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1.
Pediatr Blood Cancer ; 71(9): e31099, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38845144

RESUMO

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.


Assuntos
Histiocitose de Células de Langerhans , Leucócitos Mononucleares , Mutação , Proteínas Proto-Oncogênicas B-raf , Humanos , Histiocitose de Células de Langerhans/genética , Histiocitose de Células de Langerhans/mortalidade , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/terapia , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/sangue , Proteínas Proto-Oncogênicas B-raf/genética , Masculino , Feminino , Estudos Retrospectivos , Criança , Pré-Escolar , Prognóstico , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/metabolismo , Lactente , Adolescente , Seguimentos , Taxa de Sobrevida
2.
JAMA Oncol ; 10(7): 956-960, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38753317

RESUMO

Importance: Artificial intelligence (AI) chatbots pose the opportunity to draft template responses to patient questions. However, the ability of chatbots to generate responses based on domain-specific knowledge of cancer remains to be tested. Objective: To evaluate the competency of AI chatbots (GPT-3.5 [chatbot 1], GPT-4 [chatbot 2], and Claude AI [chatbot 3]) to generate high-quality, empathetic, and readable responses to patient questions about cancer. Design, Setting, and Participants: This equivalence study compared the AI chatbot responses and responses by 6 verified oncologists to 200 patient questions about cancer from a public online forum. Data were collected on May 31, 2023. Exposures: Random sample of 200 patient questions related to cancer from a public online forum (Reddit r/AskDocs) spanning from January 1, 2018, to May 31, 2023, was posed to 3 AI chatbots. Main Outcomes and Measures: The primary outcomes were pilot ratings of the quality, empathy, and readability on a Likert scale from 1 (very poor) to 5 (very good). Two teams of attending oncology specialists evaluated each response based on pilot measures of quality, empathy, and readability in triplicate. The secondary outcome was readability assessed using Flesch-Kincaid Grade Level. Results: Responses to 200 questions generated by chatbot 3, the best-performing AI chatbot, were rated consistently higher in overall measures of quality (mean, 3.56 [95% CI, 3.48-3.63] vs 3.00 [95% CI, 2.91-3.09]; P < .001), empathy (mean, 3.62 [95% CI, 3.53-3.70] vs 2.43 [95% CI, 2.32-2.53]; P < .001), and readability (mean, 3.79 [95% CI, 3.72-3.87] vs 3.07 [95% CI, 3.00-3.15]; P < .001) compared with physician responses. The mean Flesch-Kincaid Grade Level of physician responses (mean, 10.11 [95% CI, 9.21-11.03]) was not significantly different from chatbot 3 responses (mean, 10.31 [95% CI, 9.89-10.72]; P > .99) but was lower than those from chatbot 1 (mean, 12.33 [95% CI, 11.84-12.83]; P < .001) and chatbot 2 (mean, 11.32 [95% CI, 11.05-11.79]; P = .01). Conclusions and Relevance: The findings of this study suggest that chatbots can generate quality, empathetic, and readable responses to patient questions comparable to physician responses sourced from an online forum. Further research is required to assess the scope, process integration, and patient and physician outcomes of chatbot-facilitated interactions.


Assuntos
Inteligência Artificial , Neoplasias , Mídias Sociais , Humanos , Neoplasias/psicologia , Relações Médico-Paciente , Masculino , Feminino , Médicos/psicologia , Empatia
3.
EBioMedicine ; 103: 105089, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579363

RESUMO

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.


Assuntos
Fibrose , Lesões por Radiação , Humanos , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Animais , Radioterapia/efeitos adversos , Radioterapia/métodos , Neoplasias/etiologia , Neoplasias/radioterapia , Neoplasias/patologia , Radiação Ionizante
4.
Sci Rep ; 14(1): 5688, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454087

