio/análise
3.
Indoor Air ; 29(5): 761-779, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31264732

RESUMO

The air composition and reactivity from outdoor and indoor mixing field campaign was conducted to investigate the impacts of natural ventilation (ie, window opening and closing) on indoor air quality. In this study, a thermal desorption aerosol gas chromatograph (TAG) obtained measurements of indoor particle- and gas-phase semi- and intermediately volatile organic compounds both inside and outside a single-family test home. Together with measurements from a suite of instruments, we use TAG data to evaluate changes in indoor particles and gases at three natural ventilation periods. Positive matrix factorization was performed on TAG and adsorbent tube data to explore five distinct chemical and physical processes occurring in the indoor environment. Outdoor-to-indoor transport is observed for sulfate, isoprene epoxydiols, polycyclic aromatic hydrocarbons, and heavy alkanes. Dilution of indoor species is observed for volatile, non-reactive species including methylcyclohexane and decamethylcyclopentasiloxane. Window opening drives enhanced emissions of semi- and intermediately volatile species including TXIB, DEET, diethyl phthalate, and carvone from indoor surfaces. Formation via enhanced oxidation was observed for nonanal and 2-decanone when outdoor oxidants entered the home. Finally, oxidative depletion of gas-phase terpenes (eg, limonene and α-pinene) was anticipated but not observed due to limited measurement resolution and dynamically changing conditions.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Ventilação/métodos , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Gases , Habitação , Humanos , Missouri , Tamanho da Partícula , Material Particulado , Ácidos Ftálicos/análise , Hidrocarbonetos Policíclicos Aromáticos
4.
Disaster Med Public Health Prep ; 16(4): 1482-1489, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34176549

RESUMO

OBJECTIVE: Stretcher transport isolators provide mobile, high-level biocontainment outside the hospital for patients with highly infectious diseases, such as Ebola virus disease. Air quality within this confined space may pose human health risks. METHODS: Ambient air temperature, relative humidity, and CO2 concentration were monitored within an isolator during 2 operational exercises with healthy volunteers, including a ground transport exercise of approximately 257 miles. In addition, failure of the blower unit providing ambient air to the isolator was simulated. A simple compartmental model was developed to predict CO2 and H2O concentrations within the isolator. RESULTS: In both exercises, CO2 and H2O concentrations were elevated inside the isolator, reaching steady-state values of 4434 ± 1013 ppm CO2 and 22 ± 2 mbar H2O in the first exercise and 3038 ± 269 ppm CO2 and 20 ± 1 mbar H2O in the second exercise. When blower failure was simulated, CO2 concentration exceeded 10 000 ppm within 8 minutes. A simple compartmental model predicted CO2 and H2O concentrations by accounting for human emissions and blower air exchange. CONCLUSIONS: Attention to air quality within stretcher transport isolators (including adequate ventilation to prevent accumulation of CO2 and other bioeffluents) is needed to optimize patient safety.


Assuntos
Poluição do Ar , Dióxido de Carbono , Humanos , Dióxido de Carbono/análise , Ventilação , Temperatura
5.
Radiother Oncol ; 167: 226-232, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34990726

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether single nucleotide polymorphisms disrupting microRNA targets (mirSNPs) can serve as predictive biomarkers for toxicity after radiotherapy for prostate cancer and whether these may be differentially predictive depending on radiation fractionation. MATERIALS AND METHODS: We identified 201 men treated with two forms of definitive radiotherapy for prostate cancer at two institutions: 108 men received conventionally-fractionated radiotherapy (CF-RT) and 93 received stereotactic body radiotherapy (SBRT). Germline DNA was evaluated for the presence of functional mirSNPs. Random forest, boosted trees and elastic net models were developed to predict late grade ≥2 GU toxicity by the RTOG scale. RESULTS: The crude incidence of late grade ≥2 GU toxicity was 16% after CF-RT and 15% after SBRT. An elastic net model based on 22 mirSNPs differentiated CF-RT patients at high risk (71.5%) versus low risk (7.5%) for toxicity, with an area under the curve (AUC) values of 0.76-0.81. An elastic net model based on 32 mirSNPs differentiated SBRT patients at high risk (64.7%) versus low risk (3.9%) for toxicity, with an area under the curve (AUC) values of 0.81-0.87. These models were specific to treatment type delivered. Prospective studies are warranted to further validate these results. CONCLUSION: Predictive models using germline mirSNPs have high accuracy for predicting late grade ≥2 GU toxicity after either CF-RT or SBRT, and are unique for each treatment, suggesting that germline predictors of late radiation sensitivity are fractionation-dependent. Prospective studies are warranted to further validate these results.


