bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR blockade leads to singular oncogene-addiction in ETV6-NTRK3 transformed human epithelial cells and hypersensitization to entrectinib.
Authors: Kannan Nagarajan , Kalthur Guruprasad , Aalam Musheer , Viringipurampeer Ishaq , Emperumal Chitra Priya , Beer Philip A , Sadanandam Anguraj , Garcia Joaquin J. , Janus Jeffrey R. 
Published: June 2021

e18055 Background: Entrectinib, a TRK kinase inhibitor, has been approved for the treatment of tissue agnostic rare tumors positive for TRK fusions. A very low frequency molecular subset of TRK fusion tumors dubbed as secretory carcinoma (SC) are characterized by organ-agnostic epithelial origin, ETV6-NTRK3 (EN) fusion and distinguishable secretory-type tumor cells. These tumors have been frequently miscategorized as acinic cell carcinoma or adenocarcinoma. A previous mouse study identified EGF dependent epithelial progenitors as putative cell-of-origin for SC. Methods: To test the role of EGFR signaling in EN mediated transformation and therapy resistance, we expressed EN, kinase-dead EN-K380M, and drug-resistant EN-G623R in human epithelial MCF10A cells with EGF-dependent primitive function and investigated their ability to grow in the presence and absence of EGF and/or entrectinib. To understand the significance of findings based on our model, we analyzed a total of 22 ‘rare’ patients from Mayo Clinic Tissue Registry and analyzed TCGA PanCan datasets. Results: We report herein that EGF signaling is essential for normal growth but dispensable during EN driven transformation. Our findings suggest that levels equivalent to circulating EGF (0.5-1ng/ml) is sufficient to drive 100% resistance to entrectinib in vitro. Three different strategies to blockade EGF/EGFR axis including depletion of EGF in culture system, genetic depletion of EGFR using shRNA as well as cetuximab antibody-based EGFR neutralization potentiated oncogene-addiction and hypersensitivity to entrectinib in our models. As predicted, models with G623R mutation in EN was refractory to entrectinib under all experimental conditions. Further omics analysis of TCGA PanCan suggested that EN and EGFR mutations are mutually exclusive and entrectinib-resistant G623R mutation were uncommon. Interestingly, nearly all EN tumors from Mayo Clinic Tissue Registry immunostained weakly or strongly for EGFR and showed perfect concordance with pEGFR suggesting pathway activation. Conclusions: Together, these findings raise an important question whether blockade of ‘wildtype’ EGFR signaling could improve medical intervention in SC patients presenting with wildtype EGFR and no drug-resistant mutation in entrectinib, by improving oncogene-addiction and attendant hypersensitization of transformed cells to entrectinib.
Pediatric cancer communication in Guatemala.
Authors: Graetz Dylan E. , Rivas Silvia Elena , Wang Huiqi , Vedaraju Yuvanesh , Devidas Meenakshi , Fuentes Ana Lucia , Caceres-Serrano Annie , Antillon-Klussmann Federico , Metzger Monika , Rodriguez-Galindo Carlos , Mack Jennifer W. 
Published: June 2021

e18508 Background: Effective diagnostic communication is a cornerstone of cancer care. While > 90% of children with cancer live in low- and middle-income countries, little is known about patients’ and families’ communication priorities and experiences. We examined parent priorities for communication and the quality of information-exchange and decision-making during diagnostic communication in Guatemala. Methods: This study was conducted at Unidad Nacional de Oncologia Pediatrica. A cross-sectional survey was verbally administered in Spanish to 100 parents of children with cancer within 8 weeks of diagnosis. The survey included items utilized in pediatric communication studies from high-income countries and novel questions developed specifically for the study population. Results: Guatemalan parents prioritized communication functions including information exchange (99%), fostering healing relationships (98%), decision-making (97%), enabling self-management (96%) and managing uncertainty (94%) over functions such as responding to emotions (66%) and cultural awareness (48%). Almost all Guatemalan parents (96%) wanted as many details as possible about their child’s cancer. However, only 67% reported that they were always given the information they needed without asking for it, and most said they sometimes (56%) or always (18%) had questions they wanted to discuss with the doctor but did not. Half of parents (54%) correctly identified their child’s diagnosis, primary site, extent of disease (localized versus metastatic), length of proposed treatment, and treatment intent (curative versus palliative). Parents of children diagnosed with leukemia were more likely to understand all pieces of information than those whose children had solid tumors (p < 0.001). Most parents (76%) preferred to share in decision-making with oncologists. Two-thirds of parents (65%) held their preferred role in decision-making, with fathers more likely to hold their preferred role than mothers (p = 0.02). Reflecting on decisions they had made, 94% of parents strongly agreed they had made the right decisions. However, 17% of parents endorsed feeling that their choices had caused their children harm. Conclusions: Similar to findings from the United States, parents in Guatemala prioritize many aspects of diagnostic communication, especially information exchange, development of healing relationships, and decision-making. Nonetheless, many parents report challenges in information exchange and decision-making, suggesting a need for interventions to support communication processes.
