bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Medicare Advantage associated with more favorable health care access, acute care utilization, and affordability among beneficiaries with cancer?
Authors: Patel Vishal R. , Jafri Faraz , Gupta Arjun , Hussaini S. M. Qasim 
Published: June 2023

1597 Background: The Medicare Advantage (MA) program provides care to nearly half of Medicare beneficiaries, including a rapidly growing population of cancer survivors. Although MA was designed to optimize healthcare access, outcomes, and affordability, it is unknown whether these effects have been achieved in cancer survivors. Methods: We performed a cross-sectional study of Medicare beneficiaries ≥65 years with a self-reported history of cancer in the 2019 National Health Interview Survey. We used multivariable logistic regression to evaluate the association between Medicare program type (MA vs traditional Medicare, TM) and measures of healthcare access, acute care utilization, and affordability. Results: We identified 4,451 beneficiaries with a history of cancer, corresponding to 26.6 million weighted cancer survivors in 2019. Of beneficiaries, 35.8% were enrolled in MA while 64.2% were enrolled in TM. The age, sex, racial and ethnic composition, household income, primary site of cancer, and co-morbidity burden of MA and TM beneficiaries were similar. In adjusted analysis, there were no differences in health care access or acute care utilization between TM and MA beneficiaries. However, survivors enrolled in MA were more likely to worry about (34.3% vs 29.4%; aOR, 1.3 [95% CI, 1.1-1.5]) or have problems paying (13.6% vs 11.1%; aOR, 1.4 [95% CI, 1.1-1.8]) medical bills. Conclusions: MA beneficiaries with a previous cancer diagnosis more often struggle paying medical bills despite similar healthcare access and preventive care as TM. Despite generous benefits and attractive incentives for care coordination and health management, privately run MA plans may not be more cost-effective than TM for cancer survivors. Our study informs ongoing congressional deliberations to re-evaluate the role of MA in promoting equity among beneficiaries.[Table: see text]
System-wide approach on biosimilars adoption in oncology: Strategic plan on switching and cost savings.
Authors: Limvorasak Suwicha , Kim Kyung , Dobbs Crystal Leung , Posadas Edwin Melencio , Scher Kevin , Chang Johnny , Chiu Vi Kien , Diniz Marcio A. , Rogatko Andre , Teaford Hilary , Sakamoto Leanne , Vinson Bruce , Patel Vipul , Figlin Robert A. , Shane Rita , Reckamp Karen L. 
Published: June 2023

1600 Background: Biosimilars provide competitive, lower-cost alternatives to biologic drugs in cancer treatment. As more agents become available in the US, institutions have to implement a strategy for successful adoption that is feasible, safe and provide price competition among biosimilar manufacturers. Methods: We aimed to standardize biosimilar utilization across the Cedars-Sinai Health System (CSHS) by integrating institutionally developed clinical pathways and insurance prior-authorization into the existing electronic health record (EHR). The initial study was limited to bevacizumab, rituximab and trastuzumab. To align with CSHS guideline recommendations, biosimilar indications for use were reviewed by each disease related group (DRG). Biosimilar brands for each drug were selected through a formulary process vetted by the Pharmacy & Therapeutics Committee. Physicians were permitted to opt-out of switching via an option provided within the electronic order set. To test feasibility of this approach, patients were divided into two groups as 1) main medical center (Cedars Sinai Medical Center) and 2) Cedars-Sinai Cancer affiliated sites. Feasibility was defined as a compliance rate of 80% or greater at the main medical center and 75% or greater at the affiliated sites. This study was powered to detect a minimum difference at 5.7% and 8.9%, respectively. Results: Between January 2021 to September 2022, a total of 1,139 cancer patients who initiated treatment with bevacizumab, rituximab or trastuzumab were identified through the EHR, of whom 650 were eligible (age 18-96; 61% female, 39% male). Using our approach, the compliance rate was 86% at the main site (p<0.001, 95%CI: 82.5-89.1) and 88% (p<0.001, 95%CI: 82.1-91.7) at the affiliated sites, resulting in a 56% improvement from baseline (86% vs. 55%, p<0.001). Among 14% of patients who did not switch to institutional-preferred biosimilar brands, the most common reasons for this were payer mandated use of an alternate brand (5%), off-label indication (4%), enrolled in patient assistance program (3%) and physician preference (2%). Five patients (<1%) did not switch to biosimilars due to history of infusion reactions. Insurance type (HMO, PPO, Medicare, others) was not associated with non-compliance (p=0.876). Cost savings were projected to be over $4 million over a duration of two years. Conclusions: Enterprise-wide switching to one specific biosimilar brand is feasible and facilitated through leveraging of the EHR. This approach optimized exiting organizational infrastructure to standardize biosimilar utilization and promote substantial cost savings.[Table: see text]
Correlation between Oncotype DX, Predict, and Nottingham Prognostic Index on HR+, HER2- early breast cancer treatment: The current value of molecular testing.
