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OBJECTIVES: Studies investigating preoperative 5-fraction radiation therapy (RT) for soft tissue sarcoma (STS) are limited. We performed a meta-analysis to determine the efficacy and safety of this treatment paradigm. METHODS: This study-level meta-analysis was conducted using Bayesian methods. Statistical estimation for risk of outcome rates was conducted by posterior mean and 95% highest posterior density (HPD) intervals. Studies with 2-year local control (LC) and description of major wound complications (MWC) per the CAN-NCIC-SR2 study were included and served as the primary endpoints. Secondary endpoints included rates of acute and late toxicity. A total of 10 studies were identified and 7 met the inclusion criteria. Subgroup analyses were performed for ≥30 Gy vs <30 Gy. RESULTS: A total of 209 patients from 7 studies were included. Five studies used ≥30 Gy (n=144), and 2 studies <30 Gy (n=64). Median follow-up was 29 months (range: 21 to 57 mo). Primary tumor location was lower extremity in 68% and upper extremity in 22%. Most tumors were intermediate or high grade (95%, 160/169), and 50% (79/158) were >10 cm. The two-year LC for the entire cohort was 96.9%, and the rate of MWC was 30.6%. There was a trend toward improved LC with ≥ 30 Gy (95% HPD: 0.95 to 0.99 vs 0.84 to 0.99). There was no difference in MWC (95% HPD: 0.18 to 0.42 vs 0.17 to 0.55) or late toxicity between the groups. CONCLUSIONS: Preoperative 5-fraction RT for STS demonstrates excellent 2-year LC with MWC and toxicity similar to standard fractionation preoperative RT. Multi-institutional trials with a universal RT protocol are warranted.
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Fracionamento da Dose de Radiação , Sarcoma , Humanos , Teorema de Bayes , Cuidados Pré-Operatórios , Sarcoma/radioterapia , Sarcoma/cirurgia , Sarcoma/patologiaRESUMO
PURPOSE/OBJECTIVE(S): Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. MATERIALS/METHODS: We performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. RESULTS: Mean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). CONCLUSION: Low-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.
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Neoplasias da Mama , Radioterapia de Intensidade Modulada , Humanos , Idoso , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/cirurgia , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Mastectomia Segmentar , Cuidados IntraoperatóriosRESUMO
BACKGROUND: Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completion of treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Our institution had used low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate with a short follow-up period of 2 years. This report presents updated outcomes during with 5-year follow-up. METHODS: A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with 20 Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). RESULTS: The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. CONCLUSIONS: The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation following breast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Terapia Combinada , Cuidados Intraoperatórios/métodos , Mastectomia Segmentar/métodos , Recidiva Local de Neoplasia/cirurgia , Estudos ProspectivosAssuntos
Tosse , Adulto , Humanos , Tosse/diagnóstico , Tosse/etiologia , Tosse/terapia , Doença CrônicaRESUMO
Background: Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods: We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results: An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions: The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.
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PURPOSE: Persons experiencing homelessness (PEH) have low rates of cancer screening and worse cancer mortality compared with persons not experiencing homelessness. Data regarding cancer diagnosis and treatment in PEH are limited. We investigated cancer prevalence and use of radiation therapy (RT) in PEH. METHODS AND MATERIALS: Patients presenting between January 1, 2014, and September 27, 2021, at a large metropolitan hospital system were assessed for homelessness via intake screening or chart search. PEH data were cross-referenced with the institution's cancer database to identify PEH with cancer diagnoses. Demographic, clinical, and treatment variables were abstracted. RESULTS: Of a total of 9654 (9250 evaluable) PEH with a median age of 42 years, 81 patients (0.88%) had at least 1 cancer diagnosis and 5 had multiple diagnoses, for a total of 87 PEH with at least 1 cancer diagnosis. The median age at diagnosis was 60 years. In total, 43% were female and 51% were Black, and 43% presented with advanced or metastatic disease. Lung (17%), prostate (15%), leukemia/lymphoma (13%), and head/neck (9%) were the most common diagnoses. In total, 17% of patients underwent surgery alone, 13% received chemotherapy alone, 14% received RT alone, and 6% received hormone therapy alone. A total of 8% of patients underwent no treatment, and 43% underwent multimodality therapy. In total, 58% of treated patients never achieved disease-free status. Of the 31 patients who received RT, 87% received external beam RT. Most patients (70%) received hypofractionated regimens. For patients who had multifraction treatment, the treatment completion rate was 85%, significantly lower than the departmental completion rate of 98% (P < .00001). CONCLUSIONS: In a large cohort of PEH in a metropolitan setting, cancer diagnoses were uncommon and were frequently in advanced stages. Most patients underwent single-modality treatment or no treatment at all. Despite the use of hypofractionation, the RT completion rate was low, likely reflecting complex barriers to care. Further interventions to optimize cancer diagnosis and treatment in PEH are urgently needed.
