bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between social determinants of health and time to treatment for newly diagnosed multiple myeloma.
Authors: Gasoyan Hamlet , Anwer Faiz , Kovach Jeffrey D. , Casacchia Nicholas J. , Wang Ming , Rothberg Michael B.
Published: May 2024

1583

Background: Delayed access to costly anti-myeloma agents due to insurance precertification process or out-of-pocket costs results in treatment initiation with less-costly corticosteroids in some patients with newly diagnosed multiple myeloma (NDMM). Less is known about the scope of the delay and the factors associated with it. Methods: This retrospective cohort study used Taussig Cancer Center’s Myeloma Patient Registry to identify adults with NDMM between January 1, 2017 and December 31, 2021. Electronic health records data captured (1) time from initial diagnosis to receipt of FDA-approved anti-myeloma agent including vs. excluding corticosteroids, (2) time to initial prescription fill for FDA-approved anti-myeloma drug excluding corticosteroids, and (3) association of race, sex, primary insurance type, area deprivation index (ADI), urbanicity, and time to initial fill for anti-myeloma drug excluding corticosteroids. The latter was examined via cumulative incidence at 30 days since initial diagnosis using the log-rank test and multivariable Cox regression model. Results: We identified 723 patients with a mean age at diagnosis of 67 years ±11; 55% were male, 77% White, 22% Black, and 1% other races, covered by private insurance (36%), traditional Medicare (28%), Medicare Advantage (25%), Medicaid (8.4%), and self-pay/other (1.8%); and median follow-up of 784 days (interquartile range [IQR], 415, 1313). Over a third of patients (37%) resided in an area in the most disadvantaged quartile of the ADI; 83% resided in a metropolitan area. Median time to receipt of anti-myeloma treatment was 10 days (IQR, 2, 24) including corticosteroids vs. 18 days (IQR, 8, 37) excluding corticosteroids. Median time to initial prescription fill for an anti-myeloma drug excluding corticosteroids was 31 days (IQR, 16, 75). The cumulative incidence of prescription fill for anti-myeloma drug excluding corticosteroids at 30 days was 40% (95% CI, 36%, 44%) in White individuals, 28% (95% CI, 21%, 36%) in Black patients, and 17% (95% CI, 0.42%, 64%) in other races (P=.009) [adjusted HR for Black patients (v. White), 0.63, 95% CI, 0.44, 0.90]; 31% (95% CI, 25%, 38%) in patients with traditional Medicare, 37% (95% CI, 30%, 44%) with Medicare Advantage, 44% (95% CI, 38%, 50%) with Private Insurance, 34% (95% CI, 23%, 48%) with Medicaid, and 31% (95% CI, 9.1%, 61%) self-paying/with other insurance (P=.07) [adjusted HR for private insurance (v. traditional Medicare), 1.41, 95% CI, 1.04, 1.93]; 40% (95% CI, 36%, 44%) treated in Taussig Cancer Center and 25% (95% CI, 17%, 34%) in regional hospitals (P=.003) [adjusted HR for regional hospitals, 0.59, 95% CI, 0.40, 0.89]. Conclusions: Disparities in time to prescription fill for anti-myeloma drugs exist based on socio-demographic factors. Future research should examine the role of precertification criteria and out-of-pocket costs in delays with recommended care.
Improving lung cancer health equity by applying deep learning to low dose CT screening of minority and disadvantaged patients.
Authors: Zakkar Abdul , Krule Alexander , Miglani Mehak , Gadi VK , Kovitz Kevin , Pasquinelli Mary , Weinberg Frank , Molina Yamile , Kim Sage J , Khan Aly , Nguyen Ryan Huu-Tuan , Salahudeen Ameen Abdulla
Published: May 2024

1584

Background: In the US, disparities in lung cancer mortality exist for African American, Hispanic, and other minorities. Standard of care low dose CT screening (LDCT) detects early-stage disease and improves mortality, yet disparities are perpetuated in screening by eligibility criteria derived from cohorts underrepresenting these minorities. One such cohort is the National Lung Screening Trial (NLST) cohort which is 92% White. Consequently, guidelines for lung cancer screening may be insufficient to address the unique needs of diverse populations. We hypothesize that Artificial Intelligence prediction of future lung cancer risk from an individual’s LDCT can partially mitigate racial and ethnic disparities and improve health system practice guidelines by individualizing screening risk as compared to current general guidelines. Here, we benchmark a Resnet18 3D neural network trained on NLST LDCT images, Sybil, on the diverse patient population of the University of Illinois Health system (UIH) which is 20% White and 60% African American. Methods: A real-world cohort from UIH consisting of 1,450 CT studies was evaluated alongside 60,378 CT studies from the NLST cohort. All CT studies evaluated by the model were not used in model training. Using Youden’s J index as a probability cutoff, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were evaluated. Receiver operating characteristic (ROC) and precision-recall (PR) curves were generated to assess model performance between cohorts. NLST data were truncated to achieve equivalent incidence of lung cancer with UIH when generated PR curves. Results: Multi-year prediction performance (ROC-AUC and PR-AUC) between cohorts are summarized (Table). For prediction of lung cancer within 1-year of LDCT in the UIH cohort, the model respectively demonstrated sensitivity, specificity, positive predictive value, and negative predictive value among White (0.80, 0.77, 0.54, 0.92), African American (0.84, 0.78, 0.39, 0.97) races and Hispanic (0.75, 0.73, 0.60, 0.84) and non-Hispanic (0.87, 0.77, 0.42, 0.97) ethnicities. Conclusions: Model performance was similar between the NLST (92% White) and a diverse, real-world cohort at UIH (20% White) though decreases in ROC-AUC performance in year 1 predictions and may be due to insufficient representation of minority populations during model training. Prospective studies involving larger and more representative patient populations should be conducted to further optimize the model and evaluate its clinical utility to improve lung cancer health equity in minority populations.[Table: see text]
Start low, go slow: A systematic review and meta-analysis of upfront tailored treatment dosing in older adults with advanced cancer.
Authors: Aleixo Gabriel , Ferrell William J. , Ani Julianne , Patel Tej A. , Parikh Ravi Bharat , Sedhom Ramy
Published: May 2024

