tbuckley/cabot-search huggingface dataset:
Distress screening for patients with a history of cancer during the COVID-19 pandemic.
Authors: Brooke Worster, Lauren Waldman, Gregory D. Garber, Subecha Dahal, Adam F Binder, Valerie Pracilio Csik, Nathan Handley, Alexandra Gentsch, Kristin Rising, Olivia Trachtenberg, Ana Maria Lopez
Journal: Journal of Clinical Oncology (2021)

e13537 Background: Although a diagnosis of cancer is widely accepted as resulting in significant levels of distress, distress itself cannot be considered benign and screening for distress is considered a best practice metric for patients receiving oncological care. Endorsed by NCCN, the Distress Thermometer (DT) considers a cutoff score of 4 or greater to identify patient with clinically relevant levels of distress. We hypothesized that the COVID-19 pandemic would manifest with higher levels of stress and anxiety in most persons by compounding the distress experienced by patients with a diagnosis of cancer. Methods: Patients with a new diagnosis of cancer underwent distress screening with the DT prior to a clinical appointment at a NCI-designated academic cancer center. Patients who scored 4 or higher were discussed at an Interprofessional Supportive Medicine patient conference or referred to oncology social work for appropriate evaluation and therapeutic care. By mid-March 2020, the SKCC catchment area was under a public health emergency with limited access to non-essential healthcare; therefore, we present data from 1/1-3/15/20 (pre-pandemic), 3/16-6/7/20 (pandemic peak with 2000+ daily cases in late April and peak daily deaths 300+ in May), and 6/8-8/30/20 (daily cases generally less than 700 except for occasional levels of 1000-in July and daily deaths less than 40 daily). Results: In the pre-pandemic time period, 60% of patients assessed reported a score of 4 or higher. During the subsequent periods—the first pandemic peak and the first post-pandemic period—the incidence of an elevated distress screen (4 or higher) was relatively stable at about 30%. Conclusions: Contrary to expectations, the DT screen identified less patient distress during the pandemic compared to pre-pandemic. Our results may be due to multiple factors—changes in processes and procedures to prioritize DT screening as pandemic risk became more apparent; an increased use of telemedicine; and the compounding of new, non-cancer related stressors resulting in the greater resiliency noted in disaster psychology. For example, during the first pandemic peak when the majority of patients were seen via telemedicine, the opportunity afforded by telemedicine for safety and decreased risk for COVID-19 infection may have reduced the overall distress experience. In addition, the compounding of stressors—the diagnosis of cancer, the risk of the pandemic, and its economic and financial stressors—may have influenced distress perception. Future work incorporating multiple distress assessment points may help better understand the impact of the layers of stress experienced by persons with cancer.[Table: see text]
Тактика и хирургическое лечение механической желтухи различной этиологии
Authors: V.M. Ratchik, N.V. Prolom, D.V. Orlovskyi, A.N. Burenko
Journal: GASTROENTEROLOGY (2014)

В отделении хирургии органов пищеварения ГУ «Институт гастроэнтерологии НАМН Украины» за период с 2003 по 2013 г. оперировано 567 пациентов с патологией гепатопанкреатобилиарной зоны различной этиологии, осложненной механической желтухой. Двухэтапному лечению подлежали 197 (34,7 %) больных с билирубинемией более 200 мкмоль/л и III степенью печеночной недостаточности. Эндоскопические (двухмоментные) методики применялись при лечении 143 (25,2 %) пациентов с холедохолитиазом. Одномоментные мини-инвазивные вмешательства — лапароскопическая холецистэктомия, наружное дренирование холедоха, литэкстракция, баллонная дилатация сфинктера Одди — выполнены у 41 (10,4 %) пациента. При осложненном хроническом панкреатите дренирующие оперативные вмешательства проводились у 20 (25,6 %) пациентов и резекционно-дренирующие — у 39 (50,0 %), с коррекцией желчеоттока, а также осуществлялись эндоскопические, лапароскопические и мини-инвазивные пункционно-дренирующие операции. 2 (2,6 %) больным выполнена панкреатодуоденальная резекция по Whipple. Двухэтапные оперативные вмешательства были выполнены 26 (33,3 %) пациентам. При опухолях холангиопанкреатодуоденальной зоны у 18 (30,5 %) больных провели чрескожные эндобилиарные разгрузочные вмешательства с последующим радикальным хирургическим лечением 10 (16,9 %) пациентов.