RESUMO

In Canada, the absolute number of cancer deaths has been steadily increasing, however, age-standardized cancer mortality rates peaked decades ago for most cancers. The objective of this study was to estimate the reduction in deaths for each cancer type under the scenario where peak mortality rates had remained stable in Canada. Data for this study were obtained the Global Cancer Observatory and Statistics Canada. We estimated age-standardized mortality rates (ASMR, per 100,000) from 1950 to 2022, standardized to the 2011 Canadian standard population. We identified peak mortality rates and applied the age-specific mortality rates from the peak year to the age-specific Canadian population estimates for subsequent years (up to 2022) to estimate the number of expected deaths. Avoided cancer deaths were the difference between the observed and expected number of cancer deaths. There have been major reductions in deaths among cancers related to tobacco consumption and other modifiable lifestyle habits (417,561 stomach; 218,244 colorectal; 186,553 lung; 66,281 cervix; 32,732 head and neck; 27,713 bladder; 22,464 leukemia; 20,428 pancreas; 8863 kidney; 3876 esophagus; 290 liver). There have been 201,979 deaths avoided for female-specific cancers (breast, cervix, ovary, uterus). Overall, there has been a 34% reduction in mortality for lung cancer among males and a 9% reduction among females. There has been a significant reduction in cancer mortality in Canada since site-specific cancer mortality rates peaked decades ago for many cancers. This shows the exceptional progress made in cancer control in Canada due to substantial improvements in prevention, screening, and treatment. This study highlights priority areas where more attention and investment are needed to achieve progress.


Assuntos
Leucemia , Neoplasias Pulmonares , Neoplasias , Masculino , Humanos , Feminino , Canadá/epidemiologia , Mama , Estilo de Vida , Mortalidade , Incidência
5.
Lab Invest ; 104(5): 100341, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38280634

RESUMO

Ki-67 is a nuclear protein associated with proliferation, and a strong potential biomarker in breast cancer, but is not routinely measured in current clinical management owing to a lack of standardization. Digital image analysis (DIA) is a promising technology that could allow high-throughput analysis and standardization. There is a dearth of data on the clinical reliability as well as intra- and interalgorithmic variability of different DIA methods. In this study, we scored and compared a set of breast cancer cases in which manually counted Ki-67 has already been demonstrated to have prognostic value (n = 278) to 5 DIA methods, namely Aperio ePathology (Lieca Biosystems), Definiens Tissue Studio (Definiens AG), Qupath, an unsupervised immunohistochemical color histogram algorithm, and a deep-learning pipeline piNET. The piNET system achieved high agreement (interclass correlation coefficient: 0.850) and correlation (R = 0.85) with the reference score. The Qupath algorithm exhibited a high degree of reproducibility among all rater instances (interclass correlation coefficient: 0.889). Although piNET performed well against absolute manual counts, none of the tested DIA methods classified common Ki-67 cutoffs with high agreement or reached the clinically relevant Cohen's κ of at least 0.8. The highest agreement achieved was a Cohen's κ statistic of 0.73 for cutoffs 20% and 25% by the piNET system. The main contributors to interalgorithmic variation and poor cutoff characterization included heterogeneous tumor biology, varying algorithm implementation, and setting assignments. It appears that image segmentation is the primary explanation for semiautomated intra-algorithmic variation, which involves significant manual intervention to correct. Automated pipelines, such as piNET, may be crucial in developing robust and reproducible unbiased DIA approaches to accurately quantify Ki-67 for clinical diagnosis in the future.


Assuntos
Neoplasias da Mama , Processamento de Imagem Assistida por Computador , Antígeno Ki-67 , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Reprodutibilidade dos Testes , Processamento de Imagem Assistida por Computador/métodos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Algoritmos , Imuno-Histoquímica/métodos
6.
Sci Rep ; 14(1): 1283, 2024 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218973

RESUMO

The Ki-67 proliferation index (PI) guides treatment decisions in breast cancer but suffers from poor inter-rater reproducibility. Although AI tools have been designed for Ki-67 assessment, their impact on pathologists' work remains understudied. 90 international pathologists were recruited to assess the Ki-67 PI of ten breast cancer tissue microarrays with and without AI. Accuracy, agreement, and turnaround time with and without AI were compared. Pathologists' perspectives on AI were collected. Using AI led to a significant decrease in PI error (2.1% with AI vs. 5.9% without AI, p < 0.001), better inter-rater agreement (ICC: 0.70 vs. 0.92; Krippendorff's α: 0.63 vs. 0.89; Fleiss' Kappa: 0.40 vs. 0.86), and an 11.9% overall median reduction in turnaround time. Most pathologists (84%) found the AI reliable. For Ki-67 assessments, 76% of respondents believed AI enhances accuracy, 82% said it improves consistency, and 83% trust it will improve efficiency. This study highlights AI's potential to standardize Ki-67 scoring, especially between 5 and 30% PI-a range with low PI agreement. This could pave the way for a universally accepted PI score to guide treatment decisions, emphasizing the promising role of AI integration into pathologist workflows.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Antígeno Ki-67 , Patologistas , Reprodutibilidade dos Testes , Imuno-Histoquímica
7.
Pharmacoecon Open ; 8(2): 171-190, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38198111

