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Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only. Results: Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.
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BACKGROUND: With advances in understanding liver tolerance, conformal techniques, image guidance, and motion management, dose-escalated radiotherapy has become a potential treatment for inoperable hepatocellular carcinoma (HCC). We aimed to evaluate the possible impact of biologically effective dose (BED) on local control and toxicity among patients with HCC. METHODS AND MATERIALS: Patients treated at our institution from 2009 to 2018 were included in this retrospective analysis if they received definitive-intent radiotherapy with a nominal BED of at least 60 Gy. Patients were stratified into small and large tumors using a cutoff of 5 cm, based on our clinical practice. Toxicity was assessed using ALBI scores and rates of clinical liver function deterioration. RESULTS: One hundred and twenty-eight patients were included, with a mean follow-up of 16 months. The majority of patients (90.5%) had a good performance status (ECOG 0-1), with Child-Pugh A (66.4%) and ALBI Grade 2 liver function at baseline (55.4%). Twenty (15.6%) patients had a local recurrence in the irradiated field during the follow-up period. Univariate and multivariate Cox proportional hazard analyses showed that only BED significantly predicted local tumor recurrence. Higher BED was associated with improved local control in tumors with equivalent diameters over 5 cm but not in smaller tumors. There was no difference in liver toxicity between the low and high-dose groups. CONCLUSIONS: Higher radiotherapy dose is associated with improved local control in large tumors but not in tumors smaller than 5 cm in diameter. High-dose radiotherapy was not associated with increased liver toxicity.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Doses de RadiaçãoRESUMO
CHADS2 and CHA2DS2-VASc scores are widely used in clinical practice and include similar risk factors for the development of coronary artery disease (CAD). It is known that the factors comprising the newly defined CHA2DS2-VASC-HSF score promote atherosclerosis and associated with severity of CAD. Objective of the study was to find out the association of the CHA2DS2-VASC-HSF score with the severity of CAD in patients with ST elevation myocardial infarction (STEMI). One hundred (100) patients with STEMI were enrolled in this study after considering inclusion and exclusion criteria over a one year period from October, 2017 to September, 2018 in the Department of Cardiology, National Institute of Cardiovascular Diseases, Dhaka, Bangladesh. Coronary angiogram was done within index hospitalization and coronary artery disease severity was assessed by SYNTAX score system. Patients were divided into two groups on the basis of SYNTAX score. Patients with SYNTAX score ≥23 assigned as Group I and SYNTAX score <23 assigned as Group II. The CHA2DS2-VASC-HSF score was calculated. Cut-off value of high CHA2DS2-VASC-HSF score was ≥4.0. In this study mean age of study population was 51.8±9.8, male patients were predominant (79.0%). Among the studied patients, highest percentage had history of smoking followed by hypertension, diabetes mellitus and family history of CAD in Group I patients. It was found that DM and family history of CAD and history of stroke/TIA were significantly higher in Group I than Group II. An increasing trend of SYNTAX score was observed according to the CHA2DS2-VASc-HSF score. SYNTAX score was significantly higher in CHA2DS2-VASc-HSF score ≥4 than CHA2DS2-VASc-HSF score <4 (26.3±6.3 vs. 12.1±7.7, p<0.001). Patients with CHA2DS2-VASC-HSF score ≥4 had severe coronary artery disease than CHA2DS2-VASC-HSF score <4 assessed by SYNTAX score with 84.4% sensitivity and 81.9% specificity (AUC:0.83, 95% CI: 0.746-0.915, p<0.001). CHA2DS2-VASc-HSF score was positively correlated with the severity of CAD. This score could be considered as a predictor of coronary artery disease severity.