1625

Background: Older adults aged ≥65 with advanced cancer are underrepresented in treatment trials. This gap limits informed decision-making regarding the dose and tolerability of proposed therapies. Standard chemotherapy is associated with >50% serious adverse event rate among older adults, with frequent dose reduction and early treatment discontinuation. A "start low, go slow" (SLGS) approach begins systemic therapy at lower-than-standard doses and increases the dose if well-tolerated. This alternative dosing strategy has shown value in minimizing adverse events and functional decline without compromising the overall effectiveness of treatments. We conducted the first systematic review and meta-analysis of SLGS effectiveness among older adults across advanced cancers. Methods: This review, was registered with PROSPERO and adhered to PRISMA criteria, covering PubMed, Journal of Geriatric Oncology and EMBASE from January 2000 until December 15, 2024. Eligible study designs were randomized controlled trials, retrospective trials, and non-randomized clinical trials with patients with advanced cancers who underwent systemic therapy. We reported all studies that studied the SLGS approach. Our studied outcomes were overall survival (OS), progression-free survival (PFS), treatment discontinuation, and toxicity. Data extraction included author, patient, cancer type, treatment, and survival outcomes. A meta-analysis using fixed effects and risk ratios (RR) was performed when sufficient data was available; significant outcomes had α<0.05. Results: Our search identified 13 studies testing SLGS strategies in oncology, including 3,508 patients, with a median age 63-78 years. The -represented cancers included colorectal (6 studies, 3059 patients total), lung (2 studies, 113 pts), chronic myeloid leukemia (2 studies, 127 pts), non-Hodgkin lymphoma (1 study, 45 pts), and prostate (2 studies, 164 pts) cancers. Ten (77%) studies assessed OS and PFS. Five studies (39%) compared SLGS against standard doses, finding no significant differences in PFS and OS across all trials. Dose escalation rates for SLGS ranged from 5% to 60%. The ability to complete planned cycles was higher with SLGS compared to standard dose (1 study, 43% vs 26%, p=0.04). Treatment discontinuation was not different for SLGL vs. standard dose (5 studies, meta-analysis RR 1.07, 95% CI 0.90-1.27, p=0.42). Toxicity ranged from 5% to 89% across studies; SLGS had lower grade ≥3 adverse events compared to standard dose (4 studies, meta-analysis RR 0.88, 95% CI 0.80-0.94, p < 0.001). Conclusions: This is the first systematic review and meta-analysis analyzing the SLGS approach to systemic therapy dosing in older adults with advanced cancer. Compared to standard-dose systemic therapy, older adults pursuing a SLGS strategy had greater completion of planned cycles, reduced toxicity, and similar survival.
Prognostic value of Oncotype recurrence score (RS) and Mammaprint (MP) in premenopausal patients with hormone positive (HR+) breast cancer (BC) with low genomic risk, stratified by race: A study of the National Cancer Database (NCDB).
Authors: Sivapiragasam Abirami , Ashok Kumar Prashanth , Huang Danning , Wang Dongliang
Published: May 2024

551

Background: It is hypothesized that in African American (AA) women, RS has a lower prognostic accuracy. We evaluated this with a large population based national database. Methods: The 2021 NCDB PUF was used to include premenopausal female BC patients aged 18-50 years. Inclusion criteria were N0, M0 patients with any T stage, RS ≤ 15 or MP low risk, estrogen or progesterone receptor+ and HER2-. Patients were stratified by their recorded race (Caucasians vs AA). Univariate analysis was used to study the distribution. Kaplan-Meier (KM) and multivariate (MV) propensity score (PS) weighted Cox model were used to compare survival between the cohorts. Results: 27523 patients had an RS≤15 [Caucasian-25227(91.66%) AA-2296(8.34%)] and 4818 had MP low [Caucasian-4393(91.18%) AA-425(8.82%)]. >99% had regional lymph node surgery and >90% of the patients did not get chemotherapy. >70% of the patients were T1. Majority did get hormonal therapy (HT) [RS≤15 Caucasian-92.97% AA-91.81%, MP low- Caucasian-92.42% AA-89.65%]. On analyzing grade, AA had more poorly differentiated tumors [RS≤15 Caucasian-6.18% AA-9.46% p=<0.001 MP low- Caucasian-9.1% AA-16.02% p=<0.001]. KM survival estimates for RS≤15 at 5 years [Caucasian-99.3(99.2,99.5) %, AA-98.8(98.0,99.3) %] were similar and 10 years [Caucasian-97.5(97.0,97.9) %, AA-94.6(91.6,96.6)] showed a small difference. For MP low, the survival at 5 years [Caucasian- 99.0(98.6,99.3) %, AA-98.9(97.0,99.6) %] and 10 years [Caucasian- 97.0(95.9,97.8) %, AA-95.8(91.0,98.1) %] were almost equal. Adjusted Hazard Ratio estimate for Caucasian vs AA for RS≤15 did not reach significance overall [0.802 (95% CI 0.47-1.37)] nor when stratified by grade, histology, or T stage. Conclusions: Through our analysis, we show that there was no major difference in overall survival between Caucasians and AA among low genomic risk, premenopausal, hormone positive, N0 BC patients. There was a 2.9% difference between the racial groups at 10 years, but this was not seen in the adjusted analysis. The results show that genomic scores like RS and MP retain their prognostic utility even in the low-risk spectrum in both Caucasians and AAs. These results differ from other database studies, where the utility of these tools in the low-risk AA groups were questionable. Confounding associated with retrospective studies could be contributing to this and the predictive ability of genomic scores in varied racial groups needs to be analyzed in prospective models.
Patient-derived tumor cell clusters (PTC) guiding-neoadjuvant therapy of HER2-positive breast cancer: A prospective randomized phase II clinical trial.
Authors: Yu Xingfei , Wu Xiaofan , Wang Chen , Feng Weiliang , Zheng Yabing , Yang Hongjian
Published: May 2024

