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PURPOSE: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors. METHODS: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS. RESULTS: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively. CONCLUSION: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.
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Neoplasias da Mama , Feminino , Humanos , Idoso , Pessoa de Meia-Idade , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar/efeitos adversos , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Radioterapia Adjuvante , GenômicaRESUMO
Purpose: Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation. Methods and Materials: Intensity modulated EBRT and 103Pd-based LDR treatment plans were combined for 138 patients using biological effective dose (BED) and deformable image registration. GU and gastrointestinal (GI) toxicity were compared with combined dosimetry for the urethra, bladder, and rectum. Differences between doses in each toxicity grade were assessed by analysis of variance (α = 0.05). Combined dosimetric constraints are proposed using the mean organ-at-risk dose, subtracting 1 standard deviation for a conservative recommendation. Results: The majority of our 138-patient cohort experienced grade 0 to 2 GU or GI toxicity. Six grade 3 toxicities were noted. Mean prostate BED D90 (± 1 standard deviation) was 165.5±11.1 Gy. Mean urethra BED D10 was 230.3±33.9 Gy. Mean bladder BED was 35.2±11.0 Gy. Mean rectum BED D2cc was 85.6±24.3 Gy. Significant dosimetric differences between toxicity grades were found for mean bladder BED, bladder D15, and rectum D50, but differences between individual means were not statistically significant. Given the low incidence of grade 3 GU and GI toxicity, we propose urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy as preliminary dose constraints for combined modality therapy. Conclusions: We successfully applied our dose integration technique to a sample of patients with intermediate- and high-risk prostate cancer. Incidence of grade 3 toxicity was low, suggesting that combined doses observed in this study were safe. We suggest preliminary dose constraints as a conservative starting point to investigate and escalate prospectively in a future study.
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Five-fraction adjuvant whole breast radiation has been shown to be a safe and effective alternative to longer fractionation regimens. Given the lack of international consensus on patient selection for the protocol, we developed a consensus protocol to guide patient selection and facilitate safe and efficient five-fraction radiation in our radiation medicine department. In developing the directive, we surveyed departmental physicians about their choice of adjuvant breast regimen for various clinical scenarios. Patient travel burden was the factor most strongly impacting radiation oncologists' decision-making when considering prescribing a five-fraction course of adjuvant breast radiation; the length of clinical trial follow-up data and acute and late normal tissue effects also impacted it, along with personal clinical experience and experience of dosimetry and physics personnel. Relative value unit (RVU) reimbursement and financial toxicity to the patient were reported to be less important in decision-making. Physicians were most comfortable using five-fraction radiation in women >50 years of age with low-risk cancer and for patients unable to attend for longer treatment courses. Eight months after implementation, the protocol accounts for 4.7% of breast irradiation delivered in our department.
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This study aimed to evaluate rectal dose reduction in prostate cancer patients who underwent a combination of volumetric modulated arc therapy (VMAT) and low-dose-rate (LDR) brachytherapy with insertion of hydrogel spacer (SpaceOAR). For this study, 35 patients receiving hydrogel spacer and 30 patients receiving no spacer were retrospectively enrolled. Patient was treated to doses of 45 Gy to the primary tumor site and nodal regions over 25 fractions using VMAT and 100 Gy to the prostate using prostate seed implant (PSI). In VMAT plans of patients with no spacer, mean doses of rectal wall were 43.6, 42.4, 40.1, and 28.8 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively. In patients with SpaceOAR, average rectal wall doses decreased to 39.0, 36.9, 33.5, and 23.9 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively (p < 0.01). In PSI plans, rectal wall doses were on average 78.5, 60.9, 41.8, and 14.8 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively, in patients without spacer. In contrast, the doses decreased to 34.5, 28.4, 20.6 (p < 0.01), and 8.5 Gy (p < 0.05) to rectal wall volume of 0.5, 1, 2, and 5 cm3 , respectively, in patient with SpaceOAR. To demonstrate rectal sum dose sparing, dose-biological effective dose (BED) calculation was accomplished in those patients who showed >60% overlap of rectal volumetric doses between VMAT and PSI. In patients with SpaceOAR, average BEDsum was decreased up to 34%, which was 90.1, 78.9, 65.9, and 40.8 Gy to rectal volume of 0.5, 1, 2, and 5 cm3 , respectively, in comparison to 137.4, 116.7, 93.0, and 50.2 Gy to the volume of 0.5, 1, 2, and 5 cm3 , respectively, in those with no spacer. Our result suggested a significant reduction of rectal doses in those patients who underwent a combination of VMAT and LDR with hydrogel spacer placement.