Healthcare access disparity among U.S. cancer population and evaluation of social determinants of health using NHANES data for 2013-18.
Authors: Wahab Ahsan , Rafae Abdul , Mushtaq Kamran , Masood Adeel , Ehsan Hamid , Khakwani Maria , Khan Aqsa , Khakwani Muhammad Shahzeb Khan , Haider Mobeen Zaka , Mushtaq Muhammad Umair 
Published: June 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]
Change in facility-level share of Medicaid patients with cancer following implementation of the affordable care act.
Authors: Buck Matthew , Demkowicz Patrick C , Nie James , Marks Victoria A. , Salazar Michelle C. , Kenney Patrick Aloysius , Boffa Daniel J. , Leapman Michael S. 
Published: June 2021

e18543 Background: Although Medicaid expansions associated with the Affordable Care Act (ACA) significantly increased insurance coverage for Americans with cancer, there is evidence that some facilities limit the number of Medicaid patients they treat due to lower reimbursement. We aimed to assess facility-level changes in the proportion of patients with Medicaid who were diagnosed with cancer in relation to Medicaid expansions associated with the ACA. Methods: We identified adult patients with the 19 most commonly diagnosed cancers using the National Cancer Database who were diagnosed with cancer from 2010 through 2017. We clustered Commission on Cancer (CoC) accredited institutions and included those diagnosing at least 10 patients in each year. The primary study endpoint was the change in the proportion of Medicaid-insured individuals relative to the implementation of the ACA (pre- and post-Jan 1, 2014). We used adjusted difference-in-differences (DID) estimation and multivariable logistic regression to examine patient and facility-level factors associated with changes in the proportion of Medicaid insured individuals. Results: We identified 1,064 eligible facilities in the study period. There were considerable changes in the share of Medicaid insured patients at the facility-level (range -20.0% to +44.7%, IQR -0.64% to +5.63%). There were significantly larger changes in facilities located in Medicaid expansion states (11.5 to 16.5% percentage points) versus non-expansion states (9.2 to 8.9% percentage points) with adjusted DID +5.79% (p < 0.001). Despite overall increases, 14.6% of facilities in expansion states experienced reductions in their share of Medicaid insured patients. Facility factors associated with decreasing share of Medicaid patients were non-expansion status (OR: 6.25, 95% CI 3.89 – 9.98, p < 0.001) and higher baseline Medicaid population (OR: 2.93, 95% CI 2.00 – 4.35, p < 0.001). There was also significant regional variation with larger decreases in the West South Central (OR: 5.86, 95% CI 2.30 – 15.74, p < 0.001) and West North Central (OR: 2.46, 95% CI 1.07 – 5.87, p = 0.037) regions. Conclusions: Although state expansions associated with the ACA led to increases in the share of Medicaid-insured patients diagnosed with cancer at CoC facilities, there was considerable variation in changes at the facility-level. These findings highlight that improved insurance coverage may not be sufficient to improve access to care, and facility-level policies may remain a source of access disparity.
Concrete case: An opportunity to improve cervical cancer prevention—Primary and secondary prevention of cervical cancer in patients with cervical cancer and their families.