581

Background: In a previous study, the patient-derived tumor-like cell clusters (PTC) were confirmed to be an accurate medicine effect-predicting model in vitro for clinical practice (1). We designed this prospective randomized phase II trial to research if this PTC-guiding strategy could improve the effect of neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer (NCT05103293). Methods: We enrolled HER2-positive early breast cancer patients planning for neoadjuvant therapy to accept the PTC-guiding regimen as an experimental group or regimens of the physician's choice as a control group randomly. All eligible patients in the experimental group would receive medicine-sensitive testing by PTC then accepted the regimen with the highest PTC killing rate (30% as the lowest cut-off value) from the three candidate regimens (Cyclophosphamide combined with epirubicin -- Docetaxel combined with trastuzumab and pertuzumab, EC-THP, Docetaxel and carboplatin with trastuzumab and pertuzumab, TCbHP and Docetaxel with trastuzumab and pyrotinib, THPy). The primary endpoint is pathological complete response (pCR) in two groups using superiority odd ratio Fisher's exact test (one-sided alpha =0.05, power of 80%, and superiority margin at 0.1). The secondary endpoints are Miller-Payne (MP) grade 4~5 proportion, objective response rate (ORR), disease-free survival (DFS), and overall survival (OS). Results: Finally, 86 patients were enrolled in this study, 44 in the experimental and 42 in the control groups. The experimental group had 65.9% of pCR, significantly higher than 42.9% in the control group (Hazard ratio=0.388, P=0.033). The PTC-guiding treatment also considerably increased MP 4~5 proportion (79.5% vs. 59.4%, Hazard ratio=0.283, P=0.009) and objective response rate (90.9% vs 71.4%, Hazard ratio=0.250, P=0.027). After a two-year medium follow-up, the disease-free survival of the PTC-guiding treatment group was 84.1% higher than 71.4% of the control group without a significant difference (Log Rank, P=0.106). The two groups had similar overall survival (Log Rank, P=0.958). Furthermore, the PTC-guiding strategy significantly impacted pCR in univariate and multivariate regression analyses but not survival. Conclusions: In this trial, we concluded that the PTC-guiding neoadjuvant therapy could improve the effect, including pCR, MP score, and ORR in HER2-positive breast cancer. 1. Yin et al., Sci.Transl. 2020. Clinical trial information: NCT05103293 .
Prediction of pCR with pretreatment MRI radiomics in triple negative breast cancer treated with neoadjuvant chemo-immunotherapy.
Authors: Ramtohul Toulsie , Lepagnay Victoire , Bonneau Claire , Jin Maxime , Menet Emmanuelle , Sauge Juliette , Laas Enora , Romano Emanuela , Bello Diana , Mechta-Grigoriou Fatima , Bidard Francois Clement , Langer Adriana , Malhaire Caroline , Cabel Luc , Tardivon Anne
Published: May 2024

589

Background: Neoadjuvant chemo-immunotherapy (NACI) has become the new standard of care for stage II-III triple-negative breast cancers (TNBC). This approach is linked to high rates of pathological complete responses (pCR), yet factors influencing responses to this regimen remain poorly characterized. Our objective was to investigate whether pretreatment MRI perfusion-based radiomics could serve as a predictive tool for pCR to NACI in patients with TNBC. Methods: This prospective study enrolled women with early-stage TNBC undergoing NACI at two different centers from August 2021 to July 2023. Tumor segmentation and pharmacokinetic analyses of pretreatment multi-vendor dynamic-contrast-enhanced (DCE)-MRI were conducted using the standard perfusion Tofts model. Radiomics features were extracted from the Ktrans, Ve, and Slopemax maps. Unsupervised correlation analysis of reproducible features and least absolute shrinkage and selector operation were employed to construct a radiomics score. The performance of the radiomic score was evaluated using the area under the receiver operating characteristic curve (AUC). A multivariable logistic regression model was employed to establish a multimodal nomogram. Performance metrics included discrimination, calibration, and clinical usefulness, assessed on the external validation set. Results: The training set comprised 112 patients from center 1 (mean age, 52 years ± 11 [SD]), and the external validation set included 83 participants from center 2 (mean age, 49 years ± 11 [SD]). Overall, the pCR rate was 70% (137/195). In the validation set, the radiomic score achieved an AUC of 0.80 (95% CI: 0.70, 0.89) for predicting pCR. A nomogram incorporating the radiomics score, tumor grade, and Ki67 yielded an AUC of 0.86 (95% CI: 0.78, 0.94) and demonstrated superior predictive efficacy compared to the histological prediction model (AUC, 0.76 [95% CI: 0.66, 0.87]; P = .02) in the validation set. Calibration curves of the nomogram exhibited good concordance between predicted and observed pCR in both sets. The radiomic score correlated with tumor size, washout enhancement curve, androgen receptor (AR), and combined positive score (CPS) PD-L1 levels (all P < 0.05). Conclusions: PretreatmentMRI-based radiomics is a reliable predictor of pCR to NACI and might help customizing treatment choice for early-stage TNBC patients.
Pathological complete response (pCR) association with a novel homologous recombination deficiency HRD signature (HRDsig) in patients with triple-negative breast cancer (TNBC) receiving neoadjuvant therapy (Tx).
Authors: Gupta Tanya , Graf Ryon P , Schrock Alexa B. , Madison Russell , Ross Jeffrey S. , Levy Mia Alyce , Quintanilha Julia
Published: May 2024

