Category: Nevin Manimala

JAMA Oncol. 2023 May 11. doi: 10.1001/jamaoncol.2023.0646. Online ahead of print.

ABSTRACT

IMPORTANCE: Combination of chemotherapy with (dual) ERBB2 blockade is considered standard in hormone receptor (HR)-positive/ERBB2-positive early breast cancer (EBC). Despite some promising data on endocrine therapy (ET) combination with dual ERBB2 blockade in HR-positive/ERBB2-positive BC, to our knowledge, no prospective comparison of neoadjuvant chemotherapy vs ET plus ERBB2 blockade in particular with focus on molecular markers has yet been performed.

OBJECTIVE: To determine whether neoadjuvant de-escalated chemotherapy is superior to endocrine therapy, both in combination with pertuzumab and trastuzumab, in a highly heterogeneous HR-positive/ERBB2-positive EBC.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, neoadjuvant randomized clinical trial allocated 207 patients with centrally confirmed estrogen receptor-positive and/or progesterone receptor-positive (>1%) HR-positive/ERBB2-positive EBC to 12 weeks of standard ET (n = 100) vs paclitaxel (n = 107) plus trastuzumab and pertuzumab. A total of 186 patients were required to detect a statistically significant difference in pathological complete response (pCR) (assumptions: 19% absolute difference in pCR; power, ≥80%; 1-sided Fisher exact test, 2.5% significance level).

INTERVENTIONS: Standard ET (aromatase inhibitor or tamoxifen) or paclitaxel, 80 mg/m2, weekly plus trastuzumab and pertuzumab every 21 days.

MAIN OUTCOMES AND MEASURES: The primary end point was pCR (ypT0/is, ypN0). Secondary end points included safety, translational research, and health-related quality of life. Omission of further chemotherapy was allowed in patients with pCR. PAM50 analysis was performed on baseline tumor biopsies.

RESULTS: Of the 207 patients included (median [range] age, 53 [25-83] years), 121 (58%) had cT2 to cT4 tumors, and 58 (28%) had clinically node-positive EBC. The pCR rate in the ET plus trastuzumab and pertuzumab arm was 23.7% (95% CI, 15.7%-33.4%) vs 56.4% (95% CI, 46.2%-66.3%) in the paclitaxel plus trastuzumab and pertuzumab arm (odds ratio, 0.24; 95% CI, 0.12-0.46; P < .001). Both immunohistochemical ERBB2 score of 3 or higher and ERBB2-enriched subtype were independent predictors for pCR in both arms. Paclitaxel was superior to ET only in the first through third quartiles but not in the highest ERBB2 quartile by messenger RNA. In contrast with the paclitaxel plus trastuzumab and pertuzumab arm, no decrease in health-related quality of life after 12 weeks was observed in the ET plus trastuzumab and pertuzumab arm.

CONCLUSIONS AND RELEVANCE: The WSG-TP-II randomized clinical trial is, to our knowledge, the first prospective trial comparing 2 neoadjuvant de-escalation treatments in HR-positive/ERBB2-positive EBC and demonstrated an excellent pCR rate after 12 weeks of paclitaxel plus trastuzumab and pertuzumab that was clearly superior to the pCR rate after ET plus trastuzumab and pertuzumab.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03272477.

PMID:37166817 | DOI:10.1001/jamaoncol.2023.0646

CPT Pharmacometrics Syst Pharmacol. 2023 May 11. doi: 10.1002/psp4.12976. Online ahead of print.

