Definitive local therapy is often utilized in patients with metastatic soft tissue sarcomas (STS) to reduce morbidity associated with local tumor progression. We hypothesize that it is associated ...with improved overall survival (OS).
Patients with newly diagnosed metastatic STS treated with chemotherapy were identified from the National Cancer Database and dichotomized into cohorts: 1. definitive local therapy (defined as either definitive dose radiotherapy, definitive surgery, or surgery with perioperative radiotherapy) or 2. conservative therapy (defined as systemic therapy with or without palliative therapy). The association between definitive local therapy and OS, and factors associated with the receipt of definitive local therapy were assessed.
Total of 4180 patients were identified. Compared with the conservative therapy, receipt of any definitive local therapy was associated with improved OS (median 17.9 vs. 10.1 months). The survival benefit remained on multivariate analyses and propensity-score matched analyses, with a stepwise improvement with surgery and combined modality local therapy, specifically radiotherapy (HR: 0.77;
< 0.001), surgery (HR: 0.67;
< 0.001), and combined surgery and radiotherapy (HR: 0.42;
< 0.001).
Analysis of a large national cancer registry of patients with metastatic STS suggests that chemotherapy plus definitive local therapy is associated with a significant survival benefit compared to the standard chemotherapy alone.
Background
Numerous studies across a variety of malignancies have demonstrated that health insurance status is associated with differences in clinical presentation, type of treatments received, and ...survival. The effect of insurance status on the management of soft tissue sarcoma is unknown. We assessed the association of insurance on (a) stage at diagnosis, (b) receipt of neoadjuvant/adjuvant radiation therapy, and (c) overall survival (OS) in patients with soft tissue sarcoma.
Methods
The study cohort was identified from the National Cancer Database (NCDB) and consisted of patients with stage I‐IV soft tissue sarcoma of various histologies diagnosed from 2004 to 2015. The patients were stratified by age (<65 and ≥65 years) and by insurance status (commercial, Medicare, Medicaid and uninsured). Using multivariable logistic regression analysis, we evaluated the association between insurance status and (a) stage at diagnosis (Stage I‐III vs IV), and (b) receipt of neoadjuvant/adjuvant radiation therapy in patients with locally advanced disease. The association of insurance status on OS was assessed using Kaplan‐Meier and multivariable Cox proportional hazards analyses. A propensity score matched survival analysis was performed to account for measured confounders.
Results
49 754 patients were identified of whom 23 677 (48%) had commercial insurance, 20 867 (42%) had Medicare, 3229 (6%) had Medicaid, and 1981 (4%) were uninsured. In patients <65 years, those with Medicaid (OR = 1.74, 95% CI: 1.57‐1.93, P < .001) and the uninsured (OR = 1.71, 95% CI: 1.51‐1.94, P < .001) were more likely to present with stage IV vs Stage I‐III disease. Furthermore, among patients with locally advanced disease treated with limb sparing surgery, those with Medicaid (OR = 0.87, 95% CI: 0.77‐ 0.98, P = .021) and the uninsured (OR = 0.73, 95% CI: 0.63‐0.85, P < .001) were less likely to receive neoadjuvant or adjuvant radiotherapy as compared to those with commercial insurance. Lastly, having Medicaid (HR = 1.26, 95% CI: 1.17‐1.34, P < .001) and no insurance (HR = 1.30, 95% CI: 1.20‐1.41, P < .001) was associated with worse OS compared to having commercial insurance, a finding which remained significant after propensity score matching. In contrast, in patients ≥65 years, there were no statistically significant differences between those with Medicare and commercial insurance with regards to disease presentation, receipt of radiotherapy, or survival.
Conclusions
In a large modern cohort identified from the NCDB, commercial insurance status in patients <65 years was associated early diagnosis, receipt of neoadjuvant/adjuvant radiation therapy, and overall survival for patients with soft tissue sarcoma. Further efforts are warranted to understand disparities in care based on health insurance in the United States.
Using a national cancer registry, we demonstrate that insurance status is associated with differences in stage of diagnosis, receipt of neoadjuvant or adjuvant radiation therapy, and overall survival for patients with soft tissue sarcoma in the United States. These insurance related disparities are most prominent in Medicaid and uninsured patients <65 years of age.
Mitigating Bias in Clinical Machine Learning Models Perez-Downes, Julio C.; Tseng, Andrew S.; McConn, Keith A. ...