591

Background: The current standard of care for stage II-III TNBC is neoadjuvant Tx combining carboplatin, paclitaxel, and immune checkpoint inhibitor (ICI) followed by doxorubicin and cyclophosphamide (AC) + ICI. This regimen is often associated with significant toxicity. This study aimed to investigate if HRDsig could identify patients with TNBC who have a greater benefit from the addition of platinum in the neoadjuvant Tx regimen. Methods: This study included patients with TNBC who underwent genomic testing using Foundation Medicine tissue comprehensive genomic profiling (CGP) assays and had records of neoadjuvant Tx. Patient clinical data was obtained by the US-wide de-identified Flatiron Health and Foundation Medicine real-world clinicogenomic breast cancer database (CGDB), originated from ~280 US cancer clinics between January 2011 and June 2023. pCR rates were compared between patients HRDsig(+) vs. HRDsig(-) who were stratified by having received platinum vs. non-platinum Tx and between patients receiving non-platinum vs. platinum neoadjuvant Tx stratified by HRDsig status. The interaction effect of HRDsig and platinum Tx in relation to pCR was evaluated by logistic regression. Results: 497 patients met the inclusion criteria, 159 (32%) with HRDsig(+) and 338 (68%) with HRDsig(-). Among HRDsig(+) patients, 54 (34%) received platinum and 105 (66%) non-platinum Tx. HRDsig(+) vs. HRDsig(-) patients were more likely to have pCR receiving both platinum Tx (37.0% vs. 4.4%, p<0.001) and non-platinum Tx (23.8% vs. 5.2%, p<0.001). Platinum vs. non-platinum Tx showed a trend towards moderately enriched pCR rates in the HRDsig(+) group (37.0% vs. 23.8%, odds ratio [OR]=1.87, 95% confidence interval [CI] 0.97-3.84, p=0.08), but not in the HRDsig(-) group (4.5% vs. 5.2%, OR=0.86, 95% CI 0.23-2.55, p=0.767). HRDsig(+) was independently associated with pCR (OR=5.65, 95% CI 2.80-11.89, p<0.001), while platinum Tx and pCR were not associated (OR=0.84, 95% CI 0.23-2.45, p=0.767). A strong treatment interaction between HRDsig status and platinum Tx was not observed (p=0.242, OR=2.24, 95% CI 0.61-9.58). Conclusions: In the neoadjuvant Tx setting, patients with TNBC that were HRDsig(+) were substantially more likely to achieve a pCR. There was a trend towards higher pCR rates among HRDsig(+) patients receiving platinum vs. non-platinum Tx, while this effect was not observed among HRDsig(-) patients. TNBC patients (especially stage II) often experience significant toxicity from chemotherapy regimens. These hypothesis-generating results suggest that HRDsig may help identify patients who achieve additional benefit from platinum agents. These results warrant further evaluation in randomized cohorts to potentially validate this utility.
Effect of a novel artificial intelligence (AI) –enabled multi-trial matching system on patient matching using real-world data.
Authors: Kurnaz Selin , Loaiza-Bonilla Arturo , Carvallo Castañeda Darla , Huner Oz , Giritlioglu Dersu ,   Precision Cancer Consortium
Published: May 2024

e13501

Background: Currently clinical research teams at sites are manually matching patients to clinical trials, where each trial in our experience takes at least 25 minutes using highly trained dedicated resources. This limits cancer patients’ clinical trial options and enrollment rates. Moreover, the lack of NGS testing results may also negatively impact matching to clinical trials in targeted therapies. PCC, a consortium of 7 of the Top 20 Pharmaceutical companies, collaborated with Massive Bio to demonstrate how cancer patients’ matching rates can be increased if patients are prescreened to multiple trials simultaneously (i.e. multi-trial matching) instead of a single trial and NGS testing results are integrated into the matching process. Methods: Massive Bio has developed a first-in-class AI-enabled matching system to extract 180 structured clinical data from medical records using computer vision and natural language processing and a recommendation system for matching patients to parameterized inclusion/exclusion (I/E) criteria from over 14,000 actively recruiting interventional clinical trials.Our analysis included a sample of 5,707 cancer patients from the Massive Bio Synergy AI real-world database, corresponding to tumor types in 23 selected trials. We developed a decision-tree algorithm for retrospective matching analysis using modeled I/E criteria and compared these results to the theoretical matching rate (TMR) for each trial based on tumor type and biomarker prevalence, extent of disease at diagnosis and prior treatment history. Results: 690 patients matched to at least one trial were matched to 1.82 times more trials in multi-trial matching; 2.10 times more potential matches were obtained with hypothetical 100% NGS testing; and 99.9% matching time was reduced with AI enabled system; key findings are summarized (Table). Conclusions: This study confirms the underutilization of NGS technology and substantial benefits of AI and NGS in cancer trial matching. Their use resulted in a nearly two-fold increase in potential patient eligibility for trials, and an unprecedented reduction in manual effort, underscoring a significant advancement in the efficiency of the clinical trial matching process. A prospective country-wide analysis is under consideration.[Table: see text]
NGS panels' capture of biomarkers associated with targeted therapies in clinical trials.
Authors: Fox John Leonard , Daniel Sugganth , Abrol Manavi
Published: May 2024