Authors: Campoverde Leticia , Camacho Felipe , Sanchez Adriana , Lugo Paulina 
Published: June 2023

1601 Background: The Oncotype DX Breast Recurrence Score (ODX) assay is a 21-gene assay validated in hormone receptor-positive, HER2 negative invasive breast cancer (BC) to predict chemotherapy benefit and risk of distant recurrence at 10 years regardless of node status and is also a strong predictor of mortality. ODX can minimize the misuse of chemotherapy, financial burden, and improve clinical outcomes. ODX is not widely used in Ecuador due to socioeconomic and healthcare access disparities; instead, many physicians stratify patients' risk according to clinicopathological and immunohistochemical features. We aim to compare the differences between ODX and two of the most common stratification clinical tools: Predict Score (PS) and Nottingham prognostic index (NPI). Methods: Retrospective analysis of women with early BC who underwent ODX testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3 / N0-N1a); estrogen receptor (ER) positive; HER2 negative by immunohistochemistry; and available data of tumor size, grade, lymph node status, and Ki67 proliferation index. Exclusion criteria: patients with recurrent BC, incomplete pathology, or immunohistochemistry data. PS and NPI were calculated using online tools. The correlation between PS, NPI, and ODX scores was analyzed using Spearman's correlation coefficient in SPSS. Results: 77 patients underwent ODX testing, of which 58 patients (mean age 55 years old) met the inclusion criteria. Invasive breast carcinoma not otherwise specified was the most common type (48 patients (82%). Risk scores generated by PS correlated strongly with NPI for all patients (r=0.47; p ≤ 0.001). A strong correlation was also found between ODX and NPI (0.79, p<0.027). Risk scores were then stratified by patient risk category. For low-risk patients, 68% of correspondence between ODX and PS was found, and 98% between ODX and NPI. Intermediate-risk patients showed a correspondence between ODX and PS of 5% and 9% for ODX and NPI. High-risk patients showed a correspondence of 50% between ODX and PS and 17% between ODX and NPI. Conclusions: ODX risk recurrence for low-risk patients is highly correlated with PS and NPI. For Intermediate and high-risk patients determined by PS and NPI, ODX testing provided valuable and prognostic information and should be considered to guide adjuvant treatment. [Table: see text]
RANO 2.0: Proposal for an update to the Response Assessment in Neuro-Oncology (RANO) criteria for high- and low-grade gliomas in adults.