Authors: Telles O Lima Jurema , Azevedo Carla Rameri Alexandre Silva De , Lima Candice Lima , Katz Leticia , Sales Mozart j t , Pinto Rodrigo alves , Andrade Gabriela Arruda de , Keller Fernanda Araújo , Santos Paula Marina Carneiro , Soares Igor Gouveia , Moura Beatriz Vieira , Coutinho Ana Luísa Lopes Marques , Mello Maria Julia Gonçalves 
Published: June 2021

e18571 Background: cervical cancer (CC) reveals regional and social inequalities and should be understood not only as an oncological indicator, but essentially as an indicator of social vulnerability and health care needs.CC is the second most incident and the most deadly among women from the Northeast’S Brazil and the third most incident in Brazil Although the HPV vaccine coverage and the Pap smear test are available through the Brazilian public health system, the coverage of the target population is low. objective: Verify the conditions of access/use of the health system by women with cervical cancer (CC) and their families. Methods: Cross-sectional study involving cancer patients admitted to IMIP between 2016 and 2019. The variable data were related to the sociodemographic profile, preventive examination, Human Papillomavirus (HPV) and the influence of the diagnosis of CC on the search for preventive and screening measures by women's family members. Results: Out of the 285 participants,between 9-21 years old and 101 between 25-69 years old. Of the patients studied,55,8% lives urban area. It has a higher performance of biopsies in the public sector (59,5%). The sociodemographic analysis highlights the non-white race (78,2%) and only 6,8% with complete high school. The knowledge about performing the Pap smear reached 88,9% and the disinformation about the HPV reached 44,4%.the school was the largest source of information about the HPV vaccine (30,6%). Related to the influence of cancer, 62,2% said that young family members underwent HPV vaccination and 82,2% related their diagnosis to search for preventive in family members over 25 years old. a much higher percentage than vaccination coverage and preventive exam in the study region report that the diagnosis of cancer influenced the decision to vaccinate (42%) and update the pap test (69%). about 30% of patients had never taken the pap test. the early start (15 - 19y) of the pap test was not significant for the periodic performance of the pap test. 46% reported the lack of information about the importance of the exam as a reason for not performing it and 34% reported fear. conclusion :Strengthening educational activities and offering vaccines against HPV and Pap smears in the diagnosis of a case of cervical cancer can be an opportunity to expand the coverage of preventive measures more effectively among people close to the patient and her community, which cannot be missed. The school was an important source of information about the HPV vaccine and should be directly involved in this fight.Reducing an inequality cycle.
Non-fatal self-injury after a diagnosis of cancer: A population-based study.
Authors: Noel Christopher , Eskander Antoine , Sutradhar Rinku , Mahar Alyson , Vigod Simone , Isenberg-Grzeda Elie , Bolton James , Deleemans Julie , Chan Wing , Zuk Victoria , Haas Barbara , Mason Stephanie , Coburn Natalie G. , Hallet Julie ,   Enhanced Supportive Psycho-oncology Canadian Care (ESPOC) Group
Published: June 2021

e18577 Background: Psychological distress is a key construct of patient-centred cancer care. While an increased risk of suicide for cancer patients has been reported, more frequent consequences of distress after a cancer diagnosis, such as non-fatal self-injury (NFSI), remain largely unknown. We examined the risk for NFSI after a cancer diagnosis. Methods: Using linked administrative databases we identified adults diagnosed with cancer between 2007-2019. Cumulative incidence of NFSI, defined as emergency department presentation of self-injury, was computed accounting for the competing-risk of death from all causes. Factors associated with NFSI were assessed using multivariable Fine and Gray models. Results: Of 806,910 included patients, 2,482 had NFSI and 182 died by suicide. 5-year cumulative incidence of NFSI was 0.27% [95%CI 0.25-0.28%]. After adjusting for key confounders, prior severe psychiatric illness whether requiring inpatient care (sub-distribution hazard ratio (sHR) 12.6, [95% CI 10.5-15.2]) or outpatient care (sHR 7.5, 95% CI 6.48-8.84), and prior self-injury (sHR 6.6 [95% CI 5.5-8.0]) were associated with increased risk of NFSI. Young adults (age 18-39) had the highest NFSI rates, relative to individuals >70 (sHR 5.4, [95% CI 4.5-6.5]). The magnitude of association between prior severe psychiatric illness and NFSI was greatest for young adults (interaction term p < 0.01). Certain cancer subsites were also at increased risk, including head and neck (sHR1.52, [95%CI 1.19-1.93]). Conclusions: Patients with cancer have higher incidence of NFSI than suicide after diagnosis. Younger age, prior severe psychiatric illness, and prior self-injury were independently associated with NFSI. These exposures act synergistically, placing young adults with a prior mental health history at greatest risk for NFSI events. Those factors should be used to identify at-risk patients for psycho-social assessment and intervention.
