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1.
South Med J ; 110(3): 188-194, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28257543

RESUMO

OBJECTIVES: The National Lung Screening Trial (NLST) reported that the prevalence of lung cancer in individuals at high risk for the disease is 1%, and that screening these individuals using low-dose helical computed tomography of the chest saves lives. To increase screening accessibility in the underserved southeastern United States, we developed a free lung screening program, modeled after the Lahey Hospital & Medical Center Free Lung Screening Program, for individuals meeting National Comprehensive Cancer Network high-risk criteria. METHODS: This was a chart review of 264 participants screened in the first year of our program. Participants were divided into categories based on the Lung Imaging Reporting and Diagnostic System. Categories three and four were considered positive findings, with demographic and disease criteria collected on these patients. RESULTS: Of 264 participants screened, 28 (10.6%) were Lung Imaging Reporting and Diagnostic System category four, 23 (8.7%) were category three, 78 (29.5%) were category two, and 135 (51.1%) were category one. Eight of the 264 participants (3.0%) had lung cancer, with 75% detected in early stages. CONCLUSIONS: We found a lung cancer prevalence in our high-risk screened population of 3.0% (8 of 264). After adjusting for patients who were symptomatic on clinical evaluation, we report a prevalence of cancer at 2.2% compared with 1.1% in the first year of the National Lung Screening Trial and a prevalence of 1.9% versus 0.6% compared with the National Comprehensive Cancer Network criteria in the first 10 months at Lahey Hospital & Medical Center. This study justifies low-dose helical computed tomography screening in high-risk regions because lung cancer treatment before symptoms appear is more effective, and the prevalence of disease in the detectable preclinical phase is high.


Assuntos
Detecção Precoce de Câncer/economia , Neoplasias Pulmonares/epidemiologia , Programas de Rastreamento/economia , Área Carente de Assistência Médica , Idoso , Feminino , Georgia/epidemiologia , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Prevalência , Tomografia Computadorizada Espiral
2.
Neuro Oncol ; 26(2): 348-361, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-37715730

RESUMO

BACKGROUND: Recurrent brain tumors are the leading cause of cancer death in children. Indoleamine 2,3-dioxygenase (IDO) is a targetable metabolic checkpoint that, in preclinical models, inhibits anti-tumor immunity following chemotherapy. METHODS: We conducted a phase I trial (NCT02502708) of the oral IDO-pathway inhibitor indoximod in children with recurrent brain tumors or newly diagnosed diffuse intrinsic pontine glioma (DIPG). Separate dose-finding arms were performed for indoximod in combination with oral temozolomide (200 mg/m2/day x 5 days in 28-day cycles), or with palliative conformal radiation. Blood samples were collected at baseline and monthly for single-cell RNA-sequencing with paired single-cell T cell receptor sequencing. RESULTS: Eighty-one patients were treated with indoximod-based combination therapy. Median follow-up was 52 months (range 39-77 months). Maximum tolerated dose was not reached, and the pediatric dose of indoximod was determined as 19.2 mg/kg/dose, twice daily. Median overall survival was 13.3 months (n = 68, range 0.2-62.7) for all patients with recurrent disease and 14.4 months (n = 13, range 4.7-29.7) for DIPG. The subset of n = 26 patients who showed evidence of objective response (even a partial or mixed response) had over 3-fold longer median OS (25.2 months, range 5.4-61.9, p = 0.006) compared to n = 37 nonresponders (7.3 months, range 0.2-62.7). Four patients remain free of active disease longer than 36 months. Single-cell sequencing confirmed emergence of new circulating CD8 T cell clonotypes with late effector phenotype. CONCLUSIONS: Indoximod was well tolerated and could be safely combined with chemotherapy and radiation. Encouraging preliminary evidence of efficacy supports advancing to Phase II/III trials for pediatric brain tumors.


Assuntos
Neoplasias Encefálicas , Neoplasias do Tronco Encefálico , Humanos , Criança , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Temozolomida , Triptofano , Fatores Imunológicos , Imunoterapia , Neoplasias do Tronco Encefálico/patologia
3.
JCO Precis Oncol ; 6: e2100201, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35201853

