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BACKGROUND: Phase 1 trials are increasingly important in the molecularly driven era of oncology, but few studies have examined phase 1 participation disparities. The authors of this study investigated factors associated with phase 1 versus phase 2/3 trial enrollment. METHODS: They authors conducted a cross-sectional study using serial samples of patients age ≥18 years enrolling on cancer trials from October 2011 to November 2014 at an academic cancer center. They used univariable and multivariable logistic regression models to analyze sociodemographic and clinical associations with phase 1 versus phase 2/3 trial enrollment. RESULTS: Among 3103 patients enrolled in cancer trials, 2657 unique patients participated in phase 1/2/3 trials. For patients enrolled in phase 1 (n = 1401) versus phase 2/3 (n = 1256) trials, we found no significant differences by age, insurance status, marital status, and income. Overall, 1216 (93%) White, 72 (6%) Asian, and 21 (2%) Black patients enrolled on phase 1 trials, whereas 1068 (93%) White, 40 (3%) Asian, and 43 (4%) Black patients enrolled on phase 2/3 trials. Adjusting for age, sex, race, ethnicity, insurance status, marital status, income, cancer type, disease status, travel distance, and trial year, compared with White patients, Black patients had lower phase 1 enrollment (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25-0.82), as did Hispanic/Latino (OR, 0.25; 95% CI, 0.08-0.79) and male patients (OR, 0.77; 95% CI, 0.62-0.94). Asian patients had higher phase 1 enrollment (OR, 1.38; 95% CI, 0.88-2.16). CONCLUSIONS: Disparities in phase 1 versus phase 2/3 cancer clinical trial enrollment underscore the urgent need for interventions addressing inequities in early-phase trial participation. LAY SUMMARY: Phase 1 trials are of increasing importance in oncology. The authors of the study analyzed all patients enrolling on cancer clinical trials at a large academic cancer center from October 2011 to November 2014. Among the 2657 trial participants, when age, sex, race, ethnicity, insurance status, marital status, income, cancer type, disease status, travel distance, and trial year were taken into account, Black, Hispanic/Latino, and male patients were less likely to enroll on phase 1 trials versus phase 2/3 trials. These findings suggest a need for targeted interventions to improve access to and education about phase 1 trials for Black and Hispanic/Latino patients.
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Población Negra , Neoplasias , Adolescente , Estudios Transversales , Etnicidad , Disparidades en Atención de Salud , Humanos , Cobertura del Seguro , Masculino , Neoplasias/terapiaRESUMEN
BACKGROUND: Philanthropic donations are important funding sources in academic oncology but may be vulnerable to implicit or explicit biases toward women. However, the influence of gender on donations has not been assessed quantitatively. METHODS: We queried a large academic cancer center's development database for donations over 10 years to the sundry funds of medical and radiation oncologists. Types of donations and total amounts for medical oncologists and radiation oncologists hired prior to April 1, 2018 (allowing ≥2 years on faculty prior to query), were obtained. We also obtained publicly available data on physician/academic rank, gender, specialty, disease site, and Hirsch-index (h-index), a metric of productivity. RESULTS: We identified 127 physicians: 64% men and 36% women. Median h-index was higher for men (31; range, 1-100) than women (17; range, 3-77; P=.003). Men were also more likely to have spent more time at the institution (median, 15 years; range, 2-43 years) than women (median, 12.5 years; range, 3-22 years; P=.025). Those receiving donations were significantly more likely to be men (70% vs 30%; P=.034). Men received significantly higher median amounts ($259,474; range, $0-$29,507,784) versus women ($37,485; range, $0-$7,483,726; P=.019). On multivariable analysis, only h-index and senior academic rank were associated with donation receipt, and only h-index with donation amount. CONCLUSIONS: We found significant gender disparities in receipt of philanthropic donations on unadjusted analyses. However, on multivariable analyses, only productivity and rank were significantly associated with donations, suggesting gender disparities in productivity and promotions may contribute to these differences.
