tbuckley/cabot-search huggingface dataset:
Efficacy of a clinical risk prediction tool to prioritize outreach for high-risk cancer patients.
Authors: Megan Croyle, Nathan Handley, Michael Li, Adam F Binder, Valerie Pracilio Csik
Journal: Journal of Clinical Oncology (2021)

e13524 Background: Acute care utilization (ACU), including emergency department visits and hospitalizations, is common in patients with cancer. Prospectively identifying patients’ risk status may enable interventions to reduce ACU. We developed a REDUCE score (Reducing ED Utilization in the Cancer Experience for active oncology patients (defined as patients with an active cancer diagnosis in the last 12 months who had a Medical Oncology encounter in a 180-day period) to prospectively determine risk of ACU. The intended intervention was outreach to all high-risk patients. We evaluated the high risk group over an 11-month period (February through December 2020) to better characterize those who received outreach. Methods: Analysis of high-risk patients was conducted using a case-control method over two periods: February through June 2020 (Period 1) and July through December 2020 (Period 2) to account for a change in the type of outreach deployed. High risk was defined as REDUCE ≥2. High risk scores were stratified by those with REDUCE =2 and those with REDUCE &gt;2. Control Group 1 consisted of high-risk patients with REDUCE =2 who did not receive outreach, and Control Group 2 included high-risk patients with REDUCE &gt;2 who did not receive outreach. Case Group 1 consisted of high-risk patients with REDUCE =2 who had outreach, and Case Group 2 included patients with REDUCE &gt;2 who had outreach. Average ACU per patient was compared across all groups over both periods. Descriptive statistics were applied. Results: Results are described in table 1. Average ACU per patient was higher in Periods 1 and 2 for both Case Groups, compared to both Control Groups. Over time, there was a trend in decreased ACU in the intervention group with stable to increasing ACU in the control groups. The proportion of patients who received outreach across both periods decreased in Case Group 1, but increased in Case Group 2. Conclusions: These findings suggest that patients who received outreach were at a higher risk of ACU. Further investigation revealed that there was not consistent prioritization of patients with the highest risk scores within the high-risk group for outreach. In addition to the REDUCE , ongoing efforts incorporate clinical judgment of the outreach team in assessing additional clinical risk factors to determine an intervention, which is meaningful. The REDUCE tool may provide value as an initial screening mechanism. Average ACU per patient by study group.[Table: see text]
Clinical efficacy and safety of proton beam or photon radiation in combination with immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.
Authors: Chung Wei Su, Pei-Wei Huang, Yung-Chih Chou, Chen-Chun Lin, Ji-Hong Hong, Ming-Mo Hou
Journal: Journal of Clinical Oncology (2021)

e16113 Background: Management of advanced hepatocellular carcinoma (HCC) remains a challenge. IMbrave150, a pivotal trial reported impressive overall survival benefit using combination strategy of atezolizumab and bevacizumab compared to sorafenib. We wonder the efficacy and safety when combining radiotherapy with immune checkpoint inhibitors (ICIs), which radiation might provide better local treatment and possible trigger abscopal effect. The aim of this study is retrospectively reporting the real-world efficacy and tolerability of proton beam or photon radiation plus ICIs in patients with advance stage HCC. Methods: We retrospectively reviewed all BCLC stage C HCC patients who have received combination therapy with ICIs plus proton or photon therapy with well documented basic characteristics and prompt treatment efficacy evaluation between 1st of January 2016 to 31st of October 2019 at a single medical center in Taiwan. 20 patients had ICIs plus proton and 32 patients had ICIs plus photon were included for analysis. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier estimator. Results: Baseline characteristics were generally similar between ICIs plus proton or ICIs plus photon, while most patients in proton group did not receive prior systemic treatment and had less local therapies prior ICIs combine with radiotherapy. Median follow-up time was 10.7 months. The median Progression free survival (PFS) was not reached in ICIs plus proton group and 3.6 months (95% CI 2.7-4.6) in ICIs plus photon group (P = 0.007). The median OS was not reach in ICIs plus proton group and 12.1months (95% CI 6.4-17.7) in ICIs plus photon group (P = 0.007). Comparing ICIs plus proton group versus photon group, objective tumor response is 50% versus 9%, disease control rate is 80% versus 47% in each group. During follow-up, 7 patients (35%) in proton group achieved complete remission (CR). There was difference in radiation filed, 19 patients (95%) in proton group and 15 patients (47%) in photon group targeted on liver tumors, and more patient received &gt; 50Gy treatment dose in proton group compared to photon group (90% versus 20%). Proton group has lower failure rate in both inner- or out-field compared to photon group. Grade 1 to grade 2 skin-dermatological and gastrointestinal toxicity remained the most frequent reported adverse events in both groups. There are only one therapy related grade 3 dermatitis in ICIs plus proton group and one grade 3 hepatitis, one grade 5 pneumonitis in ICIs plus photon group. Conclusions: This study reported real-world efficacy and safety of ICIs in combination with proton or photon therapy. Most adverse events were manageable. The combination of ICIs and proton therapy has impressive CR rate and OS benefit. Further prospective randomized trial is warranted for confirm our finding.
Comprehensive characterization of genomic and radiologic features reveals distinct driver patterns of RTK/RAS pathway in pulmonary nodules presenting as ground-glass opacity.
Authors: Muyun Peng, Fenglei Yu, Xiaofeng Chen, Jing Bai, Xuefeng Xia, Guanlan Xing
Journal: Journal of Clinical Oncology (2021)