Assuntos
MicroRNAs , Neoplasias da Próstata , Radiocirurgia , Células Germinativas , Humanos , Masculino , MicroRNAs/genética , Próstata , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Sistema Urogenital
6.
Pract Radiat Oncol ; 12(4): 300-304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35717044

RESUMO

Treatment options for men with metastatic castration-resistant prostate cancer are rapidly changing. In addition to novel anti-androgens and taxane-based chemotherapy, radiopharmaceuticals are having an increasing role. Although calcium-mimetic theranostics have been in use for years, newer approaches use molecularly targeted radiation therapy by conjugating isotopes to prostate-specific membrane antigen (PSMA) and in so doing directly target prostate cancer cells; 177Lutetium-PSMA-617 is perhaps the best-known member of this new class. Expanding our capacity to deliver targeted beta-emitters requires additional planning and equipment. Having delivered close to 200 doses of 177Lutetium-PSMA-617 at our center, we offer practical advice about patient selection, radiation safety, treatment administration, and toxicity monitoring. Although this blueprint is not the only way to expand a theranostics program beyond Radium-223, we offer our institutional experience with 177Lutetium-PSMA-617 as an example to programs seeking to expand their radiopharmaceutical programs. We must rise to meet the patient-driven demand for these innovative and effective therapies.


Assuntos
Lutécio , Neoplasias de Próstata Resistentes à Castração , Humanos , Lutécio/uso terapêutico , Masculino , Medicina de Precisão , Próstata/patologia , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioisótopos , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do Tratamento
7.
Materials (Basel) ; 14(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918714

RESUMO

The use of facemasks is proven to mitigate the spread of the coronavirus and other biological agents that cause disease. Various forms of facemasks, made using different materials, are being used extensively, and it is important to determine their performance characteristics. The size-dependent filtration efficiency and breathing resistance of household sterilization wrap fabrics, and isolation media (American Society for Testing and Materials (ASTM)- and non-ASTM-rated), were measured in filter-holder- and mannequin-in-chamber-based systems, focusing on particles sizes between 20 nm and 2 µm. Double-layer MERV-14 (Minimum Efficiency Reporting Values with rating 14) showed the highest filtration efficiency (94.9-73.3%) amongst household filter media, whereas ASTM-rated isolation masks showed the highest filtration efficiencies (95.6-88.7) amongst all the masks considered. Filtration efficiency of 3D-printed masks with replaceable filter media was found to depend on the degree of sealing around the media holder, which depended on the material's compressibility. Filtration efficiencies of triple-layer combinations (95.8-85.3%) follow a profile similar to single layers but with improved filtration efficiencies.

8.
BMJ Open ; 11(9): e045557, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475144

RESUMO

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories. SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies. PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators. METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute for Occupational Safety and Health (NIOSH)-approved N95 respirators as controls. Fit testing using the 7-minute standardised Occupational Safety and Health Administration fit test was performed. In addition, protocols that can be performed in university laboratories for materials testing (filtration efficiency, air resistance and fluid resistance) were developed to evaluate alternate filtration materials. RESULTS: Among five open-source, improvised substitutes evaluated in this study, only one (which included a commercial elastomeric mask and commercial HEPA filter) passed a standard quantitative fit test. The four alternative materials evaluated for filtration efficiency (67%-89%) failed to meet the 95% threshold at a face velocity (7.6 cm/s) equivalent to that of a NIOSH particle filtration test for the control N95 FFR. In addition, for all but one material, the small surface area of two 3D-printed substitutes resulted in air resistance that was above the maximum in the NIOSH standard. CONCLUSIONS: Testing protocols such as those described here are essential to evaluate proposed improvised respiratory protection substitutes, and our testing platform could be replicated by teams with similar cross-disciplinary research capacity. Healthcare professionals should be cautious of claims associated with improvised respirators when suggested as FFR substitutes.


