tbuckley/cabot-search huggingface dataset:
Computational extraction and analysis of de-identified medical records to characterize hyperammonemia in patients with fibrolamellar carcinoma (FLC).
Authors: Travis Zack, Samantha Maisel, Allison Frances O'Neill, Michael P. La Quaglia, Michael Herman, Jennifer J. Knox, Amin Yaqubie, Alan P. Venook, Robert J. Mayer, John Dozier Gordan, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2021)

e16169 Background: Rare cancers including FLC make up 25% of adult tumors, but are difficult to study due to low incidence and incomplete case identification. FLC occurs in adolescents and young adults without liver dysfunction. Hyperammonemia has been frequently reported in FLC patients, but is poorly understood. Methods: Data from three clinical trials allowed us to establish the incidence of hyperammonemia (serum ammonia value &gt; 75 µmol/L) in FLC. In these studies, FLC patients received everolimus, estrogen deprivation therapy (EDT) with leuprolide + letrozole or everolimus + EDT (Oncologist. 2020 25(11):925-e1603), ENMD-2076 (Oncologist. 2020 25(12):e1837-e1845), or neratinib (J Clin Oncol 39, 2021 (suppl 3; abstr 310); ammonia was tested prospectively in the latter two studies. To assess impacts of cancer therapy or liver dysfunction, we studied hyperammonemia in FLC and non-FLC patients at UCSF in parallel. Using Natural Language Processing (NLP) of pathology reports and oncology notes from &gt; 2300 liver cancer patients from the last 12 years of UCSF records, we identified a cohort of patients with FLC, contrasting their laboratory data to all UCSF patients with ammonia testing for the last 10 years. We used leiden clustering and umap dimensionality reduction to contrast FLC and other patients to assess the clinical context of hyperammonemia. Results: Data from the 3 trials showed hyperammonemia in 10 of 32 (31.3%) FLC patients during study participation, independent of the therapy received. These patients exhibited hyperammonemia with varying levels, and at different points in their treatment. NLP identified 37 patients with FLC ( &lt; 0.1% of liver cancer patients), with 33% showing hyperammonemia. Across all UCSF patients, we found 24,000 independent visits where ammonia was tested, with &gt; 2400 demonstrating hyperammonemia. Using leidan clustering on all encounters with ammonia &gt; 75 µmol/L, we found distinct subsets of hyperammonemia corresponding to known metabolic and physiologic processes (e.g., fulminant liver failure, tumor lysis syndrome, etc). FLC patients clustered separately from hepatocellular carcinoma patients with hyperammonemic encephalopathy due to cirrhosis. Conclusions: NLP of large EMRs is a valuable tool to study FLC, a rare cancer. Herein, we have defined hyperammonemia as a frequent event in FLC, not directly linked to hepatic dysfunction or individual therapies. Further investigation may determine whether hyperammonemia is related to FLC tumor biology.
Sexual harassment of oncologists.
Authors: Ishwaria Mohan Subbiah, Merry Jennifer Markham, Stephanie L. Graff, Laurie Beth Matt-Amaral, Julia Lee Close, Kent A. Griffith, Reshma Jagsi
Journal: Journal of Clinical Oncology (2021)