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Doença da Artéria Coronariana , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Medição de Risco , Prognóstico , Bangladesh , Fatores de Risco , Índice de Gravidade de Doença , Estudos RetrospectivosRESUMO
OBJECTIVES: Disparities in asthma prevalence present a persistent challenge to public health. The complex nature of the issue requires studies through a wide range of lenses. To date, little research has examined associations between asthma and multiple social and environmental factors simultaneously. This study aims to fill the gap with a focus on the impacts of multiple environmental characteristics and social determinants of health on asthma. STUDY DESIGN: This study uses secondary analysis with data from a variety of sources to analyze the effects of environmental and social factors on adult asthma occurrence in North Central Texas. METHOD: Hospital records and demographic and environmental data for four urban counties in North Central Texas (Collin, Dallas, Denton, and Tarrant) come from the Dallas/Fort Worth Hospital Council Foundation, the US census, the North Central Texas Council of Governments, and the Railroad Commission of Texas. The data were integrated using ArcGIS. A hotspot analysis was performed to inspect the spatial patterns of hospital visits for asthma exacerbations in 2014. The impacts of multiple environmental characteristics and social determinants of health were modeled using negative binomial regression. RESULTS: The results revealed spatial clusters of adult asthma prevalence and disparities by race, class, and education. The occurrence of asthma exacerbations was positively associated with exposure to traffic-related air pollution, energy-related drilling activities, and older housing stock and negatively linked to green space. CONCLUSIONS: Associations between built environmental characteristics and asthma prevalence have implications for urban planners, healthcare professionals, and policy makers. Empirical evidence for the role of social determinants of health supports continuing efforts in policies and practices to improve education and reduce socio-economic inequities.
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Asma , Humanos , Adulto , Texas/epidemiologia , Asma/epidemiologia , Habitação , Escolaridade , Hospitais , Exposição AmbientalRESUMO
BACKGROUND: For patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making. MATERIALS AND METHODS: Patients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS). RESULTS: In total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS. CONCLUSION: This single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.
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Colite , Melanoma , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Humanos , Ipilimumab/efeitos adversos , Melanoma/terapia , Estudos Retrospectivos , Esteroides/uso terapêuticoRESUMO
PURPOSE: Concurrent chemoradiation therapy is a curative treatment for squamous cell carcinoma of the anus, but patients can suffer from significant treatment-related toxicities. This study was undertaken to determine whether intensity modulated proton therapy (IMPT) is associated with less acute toxicity than intensity modulated radiation therapy (IMRT) using photons. MATERIALS AND METHODS: We performed a multi-institutional retrospective study comparing toxicity and oncologic outcomes of IMRT versus IMPT. Patients with stage I-IV (for positive infrarenal para-aortic or common iliac nodes only) squamous cell carcinoma of the anus, as defined by the American Joint Committee on Cancer's AJCC Staging Manual, eighth edition, were included. Patients with nonsquamous histology or mixed IMPT and IMRT treatment courses were excluded. Acute nonhematologic toxicities, per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 4, were recorded prospectively at all sites. Acute and late toxicities, dose metrics, and oncologic outcomes were compared between IMRT and IMPT using univariable and multivariable statistical methods. To improve the robustness of our analysis, we also analyzed the data using propensity score weighting methods. RESULTS: A total of 208 patients were treated with either IMPT (58 patients) or IMRT (150 patients). Of the 208 total patients, 13% had stage I disease, 36% stage II, 50% stage III, and 1% stage IV. IMPT reduced the volume of normal tissue receiving low-dose radiation but not high-dose radiation to bladder and bowel. There was no significant difference between treatment groups in overall grade 3 or greater acute toxicity (IMRT, 68%; IMPT, 67%; P = .96) or 2-year overall grade 3 or greater late toxicity (IMRT, 3.5%; IMPT, 1.8%; P = .88). There was no significant difference in 2-year progression-free survival (hazard ratio, 0.8; 95% CI, 0.3-2.0). CONCLUSIONS: Despite reducing the volume of normal tissue receiving low-dose radiation, IMPT was not associated with decreased grade 3 or greater acute toxicity as measured by CTCAE. Additional follow-up is needed to assess whether important differences arise in late toxicities and if further prospective evaluation is warranted.
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Oral proliferative verrucous leukoplakia (PVL) is a rare, progressive form of leukoplakia with a high rate of malignant transformation. No therapies are known to lower the rate of malignant transformation and prevent a recurrence. An 84-year-old patient with a years-long history of symptomatic PVL of the hard palate refractory to CO2 laser ablation presented to the radiation oncology clinic for consideration of non-surgical management. High dose rate brachytherapy was used to deliver 36 Gy in 12 fractions to the hard palate using an Ir-192 source with a custom-molded applicator. By three months of follow-up, the patient had complete regression of the PVL and resolution of acute mucositis. With 18 months of follow-up, the patient remains disease- and symptom-free without toxicities of treatment. High dose rate surface applicator brachytherapy is a feasible and potentially effective treatment for oral PVL, yielding durable control with low long-term toxicity.