e13508

Background: ASCO and NCCN guidelines strongly encourage participation in clinical trials though participation rates remain low. Although up to 60% of trials require biomarker information as a prerequisite to participation, guidelines are silent on biomarker testing to assess eligibility. To help inform policy development, we analyzed commercially available NGS panels to assess the capture rate of the specific gene variants required for targeted therapies in clinical trials. Methods: Publicly available gene variant information on 12 high volume NGS tissue and plasma commercial assays representative of panel size was accessed. The JAX-CKB database was queried to identify genomic prerequisites in active phase I-III clinical trials; mRNA and protein expression biomarkers were excluded. We used unpaired t-testing to compare the ability of large versus small panels to detect variants required for targeted treatments. (Somatic gene variant annotations and related content have been powered by The Jackson Laboratory Clinical Knowledgebase (JAX-CKBTM)). Results: Overall, 185 genes were linked to eligibility for targeted therapies in clinical trials (Table). Large panel assays (>80 genes) had a higher average capture rate compared to smaller panels, (84% vs. 46%, p value < 0.000002). Similarly, capture rates in select cancers were higher in larger panels: lung (85% vs 59%), breast (92% vs 54%), prostate (86% vs 34%), pancreatic (84% vs 54%), colorectal (88% vs 52%). All results were statistically significant (p < 0.05). Smaller panels were more likely to exclude large genes (e.g. BRCA), genome-wide signatures (e.g. TMB), fusions, and copy number variants. Conclusions: NGS-based panels with more than 80 genes had higher capture rates for biomarkers required for clinical trials of targeted therapies. Clinicians searching for all relevant treatment options for patients should include large genomic sequencing panels to maximize identification of potential clinical trial eligibility. Professional societies and policy makers interested in enhancing clinical trial enrollment rates should consider the panel size-related variability in capture rates of genetic variants when developing recommendations. [Table: see text]
Disparities in access to antineoplastic immunotherapy and outcomes by insurance status: A nationwide analysis.
Authors: Javaid Saad , Frasier Kelly , Li Vivian , Vinagolu-Baur Julia , Ortega Yaguachi Nataly , Rodriguez Evadne , Del Castillo Olivia , Batista Raquel , Jonas Kenlee , Palma Laura
Published: May 2024

e13523

Background: Immunotherapy has emerged as a pivotal component in the treatment of cancer, particularly owing to the progress made in targeted therapies. Our analysis aimed to quantify the disparities in access to immunotherapy and the associated outcomes. Methods: We used National Inpatient Sample data (2017-2020) to identify patients hospitalized with a primary diagnosis of antineoplastic immunotherapy, stratifying them by either Medicaid or private insurance. The aim was to determine disparities in the likelihood of immunotherapy across various demographic factors and differences in outcomes, such as mortality and healthcare resource utilization. Results: A total of 14,530 patients were hospitalized for antineoplastic immunotherapy, with 2,960 (20%) having Medicaid insurance and 7,760 (53%) having private insurance. Patients with Medicaid were younger than those with private insurance (17.22% vs 38.53%). Compared to Medicare, patients with private insurance were more likely to undergo immunotherapy (OR=2.65(2.31-3.04); p<0.001), while those with Medicaid had decreased odds (OR=0.75(0.61-0.92); p=0.007). Older patients were less likely to undergo immunotherapy than younger patients (36-45: OR=0.69(0.56-0.85), p=0.001; 46-64: OR=0.7(0.59-0.82), p<0.001; >65: OR=0.48(0.4-0.59), p<0.001). Compared to the White population, Hispanics (OR=1.3(1.12-1.51); p<0.001) and patients of other races (OR=3.33(2.86-3.88); p<0.001) had increased odds of undergoing immunotherapy, while Black patients had decreased odds (OR=0.43(0.35-0.53); p<0.001).The individuals with the highest median income were found to have the highest likelihood of undergoing immunotherapy (>$86,000, OR=2.23(1.92-2.59); p<0.001), followed by those in the less income groups ($65,000-$85,999: OR=1.6(1.38-1.86), p<0.001; $50,000-$64,999: OR=1.48(1.28-1.73), p<0.001). Patients in medium-sized (OR=1.27(1.03-1.55); p=0.022) and large (OR=3.49(2.93-4.15); p<0.001) hospitals were more likely to receive immunotherapy compared to those in small hospitals. Patients with Medicaid had a higher total hospitalization cost than those with private insurances (+$219,484(83,731-355,238); p=0.002). There was no observed difference in mortality rates among patients with Medicaid or private insurance who received immunotherapy (Medicaid: OR=0.86(0.1-6.98), p=0.88; Private: OR=0.67(0.11-3.96), p=0.66). Conclusions: The utilization of immunotherapy among Medicaid patients is found to be lower when compared to those with private insurance and Medicare. This disparity is also related to a higher overall cost of hospitalization in Medicaid patients. However, there was no difference in mortality between the different insurance types who received immunotherapy.
Contemporary management of patients with advanced melanoma: Utility of an online interactive decision support tool to assess concordance of healthcare professional treatment patterns with expert recommendations.
Authors: Becker Marie N. , Rosenthal Kristen M. , Betof Warner Allison , Daud Adil , Lipson Evan J. , Tarhini Ahmad A. , Tawbi Hussein A.
Published: May 2024

