Treatment Decisions For Patients Research Articles

Bayesian hierarchical profile regression for binary covariates.

Dysphagia, a common result of other medical conditions, is caused by malfunctions in swallowing physiology resulting in difficulty eating and drinking. The Modified Barium Swallow Study (MBSS), the most commonly used diagnostic tool for evaluating dysphagia, can be assessed using the Modified Barium Swallow Impairment Profile (MBSImP™). The MBSImP assessment tool consists of a hierarchical grouped data structure with multiple domains, a set of components within each domain which characterize specific swallowing physiologies, and a set of tasks scored on a discrete scale within each component. We lack sophisticated approaches to extract patterns of physiologic swallowing impairment from the MBSImP task scores within a component while still recognizing the nested structure of components within a domain. We propose a Bayesian hierarchical profile regression model, which uses a Bayesian profile regression model in conjunction with a hierarchical Dirichlet process mixture model to (1) cluster subjects into impairment profile patterns while respecting the hierarchical grouped data structure of the MBSImP, and (2) simultaneously determine associations between latent profile cluster membership for all components and the outcome of dysphagia severity. We apply our approach to a cohort of patients referred for an MBSS and assessed using the MBSImP. Our research results can be used to inform appropriate intervention strategies, and provide tools for clinicians to make better multidimensional management and treatment decisions for patients with dysphagia.

T-Cell Expression of CXCL13 is Associated with Immunotherapy Response in a Sex-Dependent Manner in Patients with Lung Cancer.

Emerging evidence in preclinical models demonstrates that antitumor immunity is not equivalent between males and females. However, more investigation in patients and across a wider range of cancer types is needed to fully understand sex as a variable in tumor immune responses. We investigated differences in T-cell responses between male and female patients with lung cancer by performing sex-based analysis of single cell transcriptomic datasets. We found that the transcript encoding CXC motif chemokine ligand 13 (CXCL13), which has recently been shown to correlate with T-cell tumor specificity, is expressed at greater levels in T cells isolated from female compared with male patients. Furthermore, increased CXCL13 expression was associated with response to PD1-targeting immunotherapy in female but not male patients. These findings suggest that there are sex-based differences in T-cell function required for response to anti-PD1 therapy in lung cancer that may need to be considered during patient treatment decisions. See related Spotlight by Cruz-Hinojoza and Stromnes, p. 952.

Impact of peridiagnostic genetic counseling and germline testing on treatment decisions for patients with triple negative breast cancer undergoing pembrolizumab-chemotherapy neoadjuvant approach.

e12633 Background: Triple negative breast cancer (TNBC) has been globally associated with a high risk of carrying pathogenic or likely pathogenic (P/LP) variants in germline breast cancer (BC) susceptibility genes (BCSG). Immunotherapy- based Neoadjuvant (pembro-NA) treatment is the preferred approach for localized, T2 or node positive TNBC. To the best of our knowledge, information about peridiagnostic genetic counseling (PGC), germline status and their impact on patients (pts) undergoing this treatment approach has not been reported yet. Our aim was to describe the feasibility and impact of PGC in TNBC pts treated with pembro-NA and to compare clinical benefits between carriers and wild type (WT) pts in a real- world (RW) setting. Methods: Consecutive, localized TNBC pts who received pembro-NA were enrolled, between March 2022 and August 2023 in a private Argentinian institution. Informed consent was obtained, and medical information collected from medical records and an institutional GC registry. Clinical benefit in terms of pathological complete response (pCR) was analyzed according to BCSG status. Univariate analyses, including chi-square, Fisher and Wilcoxon tests were performed when appropriate. p<0.05 was considered for statistical significance. Results: 47 pts were ascertained. 36.5% (15/41) tested positive for BCSG: 93% (14/15) for BRCA1-2 genes (gBRCA+). No differences were observed in pts ages, with medians of 45 years [IQR 40-50.5] vs 40 [IQR 35-48] among non-carriers versus carriers, respectively (p=0.56). Also, stage at presentation was similar for both subgroups (II: 77.8% vs 60%, III: 14.8% vs 33.3; p=0.37). PGC outcomes: 1/47 (2%) was previously diagnosed as BRCA1 positive (gBRCA+), 1/47 (2%) died before PGC assessment; 85% (40/47) were assessed locally; 64% (30/47) revealed a positive cancer family history; 93% (38/41) were tested through multi-gene panel testing. Median time from diagnosis to first GC appointment was 11.4 weeks (wk) and to disclosure of genetic results by a geneticist or oncologist was 13 wk. Treatment outcomes: 81% (38/47) had completed pembro-NA; one (2%) progressed in the WT group. pCR was achieved in 78.9% (30/38), with no differences between groups (p=0.46). Olaparib or capecitabine were added in pts that did not achieve pCR according to gBRCA status. Notably, 73% carriers versus 37.5% WT pts underwent risk-reducing bilateral mastectomy (p=0.0304). Conclusions: PGC is feasible in a RW scenario of limited resources such as in Argentina. We found a high rate of carriers, mostly gBRCA+, in which surgical decisions and post-NA treatments were determined considering germline status findings. Although efficacy differences between gBRCA+ and WT were not found, further research and data on long-terms outcomes are needed to assess comparative results.

