bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world response endpoints in patients with mNSCLC treated with chemotherapy across real-world datasets.
Authors: McKelvey Brittany Avin , Garrett-Mayer Elizabeth , Belli Andrew J. , Brown Thomas D. , Dow Jessica , Espirito Janet L. , Kluetz Paul , Ma Xinran , McCracken Andrea , Mishra-Kalyani Pallavi Shruti , Natanzon Yanina , Potter Danielle , Rivera Donna , Stires Hillary , Stewart Mark , Allen Jeff 
Published: June 2023

6595 Background: Response Evaluation Criteria in Solid Tumors (RECIST) based response rate (RR) is used for efficacy evaluation in clinical trials and relies on imaging data collected at specified timepoints for uniform assessment. In routine clinical practice, the method and timing of response assessment can vary, and imaging data from electronic health records (EHR) and other real world (rw) sources may not be available, making RECIST-based assessment of rw-response rate (rwRR) using rw data (RWD) challenging. Friends of Cancer Research formed a multi-stakeholder partnership to assess available data attributes to measure response across RWD sources to inform development of a consistent method for measurement. Methods: The study included seven EHR data partners who identified and analyzed a cohort of 1,380 patients (pts) with metastatic non-small cell lung cancer (mNSCLC) treated with first-line platinum doublet chemotherapy, following a common protocol and statistical analysis plan. The availability and frequency of data components to assess response including raw images, radiology imaging reports, and clinician response assessments from provider notes were assessed. Response endpoints measured included rwRR, rw-duration of response (rwDOR), and the association of rwR with rw-overall survival (rwOS), rw-time to treatment discontinuation (rwTTD), and rw-time to next treatment (rwTTNT). Results: The availability of data components varied across RWD sources (Table). Images were not widely accessible, thus response was analyzed using clinician response assessments (median proportion of pts evaluable, 77.5%). Of these assessments, the majority relied on imaging interpretation. The median rwRR was 46% with a median rwDOR of 119 days. The table provides median rwTTD, rwTTNT, and rwOS across data sources. Conclusions: The rwRR among pts with mNSCLC calculated using the clinician assessment was relatively consistent across all RWD sources, with consistent trends in time to event endpoints. While variability in the availability of data components to assess response was observed, the demonstrated feasibility of response endpoints based on clinician assessment suggests further exploration may inform drug effectiveness evaluation with RWD. [Table: see text]
Molecular testing utilization in patients with advanced non-small cell lung cancer (NSCLC) in Washington (WA) state.
Authors: Shih Lauren , Sun Qin , Fedorenko Catherine R. , Yu Kaiyue , Li Li , Kreizenbeck Karma L. , Shankaran Veena , Ramsey Scott David 
Published: June 2023

6596 Background: Therapies targeted at driver mutations (e.g. EGFR, ALK) in NSCLC have contributed to improved patient survival. While current guidelines recommend that all patients diagnosed with stage IV NSCLC undergo molecular testing to determine eligibility for targeted therapies, real-world testing patterns have not been well described. In a retrospective study using cancer registry and insurance claims, we evaluated rates of molecular testing in a population-based sample of NSCLC patients in WA. Methods: We linked WA state cancer registry records from 2017-2019 with claims records for Medicare, Medicaid, and two large commercial insurers. Patients diagnosed with stage IV NSCLC who had continuous insurance enrollment for 2 months prior to and 12 months following diagnosis were identified. Using insurance claims data, we identified patients who received any molecular testing (either testing for specific markers or comprehensive molecular profiling). We compared proportions of patients who received and did not receive molecular testing by insurance type, race, ethnicity, gender, and diagnosis (Dx) year. We performed a multivariate regression analysis to determine factors associated with completion of molecular testing. Results: 1048 eligible patients were identified. The median age was 70. Patients were predominately insured by Medicare (62.6%) and non-Hispanic white. 90.3% of all patients underwent molecular testing. Molecular testing rates were similar between white and non-white patients (90.4% vs 89.2%, p=0.647). Testing rates were significantly lower among Hispanic patients vs non-Hispanic patients (77.8% vs 90.7%, p=0.018). Testing rates were lowest among Medicaid enrollees (86.4%) compared to Medicare (88.4%), commercial (97.2%) or multiple insurances (94.9%) (p=0.0018). A multivariate analysis demonstrated that patients age ≥65 and Medicaid patients were less likely to receive molecular testing while females were more likely to receive testing; year of Dx did not impact testing rates (Table). Conclusions: While the rate of adherence to recommended molecular testing was high in the overall cohort, testing rates were lower in Hispanic patients, older patients, males, and those with Medicaid insurance. Given the therapeutic implications of testing, drivers of these observed disparities warrant further study to ensure equitable access to efficacious treatment. [Table: see text]
Disparities in PI3K/mTOR inhibitor use, toxicities, and outcomes among patients with metastatic breast cancer.
