tbuckley/cabot-search huggingface dataset:
An assessment of the NAVIFY clinical trial match application using clinical simulation-based research methods.
Authors: Matthew Stewart Prime, Chaohui Guo, Gianluca Fontana, Saira Ghafur, Jack Halligan, Clarissa Gardner
Journal: Journal of Clinical Oncology (2021)

e13552 Background: Cancer clinical trials require matching patients to strict, and sometimes lengthy, eligibility criteria. NAVIFY Clinical Trial Match (CTM) is a digital solution that uses data on an individual patient’s condition, genomic alterations and institution’s postal code to automatically find suitable clinical trials. We assessed the efficiency, accuracy and cognitive burden of NAVIFY CTM on matching patients to cancer clinical trials in the UK. Methods: 10 clinicians (8 medical doctors, 2 clinical trial practitioners) participated. Synthetic patient cases were developed with input from two oncologists, a histopathologist and a radiologist. Participants were instructed to identify appropriate trials for five patients using the NAVIFY CTM and five patients with the legacy approach (i.e. online trial databases) within one hour. For each method, participants were advised to approach the exercise with the level of scrutiny employed in a normal clinical setting. The efficiency, quality, and cognitive burden of trial matching was measured for each participant. The quality of trial matches was independently scored by an oncologist who did not participate in the simulations. The cognitive burden was measured subjectively, via a single-item questionnaire used to measure mental effort (Paas scale), and objectively, via Stroop test before and after each method. A survey was also conducted. Results: Efficiency: Participants completed the trial matching more efficiently using NAVIFY CTM, with trial matches completed on average one minute and 42 seconds faster using the digital solution (n = 73 matches) compared with the most commonly used online trial database, ClinicalTrials.gov (n = 52). Participants were more likely to ‘completely agree’ that they had enough time to complete the task using the NAVIFY CTM (70%) compared to online trial databases (40%). Quality of the matches: On the survey, more participants reported that trial suggestions were ‘mostly relevant’ for NAVIFY CTM (70%) compared with ClinicalTrials.gov (30%). The quality of trial matches was the same for both methods (as scored independently by an oncologist). Cognitive burden: On the subjective measure of cognitive burden, more participants required ‘low’ or ‘rather low’ mental effort to use NAVIFY CTM (50%) compared to online trial databases (7%). On the objective measure, there is a seemingly less pronounced Stroop effect (often interpreted as higher mental agility) using NAVIFY CTM vs. legacy approach. Conclusions: Preliminary findings suggest that, compared to online trial databases, the NAVIFY CTM can reduce the amount of time to match patients to clinical trials, provide more relevant trial suggestions, and decrease self-reported mental effort for the decision-maker.
Final report and long-term outcomes: Phase I trial of a HER2 intracellular plasmid-based vaccine in HER2+ advanced stage breast cancer.
Authors: Mary L. Disis, Yushe Dang, Andrew L. Coveler, Doreen Higgins, Jennifer Childs, Lupe G Salazar
Journal: Journal of Clinical Oncology (2021)