Role of biomarkers in community-acquired pneumonia management

Community-acquired pneumonia (CAP) poses a significant global health threat, particularly affecting vulnerable populations. Biomarkers and scoring systems play a crucial role in diagnosing, assessing severity, and guiding treatment decisions for CAP patients. Biomarkers like C reactive protein, procalcitonin, and the neutrophil-to-lymphocyte ratio aid in diagnosis and severity assessment, while scoring systems such as CURB-65 and Pneumonia Severity Index classify patients into risk categories. Emerging biomarkers (uremia, elevated respiratory rate, hypotension, and age ≥ 65) like serum amyloid A and S100 proteins show promise in predicting disease severity and prognosis. However, further research is needed to determine their precise roles and clinical utility in CAP management.

Relationship between receipt of combined axillary dissection and nodal irradiation and age.

11043 Background: Combined axillary lymph node dissection and regional nodal irradiation (ALND+RNI) is the greatest risk factor for breast cancer-related lymphedema (BCRL), a lifelong ailment that negatively impacts quality of life. As disability from BCRL may be particularly profound for adults <45 yo with longer life expectancy, we examined the association of age and other sociodemographics with receipt of ALND+RNI to further our understanding of patients at greatest risk for BCRL. Methods: The National Cancer Database (NCDB) was used to examine age-based differences in receipt of ALND+RNI in patients with stage I-III breast cancer treated from 2018-2020. Cohort characteristics were compared by age (<45 yo, 45-64 yo, and 65 yo). Multivariable regression examined the association between age and ALND+RNI adjusting for relevant factors. Sensitivity analyses explored associations between covariates and combined ALND+RNI by age group. Results: Of 155,010 patients, 5.4% were <45 yo, 47.2% were 45-64 yo, and 47.4% were 65 yo. Clinical and pathological node (cN, pN) positive disease, and receipt of ALND, RNI, and ALND+RNI were more common in patients <45 yo (Table). Age <45 yo was independently associated with ALND+RNI (<45 yo OR 1.40; 45-64 yo OR 1.26 vs 65, p<0.001). Residing in areas with a high proportion of high-school graduates (%HSG), Hispanic ethnicity but not race, and lower income were also associated with ALND+RNI in adjusted analyses (all p<0.05). Medicare (p=0.02 vs private insurance) was inversely associated with ALND+RNI. Among clinical factors, pN+ was the greatest risk factor for receipt of ALND+RNI (all p<0.001 vs pN0). Higher cT, cN1 and cN2 categories, lobular tumors, mastectomy, not receiving endocrine therapy, and having chemotherapy were also associated with ALND+ RNI (all p<0.05). Sensitivity analyses showed that while sociodemographics influenced receipt of ALND+RNI for women 45 yos, only clinical factors were significant for ALND+RNI for <45 yo. Among 45-64 yo, high %HSG (p<0.001) and low household incomes (p<0.01) were associated with ALND+RNI. In the 65 yo cohort, high %HSG (p=0.028), and Asian race (p=0.011) were more likely to receive ALND+RNI while Medicare patients were less likely to have ALND+RNI (p=0.012). Conclusions: Our findings suggests that clinical factors predominate in axillary treatment decisions for younger patients; while sociodemographic factors are more prominent for those 45 yo. Given their higher odds of receiving ALND+RNI, BCRL screening may be especially important in patients <45 yo. Further studies are needed to understand the interplay between age and sociodemographics on receipt of ALND+RNI. [Table: see text]

Clinical-pathological characteristics associated with multigene assay risk scores, and prognostic impact of multigene risk scores in patients with invasive lobular carcinoma.