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Pessoas Mal Alojadas , Neoplasias , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Terapia Combinada , Neoplasias/radioterapiaRESUMO
Understanding the risk factors for breakthrough coronavirus disease 2019 (COVID-19) (BC19) is critical to inform policy. Herein, we assessed Delta (Lineage B.1.617.2) variant-specific effectiveness of the BNT162b2 (Pfizer) vaccine and characterized Delta-driven BC19 cases (fully vaccinated individuals who get infected) with known-time-since-vaccination. In this longitudinal prospective study (January 21-October 30, 2021), 90 naïve and 15 convalescent individuals were enrolled at the initiation of vaccination. Samples from 27 unvaccinated individuals with previous laboratory-confirmed COVID-19 diagnosis were collected at a single time point. Longitudinal serology profile (antibodies against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] S and N proteins) and live-virus-based neutralization capacities were assessed while controlling for age. Sex, age, history of reactions to the COVID-19 vaccine, and viral neutralization capacities were identified as significant risk factors for breakthrough COVID-19. At 8 months postvaccination, male sex, individuals ⩾65 years of age, and individuals who experienced noticeable side effects with the COVID-19 vaccine were at 5.47 (p-value = 0.0102), 4.33 (p-value = 0.0236), and 4.95 (p-value = 0.0159) fold greater risk of BC19 as compared to their peers, respectively. Importantly, every five-fold increase in viral neutralization capacities (by live-virus-based assays) was significantly associated with ~4-fold reduction in the risk occurrence of breakthrough COVID-19 (p-value = 0.045). Vaccine boosting remarkably increased these viral neutralization capacities by 16.22-fold (p- value = 0.0005), supporting the importance of the BNT162b2 booster in efforts to control the incursion of future variants into the population at large. Strikingly, BC19 cases exhibited a delayed/absent antibody response to the N protein, suggesting limited exposure to the virus. Since antibodies against N protein are widely used to evaluate the extent of virus spread in communities, our finding has important implications on the utility of existing serological diagnostic and surveillance for COVID-19.
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Vacinas contra COVID-19 , COVID-19 , Masculino , Humanos , Formação de Anticorpos , SARS-CoV-2 , Vacina BNT162 , Teste para COVID-19 , Estudos Prospectivos , COVID-19/prevenção & controle , AnticorposRESUMO
PURPOSE: The purpose of this study was to assess prostate-specific antigen (PSA) testing rates in persons experiencing homelessness (PEH), identify factors associated with screening, and compare PSA screening rates in PEH with a matched cohort of persons not experiencing homelessness (non-PEH). MATERIALS AND METHODS: We identified 9,249 potentially eligible PEH cared for at a large metropolitan hospital system from an institutional registry of all patients who presented to the health care system as homeless from 2014 to 2021. Homelessness was defined by the presence of the Z-code for homelessness (Z59), the listed address matching to the address of a homeless shelter or other transitional housing or a positive screen for homelessness. A matched cohort of 10,000 non-PEH was generated for comparison. Univariate chi-square analysis and multivariate logistic regression were performed to evaluate variables associated with PSA testing. RESULTS: A total of 1,605 PEH and 3,413 non-PEH were eligible for PSA screening within the study timeframe. Half of PEH were Black (50%). Medicaid was the most common insurance (51%), followed by Medicare (18%). PEH were less likely to have a PCP (58% v 81%, P < .001) and had a significantly lower PSA testing rate (13% v 34%, P < .001) compared with non-PEH. Univariate analysis revealed that PSA testing was more common in PEH who were employed (P < .001), had private insurance or Medicare (P < .001), or had an established primary care provider (PCP; P < .001). Multivariate analysis confirmed that having a PCP (OR, 2.54; 95% CI, 1.62 to 4.00; P < .001) significantly increased the likelihood of PSA testing in PEH. CONCLUSION: PEH experience low rates of prostate cancer screening. Interventions to increase screening in this population, including increased PCP access, are needed.