2619 Background: Vaccination with the intracellular domain (ICD) of HER2 in pre-clinical models is both immunogenic and protective against the development of mammary tumors. This study (NCT00436254) was designed to examine the safety and optimal immunogenic dose of a DNA-based vaccine encoding the HER2 ICD in subjects with HER2+ breast cancer. Methods: Sixty-six patients with stage III or IV HER2 + breast cancer in remission or with stable bone only disease were enrolled into three vaccine arms: 1 (10mcg dose of plasmid), 2 (100mcg) and 3 (500mcg). Vaccines were administered i.d. monthly for three immunizations. Endpoints included safety and optimal dose. HER2 specific IFN-gamma immune responses were evaluated and DNA persistence at the vaccine site was assessed. Toxicity and clinical outcomes were followed for 10 years. Results: The majority of vaccine-related toxicity was grade 1 (89%) and grade 2 (11%) and was not significantly different between the three dose arms. All Arms developed HER2 ICD immunity after vaccination, however, patients in Arm 2 and Arm 3 had significantly better immune responses (of higher magnitude and at most time points) than patients in Arm 1 (p=0.003 and p&lt;0.001, respectively) after adjusting for baseline factors. At 60 weeks, the number of patients who maintained the greatest fold-difference in HER2 ICD immune responses from their baseline was highest in Arm 2 (73%) when compared to Arm 1 (47%) and Arm 3 (45%). Associations between ICD responses and plasmid DNA persistence at the vaccine site were estimated via linear regression models. HER ICD immunity after the end of immunizations, relative to baseline, was significantly lower in patients with DNA persistence at week 16 compared to those without persistence (p=0.02). Patients at the highest dose demonstrated the greatest incidence of plasmid persistence (92%) as compared to 33% in Arm 1 and 10% in Arm 2. The median time of follow-up was 118.6 months (Arm 1), 99.7 months (Arm 2), and 73.5 months (Arm 3). The median OS and PFS has not been reached in any Arm and did not differ with respect to treatment arm (Log-rank p-value 0.36 for OS, and 0.63 for PFS). However, we observed a separation of Kaplan-Meier curves for OS from about 40 months and curves for PFS from about 30 months, and the separation maintained until the end of the study for Arm 2 versus Arm 1 and Arm 3. One patient in Arm 2 developed lymphocytic colitis 2.2 years from enrollment deemed possibly related to vaccination. Conclusions: An intermediate dose (100mcg) of vaccine was immunogenic and associated with persistence of immunity at 60 weeks. A randomized phase II trial of the HER2 ICD plasmid-based vaccine in the neoadjuvant setting is in development. Clinical trial information: NCT00436254.
Modeling Medicare’s Oncology Care Model bundles at more clinically granular levels: Evaluating the impact on provider performance.
Authors: Andrew Yue, Nora Connor, Lucio N. Gordan, Lisa Tran, Basit Iqbal Chaudhry
Journal: Journal of Clinical Oncology (2021)

e18854 Background: Aggregating different subtypes of cancers into bundles is an important methodology in oncology payment reform as an alternative to fee for service. However, expected resource utilization can vary significantly across cancer subtypes. We evaluated the impact that modeling Chronic Leukemia into a more clinically granular two part framework of chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia would have on OCM results and the risk that the distribution of clinical subtypes at a practice would influence overall performance in the bundle. Methods: OCM episodes of chronic leukemia initiating between July 2016 and June 2019 were subdivided on the basis of individual ICD-10 coded diagnoses on cancer-related E&amp;M visits. From a total of 4,658 episodes, we randomly sampled with replacement 3,500 episodes from 16 practices using empirical data distributions. Data models and mappings were developed based on clinical knowledge and exploratory data analyses to subdivide the OCM bundle of Chronic Leukemias into CLL and CML. Total cost of care and episode target prices were calculated through implementation of the OCM methodology. The distributional consistencies of episode target, cost, cost above target, and percent above target for the two diseases were evaluated by two-sample Kolmogorov-Smirnov (KS) tests. Results: The CML and CLL subtypes modeled from the aggregate OCM bundle demonstrated significantly different cost distributions relative to each other. As anticipated, treatments used in each subtype varied significantly marking different patterns of expected resource utilization. In our model, CLL episodes were on average 13.7% over target. Average CLL episode costs were $52.2K vs. an average target of $47.6K with 54% of episodes running over target. In contrast, CML episodes were 6.1% under target. Average CML episode costs were $45.2K vs. an average target of $50.3K with 43% of episodes running over target. Conclusions: Value based payment models in oncology such as OCM can be improved by modeling cancer bundles in more clinically granular ways that better reflect expected resource utilization for appropriate, standard of care. Insufficient clinical granularity in bundle construction can lead to provider performance being influenced by the distribution of patient subtypes at the practice. This can lead to inappropriate shifts of risk from payers to providers in value based models. Aggregate vs. subtype episode costs (mean, 5th, and 95th percentiles).[Table: see text]
Limited stage mantle cell lymphoma: Results of overall survival based on treatment modality using SEER database.
Authors: Apoorva Jayarangaiah, Shuai Wang, Tarek N. Elrafei, Lewis Steinberg, Abhishek Kumar
Journal: Journal of Clinical Oncology (2021)