e13548

Background: The treatment landscape for patients with melanoma continues to evolve with approvals of novel therapeutic agents for advanced disease and new indications for therapy in earlier-stage disease. Using an online decision support tool, we compared practice patterns and treatment recommendations between community healthcare professionals (HCPs) and key opinion leaders (KOLs). Methods: The online decision support tool was developed with input from 5 KOLs who provided treatment recommendations for 151 hypothetical patients. Case scenarios covered a spectrum of stages (III, IV), central nervous system (CNS) metastases, BRAF mutation status, and treatment histories. HCPs entered specific patient criteria into the tool to define a case and their intended therapy choice and the tool then showed 5 KOL recommendations for that patient case. An analysis of KOL recommendations and HCP-selected therapy was performed. Results: Between August 2023 and January 2024, 156 patient cases were entered by 100 HCPs. HCP and KOL recommendations were concordant in 51% (80/156) of cases. The highest level of discord among HCPs and KOLs was 72% for patients with completely resected stage IIIA melanoma and no positive lymph nodes having a metastatic focus ≥1mm (n = 25) (Table). A lower level of discordance (31%, n = 35) was observed in therapy selection for patients with stage IIIA melanoma and ≥1 positive lymph node. For first-line therapy in patients with unresectable stage III or IV BRAF wild-type melanoma (n = 16), discordance was 50% between HCPs and KOLs. The level of discordance was higher for first-line therapy for patients with BRAF-mutant melanoma (68%, n = 19). For the management of patients with CNS metastases, 40% of HCP therapy selections were not aligned with KOLs (n = 40). More than one half (56%) of HCPs noted that the tool confirmed their treatment plan, and 21% intend to change practice to align with KOLs. Conclusions: This analysis identified areas of discordance in clinical practice between HCPs and KOLs for advanced melanoma that can guide further education and enhance communication of evolving evidence to HCPs. Our data suggest that use of the decision tool can confirm best practices with KOL recommendations and improve alignment of treatment choices with KOLs. [Table: see text]
Clinical decision making by ChatGPT vs medical oncologists: A retrospective concordance study.
Authors: Rushanyan Marine , Aghabekyan Tigran , Tamamyan Gevorg , Zohrabyan Davit , Safaryan Liana , Bedirian Karen , Sargsyan Karine , Mkrtchyan Gohar
Published: May 2024

e13634

Background: This research explores the application of AI language models in clinical decision-making within the context of oncology, focusing on the concordance between AI-generated recommendations and actual treatment decisions made by physicians. Leveraging ChatGPT version 4.0, a large language model, we conducted a concordance study using retrospective patient cases from Yeolyan Hematology and Oncology Center. The hypothesis, centered on the alignment of AI chatbots with human decisions, spurred an in-depth exploration of concordance rates. Methods: A total of 228 adult solid malignancy cases from Yeolyan Hematology and Oncology Center (Jan 2020 - Sep 2021) were analyzed, focusing on primary cancers and data from multidisciplinary tumor board meetings. We scored concordance and analyzed the response times as well. Results: The study unveiled an overall 62.3% concordance rate, with varying rates among different cancer types: lung (50%), breast (50%), gastrointestinal (66%), and gynecological (81.8%) cancers. Despite promising results, challenges emerged, including variability in ChatGPT-4 responses and concerns about reliability and reproducibility. The study acknowledges the influence of prior assessments from other healthcare facilities, financial disparities impacting treatment decisions, and potential oversimplification of chemotherapy regimens. Conclusions: AI-based language models like ChatGPT present intriguing possibilities for healthcare, yet further research, controlled trials, and prospective studies are imperative to comprehensively understand and enhance their applicability in personalized patient care. This research sheds light on the complexities and considerations associated with integrating AI into oncological decision-making, offering valuable insights for future advancements in this evolving field.
Patient experience and pain outcomes among Black women with early-stage breast cancer after mastectomy.
Authors: Smith-Graziani Demetria Joy , Cao Yichun , Switchenko Jeffrey M. , Acheson Meghan , McHenry Jessica , Rimawi Mothaffar F. , Kalinsky Kevin , Brewster Abenaa M.
Published: May 2024

e13751

Background: Racial pain disparities in breast cancer (BC) are well-described and persist despite prior trials to improve disparate pain outcomes. We previously found Black women (BW) reported more pain severity (PS) and interference with life (PI) after breast surgery compared to White women. Pain expression is multifactorial, and structural factors affect the ability to report and control pain. Perceived discrimination is associated with mistrust of medical providers, which affects clinical outcomes. Their impact on pain is understudied. We evaluated the association between discrimination, trust, and pain among BW with early-stage BC after mastectomy. Methods: BW with stage 0-III BC who had mastectomy ≤2 years of enrollment at academic and safety net hospitals in Houston, TX and Atlanta, GA, completed a demographic survey, Brief Pain Inventory (BPI), Discrimination in Medical Settings Scale (DMS), and Trust in Physician Scale (TPS). In BPI, worst, least, and average PS were reported from 0-10. PI from 0-10, pain treatments, and % relief were reported. DMS and TPS questions were on a 5-point Likert scale. We performed chart review to obtain baseline clinical data related to BC diagnosis, treatment and comorbidities. PI and DMS were scored as a mean of the total items of each survey. Mean Trust and Mistrust scores used means of TPS questions related to each category. Higher scores mean more PS, PI, discrimination, trust, or mistrust. We used ANOVA to examine associations between categorical variables and Pearson correlation coefficient for continuous variables. We performed univariate linear regression and multi-linear regression between specific variables and outcomes, accounting for collinearity. Results: Of the 77 BW surveyed, 66.2% received chemotherapy. 47.2% had a household income < $25,000, and 40.3% had private health insurance. PS, PI, DMS, and trust scores are shown (Table). Univariate analysis showed an association between DMS and mistrust (p=0.01), lower income and higher PS (p=0.01) and PI (p=0.04), and insurance status and PS (p=0.02) and PI (p=0.02). Associations between mistrust or DMS and pain were not statistically significant. A multivariate analysis with DMS as outcome showed an association with mistrust (p=0.04). Multivariate analysis also showed receipt of chemotherapy was associated with higher PS (p=0.02) and PI (p=0.03). Conclusions: BW have moderate pain up to 2 years following mastectomy. Participants reported low levels of discrimination and high trust. More discrimination was associated with more physician mistrust, but not PS or PI. Lower income and lack of private health insurance were associated with higher PS and PI. Future studies should address discrimination and trust in clinical settings and financial barriers to pain control. [Table: see text]
Patient’s perception of cancer treatment outcomes in geriatric age groups: A retrospective analysis from a tertiary care centre in India.
Authors: Choudhary Jatin , Noronha Vanita , Menon Nandini Sharrel , Shah Minit Jalan , Pillai Anupa , Kumar Anita , Rao Abhijith Rajaram , Pawar Akash , Dhekale Ratan , Prabhash Kumar
Published: May 2024