RESUMO

BACKGROUND: In this ever-expanding treatment landscape, there is a lack of consolidated health-related quality of life (HRQOL) outcomes and utility reports in relapsed or refractory (R/R) large B cell lymphoma (LBCL) to inform health care policy and decision-maker assessments for both old and new products. These assessments can have a direct effect on what treatment options are available to patients and physicians. OBJECTIVE: A systematic literature review (SLR) was performed to understand the HRQOL evidence for treatments in R/R LBCL and identify associated health utility values. METHODS: The SLR searched and screened literature published from 1 January 2003 to 2 May 2022. Studies were screened based on Population, Intervention, Comparator, Outcome, Study design criteria established a priori and were assessed by two independent reviewers; quality assessments of the evidence were performed in accordance with health technology assessment recommendations from the National Institute for Health and Care Excellence. Several types of therapies were included, such as chimeric antigen receptor (CAR) T cell products (lisocabtagene maraleucel, axicabtagene ciloleucel, tisagenlecleucel), novel therapies (selinexor, nivolumab, polatuzumab vedotin, and bendamustine), salvage therapies, and rituximab. RESULTS: The review identified 33 unique studies reporting HRQOL, including 15 economic studies that reported health state utility values, 9 clinical trials, 7 health technology assessment reports, and 1 each of a vignette-based study and a point-in-time survey. Improvements in general and/or lymphoma-specific HRQOL measures were observed with CAR T cell therapy in both the second-line and third-line or later settings. On-treatment utility values for CAR T cell therapies ranged from 0.50 to 0.74. Values for remission/progression-free survival (0.70-0.90) and for disease progression (0.39-0.59) were similar across studies. For novel therapies, utility values were 0.83 for progression-free survival and ranged from 0.39 to 0.71 for disease progression. On-treatment utility values for salvage chemotherapy ranged from 0.63 to 0.67. CONCLUSIONS: Overall, the evidence synthesized in this SLR provides a comprehensive understanding of the HRQOL evidence in R/R LBCL. This article identified several sources for utility values in the published literature showing variation in the HRQOL outcomes for patients across a variety of therapeutics. Treatment of R/R LBCL with CAR T cell therapies was associated with improvement in health utility values. Mixed results were found for novel therapies and salvage therapies. More data are needed as new therapies are used in this patient population to inform treatment decision-making.

8.
J Natl Cancer Inst ; 116(1): 172, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-37934149
9.
Haematologica ; 109(3): 857-866, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37646670

RESUMO

In the single-arm, open-label, multicenter, phase II PILOT study, second-line treatment with the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) for whom hematopoietic stem cell transplantation (HSCT) was not intended resulted in high response rates, durable responses, and a safety profile consistent with previous reports. Here, we analyzed changes in health-related quality of life (HRQOL) in patients who received liso-cel in PILOT. Patients received liso-cel, an autologous, CD19-directed, 4-1BB CAR T-cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells, for a total target dose of 100×106 CAR+ T cells. HRQOL, a secondary endpoint of PILOT, was assessed as prespecified using three patient-reported outcome instruments (EORTC QLQ-C30; FACT-LymS; EQ-5D-5L). Evaluable datasets for the EORTC QLQ-C30, FACT-LymS, and EQ-5D-5L health utility index, and visual analog scale (EQ-VAS) included 56 (92%), 49 (80%), 55 (90%), and 54 (89%) patients, respectively. Clinically meaningful improvement was achieved across most post-treatment visits for EORTC QLQ-C30 fatigue and FACT-LymS. Overall mean changes from baseline through day 545 showed significant improvements in EORTC QLQ-C30 fatigue, pain, and appetite loss, FACT-LymS, and EQ VAS. In within-patient analyses, clinically meaningful improvements or maintenance in scores were observed in most patients at days 90, 180, 270, and 365. HRQOL was maintained or improved in patients who received liso-cel as second-line therapy in PILOT. These findings support liso-cel as a preferred second-line treatment in patients with R/R LBCL not intended for HSCT (clinicaltrials gov. Identifier: NCT03483103).