e19566 Background: Limited stage mantle cell lymphoma (MCL) (stage I-II) is rare and occurs in 5-15% of patients. The ideal treatment approach among radiation (RT), chemotherapy (CT), chemoradiotherapy (CRT) or close monitoring (NT) has not been defined. Methods: A retrospective analysis of SEER database (1975 to 2018) was conducted for patients with stage I-II MCL to compare overall survival (OS) among the various treatment modalities in patients &gt;18 years. We excluded patients lacking information on demographic characteristics and survival. Patients were analyzed in 4 groups; RT only, CT only, CRT and no treatment groups. ANOVA test and Chi-square test were used to evaluate parametric and non-parametric variables between groups, respectively. Cancer specific survival (CSS) and OS were assessed by Kaplan-Meier. SPSS 26.0 was used for data analysis. Results: There were in total 2266 patients with limited stage MCL. Median age was 71 years (61-78.25) and predominantly male (65.7%). Stage I MCL was noted in 55.6% and stage II in 44.4% of the patients. The number of patients in each group; RT only, CT only, CRT and NT along with the OS are presented in Table. CSS among these four groups showed no statistically significant differences (p &lt;0.26). OS showed that CT only group has worse survival compared to RT only and CRT groups (p &lt;0.001). CRT has no significant difference in survival compared to RT only (p&lt;0.001). NT was associated with poorest survival rates (p&lt;0.001). Conclusions: In limited stage MCL, RT only and CRT resulted in superior OS compared to CT only. Results suggest a role for incorporation of RT in treatment regimens. One limitation of the study is that the SEER database lacks the ability to distinguish between no receipt of therapy versus lack of availability of data.[Table: see text]
Isatuximab plus carfilzomib and dexamethasone in patients with relapsed multiple myeloma according to prior lines of treatment and refractory status: IKEMA subgroup analysis.
Authors: Roman Hajek, Philippe Moreau, Bradley Augustson, Nelson Castro, Tomas Pika, Sosana Delimpasi, Javier de La Rubia, Angelo Maiolino, Tony J. Reiman, Irina Kryuchkova, Joaquin Martinez-Lopez, Thomas G. Martin, Joseph Mikhael, Kwee Yong, Marie-Laure Risse, Gaëlle Asset, Sylvia Marion, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2021)

8034 Background: Patients (pts) with multiple myeloma (MM) often relapse and become refractory to successive lines of therapy, warranting better treatment options. The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in pts with relapsed MM (RMM) (HR 0.53; 99% CI 0.32–0.89; P= 0.0007). We evaluated the efficacy and/or safety of Isa-Kd by number of prior lines of therapy (1 vs &gt; 1) and refractoriness to lenalidomide (Len) or bortezomib (Bor). Methods: Pts were randomized (3:2) to Isa-Kd (n = 179) or Kd (n = 123). Isa (10 mg/kg IV) was given weekly for 4 weeks, then every 2 weeks. K (20 mg/m² days 1-2, then 56 mg/m²) was given twice-weekly 3 of 4 weeks, and d (20 mg) twice-weekly. The primary endpoint was PFS; key secondary endpoints were very good partial response or better (≥VGPR), minimal residual disease negativity (MRD-), and complete response (CR) rates. Results: Of the 302 randomized pts, 44.7% had 1 prior line, 55.3% had &gt; 1 prior line, 32.8% were Len-refractory, and 30.1% were Bor-refractory. PFS was improved with Isa-Kd vs Kd in pts who received 1 prior line and &gt; 1 prior line, as well as in pts refractory to Len, Len at last regimen, Bor, or Bor at last regimen (Table). The addition of Isa to Kd improved depth of response (≥VGPR, MRD-, and CR rates) in all subpopulations analyzed by prior treatment. Grade ≥3 treatment-emergent adverse events (TEAEs) were generally similar between the prior line subgroups (77.2% [Isa-Kd] vs 64.8% [Kd], 1 prior line; 76.5% [Isa-Kd] vs 69.1% [Kd], &gt; 1 prior line) and the overall safety population (76.8% [Isa-Kd] vs 67.2% [Kd]). Serious AEs were 62.0% vs 48.1% in the 1 prior line subgroup, and 57.1% vs 64.7% in the &gt; 1 prior line subgroup; TEAEs leading to discontinuations were 8.9% vs 11.1%, 1 prior line and 8.2% vs 16.2%, &gt; 1 prior line. Conclusions: The addition of Isa to Kd improved PFS and depth of response, irrespective of prior lines of therapy or refractory status, consistent with the benefit observed in the overall IKEMA study population. Isa-Kd had a manageable safety profile regardless of number of prior lines. Isa-Kd is a potential new treatment option for pretreated pts with RMM. Clinical trial information: NCT03275285. [Table: see text]
Expression of Netosis Regulators and Correlation with Inflammatory and Coagulation Biomarkers in Sickle Cell Anemia Patients
Authors: Bidossessi Wilfried Hounkpe, Francine Chenou, Igor de Farias Domingos, Marcos Andre Cavalcanti Bezerra, Aderson da Silva Araujo, Dulcinéia Martins de Albuquerque, Rômulo Tadeu Dias de Oliveira, Maria Heloisa Blotta, Maria de Fátima Sonati, Fernando Ferreira Costa, Magnun Nueldo dos Santos, Erich Vinicius De Paula
Journal: Blood (2017)
Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor versus second-line chemotherapy for patients with recurrent small cell lung cancer.
Authors: Fengchun Mu, Bingjie Fan, Butuo Li, Wenru Qin, Xinyu Fan, Shijiang Wang, Chunni Wang, Bing Zou, Linlin Wang
Journal: Journal of Clinical Oncology (2021)