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Obtención de Fondos , Médicos , Docentes Médicos , Femenino , Humanos , Masculino , Oncología Médica , Oncólogos de Radiación , Factores Sexuales , Estados UnidosRESUMEN
The treatment of patients with cancer who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses unique challenges. In this commentary, the authors describe the ethical rationale and implementation details for the creation of a novel, multidisciplinary treatment prioritization committee, including physicians, frontline staff, an ethicist, and an infectious disease expert. Organizational obligations to health care workers also are discussed. The treatment prioritization committee sets a threshold of acceptable harm to patients from decreased cancer control that is justified to reduce risk to staff. The creation of an ethical, consistent, and transparent decision-making process involving such frontline stakeholders is essential as departments across the country are faced with decisions regarding the treatment of SARS-CoV-2-positive patients with cancer.
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Betacoronavirus , Infecciones por Coronavirus/complicaciones , Atención a la Salud/ética , Personal de Salud/ética , Neoplasias/complicaciones , Pandemias/ética , Neumonía Viral/complicaciones , Calidad de la Atención de Salud/ética , Atención Ambulatoria/ética , Atención Ambulatoria/organización & administración , COVID-19 , Toma de Decisiones Clínicas , Infecciones por Coronavirus/virología , Atención a la Salud/organización & administración , Personal de Salud/organización & administración , Humanos , Neoplasias/radioterapia , Seguridad del Paciente , Neumonía Viral/virología , Calidad de la Atención de Salud/organización & administración , SARS-CoV-2RESUMEN
BACKGROUND: Moral distress is a reason for burnout in healthcare professionals, but the clinical settings in which moral distress is most often experienced by medical students, and whether moral distress is associated with burnout and career choices in medical students is unknown. We assessed moral distress in medical students while caring for older patients, and examined associations with burnout and interest in geriatrics. METHODS: A cross-sectional survey study of second-, third-, and fourth-year medical students at an American medical school. The survey described 12 potentially morally distressing clinical scenarios involving older adult patients. Students reported if they encountered each scenario, and whether they experienced moral distress, graded on a 1-10 scale. We conducted a principal axis factor analysis to assess the dimensionality of the survey scenarios. A composite moral distress score was calculated as the sum of moral distress scores across all 12 scenarios. Burnout was assessed using the Maslach Abbreviated Burnout Inventory, and interest in geriatrics was rated on a 7-point Likert scale. RESULTS: Two-hundred and nine students responded (47%), of whom 90% (188/209) reported moral distress in response to ≥1 scenario with a median (IQR) score of 6 (4-7). Factor analysis suggested a unidimensional factor structure of the 12 survey questions that reliably measured individual distress (Cronbach alpha = 0.78). Those in the highest tertile of composite moral distress scores were more likely to be burnt out (51%) than those in the middle tertile of scores (34%), or lowest tertile of scores (31%) (p = 0.02). There was a trend towards greater interest in geriatrics among those in the higher tertiles of composite moral distress scores (16% lowest tertile, 20% middle tertile, 25% highest tertile, p-for-tend = 0.21). Respondents suggested that moral distress might be mitigated with didactic sessions in inpatient geriatric care, and debriefing sessions with peers and faculty on the inpatient clerkships on medicine, neurology, and surgery, where students most often reported experiencing moral distress. CONCLUSIONS: Moral distress is highly prevalent among medical students while caring for older patients, and associated with burnout. Incorporating geriatrics education and debriefing sessions into inpatient clerkships could alleviate medical student moral distress and burnout.