Characteristics of the Multi Disciplinary Cancer Conference (Tumor Boards) in the COVID 19 era.
Authors: Lijo Simpson, Anju Mathew, Robert Wojciechowski
Journal: Journal of Clinical Oncology (2021)

e13561 Background: Cancer centers in the US are required to discuss a minimum of 15% analytic cases and prospective presentation (minimum 80%) in the multidisciplinary case conference (tumor board, MDCC), per the Commission on Cancer accrediting standards. Tumor board discussion have been shown to improve treatment decision making and patient outcomes. These meetings were in person meetings in the Pre-COVID era. The COVID 19 pandemic and the subsequent requirements for social distancing forced hospitals to move most MDCCs to a virtual format. We report on the large scale utilization of a propriety Care-Coordination platform OncoLens to run MDCCs across the country. Methods: Technology quality metrics were collected from the ongoing daily usage of the platform including time characteristics, care team utilization metrics, average attendance, quality metrics collected for accreditation and clinical trials matching on the OncoLens platform. Results: The virtual platform was accessible to around 8000 providers across the United States. On average per month there were 250 virtual meetings with over 290,000 meeting minutes. Conferences ranged from 30 minutes to 4 hours. 75% of users used the web application 25% of users utilized their smart phones .System uptime was 99.99%. Hospitals were able to conduct General and Site specific conferences. Virtual attendance of the required specialties of Medical Oncology, Radiation Oncology, Surgery, Pathology and Radiology was attained, with the average conference attendance being 14. On average hospitals required 2 administrative training sessions. Most of the case presentations were prospective. This format does enable cancer programs to collect quality metrics around Cancer program accreditation by the American College of Surgeons. A wide variety of common and rare cancer types were discussed in the virtual format. 66% of patients discussed potentially matched to clinical trials during the discussion. Conclusions: The shift of MDCCs to a mostly virtual environment occurred quickly in response to the COVID 19 pandemic. It took an average of 2 training classes to get the cancer care team on board with the use of new technology. It is possible to have high quality discussions and attain metrics for Commission On Cancer accreditation utilizing a virtual platform.
Optimal dose selection in oncology biologics development: Need for a paradigm shift.
Authors: Rajendar K Mittapalli, Kai Hsin Liao, Jason Williams, Rameshraja Palaparthy, Donghua Yin
Journal: Journal of Clinical Oncology (2021)

3093 Background: In oncology, the recommended phase 2 dose (RP2D) is typically selected from the first-in-patient (FIP) dose escalation and then carried forward to late stage trials. The RP2D is often informed by limited data from a relatively small number of patients. Further dose optimization in late stage trials is rare as these trials often evaluate only one dose/dosing regimen. Traditionally oncology development relied on establishing an MTD with the expectation this dose would ultimately provide an optimal benefit/risk profile. However, for biologics there are clear examples suggesting a need to reconsider this approach to dose selection during drug development. The present review attempts to evaluate the dose selection approaches for approved oncology biologics to identify opportunities for improved dose optimization of future oncology drugs. Methods: The dose selection steps for oncology biologics approved by the USFDA from 2010 to 2020 were reviewed. The primary focus of the review was RP2D selection based on early clinical data, doses tested in pivotal trials, exposure-response and dose justification for the proposed dose, and post-marketing requirements (PMR) or post-marketing commitments (PMC) related to dose optimization. Results: The dose selection process for a total of 22 biologics was analyzed. Among these, 17 (77%) did not identify MTD during the FIP trial, and 6 (27%) tested more than one dose in the registration trials. In the initial approval, 2 (10%) had PMR or PMC for further dose optimization. For majority of the biologics the dose justification was based on 1) receptor occupancy 2) biomarker response 3) early clinical activity and 4) target efficacious concentration based on xenograft data. The majority of biologics had shown a shallow exposure-response relationship in safety or efficacy end points which partly can be attributed to the common practice of testing single dose level in the registrational trial. The dose recommended in the FDA label appears to be highly correlated to the RP2D determined in FIP studies. Conclusions: Oncology biologics have heavily relied on pharmacodynamic, early signs of efficacy, and safety data from the limited number of patients in the FIP dose escalation to identify the dose for pivotal trials. In most cases, there have been no dose ranging or optimization based on the final therapeutic outcome. While integration of relevant biomarker, PK, and PD data for optimal dose selection is an important aspect, there is a need to change the paradigm to consider more robust dose optimization, especially in early stage development. Dose ranging assessments incorporating therapeutically relevant endpoints and adequate sample size should be considered, ideally prior to pivotal trials.
