tbuckley/cabot-search huggingface dataset:
Assessment of solid tumor oncology perception and knowledge gain in internal medicine (IM) residents through oncology video library: Educational intervention in progress.
Authors: Alison L. Raybould, Jonathan D Sorah, Moriah Forster, Jon Powell, Tim Poe, Frances A. Collichio
Journal: Journal of Clinical Oncology (2021)

e23000 Background: ACGME and internal surveys performed at the University of North Carolina (UNC) demonstrate that IM residents have historically been dissatisfied with their inpatient oncology experience. Other institutions have demonstrated that a resident oncology video library is feasible and effective in improving clinical knowledge, but formal protected time for module use limited engagement. We created an oncology video library targeted to the resident learner. To enhance impact, we incorporated dedicated time during elective rotations to access the modules. Methods: We performed a pre-survey using a Likert scale to assess resident knowledge perception of solid tumor cancers. We designed a curriculum based on the ABIM blueprint and those cancers frequently encountered on service. We filmed 21 videos of UNC oncologists discussing content they selected for the resident learner. To improve engagement, we provided a half-day of independent study during their outpatient oncology elective. As this study is ongoing, we plan to conduct a post-survey and post-test to evaluate long-term knowledge acquisition. Results: Twenty-seven of the 85 IM residents completed the pre-survey. Eleven (40.8%) reported feeling extremely or somewhat satisfied with inpatient oncology teaching; the remainder felt neutral (29.6%), somewhat (25.9%) or extremely dissatisfied (3.7%). Among oncologic emergencies, most residents felt comfortable managing hypercalcemia (88.9%) and cord compression (55.6%), but not SVC syndrome (29.6%). Prior to implementation of the videos, most reported little/no knowledge gain from their clinical rotations alone across nearly all 20 domains assessed. The only domain in which a majority (65.39%) reported some or significant knowledge gain was chemotherapy toxicities. These domains were selected as video lecture topics. In the five months since their release, each video has been viewed an average 21.5 times. The most viewed video (39 views) was on traditional chemotherapy pharmacology; the least viewed video (9 views) was on pancreas cancer. 28% of residents surveyed reported utilizing the videos, and for those who did access them, half (56.2%) felt that the time for the videos was sufficient, while the other half (43.8%) wished for more dedicated time. Conclusions: IM residents may benefit from an online video library to improve knowledge acquisition and perception of oncology rotations. However, to maximize impact, residents must be given adequate time separate from their service requirements to access the modules. This is a study in progress, and while initial data regarding video utilization appears promising, we await additional information to ascertain knowledge improvement.
Uptake of genetic counseling and testing in a clinic based population of women with breast cancer.
Authors: Alexandra Wehbe, Mark A. Manning, Hadeel Assad, Kristen Purrington, Michael S. Simon
Journal: Journal of Clinical Oncology (2021)

10524 Background: Carriers of pathogenic variants in cancer susceptibility genes have an elevated risk of developing breast, ovarian, and other cancers. We conducted a medical record review to determine the uptake of genetic counseling and testing in a clinic-based population of women with breast cancer. Methods: Medical records of 150 women with breast cancer seen at the Karmanos Cancer Institute between January-December 2018 were reviewed to determine the proportion eligible for genetic testing according to National Comprehensive Cancer Network guidelines. We also assessed genetics referral rates, appointment completion and results of genetic testing. Using chi-square and ANOVA tests, we analyzed the association of demographic and clinical factors with eligibility and referral to genetic counseling. Results: The average age of diagnosis was 57.1 years old, with 68.7% of women diagnosed with stage I-III disease, and 31.3% diagnosed with stage IV disease. There were 91 (60.7%) women who met NCCN criteria for genetic testing, of which 46.2% ultimately underwent genetic testing. Eligible women were more likely to be younger (52.6 vs. 64.0 years old), White (75.0% vs. 54.5%), and have Medicaid (75.0%) or private insurance (72.9%) vs. Medicare (44.8%). Women who met NCCN criteria were 3.5 times more likely to be referred for genetic counseling than those that did not meet eligibility criteria. Women were also more likely to be referred if they had early-stage disease compared to stage IV (67.8% vs. 48.3%), and Medicaid or private insurance compared to Medicare (71.4%, 72.0% and 40.0%, respectively). Of eligible women, 59.3% had a genetic counseling appointment scheduled, and of those, 78.0% attended their appointment. There were no apparent differences in appointment completion based on race with similar percentages of Black and White women completing their appointments (74.0% and 77.0% respectively). Women with stage IV disease were more likely to complete their appointments (83.0%) compared to women with stages I-III (74.0%) and fewer women with Medicare completed their genetic counseling appointment (56.0%) compared to women with Medicaid (83.0%) and women with private insurance (83.0%). Among women who attended their appointment, 95.9% underwent genetic testing. Of women who had genetic testing, 8.5% had a pathogenic variant and 30.4% had a variant of unknown significance. Conclusions: The results of this study indicate that lack of genetic counseling referrals contribute to a gap between the need for and completion of genetic testing. By understanding barriers to genetic counseling and testing, future clinical initiatives could effectively improve accessibility to genetic counseling services.
Impact of age on efficacy and safety of relugolix: A subgroup analysis from the randomized, phase 3 hero study versus leuprolide in men with advanced prostate cancer.
Authors: Michael Cookson, Neal D. Shore, Daniel J. George, Hideyuki Akaza, Daniel Saltzstein, Ronald F. Tutrone, Alberto Bossi, Bruce Brown, Bryan Selby, Sophia Lu, Jacqueline M. Walling, Bertrand F. TOMBAL, Fred Saad
Journal: Journal of Clinical Oncology (2021)