e20516 Background: GGO-associated pulmonary nodule has been known as radiological appearances of early stage and exhibit more indolent biological behavior. The correlation of different driver gene and radiological features remain poorly understood. Methods: We performed high-depth sequencing of 334 resected pulmonary nodules presenting as GGO from 262 Chinese patients with a custom 1021-gene panel. 130 were multiple pulmonary nodules from 58 patients (2-4 samples per patient). Clinical-pathologic and radiologic parameters of these pulmonary nodules were collected. Immunohistochemistry and multiplex immunofluorescent staining were applied to analyze proliferation and immune cell markers of GGO-associated pulmonary nodules. Results: Mixed GGO enriched in the pathology of invasive LUAD comparing to pure GGO (182/216 vs 73/118, p &lt; 0.001). 88.0% (294/334) of GGO-associated nodules carried at least one gene mutation in EGFR/ERBB2/BRAF/KRAS/MAP2K1 of the RTK/RAS signaling pathway and these driver genes were mutual exclusive to each other. T790M mutation was detected in one patient who had a nodule with CTR &gt; 0.5 and was pathologically defined as MIA. 96.4% (54/56) multiple pulmonary nodules from the same patients showed distinct oncogenic alterations, but 72.4% (42/58) patients carried at least one mutant gene in RTK/RAS pathway across each pulmonary nodule. Nodules with ERBB2/ BRAF/ MAP2K1 mutations tended to be more indolent than those with EGFR and KRAS mutations, showing fewer mutations in radiology status of mGGO or pathology of invasive LUAD. KRAS-mutant subgroup possessed the highest expression of Ki-67 and PD-L1, more infiltration of CD4+ T cell and CD8+T cell. The second highest Ki67-expression was in EGFR-mutant subgroup, together with more CD8+T cell. For EGFR-mutant nodules, co-mutations with TP53 or RBM10 enriched in nodules with CTR &gt; 0.5 and showing higher values of mean CT attenuation and TMB, which may relate to GGO evolution or invasiveness progression. Conclusions: This study elucidated a comprehensive genomic landscape of Chinese radiologically detected GGO-associated pulmonary nodules and highlighted different driver patterns of RTK/RAS pathway corresponding to radiologic features. Our findings provided valuable insight for further research on driver event of RTK/RAS pathway and cancer interception of GGO-associated pulmonary nodules.
Bundling cancer subtypes in value-based care: A pilot analysis of lymphoma episodes in the Oncology Care Model.
Authors: Andrew Yue, Basit Iqbal Chaudhry, Stephen Matthew Schleicher, Scott F. Huntington, Aaron J. Lyss, Nora Connor, Lisa Tran, Kerin B. Adelson
Journal: Journal of Clinical Oncology (2021)