e20591 Background: The main aim of this study was to evaluate the efficiency of albumin-bound paclitaxel (nab-PTX) plus PD-1/PD-L1 inhibitor versus second-line chemotherapy in small cell lung cancer (SCLC) patients who have failure to the first-line standard treatment. Methods: We retrospectively collected patients’ data from medical records between January 2015 to July 2020 in Shandong Cancer Hospital and Institute. Consecutive 42 patients who were treated with nab-PTX plus PD-1/PD-L1 inhibitor were enrolled and compared with, 126 patients who received second-line chemotherapy (1:3 matched with patient and tumor characteristics). Progress free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Results: Patients treated with nab-PTX plus immunotherapy group and second-line chemotherapy group achieved the median PFS of 5.6 months and 3.3 months ( p = 0.043), respectively. The median OS were 7.7 months and 6.3 months ( p = 0.021), respectively. The ORR and DCR were also higher in nab-PTX plus PD-1/PD-L1 inhibitor group (ORR: 33.3% vs 20.6%, p = 0.094; DCR: 61.9% vs 41.3%, p = 0.020, respectively). The most common incidences of grade ≥3 adverse events were leukopenia and neutropenia, there were no significance difference between the two groups. Conclusions: Albumin-bound paclitaxel plus PD-1/PD-L1 inhibitor conferred higher ORR and DCR, and improved PFS and OS in SCLC patients failed with first-line treatment. Further prospective and randomized trial that directly compares the treatments is urgently warranted.
Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy
Authors: Andrea Di Marco, Pamela Frances Brown, Joshua Bradley, Gaetano Nucifora, Eduard Claver, Fernando de Frutos, Paolo Domenico Dallaglio, Josep Comin-Colet, Ignasi Anguera, Christopher A. Miller, Matthias Schmitt
Journal: Journal of the American College of Cardiology (2021)
EPEN-01. C11ORF95-RELA DICTATES ONCOGENIC TRANSCRIPTIONAL PROGRAMS TO DRIVE AGGRESSIVE SUPRATENTORIAL EPENDYMOMA
Authors: Amir Arabzade, Yanhua Zhao, Srinidhi Varadharajan, Hsiao-Chi Chen, Kelsey Bertrand, Benjamin Deneen, Stephen Mack
Journal: Neuro-Oncology (2021)

Abstract Over 60% of supratentorial (ST) ependymomas harbor a gene fusion between C11orf95, an uncharacterized gene, and RELA (also known as p65), a main component of the NF-ĸB family of transcription factors. While its sufficiency to drive tumor has been established, the mechanism of tumorigenesis remains elusive. To tackle this question, we developed a natively forming mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain and performed integrative epigenomic and transcriptomic mapping. Our findings indicate that in addition to direct canonical NF-ĸB pathway activation, C11orf95-RELA (CRfus) dictates a neoplastic transcriptional program and binds to unique sites across the genome enriched with Plagl family transcription factor motifs. CRfus modulates the transcriptional landscape by recruiting transcription co-activators (Brd4, EP300, Cbp, Pol2) which are amenable to pharmacologic inhibition. Downstream CRfus target genes converge on developmental programs marked by Plagl family of transcription factors and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks, many of which contain previously unreported therapeutic leads in C11orf95-RELA ependymoma.
Dose-painting radiation with concurrent chemotherapy for locally advanced non-small cell lung cancer: A single-center observational study.
Authors: Jiahua Lv, Junchao Wang, Hongyuan Jia, Long Liang, Lei Wu, Yi Wang, Qifeng Wang, Tao Li
Journal: Journal of Clinical Oncology (2021)