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Neoplasias da Próstata , Radioterapia de Intensidade Modulada , Humanos , Hidrogéis , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Reto , Estudos RetrospectivosRESUMO
BACKGROUND: Long-term breast cancer survivors are at risk for cardiotoxicity after treatment, but there is insufficient evidence to provide long-term (~10 years) cardiovascular disease (CVD) screening recommendations. We sought to evaluate a tri-modality CVD screening approach. METHODS: This single-arm, feasibility study enrolled 201 breast cancer patients treated ≥6 years prior without CVD at diagnosis. Patients were sub-grouped: cardiotoxic (left-sided) radiation (RT), cardiotoxic (anthracycline-based) chemotherapy, both cardiotoxic chemotherapy and RT, and neither cardiotoxic treatment. Patients underwent electrocardiogram (EKG), transthoracic echocardiogram with strain (TTE with GLS), and coronary artery calcium computed tomography (CAC CT). The primary endpoint was preclinical or clinical CVD. RESULTS: Median age was 50 (29-65) at diagnosis and 63 (37-77) at imaging; median interval was 11.5 years (6.7-14.5). Among sub-groups, 44% had no cardiotoxic treatment, 31.5% had cardiotoxic RT, 16% had cardiotoxic chemotherapy, and 8.5% had both. Overall, 77.6% showed preclinical and/or clinical CVD and 51.5% showed clinical CVD. Per modality, rates of any CVD and clinical CVD were, respectively: 27.1%/10.0% on EKG, 50.0%/25.3% on TTE with GLS, and 50.8%/45.8% on CAC CT. No statistical difference was seen among the treatment subgroups (NS, χ2 test, p = 0.58/p = 0.15). CONCLUSION: This study identified a high incidence of CVD in heterogenous long-term breast cancer survivors, most >10 years post-treatment. Over half had clinical CVD findings warranting follow-up and/or intervention. Each imaging test independently contributed to the detection rate. This provides early evidence that long-term cardiac screening may be of value to a wider group of breast cancer survivors than previously recognized.
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Sobreviventes de Câncer , Cardiotoxicidade/diagnóstico por imagem , Neoplasias Unilaterais da Mama/tratamento farmacológico , Neoplasias Unilaterais da Mama/radioterapia , Adulto , Idoso , Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/epidemiologia , Ecocardiografia/métodos , Eletrocardiografia/métodos , Estudos de Viabilidade , Feminino , Coração/efeitos dos fármacos , Coração/efeitos da radiação , Humanos , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Análise de Regressão , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologiaRESUMO
PURPOSE: Low-dose-rate (LDR) brachytherapy and stereotactic body radiation therapy (SBRT) have both shown acceptable outcomes in the treatment of low- and intermediate-risk prostate cancer. Minimal data have been published directly comparing rates of biochemical control and toxicity with these 2 modalities. We hypothesize that LDR and SBRT will provide similar rates of biochemical control. METHODS AND MATERIALS: All low- and intermediate-risk patients with prostate cancer treated definitively with SBRT or LDR between 2010 and 2018 were captured. Phoenix definition was used for biochemical failure. Independent t tests were used to compare baseline characteristics, and repeated measure analysis of variance test was used to compare American Urologic Association (AUA) and the Expanded Prostate Cancer Index Composite (EPIC) scores between treatment arms over time. Biochemical control was estimated using the Kaplan-Meier method. Differences in acute and late toxicity were assessed via Pearson χ2. RESULTS: In the study, 219 and 118 patients were treated with LDR and SBRT. Median follow-up was 4.3 years (interquartile range, 3.1-6.1). All patients treated with LDR received 125.0 Gy in a single fraction. SBRT consisted of 42.5 Gy in 5 fractions. Five-year biochemical control for LDR versus SBRT was 91.6% versus 97.6% (P = .108). LDR patients had a larger increase in mean AUA scores at 1 month (17.2 vs 10.3, P < .001) and 3 months posttreatment (14.0 vs 9.7, P < .001), and in mean EPIC scores at 1 month (15.7 vs 13.8, P < .001). There was no significant difference between LDR and SBRT in late grade 3 genitourinary toxicity (0.9% vs 2.5%, P = .238); however, LDR had lower rates of late grade 3 gastrointestinal toxicity (0.0% vs 2.5%, P = .018). CONCLUSIONS: Our data show similar biochemical control and genitourinary toxicity rates at 5 years for both SBRT and LDR, with slightly higher gastrointestinal toxicity with SBRT and higher AUA and EPIC scores with LDR.