e18850 Background: Value based models (VBMs) in which cancers are bundled are a growing alternative to fee for service, as in the Oncology Care Model (OCM). However, bundles in OCM may not capture the clinical granularity needed to predict resource utilization for cancer subtypes. One such bundle is lymphoma, which groups highly heterogeneous diseases with distinct treatments and differing intensity of care. Here, we compare OCM predicted episode costs (targets) to actual episode costs by lymphoma subtype. Methods: Our cohort study used OCM data from a large academic medical center (AMC) and large community oncology practice (COP). Six-month episodes of lymphoma beginning between July 2016 and June 2019 were categorized based on ICD-10 diagnoses on antineoplastic infusions and E&amp;M visits, as well as disease and data modeling. Episodes were subdivided into follicular (FL), diffuse large B (DLBCL), small B (SBCL), mantle (MCL), Hodgkin (HL), Waldenstrom macroglobulinemia (WM), mature T/NK (T/NK), and Other. The distributional consistency of episode costs and targets for each subtype relative to the rest of the episodes was evaluated by Kolmogorov-Smirnov tests. We also compared the proportion of subtypes contributing to episodes in the AMC vs. COP. Results: A total of 1801 lymphoma episodes were identified (44% in AMC, 56% in COP). The most common subtypes (DLBCL and FL) contributed a larger proportion of episodes in the COP, while less frequent subtypes (T/NK, WM) were more prevalent at the AMC. Further, episode costs are significantly different across individual subtypes. Target variance was significantly lower than cost variance across subtypes. For example, the average target for WM was $50.4K, average costs were $40.2K, with 26% of episodes over target. In contrast, the average target for T/NK was $55.9K, average costs were $72.7K, with 64% of episodes over target. Conclusions: VBMs such as OCM currently aggregate cancer types and lack clinical granularity. Our evaluation of OCM episodes at an AMC and COP found considerable differences in lymphoma populations and in costs by subtype. Failure to account for clinical features (i.e. lymphoma history) could lead to inappropriate shifts of risk from payers to providers in VBMs.[Table: see text]
Identification of cell cycle and apoptosis related gene expression by curcumin in an in vitro model for ductal carcinoma in situ
Authors: Carl V. Crawford, Michael P. Osborne, Meena Katdare
Journal: Cancer Research (2005)

4279  The amplification and/or over-expression of oncogene HER-2/neu is reported in up to 30% of Ductal Carcinoma in Situ (DCIS) lesions of breast cancer. Despite intensive management, post-operative survival and remission are challenged by dose limiting side effects of current therapies. Natural phytochemicals are known to reduce the risk of tumorignesis in a variety of solid tumors. Curcumin (diferuloylmethane) the biologically active component of the spice Turmeric (Curcuma longa Linn) possesses anti-inflammatory, anti-oxidant and anti-tumorigenic properties and has been studied vigorously as a chemopreventive agent in several cancer models. Previous work from our lab showed preventive efficacy of curcumin, due to cytostatic arrest of growth (S:G2/M phase of cell cycle), and induction of apoptosis in a murine model for breast cancer. Our aim is to determine the modification of gene expression by curcumin in a preclinical in vitro model for human DCIS using cDNA microarray technology. Immortalized normal breast epithelial cells, 184-B5, established from reduction mammoplasty lack anchorage-independent growth and are non-tumorigenic. The preclinical epithelial cell culture model for DCIS represented by transformed 184-B5/HER cells exhibits hyperproliferation, shorter population doubling time, higher saturation density, high anchorage independent growth and tumorigenicity. Normal or transformed cells were treated for 24 hours with 0 uM or 20 uM curcumin. cDNA libraries were constructed using 5ug of total RNA from cells of each group. Biotin-labeled RNA was transcribed from the cDNA libraries and hybridized to Human Genome U133A (Affymetrix) microarrays. Genesifter software was used to identify changes in gene expression of greater than five fold using a Z-score cut-off of 2. Comparison of genes expressed in transformed cells with normal cells exhibited upregulated EGFR, p53 and several MAPK related genes. In addition, increased expression in cell cycle related genes including BUB1, CDC2, 6, 20, 25C, 45L, cyclins A and B, cyclin dependent kinase 2, PLK1 and RB1 was observed. These results positively correlate with aberrant hyperproliferation of 184B5/HER cells. Exposure of curcumin to 184B5 cells showed no change in the expression of genes related with cell cycle or apoptosis indicating a non-responsive effect. On the contrary, curcumin treated 184-B5/HER showed upregulation of the apoptosis-related genes BAX and TRAF1. The downregulated genes included cyclins A and B, CDC 2, 20 and 25C and BUB1. These results indicate curcumin exerts its anti-proliferative activity by reduction of cell cycle progression in S:G2/M and by induction of apoptosis through BAX and TRAF1 related mechanisms. These effects were not observed under identical conditions in normal cells and indicate that the therapeutic potential of curcumin in breast cancer is worthy of further investigation.
Paediatric outpatient prescriptions in France between 2010 and 2019: A nationwide population-based study
Authors: Marion Taine, Lucile Offredo, Rosemary Dray-Spira, Alain Weill, Martin Chalumeau, Mahmoud Zureik
Journal: The Lancet Regional Health - Europe (2021)