546 Background: Invasive Lobular Carcinoma (ILC), a unique breast cancer subtype, exhibits distinct clinical and pathological features. Multigene assays, notably the Oncotype DX (ODX) test, provide personalized prognostic insights in breast cancer. However, a research gap exists for clinical-pathological characteristics affecting multigene assay risk scores in ILC. This study aims to address this gap, investigating factors specific to ILC, distinct from those in invasive ductal carcinoma (IDC), contributing to refined risk stratification and personalized treatment decisions for ILC patients. Methods: Retrospective analysis was conducted on 238 ILC type breast cancer patients who underwent surgery at AMC between 2012 and 2022 and had undergone the ODX test. The ODX test assessed the Recurrence Score (RS) with defined categories: low (0-15), intermediate (16-25), and high (26 or above). Additionally, binary analysis categorized patients into low and high-risk groups using a cutoff of 25. The cutoffs were determined based on existing research findings. Results: Among patients undergoing ODX testing, the distribution of RS differed significantly between ILC and invasive ductal carcinoma (IDC) patients. Notably, the percentage of high-risk cases was higher in ILC (4.2%) compared to IDC (16.9%). Examination of patient characteristics revealed a prevalence of younger individuals, premenopausal status, and those undergoing breast-conserving surgery (BCS) among the low-risk binary group. In multivariate logistic regression analysis, PR negativity emerged as a significant factor influencing ODX high risk across the entire cohort (OR 23.224, 95% CI 3.732-144.527, p=0.001). Subgroup analysis by age identified specific risk factors, including PR negativity in younger patients (OR 11.896, 95% CI 1.247-113.523, p=0.031), larger tumor size (more than 2cm) (OR 4.180, 95% CI 1.229-14.214, p=0.022), and PR negativity in older patients (OR 25.030, 95% CI 3.505-178.756, p=0.001). Conclusions: In ILC, factors predicting ODX differ from IDC, emphasizing the need for tailored risk prediction models. PR negativity emerged as a consistent predictor of ODX high risk, warranting attention in risk stratification models. Recognizing this distinction is crucial for enhancing precision in prognostic assessments and optimizing patient management in ILC.

A meta-analysis of models for predicting the incidence of brain metastasis in patients with lung cancer.

e13613 Background: Brain metastasis (BM) represents a significant clinical challenge in the management of lung cancer, impacting patient prognosis and treatment decisions. While various predictive models have been developed to assess the risk of BM development, their performance and applicability remain under scrutiny. Understanding the accuracy and reliability of these models is crucial for informing clinical practice and improving patient care. We sought to evaluate the predictive ability of existing models predicting BM incidence in lung cancer patients, providing valuable insights into their clinical utility and areas for further refinement. Methods: Two reviewers conducted a systematic search of numerous databases, including PubMed, EMBASE, Cochrane Library, and CINAHL, and then extracted the relevant information from the eligible studies. For this study, we conducted a meta-analysis using a random-effects model. Pooled estimates were calculated for any combination of outcomes and population when at least two studies had relevant data. Study heterogeneity was assessed using I² statistics. The area under the curve (AUC) of the best model and 95% confidence intervals were set as effect measures. Additionally, funnel plots and results from meta-regression analysis were reported. Meta-analysis was performed with R software ver. 4.3.1, and quality evaluation of evidence was conducted according to the GRADE standard. Results: A total of seven studies with 535,418 participants were eligible. A random-effects model showed that models that could predict the risk of developing BM among lung cancer cases had a pooled AUC of 81% (95% CI: 74% to 87%). However, the studies had significantly higher heterogeneity, with an I2 = 99% (p<0.01). Results from meta-regression analysis, accounting for the year of publication (?=-0.013), sample size (?< 0.00), number of variables (?=-0.015), and latitude (?=0.0024) did not show any statistically significant associations with a p>0.05. Egger’s regression test for publication bias did not indicate small study effects (Bias estimate: 4.91, SE = 6.01, p< 0.44). Conclusions: Our meta-analysis underscores the utility of existing models in predicting the incidence of BM in LC patients, with a pooled AUC of 81%. Further research aimed at refining predictive models and addressing sources of heterogeneity is imperative to enhance clinical decision-making and improve patient outcomes in this population. [Table: see text]

Real-world tumor BRCA testing patterns and PARP inhibitor use in HER2-negative metastatic breast cancer.