Authors: Sathe Claire , Accordino Melissa Kate , DeStephano David , Shah Mansi , Wright Jason Dennis , Hershman Dawn L. 
Published: June 2023

6597 Background: Advances in breast cancer treatment have led to improvements in survival among patients with metastatic breast cancer (MBC). Nevertheless, Black patients and patients with lower socioeconomic status (SES) continue to bear a disproportionate mortality burden. Furthermore, because landmark trials for novel anticancer agents lacked racial diversity, their toxicity profile for minority patients remains uncertain. Our study examines the impact of race and other sociodemographic characteristics in the use and toxicity outcomes of PI3K and mTOR inhibitors (PI3K/mTORi). Methods: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include patients with hormone receptor-positive, HER2-negative MBC diagnosed between 1/1/2011 and 1/31/2022. Outcomes included PI3K/mTORi use, rates of hyperglycemia and dose reduction, and time on treatment. Multivariable logistic regression was used to evaluate factors associated with use and outcomes. Results: A total of 13,388 patients with MBC were included in our analysis, of which 2,620 (19.6%) received PI3K/mTORi (78.3% everolimus, 14.7% alpelisib, 6.9% both agents). Overall, 67.5% of all patients were categorized as White, 9.8% as Black/African-American (Black/AA); 18.9% were >75 years old; 10.1% were treated at an academic site; 4.0% had Medicaid insurance. Insurance through Medicaid was associated with lower use of PI3K/mTORi compared to commercial insurance (15.6% vs 18.8%; OR: 0.76, 95% CI: 0.59-0.99, p=0.04), as was advanced age (10.9% for >75 years old vs 22.9% for <60 years old; OR: 0.68, 95% CI: 0.58-0.80, p<0.001) and poorer performance status at diagnosis (15.1% for ECOG ≥2+ vs 22.9% for ECOG 0; OR: 0.84, CI: 0.72-0.98, p=0.03). Odds of PI3K/mTORi use were almost 50% higher for patients treated at an academic center (OR: 1.46, CI: 1.06-2.05, p=0.02). While Black/AA patient had lower rates of use than White patients (17.4% vs 20.1%), they had similar odds of receiving PI3K/mTORi on multivariable analysis (OR: 1.00, CI: 0.85-1.17, p>0.9). Black/AA patients experienced higher rates of hyperglycemia on PI3K/mTORi than White patients (67.6% vs 52.5%). On multivariable analysis, odds of hyperglycemia were twice as high for Black/AA patients (OR: 2.1, CI: 1.33-3.35, p<0.01). However, rates of dose reductions and time on PI3K/mTORi therapy did not differ significantly among White vs Black/AA patients. Conclusions: This analysis of real-world data suggests that lower SES is associated with decreased PI3K/mTORi use. Efforts to improve access to these life-prolonging agents are warranted. Of concern, we also found racial disparities in toxicity outcomes, with Black patients having twice the risk of hyperglycemia. Greater attention to the tolerability of novel agents in diverse populations is warranted.
Decomposing racial differences in financial hardship among older cancer survivors.
Authors: Davis Elizabeth , Yarbro Alaina , Bhatia Smita , Kenzik Kelly 
Published: June 2023

6598 Background: Despite Medicare coverage, financial hardship is a prevalent issue among older cancer survivors, particularly among those belonging to a racial/ethnic minority. Sociodemographic, clinical, and area-level factors may mediate this relationship; however, no studies have assessed the extent to which these factors contribute to disparities. Methods: Surveys assessing financial hardship after cancer were completed by 721 patients age 65y+ of Black or white race completing primary cancer treatment for breast, prostate, colorectal, prostate cancer or lymphoma at University of Alabama at Birmingham between 2000 and 2019. Financial hardship included material, psychological, and behavioral domains. Material hardship included ever 1) borrowing money/going into debt, 2) filed for bankruptcy, 3) worried about paying large medical bills, and 4) made any other financial sacrifices due to cancer. Psychological hardship was measured by asking if participants were ever worried about paying large medical bills related to cancer, its treatment or effects of treatment. Behavioral hardship was measured by asking if participants were unable or delayed in obtaining medical care, tests, treatments or prescriptions in the last 6 months. Non-linear Blinder-Oaxaca effect decomposition methods evaluated the extent to which individual-level sociodemographic, clinical, and area-level factors contributed to racial disparities in financial hardship. Results: Median age at survey was 78 (IQR = 73-82), majority were female (53%) and non-Hispanic White (84%). The most common cancers were breast (34%) and prostate (27%), followed by lung (17%), lymphoma (9%) and colorectal (14%). Ninety percent were diagnosed at an early stage and median time from diagnosis to survey was 8y (IQR = 5-12). There were no significant clinical differences between Black and white patients. Overall, 22% reported any financial hardship; 14% material, 3% behavioral, and 14% psychological. Black, compared to White participants reported significantly (p < 0.001) higher rates of overall (39% v 18%), material (29% v 11%), and psychological (27% v 11%) financial hardship. Notably, Black patients had higher rates of being unable to cover cancer-related costs (23% v 7%), worrying about paying large medical bills (27% v 11%), and having to borrow money or go into debt (9% v 3%). Overall, the observed characteristics explained 81% of racial differences in financial hardship among cancer survivors, primarily by differences in income (24%), cancer diagnosis and stage (22%), and area deprivation (15%). Conclusions: These results identify primary contributors to racial disparities in financial hardship among older cancer survivors, which can be used to develop interventions aimed at eliminating inferior healthcare outcomes experienced by certain racial groups, inform policy, and allocate resources to those at greatest risk for financial hardship.
Intrathecal drug delivery systems for cancer pain control: Insights on current contemporary practices in the US.
Authors: Goel Vasudha , Geller Melissa Ann , Blaes Anne Hudson , Gulati Amitabh 
Published: June 2023

6605 Background: About a third of cancer survivors report moderate to severe pain. Intrathecal drug delivery system (IDDS) is an implantable pain control option for treating intractable chronic pain not responsive to systemic opioid therapy. Studies on the current practices in the US around the utilization of IDDS for cancer pain are lacking. Methods: The Nationwide inpatient sample (NIS) dataset is funded by the Agency for healthcare research and quality (AHRQ) for multistate healthcare research & decision-making. Adult patients admitted to hospitals with a primary or secondary cancer diagnosis between 2016-19 were included. Patients undergoing IDDS implantation were identified using the validated International Classification of Diseases, 10th Revision, Procedure Coding System codes (00HU33Z Insertion of infusion device into spinal canal, percutaneous approach and 0JH80VZ Insertion of infusion pump into abdomen subcutaneous tissue and fascia, open). Baseline demographics, hospital characteristics, and type of cancer associated with IDDS implantation were evaluated in the study. Results: 22,895 patients underwent IDDS surgery amongst 7.06 million hospitalizations from 2016-19. The IDDS cohort consisted of patients in the 65-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). Most IDDS surgeries were performed in large, urban teaching hospitals. Conclusions: Despite recommendations supporting IDDS use, a small minority received the treatment with significant racial & socioeconomic disparities in IDDS use. [Table: see text]
Development of natural language processing (NLP) models for extracting key features from unstructured notes to create real-world data (RWD) assets for clinical research at scale.
Authors: Agrawal Smita , George Rohini , Vaidya Vivek Prabhakar , Chakkrapani Sangavai , Prajapati Rambaksh , Tankala Srikanth , Parmar Dhaval , Lakkimsetty Vinay Phani Santosh , Bhardwaj Tapasya , Ashwani Ashwani , Mendonca Emma , Narayanan Babu , Swaminathan Krishna Kumar , Mukherjee Pranay 
Published: June 2023

6607 Background: RWD derived from Electronic Health Records (EHR) has detailed clinical information about patient journeys that can assist in clinical research, trial design, safety assessments etc. However, much of the vital information is locked away in unstructured clinical texts and needs to be converted to structured format to be useful for downstream applications. We demonstrate how this can be achieved at scale with a high degree of accuracy through NLP. Methods: NLP models were developed to extract data for 11 clinical variables from unstructured notes of ~98k lung cancer patients and merged with the structured data into a common data model (Table). These models were a combination of domain knowledge, rule-based models, machine learning models, and deep learning models. The increase in fill rate per variable over structured data only was used to quantify the improvement by NLP. The accuracy of the models was assessed against a manually curated dataset comprising of 752 patients. Results: The NLP models significantly improved the fill rate of key clinical variables and were able to extract the information from clinical notes with high accuracy (Table). For some variables such as NSCLC/SCLC status, surgery, tumor grade and histology, all or most of the data was extracted via NLP. Metastatic status via NLP included distant metastasis, locally advanced disease and no metastasis whereas in the structured data, only data for distant metastasis was present. In the case of Performance Status (PS), even though a significant number of patients had at least 1 PS recorded in the structured data, NLP significantly increased longitudinal capture, thus increasing the density of this variable per patient. Conclusions: NLP models can be developed and used to enrich structured RWD data by extracting information from unstructured documents thus significantly improving the utility of this data for downstream applications. Given the high accuracy of these models and the scale at which they can be run, this can be a good alternative to human curation or can augment human curation enabling the creation of very large-scale datasets for clinical research. [Table: see text]
Using real-world evidence (RWE) in regulatory decision making: A study of 6 oncology approvals with RWE included in the product label.
Authors: Zong Jihong , Jiao Xiaolong , Pan Lucy , Castelo Sarah , Campbell Chelsey , Lennert Barb , Bruno Amanda 
Published: June 2023

6611 Background: The 21st Century Cures Act in 2016 enhanced the FDA’s ability to include the use of real-world data (RWD) and consideration of RWE in the development and approval of new medical products. Currently, limited assessments of the use of RWE in FDA approved oncology product reviews exist in the literature. This study was conducted to determine how RWE was used in FDA decisions for oncology drug approvals between 2015 and 2022. Methods: A systematic review of FDA submission documents and product labels available on the FDA website from 2020 to 2022, in addition to an exhaustive manual search of grey literature and the results of a targeted literature search from 2015 to 2019 were used to identify RWE that were included in FDA submission documents and in approved product labels. Results: In total, 124 oncology product evaluations were reviewed in the 2020 to 2022 literature search. Twenty-nine oncology product NDAs and BLAs included RWE to support efficacy, safety, or indication, of which the majority (n=26) ultimately had RWE accepted as evidence by the FDA for the submission. In these cases, RWE was used to add context (n=16), to support the indication or safety (n=7), to provide substantial basis for indication or safety (n=2), as a statistical comparison (n=2), or for informational purposes only (n=1). Feedback from the FDA reviewers for reasons RWE studies were not considered during product approval reviews included methodology issues, sample size concerns, and omission of patient level data. Ultimately, across the 2015 to 2019 targeted literature review and the 2020 to 2022 FDA submission document review, 6 oncology product labels incorporated RWE: palbociclib, uridine triacetate, lutetium Lu 177 DOTATATE, bevacizumab-adcd, naxitamab-gqgk, and decitabine/cedazuridine. RWE was used to support the initial indication for the majority of products (n=5) and also supported label expansion (n=1). RWE was incorporated in the product label postmarketing experience section (n=3), the clinical studies section (n=2), and the warnings/precautions section (n=1). Conclusions: These results suggest that RWE has become an important part of regulatory decision-making for oncology drug approval. Twenty-six of 29 RWE studies were accepted as evidence for the submission. For the 6 oncology products that include RWE in the product label, RWE was most frequently used to support the initial indication and was included in the postmarketing experience section. These examples show consistent use of RWE since the approval of the 21st Century Cares Act and provide evidence of a promising new direction with the creation of the FDA guideline/program for RWE.
Racial disparities in survival and stage at diagnosis among adolescent and young adult patients with cancer.
Authors: Taparra Kekoa A. , Kekumano Kāʻeo , Benevente Ryan , Gimmen Megan Y. , Kinslow Connon , Deville Curtiland , Pollom Erqi L. 
Published: June 2023

6615 Background: Adolescent and young adult (AYA) patients (15-39 years) are an underrecognized population with high risk of select malignancies. Compared to pediatric and adult patients, AYA patients have not achieved improvements in cancer survival. No studies have evaluated overall survival (OS) and stage at diagnosis among all 5 federally recognized races in the US. Here we aim to investigate OS and stage at diagnosis among AYA patients by race. Methods: A retrospective cohort study of AYA patients diagnosed between 2004-2017 was conducted with the National Cancer Database. Patients with the 10 deadliest AYA cancers with at least 6 months of follow-up were included. Primary endpoints were OS (time from diagnosis to death) and late stage at diagnosis (stage III/IV or Grade III/IV for central nervous system [CNS] cancer). Kaplan-Meier estimates and log-rank tests assessed OS. OS and late stage were evaluated by race using multivariable Cox proportional hazard (adjusted hazard ratio [aHR]) and logistic (adjusted odds ratio [aOR]) regressions, respectively, with 95% confidence intervals (95%CI). All regressions were adjusted for sociodemographic and cancer characteristics. Results: 291,899 AYA patients were included: 64% female, 65% stage I/II, and 62 month median follow-up. Cancer sites included 27% breast, 16% lymphoma, 13% melanoma, 11% testis, 9% CNS, 7% colorectal, 7% cervix, 5% sarcoma, 3% ovary, and 2% lung. Race included 82.3% Non-Hispanic White (NHW), 14.0% Black, 2.9% Asian, 0.5% American Indian and Alaska Native (AIAN), and 0.3% Native Hawaiian and other Pacific Islander (NHPI). OS differed for all cancers by race (p<.0001), except for lung (p=.008), CNS (p=.32), and ovary (p=.28). OS was significantly inferior for NHPI, Black, and AIAN but superior for Asian, versus NHW (Table). NHPI had inferior OS (aHR, 95%CI) for melanoma (4.5, 2.0-10.0), colorectal (1.8, 1.3-2.4), lymphoma (1.7, 1.1-2.1), and cervix (1.6, .1-2.4) cancers. Black patients had inferior OS for melanoma (1.6, 1.2-2.2), lymphoma (1.5, 1.4-1.6), and breast (1.4, 1.3-1.4) cancers. Asian patients had superior OS for breast (0.7, 0.7-0.8) and lung (0.7, 0.6-0.9) but inferior survival for testis (1.9, 1.3-2.9) cancers. AIAN patients had inferior OS for colorectal (1.4, 1.0-1.9). Late stage at diagnosis was higher for NHPI, Black, and Asian patients, compared to NHW patients (Table). Conclusions: Both NHPI and Black AYA patients with cancer have higher risk of death and late stage disease at diagnosis, compared to NHW patients. Our data reveal racial disparities among Indigenous AYA patients masked by prior data omission. [Table: see text]