RESUMO
OBJECTIVE: To determine the accuracy of photon-counting-detector CT (PCD-CT) at deriving bone morphometric indices and demonstrate utility in vivo in the distal radius. METHODS: Ten cadaver wrists were scanned using PCD-CT and high-resolution peripheral quantitative CT (HRpQCT). Correlation between PCD-CT and HRpQCT morphometric indices was determined. Agreement was assessed by Lin's concordance correlation coefficient (Lin's CCC). Wrist PCD-CTs of patients between 02/2022 and 08/2023 were also evaluated for clinical utility. Morphometric indices of the in vivo distal radii were extracted and compared between patients with or without osteoporosis. RESULTS: In cadavers, strong correlation between PCD-CT and HRpQCT was observed for cortical thickness (Spearman correlation, ρ, 0.85), trabecular spacing (ρ = 0.98), and trabecular bone volume fraction (ρ = 0.68). Moderate negative correlation (ρ = - 0.49) was observed for trabecular thickness. PCD-CT shows good agreement to HRpQCT for cortical thickness, trabecular spacing, and trabecular bone volume fraction (Lin's CCC = 0.80, 0.94, and 0.86, respectively) but poor agreement (Lin's CCC = - 0.1) for trabecular thickness. In forty participants (31 adults and 9 pediatric), bone morphometrics indices for cortical thickness, trabecular thickness, trabecular spacing, and trabecular bone volume fraction were 0.99 mm (IQR, 0.89-1.06), 0.38 mm (IQR, 0.25-0.40), 0.82 mm (IQR, 0.72-1.05), and 0.28 (IQR, 0.25-0.33), respectively. Patients with osteoporosis had statistically significantly larger trabecular spacing (p = 0.025) and lower trabecular volumetric bone mineral density (p = 0.042). CONCLUSION: This study demonstrates the agreement of PCD-CT to HRpQCT in cadavers of most cortical and bone morphometrics examined and provide in vivo quantitative metrics of bone microarchitecture from routine clinical PCD-CT images of the distal radius.
RESUMO
BACKGROUND: Proton therapy is under investigation in breast cancer as a strategy to reduce radiation exposure to the heart and lungs. So far, studies investigating proton postmastectomy radiotherapy (PMRT) have used conventional fractionation over 25-28 days, but whether hypofractionated proton PMRT is feasible is unclear. We aimed to compare conventional fractionation and hypofractionation in patients with indications for PMRT, including those with immediate breast reconstruction. METHODS: We did a randomised phase 2 trial (MC1631) at Mayo Clinic in Rochester (MN, USA) and Mayo Clinic in Arizona (Phoenix, AZ, USA) comparing conventional fractionated (50 Gy in 25 fractions of 2 Gy [relative biological effectiveness of 1·1]) and hypofractionated (40·05 Gy in 15 fractions of 2·67 Gy [relative biological effectiveness of 1·1]) proton PMRT. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0-2, and breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Patients were randomly assigned (1:1) to either conventional fractionation or hypofractionation, with presence of immediate reconstruction (yes vs no) as a stratification factor, using a biased-coin minimisation algorithm. Any patient who received at least one fraction of protocol treatment was evaluable for the primary endpoint and safety analyses. The primary endpoint was 24-month complication rate from the date of first radiotherapy, defined as grade 3 or worse adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. The inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% CI for the difference in 24-month complication rate between the two groups was greater than 10%. This trial is registered with ClinicalTrials.gov, NCT02783690, and is closed to accrual. FINDINGS: Between June 2, 2016, and Aug 23, 2018, 88 patients were randomly assigned (44 to each group), of whom 82 received protocol treatment (41 in the conventional fractionation group and 41 in the hypofractionation group; median age of 52 years [IQR 44-64], 79 [96%] patients were White, two [2%] were Black or African American, one [1%] was Asian, and 79 [96%] were not of Hispanic ethnicity). As of data cutoff (Jan 30, 2023), the median follow-up was 39·3 months (IQR 37·5-61·2). The median mean heart dose was 0·54 Gy (IQR 0·30-0·72) for the conventional fractionation group and 0·49 Gy (0·25-0·64) for the hypofractionation group. Within 24 months of first radiotherapy, 14 protocol-defined complications occurred in six (15%) patients in the conventional fractionation group and in eight (20%) patients in the hypofractionation group (absolute difference 4·9% [one-sided 95% CI 18·5], p=0·27). The complications in the conventionally fractionated group were contracture (five [12%] of 41 patients]) and fat necrosis (one [2%] patient) requiring surgical intervention. All eight protocol-defined complications in the hypofractionation group were due to infections, three of which were acute infections that required surgical intervention, and five were late infections, four of which required surgical intervention. All 14 complications were in patients with immediate expander or implant-based reconstruction. INTERPRETATION: After a median follow-up of 39·3 months, non-inferiority of the hypofractionation group could not be established. However, given similar tolerability, hypofractionated proton PMRT appears to be worthy of further study in patients with and without immediate reconstruction. FUNDING: The Department of Radiation Oncology, Mayo Clinic, Rochester, MN, the Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA, and the US National Cancer Institute.