Patient-reported outcomes predicting non-fatal self-injury after a cancer diagnosis: A population-based case-control study.
Authors: Hallet Julie , Sutradhar Rinku , Isenberg-Grzeda Elie , Noel Christopher , Mahar Alyson , Vigod Simone , Bolton James , Deleemans Julie , Chan Wing , Zuk Victoria , Coburn Natalie G. , Eskander Antoine 
Published: June 2021

e18583 Background: Psychological distress is key in cancer care. Non-fatal self-injury (NFSI) represents a patient-centred, objectively measured manifestation of the greatest level of distress occurring in 3 out of 1,000 patients after a new cancer diagnosis. How to identify patients at high risk for NFSI remains unknown. We examined the relationships between routinely collected patient-reported outcomes measures and the risk of subsequent NFSI following a cancer diagnosis. Methods: We conducted a population-based case-control study of patients with a new cancer diagnosis (2007-2019) reporting a Edmonton Symptom Assessment (ESAS) score within 36 months of diagnosis. Cases were patients with NFSI within 36 months of diagnosis and controls those without NFSI (assigned a dummy index date corresponding to the case’s NFSI). Cases and controls were matched 1:4 on time from cancer diagnosis, ESAS record in 180 days prior index, age, sex, cancer site, and history of self-injury. Multivariable conditional logistic regression assessed the association between moderate-to-severe ESAS symptoms and total ESAS (t-ESAS) score with NFSI within 180 days. Results: Of 408,858 patients reporting >1 ESAS within 36 months of cancer diagnosis, 748 patients had a NFSI, including 425 patients with an ESAS score within 180 days preceding the NFSI event. Of those 406 cases were matched to 1,624 controls without NFSI. Cases reported a higher proportion of moderate-to-severe symptoms and higher t-ESAS than controls prior to the event (p < 0.01 for all). After adjusting for psychiatric illness history and cancer therapy received, reporting of moderate-to-severe anxiety (odds ratio – OR 1.61, 95%CI 1.14-2.27), depression (OR 1.66, 95%CI 1.2-2.31), and shortness of breath (OR 1.65, 955CI 1.18-2.31) were independently associated with higher risk of NFSI within 180 days. Each 10-point increase in t-ESAS (score 0-90) was independently associated with increased risk of NFSI within 180 days (OR 1.51; 95%CI 1.40-1.63). Conclusions: Reporting moderate-to-severe anxiety, depression, and shortness of breath, and increasing t-ESAS after cancer diagnosis are associated with higher odds of NFSI in the following 180 days. These data support the prospective identification of patients at high risk for NFSI via routine ESAS screening to improve supportive care. Patients with at-risk ESAS scores should receive tailored assessment, management, and longitudinal follow-up.
Bone modifying agents and skeletal related events in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.
