tbuckley/cabot-search huggingface dataset:
Design of eSyM: An ePRO-based symptom management tool fully integrated in the electronic health record (Epic) to foster patient/clinician engagement, sustainability, and clinical impact.
Authors: Michael J. Hassett, Hannah Hazard, Raymond U. Osarogiagbon, Sandra L. Wong, Jessica J Bian, Don S. Dizon, Jason Wedge, Ethan M. Basch, Jennifer Mallow, Nadine Jackson McCleary, David W. Dougherty, Scot C. Remick, Gabriel A. Brooks, John Mecchella, Peter Solberg, Laura Tasker, Nicholas Faris, Alicia Pacheco, Christine Cronin, Deborah Schrag
Journal: Journal of Clinical Oncology (2020)

164 Background: Chemotherapy and surgery can cause distressing symptoms, which can be a burden for health systems to address. Programs that directly engage patients, including electronic tracking of patient-reported outcomes (ePROs), can improve symptom control and decrease the need for acute care. Previous ePRO programs have relied on third party vendors with limited EHR integration, constraining their clinical utility and scalability. An integrated solution could offer distinct advantages. Methods: As part of NCI’s Moonshot-funded IMPACT consortium, 6 health systems and Epic built an electronic symptom management program (eSyM) based on the PRO-CTCAE questionnaire that is fully integrated into the EHR. The agile, user-centered design process engaged patients, clinicians, and institutions. The core functional components include: 1) symptom surveys in the postoperative period or between chemotherapy visits, 2) self-management tip sheets, 3) clinician alerts, and 4) dashboards for population management. Critical points of integration with supporting EHR functions and workflow impacts were identified; and major challenges of integration and implementation were described. Results: eSyM, which was implemented at two health systems (Baptist Memorial in Tennessee and Mississippi and West Virginia University Health) in the fall of 2019, required multiple supporting EHR functions: 1) access a secure, HIPPA-compliant patient portal/messaging system (MyChart); 2) record diagnosis, procedure and chemotherapy treatment plan data; 3) identify target populations and track metrics/events; 4) define and execute autonomous logic-based workflow rules; 5) generate reports for clinicians/patients; and 6) documentation. Major challenges included: 1) working within pre-existing EHR system standards and capabilities, which limited the ability to customize interfaces and workflows specifically for the eSyM use case; and 2) adapting to different EHR configurations and polices across multiple health systems. Conclusions: The eSyM build leveraged many existing EHR capabilities and overcame regulatory hurdles; but it required design and workflow compromise. Integration of ePRO-based symptom management programs into the EHR could help overcome barriers, consolidate clinical workflows, and foster scalability/sustainability. Ongoing efforts include launching eSyM at four more sites and evaluating its adoption, usability, and impact on clinical outcomes.
Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb/V and dialysis in Spanish clinical practice – preliminary data Vie-KinD study
Authors: M.-C. Londoño, L. Garcia-Buey, J. Mallolas, G. Barril, A. Ahumada, M. Riveiro-Barciela, R. Muñoz-Gomez, M. Roget, M.A. Serra, M.J. Devesa, C. Navascues, C. Baliellas, T. Aldamiz-Echevarria, M.L. Gutierrez, I. Carmona, B. Polo-Lorduy, L. Bonet, J. Garcia-Samaniego, M. Jiménez, M. Prieto, S. Moran, A. Castro, M. Delgado, F. Gea, I. Martin-Granizo, M. Montes, L. Morano, M.A. Castaño, I. De los Santos, M. Laguno, J.E. Losa, M. Montero, A. Rivero, A. Manzanares, C. De Alvaro
Journal: Journal of Hepatology (2017)
Genomic characterization of metastatic lung cancers.
Authors: Hui Yu, Hua Bao, Yulin Wei, Min Wu, Shuyu Wu, Xue Wu, Yang Shao, Xinmin Zhao
Journal: Journal of Clinical Oncology (2020)