Assuntos
Linfoma Difuso de Grandes Células B , Qualidade de Vida , Humanos , Projetos Piloto , Linfoma Difuso de Grandes Células B/terapia , Fadiga , Medidas de Resultados Relatados pelo Paciente
10.
JNCI Cancer Spectr ; 7(6)2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-38085245

RESUMO

It is currently not known how many more cancer deaths would have occurred among Canadians if cancer mortality rates were unchanged following various modern human interventions. The objective of this study was to estimate the number of cancer deaths that have been avoided in Canada since the age-standardized overall cancer mortality rate peaked in 1988. We applied the age-specific overall cancer mortality rates from 1988 to the Canadian population for all subsequent years to estimate the number of expected deaths. Avoided cancer deaths were estimated as the difference between the observed and expected number of cancer deaths for each year. Since 1988, there have been 372 584 (standardized mortality ratio = 0.77) and 120 045 (standardized mortality ratio = 0.90) avoided cancer deaths in males and females, respectively (492 629 total). Nearly half a million cancer deaths have been avoided in Canada since the overall cancer mortality rate peaked, which demonstrates the exceptional progress made in modern cancer control in Canada.


Assuntos
Neoplasias , Feminino , Humanos , Masculino , Canadá/epidemiologia , Neoplasias/mortalidade , Neoplasias/prevenção & controle
11.
N Engl J Med ; 389(7): 612-619, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37585627

RESUMO

BACKGROUND: Adjuvant radiotherapy is prescribed after breast-conserving surgery to reduce the risk of local recurrence. However, radiotherapy is inconvenient, costly, and associated with both short-term and long-term side effects. Clinicopathologic factors alone are of limited use in the identification of women at low risk for local recurrence in whom radiotherapy can be omitted. Molecularly defined intrinsic subtypes of breast cancer can provide additional prognostic information. METHODS: We performed a prospective cohort study involving women who were at least 55 years of age, had undergone breast-conserving surgery for T1N0 (tumor size <2 cm and node negative), grade 1 or 2, luminal A-subtype breast cancer (defined as estrogen receptor positivity of ≥1%, progesterone receptor positivity of >20%, negative human epidermal growth factor receptor 2, and Ki67 index of ≤13.25%), and had received adjuvant endocrine therapy. Patients who met the clinical eligibility criteria were registered, and Ki67 immunohistochemical analysis was performed centrally. Patients with a Ki67 index of 13.25% or less were enrolled and did not receive radiotherapy. The primary outcome was local recurrence in the ipsilateral breast. In consultation with radiation oncologists and patients with breast cancer, we determined that if the upper boundary of the two-sided 90% confidence interval for the cumulative incidence at 5 years was less than 5%, this would represent an acceptable risk of local recurrence at 5 years. RESULTS: Of 740 registered patients, 500 eligible patients were enrolled. At 5 years after enrollment, recurrence was reported in 2.3% of the patients (90% confidence interval [CI], 1.3 to 3.8; 95% CI, 1.2 to 4.1), a result that met the prespecified boundary. Breast cancer occurred in the contralateral breast in 1.9% of the patients (90% CI, 1.1 to 3.2), and recurrence of any type was observed in 2.7% (90% CI, 1.6 to 4.1). CONCLUSIONS: Among women who were at least 55 years of age and had T1N0, grade 1 or 2, luminal A breast cancer that were treated with breast-conserving surgery and endocrine therapy alone, the incidence of local recurrence at 5 years was low with the omission of radiotherapy. (Funded by the Canadian Cancer Society and the Canadian Breast Cancer Foundation; LUMINA ClinicalTrials.gov number, NCT01791829.).