RESUMO

PURPOSE: Treatment of breast cancer (BC) with borderline or low (1%-9%) estrogen and progesterone expression remains controversial, with recent data disputing ASCO/College of American Pathologists 2010 guidelines that lowered the threshold of receptor positivity from 10% to 1%. The objective of this retrospective study was to validate these guidelines at the Georgia Cancer Center with a high percentage of Black race. METHODS: All female patients with invasive BC diagnosed between 2005 and 2010 at the Georgia Cancer Center were chart reviewed up to an 11-year follow-up with data cutoff at 2016. We used Cox regression to explore survival among three hormonal status (HS) groups (< 1%, 1%-9%, and ≥ 10%) adjusting for all known BC clinicopathologic variables. Fisher's exact test was used to evaluate response to endocrine therapy (ET). RESULTS: Among 431 patients with mean age 59 years, 24.75% had HS < 1%, 17.5% HS 1%-9%, and 57.75% HS ≥ 10%. Race was 43.75% Black and 54% White. Disease stages were early (I-IIIA) in 84.4% and advanced (IIIB-IV) in 15.56%. Mortality in HS < 1% was significantly higher than that in HS ≥ 10% (hazard ratio [HR]: 1.8; 95% CI, 1.07 to 3.02), whereas no significant mortality difference between HS 1%-9% and HS ≥ 10% (HR: 1.05; 95% CI, 0.48 to 2.30) was observed. ET was protective, and treated patients had higher predicted survival than untreated patients in the 1%-9% group (HR: 0.10; 95% CI, 0.01 to 0.85). There was no significant mortality difference between ET-treated HS 1%-9% and ≥ 10% groups. CONCLUSION: One percent cutoff predicted superior survival on treatment with ET compared with the other groups, and HS as low as 1%-9% was equiprognostic to HS ≥ 10%. Whether other factors such as lymphovascular invasion, grade, and other parameters change the behavior of the 1%-9% HS group remains to be explored.


Assuntos
Neoplasias da Mama , Patologistas , Neoplasias da Mama/tratamento farmacológico , Feminino , Georgia/epidemiologia , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
4.
Ann Thorac Surg ; 107(3): 885-890, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30419190

RESUMO

BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) chest scans in high-risk populations has been established as an effective measure of preventive medicine by the National Lung Screening Trial. However, the sustainability of funding a program is still controversial. We present a 2.5-year profitability analysis of our screening program by using the broader National Comprehensive Cancer Network criteria. METHODS: Retrospective chart review was performed on the initial 2.5-year data set of a free LDCT chest scan program that targeted the underserved Southeastern United States. Patients were selected by the National Comprehensive Cancer Network high-risk criteria, screening twice as many patients compared with Centers for Medicare and Medicaid Services criteria. LDCT scans were performed during the off-service hours of our positron emission tomography CT scanner. Analysis of fiscal years 2015 to 2017 was done to evaluate indirect cost, direct cost, and adjusted net margin per case after factoring downstream revenue from positive scans and other findings. RESULTS: A total of 705 scans were performed with 418 patients referred for subsequent procedures or specialist evaluations. The mean overhead cost over total cost was 42.3%. The adjusted net margin per case was -$212 in the first year but turned positive to $177 in the third fiscal year. The total break-even point of adjusted net margin was between 6% and 7% of indirect cost as a function of charges. Of the 60 new patients introduced to the hospital system, a gross margin per case of $211 was found. CONCLUSIONS: Free lung cancer screening can demonstrate profitability from downstream revenue with a lag time of 2 years.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/economia , Idoso , Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Feminino , Seguimentos , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos
5.
J Acquir Immune Defic Syndr ; 34(3): 320-30, 2003 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-14600579

RESUMO

BACKGROUND: The rates and risk factors for overall and medical condition-specific hospitalizations in HIV-positive women have not been examined in detail or compared with rates in risk factor-matched HIV-negative women. OBJECTIVE: To determine the rates and risk factors for overall and condition-specific hospitalizations. METHODS: Prospective cohort study of 885 HIV-positive women and 425 HIV-negative women followed for semiannual research visits between 1993 and 2000 in 4 urban locations in the United States. Outcome measures were hospitalization diagnoses with diabetes mellitus, nonacute renal conditions, cardiovascular conditions, liver conditions, AIDS defining conditions, and overall hospitalizations. Clinical and laboratory risk factors were assessed at research visits every 6 months, and effects of risk factors on hospitalization rates were calculated using generalized estimating equations and Poisson regression. RESULTS: Renal laboratory abnormalities, hypertension, and clinical AIDS were each associated with 3 of the 5 condition-specific hospitalization rates. Over time, diabetes-, nonacute renal-, and cardiovascular-related rates were flat or slightly increased and liver-related rates were significantly increased in HIV-positive women. Hospitalization rates with an AIDS-defining condition declined sharply in the latter half of the study period. CONCLUSIONS: In this population of largely African-American, inner-city, HIV-infected women, renal abnormalities, hypertension, and hepatitis C virus infection were common. Rate ratios indicated that "non-AIDS" risk factors were important predictors of hospitalization. In the highly active antiretroviral therapy era, clinicians must pay attention to these risk factors for morbidity and should closely monitor renal abnormalities, hypertension, and hepatitis status.


Assuntos
Infecções por HIV/complicações , Infecções por HIV/epidemiologia , HIV-1 , Adolescente , Adulto , Consumo de Bebidas Alcoólicas , Anticorpos Antivirais/sangue , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Estudos de Coortes , Creatinina/sangue , Complicações do Diabetes , Diabetes Mellitus/epidemiologia , Feminino , Hepatite C/complicações , Hepatite C/epidemiologia , Hospitalização , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Nefropatias/complicações , Nefropatias/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias , Estados Unidos/epidemiologia
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