Assuntos
COVID-19 , Exposição Ocupacional , Dispositivos de Proteção Respiratória , Adulto , Desenho de Equipamento , Humanos , Respiradores N95 , Pandemias/prevenção & controle , SARS-CoV-2 , Estados Unidos , Ventiladores Mecânicos
9.
Radiother Oncol ; 154: 207-213, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035622

RESUMO

BACKGROUND AND PURPOSE: The optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens. MATERIALS AND METHODS: In 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35 Gy/5 fractions [35/5, n = 265, 13.4%], 36.25 Gy/5 fractions [36.25/5, n = 711, 37.3%], 40 Gy/5 fractions [40/5, n = 684, 35.8%], and 38 Gy/4 fractions [38/4, n = 257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5 ng/mL, and BCR-free survival (BCRFS). RESULTS: Median follow-up was 72.3 months. Median nPSA was 0.01 ng/mL for 38/4, and 0.17-0.20 ng/mL for 5-fraction regimens (p < 0.0001). The 38/4 cohort demonstrated the steepest PSA decay slope and greater odds of nPSA ≤0.2 ng/mL (both p < 0.0001 vs. all other regimens). BCR occurred in 6.25%, 6.75%, 3.95%, and 8.95% of men treated with 35/5, 36.25/5, 40/5, and 38/4, respectively (p = 0.12), with the highest BCRFS after 40/5 (vs. 35/5 hazard ratio [HR] 0.49, p = 0.026; vs. 36.25/5 HR 0.42, p = 0.0005; vs. 38/4 HR 0.55, p = 0.037) including the entirety of follow-up, but not for 5-year BCRFS (≥93% for all regimens, p ≥ 0.21). CONCLUSION: Dose-escalation was associated with greater prostate ablation and PSA decay. Dose-escalation to 40/5, but not beyond, was associated with improved BCRFS. Biochemical control remains excellent, and prospective studies will provide clarity on the benefit of dose-escalation.


Assuntos
Neoplasias da Próstata , Radiocirurgia , Humanos , Cinética , Masculino , Estudos Prospectivos , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia
10.
Case Rep Ophthalmol Med ; 2020: 8873078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963860

RESUMO

BACKGROUND: IgG4-related ophthalmic disease is a rare, newly recognized entity with high failure rates on first-line therapy of systemic corticosteroids and no other proven management options. Case Presentation. Here, we present the clinical course of a patient with IgG4 ophthalmic disease who achieved a favorable response from radiotherapy. Our patient initially presented with a history of recurrent painful flares of orbital inflammation, a pathologic diagnosis follicular lymphoid hyperplasia from a right lacrimal gland biopsy, and MRI imaging noting expansion of the lateral rectus muscle of the right eye. Initial treatment with dacryoadenectomy and multiple courses of corticosteroids failed to keep his symptoms at bay. Further evaluation revealed florid IgG4 staining. In this context, he was evaluated for image-guided intensity-modulated radiotherapy (IG-IMRT) to the orbit to 20 Gy in 10 fractions. His ophthalmic symptoms resolved. CONCLUSIONS: This treatment experience suggests radiotherapy may be a favorable option for symptom relief in patients with IgG4-related ophthalmic disease not controlled by corticosteroids.

11.
Front Oncol ; 10: 786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509582

RESUMO

Purpose: Dosimetric predictors of toxicity after Stereotactic Body Radiation Therapy (SBRT) are not well-established. We sought to develop a multivariate model that predicts Common Terminology Criteria for Adverse Events (CTCAE) late grade 2 or greater genitourinary (GU) toxicity by interrogating the entire dose-volume histogram (DVH) from a large cohort of prostate cancer patients treated with SBRT on prospective trials. Methods: Three hundred and thirty-nine patients with late CTCAE toxicity data treated with prostate SBRT were identified and analyzed. All patients received 40 Gy in five fractions, every other day, using volumetric modulated arc therapy. For each patient, we examined 910 candidate dosimetric features including maximum dose, volumes of each organ [CTV, organs at risk (OARs)], V100%, and other granular volumetric/dosimetric indices at varying volumetric/dosimetric values from the entire DVH as well as ADT use to model and predict toxicity from SBRT. Training and validation subsets were generated with 90 and 10% of the patients in our cohort, respectively. Predictive accuracy was assessed by calculating the area under the receiver operating curve (AROC). Univariate analysis with student t-test was first performed on each candidate DVH feature. We subsequently performed advanced machine-learning multivariate analyses including classification and regression tree (CART), random forest, boosted tree, and multilayer neural network. Results: Median follow-up time was 32.3 months (range 3-98.9 months). Late grade ≥2 GU toxicity occurred in 20.1% of patients in our series. No single dosimetric parameter had an AROC for predicting late grade ≥2 GU toxicity on univariate analysis that exceeded 0.599. Optimized CART modestly improved prediction accuracy, with an AROC of 0.601, whereas other machine learning approaches did not improve upon univariate analyses. Conclusions: CART-based machine learning multivariate analyses drawing from 910 dosimetric features and ADT use modestly improves upon clinical prediction of late GU toxicity alone, yielding an AROC of 0.601. Biologic predictors may enhance predictive models for identifying patients at risk for late toxicity after SBRT.