Assuntos
Neoplasias da Mama , Mastectomia Segmentar , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Feminino , Humanos , Neoplasias da Mama/classificação , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Canadá , Antígeno Ki-67/biossíntese , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estudos Prospectivos , Prognóstico , Pessoa de Meia-Idade , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Receptor ErbB-2/biossíntese , Antineoplásicos Hormonais/uso terapêutico
12.
Pharmacoecon Open ; 7(6): 941-950, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37651087

RESUMO

BACKGROUND: Durable remission has been observed in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with chimeric antigen receptor (CAR) T-cell therapy. Consequently, hazard functions for overall survival (OS) are often complex, requiring the use of flexible methods for extrapolations. OBJECTIVES: We aimed to retrospectively compare the predictive accuracy of different survival extrapolation methods and evaluate the validity of goodness-of-fit (GOF) criteria-based model selection for CAR T-cell therapies in R/R LBCL. METHODS: OS data were sourced from JULIET, ZUMA-1, and TRANSCEND NHL 001. Standard parametric, mixture cure, cubic spline, and mixture models were fit to multiple database locks (DBLs), with varying follow-up durations. GOF was assessed using the Akaike information criterion and Bayesian information criterion. Predictive accuracy was calculated as the mean absolute error (MAE) relative to OS observed in the most mature DBL. RESULTS: For all studies, mixture cure and cubic spline models provided the best predictive accuracy for the least mature DBL (MAE 0.013‒0.085 and 0.014‒0.128, respectively). The predictive accuracy of the standard parametric and mixture models showed larger variation (MAE 0.024‒0.162 and 0.013‒0.176, respectively). With increasing data maturity, the predictive accuracy of standard parametric models remained poor. Correlation between GOF criteria and predictive accuracy was low, particularly for the least mature DBL. CONCLUSIONS: Our analyses demonstrated that mixture cure and cubic spline models provide the most accurate survival extrapolations of CAR T-cell therapies in LBCL. Furthermore, GOF should not be the only criteria used when selecting the optimal survival model.

13.
Cancer Res Commun ; 3(6): 1140-1151, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37397861

RESUMO

Artificial intelligence (AI) and machine learning (ML) are becoming critical in developing and deploying personalized medicine and targeted clinical trials. Recent advances in ML have enabled the integration of wider ranges of data including both medical records and imaging (radiomics). However, the development of prognostic models is complex as no modeling strategy is universally superior to others and validation of developed models requires large and diverse datasets to demonstrate that prognostic models developed (regardless of method) from one dataset are applicable to other datasets both internally and externally. Using a retrospective dataset of 2,552 patients from a single institution and a strict evaluation framework that included external validation on three external patient cohorts (873 patients), we crowdsourced the development of ML models to predict overall survival in head and neck cancer (HNC) using electronic medical records (EMR) and pretreatment radiological images. To assess the relative contributions of radiomics in predicting HNC prognosis, we compared 12 different models using imaging and/or EMR data. The model with the highest accuracy used multitask learning on clinical data and tumor volume, achieving high prognostic accuracy for 2-year and lifetime survival prediction, outperforming models relying on clinical data only, engineered radiomics, or complex deep neural network architecture. However, when we attempted to extend the best performing models from this large training dataset to other institutions, we observed significant reductions in the performance of the model in those datasets, highlighting the importance of detailed population-based reporting for AI/ML model utility and stronger validation frameworks. We have developed highly prognostic models for overall survival in HNC using EMRs and pretreatment radiological images based on a large, retrospective dataset of 2,552 patients from our institution.Diverse ML approaches were used by independent investigators. The model with the highest accuracy used multitask learning on clinical data and tumor volume.External validation of the top three performing models on three datasets (873 patients) with significant differences in the distributions of clinical and demographic variables demonstrated significant decreases in model performance. Significance: ML combined with simple prognostic factors outperformed multiple advanced CT radiomics and deep learning methods. ML models provided diverse solutions for prognosis of patients with HNC but their prognostic value is affected by differences in patient populations and require extensive validation.