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Actitud del Personal de Salud , Agotamiento Profesional/psicología , Relaciones Profesional-Paciente , Estudiantes de Medicina/psicología , Adaptación Psicológica , Anciano , Estudios Transversales , Educación de Pregrado en Medicina/métodos , Femenino , Humanos , Relaciones Interprofesionales , Masculino , Estrés Psicológico/psicologíaAsunto(s)
Atención a la Salud , Disparidades en Atención de Salud , Neoplasias/terapia , Prisioneros , Atención a la Salud/ética , Política de Salud , Disparidades en el Estado de Salud , Humanos , Evaluación de Necesidades , Relaciones Médico-Paciente , Prisioneros/estadística & datos numéricos , Calidad de la Atención de Salud , Sistema de Registros , Confianza , Estados UnidosRESUMEN
PURPOSE: Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE. METHODS AND MATERIALS: An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE timing. Thematic analysis was used for qualitative responses. RESULTS: One hundred thirteen Radiation Oncology Education Collaborative Study Group members completed the survey (28.2% response rate); RO attendings comprised 68.1% of respondents. Most practiced in an academic setting (85.8%) in North America (80.5%). Institution-specific materials were the most common PE resource used by radiation oncologists (67.6%). Almost half (40.2%) reported that their PE practices differed based on clinical encounter type, with paper handouts commonly used for in-person and multimedia for telehealth visits. Only 57.7% reported access to non-English PE materials. PE practices among radiation oncologists differed according to RT clinical workflow timing (consultation versus simulation versus first RT, respectively): one-on-one teaching: 88.5% versus 49.4% versus 56.3%, P < .01, and paper handouts: 69.0% versus 28.7% versus 16.1%, P < .01. Identified challenges for PE delivery included limited time, administrative barriers to the development or implementation of new materials or practices, and a lack of customized resources for tailored PE. Effective strategies for PE included utilization of visual diagrams, multimedia, and innovative education techniques to personalize PE delivery/resources for a diverse patient population, as well as fostering interprofessional collaboration to reinforce educational content. CONCLUSIONS: Radiation oncologists and interprofessional RO team members engage in PE, with most using institution-specific materials often available only in English. PE practices differ according to clinical encounter type and RT workflow timing. Increased adoption of multimedia materials and partnerships with patients to tailor PE resources are needed to foster high-quality, patient-centered PE delivery.
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Grupo de Atención al Paciente , Educación del Paciente como Asunto , Oncólogos de Radiación , Humanos , Oncología por Radiación/educación , Encuestas y Cuestionarios , Prioridad del Paciente , Masculino , FemeninoRESUMEN
OBJECTIVE: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. METHODS: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. RESULTS: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. CONCLUSIONS: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.
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Purpose: Radiation induced carotid artery disease (RICAD) is a major cause of morbidity and mortality among survivors of oropharyngeal cancer. This study leveraged standard-of-care CT scans to detect volumetric changes in the carotid arteries of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer, and to determine dose-response relationship between RT and carotid volume changes, which could serve as an early imaging marker of RICAD. Methods and Materials: Disease-free cancer survivors (>3 months since therapy and age >18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Pre- and post-treatment CTs were registered to the planning CT and dose grid. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery subvolumes in 5 Gy increments (i.e. received 50-55 Gy, 55-60 Gy, etc.). The percent-change in sub-volumes across each dose range was statistically examined using the Wilcoxon rank-sum test. Results: Among 46 patients analyzed, 72% received RT alone, 24% induction chemotherapy followed by RT, and 4% concurrent chemoradiation. The median interval from RT completion to the latest, post-RT CT scan was 43 months (IQR 32-57). A decrease in the volume of the irradiated carotid artery was observed in 78% of patients, while there was a statistically significant difference in mean %-change (±SD) between the total irradiated and spared carotid volumes (7.0±9.0 vs. +3.5±7.2, respectively, p<.0001). However, no significant dose-response trend was observed in the carotid artery volume change withing 5 Gy ranges (mean %-changes (±SD) for the 50-55, 55-60, 60-65, and 65-70+ Gy ranges [irradiated minus spared]: -13.1±14.7, -9.8±14.9, -6.9±16.2, -11.7±11.1, respectively). Notably, two patients (4%) had a cerebrovascular accident (CVA), both occurring in patients with a greater decrease in carotid artery volume in the irradiated vs the spared side. Conclusions: Our data show that standard-of-care oncologic surveillance CT scans can effectively detect reductions in carotid volume following RT for oropharyngeal cancer. Changes were equivalent between studied dose ranges, denoting no further dose-response effect beyond 50 Gy. The clinical utility of carotid volume changes for risk stratification and CVA prediction warrants further evaluation.
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Background: Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT). Methods: A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses. Results: Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS (P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group (P = .12). Conclusions: This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches.
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(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p < 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE.
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With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.
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Neoplasias Encefálicas , Imagen por Resonancia Magnética , Radiocirugia , Radiocirugia/métodos , Humanos , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Melanoma/patología , Adulto , Resultado del Tratamiento , Carga Tumoral , Anciano de 80 o más Años , Insuficiencia del Tratamiento , Estudios RetrospectivosRESUMEN
The concept of informed consent has evolved considerably over the course of the 20th century, leading to its establishment as a foundational ethical principle for the conduct of biomedical research in the United States. Even though it is now a highly regulated part of cancer research, the process of obtaining informed consent is often impeded by systemic, clinician, and patient factors that require both small- and large-scale intervention. New challenges and considerations continue to emerge due to innovations in clinical trial design, increases in utilization of genomic sequencing, and advances in genomic editing and artificial intelligence. We present a review of the history, policy, pragmatic challenges, and evolving role of the central ethical tenet of informed consent in clinical trials.