1113 Background: Testing for BRCA1/BRCA2 mutations (BRCAm) aids systemic treatment decisions for patients (pts) with metastatic breast cancer (mBC). This retrospective study explored real-world germline/tumor (g/t) BRCA testing patterns and PARP inhibitor (PARPi) use in US pts with mBC. Methods: Data from pts ≥18 years old diagnosed with HER2-negative mBC from 2014–2022 were captured in the nationwide Flatiron Health electronic health record-derived deidentified database. Patterns and timing of prospective or incidental BRCA testing were compared across mBC subtypes (hormone receptor-positive [HR+ mBC]/triple-negative mBC [mTNBC]) and disease stage (recurrent/ de novo). BRCAm prevalence was compared by testing modality and mBC subtype. PARPi initiation was assessed in pts with mBC diagnosed from 2018 onwards and a positive BRCAm test result. Clinical characteristics were compared by receipt of a BRCA test, testing modality, and PARPi initiation. Real-world overall survival (OS) by PARPi use was estimated using the Kaplan-Meier method. Results: Of 15,006 pts (including 12,349 with HR+ mBC; 1998 with mTNBC), 8178 (54.5%) did not receive any type of BRCA test, 4654 (31.0%) received a gBRCA test, 3075 (20.5%) received a tumor tissue DNA (ttDNA) test, and 1418 (9.4%) received a circulating tumor DNA (ctDNA) test. BRCA testing prevalence was numerically higher in pts with mTNBC (n=1164; 58.3%) than in pts with HR+ mBC (n=5323; 43.1%). As expected, testing prevalence was higher with ttDNA than with ctDNA (mTNBC: n=569 [28.5%] vs n=137 [6.9%]; HR+ mBC: n=2339 [18.9%] vs n=1224 [9.9%]). Over 93% of pts (recurrent and de novo) who received a tBRCA test were tested after an mBC diagnosis, and >1/3 were tested after first-line therapy, with median times from diagnosis to a ttDNA and ctDNA test of 127 and 431 days, respectively. Both gBRCA and tBRCA testing rates increased from 2014–2022, and testing occurred earlier in pts with recurrent than de novo disease. Among pts with tBRCAm, 66.0% had HR+ mBC, and 25.6% had mTNBC. BRCA1 mutations were more common in mTNBC (59.0%) than in HR+ mBC (22.9%) tumors. Of 219 pts with tBRCAm tumors who were diagnosed with mBC from 2018 onwards, PARPi was initiated in 39/74 (52.7%) pts with gBRCAm, 15/71 (21.1%) pts who were gBRCAm-negative, and 19/74 (25.7%) pts with gBRCAm status unknown. Among pts with g or tBRCAm and available OS data, median OS was numerically longer in pts who received PARPi (32.3 months [95% CI: 24.2, 47.4], n=128) versus pts who did not (29.0 months [95% CI: 21.9, 31.9], n=204; median follow-up time 23.2 months). Conclusions: While NCCN guidelines recommend gBRCA testing for all pts with mBC, more than half of pts with HER2-negative mBC (56.9% of pts with HR+ mBC) did not receive any BRCA test. Among pts with tBRCAm, ~2/3 had HR+ disease. Despite the potential benefits of PARPi for pts with BRCAm mBC, utilization remained low from 2018–2022.

Clinical Utility of Tumor Next-Generation Sequencing Panel Testing to Inform Treatment Decisions for Patients With Advanced Solid Tumors in a Tertiary Care Center.