ABSTRACT

The dose/exposure-efficacy analyses are often conducted separately for oncology end points like best overall response, progression-free survival (PFS) and overall survival (OS). Multistate models offer to bridge these dose-end point relationships by describing transitions and transition times from enrollment to response, progression, and death, and evaluating transition-specific dose effects. This study aims to apply the multistate pharmacometric modeling and simulation framework in a dose optimization setting of bintrafusp alfa, a fusion protein targeting TGF-β and PD-L1. A multistate model with six states (stable disease [SD], response, progression, unknown, dropout, and death) was developed to describe the totality of endpoints data (time to response, PFS, and OS) of 80 patients with non-small cell lung cancer receiving 500 or 1200 mg of bintrafusp alfa. Besides dose, evaluated predictor of transitions include time, demographics, premedication, disease factors, individual clearance derived from a pharmacokinetic model, and tumor dynamic metrics observed or derived from tumor size model. We found that probabilities of progression and death upon progression decreased over time since enrollment. Patients with metastasis at baseline had a higher probability to progress than patients without metastasis had. Despite dose failed to be statistically significant for any individual transition, the combined effect quantified through a model with dose-specific transition estimates was still informative. Simulations predicted a 69.2% probability of at least 1 month longer, and, 55.6% probability of at least 2-months longer median OS from the 1200 mg compared to the 500 mg dose, supporting the selection of 1200 mg for future studies.

PMID:37165943 | DOI:10.1002/psp4.12976

Cancer Med. 2023 May 11. doi: 10.1002/cam4.6035. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer diagnosis and treatment increase the potential psychological impact on breast cancer survivors (BCS). The objective of this study was to assess the effects of an interdisciplinary intervention during follow-up in BCS and identify variables related to improvements in HRQoL.

MATERIALS AND METHODS: In a non-randomised quasi-experimental design performed on an outpatient basis in a hospital gynaecology and oncology unit, 60 BCS were assigned to an interdisciplinary experimental group (EG) or a usual care group (CG). The EG underwent 12 sessions of an interdisciplinary program which included Mindfulness and physiotherapy, for 120 min per day, once a week for 6 weeks. At baseline, at 6 weeks and at 3 months after the intervention, participants of EG and CG completed an assessment of HRQoL (EuroQol and EORTC-QLQ-C30) and symptomatology of anxiety and depression. Additionally, EG completed an assessment of satisfaction with the treatment. For data analysis, we used descriptive statistics, Wilcoxon test, Kruskal-Wallis test, Chi-square and Fisher tests and generalised linear models.

RESULTS: After 6 weeks, statistically significant differences were apparent in global and cancer-related health symptoms such as fatigue and pain in the EORTC QLQ-C30 and in anxiety and depression, among the EG (n = 30) compared with the CG (n = 30). Patients receiving the intervention reported a high degree of satisfaction with the treatment. Three months after the intervention, patients in the EG continued to show statistically significant improvements compared with the CG. In addition, allocation to the EG was identified as a variable related to improvement of HRQoL (EORTC QLQ-C30) in the multivariable model.

CONCLUSIONS: The results of our study suggest that a 6-week interdisciplinary intervention may improve HRQoL and symptomatology of anxiety and depression in BCS patients at 3 months. The study presents data that the intervention for BCS appears promising and warrants further study in a randomised controlled trial.

PMID:37165927 | DOI:10.1002/cam4.6035

J Magn Reson Imaging. 2023 May 11. doi: 10.1002/jmri.28742. Online ahead of print.

ABSTRACT

BACKGROUND: Local staging of prostate cancer (PCa) is important for treatment planning. Radiologist interpretation using qualitative criteria is variable with high specificity but low sensitivity. Quantitative methods may be useful in the diagnosis of extracapsular extension (ECE).

PURPOSE: To assess the performance of quantitative MRI markers for detecting ECE.

STUDY TYPE: Systematic review and meta-analysis.

SUBJECTS: 4800 patients from 28 studies with histopathologically confirmed PCa on radical prostatectomy were pooled for meta-analysis. Patients from 46 studies were included for systematic review.

FIELD STRENGTH/SEQUENCE: Diffusion-weighted, T2-weighted, and dynamic contrast-enhanced MRI at 1.5 T or 3 T.