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Pessoas Mal Alojadas , Neoplasias da Próstata , Masculino , Humanos , Idoso , Estados Unidos , Detecção Precoce de Câncer , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , MedicareRESUMO
INTRODUCTION: Publishing research is an important component of medical students' career development and becoming a more competitive residency applicant. Many medical schools offer structured programs to enable students to participate in research during their preclinical and clinical years, but the majority of student-mentor partnerships do not culminate in publication across a variety of institutions and medical specialties. The primary objective of this study is to determine if any factors associated with mentee-mentor partnerships are predictive of publication from two school-sponsored research programs at a single US medical school. METHODS: The PubMed-indexed publications of all student-mentor pairings from a summer internship (after year 1 of medical school) or research elective (during year 4 of medical school) at a single institution from 2008 to 2018 were retrospectively reviewed. Student/mentor demographic information was associated with the probability of publication. RESULTS: A total of 124 students participated in the summer internship with 32 (26%) achieving publication. The publication was significantly more likely for students that were from highly ranked undergraduate institutions (p = 0.04; likelihood ratio (LR) = 5.788), were future Alpha Omega Alpha (AOA) members (p = 0.03; LR = 4.597), or worked with a mentor focused on clinical rather than basic science research (p = 0.02; LR = 5.662). Forty-four students participated in the fourth-year elective with 11 (25%) achieving publication. The publication was more likely if the student worked with a mentor without a Doctor of Medicine (MD)/Doctor of Osteopathic Medicine (DO) degree (p = 0.001; LR = 7.051), with a PhD degree (p = 0.002; LR = 7.820), or a mentor with prior publication(s) with prior mentee(s) (p = 0.03; LR = 5.368). CONCLUSION: Only one-quarter of mentor-mentee research pairings resulted in publication, with student-related factors more predictive for publication from the internship and mentor-related factors more predictive of publication from the elective. Approaches to promote successful completion of medical student research projects should be considered to yield the greatest value from students' work and strengthen the development of future physician-scientists.
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OBJECTIVE: Airway sensory nerves involved in the cough reflex are activated by adenosine triphosphate (ATP) agonism of P2X purinoceptor 3 (P2X3) receptors. Transient receptor potential vanilloid 4 (TRPV4) channel activation causes ATP release from airway cells, and it is hypothesised that a TRPV4-ATP-P2X3 axis contributes to chronic cough. An adaptive study was run to determine if TRPV4 inhibition, using the selective TRPV4 channel blocker GSK2798745, was effective in reducing cough. METHODS: A two-period randomised, double blinded, placebo-controlled crossover study was designed with interim analyses for futility and sample size adjustment. Refractory chronic cough patients received either GSK2798745 or placebo once daily for 7â days with a washout between treatments. Pharmacokinetic samples were collected for analysis of GSK2798745 at end of study. The primary end-point was total cough counts assessed objectively during day-time hours (10â h) following 7â days of dosing. RESULTS: Interim analysis was performed after 12 participants completed both treatment periods. This showed a 32% increase in cough counts on Day 7 for GSK2798745 compared to placebo; the pre-defined negative criteria for the study were met and the study was stopped. At this point 17 participants had been enrolled (mean 61â years; 88% female), and 15 had completed the study. Final study results for posterior median cough counts showed a 34% (90% credible interval: -3%, +85%) numerical increase for GSK2798745 compared to placebo. CONCLUSION: There was no evidence of an anti-tussive effect of GSK2798745. The study design allowed the decision on lack of efficacy to be made with minimal participant exposure to the investigational drug.
