Accuracy and correlation of bed and standing scale weights in monitoring volume status in heart failure patients.

Introduction: Accurate volume status monitoring is crucial for effective diuretic therapy in patients with acute decompensated heart failure (ADHF). While guidelines recommend daily standing body weight measurement as an indicator of volume status, bed scales are commonly used in healthcare facilities. Methods: A method-comparison design was used to compare bed and standing scale weights among adults hospitalized with ADHF at Los Angeles County-University of Southern California Medical Center between March and April 2023. Results & Conclusion: Among 51 weight pairs from 43 participants, a clinically significant mean difference of 1.42 ± 1.18 kg was observed, exceeding the recommended threshold. Inaccuracies, with 71% showing differences >0.6 kg, highlight potential fluid management errors when relying on bed scales in ADHF hospitalizations.

Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center.

We retrospectively analyzed non-small cell lung cancer (NSCLC) patients from a single center treated with pembrolizumab on the KEYNOTE-001 trial and evaluated the association between treatment-related adverse events (trAEs) and clinical outcomes. Investigators reported AEs on trial and graded them according to Common Terminology Criteria for Adverse Events v4.0, labeling them as unlikely, possibly, or probably treatment-related. AEs labeled as possibly/probably related were considered trAEs for this analysis. The relationship between the incidence of a trAE and clinical outcomes was evaluated. Ninety-seven NSCLC patients treated on KEYNOTE-001 at the University of California, Los Angeles were evaluated. Ten percent (85/826) of AEs were trAEs, occurring in 40% (39/97) of patients. The most frequent trAEs were rash (21% patients), fatigue (6% patients), and hypothyroidism (6% patients). The 39 patients that experienced a trAE had increased objective response rate (ORR, 38.5%), progression-free survival (PFS: median, 248 days), and overall survival (OS: median, 493 days), compared with the 58 patients that did not (ORR: 8.9%, PFS: median 60 days, OS: median 144.5 days). The observed association between trAEs and improved clinical outcome persisted when using Cox proportional hazards regression models to assess the confounding effect of covariates and mitigate guarantee-time bias. The association also remained when data were substratified by grade, degree of association, and treatment-related select AE designation. This single-center analysis revealed that trAEs predicted for improved clinical outcome with pembrolizumab, and when controlling for guarantee-time bias and plausible confounders, this association remained. This observed relationship adds to our understanding of anti-PD-1 therapy and could aid clinicians in identifying patients most likely to benefit from therapy. Cancer Immunol Res; 6(3); 288-94. ©2018 AACR.

Clinical Implications of the T790M Mutation in Disease Characteristics and Treatment Response in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC).

BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI. Medical records were retrospectively analyzed for demographic data, PFS, and best response to previous therapies. RESULTS: Our patient cohort included 69 T790M+ patients and 28 T790M- patients. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 vs. 9.0 months, P = .021), but overall response rate (ORR) was the same (75.0% vs. 81.0%, P = .76). There was no difference in PFS on TKI rechallenge (4.0 vs. 3.0 months, P = .94), although there was a trend toward higher ORR in T790M+ patients (22.2% vs. 0%, P = .12). T790M+ patients had a longer PFS on initial chemotherapy treatment (5.0 vs. 4.0 months, P = .025) and a trend toward higher ORR (40.0% vs. 21.4%, P = .31). CONCLUSION: Our study confirms that tumors expressing T790M have a more indolent progression of disease compared with their T790M- counterparts when treated with both first-line TKI and cytotoxic chemotherapy.

Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

BACKGROUND: Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. METHODS: The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. RESULTS: In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. CONCLUSIONS: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society.

Representing and extracting lung cancer study metadata: study objective and study design.

This paper describes the information retrieval step in Casama (Contextualized Semantic Maps), a project that summarizes and contextualizes current research papers on driver mutations in non-small cell lung cancer. Casama׳s representation of lung cancer studies aims to capture elements that will assist an end-user in retrieving studies and, importantly, judging their strength. This paper focuses on two types of study metadata: study objective and study design. 430 abstracts on EGFR and ALK mutations in lung cancer were annotated manually. Casama׳s support vector machine (SVM) automatically classified the abstracts by study objective with as much as 129% higher F-scores compared to PubMed׳s built-in filters. A second SVM classified the abstracts by epidemiological study design, suggesting strength of evidence at a more granular level than in previous work. The classification results and the top features determined by the classifiers suggest that this scheme would be generalizable to other mutations in lung cancer, as well as studies on driver mutations in other cancer domains.

Clinical Trials in Non-Small Cell Lung Cancer with Biomarker-Driven Treatment Allocation: Ready or Not, Here We Come.

Lung cancer is the leading cause of cancer mortality. Great advances in non-small cell lung cancer therapy have been seen in the last decade, beginning with the success in treating lung cancer harboring EGFR mutations and ALK-gene rearrangements. The potential of these biomarker-driven therapies has propelled research in biomarker targeted approaches to the forefront of lung cancer research. The successful development of immunotherapeutic agents targeting PD-L1 and PD-1 with an associated non-genomic biomarker has opened a new front in the effort for targeted approaches. Although early-phase lung cancer studies have hinted at the potential to use biomarkers to select patients for allocation to treatment in the conduct of clinical trials, data from late-phase studies have tempered expectations. The data leave unclear the wisdom of routinely restricting enrollment on lung cancer clinical trials to biomarker restricted populations, particularly non-genomic biomarkers.