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Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Idoso , Análise de Variância , Braquiterapia/efeitos adversos , Trato Gastrointestinal/efeitos da radiação , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Órgãos em Risco/efeitos da radiação , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Risco , Fatores de Tempo , Sistema Urogenital/efeitos da radiaçãoRESUMO
The coronavirus disease 2019 (SARS-Cov-2 or COVID-19) pandemic has resulted in unprecedented clinical challenges across the globe. Outcomes of patients with this infection are likely dependent on underlying comorbidities that predict worse outcome in older patients. However, it is unknown whether COVID-19 infected cancer patients receiving radiation therapy (RT) have any different outcome than non-infected patients. We present the first series from our center of COVID-19 infected patients who received RT for malignancy, their outcome, and toxicities.
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PURPOSE: This study presents a prospective phase 1, institutional review board-approved dose-escalated stereotactic body radiation therapy trial for prostate cancer (CaP) to assess the impact of dose level on quality of life, toxicity, and clinical outcomes. METHODS AND MATERIALS: From 2011 to 2016, 26 patients with low- and intermediate-risk CaP received 40, 45, and 50 Gy in 5 fractions to the prostate in cohorts of 9, 10, and 7 patients. Self-reported quality of life was prospectively measured from the Expanded Prostate Cancer Index Composite and American Urological Association. Common Terminology Criteria for Adverse Events (version 4.03) data were collected to observe acute and late toxicities. The Phoenix definition was used to calculate outcome. No patients received androgen deprivation therapy. RESULTS: Median follow-up was 67.2 months (range, 71-230 months). There was an increase in Expanded Prostate Cancer Index Composite and American Urological Association scores followed by a return to baseline over 2 years for all cohorts. There were no grade 3 or higher toxicities or significant differences in toxicity between treatment arms. The prostate-specific antigen (PSA) nadir was significantly lower in the 45-Gy and 50-Gy cohorts when compared with the 40-Gy cohort (P < .05). Two biochemical failures were observed in the 40-Gy arm after 43 and 62 months, resulting in a freedom from biochemical failure rate of 92%. PSA survival was 100%, and actuarial overall survival was 96%. PSA nadir was 0.6, 0.1, and 0.1 ng/mL, in the 40-Gy, 45-Gy, and 50-Gy cohorts, respectively. CONCLUSIONS: This prospective, phase 1 dose-escalation study of stereotactic body radiation therapy for CaP identified acceptable genitourinary and gastrointestinal toxicity for each dose level of 40, 45, and 50 Gy. Although there was no difference in biochemical failure between the groups, we showed that higher doses of 45 and 50 Gy are associated with improved PSA nadir. The results of this study will be used to develop a larger prospective study to confirm the findings.
