Are the chronological age cutoffs used in clinical oncology guidelines biologically meaningful?
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ABSTRACT:
SUBMITTER: Carleton N
PROVIDER: S-EPMC9675711 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Are the chronological age cutoffs used in clinical oncology guidelines biologically meaningful?
Carleton Neil N McAuliffe Priscilla F PF
Nature reviews. Clinical oncology 20221201 12
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Project description:Identifying along which lineages shifts in diversification rates occur is a central goal of comparative phylogenetics; these shifts may coincide with key evolutionary events such as the development of novel morphological characters, the acquisition of adaptive traits, polyploidization or other structural genomic changes, or dispersal to a new habitat and subsequent increase in environmental niche space. However, while multiple methods now exist to estimate diversification rates and identify shifts using phylogenetic topologies, the appropriate use and accuracy of these methods are hotly debated. Here we test whether five Bayesian methods-Bayesian Analysis of Macroevolutionary Mixtures (BAMM), two implementations of the Lineage-Specific Birth-Death-Shift model (LSBDS and PESTO), the approximate Multi-Type Birth-Death model (MTBD; implemented in BEAST2), and the Cladogenetic Diversification Rate Shift model (ClaDS2)-produce comparable results. We apply each of these methods to a set of 65 empirical time-calibrated phylogenies and compare inferences of speciation rate, extinction rate, and net diversification rate. We find that the five methods often infer different speciation, extinction, and net-diversification rates. Consequently, these different estimates may lead to different interpretations of the macroevolutionary dynamics. The different estimates can be attributed to fundamental differences among the compared models. Therefore, the inference of shifts in diversification rates is strongly method dependent. We advise biologists to apply multiple methods to test the robustness of the conclusions or to carefully select the method based on the validity of the underlying model assumptions to their particular empirical system.
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Project description:PurposeSignificant concerns exist regarding the content and reliability of oncology clinical practice guidelines (CPGs). The Institute of Medicine (IOM) report "Clinical Practice Guidelines We Can Trust" established standards for developing trustworthy CPGs. By using these standards as a benchmark, we sought to evaluate recent oncology guidelines.MethodsCPGs and consensus statements addressing the screening, evaluation, or management of the four leading causes of cancer-related mortality in the United States (lung, breast, prostate, and colorectal cancers) published between January 2005 and December 2010 were identified. A standardized scoring system based on the eight IOM standards was used to critically evaluate the methodology, content, and disclosure policies of CPGs. All CPGs were given two scores; points were awarded for eight standards and 20 subcriteria.ResultsNo CPG fully met all the IOM standards. The average overall scores were 2.75 of 8 possible standards and 8.24 of 20 possible subcriteria. Less than half the CPGs were based on a systematic review. Only half the CPG panels addressed conflicts of interest. Most did not comply with standards for inclusion of patient and public involvement in the development or review process, nor did they specify their process for updating. CPGs were most consistent with IOM standards for transparency, articulation of recommendations, and use of external review.ConclusionThe vast majority of oncology CPGs fail to meet the IOM standards for trustworthy guidelines. On the basis of these results, there is still much to be done to make guidelines as methodologically sound and evidence-based as possible.
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Project description:Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.
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Project description:BackgroundThe ability to construct biologically meaningful gene networks and modules is critical for contemporary systems biology. Though recent studies have demonstrated the power of using gene modules to shed light on the functioning of complex biological systems, most modules in these networks have shown little association with meaningful biological function. We have devised a method which directly incorporates gene ontology (GO) annotation in construction of gene modules in order to gain better functional association.ResultsWe have devised a method, Semantic Similarity-Integrated approach for Modularization (SSIM) that integrates various gene-gene pairwise similarity values, including information obtained from gene expression, protein-protein interactions and GO annotations, in the construction of modules using affinity propagation clustering. We demonstrated the performance of the proposed method using data from two complex biological responses: 1. the osmotic shock response in Saccharomyces cerevisiae, and 2. the prion-induced pathogenic mouse model. In comparison with two previously reported algorithms, modules identified by SSIM showed significantly stronger association with biological functions.ConclusionsThe incorporation of semantic similarity based on GO annotation with gene expression and protein-protein interaction data can greatly enhance the functional relevance of inferred gene modules. In addition, the SSIM approach can also reveal the hierarchical structure of gene modules to gain a broader functional view of the biological system. Hence, the proposed method can facilitate comprehensive and in-depth analysis of high throughput experimental data at the gene network level.
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Project description:This fifth revised version of the Korean Society of Gynecologic Oncology practice guidelines for the management of cervical cancer incorporates recent research findings and changes in treatment strategies based on version 4.0 released in 2020. Each key question was developed by focusing on recent notable insights and crucial contemporary issues in the field of cervical cancer. These questions were evaluated for their significance and impact on the current treatment and were finalized through voting by the development committee. The selected key questions were as follows: the efficacy and safety of immune checkpoint inhibitors as first- or second-line treatment for recurrent or metastatic cervical cancer; the oncologic safety of minimally invasive radical hysterectomy in early stage cervical cancer; the efficacy and safety of adjuvant systemic treatment after concurrent chemoradiotherapy in locally advanced cervical cancer; and the oncologic safety of sentinel lymph node mapping compared to pelvic lymph node dissection. The recommendations, directions, and strengths of this guideline were based on systematic reviews and meta-analyses, and were finally confirmed through public hearings and external reviews. In this study, we describe the revised practice guidelines for the management of cervical cancer.
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Project description:ObjectiveIn this phase II psychometric study on the Montreal cognitive assessment (MoCA), we tested the clinicometric properties of Italian norms for patients with mild cognitive impairment (PwMCI) and early dementia (PwD) and provided optimal cutoffs for diagnostic purposes.MethodsRetrospective data collection was performed for consecutive patients with clinically and biologically defined MCI and early dementia. Forty-five patients (24 PwMCI and 21 PwD) and 25 healthy controls were included. Raw MoCA scores were adjusted according to the conventional 1-point correction (Nasreddine) and Italian norms (Conti, Santangelo, Aiello). The diagnostic properties of the original cutoff (< 26) and normative cutoffs, namely, the upper limits (uLs) of equivalent scores (ES) 1, 2, and 3, were evaluated. ROC curve analysis was performed to obtain optimal cutoffs.ResultsThe original cutoff demonstrated high sensitivity (0.93 [95% CI 0.84-0.98]) but low specificity (0.44 [0.32-0.56]) in discriminating between patients and controls. Nominal normative cutoffs (ES0 uLs) showed excellent specificity (SP range = 0.96-1.00 [0.88-1.00]) but poor sensitivity (SE range = 0.09-0.24 [0.04-0.36]). The optimal cutoff for Nasreddine's method was 23.50 (SE = 0.82 [0.71-0.90]; SP = 0.72 [0.60-0.82]). Optimal cutoffs were 20.97, 22.85, and 22.29 (SE range = 0.69-0.73 [0.57-0.83], SP range = 0.88-0.92 [0.77-0.97]) for Conti's, Santangelo's, and Aiello's methods, respectively.ConclusionUsing the 1-point correction, combined with a cutoff of 23.50, might be useful in ambulatory settings with a large turnout. Our optimal cutoffs can offset the poor sensitivity of Italian cutoffs.
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