5075 Background: In the phase 3 HERO study, the oral GnRH receptor antagonist relugolix demonstrated sustained testosterone suppression superior to that of leuprolide and a comparative 54% decrease in risk of major adverse cardiovascular events. Relugolix was recently approved for use in the US for the treatment of adult patients with advanced prostate cancer. Here, we further characterize the impact of age on the use of relugolix in advanced prostate cancer from the HERO study. Methods: The HERO study was a randomized, open-label, parallel group study evaluating relugolix in men with advanced prostate cancer. Overall, 934 men with advanced prostate cancer underwent 2:1 randomization to receive relugolix 120 mg orally once daily after a single loading dose of 360 mg or leuprolide 3-month injections for 48 weeks. Subgroups analyzed by age were &lt;65 years or ≥65 years and ≤75 years or &gt;75 years. Assessments analyzed included sustained testosterone suppression to castrate levels (&lt;50 ng/dL) from day 29 through 48 weeks, early and profound (&lt;20 ng/dL) castration rates, prostate-specific antigen (PSA) levels, and safety. Testosterone recovery (≥280 ng/dL) was evaluated in 184 patients who enrolled in the testosterone recovery substudy. Results: Of the 930 patients (relugolix:622;leuprolide:308) that received study drug in the HERO study, 173 (18.6%) were &lt;65 years and 757 (81.4%) were ≥65 years of age, while 664 (71.4%) were ≤75 years and 266 (28.6%) were &gt;75 years of age. Across all age subgroups, point estimates for sustained castration rates through 48 weeks for relugolix patients were consistent with the overall estimate of relugolix sustained castration rate observed in the overall population. Differences in sustained castrations rates at week 48 between relugolix and leuprolide groups were similar regardless of the age subgroup (table). The likelihood of testosterone recovery at 90 days after completion of treatment was higher in the relugolix group versus the leuprolide group in all age subgroups: &lt;65 (79.1% vs 16.7%), ≥65 (48.6% vs 0%), ≤75 (60.0% vs 4.0%),and &gt;75 years (40.7% vs 0%). No clinically relevant differences were noted in the incidence or types of adverse events within treatment groups in all the age subgroups analyzed. Conclusions: In this subgroup analysis of the HERO study, relugolix was effective regardless of age, and the benefit/risk profile remained favorable for relugolix compared with leuprolide, consistent with the overall population. Testosterone recovery was higher in the relugolix group than the leuprolide group for all age subgroups analyzed, with higher rates of recovery in younger versus older men. Clinical trial information: NCT03085095. [Table: see text]
Pre-Transplant Minimal Residual Disease Determined By Multiparameter Flow Cytometry Is Better Than RQ-PCR to Predict the Outcomes of Ph+ALL Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Xiaosu Zhao, Yanrong Liu, Yazhen Qin, Yu Wang, Xiaohui Zhang, Lanping Xu, Xiaojun Huang, Yingjun Chang
Journal: Blood (2017)
Performance status and activity level of lung cancer patients using wearable devices as passive monitoring: A scoping review.
Authors: Santiago Ponce Aix, Leonardo Crama, Francisco J. Núñez-Benjumea, Sergio Sánchez, Sergio Cervera-Torres, Mar López, Pablo Arnáiz, Luis Fernández-Luque
Journal: Journal of Clinical Oncology (2021)