e13774

Background: Geriatric population forms a significant part of the total cancer patients in any given country and their expectations, their needs and challenges are different from younger patients. Patients may perceive their “chances” differently from what is expected with cancer treatment. In our analysis we aimed to look at such perceived intent of therapy in geriatric patients and factors that might influence these perceptions. Methods: We retrospectively looked at data of comprehensive geriatric assessment (CGA) which is maintained by the geriatric clinic at our institute. Patients are referred to our geriatric clinic after their joint clinic meetings and after their meetings with their primary oncologists. We identified 2962 patients who underwent CGA and collected data of age, gender, social support, marital status, education level, actual intent of therapy, patients’ perception of intent, their desire of disclosure of disease status. We also collected objective scores of GDS, GAD 7, TUG and ECOG performance status. Descriptive statistics were performed to find out the factors significantly affecting patient’s perception of intent of therapy. Results: The median age of our cohort was 68 years (Interquartile range- 64-72 years). Results are shown (Table). 70.6% wanted full disclosure of disease. Out of 1404 patients who were in palliative setting, 40.2 percent patient had misperception of treatment. Conclusions: Our data highlights the significant impact of patient’s general wellbeing both physical and mental on the perception of their treatment goals. It brings forth the need to address these issues along with cancer therapy in an already vulnerable geriatric population. Our data also highlights the desire to know about the disease status in majority which may empower terminal patients to spend their time and energy on things they value. A nearly 41% misperception in palliative patients is indicative of an urgent need for better communication practices to help patients be more aware of outcomes and thus may be able to put more quality in the limited time they have. [Table: see text]
A window-of-opportunity (WOO) trial of giredestrant +/- LHRHa vs anastrozole+LHRHa in premenopausal women with ER+/HER2- early breast cancer (EBC; IBCSG 67-22; PREcoopERA).
Authors: Munzone Elisabetta , Shi Ruichao , Loi Sherene , Colleoni Marco , Viale Giuseppe , Bjelic-Radisic Vesna , Perello Antonia , Karlsson Per , Madaras Balazs , Connolly Roisin M. , Ribeiro Joana M. , Roschitzki-Voser Heidi , Kammler Roswitha , Ruepp Barbara , Regan Meredith M. , Dubsky Peter Christian ,   PREcoopERA Collaborators
Published: May 2024

TPS628

Background: Adjuvant endocrine therapy (ET) for premenopausal women with ER+/HER2- EBC often includes ovarian function suppression (OFS) via a GnRH or LHRH agonist (LHRHa) plus an aromatase inhibitor (AI) or tamoxifen. Younger age is associated with lower rates of ET adherence indicating side effects are less acceptable to these women. The development of drug regimens without OFS are clearly an unmet medical need in this setting. New oral selective ER degraders (SERDs) are emerging as potentially useful ETs in the (neo)adjuvant settings. Giredestrant is an efficient and potent SERD and a full antagonist, which translates into better anti-proliferation activity than known SERDs. PREcoopERA is a WOO trial aiming to determine, among premenopausal women with ER+/HER2- EBC: if giredestrant+LHRHa provides greater anti-proliferative activity than anastrozole+LHRHa; and if giredestrant without LHRHa provides similar (non-inferior) anti-proliferative activity to giredestrant+LHRHa. Results would provide rationale for subsequent (neo)adjuvant clinical trials. Methods: PREcoopERA (NCT05896566) is a randomized, open-label, 3-arm, WOO trial evaluating the anti-proliferative activity and safety of the oral SERD giredestrant +/- LHRHa triptorelin, as compared to the AI anastrozole + triptorelin. Eligible are premenopausal women with untreated ER+/HER2- operable stage I-III (excl. T4) EBC, with Ki-67 ≥10%. 220 women will be randomized in 2:2:1 ratio to giredestrant (30 mg/d po for 4 weeks until rebiopsy) + triptorelin (3.75 mg IM on D1); giredestrant alone; or anastrozole (1 mg/d po) + triptorelin. Rebiopsy is planned for D29, either during primary surgery or standalone procedures. The primary endpoint is change in Ki-67 labeling index between pre-treatment diagnostic tumor biopsy and post-treatment rebiopsy, as assessed by the IBCSG Pathology Office. Sample size of 80:80:40 randomized women are planned to test superiority of 4 weeks giredestrant+triptorelin vs anastrozole+triptorelin to reduce Ki-67 (hypothesized percentage changes -80% vs -65%) and to test non-inferiority of 4 weeks giredestrant vs giredesrant+triptorelin (within 10% as non-inferiority margin). The trial was activated on 9 October 2023. The first woman was enrolled on 25 January 2024. Clinical trial information: NCT05896566 .
Multidisciplinary Management of Advanced Thyroid Cancer
Authors: Bruce Justine Y. , Glazer Tiffany A. , Kimple Randall J.
Published: May 2024

Bruce, Glazer, and Kimple discuss advances in the management of advanced thyroid carcinoma and the role of surgery and radiation to provide context to the review by Yun and Cohen focused on systemic therapy.
Optimal placement of a dissimilar node for chaos suppression in networks
Authors: Chawla Komal , Sinha Sudeshna
Published: May 2024