e20529 Background: Dose-painting radiotherapy is a promising technique which enables different dose distribution to different areas within the lung cancer. However, the efficacy and safety of this irradiation technique are still uncertain. In this study, we observed and analyzed the outcomes of dose-painting radiotherapy with chemotherapy for the locally advanced non-small cell lung cancer. Methods: Patients with stage III non-small cell lung cancer undergoing chemoradiotherapy were enrolled in this study. The dose-painting target was defined according to the distance between the tumor and the mediastinum (GTVwithin 2cm and GTVout-of 2cm). Doses of 60-80 Gy( 3-4Gy/fraction, bid) and 40-60 Gy (2-3Gy/fraction, bid) were prescribed to the GTVwithin 2cm and GTVout-of 2cm, respectively, in 20 fractions, using simultaneous integrated boost. All the patients received 2-4 cycles of chemotherapy using cisplatin plus paclitaxel or pemetrexed. Results: In total, 65 patients were included in this study. Median follow-up was 66.1 months (range 8.0-117.3months). The incidence of ≥Grade 2 radiation pneumonitis and esophagitis were was 30.8% and 38.5%, respectively. The 1, 3, 5-year OS and PFS were 78.4% and 58.5%, 32.3% and 26.1%, 18.5% and 13.8%, respectively. Late radiation esophagitis were seen in 3 patients and 2 patients were observed severe pulmonary fibrosis. None of the patients experienced fatal bronchopulmonary hemorrhage or tracheal fistula. Conclusions: Radiation dose painting with concurrent chemotherapy is feasible and well tolerated for locally advanced non-small cell lung cancer. It needs to be further confirmed by large randomized controlled clinical studies.
Impact on second-line treatment after failure of immune checkpoint inhibitor (ICI) combination chemotherapy in extensive-disease small cell lung cancer: Experience of the Okayama Lung Cancer Study Group.
Authors: Yuka Kato, Taku Noumi, Kazuhiko Saeki, Kiichiro Ninomiya, Toshio Kubo, Masanori Fujii, Kammei Rai, Eiki Ichihara, Kadoaki Ohashi, Masahiro Tabata, Katsuyuki Hotta, Toshiyuki Kozuki, Yoshinobu Maeda, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2021)

e20590 Background: For patients with extensive-disease small cell lung cancer (ED-SCLC), amrubicin monotherapy is an important therapy in the treatment of recurrence, but there has been no adequate evaluation of how effective it actually is after failure of first-line chemotherapy including immune checkpoint inhibitor (ICI). Therefore, the purposes of this study are to determine the proportion of patients who received amrubicin monotherapy in the treatment of relapse after first-line treatment with ICI (arm A) and to investigate the efficacy of amrubicin therapy after arm A compared with after chemotherapy without ICI (arm B). Methods: Consecutive 40 pts with ED-SCLC NSCLC were retrospectively assessed who underwent ICI-containing chemotherapy (n = 19) or standard cytotoxic chemotherapy (n = 21) in the 1st-line setting between 2017 and 2020. Results: In arm A, 3 of 19 patients (16%) were still on first-line ICI maintenance therapy, 2 (2/19; 11%) had ICI treatment adverse events (interstitial pneumonia, cardiopulmonary arrest), and 1 patient could not receive second-line therapy due to a decrease in performance status (PS) to 3. In arm B, 11 of 21 patients (52%) did not receive amrubicin as second-line therapy, including 1 patient with worsening PS, 1 patient with adverse events (hematologic toxicity), 1 patient refusal, and 6 patients with combination of ICI and chemotherapy. 23 patients (arm A; 13 (57%), arm B; 10 (43%)) were able to receive amrubicin monotherapy, including 7 patients (6 cases vs 1 case) were sensitive relapses, and 16 (7 vs 9 cases) were refractory relapses. There was no significant difference in either PFS or survival after first-line treatment in 16 patients with refractory relapse who received amrubicin as second-line treatment (PFS: 4.8 vs 5.2 months, p = 0.51), (median survival after first-line treatment: 9.6 vs 12.8, p = 0.75). Conclusions: Patients who received ICI in the first-line treatment were fully eligible to receive amrubicin in the second-line treatment. The recurrence pattern tended to be sensitive relapse and we found that the efficacy of amrubicin in refractory relapse was not affected by the administration of ICI in the first-line treatment.