9584 Background: Lung carcinomas are most often diagnosed at stage IV, with metastases, which contribute to 90% of deaths of patients. Enormous efforts have been made in previous studies in seek of underlying mechanisms and treatments that prevent or cure metastases. However, few comprehensive conclusions have been drawn on organ-specific genomic landscapes and molecular dependencies of lung cancer metastases, largely due to limited sample sizes. Methods: We employed massive targeted next generation sequencing (NGS) with a panel covering 425 cancer-related genes on 10409 samples from 8619 patients with lung cancer, including 8479 from primary tumors and 1930 from metastases to the brain, liver, pleura, bones, and lymph nodes. We investigated single nucleotide variants (SNVs), copy number variants (CNVs), structural variations (SVs), mutational signatures, and other genomic characteristics at all primary and metastatic sites. With data of primary-metastatic tumor pairs, we also examined genomic evolutionary patterns. Results: Our data revealed that metastases harbored more instable and complicated genomes. Most SNVs (5/6), CNVs (41/47), and SVs (2/3) that showed significant differences of prevalence between primary tumors (PTs) and metastases (MTs) were MT-enriched. Among them, we identified a novel MT-enriched event, PTK2 amplification (2.33 folds), as well as known ones including mutations of TP53, ARID1A, and BRCA1 (1.23, 1.74, and 2.29 folds) , and amplifications of MYC, RICTOR, and EGFR (2.04, 2.15, and 1.59 folds). In addition, almost all actionable CNV alterations (6/7) showed higher frequencies in MTs. ALK fusions and EGFR mutations, which indicate distinct target therapies, exhibited opposite preference in MTs and PTs, respectively. We also identified MT site-specificity of alterations, such as NF2, TSC2, and LRP1B mutations enriched in the brain, BRAF and GNAS mutations absent in the liver, and APOBEC-associated mutational signatures enriched in lymph nodes. Moreover, we unraveled organ-specific patterns of genomic evolutionary trajectories in metastatic diseases. Conclusions: The genomic profile and evolutionary pattern of metastatic lung cancer differed from that of primary tumors. The identification of site-specific characteristics that may have empowered directional metastasis, such as NF2, TSC2, and LRP1B mutations in the brain and APOBEC-associated mutational signatures in lymph nodes, may guide personalized disease management, design of clinical trials, and/or discovery of therapeutic targets for metastatic lung cancer at different body regions.
Impact of absolute lymphocyte count on the efficacy of eribulin and capecitabine in patients with metastatic breast cancer.
Authors: Ayako Ueno, Reina Maeda, Kyeongduk KIM, Mitsuya Ito, Kensuke Kawasaki, Shoichiro Ohtani
Journal: Journal of Clinical Oncology (2020)

e13082 Background: In a phase 3 trial (Study 301), which compared eribulin and capecitabine for metastatic breast cancer did not show the superiority of one to the other on overall survival. Recently, a post-hoc analysis has revealed that efficacy of eribulin was greater in patients with high levels of absolute lymphocyte count (ALC), probably because the drug has immunologic mechanisms of action. Here we investigated whether the favorable impact of high ALC levels on the efficacy was specific to eribulin or shared with capecitabine. Methods: A total of 275 patients with metastatic breast cancer who were treated with eribulin (n = 125) or capecitabine (n = 150) in our hospital between July 2011–April 2019 were retrospectively analyzed. Progression-free survival (PFS) was compared between patients with higher ALC levels (≥1500/μL) and those with lower ALC levels ( &lt; 1500/μL) in each treatment group. Then, we investigated how hazard ratio (HR) of PFS (eribulin vs. capecitabine) changed when we excluded patients with low ALC levels one by one; a scatter plot was made (X = cut-off value of ALC, Y = adjusted HR). PFS was compared by using the Cox proportional hazards model and covariates included age, hormonal and HER2 status, presence/absence of liver and other visceral metastasis, the number of involved organs and the number of previous chemotherapy regimens. Results: In eribulin group, PFS was significantly better in patients with higher ALC than those with lower ALC (adjusted HR, 0.50 [95% confidence interval (CI), 0.29–0.85]; p = .010). Contrarily, in capecitabine group, PFS was not significantly different between the two groups (adjusted HR, 0.86 [95% CI, 0.58–1.28], p = .456). According to the scatter plot, as the cut-off value of ALC (X) was increased, the hazard ratio of PFS (Y) changed biphasically, being almost flat when X was less than 1500, and a linear decrease when X was 1500 or more. Adjusted HR were (i) 1.07 [95% CI, 0.64–1.82], (ii) 0.79 [95% CI, 0.29–2.11] and (iii) 0.67 [95% CI, 0.18–2.41] when inclusion criteria of patients were (i) ALC ≥1500/μL, (ii) ALC ≥1900/μL and (iii) ALC ≥2200/μL, respectively. Conclusions: The efficacy of eribulin was significantly better in patients with higher ALC levels, whereas that of capecitabine was not significantly different. “The more, the better” relationship between ALC and the efficacy of eribulin (vs. capecitabine) was recognized when ALC was 1500/μL or more.
Clinically relevant multi-omic analysis of colorectal cancer.
Authors: Silvia von der Heyde, Margarita Krawczyk, Julia Bischof, Thomas Corwin, Peter Frommolt, Jonathan Woodsmith, Hartmut Juhl
Journal: Journal of Clinical Oncology (2020)