There is limited information about the clinical utility of targeted next-generation sequencing (NGS) panel testing to inform decision making for patients with advanced solid tumors. The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) is a prospective study that enrolled more than 4,500 patients with solid tumor for NGS panel testing. We performed a retrospective survey of medical oncologists to evaluate the impact of NGS testing on treatment decisions. Patients and treating oncologists were identified at the Princess Margaret Cancer Center between 2016 and 2021. Tumor-only sequencing was performed using a gene panel of either 555 or 161 cancer genes. Oncologists were asked to review testing results and complete a survey indicating whether NGS testing affected treatment decisions. The primary outcome of this study was rate of treatment change on the basis of mutation results. Patient, test, and physician factors were evaluated for association with treatment changes using univariate analyses and a mixed-effects model. Of the 582 surveys sent, 394 (67.7%) were completed. We found that 188 (47.7%) patients had testing results classified as actionable by the oncologist and 62 (15.7%) patients were matched to treatment, of whom 37 (60%) were enrolled in a clinical trial, 13 (21%) received an approved drug, four (6%) were prescribed off-label therapy, and eight (13%) avoided ineffective treatment. Patient, test, and physician characteristics were not significantly associated with treatment change. There was no difference in overall survival between patients who received matched treatment versus those who did not (P = .55, median survival not reached). OCTANE testing led to a change in drug treatment in 15.7% of patients, supporting the clinical utility of NGS panel testing for patients with advanced solid tumors.

Comparing rates of immune checkpoint inhibitor toxicity in different treatment settings (neoadjuvant, adjuvant, and palliative) in non-small cell lung cancer (NSCLC): A meta-analysis of phase III clinical trials.

8645 Background: Immunotherapy has created a paradigm shift in the treatment of NSCLC. There is growing interest in the utility of immunotherapy alone or in combination with chemotherapy for NSCLC in the peri-operative setting with practice changing results demonstrated in several pivotal phase III clinical trials. Nevertheless, immune related adverse events (irAEs) are the main barrier in the care of patients treated with immune checkpoint inhibitors (ICIs) with grade ≥ 3 irAEs seen in 10-15% of patients. The present meta-analysis aims to compare rates of irAEs across different treatment settings in NSCLC to aid in individual patient treatment decisions. Methods: We extracted data from selected published phase III clinical trials which have led to the approval of PD-1/PDL-1 ICIs in the neoadjuvant, adjuvant, peri-operative and in the palliative setting. We excluded trials which did not have supplemental data on irAEs included with published results and trials of CTLA-4 inhibitors. A sensitivity analysis was performed to assess whether number of cycles correlated with toxicity rates. Results: Pooled data from 15 published phase III NSCLC clinical trials including 5918 patients were included. This included 1 neoadjuvant, 2 peri-operative, 3 adjuvant, and 9 palliative studies. One of the peri-operative trials included data on irAEs which occurred during the neoadjuvant/surgery phase only and this data was pooled within the neoadjuvant group. The ICI drugs included nivolumab, pembrolizumab, atezolizumab, durvalumab, cemiplimab +/- chemotherapy. This included a total of 2523 stage 1B-3C and 3395 stage IV patients. We found a 9.5% rate of grade 3-5 and 35.8% rate of all grade irAEs in palliative trials (n=3395). In contrast, neoadjuvant ICI (n=572) had a 3.5% rate of grade 3-5 and 16.8% of all grades irAEs. Peri-operative ICI (n=797) had a 5.4% rate of grade 3-5 and 24.47% all grades irAEs. Adjuvant ICI (n=1550) had a 7% rate of grade 3-5 and 38.52% rate of all grade irAEs. The relative risk (RR) between the palliative and the neoadjuvant setting of a grade 3-5 irAE is 2.35 (95% CI:1.54 to 3.59; p = 0.0001) and the RR of any irAE is 2.03 (95% CI: 1.69 to 2.43; p=0.0001). The following median number of ICI cycles was seen: neoadjuvant = 3.5, adjuvant = 18, peri-operative = 18, palliative = 10. Lower number of cycles did correlate with lower toxicity in the neoadjuvant setting but this was not seen in other treatment settings. Conclusions: Neoadjuvant, peri-operative and adjuvant ICI’s are associated with a lower rate of irAEs than that seen in palliative trials. A neoadjuvant-only approach is associated with the lowest rates of irAEs and this may be due to the lower number of cycles received. These findings have implications for individual patient treatment decisions and support the use of neoadjuvant immunotherapy in NSCLC.

The Association between the Body Mass Index, Chronic Obstructive Pulmonary Disease and SUV of the Non-Tumorous Lung in the Pretreatment [18F]FDG-PET/CT of Patients with Lung Cancer.