Assuntos
Aprendizado Profundo , Neoplasias de Cabeça e Pescoço , Humanos , Prognóstico , Estudos Retrospectivos , Inteligência Artificial , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem
15.
Adv Radiat Oncol ; 8(5): 101210, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152892

RESUMO

Purpose: Advancing equity, diversity, and inclusion in the physician workforce is essential to providing high-quality and culturally responsive patient care and has been shown to improve patient outcomes. To better characterize equity in the field of radiation oncology, we sought to describe the current academic radiation oncology workforce, including any contemporary differences in compensation and rank by gender and race/ethnicity. Methods and Materials: We conducted a retrospective cohort study using data from the Society of Chairs of Academic Radiation Oncology Programs (SCAROP) 2018 Financial Survey. Multivariable logistic regression models were used to identify factors associated with associate or full professor rank. Compensation was compared by gender and race/ethnicity overall and stratified by rank and was further analyzed using multivariable linear regression models. Results: Of the 858 academic radiation oncologists from 63 departments in the United States in the sample, 33.2% were female, 65.2% were White, 27.2% were Asian, and 7.6% were underrepresented in medicine (URiM). There were 44.0% assistant professors, 32.0% associate professors, and 22.8% full professors. Multivariable logistic regression analysis for factors associated with associate or full professor rank did not reveal statistically significant associations between gender or race/ethnicity with academic rank (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.56-1.32; P = .48 for gender; OR, 0.81; 95% CI, 0.5-1.30; P = .37 for Asian vs White; and OR, 0.69; 95% CI, 0.31-1.55; P = .37 for URiM vs White), but CIs were wide due to sample size, and point estimates were <1. Similarly, multivariable linear regression analysis modeling the log relative total compensation did not detect statistically significant differences between radiation oncologists by gender (-1.7%; 95% CI, -6.8% to 3.4%; P = .51 for female vs male) or race/ethnicity (-1.6%; 95% CI, -7.3% to 4.0%; P = .57 for Asian vs White and -3.0%; 95% CI, -12.1% to 6.0%; P = .51 for URiM vs White). Conclusions: The low numbers of women and faculty with URiM race/ethnicity in this radiation oncology faculty sample limits the ability to compare career trajectory and compensation by those characteristics. Given that point estimates were <1, our findings do not contradict larger multispecialty studies that suggest an ongoing need to monitor equity.

16.
Adv Ther ; 40(5): 2355-2374, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36947328

RESUMO

INTRODUCTION: The objective of this study was to evaluate the cost-effectiveness of lisocabtagene maraleucel (liso-cel) versus other available chimeric antigen receptor T-cell therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), in patients who had received at least two prior therapies from a United States (US) commercial third-party payer perspective. METHODS: To capture this heterogeneity in survival outcomes, we used mixture cure models to extrapolate progression-free survival (PFS) and overall survival (OS). Patient-level data from TRANSCEND NHL 001 for liso-cel and reconstructed patient-level data from ZUMA-1 for axi-cel, JULIET for tisa-cel, and SCHOLAR-1 for salvage chemotherapy, derived using the Guyot method, were used for OS and PFS. The model included adverse events associated with liso-cel, axi-cel, and tisa-cel. RESULTS: Liso-cel was less costly (incremental cost of - $74,980) and marginally more effective (0.002 incremental quality-adjusted life-years [QALY]) than axi-cel and had an incremental cost of $67,925 and 2.02 incremental QALYs over tisa-cel in the base case. Results remained consistent in sensitivity analyses, with the liso-cel OS cure fraction being the main driver of cost-effectiveness compared with both axi-cel and tisa-cel. CONCLUSION: This analysis estimated that liso-cel is cost-effective compared with tisa-cel and axi-cel from a commercial US payer perspective.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Análise Custo-Benefício , Imunoterapia Adotiva
17.
Leuk Lymphoma ; 64(3): 573-585, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36755418

RESUMO

This study used a real-world population as a synthetic comparator for the single-arm TRANSCEND NHL 001 study (TRANSCEND; NCT02631044) to evaluate the efficacy of lisocabtagene maraleucel (liso-cel) compared with conventional (noncellular) therapies in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Inclusion and exclusion criteria for the real-world study closely matched the enrollment criteria in TRANSCEND. The analytic comparator cohort was created by matching and balancing observed baseline characteristics of real-world patients with those in TRANSCEND using propensity score methodology. Efficacy outcomes comparing liso-cel- (n = 257) and conventional therapy-treated (n = 257) patients, respectively, significantly favored liso-cel: overall response rate (74% vs 39%; p < 0.0001), complete response rate (50% vs 24%; p < 0.0001), median overall survival (23.5 vs 6.8 months; p < 0.0001), and median progression-free survival (3.5 vs 2.2 months; p < 0.0001). These results demonstrated a statistically significant and clinically meaningful benefit of liso-cel in patients with third- or later-line R/R LBCL relative to conventional therapies.Clinical trial registration: ClinicalTrials.gov identifier: NCT02631044.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Antígenos CD19 , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Intervalo Livre de Progressão , Pontuação de Propensão
18.
J Clin Oncol ; 41(8): 1533-1540, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36599119