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BACKGROUND: ATP acting via P2X3 receptors is an important mediator of refractory chronic cough (RCC). This phase 2a double-blinded crossover study assessed the safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 receptor antagonist, in adults with RCC attending specialist centres. METHODS: In period A, patients received placebo for 2â weeks then eliapixant 10â mg for 1â week. In period B, patients received eliapixant 50, 200 and 750â mg twice daily for 1â week per dose level. Patients were randomised 1:1 to period A-B (n=20) or B-A (n=20). The primary efficacy end-point was change in cough frequency assessed over 24â h. The primary safety end-point was frequency and severity of adverse events (AEs). RESULTS: 37 patients completed randomised therapy. Mean cough frequency fell by 17.4% versus baseline with placebo. Eliapixant reduced cough frequency at doses ≥50â mg (reduction versus placebo at 750â mg: 25% (90% CI 11.5-36.5%); p=0.002). Doses ≥50â mg also significantly reduced cough severity. AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 41-49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with placebo and 5-21% with eliapixant; all were mild. CONCLUSIONS: Selective P2X3 antagonism with eliapixant significantly reduced cough frequency and severity, confirming this as a viable therapeutic pathway for RCC. Taste-related side-effects were lower at therapeutic doses than with the less selective P2X3 antagonist gefapixant. Selective P2X3 antagonism appears to be a novel therapeutic approach for RCC.
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Tosse , Antagonistas do Receptor Purinérgico P2X , Adulto , Doença Crônica , Tosse/tratamento farmacológico , Estudos Cross-Over , Método Duplo-Cego , Humanos , Receptores Purinérgicos P2X3 , Resultado do TratamentoRESUMO
Background: Entrepreneurship education has demonstrated positive impacts in low-resource contexts. However, there is limited evidence of such programs evaluated among Native American (NA) youth in a rural reservation. Methods: A 2:1 randomized controlled trial evaluated the impact of the Arrowhead Business Group (ABG) entrepreneurship education program on entrepreneurship knowledge, economic empowerment, and social well-being among 394 NA youth. An intent to treat analysis using mixed effects regression models examined within and between study group differences from baseline to 24 months. An interaction term measured change in the intervention relative to change in the control. ABG participants were purposively sampled to conduct focus groups and in-depth interviews. Results: Significant intervention vs. control group improvements were sustained at 12 months for entrepreneurship knowledge and economic confidence/security. Significant within-group improvements were sustained for ABG participants at 24 months for connectedness to parents, school, and awareness of connectedness. Qualitative data endorses positive impacts on social well-being among ABG participants. Conclusion: Observed effects on entrepreneurship knowledge, economic empowerment, and connectedness, supplemented by the experiences and changes as described by the youth themselves, demonstrates how a strength-based youth entrepreneurship intervention focused on developing assets and resources may be an innovative approach to dually address health and economic disparities endured in Native American communities.
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Empreendedorismo , Indígenas Norte-Americanos , Autoimagem , Adolescente , Educação , Grupos Focais , Disparidades nos Níveis de Saúde , Humanos , Grupos Minoritários , Instituições AcadêmicasRESUMO
Nonpharmacological cough control therapy (CCT) is effective for refractory chronic cough but there is a significant subgroup of nonresponders. CCT appears to be effective in cough associated with underlying disease such as asthma. http://bit.ly/2uCCwu3.
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OBJECTIVE: To describe a community-based obesity-prevention initiative that promoted cultural connectedness and traditional food revitalization and gained insight into youth participants' perspectives on the program through a photovoice methodology. METHODS: Photovoice methods were used with fourth- and fifth-grade youths (aged 9-11 years) in the US Southwest who had participated in the Feast for the Future program. A total of 44 youths from 3 communities met for 8-9 sessions; they took photos of current food environments and traditional food systems, and discussed them as well as Feast for the Future and hopes for the future, and then prepared a final presentation. Photovoice sessions were recorded, transcribed verbatim, then open coded using Atlas.ti. RESULTS: Five common themes emerged: traditional food is farmed or gardened, traditional foods are healthy, Feast for the Future supported positive connections to culture, hope for more farming or gardening for future generations, and store or less nutrient-dense food is unhealthy. CONCLUSIONS AND IMPLICATIONS: Photovoice can be an effective way to engage Indigenous youths in conversations about their culture and food environments. The findings suggest that attention to revitalizing traditional food systems and supporting cultural connectedness may be an effective approach to obesity prevention in tribal communities, although future research would be needed to assess the impact of the intervention on obesity rates.