Background: A debate persists on the prognostic value of the pre-therapeutic standardized uptake value (SUV) of non-tumorous lung tissue for the risk assessment of therapy-related pneumonitis, with most studies lacking significant correlation. However, the influence of patient comorbidities on the pre-therapeutic lung SUV has not yet been systematically evaluated. Thus, we aimed to elucidate the association between comorbidities, biological variables and lung SUVs in pre-therapeutic [18F]FDG-PET/CT. Methods: In this retrospective study, the pre-therapeutic SUV in [18F]FDG-PET/CT was measured in non-tumorous areas of both lobes of the lung. SUVMEAN, SUVMAX and SUV95 were compared to a multitude of patient characteristics and comorbidities with Spearman's correlation analysis, followed by a Bonferroni correction and multilinear regression. Results: In total, 240 patients with lung cancer were analyzed. An elevated BMI was significantly associated with increased SUVMAX (β = 0.037, p < 0.001), SUVMEAN (β = 0.017, p < 0.001) and SUV95 (β = 0.028, p < 0.001). Patients with chronic obstructive pulmonary disease (COPD) showed a significantly decreased SUVMAX (β = -0.156, p = 0.001), SUVMEAN (β = -0.107, p < 0.001) and SUV95 (β = -0.134, p < 0.001). Multiple other comorbidities did not show a significant correlation with the SUV of the non-tumorous lung. Conclusions: Failure to consider the influence of BMI and COPD on the pre-therapeutic SUV measurements may lead to an erroneous interpretation of the pre-therapeutic SUV and subsequent treatment decisions in patients with lung cancer.

Comparative analysis of treatment decision-making in patients with localized prostate and cervical cancer: what influences receiving surgery or radiotherapy?

PurposeThis study focused on identifying the factors influencing the decision-making process in patients with localized prostate and cervical cancer in Japan and specifically examining the choice between surgery and radiotherapy.MethodsPatients with specific cancer stages registered with a healthcare research company for whom radical surgery or radiotherapy was equally effective and recommended participated in this cross-sectional online survey.ResultsThe responses of 206 and 231 patients with prostate and cervical cancer, respectively, revealed that both groups relied heavily on the physicians’ recommendations (prostate: odds ratio (OR) = 40.3, p < 0.001; cervical: OR = 5.59, p < 0.001) and their impression of radiotherapy (prostate: OR = 9.22, p < 0.001; cervical: OR = 2.31, p < 0.001). Factors such as hypertension (OR = 6.48, p < 0.05), diabetes mellitus (OR = 9.68, p < 0.05), employment status (OR = 0.08, p < 0.01), and impressions of surgery (OR = 0.14, p < 0.01) also played a significant role in patients with prostate cancer. In contrast, the specialty of the physician (OR = 4.55, p < 0.05) proposing the treatment influenced the decision-making process of patients with cervical cancer. Information sources varied between the two groups: patients with prostate cancer were more inclined towards printed materials, whereas patients with cervical cancer were more inclined towards interpersonal relationships.ConclusionAlthough several limitations, such as the sample and recall bias, were noted, this study emphasizes the role of psychosocial factors in the decision-making process and the requirement for tailored information sources.

Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders

Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking. To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients. MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses. Using these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria. Following the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The primary outcome, pooled pre-post placebo effect sizes (dav) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate. A total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses (Q = 88.5; df = 8; P < .001), with major depressive disorder (dav = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder (dav = 1.23; 95% CI, 1.06-1.41) exhibiting the largest dav. Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed dav between 0.68 and 0.92, followed by OCD (dav = 0.65; 95% CI, 0.51-0.78) and schizophrenia (dav = 0.59; 95% CI, 0.41-0.76). This systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.