Authors: Das Parthib , Zhao Songzhu , Wei Lai , Miah Abdul , Li Mingjia , Lopez Gabrielle , Patel Sandip H. , Johns Andrew , Grogan Madison , Bertino Erin Marie , He Kai , Shields Peter G. , Carbone David Paul , Otterson Gregory Alan , Presley Carolyn J , Owen Dwight Hall 
Published: June 2021

e18593 Background: Bone metastases and skeletal related events (SREs) are a common cause of morbidity among patients with metastatic non-small cell lung cancer (mNSCLC). SREs include pathologic bone fractures, spinal cord compression, orthopedic surgery/stabilization, and palliative radiation to bone. Bone modifying agents (BMA) such as bisphosphonates and RANK ligand inhibitors are often used for mNSCLC patients with bone metastases to reduce the incidence of SRE. Data on the associations between BMA use and overall survival (OS) and the development of SRE among patients with mNSCLC treated with immune checkpoint inhibitors (ICI) is limited. Methods: We conducted a retrospective study of patients with mNSCLC treated with first line pembrolizumab or pembrolizumab plus chemotherapy at The Ohio State University from 2017-2020. The associations between SRE and categorical variables were studied using Fisher’s exact test and with continuous variables using the Kruskal-Wallis test. The association between BMA and risk of osseous progression was studied using Fisher’s exact test. The association between BMA and OS was examined using a Cox proportional hazard model. Median OS was estimated using the Kaplan-Meier method with 95% CI. OS was calculated from date of ICI initiation to death from any cause or last follow up. Results: We identified a cohort of 228 patients: 107 (47%) treated with pembrolizumab and 121 (53%) treated with pembrolizumab plus chemotherapy; 48 (21%) had squamous histology and 179 (79%) had nonsquamous histology (1 had NSCLC histology not specified); median age 62.6 years; median OS was 26.8 months (95% CI: 17.2 – 34.5 months). A total of 95/228 (42%) patients had bone metastases at time of ICI initiation; 45/95 (42%) had treatment with BMA and 50/95 (58%) were not treated with BMA. Among patients with bone metastases at time of ICI, 45 (42%) developed SRE after ICI initiation and BMA use was not associated with risk of SRE (p = 1). BMA use was not significantly associated with risk of osseous progression (p = 0.21). For patients with baseline bone metastases prior to ICI, the use of BMA was not associated with OS (p = 0.24); the type of BMA used (bisphosphonate vs RANK ligand inhibitor) was also not associated with OS (p = 0.13). Conclusions: In patients with metastatic NSCLC treated with first line pembrolizumab alone or with chemotherapy, bone modifying agents were not associated with OS, decreased risk of osseous progression, or development of SRE in patients with baseline bone metastases prior to ICI initiation. The type of BMA used was also not associated with survival. Further studies evaluating the utility and impact of BMA use in this patient population are needed.
A cross-sectional analysis of muscle density and physical function in head and neck cancer patients.
Authors: Shaver Amy L. , Ray Andrew , Platek Mary Elizabeth , Singh Anurag K. , Erickson Kayleigh , Wendel Elizabeth , Wilding Gregory , Ochs-Balcom Heather , Noyes Katia 
Published: June 2021

e18597 Background: Head and neck cancer (HNC) is a debilitating disease that affects tens of thousands each year and both the disease and its treatment can cause long-term morbidity. HNC patients with greater physical function at baseline may better withstand both disease and treatment, therefore we hypothesized that baseline physical function is associated with baseline skeletal muscle density (SMD). Methods: A cross-sectional study of existing medical records was conducted. SMD was classified using pre-treatment PET-CT scans and interpreted using Sliceomatic software, and pre-treatment physical function assessed in three ways: hand grip strength, timed up and go, and short physical performance battery. Linear regression models were utilized to assess the association between SMD and each measure of physical function, with adjustment for muscle mass, sex and cancer stage in the hand grip strength model and adjustment for muscle mass and age in both the timed up and go, and short physical performance battery models. Results: The sample of 90 HNC patients, was mostly white, male, former smokers with an average BMI of 28 kg/m2. In adjusted models that included men only, we observed that for every Hounsfield unit increase in SMD there was a 0.08 increase in SPPB score (p=0.005), a 0.31 kg increase in hand grip strength (p=0.04), and a 0.13 second decrease in timed up and go (p=0.0007). In adjusted models that included women only, we observed that for every Hounsfield unit increase in SMD there was a 0.03 decrease in SPPB score (p=0.75), a 0.12 kg increase in hand grip strength (p=0.65), and a 0.01 second increase in timed up and go (p=0.84). Conclusions: Baseline physical function is associated with higher baseline physical SMD. Larger studies involving a more women are needed to replicate these findings and to further examine the potential role of effect modification by both sex and muscle mass.