Current treatment options in cardiovascular medicine,
03/2024, Letnik:
26, Številka:
3
Journal Article
Recenzirano
Purpose of review
Identifying the risk for and addressing bias in clinical machine learning models is essential to reap its full benefits and ensure health equity. We provide a review of the machine ...learning landscape in clinical medicine, highlight ethical concerns with a particular focus on algorithmic bias, and offer a framework for mitigating bias.
Recent findings
Machine learning, the computational framework that supports artificial intelligence, now plays a significant role in everyday life and its potential role in clinical medicine continues to increase exponentially. Multiple machine learning models have demonstrated outstanding performance, surpassing human abilities with specific tasks, and are poised to revolutionize clinical research and practice over the next few years. While machine learning can augment clinician’s diagnostic capabilities, support clinical decision-making, and improve health care efficiency, they are not infallible. One key concern with the use of machine learning models is algorithmic bias, which if present poses a non-trivial risk to patient care particularly if algorithms are used in a population different from that used to create the algorithm. Recommendations and methods to identify and mitigate algorithmic bias to ensure responsible development of machine learning models are summarized.
Summary
With the anticipated widespread adoption of machine learning in medicine, significant ethical concerns remain, particularly the risk for bias. Researchers, model developers, and end users need to be aware of the potential for bias, its associated risk, and methods to guard against it prior to deploying it for clinical use.
PurposeChest X-ray (CXR) use in pre-MRI safety screening, such as for lead-less implanted electronic device (LLIED) recognition, is common. To assist CXR interpretation, we "pre-deployed" an ...artificial intelligence (AI) model to assess (1) accuracies in LLIED-type (and consequently safety-level) identification, (2) safety implications of LLIED nondetections or misidentifications, (3) infrastructural or workflow requirements, and (4) demands related to model adaptation to real-world conditions.ApproachA two-tier cascading methodology for LLIED detection/localization and identification on a frontal CXR was applied to evaluate the performance of the original nine-class AI model. With the unexpected early appearance of LLIED types during simulated real-world trialing, retraining of a newer 12-class version preceded retrialing. A zero footprint (ZF) graphical user interface (GUI)/viewer with DICOM-based output was developed for inference-result display and adjudication, supporting end-user engagement and model continuous learning and/or modernization.ResultsDuring model testing or trialing using both the nine-class and 12-class models, robust detection/localization was consistently 100%, with mAP 0.99 from fivefold cross-validation. Safety-level categorization was high during both testing ( AUC ≥ 0.98 and ≥ 0.99 , respectively) and trialing (accuracy 98% and 97%, respectively). LLIED-type identifications by the two models during testing (1) were 98.9% and 99.5% overall correct and (2) consistently showed AUC ≥ 0.92 (1.00 for 8/9 and 9/12 LLIED-types, respectively). Pre-deployment trialing of both models demonstrated overall type-identification accuracies of 94.5% and 95%, respectively. Of the small number of misidentifications, none involved MRI-stringently conditional or MRI-unsafe types of LLIEDs. Optimized ZF GUI/viewer operations led to greater user-friendliness for radiologist engagement.ConclusionsOur LLIED-related AI methodology supports (1) 100% detection sensitivity, (2) high identification (including MRI-safety) accuracy, and (3) future model deployment with facilitated inference-result display and adjudication for ongoing model adaptation to future real-world experiences.