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Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Qualidade de Vida , Lesões por Radiação/patologia , Radiocirurgia/efeitos adversos , Reto/efeitos da radiação , Risco , Fatores de TempoRESUMO
BACKGROUND: Smoking and alcohol consumption are potential risk factors for breast cancer (BC) and may modify the risk of radiotherapy-associated second primary cancer (SPC) occurrence and total mortality. We explored the joint effect of smoking, or alcohol drinking, and radiotherapy on the risk of SPC and overall mortality among BC survivals. METHODS: We conducted a cancer registry-based study of 10,676 BC cases (stage 0-III) with data on smoking and alcohol consumption at time of diagnosis and clinical and therapeutics characteristics. Multivariable Cox proportional hazard models were used to estimate Hazard Ratios [HRs] and 95% confidence interval [CI] of total and site-specific SPC and mortality adjusting for demographic and cancer related characteristics. RESULTS: The SPC risk associated with radiotherapy was higher among ever-smokers than never-smokers (p for interaction = 0.04). Compared to never-smokers/unirradiated, the adjusted HR for ever-smokers/irradiated was 1.79 (95%CI, 1.43-2.23), and for never-smokers/irradiated was 1.31 (95%CI, 1.06-1.63). Analysis by cancer site showed that for ever-smokers/irradiated the risk for hematological, gastrointestinal, gynecological urological and lung/pulmonary cancer was significantly increased by two to five-fold. Mortality was significantly higher for ever-smokers/irradiated (HR = 1.25; 95%CI, 1.06-1.47), but was lower for never-smokers/irradiated (HR = 0.85; 95%CI, 0.73-0.99). Alcohol consumption did not alter the association between radiotherapy and SPC risk, but was associated with lower mortality risk. CONCLUSION: Patients who received radiotherapy and smoked before or at time of BC diagnosis have an increased risk for specific SPCs; drinking alcohol did not alter the effect of radiotherapy. Smoking significantly increased mortality risk reducing the protective effect of radiotherapy treatment.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias da Mama/radioterapia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Fumar Tabaco/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de RiscoRESUMO
PURPOSE: Hypofractionation (HF) of whole breast irradiation has become a standard treatment regimen because randomized trials continue to demonstrate equivalence in survival and local control compared with conventional fractionation. In 2011, the American Society for Radiation Oncology (ASTRO) adopted clinical guidelines on the proper selection of HF. Nevertheless, utilization remains lower than predicted. We evaluate the effects of clinical directives that serve as default treatment decisions and prospective contouring rounds on the implementation of HF in a large, multicenter radiation oncology department. METHODS AND MATERIALS: In 2010, we implemented consensus-driven and evidence-based clinical directives to guide treatment decisions. Five directives were available for adjuvant breast cancer treatment, including conventional fractionation and HF approaches, and were selected on the basis of disease specifics and clinical judgment. In 2012, we instituted prospective contouring rounds wherein the treating physicians presented their directive selection and patient contours for peer-review and consensus opinion. For this study, charts for patients with early stage breast cancer were reviewed. A total of 1043 cases of breast cancer were identified. Patients receiving HF were analyzed on the basis of the ASTRO 2011 guidelines and adherence to our more inclusive clinical directives. RESULTS: For the ASTRO-endorsed group (n = 685), 49% of patients received HF in 2011, and 80% received HF in 2015. For the directives-endorsed group (n = 1042), 47% of patients received HF in 2011, and 73% received HF in 2015. CONCLUSIONS: HF is underutilized despite equivalent local control, superior toxicity profile, and noninferior late effects. Our study demonstrates the possibility of achieving high levels of utilization in a large, multisite, outpatient setting. Factors responsible may include default rules established through the development of consensus-based treatment directives, peer review by faculty, and strong financial leadership to implement HF when indicated. To our knowledge, this is the first example of combining both consensus-based treatment directives and prospective contouring rounds in an attempt to change practice patterns.
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PURPOSE: This study was designed to present the results of a novel prospective contouring rounds (CR), in which peer review occurs once the contours and written directive are completed but before initiation of treatment planning. METHODS AND MATERIALS: Beginning in 2012, all patients undergoing conventionally fractionated radiation therapy at a high-volume academic center were reviewed in a newly initiated daily, prospective, multidisciplinary CR. Cases were scheduled for presentation 2 days after simulation with the expectation that contours would be complete. The clinical suitability of the clinical plan, prescription, contours, and written directive were evaluated and recorded in a prospective database. Treatment planning did not commence until CR approval. Patient information and the prospective database from the first 6 months since program inception, which represented 581 consecutive treatment plans, were pooled and analyzed retrospectively to determine the impact of the prospective peer review at this stage of care delivery. RESULTS: Sixty-four percent of cases were completed on time without correction. The remaining 36% of cases required modification before treatment planning was initiated. Incomplete contours, target-volume modifications, and alterations to the written directive were the most common corrections or reasons for delay. Decreasing rates of incomplete contours, contour modifications, and miscellaneous delays were seen over time as the program became established. The percentage of cases that had no delays or modifications increased continuously as the program matured in the first 6 months, from 59% to 70%. CONCLUSIONS: Prospective CR is a meaningful and impactful tool in the quality assurance process. More than one-third of cases required contour, directive, or scheduling modification. The establishment of CR improved quality of care, with the percentage of timely, errorless cases increasing steadily over time. The impact of clinical peer review may be optimized by implementation at this early stage of delivery of care rather than at the time of traditional chart rounds.