e16063 Background: Cancer is a highly heterogeneous disease, both intra- and inter-individually consisting of complex phenotypes and systems biology. Although genomic data has contributed greatly towards the identification of cancer-specific mutations and the progress of precision medicine, genomic alterations are only one of several important biological drivers of cancer. Furthermore, single-layer omics represent only a small piece of the cancer biology puzzle and provide only partial clues to connecting genotype with clinically relevant phenotypic data. A more integrated approach is urgently needed to unravel the underpinnings of molecular signatures and the phenotypic manifestation of cancer hallmarks. Methods: Here we characterize a colorectal cancer (CRC) cohort of 500 patients across multiple distinct omic data types. Across this CRC cohort, we defined clinically relevant whole genome sequencing based metrics such as micro-satellite-instability (MSI) status, and furthermore investigate gene expression at the transcript level using RNA-Seq, as well as at the proteomic level using tandem mass spectrometry. We further characterized a subgroup of 100 of these patients through 16s rRNA sequencing to identify associated microbiome profiles. Results: We combined these analyses with comprehensive clinical data to observe the impact of ascertained molecular signatures on the CRC patient cohort. Here, we report how patient survival correlates both with specific molecular events across individual omic data types, as well as with combined multi-omic analyses. Conclusions: This project highlights the utility of integrating multiple distinct data types to obtain a more comprehensive overview of the molecular mechanisms underpinning colo-rectal cancer. Furthermore, through combining identified aberrant molecular mechanisms with clinical reports, multi-omic data can be prioritized through their impact on patient cohort survival.
Building an international consortium for tracking coronavirus health status
Authors: Eran Segal, Feng Zhang, Xihong Lin, Gary King, Ophir Shalem, Smadar Shilo, William E. Allen, Faisal Alquaddoomi, Han Altae-Tran, Simon Anders, Ran Balicer, Tal Bauman, Ximena Bonilla, Gisel Booman, Andrew T. Chan, Ori Cohen, Silvano Coletti, Natalie Davidson, Yuval Dor, David A. Drew, Olivier Elemento, Georgina Evans, Phil Ewels, Joshua Gale, Amir Gavrieli, Benjamin Geiger, Yonatan H. Grad, Casey S. Greene, Iman Hajirasouliha, Roman Jerala, Andre Kahles, Olli Kallioniemi, Ayya Keshet, Ljupco Kocarev, Gregory Landua, Tomer Meir, Aline Muller, Long H. Nguyen, Matej Oresic, Svetlana Ovchinnikova, Hedi Peterson, Jana Prodanova, Jay Rajagopal, Gunnar Rätsch, Hagai Rossman, Johan Rung, Andrea Sboner, Alexandros Sigaras, Tim Spector, Ron Steinherz, Irene Stevens, Jaak Vilo, Paul Wilmes
Journal: Nature Medicine (2020)