Racial and Ethnic Disparities in Peripheral Artery Disease
Authors: Eddie L. Hackler, Naomi M. Hamburg, Khendi T. White Solaru
Journal: Circulation Research (2021)

Peripheral artery disease is an obstructive, atherosclerotic disease of the lower extremities causing significant morbidity and mortality. Black Americans are disproportionately affected by this disease while they are also less likely to be diagnosed and promptly treated. The consequences of this disparity can be grim as Black Americans bear the burden of lower extremity amputation resulting from severe peripheral artery disease. The risk factors of peripheral artery disease and how they differentially affect certain groups are discussed in addition to a review of pharmacological and nonpharmacological treatment modalities. The purpose of this review is to highlight health care inequities and provide a review and resource of available recommendations for clinical management of all patients with peripheral artery disease.
Trends in Venous Thromboembolism Anticoagulation in Patients Hospitalized With COVID-19
Authors: Valerie M. Vaughn, Monica Yost, Chelsea Abshire, Scott A. Flanders, David Paje, Paul Grant, Scott Kaatz, Tae Kim, Geoffrey D. Barnes
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Venous thromboembolism (VTE) is a common complication of COVID-19. It is not well understood how hospitals have managed VTE prevention and the effect of prevention strategies on mortality. <h3>Objective</h3> To characterize frequency, variation across hospitals, and change over time in VTE prophylaxis and treatment-dose anticoagulation in patients hospitalized for COVID-19, as well as the association of anticoagulation strategies with in-hospital and 60-day mortality. <h3>Design, Setting, and Participants</h3> This cohort study of adults hospitalized with COVID-19 used a pseudorandom sample from 30 US hospitals in the state of Michigan participating in a collaborative quality initiative. Data analyzed were from patients hospitalized between March 7, 2020, and June 17, 2020. Data were analyzed through March 2021. <h3>Exposures</h3> Nonadherence to VTE prophylaxis (defined as missing ≥2 days of VTE prophylaxis) and receipt of treatment-dose or prophylactic-dose anticoagulants vs no anticoagulation during hospitalization. <h3>Main Outcomes and Measures</h3> The effect of nonadherence and anticoagulation strategies on in-hospital and 60-day mortality was assessed using multinomial logit models with inverse probability of treatment weighting. <h3>Results</h3> Of a total 1351 patients with COVID-19 included (median [IQR] age, 64 [52-75] years; 47.7% women, 48.9% Black patients), only 18 (1.3%) had a confirmed VTE, and 219 (16.2%) received treatment-dose anticoagulation. Use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased over time (adjusted odds ratio [aOR], 1.46; 95% CI, 1.31-1.61 per week). Of 1127 patients who ever received anticoagulation, 392 (34.8%) missed 2 or more days of prophylaxis. Missed prophylaxis varied from 11% to 61% across hospitals and decreased markedly over time (aOR, 0.89; 95% CI, 0.82-0.97 per week). VTE nonadherence was associated with higher 60-day (adjusted hazard ratio [aHR], 1.31; 95% CI, 1.03-1.67) but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03). Receiving any dose of anticoagulation (vs no anticoagulation) was associated with lower in-hospital mortality (only prophylactic dose: aHR, 0.36; 95% CI, 0.26-0.52; any treatment dose: aHR, 0.38; 95% CI, 0.25-0.58). However, only the prophylactic dose of anticoagulation remained associated with lower mortality at 60 days (prophylactic dose: aHR, 0.71; 95% CI, 0.51-0.90; treatment dose: aHR, 0.92; 95% CI, 0.63-1.35). <h3>Conclusions and Relevance</h3> This large, multicenter cohort of patients hospitalized with COVID-19, found evidence of rapid dissemination and implementation of anticoagulation strategies, including use of treatment-dose anticoagulation. As only prophylactic-dose anticoagulation was associated with lower 60-day mortality, prophylactic dosing strategies may be optimal for patients hospitalized with COVID-19.