Paediatric outpatient prescription (POP) monitoring is pivotal to identify inadequate prescriptions and optimize drug use. We aimed at describing recent trends in POPs in France.All reimbursed dispensations of outpatient prescribed drugs (excluding vaccines) were prospectively collected for the paediatric population (<18 years old) in the French national health database in 2010-2011 and 2018-2019 (mean 117,356,938/year). POP prevalence (proportion of children receiving ≥1 drug prescriptions/year) was calculated by age groups and compared by prevalence rate ratios (PRRs). Given the large sample size, 95% confidence intervals of POP prevalences and PRRs did not differ from estimates.Among the 14,510,023 children resident in France in 2018-2019, mean POP prevalence was 857‰ children. Most prescribed therapeutic classes were analgesics (643‰), antibiotics (405‰), nasal corticosteroids (328‰), nonsteroidal anti-inflammatory drugs (NSAIDs) (244‰), antihistamines (246‰) and systemic corticosteroids (210‰). POPs decreased with age from 976‰ for infants to 782‰ for adolescents. Children <6 years old were notably more exposed to inhaled corticosteroids (PRR=3.06), non-penicillin beta-lactam antibacterial agents (PRR=3.05) and systemic corticosteroids (PRR=2.11) than older ones. The POP prevalence was slightly higher (PRR=1.04) during 2018-2019 than 2010-2011, with marked increases for anti-emetics (PRR=1.84), vitamin D (PRR=1.49), proton pump inhibitors (PRR=1.42), systemic contraceptives (PRR=1.24) and nasal corticosteroids (PRR=1.21) and decreases for propulsive/prokinetic agents (PRR=0.09), NSAIDs (PRR=0.73) and systemic antibiotics (PRR=0.88).POP remained highly prevalent in France throughout the 2010s, especially for children <6 years old, with only a few improvements for selected therapeutic classes. These findings should prompt clinical guidance campaigns and/or regulatory policies.Internal funding.
Treatment-specific risk of second malignancies in five-year survivors of diffuse large B-cell lymphoma.
Authors: Yvonne M. Geurts, Suzanne I.M. Neppelenbroek, Cynthia So-Osman, Joost S.P. Vermaat, Dick Johan van Spronsen, Wouter J. Plattel, Roel J. de Weijer, Karijn M.S. Verschueren, Josée M. Zijlstra, Harry R. Koene, Marten R. Nijziel, Erik C. Schimmel, Lara H. Böhmer, Francisca Ong, Hein Visser, Daphne van Kampen, Marie José Kersten, Berthe M.P. Aleman, Flora Van Leeuwen, Michael Schaapveld
Journal: Journal of Clinical Oncology (2021)

12072 Background: Due to the historically less favorable prognosis of diffuse large B cell lymphoma (DLBCL), the burden of second malignant neoplasms (SMNs) has been rarely studied in DLBCL survivors. However, radiotherapy and chemotherapy may increase SMN risk among DLBCL patients. Anthracyclines may increase the risk of hematological malignancies, but it is not clear whether they also increase solid cancer risk. Methods: We established a multicenter cohort of 2,384 5-year DLBCL survivors treated at ages 15-60 years with radiotherapy and/or immuno-chemotherapy between 1989 and 2012. Observed numbers of SMNs were compared with expected cancer incidence in the general population to compute standardized incidence ratios (SIRs), absolute excess risks (AERs, per 10.000 person-years) and cumulative incidence. Treatment specific incidence was compared with general population rates and assessed within the cohort using Cox regression. Results: Most DLBCL patients received alkylating agents (95%), anthracycline-containing chemotherapy (95%) or radiotherapy (61%); 46% received rituximab. Median follow-up was 13.3 years; 17% of patients was followed ≥20 years. In total, 308 5-year survivors developed an invasive SMN (SIR 1.6; 95% confidence interval (CI), 1.4 to 1.8), translating into 56.2 excess cancers per 10.000 person-years (see Table for specific sites). In 20-year survivors of DLBCL, the SIR was 1.8 (95% CI 1.3-2.6). The 20-year cumulative incidence of any SMN was 18.7% (95% CI 16.5-21.0%). The SIR for any SMN was higher in patients &lt;40 years at first treatment (SIR ≤40 years: 2.8, SIR &gt;40 years: 1.4; p&lt;0.001). Treatment specific results will be presented at ASCO21. Conclusions: DLBCL survivors experience higher risk of SMNs than the general population. Identification of patients at increased risk could improve follow-up care.[Table: see text]
Healthcare access disparity among U.S. cancer population and evaluation of social determinants of health using NHANES data for 2013-18.
Authors: Ahsan Wahab, Abdul Rafae, Kamran Mushtaq, Adeel Masood, Hamid Ehsan, Maria Khakwani, Aqsa Khan, Muhammad Shahzeb Khan Khakwani, Mobeen Zaka Haider, Muhammad Umair Mushtaq
Journal: Journal of Clinical Oncology (2021)