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Garantia da Qualidade dos Cuidados de Saúde/normas , Humanos , Estudos ProspectivosRESUMO
INTRODUCTION: While much emphasis on safety in the radiation oncology clinic is placed on process, there remains considerable opportunity to increase safety, enhance outcomes, and avoid ad hoc care by instituting detailed treatment pathways. The purpose of this study was to review the process of developing evidence and consensus-based, outcomes-oriented treatment pathways that standardize treatment and patient management in a large multi-center radiation oncology practice. Further, we reviewed our compliance in incorporating these directives into our day-to-day clinical practice. METHODS: Using the Institute of Medicine guideline for developing treatment pathways, 87 disease specific pathways were developed and incorporated into the electronic medical system in our multi-facility radiation oncology department. Compliance in incorporating treatment pathways was assessed by mining our electronic medical records (EMR) data from January 1, 2010 through February 2012 for patients with breast and prostate cancer. RESULTS: This retrospective analysis of data from EMR found overall compliance to breast and prostate cancer treatment pathways to be 97 and 99%, respectively. The reason for non-compliance proved to be either a failure to complete the prescribed care based on grade II or III toxicity (n = 1 breast, 3 prostate) or patient elected discontinuance of care (n = 1 prostate) or the physician chose a higher dose for positive/close margins (n = 3 breast). CONCLUSION: This study demonstrates that consensus and evidence-based treatment pathways can be developed and implemented in a multi-center department of radiation oncology. And that for prostate and breast cancer there was a high degree of compliance using these directives. The development and implementation of these pathways serve as a key component of our safety program, most notably in our effort to facilitate consistent decision-making and reducing variation between physicians.
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By combining incident learning and process failure-mode-and-effects-analysis (FMEA) in a structure-process-outcome framework we have created a risk profile for our radiation medicine practice and implemented evidence-based risk-mitigation initiatives focused on patient safety. Based on reactive reviews of incidents reported in our departmental incident-reporting system and proactive FMEA, high safety-risk procedures in our paperless radiation medicine process and latent risk factors were identified. Six initiatives aimed at the mitigation of associated severity, likelihood-of-occurrence, and detectability risks were implemented. These were the standardization of care pathways and toxicity grading, pre-treatment-planning peer review, a policy to thwart delay-rushed processes, an electronic whiteboard to enhance coordination, and the use of six sigma metrics to monitor operational efficiencies. The effectiveness of these initiatives over a 3-years period was assessed using process and outcome specific metrics within the framework of the department structure. There has been a 47% increase in incident-reporting, with no increase in adverse events. Care pathways have been used with greater than 97% clinical compliance rate. The implementation of peer review prior to treatment-planning and use of the whiteboard have provided opportunities for proactive detection and correction of errors. There has been a twofold drop in the occurrence of high-risk procedural delays. Patient treatment start delays are routinely enforced on cases that would have historically been rushed. Z-scores for high-risk procedures have steadily improved from 1.78 to 2.35. The initiatives resulted in sustained reductions of failure-mode risks as measured by a set of evidence-based metrics over a 3-years period. These augment or incorporate many of the published recommendations for patient safety in radiation medicine by translating them to clinical practice.