Authors: Wen Patrick Y. , Van Den Bent Martin J. , Youssef Gilbert , Cloughesy Timothy Francis , Ellingson Benjamin M. , Weller Michael , Galanis Evanthia , Barboriak Daniel , de Groot John Frederick , Gilbert Mark R. , Huang Raymond Yi-kun , Lassman Andrew B. , Mehta Minesh P. , Molinaro Annette , Preusser Matthias , Shankar Lalitha Krishna , Wick Wolfgang , Reardon David A. , Vogelbaum Michael A. , Chang Susan Marina 
Published: June 2023

2017 Background: Response Assessment in Neuro-Oncology (RANO) criteria for high-grade and low-grade glioma (HGG and LGG) were developed to improve reliability of response assessment in glioma trials. Several limitations of the original RANO criteria have been reported. Methods: To address limitations of the original RANO criteria, a large cohort of patients with newly diagnosed and recurrent glioblastoma were evaluated comparing RANO-HGG with modified RANO (mRANO) and immunotherapy RANO (iRANO) criteria to inform the following proposed updates (RANO 2.0). Results: Based on the 2021 WHO classification of glioma, we recommend a single common set of criteria for all gliomas regardless of WHO grade and IDH mutational status. These criteria will be used for all trials regardless of the treatment modalities being evaluated. In newly diagnosed glioblastoma, the post-radiotherapy MRI, usually obtained approximately 4 weeks after completion of radiotherapy, rather than the post-surgical MRI as proposed in original RANO criteria, will be used as the baseline for comparison of subsequent scans. Since the incidence of pseudoprogression is high in the first 3 months following radiotherapy, confirmation of progression during this period with a repeat MRI (in 4-8 weeks) will be required for determining radiographic progression of disease (PD) if the patient is clinically stable. However, confirmation scans are not mandatory after this period nor for recurrent tumors since these scans do not appear to improve reliability in determining progression. For agents with a high likelihood of producing pseudoprogression such as viral therapies and some other immunotherapies, mandatory confirmation of progression with a repeat MRI is an option. The primary measurement will remain the 2-dimensional maximum cross-sectional area of tumor as the simplest method, but where resources are available, volumetric measurements are an option. For IDH wild-type tumors with contrast enhancement, non-enhancing tumor will no longer be evaluated with the possible exception of patients receiving antiangiogenic therapies. However, in tumors with a significant non-enhancing component, both the contrast enhancing and non-enhancing components will be evaluated as target lesions. Conclusions: We hope that these and other proposed changes by the RANO working group will improve response assessment in glioma clinical trials and help the development of more effective therapy for patients.
EO2401 (E) peptide immunotherapy + nivolumab (N) +/- bevacizumab (B) in recurrent glioblastoma (GB): EOGBM1-18/ROSALIE.
Authors: Wick Wolfgang , Idbaih Ahmed , Vieito Maria , Ghiringhelli François , Stradella Agostina , Tabatabai Ghazaleh , Burger Michael C. , Mildenberger Iris , Herrlinger Ulrich , Wen Patrick Y. , Touat Mehdi , Wick Antje , González Macarena , Hervieu Alice , Gil-Martin Marta , Renovanz Mirjam , Maia Ana , Bonny Christophe , Fagerberg Jan , Reardon David A. 
Published: June 2023

2020 Background: EO2401 was designed to activate/expand existing memory T cells recognizing specific protein sequences from gut bacteria, which cross-react with tumor associated antigens (TAAs). E contains 3 CD8 HLA-A2 epitopes with mimicry to GB-TAAs (IL13Rα2, BIRC5, and FOXM1) and the CD4 epitope UCP2. Methods: Patients (pt) at 1st progression GB received E (300 µg/peptide, q2w x4 then q4w) with N (3 mg/kg q2w) in cohorts: 1a E x2 → EN; 2a/1, 2a/2 and 2b EN from start; 2c EN x2 → surgery → EN; 3/1 and 3/2 EN + B (10mg/kg q2w) (Table). Results: Among 100 treated pt EN+/-B was well tolerated, with E associated events limited to local skin reactions (45% of pt; 96% Grades 1/2, and 4% Grade 3) and N-/B-tox consistent with historical data. EN induced immune response against all 3 mimics in 94% of 35 tested pt (all pt responded against at least 2 mimics), detectable as early as 2 weeks after first EN, and with durations beyond 10 months. Cross-reactivity against human peptides found in 89%. Conclusions: EN +/- B was well tolerated and generated fast and durable immune responses. EN survival like current standards. Delayed N was not advantageous for outcome. sLDB increased trt duration of EN, and improved efficacy. Continuous B plus EN further improved efficacy. Neo-/adjuvant EN was clinically feasible. Updated data, including C3/2 to confirm C3/1, to be presented. Clinical trial information: NCT04116658 . [Table: see text]
Association of CDK4 amplification with duration of response to bevacizumab in glioblastoma.