11001 Background: Few studies have used comprehensive validated measures to investigate the incidence and impact of workplace sexual harassment experienced by physicians (and none, to our knowledge, by oncologists). Methods: We conducted a cross-sectional survey of ASCO’s Research Survey Pool with targeted social media outreach to examine the prevalence and types of sexual harassment (SH) experienced by oncologists. Using the Sexual Experiences Questionnaire (SEQ), we measured their work experience of three SH forms (gender harassment [GH], unwanted sexual attention [USA], sexual coercion [SC]) in the past year by institutional insiders (peers/superiors) and patients/families separately. Controlling for race, career stage &amp; specialty, multivariable (MV) regression models assess the impact of SH (independent variable) on 4 dependent variables of mental health (MHI5), perceptions of workplace safety (single item), job satisfaction (MOAQ) &amp; 3-item measure of turnover intentions (in non-trainees). Results: Of 271 respondents, 250 were physicians in practice and 21 were residents/fellows; 153 (56%] were women, 168 (62%) practiced in academic settings &amp; 227 (84%) were medical oncologists. SH by peers/superiors was reported by 189 (70%) overall, including 80% of women and 56% of men (p&lt;0.0001). GH was reported by 79% of women and 55% of men (p&lt;0.0001), USA by 22% of women and 9% of men (p=0.005), and SC by 3% of women and 2% of men (p=0.42). SH by patients and/or families was reported by 67% of women and 35% of men (p&lt;0.0001), GH by 66% of women and 34% of men (p&lt;0.0001), USA by 5% women and 6% men (p=0.80), and SC by 1% women and 1% men (p=0.72). MV analysis showed past-year SH from peers/superiors was significantly associated with decreased mental health (β -0.45, p 0.004), workplace safety (β -0.98, p&lt;0.001) and increased turnover intentions (β 0.93, P&lt;0.0001). SH from patients/families was similarly significantly associated with mental health (β -0.41, p 0.002), workplace safety (β -0.42, p 0.014) and turnover intentions (β 0.58, p 0.0004). SH from insiders (β -0.64, p 0.001) but not patients (p 0.55) was significantly associated with job satisfaction. Furthermore, there were no significant interactions between the respondents’ gender and the SH scores in any of the models of impact. Conclusions: This is the first study in oncology to systematically characterize the incidence of sexual harassment experienced by oncologists. Our findings demonstrate the impact of sexual harassment on men and women oncologists on multiple domains of workplace experience. This study provides critical data to inform the need for and design of effective protective and preventive workplace policies in oncology.
European Association of Urology Guidelines on Urethral Stricture Disease (Part 2): Diagnosis, Perioperative Management, and Follow-up in Males
Authors: Felix Campos-Juanatey, Nadir I. Osman, Tamsin Greenwell, Francisco E. Martins, Silke Riechardt, Marjan Waterloos, Rachel Barratt, Garson Chan, Francesco Esperto, Achilles Ploumidis, Wesley Verla, Konstantinos Dimitropoulos, Nicolaas Lumen
Journal: European Urology (2021)
The enduring negative effects of financial toxicity in young adult cancer survivors.
Authors: Bridgette Thom, Catherine Benedict, Danielle Novetsky Friedman, Samantha Watson, Michelle Zeitler, Fumiko Chino
Journal: Journal of Clinical Oncology (2021)

12117 Background: Due to disruptions in education, workforce entry, and career development caused by cancer and its treatment, young adult (YA) cancer survivors face financial toxicity (i.e., cancer-related financial distress) at rates higher than older survivors. Financial toxicity in YA survivors is associated with avoiding care and diminished psychosocial well-being, but enduring effects on employment, personal finances, and healthcare use and the association with YA’s financial capability are not well studied. Methods: This was a cross-sectional survey of a national sample of YAs with cancer (n = 214) recruited online and via mailing lists. It included the Comprehensive Score for Financial Toxicity (COST), demographic/clinical self-report, and questions on medical cost-coping and healthcare use. Financial capability questions considered respondents’ knowledge about finances, self-efficacy for managing health expenses, and attitudes and behaviors regarding tracking expenses, budgeting, saving, investing, and bill paying. Multiple linear regression assessed associations among financial toxicity, financial capability, and cost-coping. Results: Mean respondent age was 35.4 years ( sd= 5.40) at survey and 27.5 years ( sd= 7.23) at diagnosis. Breast cancer (28%) and lymphoma (17%) were the most common diagnoses; most respondents were white (79%) women (87%) with college degrees (74%). Financial toxicity, as measured by COST, was high (mean = 13.9, sd= 9.3; possible range 0-44, scores &lt; 26 indicate severe financial toxicity). Nearly all of the sample (96%) had health insurance, but 30% said their insurance does not meet their needs. One-half of the sample lacked confidence to manage health expenses. Cost-coping strategies included skipping/delaying: treatment (23%), survivorship care (35%), or medications (39%); 65% relied on a family member to pay for some/all medical bills. Negative events related to medical expenses included using money from savings (58%), taking on credit card debt (45%), post-cancer credit score decrease (44%), borrowing money to pay bills (42%), debt collection contact (37%), lacking money to pay for basic necessities (23%), loan denial (20%), and thoughts about and/or filing for bankruptcy (15%). In multivariate analyses, greater financial toxicity was associated with lower self-efficacy for managing health expenses (β = -0.88, p =.01), poorer financial behaviors (β = -0.54, p =.001), lower income (β = -5.27, p =.001), and skipping/delaying: treatment (e β = 1.16, p &lt;.001), survivorship care (e β = 1.13, p &lt;.001), or prescribed medication (e β = 1.10, p =.001). Conclusions: Our findings illustrate the profound enduring impact of financial toxicity among YAs after cancer treatment. Multilevel interventions are needed to provide YAs the tools to navigate financial aspects of the healthcare system and connect them with resources toward gaining financial independence.
Preoperative pembrolizumab for MSI high, EBV positive or PD-L1 positive locally advanced gastric cancer followed by surgery and adjuvant chemoradiation with pembrolizumab: Interim results of a phase 2 multi-center trial (<i>NCT03257163</i>).
Authors: Timothy Kennedy, Mihir Maheshkumar Shah, Haejin In, Jennifer W. Chuy, Dirk F. Moore, David A. Kooby, Rafi Kabarriti, Stephen M. Szabo, Howard S. Hochster, Salma K. Jabbour
Journal: Journal of Clinical Oncology (2021)