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OBJECTIVES: To evaluate the disease and treatment-related factors for predicting biochemical freedom from recurrence (BFR) in patients with clinically localized prostate cancer undergoing permanent prostate brachytherapy. METHODS: Between November 1992 and June 1998, 883 consecutive patients with T1-T2 prostate cancer underwent permanent prostate brachytherapy. Computed tomography-based dosimetry was performed, and the minimal dose to 90% of the prostate volume relative to the prescribed dose (D(90)) was calculated. BFR was defined as three prostate-specific antigen (PSA) rises from nadir, with patients having one or two PSA rises censored early. Follow-up was calculated by censored events. Kaplan-Meier actuarial outcome was determined, and multivariate Cox regression analysis was performed to assess the significance of the D(90), initial PSA value, Gleason score, addition of external beam radiotherapy, addition of hormonal therapy, and isotope selection. RESULTS: The mean follow-up was 55 months (range 3 to 125). The 10-year BFR rate was 79.1%. Cox proportional analysis identified D(90) as a predictor of BFR (P <0.0001), along with Gleason score, initial PSA level, and clinical stage (P = 0.001, P = 0.001, and P = 0.011, respectively). The addition of external beam radiotherapy, hormonal therapy, and isotope selection did not have an impact on BFR (P = 0.128, P = 0.399, and P = 0.224, respectively). CONCLUSIONS: The quality of permanent prostate brachytherapy as measured by the D(90) was the most significant predictor for BFR in this study cohort at 10 years. Furthermore, adding external beam radiotherapy and/or hormonal therapy as adjuvant therapies did not independently predict for BFR. Overall, the reported 10-year BFR rates in this study were favorable. Strategies for ensuring the best quality implant should be used and, when reporting brachytherapy outcomes, the implant quality should be noted.
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Adenocarcinoma/radioterapia , Braquiterapia , Neoplasias da Próstata/radioterapia , Radiometria , Dosagem Radioterapêutica , Adenocarcinoma/sangue , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Idoso , Biomarcadores Tumorais/sangue , Estudos de Coortes , Seguimentos , Humanos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Resultado do TratamentoRESUMO
To define the effects of neurotrophins on oligodendrocytes, we monitored NGF, BDNF and NT-3 actions on basal forebrain (BF) and cortical populations. NGF, BDNF and NT-3 applied to BF oligodendrocytes elicited increases in expression of myelin basic protein (MBP) and enhanced the numbers of MBP+ cells, without affecting total cell numbers. In the cortex, however, while NGF and NT-3 influenced MBP expression, BDNF was without effect. To explore this apparent regional difference in BDNF action, we compared expression of the neurotrophin receptors trkA, trkB and trkC. While BF cells expressed all three trks, cortical cells did not express the full-length BDNF receptor, trkB. Interestingly, in no case was any receptor expressed by all oligodendrocytes, indicating that oligodendrocytes may be heterogeneous within a brain region. The data suggest that BF oligodendrocytes are influenced by BDNF to express MBP and are distinct in this ability from cortical cells.
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Fator Neurotrófico Derivado do Encéfalo/farmacologia , Córtex Cerebral/efeitos dos fármacos , Oligodendroglia/citologia , Oligodendroglia/efeitos dos fármacos , Prosencéfalo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Western Blotting , Diferenciação Celular , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Imuno-Histoquímica , Proteína Básica da Mielina/biossíntese , Proteína Básica da Mielina/efeitos dos fármacos , Fator de Crescimento Neural/farmacologia , Neurotrofina 3/farmacologia , Oligodendroglia/metabolismo , Prosencéfalo/citologia , Prosencéfalo/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor trkA/biossíntese , Receptor trkB/biossíntese , Receptor trkC/biossínteseRESUMO
PURPOSE: To compare PSA relapse-free survival (PSA-RFS) between African-American (AA) and white American (WA) males treated with permanent prostate brachytherapy (PPB) for clinically localized prostate cancer. METHODS AND MATERIALS: One thousand eighty-one consecutive patients, including 246 African-Americans, underwent PPB with 103Pd or 125I, alone or with external beam radiation therapy between September 1992 and September 1999. Computer-generated matching was performed to create two identical cohorts of WA and AA males, based on the use of neoadjuvant androgen ablation (NAAD), pretreatment PSA, and Gleason score. Presenting characteristics were used to define risk groups, as follows: Low risk had PSA
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População Negra , Braquiterapia , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , População Branca , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Intervalo Livre de Doença , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Paládio/uso terapêutico , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Radioisótopos/uso terapêutico , Dosagem Radioterapêutica , Resultado do TratamentoRESUMO
PURPOSE: To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation. METHODS AND MATERIALS: Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score > or = 7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses. RESULTS: HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA < or = 15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%. CONCLUSION: In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses.