bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical predication models to optimize post-treatment surveillance in HPV-associated oropharyngeal cancer.
Authors: Nair Vivek , Auger Samuel , Kochanny Sara , Howard Frederick , Ginat Daniel , Pasternak-Wise Olga , Juloori Aditya , Izumchenko Evgeny , Agrawal Nishant , Rosenberg Ari , Vokes Everett E. , Skandari Reza , Pearson Alexander T. 
Published: June 2021

6027 Background: In this study we develop post-treatment imaging surveillance schedules for locally advanced oropharyngeal carcinoma (OPC) specific to the unique recurrence patterns of tumor stage and HPV status, using mathematical models. Current post-treatment imaging surveillance recommendations for OPC are not evidence based. The exception is the use of a positron emission tomography (PET) scan at 3 months post-treatment, after which practice across institutions diverge. An optimized and personalized surveillance schedule for OPC patients can minimize costs and diagnostic delays. Methods: A Markov multi-state model defining local and distant recurrences was trained using 2159 patients from the National Cancer Database. Patients from 2010-2015 treated at an academic or major cancer center with curative radiotherapy were included. Tumors must have been stage III to IVB (AJCC 7th edition) with known p16/HPV status. Model performance was then successfully externally validated using the 2016 International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) study. Optimized radiographic surveillance schedules were created using this model, assuming a PET at month 3 and including 0 to 6 additional computed tomography (CT) scans of the neck and chest. Optimization was done for minimization of latency, defined as time between disease recurrence and radiographic discovery. Results: Model-selected schedules varied significantly from commonly utilized-surveillance schedules (such as imaging every 3 months within the first year from treatment) and showed lower mean diagnostic latency for every stage and HPV status (shown in Table). In the lowest risk cohort (Stage III HPV+), the optimized schedule had a sensitivity of 65% and latency of 3.1 months. In the highest risk group (Stage IVB HPV-), the optimized schedule had a sensitivity of 76% and latency of 1.9 months. Conclusions: Mathematical model optimization for HPV status and stage is feasible and produces non-intuitive results. These results could be used to inform surveillance if payors reimburse for fewer total scans. Across all cohorts, each added CT scan increases surveillance sensitivity and decreases latency. Incorporation of physical exam and direct visualization results into the model are still needed. Future steps include cost effectiveness research and prospective clinical trials.[Table: see text]
Quantitative immunofluorescence and mRNA analysis of immune-related biomarker groups in matched paired tumor samples from OPHELIA window study in head and neck squamous cell carcinoma (HNSCC).
Authors: Psyrri Amanda , Moutafi Myrto , Koliou Georgia-Angeliki , Papaxoinis George , Gavrielatou Niki , Economopoulou Panagiota , Kotsantis Ioannis , Gkotzamanidou Maria , Anastasiou Maria , Pectasides Dimitrios G. , Fernandez Aileen , Yaghoobi Vesal , Shafi Saba , Vathiotis Ioannis , Nwe Aung Thazin , Gkolfinopoulos Stavros , Foukas Periklis , Fountzilas George , Rimm David L. 
Published: June 2021

6064 Background: Preclinical models suggest that PARP inhibitor-induced DNA damage can promote immune priming through a range of mechanisms including STING pathway activation. PARP inhibition also leads to adaptive upregulation of PD-L1 expression in preclinical models. To understand the distinct effects that different forms of DDR defects may have on tumor immunogenicity we decided to integrate genomic profiling with gene expression profiling and immunohistochemistry (IHC)/fluorescent assessments of PD-L1 expression, CD8 T-cell infiltration, and broad immune infiltrate, in order to define the overlap between DDR and immune-related biomarker groups and to build a deeper understanding of how DNA damage interfaces with antitumor immunity. Methods: 39 patients were enrolled in OPHELIA phase II trial in which pts were randomized 3:3:3:1 to Cisplatin (C) 60 mg/m2 on d1 followed by Olaparib (O) 75mg d 1-5 (Arm A), O 300 mg bid for 21-28 days (Arm B), no treatment (ARM C) or D 1500 mg on d1 followed by O 600 mg daily for 21-28 days (Arm D). PD-L1, STING, Ki67 and γ-H2AX were assessed using quantitative immunofluorescence (QIF). The GeneXpert (GX) closed system real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used for quantitative assessment of CD274 (PD-L1), PDCD1LG2 (PD-L2), CD8A, and IRF1 multiplex mRNA panel in pre- and post-treatment samples. Results: Ki67 was decreased in 23 out of 29 (79.3%) available samples when assessed by QIF; 13 / 23 had a decrease of at least 25%. Δγ-H2AX did not differ among treatment groups. A significant increase was observed in PD-L1 and PD-L2 mRNA levels after treatment with D-O (p = 0.023 and p = 0.016, respectively). An increase trend in posttreatment CD8A mRNA was observed in 23 out of 29 cases in the three treatment arms (p = 0.21, ARM A; p = 0.082, ARM B; p = 0.16, ARM D). IRF1 mRNA and STING protein levels were not upregulated after olaparib- based treatment in the available paired treatment samples. Conclusions: This window study demonstrated a significant upregulation of PD-L1 mRNA, corresponding to our previous data of increased Combined Positive Score (CPS) in the D-O arm post-treatment. Our findings suggest that addition of D to O leads to PD-L1 upregulation. Dual blockade of PARP and PD-1 can boost immune response and antitumor activity in HNSCC. Clinical trial information: NCT02882308.
The SINTART 1 study: A phase II trial of induction chemotherapy (IC), surgery, photon-, proton-and carbon ion-based radiotherapy (RT) integration in locally advanced operable sinonasal epithelial tumors patients (pts).
Authors: Resteghini Carlo , Castelnuovo Paolo , Nicolai Piero , Orlandi Ester , Bossi Paolo , Vischioni Barbara , Schreiber Alberto , Iacovelli Nicola Alessandro , Battaglia Paolo , Mattavelli Davide , Facchinetti Nadia , Gambazza Simone , Calareso Giuseppina , Ravanelli Marco , Facco Carla , Tartaro Tiziana , Sponghini Andrea Pietro , Pagella Fabio , Mariani Luigi , Licitra Lisa F. 
Published: June 2021

6066 Background: Sinonasal epithelial tumors are rare diseases with several histotypes and poor prognosis. Multimodal approach including surgery is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment - IC, surgery and RT - modulated by histology, molecular profile and response to IC. Methods: Pts with untreated, operable squamous cell carcinoma (SCC), p53 wild type intestinal type adenocarcinoma (ITAC), sinonasal undifferentiated and neuroendocrine carcinoma (SNUC, SNEC) were enrolled in a single-arm, phase II, multicenter clinical trial from 2014 to 2018. Pts was treated with up to 5 IC cycles, whose regimen was selected according to histotype, followed either by curative radio-chemotherapy (CRT) (pts with ≥80% reduction of initial tumor volume (TV)) or surgery and adjuvant (C)RT. Photon and/or proton/carbon ion-based RT was employed according to disease site and stage. Primary endpoint was 5 years PFS, secondary endpoints were OS, IC ORR per RECIST 1.1 and safety. Results: Out of 39 enrolled pts, 35 pts were evaluable for primary endpoint. Two pts were only considered for safety analyses because definitive diagnosis on surgical specimen did not meet the study entry criteria; other two pts were screening failure due to inoperable disease. Five-year PFS was 38% (95% CI, 21 – 69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28 – 75), with a median OS of 36 months. Responses to IC are reported in table. Globally, 15 pts avoided surgery. Overall treatment safety was in line with multimodality intensive head and neck cancer treatments (5% of pts with G3-4 adverse event during IC). One sudden cardiac death was recorded. At a median follow up of 27 months, 5 G3-4 RT related late adverse events have been recorded (1 G3 neurotoxicity, 2 G3 hearing impairment, 2 G3 xerostomia). Three-year PFS - OS for pts achieving PR/CR vs SD/PD to IC were 49.8% - 56.7% vs 43.2% - 53%, respectively. Conclusions: Treatment of advanced SNC with histology-driven IC followed by locoregional therapy tailored to response to IC was safe and showed survival rate similar to surgery containing case series. In the first prospective study, a surgery sparing multimodal approach proved feasible and effective in IC responsive pts. Clinical trial information: NCT02099175. [Table: see text]
Association of state Medicaid income eligibility limits and long-term survival after cancer diagnosis in the United States.
Authors: Zhao Jingxuan , Han Xuesong , Nogueira Leticia , Jemal Ahmedin , Yabroff Robin Robin 
Published: June 2021