RESUMO
PURPOSE: In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether 18F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS). METHODS: Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus 18F-DOPA PET defined tumor. RESULTS: Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing 18F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed. CONCLUSION: 18F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.
Assuntos
Neoplasias Encefálicas , Glioma , Reirradiação , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Di-Hidroxifenilalanina/análogos & derivados , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Reirradiação/métodosRESUMO
BACKGROUND: Opioid use disorder has recently been declared a public health emergency, yet it is unknown whether opioid prescribing patterns have changed over time. Our objective is to examine opioid prescribing behavior and overdose fatalities in one large state prior to state-mandated usage of a prescription drug monitoring program (PDMP). Methods: We relied on de-identified longitudinal data from state and national databases for opioid prescriptions and overdose deaths in Texas between 2013 and 2017. Descriptive statistics and trend analyses were used to assess proportional differences and changes over time. Results: Prescriptions for opioids represented over 45% of the total controlled medications dispensed across the entire period. This equates to roughly 17.7 million opioid prescriptions dispensed per year, or 63.7 opioid prescriptions per 100 persons, slightly less than the reported national average. Hydrocodone was the most widely prescribed opioid (32.9%), followed by tramadol (26.9%) and codeine (21.5%). The overall controlled substance prescribing rate appears to be decreasing in the latest year, and the composition of opioids has shifted. We found a reduction in schedule II medications (such as hydrocodone and fentanyl) and increase in schedule IV medications such as tramadol. At the same time, total overdose fatalities increased 42% during this time, and population-adjusted rates increased 34% to 5.87 deaths per 100,000 persons. Conclusions: While prescribing rates have decreased in Texas, overdose deaths from both legal and illicit opioids are rising, suggesting that changing physician prescribing behavior alone may not be sufficient to curb the epidemic. Policies and community interventions should be considered to address increases in both prescription and illicit opioid deaths.
Assuntos
Analgésicos Opioides , Overdose de Drogas , Analgésicos Opioides/uso terapêutico , Overdose de Drogas/tratamento farmacológico , Prescrições de Medicamentos , Humanos , Hidrocodona , Padrões de Prática Médica , Texas/epidemiologiaRESUMO
The ongoing climate change crisis presents challenges to the global public health system. The risk of gastrointestinal illness (GI) related hospitalization increases following extreme weather events but is largely under-reported and under-investigated. This study assessed the association between precipitation and GI-related hospital admissions in four major cities in Texas. Daily data on GI-related hospital admissions and precipitation from 2004 to 2014 were captured from the Texas Department of State Health Services and the National Climate Data Center. Distributed lagged nonlinear modeling approaches were employed to examine the association between precipitation and GI-related hospital admissions. Results showed that the cumulative risk ratios (RRs) of GI-related hospital admissions were elevated in the 2 weeks following precipitation events; however, there were differences observed across study locations. The cumulative RR of GI-related hospitalizations was significantly higher when the amount of daily precipitation ranged from 3.3 mm to 13.5 mm in Dallas and from 6.0 mm to 24.5 mm in Houston. Yet, substantial increases in the cumulative RRs of GI-related hospitalizations were not observed in Austin or San Antonio. Age-specific and cause-specific GI-related hospitalizations were also found to be associated with precipitation events following the same pattern. Among them, Houston depicted the largest RR for overall GI and subgroup GI by age and cause, particularly for the overall GI among children aged 6 and under (RR = 1.35; 95 % CI = 1.11, 1.63), diarrhea-caused GI among children aged 6 and under (RR = 1.38, 95 % CI = 1.13, 1.69), and other-caused GI among children age 6 and under (RR = 1.46; 95 % CI = 1.12, 1.80). The findings underscore the need for public health interventions and adaptation strategies to address climate change-related health outcomes such as GI illness associated with extreme precipitation events.