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Ensayos Clínicos como Asunto , Consentimiento Informado , Neoplasias , Humanos , Inteligencia Artificial , Neoplasias/genética , Neoplasias/terapiaRESUMEN
Purpose: Oligometastatic disease (OMD) refers to a limited state of metastatic cancer, which potentially derives benefit from local treatments. Given the relative novelty of this paradigm, oncologist perspectives on OMD are not well established. We thus explored oncologist views on curability of and treatment recommendations for patients with OMD. Methods and Materials: We developed a survey focused on oncologist views of 3 subtypes of OMD: synchronous, oligorecurrent, and oligoprogressive. Eligible participants included medical and radiation oncologists at 2 large cancer centers invited to participate between May and June 2022. Participants were presented with 3 hypothetical patient scenarios and asked about treatment recommendations, rationale, and demographic information. Results: Of 44 respondents, over half (61.4%) agreed that synchronous OMD is curable. A smaller proportion (46.2% and 13.5%) agreed for oligorecurrence and oligoprogression, respectively. When asked whether they use the word "cure" or "curative" in discussing prognosis, 31.8% and 33.3% agreed for synchronous and oligorecurrent OMD, respectively, while 78.4% disagreed for oligoprogression. Views on curability did not significantly affect treatment recommendations. More medical oncologists recommended systemic treatment only compared with radiation oncologists for the synchronous OMD (50.0% vs 5.3%; P < .01) and oligoprogression cases (43.8% vs 10.5%; P = .02), not the oligorecurrent case. There were no significant differences in confidence in treatment recommendations by specialty. Conclusions: In this exploratory study, we found notable divergence in oncologists' views about curability of OMD as well as variability in treatment recommendations, suggesting need for more robust research on outcomes of patients with OMD.
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Because humans age at different rates, a person's physical appearance may yield insights into their biological age and physiological health more reliably than their chronological age. In medicine, however, appearance is incorporated into medical judgments in a subjective and non-standardized fashion. In this study, we developed and validated FaceAge, a deep learning system to estimate biological age from easily obtainable and low-cost face photographs. FaceAge was trained on data from 58,851 healthy individuals, and clinical utility was evaluated on data from 6,196 patients with cancer diagnoses from two institutions in the United States and The Netherlands. To assess the prognostic relevance of FaceAge estimation, we performed Kaplan Meier survival analysis. To test a relevant clinical application of FaceAge, we assessed the performance of FaceAge in end-of-life patients with metastatic cancer who received palliative treatment by incorporating FaceAge into clinical prediction models. We found that, on average, cancer patients look older than their chronological age, and looking older is correlated with worse overall survival. FaceAge demonstrated significant independent prognostic performance in a range of cancer types and stages. We found that FaceAge can improve physicians' survival predictions in incurable patients receiving palliative treatments, highlighting the clinical utility of the algorithm to support end-of-life decision-making. FaceAge was also significantly associated with molecular mechanisms of senescence through gene analysis, while age was not. These findings may extend to diseases beyond cancer, motivating using deep learning algorithms to translate a patient's visual appearance into objective, quantitative, and clinically useful measures.