6512 Background: Income eligibility limits for Medicaid, the health insurance programs for low-income populations in the United States, vary substantially by state for the non-elderly population. This study examined associations between state Medicaid income eligibility limits and long-term survival among newly diagnosed cancer patients. Methods: 1,426,657 adults aged 18-64 years newly diagnosed with 17 common cancers between 2010 to 2013 were identified from the National Cancer Database. States’ Medicaid income eligibility limits were categorized as < = 50%, 51%-137%, and > = 138% of Federal Poverty Level (FPL). Survival time was measured from diagnosis date through December 31, 2017, for up to 8 years of follow-up. Multivariable Cox proportional hazard models with age as time scale were used to assess associations of eligibility limits and stage-specific survival, controlling for age group, sex, race/ethnicity, metropolitan statistical area, number of health conditions other than cancer, year of diagnosis, facility type, and the random effect of state of residence. Results: Among newly diagnosed cancer patients aged 18-64 years, 22.0%, 43.5%, and 34.5% resided in states with Medicaid income eligibility limits ≤50%, 51%-137%, and ≥138% FPL, respectively. Compared to patients living in states with Medicaid income eligibility limits ≥138% FPL, patients living in states with Medicaid income eligibility limits ≤50% and 51-137% FPL were more likely to have worse survival for most cancers in both early and late stage. The highest hazard ratios (HRs) were observed among patients living in states eligibility limits ≤50% FPL (p trend < 0.05). For example, for early stage female breast cancer patients, the HRs were 1.31 (95% confidence interval [95% CI]: 1.18 – 1.46) and 1.17 (95% CI: 1.06 – 1.30) for patients living in states with Medicaid income eligibility limits ≤50% and 51%-137% compared to those living in states with Medicaid income eligibility limits ≥138% FPL. Conclusions: Lower Medicaid income eligibility limits were associated with worse long-term survival within stage, with variation below the Medicaid eligibility threshold as part of the Affordable Care Act. States that have not expanded Medicaid income eligibility limits should expand them to help improve survival among cancer patients.
National Cancer Institute (NCI) implementation of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) broadening clinical trials eligibility criteria.
Authors: Denicoff Andrea M. , Ivy S. Percy , Worthington Katherine H. , Zhao Jinxiu , Seibel Nita , Mishkin Grace E. , Mooney Margaret M. , Little Richard F. 
Published: June 2021

6518 Background: The 2017 ASCO/Friends eligibility criteria guidelines recommend inclusiveness to promote generalizable trial results and clear rationale for necessary exclusion. These guidelines focused on brain metastases, minimum age for enrollment, HIV infection, and organ dysfunction and prior and concurrent malignancies. In September 2018, the NCI Cancer Therapy Evaluation Program (CTEP) implemented modernized protocol template language to operationalize these criteria. We evaluated utilization of the new language among CTEP-sponsored treatment trials. Methods: We evaluated protocols first approved by CTEP between 11/01/2018 and 4/30/2020. The most recent approved protocol version was evaluated for consistency with the new template language for brain metastases, HIV infection, prior or concurrent malignancies, minimum age, and cardiac, liver and kidney function. If a particular criterion was not relevant for a trial, it was not included in the analysis. We did not score age in pediatric or adult-specific trials (e.g. prostate). Results: 122 trials (71% early and 29% late phase) were identified and included in the analysis. Compliance with the new criteria language ranged from a high of 87.7% for liver function to a low of 11.5% for “new or progressive brain metastases” (table). Modernized criteria language was lacking in nearly 46% of trials in the use of concurrent or prior malignancy criteria and 31% of trials for the cardiac criteria. Of the 87 trials for non-localized disease or non-brain tumor trials, 64.4% did not address brain metastases, leaving it to investigator discretion. Thus, 75.9% of trials could theoretically enroll patients with brain metastases. Only 6 trials were considered relevant for patients < 18 years old; 50% were consistent with the age criterion (not shown in table). Conclusions: Implementing ASCO/Friends eligibility criteria requires focused reviews during protocol development to ensure compliance. CTEP is using these findings to continue to improve its protocol review processes to broaden eligibility in clinical trials. Maximizing opportunities for diverse populations to participate in trials is a priority for the National Cancer Institute and CTEP will continue efforts to achieve this goal.[Table: see text]
Social determinants of health, genetic ancestry, and mortality in ECOG-ACRIN E5103.
Authors: Obeng-Gyasi Samilia , O'Neill Anne M. , Miller Kathy , Schneider Bryan P. , Partridge Ann H. , Timsina Lava R , Sledge George W. , Wagner Lynne I. , Carlos Ruth 
Published: June 2021