Authors: Villano John L. , Morgan Rachael M , Zhang Shulin , Kolesar Jill , Xiu Joanne , Seifert Hilary , Nicolaides Theodore , Rock Stephanie , Kesari Santosh , Aulakh Sonikpreet , Wong Eric T. , Glantz Michael J. 
Published: June 2023

2026 Background: Bevacizumab remains the standard second line therapy in glioblastoma (GBM) with reported improved progression free survival, but not overall survival. We investigated a large clinico-genomic database of GBM patients treated with bevacizumab for molecular alterations associated with treatment outcome. Methods: Molecular profiles of GBM were tested by next-generation sequencing (NGS) of DNA (592 genes, NextSeq or whole-exome sequencing, Novaseq) and RNA (whole transcriptome sequencing, NovaSeq) at Caris Life Sciences (Phoenix, AZ). Gene amplification was determined by NGS with a threshold of > = 6 copies. Real-world survival information was obtained from insurance claims data. Time-on-treatment (TOT) of bevacizumab was calculated from start to finish of treatment while post-bevacizumab overall survival (bevOS) from start of bevacizumab to last day of contact. Short-term (ST) and long-term (LT) responders were defined as those with TOT ≤6 months and ≥1 year, respectively. Kaplan-Meier estimates were calculated and significance was determined as p values of < 0.05. For molecular comparisons, Fisher’s exact tests and Mann-Whiney U were used when appropriate. Results: Among the total of 383 ST and 107 LT patients identified, no significant difference in gender or age were seen. The LT cohort had significantly longer bevOS compared to the ST cohort (HR 0.27, [95% CI: 0.28-0.35], p < 0.0001). Interestingly, CDK4 amplification was seen in 23% (18/78) of LT patients but only 7% (21/300, p = 0.0002) of ST. When investigating the total cohort of 498 GBM treated with bevacizumab, CDK4 amplified patients demonstrated significantly improved TOT compared to non-amplified (HR: 0.639, [0.48-0.85, p = 0.002]). Conversely, the ST cohort had significantly more EGFR amplifications than the LT cohort (43%, 130/300 vs. 19%, 15/79, p < 0.0001). In the total bevacizumab-treated cohort, EGFR-amplified GBM had significantly worse TOT on bevacizumab than non-EGFR amplified GBM (HR 1.387, [1.15-1.67], p < 0.001). No associations were seen in other alterations explored including PIK3CA mutation (HR = 0.81 [0.587-1.113], p = 0.2), EGFR mutation (HR: 1.209, [0.977-1.495], p = 0.1) or RAF1 (HR: 0.647, [0.318-1.317], p = 0.2). Conclusions: Using a large clinical genomic database with GBM subjected to comprehensive molecular profiling, we demonstrated that amplification of CDK4 and EGFR were associated with long-term and short-term responses to bevacizumab, respectively. This warrants further investigation in independent cohorts controlled for age and other prognostic factors. If confirmed, a genetic basis for treatment optimization may provide meaningful clinical outcomes.
A radiomics model developed from pre-metastatic brain magnetic resonance imaging to predict brain metastasis in non–small-cell lung cancer: Evidence to the seed-and-soil theory.