e21141 Background: Lung Cancer (LC) and particularly non-small cell lung cancer (NSCLC) is considered one of the most lethal types of cancer to date. Suitability and toxicity of treatment, or eligibility of LC patients for clinical trials usually rely on subjective indicators of Performance Status (PS) such as the Eastern Cooperative Oncology Group (ECOG) and Karnofsky indexes. In recent years, however, the use of electronic wearable devices has increasingly come to the fore with the aim of increasing objectivity of PS assessments. These devices are capable of objectively and passively monitor health-related outcomes such as daily physical activity and sleep patterns. Consequently, a comprehensive review of the current state of the art in this matter can provide further insights for future research within oncology areas in general, and lung cancer, in particular. The main goal of this scoping review is to identify and categorize scientific publications that, over the past 10 years, used wearable devices as means of monitoring activity level of LC patients. Methods: The study follows the PRISMA-ScR framework (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). Results: A total of 32 studies were identified as suitable to be included in the review where (n = 22; 68.7%) focused on physical activity and (n = 10; 31%) in sleep or circadian patterns. Approximately half of the studies used a wrist wearable. Device output included step counts, activity counts, metabolic equivalents, time active, time spent in moderate-to-vigorous activity, sedentary time, sleep duration, sleep efficiency, total sleep time/sleep duration, sleep onset latency, wake times, and wrist movement per minute. However, step counts arose as one of the most representative outcomes of physical activity (n = 17; 53%). In general, higher levels of physical activity and circadian organization (day/night activity balance) as measured by actigraphy, are associated with less fatigue, pain, and better quality of life. Conclusions: This review shows that wearable devices, and especially wrist wearables, are increasingly used in oncology settings as a reliable method to monitor physical and sleep activity and to complement PS assessment. Further research is needed, however, to determine the extent to which this methodology can be used to more directly objectivize current PS assessment itself.
Trial in progress: A phase 1, multicenter, open-label, dose-exploration and dose-expansion study evaluating the safety, tolerability, pharmacokinetics, and efficacy of AMG650 in subjects with advanced solid tumors.
Authors: Ramaswamy Govindan, Amanda Rose Townsend, Kathy D. Miller, Inderjit Mehmi, Yasutoshi Kuboki, Ecaterina Elena Dumbrava, Erika P. Hamilton, Irene Vuu, Erik Rasmussen, Linda R. Mileshkin, Sofia Genta, Hiroji Iwata, Sylvia Adams, Hisaki Fujii, Sant P. Chawla
Journal: Journal of Clinical Oncology (2021)

TPS5600 Background: KIF18A is a mitotic kinesin motor protein that regulates chromosome positioning during cell division and is overexpressed in a subset of human cancers. TP53 mutant unstable aneuploid cancer cells with chromosomal instability (CIN) features are dependent on KIF18A motor activity to prevent lethal multipolar cell division. Preclinical data demonstrate that treatment with AMG 650; an oral, first in class, selective small molecule inhibitor of KIF18A may be safe and tolerable. We are conducting a first-in-human phase 1 study with AMG 650 in adult subjects with locally advanced or metastatic solid tumors with TP53MUT, triple negative breast cancer (TNBC), high grade serous ovarian cancer (HGSOC) or serous like endometrial cancers and other solid tumors. Methods: In this phase 1, multicentric, dose escalation and dose expansion study we evaluate the safety and tolerability of AMG 650 monotherapy in patients with advanced/metastatic solid tumors (NCT04293094). The main objective is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching the MTD. Key inclusion criteria include the presence of measurable disease and diagnosis of advanced/metastatic triple negative breast cancer (TNBC), high-grade serous ovarian cancer (HGSOC), serous-like endometrial cancer or other solid tumors with documented TP53 mutations. In the dose expansion phase, participants with locally advanced or metastatic TNBC or HGSOC will be treated with the preliminary RP2D identified from the dose exploration part of the study. Primary endpoints include the incidence of Dose Limiting Toxicities (DLTs),Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment-related Adverse Events and the evaluation of the number of participants who experience a clinically significant change from baseline in vital signs, electrocardiogram and laboratory tests parameters. Secondary endpoints include Objective Response Rate, Duration of Response, Progression-free Survival, Clinical Benefit Rate, Time to Response, Time to Progression, Overall Survival (OS), Maximum Plasma Concentration (Cmax) of AMG 650, Time to Maximum Plasma Concentration (Tmax) of AMG 650 as well as Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650. Continuous monitoring of toxicity is conducted. The study began enrolling pts in March 2020 and is ongoing. For more information, please contact Amgen Medical Information: medinfo@amgen.com Clinical trial information: NCT04293094.
Phase 1A clinical trial of the first-in-class fascin inhibitor NP-G2-044 evaluating safety and anti-tumor activity in patients with advanced and metastatic solid tumors.
Authors: Vincent Chung, Komal L. Jhaveri, Daniel D. Von Hoff, Xin-Yun Huang, Edward Graeme Garmey, Jillian Zhang, Frank Yung-Chin Tsai
Journal: Journal of Clinical Oncology (2021)