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BACKGROUND: Gut microbial diversity is associated with improved response to immune checkpoint inhibitors (ICI). Based on the known detrimental impact that antibiotics have on microbiome diversity, we hypothesized that antibiotic receipt prior to ICI would be associated with decreased survival. METHODS: Patients with stage III and IV melanoma treated with ICI between 2008 and 2019 were selected from an institutional database. A window of antibiotic receipt within 3 months prior to the first infusion of ICI was prespecified. The primary outcome was overall survival (OS), and secondary outcomes were melanoma-specific mortality and immune-mediated colitis requiring intravenous steroids. All statistical tests were two-sided. RESULTS: There were 568 patients in our database of which 114 received antibiotics prior to ICI. Of the patients, 35.9% had stage III disease. On multivariable Cox proportional hazards analysis of patients with stage IV disease, the antibiotic-exposed group had statistically significantly worse OS (hazard ratio [HR] = 1.81, 95% confidence interval [CI] = 1.27 to 2.57; P <.001). The same effect was observed among antibiotic-exposed patients with stage III disease (HR = 2.78, 95% CI = 1.31 to 5.87; P =.007). When limited to only patients who received adjuvant ICI (n = 89), antibiotic-exposed patients also had statistically significantly worse OS (HR = 4.84, 95% CI = 1.09 to 21.50; P =.04). The antibiotic group had a greater incidence of colitis (HR = 2.14, 95% CI = 1.02 to 4.52; P =.046). CONCLUSION: Patients with stage III and IV melanoma exposed to antibiotics prior to ICI had statistically significantly worse OS than unexposed patients. Antibiotic exposure was associated with greater incidence of moderate to severe immune-mediated colitis. Given the large number of antibiotics prescribed annually, physicians should be judicious with their use in cancer populations likely to receive ICI.
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Antibacterianos/efeitos adversos , Microbioma Gastrointestinal/genética , Variação Genética/efeitos dos fármacos , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Intervalo Livre de Doença , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Variação Genética/genética , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Fatores Imunológicos/antagonistas & inibidores , Fatores Imunológicos/genética , Imunoterapia/efeitos adversos , Masculino , Melanoma/microbiologia , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Adulto JovemRESUMO
Aging increases risk for ischemic vascular diseases. Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) are known to stimulate vascular regeneration. Activation of either the Mas receptor (MasR) by angiotensin-(1-7) (Ang-(1-7)) or angiotensin-converting enzyme-2 (ACE2) stimulates vasoreparative functions in HSPCs. This study tested if aging is associated with decreased ACE2 expression in HSPCs and if Ang-(1-7) restores vasoreparative functions. Flow cytometric enumeration of Lin-CD45lowCD34+ cells was carried out in peripheral blood of male or female individuals (22-83 years of age). Activity of ACE2 or the classical angiotensin-converting enzyme (ACE) was determined in lysates of HSPCs. Lin-Sca-1+cKit+ (LSK) cells were isolated from young (3-5 months) or old (20-22 months) mice, and migration and proliferation were evaluated. Old mice were treated with Ang-(1-7), and mobilization of HSPCs was determined following ischemia induced by femoral ligation. A laser Doppler blood flow meter was used to determine blood flow. Aging was associated with decreased number (Spearman r = - 0.598, P < 0.0001, n = 56), decreased ACE2 (r = - 0.677, P < 0.0004), and increased ACE activity (r = 0.872, P < 0.0001) (n = 23) in HSPCs. Migration or proliferation of LSK cells in basal or in response to stromal-derived factor-1α in old cells is attenuated compared to young, and these dysfunctions were reversed by Ang-(1-7). Ischemia increased the number of circulating LSK cells in young mice, and blood flow to ischemic areas was recovered. These responses were impaired in old mice but were restored by treatment with Ang-(1-7). These results suggest that activation of ACE2 or MasR would be a promising approach for enhancing ischemic vascular repair in aging.