ASSESSMENT: PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched to identify studies on diagnostic test accuracy or association of any quantitative MRI markers with ECE. Results extracted by two independent reviewers for tumor contact length (TCL) and mean apparent diffusion coefficient (ADC-mean) were pooled for meta-analysis, but not for other quantitative markers including radiomics due to low number of studies available.

STATISTICAL TESTS: Hierarchical summary receiver operating characteristic (HSROC) curves were computed for both TCL and ADC-mean, but summary operating points were computed for TCL only. Heterogeneity was investigated by meta-regression. Results were significant if P ≤ 0.05.

RESULTS: At the 10 mm threshold for TCL, summary sensitivity and specificity were 0.76 [95% confidence interval (CI) 0.71-0.81] and 0.68 [95% CI 0.63-0.73], respectively. At the 15 mm threshold, summary sensitivity and specificity were 0.70 [95% CI 0.53-0.83] and 0.74 [95% CI 0.60-0.84] respectively. The area under the HSROC curves for TCL and ADC-mean were 0.79 and 0.78, respectively. Significant sources of heterogeneity for TCL included timing of MRI relative to biopsy.

DATA CONCLUSION: Both 10 mm and 15 mm thresholds for TCL may be reasonable for clinical use. From comparison of the HSROC curves, ADC-mean may be superior to TCL at higher sensitivities.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

PMID:37165923 | DOI:10.1002/jmri.28742

Nurs Open. 2023 May 11. doi: 10.1002/nop2.1774. Online ahead of print.

ABSTRACT

AIM: The aim of the study was to analyse the correlations among organizational justice, knowledge-hiding behaviour and nurses’ innovation ability.

DESIGN: A descriptive and cross-sectional design and the data were collected using questionnaires.

METHODS: Demographic information, professional data, innovation capacity scales, knowledge-hiding scales and organizational justice scales were used in this study. Using descriptive statistics, t-tests, one-way analysis of variance and Pearson’s or Spearman’s correlation analyses, we compared the differences and examined the correlations between participants’ demographic and innovation capacity scales, and knowledge-hiding scales and organizational fairness scales.

RESULTS: We received 1486 valid responses, with an effective response rate of 96.68%. We found team role, nursing age, number of training, literature-reading habits, organizational justice, information justice, fair distribution and deaf knowledge-hiding as the influencing factors of nurses’ innovation. Nurses’ sense of organizational fairness negatively correlated with knowledge concealment and positively correlated with innovation ability. Moreover, knowledge hiding negatively correlated with nurses’ innovation ability. Furthermore, knowledge-hiding plays a partial intermediary role between organizational fairness and nurses’ innovation ability.

PMID:37165909 | DOI:10.1002/nop2.1774

J Magn Reson Imaging. 2023 May 11. doi: 10.1002/jmri.28766. Online ahead of print.

ABSTRACT

BACKGROUND: Computed diffusion-weighted images (cDWI) of random b value could be derived from acquired DWI (aDWI) with at least two different b values. However, its comparison between aDWI and cDWI images in locally advanced rectal cancer (LARC) patients after neoadjuvant therapy (NT) is needed.

PURPOSE: To compare the cDWI and aDWI in image quality, restaging, and treatment response of LARC after NT.

STUDY TYPE: Retrospective.

POPULATION: Eighty-seven consecutive patients.

FIELD STRENGTH/SEQUENCE: 3.0 T/DWI.

ASSESSMENT: All patients underwent two DWI sequences, including conventional acquisition with b = 0 and 1000 s/mm² (aDWI_b1000 ) and another with b = 0 and 700 s/mm² on a 3.0-T MR scanner. The images of the latter were used to compute the diffusion images with b = 1000 s/mm² (cDWI_b1000 ). Four radiologists with 3, 4, 14, and 25 years of experience evaluated the images to compare the image quality, TN restaging performance, and treatment response between aDWI_b1000 and cDWI_b1000 .

STATISTICAL TESTS: Interclass correlation coefficients, weighted κ coefficient, paired Wilcoxon, and McNemar or Fisher test were used. A significance level of 0.05 was used.