We call upon the research community to standardize efforts to use daily self-reported data about COVID-19 symptoms in the response to the pandemic and to form a collaborative consortium to maximize global gain while protecting participant privacy.
African Access Initiative: A holistic, multi-sector approach to mitigating Africa’s cancer crisis.
Authors: Jennifer Dent, Katy Graef, Joseph Hargan-Calvopina, Analise LeJeune, Daniel Seymour, Callie Weber
Journal: Journal of Clinical Oncology (2020)

e19015 Background: In a dramatic reversal of trends, cancer now kills more Africans each year than malaria. Should trends continue, Africa’s cancer burden is projected to double to over 2 million new cases and over 1.4 million deaths annually by 2040. Africa’s burgeoning cancer crisis is attributable to many factors, including insufficient preventive, diagnostic, and treatment services; inadequate clinical infrastructure; and shortages of trained healthcare personnel. Methods: BVGH launched the African Access Initiative (AAI) in 2017 to address Africa’s cancer crisis. Utilizing a holistic approach that establishes sustainable access to cancer medicines, strengthens healthcare infrastructure, and builds clinical oncology capacity, BVGH is eliminating or minimizing many of the challenges African clinicians face when diagnosing and treating cancer patients. Complementing its innovative approach, BVGH engages experts across sectors to build capacity and execute programs. African ministries of health and cancer leaders are engaged to ensure AAI activities are driven by their priorities and needs. AAI is not a donation-based program. Pharmaceutical companies are engaged to ensure access to quality, lifesaving cancer drugs in a sustainable and patient-focused manner. International cancer experts are enlisted in capacity building programs that directly align with their expertise and meet their global oncology goals. Results: BVGH is applying its multi-faceted, multi-sector model in Cameroon, Côte d'Ivoire, Kenya, Nigeria, Rwanda, and Senegal. In partnership with Nigeria’s Ministry of Health, BVGH held a cancer stakeholder meeting to define the country’s priority cancers, drugs, and treatment regimens. Following the meeting, BVGH launched an RFP to pharmaceutical companies and subsequently developed reports that forecast full treatment costs based on the companies’ offerings of deeply-discounted drug prices. While simultaneously coordinating drug access, BVGH began planning training refreshers to ensure recipient Nigerian hospitals were ready to use the prioritized cancer drugs successfully. Beyond Nigeria, BVGH has improved Rwanda’s ability to diagnose cancer efficiently; improved Côte d'Ivoire’s multidisciplinary approach to diagnosing and treating cancer patients; and helped Kenya refine its cancer patient sample referral mechanisms. Conclusions: This presentation will describe BVGH’s holistic, multi-sector approach to addressing Africa’s cancer crisis, including partners, activities, lessons learned, and best practices.
Three-tier integrated model for management of type 2 diabetic patients
Authors: Zhaoxia Li, Shilu Xu, Jianxia Hu, Leping Shao, Guoxin Ma, Zhengju Fu
Journal: BMJ (2016)

Two hundred and twelve type 2 diabetes mellitus (T2DM) patients were followed up for 1 years, they were divided randomly into the control group and the study group (n=106 for each). Patients in study group were managed by a community-secondary hospital-tertiary hospital integrated system. The blood glucose, lipids, islet function, glucose control rate, self-management ability, diabetic complications, and referral rate were compared between two groups. The levels of blood glucose, lipid, blood pressure and glycosylated hemoglobin in study group were significantly lower than those in control group (P<0.05). The islet function, self-management ability and blood glucose control rate in study group were significantly higher than those of in control group after the management (P<0.05). During the 12-month follow-up the incidence rates of complications in study group and control group were 34.0%, 44.3%; and referral rates were 46.2%, 19.8%, respectively. The integrated management system is beneficial to T2DM patients with improving the control rate of blood glucose, enhancing the ability of self-management, and reducing the incidence of diabetic complications.