2548 Background: Fascin inhibitors block tumor metastasis and increase antigen uptake in intra-tumoral dendritic cells. Filopodia, finger-like protrusions on cell surfaces, are necessary for migration of metastatic tumor cells and intra-tumoral dendritic cells. Fascin is the primary actin cross-linker in filopodia and elevated levels correlate with increased risk of metastasis, disease progression and mortality. NP-G2-044 is a novel small molecule that inhibits function of fascin. Pre-clinical data demonstrate drug-associated reductions in tumor growth and metastasis, enhanced immune response and survival in treated animals, and drug-drug synergism when combined with anti-PD-1 antibodies. Methods: This multicenter phase 1A clinical trial was designed to evaluate safety and tolerability of NP-G2-044 and to identify the drug’s recommended phase 2 dose (RP2D) using a 3+3 dose escalation design. NP-G2-044 was administered to patients (pts.) with treatment-refractory solid tumor malignancies as a single oral daily dose for 6-week cycles that included 4 weeks on (daily dosing) and 2 weeks off (rest). Results: A total of 23 pts. were enrolled in 7 dose cohorts ranging from 200-2100 mg. QD. Overall, NP-G2-044 appeared well-absorbed and distributed with Tmax of ̃4 hrs and T1/2 of 20-24 hrs. Across all cohorts, no DLTs, drug-related SAEs or patient deaths were observed. Based on PK and safety findings, 1600 mg. daily was selected as the provisional RP2D. While no formal RECIST-based objective responses were observed, consistent with the drug’s non-cytotoxic mechanism of action, preliminary signals of anti-tumor and anti-metastatic activity were observed. These include dose proportional increases in duration of treatment, progression-free-survival, and metastasis-free interval, in particular for 4/4 late-stage ovarian cancer patients (table). Comparison of time on treatment (TOT) for ovarian cancer patients. Conclusions: In this first-in-human clinical trial, the novel fascin inhibitor, NP-G2-044, appeared safe and well tolerated. Signals of single-drug anti-tumor and anti-metastatic activity were observed. A phase 2A clinical trial with a particular focus on Ovarian Cancer will seek to elucidate signals of RP2D activity in both monotherapy and the combination of NP-G2-044 with anti-PD-(L)1 immune checkpoint inhibitors. Clinical trial information: NCT03199586. [Table: see text]
Impact of Medicaid expansion on pancreatic cancer care: A difference-in-difference analysis.
Authors: Ahmad Hamad, Mariam Eskander, Yaming Li, Oindrila Bhattacharyya, James L Fisher, Bridget A. Oppong, Samilia Obeng-Gyasi, Allan Tsung
Journal: Journal of Clinical Oncology (2021)