e18527 Background: Ethnic minorities in US have poorer outcomes due to poor socioeconomic determinants. We evaluated association between ethnicity and insurance status among US adults with cancer who participated in National Health and Nutrition Examination survey for 2013-18. Methods: This was a cross-sectional study involving participants with history of cancer; participants with missing insurance/ethnicity information were excluded. Outcome of interest was insurance coverage in minorities vs Whites. The comparison of baseline characteristics (Table) stratified by insurance (Yes vs No) was made using Chi-square and t-tests incorporating survey procedures in SAS v. 9.4. Logistic regression was used for adjusted and unadjusted odds ratio (OR). Results: Among 29,400 participants, 1,684 had cancer. After excluding 81 participants with missing data, 1,603 were included; 5.2% were uninsured. Table summarizes characteristics of participants stratified by insurance. The uninsured individuals were 14 years younger, predominantly females, Hispanics and non-US born, and were less educated compared to the insured. Unadjusted OR of no insurance vs insurance was 4.23 (95%CI: 2.40-7.47) for Hispanics, 1.23 (95%CI: 0.64- 2.38) for Blacks and 1.50 for others (95%CI: 0.48-4.74) when compared to Whites. After adjusting for age, sex, education, US born status and routine place for medical care, OR for Hispanics, Blacks and others were 1.31 (95%CI: 0.73-2.36), 1.00 (95%CI: 0.46-2.18) and 0.86 (95%CI: 0.26-2.78), respectively. Conclusions: Poor socioeconomic indicators among US cancer population may leave them being uninsured; thereby making them vulnerable to poor outcomes in particular in the ethnic minorities including Hispanics. [Table: see text]
EPCT-21. NEXT-GENERATION SEQUENCING OF CEREBROSPINAL FLUID FOR CLINICAL MOLECULAR DIAGNOSTICS IN ADOLESCENT AND YOUNG ADULT (AYA) BRAIN TUMOR PATIENTS
Authors: Alexandra Miller, Luca Szalontay, Nancy Bouvier, Hamza Ahmed, Katherine Hill, Johnathan Rafailov, Alex Lee, Irene Rodriguez-Sanchez, Onur Yildirim, Arti Patel, Tejus Bale, Ryma Benayed, Maria Arcila, Maria Donzelli, Ira Dunkel, Stephen Gilheeney, Yasmin Khakoo, Kim Kramer, Sameer F Sait, Jeffrey Greenfield, Mark Souweidane, Sofia Haque, Audrey Mauguen, Michael Berger, Ingo Mellinghoff, Matthias Karajannis
Journal: Neuro-Oncology (2021)

Abstract Purpose Pediatric central nervous system tumors remain a leading cause of cancer-related death in children and adolescents. Safe sampling of tumor tissue for diagnostic purposes may be challenging. Subclinical detection of disease prior to clinical or imaging progression may provide opportunity for earlier intervention and ultimately improve overall survival. Additionally, our understanding of molecular evolution in response to therapy remains limited, given the rarity of serial sampling of tumor tissue. Methods We report our experience with minimally invasive molecular diagnostics using a validated next generation sequencing assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) obtained at the time of surgery, by intraventricular catheter or lumbar puncture. All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. Results We analyzed 64 CSF samples from 45 pediatric and adolescent and young adult (AYA) patients (pediatric=25; AYA=20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n=10), medulloblastoma (n=10), pineoblastoma (n=5), low grade glioma (n=4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n=4), metastatic retinoblastoma (n=4), ependymoma (n=3), and other (n=5). Somatic alterations were detected in 28/64 samples (44.4%) and in at least one sample per unique patient in 22/45 patients (48.8%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (86.3%). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course. Conclusion We identified four general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: 1) diagnosis; 2) identification of actionable alterations; 3) track response to therapy; and 4) monitoring tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population that may improve care.