6527 Background: Social determinants of health (SDH) and genetic ancestry have been independently implicated in breast cancer presentation, treatment and mortality. However, little is known about the relationship between SDH and genetic ancestry on clinical trial outcomes. The objective of this study is to assess the association between SDH, genetic ancestry and clinical outcomes in patients enrolled in an adjuvant breast cancer clinical trial. Methods: ECOG-ACRIN (EA) 5103 randomized patients to receive AC + taxane + bevacizumab or placebo. SDH were operationalized as insurance status at trial registration (individual SES) and neighborhood socioeconomic status (nSES). Insurance categories included: (1) Private, 2) Medicare including private/Medicare, military, 3) Medicaid including Medicaid/Medicare, uninsured, 4) self-pay). The nSES index was calculated using zip codes linked to county level data on occupation, income, poverty, wealth, education and crowding. Genome-wide single-nucleotide polymorphism arrays were used to define African ancestry (AA), European ancestry (EA) and other (OA). Multivariable regression and Cox-Proportional Hazard models (odds ratios (OR) and hazard ratios (HR) with corresponding 95% confidence intervals (CI)) were used to assess associations with chemotherapy completion and overall mortality. Estimates were adjusted for the following clinical covariates: age, tumor size, nodal status, hormone receptor status, and primary surgery at randomization. Results: The study cohort included 2453 EA (79.2%), 381 AA (12.2%) and 265 OA (8.6%). Medicaid patients (OR 0.76(0.59-0.99); ref private) and those with AA (OR 0.62(0.49-0.78); ref EA) were less likely to complete chemotherapy. Regarding overall mortality, Medicaid insurance (HR 1.42(1.05-1.92) was associated with a higher mortality than private insurance. Conversely, there was no significant difference in mortality by ancestry (AA HR 1.27 (0.97-1.66); OA HR 0.90 (0.63-1.29): ref EA). Neighborhood socioeconomic status did not appear to be associated with chemotherapy completion or mortality. Conclusions: SDH reflective of individual SES, such as insurance, appear to be stronger drivers of trial completion and mortality compared to nSES among patients enrolled in E5103. Moreover, study results suggest an interplay between ancestry and individual proxies for SDH in trial completion. Nevertheless, the relationship between ancestry and lower rates of chemotherapy completion do not appear to translate into higher mortality rates among patients of AA.
Racial differences in geriatric assessment (GA) impairments, health-related quality of life (HRQOL), and body composition in older adults with gastrointestinal (GI) malignancies: Results from the Cancer and Aging Resilience Evaluation (CARE) registry.
Authors: Williams Grant Richard , Dai Chen , Foster Carson , Al-Obaidi Mustafa , Harmon Christian , Nyrop Kirsten A. , Gbolahan Olumide B. , Bhatia Smita , Giri Smith 
Published: June 2021

6537 Background: Despite recent cancer advances, racial disparities in outcomes persist. Our objective was to examine racial differences in GA impairments, HRQOL, and body composition metrics as a novel way to understand outcome disparities in older adults with GI malignancies. Methods: The CARE registry at the University of Alabama at Birmingham (UAB) is an ongoing prospective cohort study that consecutively enrolls older adults (≥60y) with GI malignancies. The CARE registry utilizes a patient-reported GA that measures a broad range of aging-related health issues. HRQOL is measured using PROMIS Global-10. Computed-Tomography (CT) images are procured to measure skeletal muscle index (SMI) and skeletal muscle density (SMD) from the L3 cross-section. For this study, we examined the adjusted odds ratio (aOR) for racial differences in GA impairments, HRQOL, sarcopenia (defined as men BMI < 25, SMI ≤43 cm2/m2; men BMI ≥25, SMI < 53 cm2/m2; women SMI < 41 cm2/m2), and myosteatosis (defined as BMI < 25, < 41 Hounsfield Units [HU]; BMI ≥25, < 33 HU), adjusting for age, sex, education, cancer type, cancer stage, and comorbidity. Results: We included 448 patients with GI malignancies, with self-reported race as White or Black, a completed GA and available CT imaging +/- 60 days of GA completion. Mean age at enrollment was 70±7.2y, 58% were male and 25% were Black. Primary cancer diagnoses included colorectal cancer (33%), pancreatic cancer (25%), and other GI malignancies (52%). Black participants had lower education (high school or < 54% vs. 38%, p< 0.01) and were less likely to be married (55% vs 71%, p< 0.01). Black participants reported more limitations in activities of daily living (aOR = 2.0 (95% confidence level [CI] 1.01-3.9, p= 0.03) and frailty (aOR = 1.9, 95% CI 1.1-3.3, p= 0.02). Similarly, Black participants reported lower HRQOL (physical: β coefficient, -2.7; p= 0.03; mental: β coefficient, -2.4; p= 0.03). Conversely, Black participants were less likely to have sarcopenia (aOR = 0.5, 95% CI 0.3-0.9, p= 0.02) and myosteatosis (aOR = 0.12, 95% CI 0.02-0.8, p= 0.02). Conclusions: Differences in frailty, HRQOL, and body composition between Black and White participants present the first step towards understanding disparities in cancer outcomes amongst older adults.
Mediators of racial disparity in the use of prostate MRI.
Authors: Leapman Michael S. , Dinan Michaela Ann , Pasha Saamir , Washington Samuel L. , Ma Xiaomei , Gross Cary Philip 
Published: June 2021