Key words: 
Diabetes, type 2; Disease management
The safety and efficacy of weekly paclitaxel and cisplatin chemotherapy for patients with ovarian cancer who developed carboplatin hypersensitivity reaction in previous chemotherapy.
Authors: Kyoko Nishikimi, Shinichi Tate, Ayumu Matsuoka, Makio Shozu
Journal: Journal of Clinical Oncology (2020)

6058 Background: Carboplatin (CBDCA) hypersensitivity reactions (HSR) often occur in patients with ovarian cancer. Once CBACA HSR occurs, it is difficult to use platinum even though the patients had platinum-sensitive disease and consequently the survival of the patients cannot be prolonged. We had administered weekly paclitaxel and cisplatin (CDDP) chemotherapy (wTP) for patients with ovarian cancer who developed CBDCA HSR in previous chemotherapy. We investigated the safety and efficacy of wTP. Methods: We investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed CBDCA HSR in previous chemotherapy (paclitaxel/CBDCA) at our institution between 2011 and 2019. After premedication was administered, paclitaxel and sequentially CDDP were administered as one hour infusion, respectively (paclitaxel 80 mg/m 2 , CDDP 25 mg/m 2 ; 1, 8, 15 day/4 weeks). Results: The median cycle of the previous chemotherapy of CBDCA was 8 (interquartile range [IQR], 6–11). The grade of CBDCA HSR was 1 in 57 (66%), 2 in 26 (30%), and, 3 in 1 (1%) patient(s). WTP was administered for the first line in 21 (24%), second line in 35 (41%) and third or more line in 30 patients (34%). The median cycles of wTP administration was 4 (IQR, 3–7). We observed that severe CDDP HSR did not occur in any patients and 15 patients (17.4%, grade 1, 10 patients; grade 2, 5) developed CDDP HSR. All CDDP HSR were successfully managed with infusion interruption and Hydrocortisone Sodium Phosphate administration. There was no relation between the grade of CBDCA HSR in the previous chemotherapy and the rate of CDDP HSR (p = 0.363). Progression-free survival and overall survival after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95%Ci: 19.0–50.2), respectively. Conclusions: 71 patients (82%) who developed CBDCA HSR in previous chemotherapy were able to continue administration of wTP without CDDP HSR. WTP was safe and effective for the patients who developed CBDCA HSR. [Table: see text]
Glasdegib in combination with azacitidine (AZA) in patients (pts) with untreated higher-risk myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML): Effects on marrow recovery and transfusion independence.
Authors: Amer Methqal Zeidan, Michael Schuster, Magalie Joris, Jurgen Krauter, Johan Maertens, Emmanuel Gyan, Tibor Kovacsovics, Amit Verma, Paresh Vyas, Eunice S. Wang, Wendy Ma, Mirjana Zeremski, Art Kudla, Geoffrey Chan, Mikkael A. Sekeres
Journal: Journal of Clinical Oncology (2020)