Safety and efficacy of murine PVSRIPO plus anti-PD-1 immune checkpoint inhibitor (ICI) in a melanoma tumor model.
Authors: Lauren Neighbours, Zachary P McKay, Matthias Gromeier, Garrett Nichols, Andrea True Kelly, Daniel Corum, Michael Brown
Journal: Journal of Clinical Oncology (2021)

2560 Background: Most patients with advanced melanoma (mel) fail/acquire resistance to ICI, including anti-(α) PD-1. PVSRIPO is a novel intratumoral immunotherapy derived from the Sabin type 1 attenuated poliovirus (PV) that targets CD155, widely expressed on solid tumors and antigen-presenting cells (APCs) of the tumor microenvironment. Therapy leads to direct tumor cell death and type I/III interferon-dominant innate inflammation, mediating priming and recruitment of tumor antigen-specific T cells. Inflammation-mediated upregulation of the PD-1/L1 IC suggests greater anti-tumor response could be achieved with PVSRIPO + αPD-1. The aim of this preclinical study was to evaluate the efficacy and safety of murine PVSRIPO (mRIPO) + αPD-1 in an aggressive mel tumor model (B16-F10.9-OVA in human-CD155 transgenic mice [C56BI/6]). Methods: Mice were randomized to 4 groups (G) of 12: (G1 [control]: vehicle [v] + IgG; G2: v + αPD-1; G3: mRIPO + IgG; G4: mRIPO + αPD-1). Tumor cells (5 x 10 5 ) were implanted into the right (R) and left (L) flanks. When tumor volume (vol) was ̃25 mm 3 , 15 µL v or 1 x 10 7 TCID 50 mRIPO was injected into R (Day 1) and L (Day 4) tumors; αPD-1 or IgG (250 µg, 100 µL ip) was given on Days 1 and 4 and q 3 days until termination (Day 13). Weight, hematology, chemistry, and inflammatory cytokines were assessed pre/post-tumor implantation. Tumor vol was assessed every other day, with gross/histologic exam at termination. Results: 47 mice without health issues were euthanized as planned; 1 G1 animal required early euthanasia for tumor ulceration. Microscopic findings: increased mononuclear cell tumor infiltrates (G2 and G4); less severe L tumor growth necrosis in G2, G3, and G4 vs G1. There were no specific treatment-related changes in serum cytokines in G4. See the table below for summary of total tumor vol changes vs control; the most significant reduction was observed in G4. No tumor cells were observed via histopathology at Day 13 in R flanks of 1 mouse in G2; 3 in G3; and 8 in G4; and only G3 (n=1) and G4 (n=5) mice had no evidence of L flank tumor cells, with regression evident before L tumor mRIPO injection (ie, abscopal response). Conclusions: mRIPO + αPD-1 had the greatest overall anti-tumor response, and the combination was well tolerated. These results suggest combination therapy is not associated with untoward immune-mediated toxicity and highlight the potential for enhanced efficacy in injected and uninjected tumors. A phase 2 clinical trial of PVSRIPO ± αPD-1 in unresectable αPD-1 refractory mel is enrolling (LUMINOS-102, NCT04577807).[Table: see text]
TIVO-3: Durability of response and updated overall survival of tivozanib versus sorafenib in metastatic renal cell carcinoma (mRCC).