We demonstrate that the presence of a single dissimilar chaotic system suppresses chaos in networks of chaotic oscillators, in a diverse set of network topologies, for sufficiently strong coupling. The key property is determined to be the sum of the path lengths between the dissimilar node and all the other nodes (or its maximum, if coupled to unconnected networks), and there exists a linear relation between this quantity and the critical coupling strength for the onset of a spatiotemporal fixed point. This holds true for a chain with the dissimilar node at different locations, a ring and complete network with one embedded dissimilar node, as well as star networks with a dissimilar hub or dissimilar peripheral node. Furthermore, we show that networks with high average degree and high clustering coefficient are more resilient to the influence of an external dissimilar system. These findings will potentially aid in the design of optimally placed dissimilar nodes for controlling chaos in complex networks.
Janne Mattila. The Eudaimonist Ethics of al-Fārābī and Avicenna
Authors: Özturan Hümeyra
Published: May 2024

The Eudaimonist Ethics of al-Fārābī and Avicenna adlı kitabın değerlendirmesi.
Sözde-Aristoteles’in Risâletü’t- Tüffâha’sı: Tarihçesi ve Muhtemel Yazarına İlişkin Açıklamalar ile İçeriğine Genel Bir Bakışla Birlikte Tahkikli Neşri
Authors: Bakır Muhammed Burak
Published: May 2024

Bu makale, Sözde-Aristoteles’in Risâletü’t-Tüffâha veya Kitâbü’t-Tüffâha’sını (Lat. Liber de Pomo) tarihçesi, muh- temel yazarı ve yazmaları itibarıyla incelemekte, içeriği hakkında genel bir bakış sunmakta ve daha önce tahkikli neşri yapılmamış olan Arapça tam versiyonunun tahkikli neşrini içermektedir. Tahkikte, risalenin orijinal Arapça versiyonuna en yakın yazma nüshası esas alınmış ve ikinci bir tam nüsha ile karşılaştırma yapılmıştır. Makalede Risâletü’t-Tüffâha’nın ilk olarak Kindî-çevresinde Arapça telif edildiği, ardından Bâtınî-İsmâilî ve Hermetik gelenek- lerde alımlandığı ve hikemiyât literatüründe ve tabakat eserlerinde dolaşıma girdiği öne sürülmektedir. Bununla birlikte, bilimsellik vurguları ve risalenin sözde bir eser olduğuna dair farkındalıkları sebebiyle Meşşâî filozoflara göre Risâletü’t-Tüffâha makbul bir risale değildir. Ayrıca, İbrânî-Latin geleneğinin risaleye ilgisi felsefenin Yahudi ve Hıristiyan toplumlarında kabul görmesini kolaylaştıracak şekilde Aristoteles’in tüm eserlerini alımlamaya yönelik geniş çaplı gayretlerinin bir parçası olduğu için dikkate değerdir. Sonuç olarak, Sözde-Aristoteles’in Risâletü’t-Tüf- fâha’sı felsefeyle dinin uzlaştırılmasını kolaylaştıran dinî-felsefî bir eser olup İslâm, Yahudi ve Hıristiyan çevrelerde özellikle bu nedenden dolayı dolaşıma girmiştir.
Timurlu Horasan’ından I. Mehmed’in Bursa’sına Bir Dânişmendin Serüveni: Haydar el-Herevî’nin el-Keşşâf Şerhi Mukaddimesinin Yeni Versiyonu ve İki Mukaddimeden Biyografi İnşası
Authors: Boyalık M. Taha
Published: May 2024

Haydar el-Herevî Horasan’dan Osmanlı topraklarına gelen önemli âlimlerdendir. Teftâzânî’nin şeçkin bir talebesi olan bu âlim I. Mehmed’ten büyük saygı görerek onun tarafından himaye edilmiştir. Herevî, Zemahşerî’nin el-Keşşâf’ı üzerine yazdığı şerhi büyük övgü ifadeleriyle I. Mehmed’e ithaf etmiş, ithafın yer aldığı mukaddimede hayat hikayesiyle ilgili önemli ayrıntılar vermiştir. Osmanlı topraklarında geçirdiği uzun yıllar sonra Timur’un oğlu Şahruh ile irtibat kuran Herevî, el-Keşşâf şerhi mukaddimesini tekrardan kaleme alarak aynı eseri bu sefer Şahruh’a ithaf etmiştir. Herevî’nin bu yeni patronaj ilişkisi mukaddimenin ikinci versiyonundan öğrenilmektedir. İkinci versiyonda sadece ithaf kısmı değiştirilmemiş, yeni haminin kimliğiyle irtibatlı olarak muhteva da yeni- den kurgulanmıştır. İlk versiyonda bulunmayan önemli biyografik ayrıntılar ikinci versiyonda yer almaktadır. Mukaddimenin iki versiyonu Herevî biyografisinin neredeyse yegâne kaynağıdır. Bu makalede mukaddimenin ikinci versiyonu ilk defa gün yüzüne çıkarılmış ve her iki versiyonda verilen bilgiler bir araya getirilerek Herevî’nin biyografisi inşa edilmiştir. İki versiyonda herhangi bir tarih verilmemiş, sadece bazı şehirlerdeki ikamet süreleri belirtilmiştir. Biyografi inşa edilirken anlatıda oluşan boşluklar tarihi olaylardan hareketle doldurulmuş ve tarihlendirme yapılmıştır. Bahsedilen olaylar, yapılan nitelemeler ve verilen ikamet süreleri itibara alınarak Herevî’nin hayatının yaklaşık kırk yıllık bölümü tam olarak tarihlendirilmiş, Serahs’tan başlayarak sırasıyla Şîraz, Tebriz, Şirvan, Bursa, Edirne ve tekrar Horasan’a uzanan yıllara dair bütünlüklü bir tablo ortaya konulmuştur. Bu hayat hikayesi ulema-sultan ilişkileri, siyasî gelişmelerin ilim hayatına yansımaları ve hayatını ilim yolculuklarında geçiren bir âlimin zihin dünyası hakkında eşsiz bilgiler sunmaktadır.