Authors: Chu Xiao , Gong Jing , Zhu Zhengfei 
Published: June 2023

2030 Background: Steven Paget’s “seed and soil” theory suggests that both the primary tumor and the target host organ play important roles in successful metastasis development. In this proof-of-concept study, we proposed that inter-individual differences exist in the brain’s congeniality for developing brain metastasis (BM), and validated the theory via developing a non-invasive radiomics BM prediction model. Methods: 256 non-small cell lung cancer (NSCLC) patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected, 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Baseline brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomics features were extracted to develop the BM prediction models. We first developed radiomics models using the training dataset and subsequently validated the models in the testing dataset. A radiomics BM score (RadBM score) was generated and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. Furthermore, a fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84[95% confidence interval: 0.80–0.89] and 0.80 [95% confidence interval: 0.71–0.88] in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank P < 0.001). Cumulative BM rate at 3-year were 75.8% and 24.2% for RadBM score-high and RadBM score-low group, respectively. Conclusions: The results demonstrated that intrinsic features of a non-metastatic organ exert a significant impact on metastasis development, which is first-in-class in metastasis prediction studies and provided novel evidence for the "seed-and-soil" theory of tumor metastasis. Radiomics BM prediction model utilizing both pre-metastatic brain and primary tumor features might provide a useful tool for identifying NSCLC patients more prone to develop BM and providing individualized management for these patients.
HER2-low breast cancer brain metastases: Incidence and treatment implications.
Authors: Chehade Rania , Nofech-Mozes Sharon , Plotkin Anna , Moravan Veronika , Jerzak Katarzyna Joanna 
Published: June 2023

2035 Background: Brain metastases (BrM) are a major cause of morbidity and mortality among women with breast cancer (BC). Central nervous system (CNS)-penetrating systemic therapies for patients with HER2-negative BrM are lacking; this is particularly problematic for patients with triple negative disease (TNBC) who have a high likelihood of developing BrM. Given CNS activity of trastuzumab deruxtecan, efficacy for patients with HER2-low BrM is of interest. Methods: A retrospective study of two cohorts of patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre between 1999-2013 and 2008-2018 were identified. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2) status were assessed based on 2018 ASCO/CAP guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH) negative status. HER2-positive was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathological features were recorded. We also assessed the prognostic association between extent of HER2 expression and i) brain-specific progression free survival (bsPFS), as well as ii) overall survival (OS). Results: Out of 137 patients with resected BrM, tissue for HER2 assessment was available in 74.5% (n=102) of cases. In this cohort, the median age at BrM diagnosis was 53.5 (range, 32-85). 18.6% (n=19) had leptomeningeal disease and 68.6% (n=70) had extracranial disease. 53% (n=54) of the BrM were HER2-positive; 29.4% (n=30) were HER2-low and 17.6% (n=18) had HER2-zero status. Among BrM that were triple negative based on ASCO/CAP guidelines, 14 out of 22 cases (63.6%) were re-classified as being HER2-low. 15/25 (60%) BrM that were hormone receptor positive/HER2 negative (HR+/HER2-) based on ASCO/CAP guidelines were re-classified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low and HER2-positive were concordant in 82.3% (n= 42/51) of cases (Cohen’s kappa 0.58, p=0.0719). In 7 cases, the primary breast tissue was HER2-zero whereas the BrM was either HER2-low (n=5) or HER2-positive (n=2). In only one case (2%), expression of HER2 was lower in the BrM (HER2-low) compared to the primary BC (HER2-positive). Median time from primary BC to the development of BrM was 35 months (IQR, 14-69) in the overall cohort; patients with HER2-zero BrM had a numerically longer time to development of BrM (45.8 months), compared to those with HER2-low (35 months) and HER2-positive (35 months) BrM (p=0.948). There was no significant association between HER2-zero, HER2-low and HER2-positive status in BrM and either bsPFS or OS. Conclusions: Among patients with surgically resected BrM, a high proportion of those with metastatic TNBC and HR+/HER2-negative disease have “HER2-low” BrM with potential to benefit from HER2-targeted therapy.