Purpose. Practice patterns for treatment of localized adult pleomorphic rhabdomyosarcoma (PRMS) remain quite variable given its rarity. Current national guidelines recommend management similar to ...that of other high-grade soft tissue sarcomas (STS), which include surgery with perioperative radiation (RT) with or without chemotherapy. Using the National Cancer Database (NCDB), we assessed practice patterns and overall outcomes of patients with localized PRMS. Patients and Methods. Patients with stage II/III PRMS treated with surgical resection from 2004 to 2015 were identified from the NCDB. Predictors of RT and chemotherapy use were assessed using multivariable logistic regression analysis. The association of radiation and chemotherapy status on overall survival was assessed using Kaplan–Meier and Cox proportional hazards analyses. Results. Of 243 total patients, RT and chemotherapy were not uniformly utilized, with 44% receiving chemotherapy and in those who did not undergo amputation 62% receiving RT. In those who did not undergo amputation, RT was associated with improved survival on both univariate (HR: 0.49, 95% CI 0.32–0.73, P<0.001) and multivariate analysis (HR: 0.40, 95% CI 0.26–0.62, P<0.001), corresponding to greater 5-year overall survival (59% vs. 38%, P<0.001). Chemotherapy was associated with a higher rate of 5-year overall survival (63% vs. 39%, P<0.001). However, the survival benefit of chemotherapy did not reach statistical significance on multivariate analysis (HR: 0.65, 95% CI 0.41–1.03, P=0.064). Notable predictors of omission of RT included female gender (OR: 0.40, 95% CI 0.22–0.74, P<0.01) and age ≥ 70 (OR: 0.55, 95% CI 0.30–1.00, P=0.05). Correspondingly, factors associated with omission of chemotherapy included age ≥70 (OR: 0.17, 95% CI 0.08–0.39, P<0.001). Conclusions. A significant proportion of patients with localized adult PRMS are not receiving RT. Likewise, use of chemotherapy was heterogeneous. Our findings note potential benefits and underutilization of RT, for which further investigation is warranted.
Chimeric antigen receptor (CAR) T cells have demonstrated promising efficacy, particularly in hematologic malignancies. One challenge regarding CAR T cells in solid tumors is the immunosuppressive ...tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including transforming growth factor (TGF)-β. We report results from an in-human phase 1 trial of castration-resistant, prostate cancer-directed CAR T cells armored with a dominant-negative TGF-β receptor (NCT03089203). Primary endpoints were safety and feasibility, while secondary objectives included assessment of CAR T cell distribution, bioactivity and disease response. All prespecified endpoints were met. Eighteen patients enrolled, and 13 subjects received therapy across four dose levels. Five of the 13 patients developed grade ≥2 cytokine release syndrome (CRS), including one patient who experienced a marked clonal CAR T cell expansion, >98% reduction in prostate-specific antigen (PSA) and death following grade 4 CRS with concurrent sepsis. Acute increases in inflammatory cytokines correlated with manageable high-grade CRS events. Three additional patients achieved a PSA reduction of ≥30%, with CAR T cell failure accompanied by upregulation of multiple TME-localized inhibitory molecules following adoptive cell transfer. CAR T cell kinetics revealed expansion in blood and tumor trafficking. Thus, clinical application of TGF-β-resistant CAR T cells is feasible and generally safe. Future studies should use superior multipronged approaches against the TME to improve outcomes.
Purpose
Positron emission tomography (PET) provides a noninvasive, functional assessment providing incremental diagnostic value over magnetic resonance imaging (MRI) and computed tomography (CT) for ...the initial staging, restaging, response assessment, and prognosis of bone and soft tissue sarcomas. The purpose of this article is to review the current state and future applications of PET in sarcoma imaging, including the clinical roles of 18F-fluorodeoxyglucose (FDG) and other PET radiotracers as well as the use of PET with concurrent MRI.
Methods
A PubMed search using the query “(‘positron emission tomography’ OR PET) AND (‘CT’ OR ‘computed tomograph*’ OR ‘MR*’ OR ‘magnetic resonance’) AND (FDG OR hypox* OR prolif*) AND sarcoma*” for PET examinations involving bone and soft tissue sarcoma studies up to February 1, 2017 were performed. Additionally, analogous Google Scholar, Scopus, and Web of Science search queries were also performed. Subsequently, references for the retrieved articles were reviewed, and the relevant publications on the subject were also included.
Discussion
A total of 30 studies were included in the review. FDG-PET with concurrent computed tomography (CT) can provide incremental diagnostic value relative to MRI to provide additional insight into the grading, staging, restaging, and response assessment in sarcomas, particularly when neoadjuvant therapy is an option. FDG-PET/CT can be used for noninvasive prediction of tumor grade and assess regional heterogeneity, providing guidance for tissue sampling and reducing the risk of undergrading and understaging. In addition, early clinical studies of sarcoma PET imaging using hypoxia and cellular proliferation agents suggest incremental diagnostic benefit over FDG-PET. The use of PET/MRI is under active investigation and may yield additional clinically impactful findings over PET/CT.
Conclusion
PET imaging used with concurrent CT or MRI provides a unique noninvasive way to assess regional biological and biochemical features for bone and soft tissue sarcomas.
PDF