6554 Background: Evidence of racial disparity in the use of prostate MRI presents new obstacles to closing recognized gaps in treatment and outcome for black men with prostate cancer. To anticipate strategies for improving equity in cancer care, we examined mediators of racial disparity in the use of prostate MRI surrounding the diagnosis of prostate cancer. Methods: We conducted a multiple mediation analysis among patients with localized prostate cancer in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 2008 and December 2015. We assessed claims for prostate MRI within the six-month period preceding or following diagnosis. We first identified candidate clinical and sociodemographic meditators based on their association with both race and prostate MRI, including the Index of Concentrations at the Extremes (ICE), a measure of racialized residential segregation calculated at the zip code or census tract level. We used non-linear Multiple Additive Regression Trees (MART) models to estimate the direct and indirect relative effects of mediators. Results: We identified 71,597 eligible patients. Black patients with prostate cancer were less likely (5.3%) to receive a prostate MRI when compared with white patients (7.0%; unadjusted odds ratio 0.75, 95% CI 0.67-0.84, p < 0.001). 33.1% (95% CI 20.6-44.9) of the racial disparity in prostate MRI use was attributable to variation in SEER region, 22.5% (95% CI 13.0-30.2) to residence in a high poverty area, 17.2% to residential segregation (ICE group 17.2%, 95% CI 8.1-27.9%), and 13.2% to dual eligibility for Medicaid (95% CI 8.6-20.2%). Clinical and pathologic factors were not significant mediators. After accounting for the mediators, the direct effects of race accounted for 6.2% of the observed disparity in prostate MRI use. Conclusions: Sociodemographic factors including geographic region, and area-level measures of income and residential segregation explain the majority of the observed racial disparity in the use of prostate MRI among older Americans with prostate cancer. The findings underscore that measurable structural factors can be readily identified that underlie racial disparity in access to emerging diagnostic tools for patients with cancer.
Comprehensive or specialty-specific cancer care in the United States: A story of continuing underperformance.
Authors: Aquina Christopher Thomas , Becerra Adan Z. , Ejaz Aslam , Monson John R.T. , Fleming Fergal J. 
Published: June 2021

6577 Background: “Textbook oncologic outcome” (TOO) is a composite measure representing the “ideal” outcome for patients undergoing cancer surgery and is associated with improved survival. Using TOO as the primary outcome, we asked whether hospitals are high-performing across multiple cancer types. Methods: Patients undergoing potentially curative breast, colon, rectal, lung, or pancreatic cancer resection were identified within the National Cancer Database (2010-2016). Organ-specific TOO was defined as: adequate lymph node yield, R0 resection, non-length of stay outlier, no hospital readmission, no 90-day postoperative mortality, and receipt of guideline-concordant chemotherapy and/or radiation. Mixed-effects analyses estimated the risk-adjusted TOO rate for each hospital stratified by cancer type. Results: Among 1,094,550 cancer resections (breast = 690,442; colon = 213,918; lung = 121,771; rectum = 40,315; pancreas = 28,104), 434 hospitals performed ≥10 resections for each cancer type. Only 11 hospitals (2.5%) ranked in the top quartile for adjusted TOO rate for all five cancer types. Of the 323 hospitals (74.4%) that ranked in the top quartile for one cancer type, 149 hospitals (46.1%) also ranked in the bottom quartile for another cancer type. There was a weak correlation between hospital rankings across cancer types with the strongest correlations between colon and rectal cancer (R2= 0.148) and lung and pancreatic cancer (R2= 0.098). Conclusions: Most U.S. hospitals do not provide high-quality care across cancer types with respect to TOO. Perhaps this knowledge should be used to guide referral for oncology care.