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PURPOSE: Cancer clinical trial (CCT) participants are at risk for experiencing adverse associations from financial toxicity, but these remain understudied. METHODS: From July 2015 to July 2017, we prospectively enrolled CCT participants referred for financial assistance and a group of patients matched by age, sex, cancer type, trial, and trial phase. We assessed financial burden of cancer care, cost concerns about CCTs, physical (Edmonton Symptom Assessment Scale [ESAS]) and psychologic (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire), and communication confidence (Perceived Efficacy in Patient-Physician Interactions). Adjusting for age, sex, race, performance status, marital status, income, insurance, and disease status, we examined associations of financial burden and cost concerns with patients' symptoms, illness perceptions, and communication confidence. RESULTS: Of 198 patients, 112 (56.6%) reported financial burden and 82 (41.4%) reported cost concerns. Higher ESAS-total (odds ratio [OR] = 1.03; 95% CI, 1.01 to 1.06; P = .001), PHQ-4 depression (OR = 1.58; 95% CI, 1.20 to 2.08; P < .001), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.02 to 1.55; P = .025), and more negative illness perceptions (OR = 1.04; 95% CI, 1.00 to 1.07; P = .029) were associated with financial burden, but not communication confidence (OR = 0.98; 95% CI, 0.02 to 1.05; P = .587). Higher ESAS-total (OR = 1.03; 95% CI, 1.01 to 1.05; P = .004), PHQ-4 depression (OR = 1.36; 95% CI, 1.08 to 1.71; P = .03), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.03 to 1.53; P = .018), more negative illness perceptions (OR = 1.06; 95% CI, 1.02 to 1.10; P = .001), and decreased communication confidence (OR = 0.93; 95% CI, 0.86 to 1.00; P = .029) were associated with cost concerns. CONCLUSION: In this study of CCT participants, greater symptom burden, more negative illness perceptions, and lower communication confidence were associated with financial toxicity, underscoring the importance of addressing these issues when seeking to alleviate adverse associations of financial toxicity.
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Estrés Financiero , Neoplasias , Costo de Enfermedad , Humanos , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/terapia , Encuestas y CuestionariosRESUMEN
BACKGROUND: Artificial intelligence (AI) and deep learning have shown great potential in streamlining clinical tasks. However, most studies remain confined to in silico validation in small internal cohorts, without external validation or data on real-world clinical utility. We developed a strategy for the clinical validation of deep learning models for segmenting primary non-small-cell lung cancer (NSCLC) tumours and involved lymph nodes in CT images, which is a time-intensive step in radiation treatment planning, with large variability among experts. METHODS: In this observational study, CT images and segmentations were collected from eight internal and external sources from the USA, the Netherlands, Canada, and China, with patients from the Maastro and Harvard-RT1 datasets used for model discovery (segmented by a single expert). Validation consisted of interobserver and intraobserver benchmarking, primary validation, functional validation, and end-user testing on the following datasets: multi-delineation, Harvard-RT1, Harvard-RT2, RTOG-0617, NSCLC-radiogenomics, Lung-PET-CT-Dx, RIDER, and thorax phantom. Primary validation consisted of stepwise testing on increasingly external datasets using measures of overlap including volumetric dice (VD) and surface dice (SD). Functional validation explored dosimetric effect, model failure modes, test-retest stability, and accuracy. End-user testing with eight experts assessed automated segmentations in a simulated clinical setting. FINDINGS: We included 2208 patients imaged between 2001 and 2015, with 787 patients used for model discovery and 1421 for model validation, including 28 patients for end-user testing. Models showed an improvement over the interobserver benchmark (multi-delineation dataset; VD 0·91 [IQR 0·83-0·92], p=0·0062; SD 0·86 [0·71-0·91], p=0·0005), and were within the intraobserver benchmark. For primary validation, AI performance on internal Harvard-RT1 data (segmented by the same expert who segmented the discovery data) was VD 0·83 (IQR 0·76-0·88) and SD 0·79 (0·68-0·88), within the interobserver benchmark. Performance on internal Harvard-RT2 data segmented by other experts was VD 0·70 (0·56-0·80) and SD 0·50 (0·34-0·71). Performance on RTOG-0617 clinical trial data was VD 0·71 (0·60-0·81) and SD 0·47 (0·35-0·59), with similar results on diagnostic radiology datasets NSCLC-radiogenomics and Lung-PET-CT-Dx. Despite these geometric overlap results, models yielded target volumes with equivalent radiation dose coverage to those of experts. We also found non-significant differences between de novo expert and AI-assisted segmentations. AI assistance led to a 65% reduction in segmentation time (5·4 min; p<0·0001) and a 32% reduction in interobserver variability (SD; p=0·013). INTERPRETATION: We present a clinical validation strategy for AI models. We found that in silico geometric segmentation metrics might not correlate with clinical utility of the models. Experts' segmentation style and preference might affect model performance. FUNDING: US National Institutes of Health and EU European Research Council.