12.
Adv Radiat Oncol ; 5(3): 404-411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32529134

RESUMO

PURPOSE: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. METHODS: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. RESULTS: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. CONCLUSIONS: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

13.
Radiother Oncol ; 151: 26-32, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32663537

RESUMO

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS). METHODS AND MATERIALS: Retrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS. RESULTS: Median follow-up was 72 months. Median nPSA and nPSA <0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA <0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control. CONCLUSION: LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.


Assuntos
Braquiterapia , Neoplasias da Próstata , Radiocirurgia , Antagonistas de Androgênios , Humanos , Cinética , Masculino , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Dosagem Radioterapêutica , Estudos Retrospectivos
14.
JAMA Netw Open ; 2(2): e188006, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30735235

RESUMO

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.


Assuntos
Neoplasias da Próstata , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Próstata/cirurgia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radiocirurgia/efeitos adversos , Radiocirurgia/mortalidade , Resultado do Tratamento
15.
Int J Radiat Oncol Biol Phys ; 105(3): 628-636, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276777

RESUMO

PURPOSE: Understanding prostate-specific antigen (PSA) kinetics after radiation therapy plays a large role in the management of patients with prostate cancer (PCa). This is particularly true in establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiation therapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT. METHODS AND MATERIALS: PSA data from 5 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2004 to 2016. Patients received 35 to 40 Gy in 5 fractions, per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models were developed to identify significant predictors of time to biochemical failure. RESULTS: A total of 1062 patients were included in this study. Median follow-up was 66 months (interquartile range [IQR], 36.4-89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/mL, median time to nPSA was 40 months, 84% of patients had an nPSA ≤0.5 ng/mL, and 54% of patients had an nPSA ≤0.2 ng/mL. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/mL (IQR, 0.3-1.0 ng/mL). Median time to PSA bounce was 18.1 months (IQR, 12.0-31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. Joint latent class models modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure. CONCLUSIONS: In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.


Assuntos
Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Radiocirurgia , Fatores Etários , Idoso , Fracionamento da Dose de Radiação , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/metabolismo , Neoplasias da Próstata/patologia , Estudos Retrospectivos
16.
Transl Androl Urol ; 7(3): 308-320, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30050792

RESUMO

Intensity-modulated radiotherapy (IMRT) has become the standard radiotherapy technology utilized for the treatment of prostate cancer, as it permits the delivery of highly conformal radiation dose distributions. Image-guided radiotherapy (IGRT) is an essential companion to IMRT that allows the treatment team to account for daily changes in target anatomy and positioning. In the present review, we will discuss the different sources of geometric uncertainty and review the rationale behind using IGRT in the treatment of prostate cancer. We will then describe commonly employed IGRT techniques and review their benefits and drawbacks. Additionally, we will review the evidence suggesting a potential clinical benefit to utilizing IGRT.

17.
Cureus ; 10(3): e2368, 2018 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-29805937

RESUMO

We present a case of durable local control achieved in a patient treated with stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) for an abdominal lymph node in the setting of oligometastatic breast cancer. A 50-year-old woman with a history of triple positive metastatic invasive ductal carcinoma of the left breast, stage IV (T3N2M1), underwent neoadjuvant chemotherapy, mastectomy, adjuvant radiotherapy and maintenance hormonal treatment with HER2 targeted therapies. At 20 months after definitive treatment of her primary, imaging showed an isolated progressive enlargement of lymph nodes between hepatic segment V/IVB and the neck of the pancreas. Radiofrequency ablation was considered, however, this approach was decided not to be optimal due to the proximity to stomach, and pancreatic duct. The patient was treated with SMART for 40 Gray in 5 fractions. Two and a half years later, the patient remains without evidence of disease progression. She experienced Grade 2 acute and late toxicity that was successfully managed with medications. This experience shows that SMART is a feasible and effective treatment to control the abdominal oligometastatic disease for breast cancer.

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