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Comportamento Alimentar/etnologia , Jardinagem/educação , Promoção da Saúde/métodos , Indígenas Norte-Americanos/etnologia , Obesidade Infantil , Criança , Pesquisa Participativa Baseada na Comunidade , Feminino , Humanos , Masculino , Obesidade Infantil/etnologia , Obesidade Infantil/prevenção & controle , Sudoeste dos Estados UnidosRESUMO
Entrepreneurship education is a strength-based approach and holds promise for promoting health equity for American Indian youth. Arrowhead Business Group (ABG) was developed by a tribal-academic research partnership and is being rigorously evaluated for impacts on psychosocial, behavioral, educational, and economic outcomes. This article describes: 1) the trial design and conceptual model under-girding the ABG program; 2) the sociodemographic, sociocultural, and family/household characteristics of participants at baseline; and 3) the baseline differences in key outcome indicators between study groups. Results demonstrate participants have baseline characteristics appropriate for study aims and are compared and contrasted with other youth from the participating tribal community and state in which the tribe resides. Findings inform future analyses to explore how baseline characteristics are associated with primary and secondary outcomes of the evaluation.
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Currículo , Empreendedorismo , Indígenas Norte-Americanos , Avaliação de Processos em Cuidados de Saúde , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa , Adolescente , Feminino , Humanos , MasculinoRESUMO
Radiation therapy (RT) can effectively palliate a variety of symptoms in patients with metastatic cancer, using relatively low doses that infrequently cause major side effects. However, palliative radiation is often underutilized and sub-optimally implemented. In this study, we surveyed the Society of Palliative Radiation Oncology (SPRO) membership to identify barriers to appropriate referral for palliative RT that they encounter in their practice, and identify specific groups of physicians who radiation oncologists believed would benefit most from further education on when to refer patients. A total of 28 radiation oncologists responded to the survey with a response rate of 20.5%. On average, participants felt that referrals for palliative RT were inappropriately delayed 46.5% [standard deviation (STD) 20.2%] of the time. The most common barrier to referral for medical oncologists was thought to be potential interference with systemic therapy (33%); for primary care physicians and surgeons it was a lack of knowledge about the benefit (42%), and for palliative care physicians it was concern for patient convenience (25%). For brain metastases and spinal cord compression radiation oncology was felt to be part of the initial referral sequence more than 50% of the time, but less so for thoracic airway obstruction/bleeding (38%), esophageal obstruction (16%), or urinary obstruction/bleeding (8%), where another subspecialist was more often consulted first. Primary care, geriatric medicine, and emergency medicine were considered among the least knowledgeable specialties about palliative radiation. These hypothesis-generating findings can guide approaches to improve referral patterns for this important aspect of supportive care.
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Neoplasias/radioterapia , Cuidados Paliativos/métodos , Radioterapia (Especialidade)/estatística & dados numéricos , Encaminhamento e Consulta/normas , Utilização de Instalações e Serviços , Humanos , Avaliação das Necessidades , Padrões de Prática Médica , Radio-Oncologistas/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricosRESUMO
Chronic refractory cough patients have persistent, unexplained, treatment-resistant symptoms. Very little is known about non-physiological processes underlying chronic refractory cough or patients' experience of the condition. In all, 14 patients participated in semi-structured interviews. Interviews were based on the comprehensive cognitive behavioural model and analysed thematically. Eight key themes emerged illustrating that the experience of the onset and persistence of chronic refractory cough is complex, often involving multiple interlinking factors. Themes highlighted the involvement of biological and psychological factors, and the prominent role of the social dimension in how the cough is experienced, perceived and managed. Implications for intervention development are discussed.