e16111 Background: Despite advances in therapy, outcomes of patients with gastric cancer in the US remain poor. Recent data demonstrated that certain subtypes of gastric cancer are less responsive to perioperative chemotherapy. Preliminary data suggest that patients with microsatellite unstable tumors (MSI-H), EBV expressing tumors, and tumors with high PD-L1 expression may benefit from immunotherapy. We initiated a clinical trial to evaluate the benefit of PD-1 checkpoint immunotherapy in this subset of patients with resectable gastric cancer. Methods: Interim analysis performed on this phase 2 multi-institutional clinical trial (NCT03257163) is presented. Patients with clinically staged T2-T4, N0-N3, M0 gastric adenocarcinoma are evaluated for loss of mismatch repair proteins, expression of EBV or PDL1 expression with CPS &gt; 1%. Consented patients receive 2 cycles of neoadjuvant pembolizumab followed by surgical resection. Following surgery, patients receive adjuvant chemoradiation (45 Gy) with 5 cycles of capecitabine and concurrent pembrolizumab, followed by up to 1 year of pembrolizumab. The primary endpoint is disease-free survival. Results: Of the 15 patients currently enrolled (planned enrollment = 40), 6 patients were MSI-H, 2 EBV (+), and 7 had PDL1 expression with CPS &gt; 1%. Two patients did not undergo surgical resection as 1 patient was found to have peritoneal disease at time of exploration and second was deemed too frail to proceed with surgery. In the 13 patients who underwent surgical resection, all are alive without evidence of recurrent disease (follow up 1 month – 22 months). After 2 cycles of pembrolizumab, 2 patients with MSI-H tumors had pathologic complete response. Clinical T stage was downstaged in 5 patients and clinical N stage was downstaged in 2 patients. PD-1 checkpoint immunotherapy was well tolerated with minimal need for dose reduction and limited toxicity. Conclusions: Early results from our phase 2 clinical trial show immunotherapy to be well tolerated with limited toxicity. Following 2 cycles of pembrolizumab, 2 patients with MSI-H had complete pathologic response and above a third of our patients were downstaged. No recurrences have been observed in the short-term follow-up of surgically resected patients. Clinical trial information: NCT03257163.
Updated outcomes for patients with completely resected pulmonary recurrent osteosarcoma: A report from the Children’s Oncology Group.
Authors: Alexander J. Chou, Mark D. Krailo, Ruxu Han, Allen Buxton, Damon R. Reed, Richard Greg Gorlick, Steven G. DuBois, Michael Isakoff, Katherine A. Janeway, Pooja Hingorani
Journal: Journal of Clinical Oncology (2021)

10023 Background: Amongst patients with recurrent osteosarcoma (OS), those with resectable pulmonary-only relapse appear to have the best outcomes. Prior analysis of patients with completely resected recurrent OS enrolled on a Children’s Oncology Group (COG) Phase 2 trial AOST0221, which studied the efficacy of inhaled GMCSF, showed a 12- month disease control rate (DCR12) of only 20% (95% CI, 10 – 34%). DCR12 based on this analysis was used as the historical benchmark for efficacy analysis in two recently completed trials, AOST1321 (completely resected cohort only) and AOST1421. We analyzed the stability of the DCR12 benchmark using data from these contemporary studies. Methods: Patients were eligible for AOST1321 if they had undergone resection of all sites of recurrent or refractory OS within 30 days of enrollment and for AOST1421 if they had lung only recurrent OS completely resected within 4 weeks of enrollment. AOST1321 evaluated denosumab while AOST1421 evaluated dinutuximab. Patients with refractory disease, extrapulmonary recurrence or without histological confirmation of relapse were excluded from this analysis. DCR12 was defined as having at least stable disease 12 months after the start of protocol therapy. We report the DCR12 observed on AOST1321, AOST1421 and AOST0221. Results: One hundred and twenty-eight evaluable patients with completely resected recurrent OS were enrolled on AOST0221 (N=49), AOST1321 (N=38) and AOST1421 (N=41). One hundred and one patients were included in this analysis (AOST0221: 37, AOST 1321: 25, AOST1421:39). DCR12 was 14 % (95% CI, 5% – 26%) for AOST0221, 24% (95%CI 10-42%) for AOST1321, and 31% (95% CI, 17% - 45%) for AOST1421. Risk for disease progression did not differ across the 3 included studies. DCR12 for all three studies combined was 23% (95% CI, 15% – 31%). Conclusions: Prognosis for recurrent OS remains dismal, even for those with resectable pulmonary-only disease. Although not statistically significant, dinutuximab may have activity in a select group of relapsed OS patients; combination studies using dinutuximab are planned. The previously described benchmark of disease control at 12 months remained relatively consistent in recent studies for those patients who have resectable pulmonary-only relapse. Therefore, DCR12 remains a useful outcome measure in fully resected OS with lung only metastases. Analyses are ongoing to better define the appropriate threshold to define investigational agent activity in this specific patient population.
BIOL-04. CYTOPLASM PROTEIN GFAP MAGNETIC BEADS CONSTRUCTION AND APPLICATION AS CELL SEPARATION TARGET FOR BRAIN TUMORS
Authors: Yang Zhao, Jie Ma
Journal: Neuro-Oncology (2021)