RESUMO

PURPOSE: Adjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach. METHODS: We analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132). RESULTS: Patients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P = .81, and HR, 1.5 [0.14 to 16], P = .74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P = .0055, and HR, 0.25 [0.07 to 0.92], P = .038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P = .066). CONCLUSION: The novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Radioterapia Adjuvante , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Mama/patologia , Mastectomia Segmentar
19.
J Natl Cancer Inst ; 115(4): 365-374, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36688707

RESUMO

BACKGROUND: The aim of this study is to provide a comprehensive understanding of the current landscape of artificial intelligence (AI) for cancer clinical trial enrollment and its predictive accuracy in identifying eligible patients for inclusion in such trials. METHODS: Databases of PubMed, Embase, and Cochrane CENTRAL were searched until June 2022. Articles were included if they reported on AI actively being used in the clinical trial enrollment process. Narrative synthesis was conducted among all extracted data: accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. For studies where the 2x2 contingency table could be calculated or supplied by authors, a meta-analysis to calculate summary statistics was conducted using the hierarchical summary receiver operating characteristics curve model. RESULTS: Ten articles reporting on more than 50 000 patients in 19 datasets were included. Accuracy, sensitivity, and specificity exceeded 80% in all but 1 dataset. Positive predictive value exceeded 80% in 5 of 17 datasets. Negative predictive value exceeded 80% in all datasets. Summary sensitivity was 90.5% (95% confidence interval [CI] = 70.9% to 97.4%); summary specificity was 99.3% (95% CI = 81.8% to 99.9%). CONCLUSIONS: AI demonstrated comparable, if not superior, performance to manual screening for patient enrollment into cancer clinical trials. As well, AI is highly efficient, requiring less time and human resources to screen patients. AI should be further investigated and implemented for patient recruitment into cancer clinical trials. Future research should validate the use of AI for clinical trials enrollment in less resource-rich regions and ensure broad inclusion for generalizability to all sexes, ages, and ethnicities.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Sensibilidade e Especificidade , Neoplasias/diagnóstico , Neoplasias/terapia , Valor Preditivo dos Testes , Curva ROC
20.
J Pediatr Hematol Oncol ; 45(3): e339-e344, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36162009

RESUMO

Low expression levels of E2F3a and caspase 8-associated protein 2 (CASP8AP2) are associated with poor outcomes in children with acute lymphoblastic leukemia. Our previous study showed that a combined assessment of E2F3a and CASP8AP2 expression was more accurate in predicting relapse in children with acute lymphoblastic leukemia. However, the underlying mechanism remains unclear. In this study, the interaction between E2F3a and CASP8AP2 and its role in the regulation of histone expression, cell proliferation, the cell cycle, and chemosensitivity were investigated. Exogenous E2F3a-GST was coprecipitated with CASP8AP2-FLAG in HEK-293T cells. E2F3a was colocalized with CASP8AP2-GFP in the nucleus. The replication-dependent histones H2A and H2B were significantly upregulated when E2F3a or CASP8AP2 was overexpressed in HEK-293T or 697 cells and downregulated by E2F3a or CASP8AP2 knockdown. E2F3a and CASP8AP2 could collaboratively enhance the transcriptional activity of HIST1H2AG and HIST1H2BK . Both CASP8AP2 and E2F3a are involved in S phase progression. E2F3a and CASP8AP2 also affected the sensitivity of leukemic cells to daunorubicin. Therefore, CASP8AP2 and E2F3a collaboratively regulated replication-dependent histone expression, cell cycle progression, and chemosensitivity of leukemic cells.


Assuntos
Histonas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Proteínas Reguladoras de Apoptose , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas de Ligação ao Cálcio
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