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Doença Crônica/psicologia , Tosse/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
PURPOSE: Stereotactic body radiation therapy (SBRT) is commonly used to treat primary or oligometastatic malignancies in the lung, but most of the available data that describe the safety and efficacy of SBRT are for smaller tumors. The purpose of this study was to evaluate the impact of tumor size, among other factors, on local control (LC) and radiation pneumonitis (RP) in patients who received lung SBRT. METHODS AND MATERIALS: This retrospective study included 144 patients with 100 primary (57.1%) and 75 metastatic (42.9%) lung tumors treated with SBRT between 2012 and 2018. Measurements of tumor size, treatment volume, histology, and radiation dose were evaluated for association with LC. Additional factors evaluated for association with the development of symptomatic RP included volume of the lung, heart, and central airway exposed to relevant doses of radiation. RESULTS: The median follow-up time was 15.0 months (interquartile range, 8.0-26.0 months). LC rates at 12 and 24 months posttreatment were 95.1% and 92.7%, respectively. LC at 1 year was higher for tumors <5 cm in diameter than for tumors >5 cm in diameter (98.2% vs 79.8%, respectively; P < .01). On univariate analysis, LC was associated with a smaller gross tumor volume (GTV) diameter (P < .01), GTV volume (P < .01), planning target volume (PTV) diameter (P < .01), PTV volume (P < .01), and larger PTV-to-GTV ratio (P = .04). Tumor histology and treatment intent were not correlated with LC. RP was associated with a higher ipsilateral lung mean lung dose (P = .02), V2.5 (P = .03), V5 (P = .02), V13 (P = .03), V20 (P = .05), V30 (P = .02), V40 (P = .02), and V50 (P = .03), and several similar total lung dose parameters and heart maximum point dose (P = .02). The optimal mean ipsilateral lung dose cutoff predictive of RP was 8.6 Gy. CONCLUSIONS: A larger tumor size and smaller PTV-to-GTV ratio was associated with local recurrence of lung tumors treated with SBRT, but ipsilateral lung doses were most associated with symptomatic RP.
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Adenocarcinoma/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Escamosas/secundário , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/diagnóstico , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos , Adenocarcinoma/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Radiation therapy (RT) and nivolumab are standard therapies for a wide range of advanced and metastatic cancers, yet little is known about the toxicity profile of their combined treatment. The rate of grade ≥3 toxicities from nivolumab monotherapy and radiation-only palliative treatments has been reported at 10% to 18% and 0% to 26%, respectively. We reviewed our experience to assess the acute toxicity profile of concurrent RT-nivolumab. METHODS AND MATERIALS: A retrospective review of all consecutive patients from January 2015 to May 2017 who received concurrent RT-nivolumab was conducted at 4 separate centers. Concurrent RT-nivolumab was defined as RT completed between 3 days prior to initial nivolumab infusion and 28 days after the last nivolumab infusion. RESULTS: Of the 261 patients who received nivolumab, 46 (17.6%) had concurrent RT to 67 treatment sites. The median follow-up was 3.3 months (interquartile range, 1.7-6.1 months) and the 1-year overall survival rate was 22%. For the 11 of 46 patients (24%) who were alive at last analysis, the median follow-up was 12.8 months (interquartile range, 8.3-14.9 months). The most common histology, RT prescription, and treatment site were non-small cell lung cancer (23 of 46 patients; 50%), 30 Gy in 10 fractions (24 of 67 patients; 35.8%), and abdomen/pelvis (16 of 67 patients; 24%), respectively. Four patients with melanoma had concurrent ipilimumab and were removed from the final toxicity analysis of RT-nivolumab. Within 3 months of treatment with RT-nivolumab, 4 of 42 patients (9.5%) experienced grade 3 toxicity and 2 of these patients' toxicities were attributed specifically to the addition of RT: grade 3 hearing loss after whole brain RT and grade 3 pancreatitis after stereotactic body RT to the left adrenal gland. One death from transaminitis was attributed to nivolumab alone because the RT field did not encompass the liver. CONCLUSIONS: Concurrent RT-nivolumab did not appear to increase the toxicity profile from the previously reported toxicity rates from nivolumab or radiation alone.