Evaluation of the Accuracy of the Use of Intravesical Prostatic Protrusion Degree as the Predictor of Benign Prostatic Hyperplasia Management

Managing symptoms of benign prostatic hyperplasia (BPH) is important but preventing the progression of the disease is also necessary. Medical therapy is commonly used to treat BPH as initial therapy. However, not every medical therapy is effective for treating BPH. Intravesical prostatic protrusion (IPP), a manifestation of BPH is used to evaluate BPH progression thus helping clinicians in choosing the effective treatment option. Patients with higher IPP degrees may experience more severe bladder outlet obstruction (BOO). They may not respond well to medical therapies, suggesting that IPP measurement can guide treatment decisions for BPH patients. This study evaluates the accuracy of using IPP degree as a predictor of BPH management by reviewing relevant literature. A comprehensive approach was undertaken, including the selection and filtering of articles from reputable databases and scholarly repositories using specific keywords related to the study's objectives. By measuring IPP degrees, the severity of clinical BPH can be categorized, allowing clinicians to choose effective treatment options and predict treatment outcomes.

Price and Location on Patient Treatment Decisions Outpatient Care in General Practitioner Practices

Price and Location on Patient Treatment Decisions Outpatient Care in General Practitioner Practices

#1686 How do older people with advanced kidney disease and their family members approach kidney treatment decision-making? A qualitative study

Abstract Background and Aims Chronic kidney disease (CKD) is common in the UK, especially amongst frail older people with multiple health problems. The survival benefit of kidney replacement therapy (KRT) for such patients is uncertain and the burdens significant, meaning patients make difficult decisions between planning for dialysis or opting for conservative kidney management (CKM). People close to individuals with advanced CKD are known to play an important role in treatment decision-making, but data exploring their perspectives are limited. This qualitative study aimed to explore older, comorbid patients’ and family members’ understanding of and views regarding treatment decision-making. Method In-depth interviews were conducted in person in 2018-2019 among older patients with advanced CKD (&amp;gt;80 years old or &amp;gt;65 with evidence of frailty or comorbidity) and least one family member (partner/spouse/child/grandchild) per patient. Interviews used open-ended questioning, supported by a topic guide based on patient input and the literature. Transcripts were analysed using inductive thematic analysis and constant comparison to identify concepts and meanings from participants’ views and reported experiences. Codes and interviews were discussed and compared among study investigators, with consideration of wider meaning, alongside reorganisation and recoding, and thematic development. Results Ten patients and 12 family members (6 spouses/partners, 5 adult children and 1 adult grandchild) were interviewed. Four themes were identified: (1) “whose decision is it anyway?”; (2) “facing uncertainty”; (3) “on death and dying” and (4) “caring and being cared for”. “Whose decision is it anyway?” speaks to perceived nuances around the ownership of decisions about kidney therapy. While some interviewees described the decision belonging solely to the patient, others described varying degrees of collaboration with and persuasion from family members (particularly partners/spouses). Clinician influence was also described by patients and family members. “Facing uncertainty” captures patients’ and their family members’ view that decisions are contingent upon largely uncertain future circumstances. “On death and dying” describes the pivotal role in treatment decision-making of patients’ and family members’ sense of life completion and feelings about death and dying. KRT was perceived as life-prolonging, while an acceptance of death and dying was seen to be important for consideration of CKM. “Caring and being cared for” elucidates the importance of caring roles between patients and their family members for decisions about the future, including the specific effect of loving relationships on the value patients and their family members assign to living. Conclusion We found both patients and family members influence treatment decisions, which they tend to view as flexible in the face of uncertainty. The desire to prolong important family relationships was a motivator for favouring KRT, in light of an understanding of KRT as life-prolonging. Kidney services should recognise the significance of family relationships to older patients’ treatment decision-making. Clinicians must ensure that patients and family members understand the implications of treatment choice for quality-of-life, prognosis, and end-of-life care. This is likely to include understanding which family members or close ones are important, involving these people in decision-making and recognising that changes in family situations may necessitate re-visiting previous decisions.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater

BackgroundAdenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting.MethodsThis investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy.ResultsFrom January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78–5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56–11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49–4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47–5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3–4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%).ConclusionsThis study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

#1089 Urinary Protein Biomarkers for Assessing Disease Activity and Chronicity in IgA Nephropathy