e18567 Background: The Affordable Care Act (ACA) increased insurance coverage for low-income individuals, which should potentially lead to better access to care and improved oncological outcomes. This study seeks to evaluate the impact of Medicaid expansion (ME) on care for pancreatic ductal adenocarcinoma (PDAC). Methods: Patients who were uninsured or on Medicaid and diagnosed with PDAC between 2004 and 2017 were queried from the National Cancer Database (NCDB). Two different expansion cohorts were included: early expansion states and 2014 expansion states. For early expansion states, the time period of pre-expansion was 2004-2009 and post-expansion was 2010-2017. As for the 2014 expansion states, the pre-expansion period was from 2004-2013 and post-expansion period was from 2014-2017. Patients in non-expansion states formed the control group. A difference-in-difference (DID) analysis was used to assess the association of ME with stage of diagnosis, treatment and survival for each expansion cohort. Results: In both early and January 2014 expansion states, there was an increase in overall Medicaid coverage (Early: DID = 0.29, 2014: DID = 0.37; P &lt; 0.001), in particular for non-Hispanic Black and Hispanic Black patients (Non-Hispanic Black: Early: DID = 0.11, 2014: DID = 0.11; P &lt; 0.001, Hispanic-Black: 2014: DID = 0.20; P = 0.003). There were no differences in early stage diagnosis (Early: DID = 0.02, 2014: DID = -0.02; P &gt; 0.05). There was an increase in the number of patients receiving surgery (Early: DID = 0.05; P = 0.001, 2014: DID = 0.03; P = 0.029) but no difference in time to surgery among patients receiving surgery upfront (Early: DID = 1.75, 2014: DID = 0.38; P &gt; 0.05). There was no difference in 30-day readmission post-surgery (Early: DID = 0.003; 2014: DID = -0.00007; P &gt; 0.05) or 90-day mortality (Early: DID = -0.007, 2014: DID = -0.035; P &gt; 0.05). Moreover, there was no difference in receipt of chemotherapy (Early: DID = 0.01, 2014: DID = 0.005; P &gt; 0.05) or time to chemotherapy for patients receiving neoadjuvant chemotherapy (Early: Early: DID = 9.62, 2014: DID = 0.01; P &gt; 0.05). Finally, there was no difference in receipt of palliative care among stage IV patients in both cohorts (Early: DID = -0.004, 2014: DID = 0.004; P &gt; 0.05). Conclusions: This study suggests that after ME, PDAC patients were more likely to be insured and had increased access to surgical care. Future, studies should evaluate the implications of improved surgical access on clinical outcomes such as mortality.
Hospital-at-Home Interventions vs In-Hospital Stay for Patients With Chronic Disease Who Present to the Emergency Department
Authors: Geneviève Arsenault-Lapierre, Mary Henein, Dina Gaid, Mélanie Le Berre, Genevieve Gore, Isabelle Vedel
Journal: JAMA Network Open (2021)

Hospitalizations are costly and may lead to adverse events; hospital-at-home interventions could be a substitute for in-hospital stays, particularly for patients with chronic diseases who use health services more than other patients. Despite showing promising results, heterogeneity in past systematic reviews remains high.
Effectiveness of osimertinib plus chemotherapy and avastin for untreated EGFR-mutated advanced non-small cell lung cancer.
Authors: Fang Wang, Hui Liu, Zhen Zeng, Shasha Wang, Haifeng Qin
Journal: Journal of Clinical Oncology (2021)

e21178 Background: Osimertinib is recommended as a novel first-line standard treatment for advanced Non-Small-Cell Lung Cancer (NSCLC) patients with EGFR mutation. However, there are also patients with concurrent mutation or/and metastases have limited benefits. According to the current remission rate, regression depth and PFS data, the main mechanism of the benefit of combined anti-angiogenesis or chemotherapy is to reduce tumor load and heterogeneous reserve to a greater extent, so as to extend the remission time, that is, to delay the occurrence of drug resistance to extend PFS. This prospective study aims to investigate the efficacy and safety of Osimertinib plus chemotherapy and Avastin for Untreated EGFR-Mutated advanced NSCLC. Methods: The study enrolled 22 patients diagnosed with untreated advanced NSCLC and tested with EGFR mutation, who received osimertinib ( 80mg QD) plus pemetrexed (500mg/m 2 ), cisplatin (75mg/m 2 ) and bevacizumab (7.5mg/kg) for 6 cycles, then maintained with osimertinib/pemetrexed/bevacizumab. The primary endpoint was progression free survival (PFS). The secondary endpoint was objective response rate (ORR). Treatment was continued until disease progression and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The toxicity was determined according to CTCAE 4.0. Results: From February, 2018 to July, 2020, 22 patients enrolled. All the patients were evaluated and showed partial response(PR) when make efficacy evaluation at the first time. The target lesions reduction were shown. The average reduction is 48%, ranged from 32% of Pt12 to 71% of Pt11. Up to January, 2021, all the patients are still under the treatment. Especially for Pt7 who has already benefited from the treatment protocol by 35months. The toxicities associated with this protocols were manageable. Only 1 patient was 3/4-grade Anemia, 1 patient was 3/4-grade Diarrhea and 3 patients was 3/4-grade Lymphopenia. Conclusions: Osimertinib in combination with chemotherapy and Bevacizumab. exhibits superior activity and generally manageable toxicities for the naive advanced NSCLC patients with EGFR mutant, especially for the patients with concurrent mutation or/and metastases. It may provide a new and effective therapy strategy for them, but large sample and additional clinical trials are also needed.