7526 Background: Glasdegib, an oral inhibitor of the Hedgehog signaling pathway, is approved in the USA in combination with low-dose cytarabine to treat pts with newly diagnosed AML unable to receive intensive chemotherapy due to comorbidities or age (≥75 years). Glasdegib + AZA showed promising remission rates and overall survival with a generally well-tolerated and manageable safety profile in an analysis of BRIGHT MDS &amp; AML 1012 in pts with MDS, AML and CMML. Here we evaluate early hematopoietic recovery and transfusion independence with glasdegib + AZA in this ongoing Phase Ib study. Methods: Untreated pts with MDS, AML and CMML ineligible for intensive chemotherapy received glasdegib (100 mg QD) + AZA (75 mg/m 2 /D on D1–7 q28D). Data cutoff: Sept 11, 2019. Results: Among pts with MDS (n=30; including 3 with CMML), median duration of treatment was 5.0 months (range, 0.4–15.5). Recovery of absolute neutrophil count (ANC), hemoglobin (Hb) and platelets at 2 thresholds started in cycle (Cyc) 1 (Table). Early platelet recovery correlated with response to treatment; 54% (7/13) of pts with platelets ≥100,000/µL at Cyc 2, D1 achieved complete or partial remission vs 0% (0/13) of pts with &lt;100,000/µL, P=0.002. Start of Cyc 2 was delayed due to AEs in 8% (2/26) of pts. 54% (7/13) of evaluable pts transfusion dependent at baseline (BL) became transfusion independent. Among pts with AML (n=30), median duration of treatment was 5.0 months (range, 0.3–14.9). ANC, Hb and platelet recoveries started in Cyc 1 (Table). 9% (2/23) of pts had Cyc 2 dose delays due to AEs. 64% (9/14) of evaluable pts transfusion dependent at BL became transfusion independent. Clinical trial information: NCT02367456 . Conclusions: Glasdegib + AZA shows promising rates of survival with early marrow recovery in the up-front treatment of pts with MDS, AML and CMML ineligible for intensive chemotherapy. The association between early hematopoietic recovery and efficacy in the MDS cohort merits further study. [Table: see text]
Cabozantinib (cabo) combined with durvalumab (durva) in gastroesophageal (GE) cancer and other gastrointestinal (GI) malignancies: Preliminary phase Ib CAMILLA study results.
Authors: Anwaar Saeed, Milind Phadnis, Robin Park, Weijing Sun, Raed Moh'd Taiseer Al-Rajabi, Joaquina Celebre Baranda, Stephen K. Williamson, Zachary Collins, Jeanette Firth-Braun, Azhar Saeed, Carolyn Foster, Benjamin Roberts, Dharmalingam Subramaniam, Anup Kasi, Shrikant Anant
Journal: Journal of Clinical Oncology (2020)

4563 Background: Cabo targets multiple tyrosine kinases, including VEGFR, MET, and AXL, and has been reported to show immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining it with PD-L1 inhibitors like durva. We conducted a phase Ib GI basket trial to evaluate the safety &amp; efficacy of this regimen in advanced GE adenocarcinoma (GEA), colorectal cancer (CRC), &amp; hepatocellular carcinoma (HCC). Methods: Patients received cabo and durva in 3+3 dose escalation then expansion to determine the dose limiting toxicity (DLT), Recommended Phase 2 Dose (RP2D), ORR, PFS &amp; OS. Cabo was dosed at 20mg QD, 40mg QD, and 60mg QD in the first, second, and third cohorts respectively. Durva was dosed at 1500mg IV Q4W in all cohorts. DLT window was 28 days. Scans were obtained every 8 wks. Treatment beyond progression was allowed. Results: 23 Pts (16 M, 7 F), median age 60 yrs (range 33-79) were currently enrolled. 12 in the dose escalation cohort with cabo 20mg (6 pts), or 40mg (3 pts), or 60mg (3 pts). 11 pts enrolled in the dose expansion cohort with cabo 60mg. 8 pts had GEA, 13 pts had CRC, and 2 pts had HCC. Median number of prior chemotherapies was 3 (range 1-3). 3 pts were not evaluable for DLT due to missing ≥30% of DLT window doses, not related to DLT. No DLTs were observed. Drug-related Grade (G) 1&amp;2 AEs included fatigue (83%), abnormal LFTs (39%), anorexia (26%), diarrhea (26%), nausea (13%), &amp; hand foot syndrome (13%). One pt each developed drug related G3 hypertension, hyperthyroidism, thrombocytopenia, &amp; thromboembolic event, all occurring outside the DLT window. 19 pts were evaluable for response: 4 PR (2 GEA &amp; 2 CRC), 12 SD, 3 PD; ORR 21%; clinical benefit rate 84%; median time to PD 16 wks (range 8-40+). Conclusions: RP2D was determined to be Cabo 60mg QD and Durva 1500mg Q4W. Enrollment to phase I dose expansion is ongoing. RP2D may be adjusted based on additional experience &amp; long-term tolerability. Early efficacy data was encouraging. This is an investigator-initiated trial funded by Exelixis &amp; Astrazeneca. Clinical trial information: NCT03539822 .