Abstract Background It is very important to develop a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function, for which the detection of circulating tumor cells (CTCs) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTCs separation target, a cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposome beads (IMLs). The validation and efficiency of this system in capturing CTCs for brain tumors were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. Results Our data show that CTCs can be successfully isolated from CSF and blood samples from 32 children with brain tumors. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. The higher the CTCs number is, the more possibly the patient will suffer from poor prognosis. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTCs was consistent with that of tumor tissue. Conclusions The results indicated that GFAP-IML CTCs isolation system, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique may play a significant role in the clinical diagnosis and drug evaluation of brain tumors.
Antiviral adsorption activity of porous silicon nanoparticles against different pathogenic human viruses
Authors: Liubov A. Osminkina, Svetlana N. Agafilushkina, Ekaterina A. Kropotkina, Nikolay Yu Saushkin, Ivan V. Bozhev, Sergei S. Abramchuk, Jeanne V. Samsonova, Alexandra S. Gambaryan
Journal: Bioactive Materials (2021)

New viral infections, due to their rapid spread, lack of effective antiviral drugs and vaccines, kill millions of people every year. The global pandemic SARS-CoV-2 in 2019-2021 has shown that new strains of viruses can widespread very quickly, causing disease and death, with significant socio-economic consequences. Therefore, the search for new methods of combating different pathogenic viruses is an urgent task, and strategies based on nanoparticles are of significant interest. This work demonstrates the antiviral adsorption (virucidal) efficacy of nanoparticles of porous silicon (PSi NPs) against various enveloped and non-enveloped pathogenic human viruses, such as Influenza A virus, Poliovirus, Human immunodeficiency virus, West Nile virus, and Hepatitis virus. PSi NPs sized 60 nm with the average pore diameter of 2 nm and specific surface area of 200 m
Relationship between insurance status and diagnosis of cutaneous immune-related adverse events.
Authors: Michael Chang, Nira A. Krasnow, Amy E. Blum, Vartan Pahalyants, William S. Murphy, Jaewon Yoon, Kerry Lynn Reynolds, Leah L. Thompson, Steven T. Chen
Journal: Journal of Clinical Oncology (2021)