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Envelhecimento , Enzima de Conversão de Angiotensina 2 , Peptidil Dipeptidase A , Células-Tronco , Animais , Feminino , Masculino , CamundongosRESUMO
Since the first recorded case of SARS-CoV-2 in Bangladesh on 8th March 2020, COVID-19 has spread widely through different regions of the country, resulting in a necessity to re-evaluate the delivery of cardiovascular services, particularly procedures pertaining to interventional cardiology in resource-limited settings. Given its robust capacity for human-to-human transmission and potential of being a nosocomial source of infection, the disease has specific implications on healthcare systems and health care professionals faced with performing essential cardiac procedures in patients with a suspected or confirmed diagnosis of COVID-19. The limited resources in terms of cardiac catheterization laboratories that can be designated to treat only COVID positive patients are further compounded by the additional challenges of unavailability of widespread rapid testing on-site at tertiary cardiac hospitals in Bangladesh. This document prepared for our nation by the Bangladesh Society of Cardiovascular Interventions (BSCI) is intended to serve as a clinical practice guideline for cardiovascular health care professionals, with a focus on modifying standard practice of care during the COVID-19 pandemic, in order to ensure continuation of adequate and timely treatment of cardiovascular emergencies avoiding hospital-based transmission of SARS-COV-2 among healthcare professionals and the patients. This is an evolving document based on currently available global data and is tailored to healthcare systems in Bangladesh with particular focus on, but not limited to, invasive cardiology facilities (cardiac catheterization, electrophysiology & pacing labs). This guideline is limited to the provision of cardiovascular care, and it is expected that specific targeted pharmaco-therapeutics against SARS-CoV-2 be prescribed as stipulated by the National Guidelines on Clinical Management of Corona virus Disease 2019 (COVID-19) published by the Director General of Health Services, Ministry of Health and Family Welfare of Bangladesh.
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Doenças Cardiovasculares , Procedimentos Cirúrgicos Cardiovasculares , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Bangladesh , Betacoronavirus , COVID-19 , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , SARS-CoV-2RESUMO
PURPOSE: Retrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT. METHODS AND MATERIALS: Data from the National Cancer Database were extracted for men aged 40-90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression. RESULTS: Patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non-dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy). CONCLUSION: In this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.
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Antagonistas de Androgênios/uso terapêutico , Braquiterapia , Neoplasias da Próstata/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
BACKGROUND: Neoadjuvant chemotherapy in breast cancer reduced mastectomy rates by 7% to 13% in randomized trials. However, the differential effects for women with different stages, receptor subtypes, and ages are unknown. We compared mastectomy rates in women who did vs did not receive neoadjuvant chemotherapy in 18 patient subgroups. The main objective was to quantify the potential benefit from neoadjuvant chemotherapy in reducing mastectomy rates for each subgroup. METHODS: Our retrospective analysis used data from the National Cancer Data Base, which includes approximately 70% of incident cancers across the United States. Absolute risk reductions for mastectomy were determined for 18 subgroups of clinical stage, receptor subtype, and age group. In each subgroup, propensity score weighting balanced measured covariates between women treated with vs without neoadjuvant chemotherapy. RESULTS: A total of 55 709 patients were analyzed. In clinical stage IIA disease, only patients with human epidermal growth factor receptor 2 (HER2)-positive tumors had reduced mastectomy rates associated with neoadjuvant chemotherapy (age < 60 years, 12%; age ≥ 60 years, 12.6%). For stage IIB cancers, neoadjuvant chemotherapy was associated with an absolute reduction in mastectomy rates of 5.9% in women younger than age 60 years with hormone receptor-positive/HER2- disease, 8.2% to 10.7% for triple-negative disease, and 11.7% to 17.4% for HER2+ disease. For stage IIIA, the reductions in mastectomy rates ranged from 6.6% to 15.9%. CONCLUSIONS: In an analysis of patients treated across the United States, we found that neoadjuvant chemotherapy was associated with a reduction in mastectomy rates to a similar magnitude overall as shown in randomized trials, but this benefit varied widely by patient subgroup. This study provides novel information to help women make informed decisions regarding treatment.
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BACKGROUND: Multiple clinical trials have shown that neoadjuvant systemic therapy has a benefit in women who are borderline lumpectomy candidates and in those with locally advanced breast cancers by reducing the mastectomy rate and making inoperable tumors operable. The study aim was to examine the patterns of neoadjuvant chemotherapy and endocrine therapy use among younger women in the United States treated at different types of cancer centers. STUDY DESIGN: Data from the National Cancer Data Base for 118,086 women younger than 65 years with clinical stage IIA (T2N0 only) to IIIC breast cancer. Following the National Comprehensive Cancer Network guideline categorization, patients were grouped into those who were borderline lumpectomy candidates (clinical stage IIA [T2N0 only], IIB, or IIIA [T3N1 only]) or those with locally advanced disease (clinical stage IIIA [T0-3N2 only], IIIB, or IIIC). The main outcome was the proportion of women who received neoadjuvant systemic therapy. RESULTS: Use of neoadjuvant chemotherapy ranged from 17% (stage IIA) to 79% (stage IIIB). Across almost all stage and receptor subtypes, the use was lower in community vs academic centers. On multivariable analysis, use of neoadjuvant chemotherapy was decreased in community vs academic centers (borderline lumpectomy candidates: adjusted risk ratio = 0.73; 95% CI, 0.69-0.77; locally advanced disease: adjusted risk ratio = 0.78; 95% CI, 0.74-0.83). CONCLUSIONS: Use of guideline-concordant neoadjuvant chemotherapy is significantly higher among women treated at academic vs community centers in young and healthy women who do not commonly have contraindications to this treatment. Our study identified a potential disparity in cancer care by type of center where patients receive treatment.