RESUMO
ABSTRACT: Although it is evident that standard-dose whole-brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the US Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with nonmyeloablative consolidation after induction therapy for PCNSL. To our knowledge, this is the first randomized trial to be initiated that eliminates whole-brain radiotherapy as a consolidative approach in newly diagnosed PCNSL. Patients aged 18 to 75 years were randomly assigned in a 1:1 manner to induction therapy (methotrexate, temozolomide, rituximab, and cytarabine) followed by consolidation with either thiotepa plus carmustine and autologous stem cell rescue vs induction followed by nonmyeloablative, infusional etoposide plus cytarabine. The primary end point was progression-free survival (PFS). A total of 113 patients were randomized, and 108 (54 in each arm) were evaluable. More patients in the nonmyeloablative arm experienced progressive disease or death during induction (28% vs 11%; P = .05). Thirty-six patients received autologous stem cell transplant, and 34 received nonmyeloablative consolidation. The estimated 2-year PFS was higher in the myeloablative vs nonmyeloablative arm (73% vs 51%; P = .02). However, a planned secondary analysis, landmarked at start of the consolidation, revealed that the estimated 2-year PFS in those who completed consolidation therapy was not significantly different between the arms (86% vs 71%; P = .21). Both consolidative strategies yielded encouraging efficacy and similar toxicity profiles. This trial was registered at www.clininicals.gov as #NCT01511562.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Pessoa de Meia-Idade , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias do Sistema Nervoso Central/mortalidade , Adulto , Feminino , Masculino , Idoso , Linfoma/terapia , Linfoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Autólogo , Adolescente , Citarabina/uso terapêutico , Citarabina/administração & dosagem , Resultado do Tratamento , Quimioterapia de Consolidação , Terapia CombinadaRESUMO
Follicular lymphoma (FL) is an indolent B-cell neoplasm of germinal center origin. Standard treatment regimens consist of anti-CD20 therapy with or without chemotherapy. While high response rates to initial therapy are common, patients ultimately relapse or have progressive disease. Clinical risk factors such as the Follicular Lymphoma International Prognostic Index (FLIPI) have been identified, but there is a need for prognostic and predictive biomarkers. We studied markers of lymphoma cells and tumor microenvironment by immunohistochemistry in tissue samples from patients enrolled in 1 of 4 phase 2 trials of anti-CD20-based biological therapy for previously untreated grades 1 to 2 or 3A FL. Results were correlated with progression-free survival (PFS) and PFS status at 24 months. The 4 trials included 238 patients (51.1% male, median age: 55 y) with stage III, IV, or bulky stage II disease. By FLIPI, 24.6% had low-risk, 56.8% had intermediate-risk, and 18.6% had high-risk disease. The outcome differed significantly for patients treated with lenalidomide and rituximab (CALGB 50803) compared with the other 3 trials (median: PFS not reached vs. 3.0 y, hazard ratio=3.47, 95% confidence interval: 2.11-5.72); therefore, data were stratified by clinical trial (CALGB 50803 vs. all others) and adjusted for FLIPI risk group. Among 154 patients with available tissue, interfollicular BCL6 positivity, interfollicular CD10 positivity, and elevated Ki67 proliferation index ≥30% within neoplastic follicles were each associated with inferior PFS and a high risk of the early event by PFS status at 24 months. We identify promising biomarkers for FL risk stratification that warrant further validation in phase 3 trials.
Assuntos
Antígenos CD20/análise , Antineoplásicos Imunológicos/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais/análise , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Linfoma Folicular/imunologia , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neprilisina/análise , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-6/análise , Recidiva , Medição de Risco , Fatores de Risco , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Microambiente Tumoral , Estados Unidos , Adulto JovemRESUMO
INTRODUCTION: With opioid-related deaths reaching epidemic levels, gaining a better understanding of access to treatment for opioid use disorder (OUD) is critical. Most studies have focused on 1 side of the equation-either provider capacity or patients' need for care, as measured by overdose deaths. This study examines the overlay between treatment program availability and opioid mortality, comparing accessibility by region. METHODS: Geospatial and statistical analyses were used to model OUD treatment programs relative to population density and opioid overdose death incidence at the state and county level. We computed a ratio between program capacity and mortality called the programs-per-death (PPD) ratio. RESULTS: There were 40â274 opioid deaths in 2016 and 12â572 treatment programs across the contiguous 48 states, yielding a ratio of 1 program for every 3.2 deaths. Texas had the lowest number of treatment programs per 100â000 persons (1.4) and Maine the highest (13.2). West Virginia ranked highest in opioid deaths (39.09 per 100â000). Ohio, the District of Columbia, and West Virginia had the greatest mismatch between providers and deaths, with an average of 1 program for every 8.5 deaths. Over 32% of US counties had no treatment programs and among those with >10 deaths, nearly 2.5% had no programs. Over 19% of all counties had a ratio ≤1 provider facility per 10 deaths. CONCLUSION: Assessing the overlay between treatment capacity and need demonstrated that regional imbalances exist. These data can aid in strategic planning to correct the mismatch and potentially reduce mortality in the most challenged geographic regions.