RESULTS: The cDWI_b1000 images were superior to the aDWI_b1000 ones in both subjective and objective image quality. In T restaging, the overall diagnostic accuracy of cDWI_b1000 images was higher than that of aDWI_b1000 images (57.47% vs. 49.43%, P = 0.289 for the inexperienced radiologist; 77.01% vs. 63.22%, significant for the experienced radiologist), with better sensitivity in determining ypT0-Tis tumors. Additionally, it increased the sensitivity in detecting ypT2 tumors for the inexperienced radiologist and ypT3 tumors for the experienced radiologist. N restaging and treatment response were found to be similar between two sequences for both radiologists.

DATA CONCLUSION: Compared to aDWI_b1000 images, the computed ones might serve as a wise approach, providing comparable or better image quality, restaging performance, and treatment response assessment for LARC after NT.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

PMID:37165908 | DOI:10.1002/jmri.28766

Health Educ Behav. 2023 May 11:10901981231168872. doi: 10.1177/10901981231168872. Online ahead of print.

ABSTRACT

BACKGROUND: In April 2016, the City of Chicago implemented an ordinance restricting the sale of all flavored (including menthol) tobacco products (FTPs), including electronic cigarettes, at retailers located within 500 feet of any public, private, or alternative elementary, middle (“primary”), or high (“secondary”) school. We examined changes in retail availability of FTPs from before to after policy implementation among policy-affected retailers compared with retailers not subject to the policy.

METHOD: Observational data were collected in June to September 2015 (Wave 1; pre-policy) and November to December 2016 (Wave 2; post-policy) from a panel of 194 randomly selected policy-area stores (located within 500 feet of a school), and a panel of 199 randomly selected comparison-area stores (located more than 500 feet from a school). Using generalized estimation equation regression, we assessed differences in FTP availability changes across study areas.

RESULTS: We observed a statistically significant policy effect on FTP availability (Area × Wave interaction, p < .05); however, more than half of policy-area retailers continued to display at least one FTP after policy implementation (87.11% at Wave 1, 57.73% at Wave 2, p < .05). Similar reductions were seen for the availability of flavored cigarillos/little cigars and menthol cigarettes, while policy effects varied across store types.

DISCUSSION: FTP availability reductions appear to be associated with policy implementation, but FTPs remained readily available at retailers subject to the policy. This study contributes to the evidence base indicating that policies with exclusions or exemptions for certain flavors, products, store types, or retailer locations have a limited effect on retail availability of FTPs.

PMID:37165868 | DOI:10.1177/10901981231168872

Stroke. 2023 May 11. doi: 10.1161/STROKEAHA.122.041397. Online ahead of print.

ABSTRACT

BACKGROUND: Based on the inclusion criteria of clinical trials, the degree of cervical carotid artery stenosis is often used as an indication for stent placement in the setting of extracranial carotid atherosclerotic disease. However, the rigor and consistency with which stenosis is measured outside of clinical trials are unclear. In an agreement study using a cross-sectional sample, we compared the percent stenosis as measured by real-world physician operators to that measured by independent expert reviewers.

METHODS: As part of the carotid stenting facility accreditation review, images were obtained from 68 cases of patients who underwent carotid stent placement. Data collected included demographics, stroke severity measures, and the documented degree of stenosis, termed operator-reported stenosis (ORS), by 34 operators from 14 clinical sites. The ORS was compared with reviewer-measured stenosis (RMS) as assessed by 5 clinicians experienced in treating carotid artery disease.