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Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Fidelidade a Diretrizes/estatística & dados numéricos , Mastectomia Segmentar , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Quimioterapia Adjuvante/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Estados UnidosAssuntos
Antagonistas de Androgênios/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias da Próstata/terapia , Radioterapia/estatística & dados numéricos , Terapia Combinada , Bases de Dados Factuais , Geografia , Humanos , Masculino , Análise Multivariada , Gradação de Tumores , Razão de Chances , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Estados UnidosRESUMO
BACKGROUND: Randomized trials have shown that androgen-deprivation therapy (ADT) improves survival for men with intermediate-risk prostate cancer treated with radiotherapy (RT). The benefit of ADT to patients with favorable intermediate-risk prostate cancer treated with modern dose-escalated RT is unknown. This study evaluated the effectiveness of ADT on survival of men with favorable intermediate-risk prostate cancer treated with dose-escalated RT. METHODS: This study was a retrospective cohort analysis of men with favorable intermediate-risk prostate cancer from 2004 to 2007 in the National Cancer Data Base. Favorable intermediate-risk disease was defined as 1 adverse risk factor (prostate-specific antigen level of 10-20 ng/mL or Gleason score of 7) and clinical T1/T2 prostate cancer. All patients were treated with primary dose-escalated RT (≥75.6 Gy or RT with a brachytherapy boost). Overall survival was analyzed with propensity score adjustment and Cox multivariate modeling. RESULTS: The study included 18,598 patients. The use of ADT decreased from 43.5% in 2004 to 39.5% in 2007. The propensity score-adjusted survival analysis demonstrated similar 8-year overall survival for men treated with dose-escalated RT and ADT and men treated with RT alone (77.7% vs 78.4%). ADT was not associated with improved survival in any age or comorbidity subgroup. In a sensitivity analysis using Cox multivariate modeling, the receipt of ADT was not associated with overall survival (hazard ratio, 0.99; 95% confidence interval, 0.91-1.07; P = .768). CONCLUSIONS: Adding ADT to modern dose-escalated RT was not associated with improved survival for patients with favorable intermediate-risk prostate cancer. The applicability of the survival benefit seen in older trials to modern patients is unclear. Because of the morbidity associated with ADT, dose-escalated RT alone for patients with favorable intermediate-risk prostate cancer may be a reasonable option. Cancer 2016;122:2341-2349. © 2016 American Cancer Society.
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Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Comorbidade , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Radioterapia/métodos , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Stereotactic body radiotherapy (SBRT) is a newer treatment option for patients with localized prostate cancer. The rates of diffusion of this technology across the United States are unknown. The goal of the current study was to describe the use of SBRT among patients with prostate cancer based on different risk groups (low, intermediate, or high risk) and by type of facility (community cancer program, comprehensive community cancer program, or academic program) in which patients were treated. METHODS: Using the National Cancer Data Base, a national registry that contains approximately 70% of patients with cancer in the United States, the authors identified 274,466 men between the ages of 40 to 80 years who were diagnosed from 2004 to 2012 with localized prostate cancer and received radiation therapy (RT) as their initial treatment. The authors described the prevalence of SBRT use each year, and multivariable analysis was used to examine factors associated with the receipt of SBRT. RESULTS: In 2004, SBRT use was low (<1% in all patient groups), and was observed to increase steadily each year. By 2012, 8.8% of low-risk patients treated at academic centers with RT received SBRT. Uptake of SBRT was highest in patients with low-risk or intermediate-risk disease. Multivariable analysis demonstrated that year of diagnosis, type of center, risk group, and race were all significantly associated with the use of SBRT. CONCLUSIONS: To the authors' knowledge, the current study is the first report of the adoption of SBRT for localized prostate cancer across the United States. Diffusion was noted to be slowest at community cancer programs, reflecting potential barriers of cost or expertise for this new technology. Adoption of SBRT was found to be highest among patients with low-risk or intermediate-risk disease, in accordance with the bulk of patients included in published SBRT studies. Cancer 2016;122:2234-41. © 2016 American Cancer Society.