e18535 Background: Cutaneous immune-related adverse events (cirAEs) are among the most common side effects of immune checkpoint inhibitor (ICI) therapy. While insurance status has been shown to influence outcomes in patients treated with ICIs, its impact on cirAE management remains underexplored. We therefore evaluated insurance status in patients with cirAEs, examining its effect on rate of and time to cirAE diagnosis. Methods: Using billing data, we retrospectively identified patients who initiated anti-PD-1/PDL-1 and/or anti-CTLA-4 therapy at Massachusetts General Hospital between January 1, 2016 and March 8, 2019 (n = 2,459) for possible cirAE. Eligible cirAEs included reactions attributed to ICI by the clinician, consistent with established morphologic categories. For each patient with confirmed cirAE (n = 358), we abstracted oncologic history, cirAE features, and insurance status. Associations between insurance and cirAE diagnosis outcomes were assessed via logistic and linear regression, and adjusted for age, sex, race, ICI type, cancer diagnosis, cirAE type, and significant covariates ( P&lt; 0.05). Results: Of the 2,459 patients who received ICIs, 2,419 (98.4%) had documented insurance status. Most ICI recipients had Medicare (n = 1,119; 46.3%) or private insurance (n = 1,156; 47.8%) relative to Medicaid (n = 104; 4.3%) or other government insurance (e.g. Tricare) (n = 40; 1.7%). We found that 358 (median age 64 years, 40.5% female) developed a cirAE. Among cirAE patients, 175 had Medicare (48.9%), 174 had private insurance (48.6%), 6 had Medicaid (1.7%), and 3 had other government insurance (0.8%). The most common cirAEs across insurance types were maculopapular rash, pruritus, and eczematous and lichenoid eruptions. In the multivariable analysis, ICI patients with Medicare insurance had a higher rate of cirAE diagnosis (adjusted odds ratio: 2.41, 95% CI: 1.00, 5.90, P= 0.05) relative to Medicaid patients. In addition, in terms of time to cirAE diagnosis at dermatology visit, Medicare insurance was associated with longer delays, with a linear regression coefficient of 132.2 (95% CI: 4.78, 259.6; P= 0.04). No significant associations were found between other insurance types and cirAE diagnosis outcomes. Conclusions: Our study shows that patients with Medicaid are less likely to be diagnosed with cirAE relative to those with Medicare, despite delays in diagnosis, when controlling for all other demographic/oncologic factors. Ultimately, these findings are reassuring that despite insurance differences, patients with cirAEs are receiving suitable care and appropriately seen by dermatologists. As insurance coverage for specialists can vary widely, these initial findings are a promising indicator that patients with cirAEs are well-connected within healthcare systems.
Anti-TL1A Antibody PF-06480605 Safety and Efficacy for Ulcerative Colitis: A Phase 2a Single-Arm Study
Authors: Silvio Danese, Maria Klopocka, Ellen J. Scherl, Jacek Romatowski, Jessica R. Allegretti, Elena Peeva, Michael S. Vincent, Uwe Schoenbeck, Zhan Ye, Mina Hassan-Zahraee, Natalie Rath, Gang Li, Srividya Neelakantan, Christopher Banfield, Christopher Lepsy, Deepa E. Chandra, Kenneth E. Hung
Journal: Clinical Gastroenterology and Hepatology (2021)
Clinical impact of pathogenic germline variants in pancreatic cancer: Results from a multicenter prospective universal genetic testing study.
Authors: Pedro Luiz Serrano Uson Junior, Douglas Riegert-Johnson, Lisa A. Boardman, Mitesh J. Borad, Daniel H. Ahn, Mohamad Bassam Sonbol, Douglas O Faigel, Norio Fukami, Rahul Pannala, Katie Kunze, Michael A Golafshar, Edward D. Esplin, Robert Luke Nussbaum, Tanios S. Bekaii-Saab, Jewel Samadder
Journal: Journal of Clinical Oncology (2021)

4118 Background: Germline variations in cancer susceptibility genes have important implications on treatment and family counseling in pancreatic cancer (PC). We report the prevalence and clinical outcomes of unselected PC patients with pathogenic germline variants (PGV) detected using a universal testing approach. Methods: We undertook a prospective multi-site study of germline sequencing using an &gt;80 gene next-generation sequencing platform among 250 PC patients (not selected for age or family cancer history) between April 1, 2018 and March 31, 2020. Demographic, tumor characteristics and clinical outcomes were compared between PGV carriers and non-carriers. Results: Of 250 patients, the mean age was 65 years (SD 8.7), 56% were male, 83.6% were white and 65.6% had advanced disease (Stage III and IV). PGV were found in 15.2% (N=38) of patients, two patients had more than one PGV. Variants of uncertain significance were found in 44.4% (N=111). Family history of cancer (OR 2.36, 95% CI: 1.14-5.19, p=0.025) was associated with a higher risk of PGV. In a median follow up of 16.5 months, median overall survival was 16.8 months in PGV carriers compared with 16.5 months in non-carriers (HR 0.51, 95 %CI, 0.25-1.01, p=0.05). Higher levels of CA 19-9 and advanced stages (III and IV) were associated with worse outcomes in both groups. Overall, 68% of PGV carriers had mutations in homologous recombination repair (HRR) genes, including BRCA1, BRCA2, PALB2, ATM, CHEK2, NBN, RAD51C. In 65% of HRR gene carrier’s systemic therapy with platinum was used. Conclusions: Universal multi-gene panel testing in pancreatic cancer reveals that 1 in 6 patients are carriers of PGV and is associated with improved survival. Multi-gene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling. Distribution of the 40 PGV by penetrance status.[Table: see text]