RESULTS: The median ORS was 90.0% (interquartile range, 80.0%-90.0%) versus a median RMS of 61.1% (interquartile range, 49.8%-73.6%), with a median difference of 21.8% (interquartile range, 13.7%-34.4%), P<0.001. The median difference in ORS and RMS for asymptomatic versus symptomatic patients was not statistically different (24.6% versus 19.6%; P=0.406). The median difference between ORS and RMS for facilities granted initial accreditation was smaller compared with facilities whose accreditation was delayed (17.9% versus 25.5%, P=0.035). The intraclass correlation between ORS and RMS was 0.16, indicating poor agreement. If RMS measurements were used, 72% of symptomatic patients and 10% of asymptomatic patients in the population examined would meet the Centers for Medicare and Medicaid Services criteria for stent placement.

CONCLUSIONS: Real-world operators tend to overestimate carotid artery stenosis compared with external expert reviewers. Measurements from facilities granted initial accreditation were closer to expert measurements than those from facilities whose accreditation was delayed. Since decisions regarding carotid revascularization are often based on percent stenosis, such measuring discrepancies likely lead to increased procedural utilization.

PMID:37165866 | DOI:10.1161/STROKEAHA.122.041397

Phys Chem Chem Phys. 2023 May 10;25(18):12863-12871. doi: 10.1039/d2cp05350k.

ABSTRACT

The characteristic cluster pattern of cross-peaks in a 2D asynchronous spectrum provides an effective way to reveal the specific physicochemical nature of subtle spectral changes caused by intermolecular interactions. However, the inevitable presence of noise in the 1D spectra used to construct a 2D asynchronous spectrum is significantly amplified, which poses a serious challenge in identifying the correct cluster pattern of the cross-peaks. While mirror symmetry occurs in some types of cross-peaks, it does not occur in other types. The Kolmogorov-Smirnov test provides a statistical means to check whether the mirror symmetry exists or not between a pair of cross-peaks covered by heavy noise. Thus, different types of cross-peak clusters can be distinguished by excavating intrinsic spectral features from the noisy 2D asynchronous spectrum. The effectiveness of this approach in investigating the nature of intermolecular interactions was showcased in both a simulated model system and a real artemisinin/N-methyl pyrrolidone system.

PMID:37165857 | DOI:10.1039/d2cp05350k

Glob Health Action. 2023 Dec 31;16(1):2203541. doi: 10.1080/16549716.2023.2203541.

ABSTRACT

BACKGROUND: Globally, steps to revitalise programmes deploying community health workers (CHWs) on a national scale have been growing, but few economic evaluations have been done on system-integrated CHW programmes. Ghana has dual cadres of CHWs: community health officers (CHOs) and community health volunteers (CHVs). CHO plays a major role in primary health services but has suffered from chronic staff shortages. We activated CHVs in communities to mitigate the negative impact due to CHO shortages. The CHVs conducted home visits and provided health education to prevent childhood diseases.

OBJECTIVE: We evaluated the cost-effectiveness and cost-benefit of activating CHVs.

METHODS: In a cluster-randomised trial with 40 communities in rural Ghana, the changes in disease incidence were inferred from a statistical model using a Bayesian generalised linear multilevel model. We evaluated the total incremental cost, benefit, and effectiveness for the intervention from an economic model. In cost-effectiveness analysis, disability-adjusted life years (DALYs) were estimated using a decision tree model. In the cost-benefit analysis, the cost-benefit ratio and net present value of benefit were estimated using a decision tree model, and a standardised sensitivity analysis was conducted. The decision tree model was a one-year cycle and run over 10-years. Costs, benefits, and effectiveness were discounted at a rate of 3% per year.

RESULTS: According to the cost-effectiveness analysis, the programme was highly likely to exceed the WHO-CHOICE threshold (1-3 times GDP per capita), but it was unlikely to exceed the conservative threshold (10-50% of GDP per capita). In the cost-benefit analysis, the mean and median cost-benefit ratios were 6.4 and 4.8, respectively.

CONCLUSION: We found the potential economic strengths in the cost-benefit analysis. To integrate CHW programmes with national health systems, we need more research to find the most effective scope of work for CHWs.

PMID:37165851 | DOI:10.1080/16549716.2023.2203541