Abstract Background and Objectives IgA nephropathy (IgAN) is a progressive kidney disease characterized by the mesangial deposition of galactose-deficient IgA1, leading to kidney damage and may eventually lead to end-stage kidney disease. Current treatment decisions for IgAN patients rely on the degree of proteinuria. However, this is a non-specific parameter that can be the result of inflammatory disease activity and/or chronic glomerular damage. In this study, we employed the Olink proximity extension assay to comprehensively analyze the urinary proteome of IgAN patients. Our goal was to identify biomarkers capable of distinguishing between IgAN disease activity and disease chronicity. Method Urine samples were collected from 41 IgAN patients and 41 age- and eGFR-matched controls. Patient characteristics are shown in Table 1. Using Olink Proteomics, we measured 276 proteins in urine, from the inflammation, organ damage, and cardiometabolic panels. Comparisons were made between IgAN patients and controls, as well as between those with mild (eGFR ≥ 60 ml/min/1.73 m2 and uPCR &amp;lt; 100 mg/mmol) and active IgAN (eGFR ≥ 60 ml/min/1.73 m2 and uPCR ≥ 100 mg/mmol) to identify biomarkers for disease activity. Additionally, we compared IgAN patients with eGFR ≥ 60 ml/min/1.73 m2 to those with eGFR ≤ 30 ml/min/1.73 m2 to identify biomarkers associated with disease chronicity. Mann-Whitney U tests were used for group comparisons. Correction for multiple testing was performed using the Benjamini-Hochberg procedure. Disease activity and chronicity scores were calculated by averaging the z-scores of the identified biomarkers. Results L-Selectin (SELL), leukocyte inhibitory factor (LIF), interleukin-6 (IL-6), and carbonic anhydrase 1 (CA1) were most prominently elevated in IgAN patients compared to controls (Fig. 1A). SELL and CA1 were also markedly elevated in the active versus mild IgAN patients, and were therefore selected as biomarkers of disease activity (Fig. 1B). Contactin 2 (CNTN2) and chemokine (C-C motif) ligand 25 (CCL25) were most prominently elevated in IgAN patients with eGFR ≤ 30 ml/min/1.73 m2, and were selected as biomarkers of disease chronicity (Fig. 1C). We plotted the disease activity and chronicity scores calculated from the identified biomarkers to distinguish the different IgAN disease stages (Fig. 1D). Conclusion This study identified urine biomarkers indicative of IgAN disease activity and chronicity. Calculating an activity and chronicity score using these biomarkers offers a new approach to distinguish between inflammatory disease activity and chronicity, providing an alternative to proteinuria for guiding treatment decisions in IgAN patients. Validation of these biomarkers, and the scores calculated from them, in a larger cohort of IgAN patients is currently underway.

Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer

BackgroundJugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery.MethodsA total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study.ResultsThyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful.ConclusionJOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.

Construction of a mortality risk prediction model for patients with acute diquat poisoning based on clinically accessible data

BackgroundTo examine the risk factors associated with mortality in individuals suffering from acute diquat poisoning and to develop an effective prediction model using clinical data.MethodsA retrospective review was conducted on the clinical records of 107 individuals who were hospitalized for acute diquat poisoning at a tertiary hospital in Sichuan Province between January 2017 and September 30, 2023, and further categorized into survivor and nonsurvivor groups based on their mortality status within 30 days of poisoning. The patient’s demographic information, symptoms within 24 h of admission, and details of the initial clinical ancillary examination, as well as the APACHE II score, were documented. The model was developed using backward stepwise logistic regression, and its performance was assessed using receiver operating characteristic curves, calibration curves, Brier scores, decision curve analysis curves, and bootstrap replicates for internal validation.ResultsMultifactorial logistic regression analysis revealed that blood pressure (hypertension, OR 19.73, 95% CI 5.71–68.16; hypotension, OR 61.38, 95% CI 7.40–509.51), white blood count (OR 1.35, 95% CI 1.20–1.52), red cell distribution width-standard deviation (OR 1.22, 95% CI 1.08–1.38), and glomerular filtration rate (OR 0.96, 95% CI 0.94–0.97) were identified as independent risk factors for mortality in patients with diquat. Subsequently, a nomogram with an area under the curve of 0.97 (95% CI: 0.93–1) was developed. Internal bootstrap resampling (1000 repetitions) confirmed the model’s adequate discriminatory power, with an area under the curve of 0.97. Decision curve analysis demonstrated greater net gains for the nomogram, while the clinical impact curves indicated greater predictive validity.ConclusionThe nomogram model developed in this study using available clinical data enhances the prediction of risk for DQ patients and has the potential to provide valuable clinical insights to guide patient treatment decisions.