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Carcinoma de Pulmón de Células no Pequeñas , Aprendizaje Profundo , Neoplasias Pulmonares , Algoritmos , Inteligencia Artificial , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estados UnidosRESUMEN
Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3+ T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3+CD8+ cytotoxic T cells (CTLs, p = .0079), CD3+CD4+FOXP3- T helper cells (Th, p = .0010), and CD3+CD4+FOXP3+ regulatory T cells (Tregs, p = .0089) with no difference in CD68+ macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor.
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Carcinoma Ductal Pancreático , Melanoma , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Factores de Transcripción Forkhead , Humanos , Melanoma/terapia , Terapia Neoadyuvante , Neoplasias Pancreáticas/terapia , Microambiente Tumoral , Neoplasias PancreáticasRESUMEN
The coronavirus disease 2019 pandemic has been intertwined with the movement for racial justice in the United States and has highlighted and risks aggravating educational and workforce disparities within radiation oncology. We discuss wide-ranging changes within radiation oncology training that are essential to developing and maintaining diversity, including utilization of competency-based educational models that allow for streamlining of training and examinations; responsiveness to the needs of residents and medical students of different gender, racial/ethnic, and socioeconomic groups; and technological integration to increase educational efficiency and decrease barriers.
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Comprehensive patient education is necessary for shared decision-making. While patient-provider conversations primarily drive patient education, patients also use published materials to enhance their understanding. In this investigation, we evaluated the readability of 2585 patient education materials published in high-impact medical journals from 1998 to 2018 and compared our findings to readability recommendations from national groups. For all materials, mean readability grade levels ranged from 11.2 to 13.8 by various metrics. Fifty-four (2.1%) materials met the American Medical Association recommendation of sixth grade reading level, and 215 (8.2%) met the National Institutes of Health recommendation of eighth grade level. When stratified by journal and material type, general medical education materials from Annals of Internal Medicine were the most readable (P < .001), with 79.8% meeting the eighth grade level. Readability did not differ significantly over time. Efforts to standardize publication practice with the incorporation of readability evaluation during the review process may improve patients' understanding of their disease processes and treatment options.
RESUMEN
IMPORTANCE: More than 1 million people in the US identify as transgender; however, few studies have examined the experiences and outcomes of transgender patients with cancer. OBJECTIVE: To examine clinical characteristics, experiences, and outcomes of transgender patients with cancer. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case series assessed transgender patients with at least 1 cancer diagnosis who were evaluated at Dana-Farber Cancer Institute or Brigham and Women's Hospital in Boston, Massachusetts, between January 1, 2005, and December 31, 2019. MAIN OUTCOMES AND MEASURES: Demographic, clinical, and treatment characteristics for all patients and documentation by oncologic practitioners of important aspects of providing gender-affirming care, including pronouns used by the patient, were recorded. RESULTS: A total of 37 transgender patients with cancer were assessed (mean [SD] age, 38.9 [21.8] years at first cancer diagnosis). Fifteen patients (40.5%) had hematologic malignant cancers, and 25 patients (67.6%) had solid malignant tumors. Sixteen patients (43.2%) initiated gender-affirming hormone therapy or surgery after their cancer diagnosis. Cancer treatment was frequently multimodal, with 24 patients (64.9%) receiving systemic therapy, 24 (64.9%) receiving surgery, and 20 (54.1%) receiving radiation therapy along with other cancer-directed treatment, such as cryoablation. Five patients (13.5%) had documentation from an oncologic practitioner that addressed a potential interaction between their gender-affirming care and their cancer treatment. Thirty-three patients had follow-up visits with oncologic practitioners after starting their transition. Of those patients, pronouns used were documented by a member of the oncologic team for 4 patients (12.1%). However, for 3 of the 4 patients, documentation did not consistently use patient-reported information. At the last follow-up, 5 patients (13.5%) had died of their disease, and 26 (70.3%) were living without disease. CONCLUSIONS AND RELEVANCE: This case series study found that transgender patients were diagnosed with diverse cancers, and many initiated gender-affirming hormone therapy or surgery after their diagnosis. Documentation by oncologic practitioners infrequently included pronouns used by the patient or discussion surrounding the interactions between cancer treatment and gender-affirming care, signifying that urgent improvements are needed in cancer care for transgender patients.