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Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/radioterapia , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Terapia Combinada , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/história , Neoplasias da Próstata/patologia , Radiocirurgia/métodos , Sistema de Registros , Fatores Socioeconômicos , Estados Unidos/epidemiologiaRESUMO
Node-positive prostate cancer represents 12% of newly diagnosed prostate cancer cases in the United States; with decreasing use of screening, this proportion is likely to increase. However, very few clinical trials have specifically compared treatment options for this group of patients. Radiotherapy has a potential role as both definitive therapy and adjuvant therapy for node-positive prostate cancer. In regard to definitive treatment, retrospective studies comparing androgen deprivation therapy (ADT) alone vs ADT plus radiotherapy consistently demonstrated better survival associated with radiotherapy. In addition, two secondary analyses of clinical trial data compared radiotherapy alone vs radiotherapy plus ADT in this setting, and showed combination treatment achieved better survival. In terms of adjuvant treatment after prostatectomy in the setting of pathologic node-positive disease, the Eastern Cooperative Oncology Group (ECOG) 3886 trial established ADT as a standard of care. Institutional retrospective studies showed that ADT plus radiotherapy was associated with improved overall survival compared with ADT alone, but an analysis of the population-based Surveillance, Epidemiology and End Results-Medicare linked data did not show a benefit from radiotherapy. Because current management is informed by mostly retrospective studies, clinical trials are needed to more definitively guide treatment decisions for patients with node-positive disease. Off trial, radiotherapy with ADT should be offered to patients with this very aggressive form of prostate cancer.
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Adenocarcinoma/radioterapia , Antineoplásicos Hormonais/uso terapêutico , Linfonodos/efeitos da radiação , Neoplasias da Próstata/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Intervalo Livre de Doença , Humanos , Metástase Linfática , Masculino , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Taxa de SobrevidaRESUMO
The combination of radiation treatment and long-term androgen deprivation therapy (ADT) has been shown in multiple clinical trials to prolong overall survival in men with high-risk prostate cancer compared with either treatment alone. New radiation technologies enable the safe delivery of high radiation doses that improve cancer control compared with lower radiation doses. Based on the results of multiple randomized trials, clinical practice guidelines for high-risk prostate cancer recommend total radiation doses of at least 75.6 Gy, with long-term (2-3 years) ADT. Ongoing research into hypofractionated radiation treatment, whole-pelvic radiation, and combinations of radiation with novel hormonal agents could further improve cancer control and survival outcomes for patients with high-risk prostate cancer.
Assuntos
Neoplasias da Próstata/radioterapia , Terapia Combinada , Fracionamento da Dose de Radiação , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Resultado do TratamentoRESUMO
Paneth cell numbers increase following intestinal damage, but mechanisms driving this process are not understood. We hypothesized that the increase in Paneth cell numbers is due to recruitment of cells from a preexisting pool of secretory progenitors. Mice were given a single injection of doxorubicin (Dox), and intestinal tissue was collected 0-168 h after treatment. Paneth, goblet, and intermediate cells were counted and evaluated for cell morphology. Quantitative RT-PCR was used to measure expression of various genes associated with Paneth cell allocation and maturation. Paneth cells were birth dated using incorporation of thymidine analogs given before or after Dox. Staining revealed "intermediate" cells, which were rarely observed in control crypts but increased significantly in number 96 and 120 h after Dox treatment. Birth dating of intermediate cells 5 days after Dox treatment revealed that 24% of these cells took up thymidine analog given prior to Dox treatment and 36% took up thymidine analog given after Dox treatment. Quantitative RT-PCR demonstrated a significant increase in Spdef, Atoh1, Sox9, EphB3, Mist, Wnt5a, FGF-9, and FGF-18 mRNAs and a significant decrease in Indian hedgehog mRNA. Expansion of the Paneth cell compartment after Dox treatment is due to generation of new cells and recruitment of cells from an existing pool. These cells express Paneth and goblet biomarkers and are found only during repair. Expansion of these cells correlates temporally with reduced Indian hedgehog and increased FGF and Wnt mRNA. These findings are significant, as they provide a first step in understanding mechanisms of Paneth cell expansion during mucosal repair.