Authors: Elena Verzoni, Bernard Escudier, Thomas E. Hutson, David F. McDermott, Sumanta K. Pal, Camillo Porta, Brian I. Rini, Michael N. Needle, Michael B. Atkins
Journal: Journal of Clinical Oncology (2021)

4546 Background: Tivozanib is a potent and highly selective VEGF receptor (R) tyrosine kinase inhibitor in clinical development for mRCC. Methods: The TIVO-3 study enrolled subjects with mRCC who failed 2 or 3 prior systemic regimens, one of which included a VEGFR TKI, stratified by IMDC risk category and type of prior therapy (two TKIs; TKI plus checkpoint; TKI + other) then randomized 1:1 to T or sorafenib. Tivozanib demonstrated PFS and ORR advantages over sorafenib. Here we report long term durability of response based on investigator assessment and updated overall survival. Results: There were 41 responders (23%) to tivozanib and 20 responders (11%) to sorafenib. The median duration of response (mDoR) was 20.3 months (95% CI: 9.8, 29.9) and 9.0 months (95% CI: 3.7, 16.6) for tivozanib and sorafenib, respectively. With prolonged follow up there were 270 deaths; the HR for overall survival favored tivozanib at 0.91 (95% CI: 0.716, 1.165). Clinical trial information: NCT02627963 . Conclusions: Tivozanib treatment in third and fourth line mRCC results in longer PFS, higher objective response rate and more durable responses compared to sorafenib. There is no difference in overall survival.[Table: see text]
Combined treatment with iodine-125 (125I) seed strand and transarterial chemoembolization (TACE) plus lenvatinib with anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma (uHCC) and portal vein tumor thrombus (PVTT): Real-world experience in China.
Authors: Zi-Han Zhang, Wen Zhang, Qing-Xin Liu, Ling-Xiao Liu, Jian-Jun Luo, Xu-Dong Qu, Zhi-Ping Yan
Journal: Journal of Clinical Oncology (2021)

e16152 Background: We reviewed real-world outcomes for patients with uHCC and PVTT receiving TACE with 125I seed and stent implantation combined with lenvatinib plus anti-PD-1 antibodies. Methods: We retrospectively reviewed medical records from 62 consecutive adult (≥18 to ≤75 years) patients with HBV-related HCC and type III and IV PVTT with Child-Pugh class A or B liver function and ECOG performance status of 0-2 who received 125I seed strand and stent implantation combined with TACE at our center between November 2018 and May 2020. Patients were divided into two groups; those who had received adjuvant lenvatinib plus anti-PD-1 inhibitors, initiated 3 days after the first interventional procedure (Group A; n=18), and those who only received locoregional therapy (Group B; n=44). Propensity score matching (PSM) with a 1:1 ratio was used to reduce selection bias. Tumor response, progression-free survival (PFS, time from the first interventional procedure to progression or death for both Group A and Group B) and time-to-progression (TTP) were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Time to untreatable progression (TTUP) and overall survival (OS) were also assessed. Adverse events (AEs) were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Results: PSM resulted in 15 matched pairs of patients, and baseline demographic parameters were comparable between the two groups. The median follow-up time was 12.4 ± 4.6 and 9.4 ± 4.8 months for patients in Groups A (n=15) and B (n=15) after PSM, respectively. Compared with patients in Group B, those in Group A had a higher overall response rate (66.7 vs. 18.2%; p=0.001) and disease control rate (72.2 vs. 43.2%; p=.038) and a longer median PFS, TTP, TTUP and OS (Table). No serious complications related to locoregional procedures were reported in either group. In Group A, 13% (n=2) of patients experienced ≥1 AE but the majority were Grade &lt;3; one patient had Grade 2 hyperthyroidism and one had Grade 2 enteritis, which were both considered related to immunotherapy. Conclusions: These real-world data show that 125I seed strand and stent implantation combined with TACE plus adjuvant lenvatinib and anti-PD-1 antibodies led to better treatment responses and survival outcomes compared with locoregional treatment alone in patients with uHCC and PVTT, with an acceptable safety profile. Summary of survival outcomes in propensity score matched groups.[Table: see text]
Driving Pressure in COVID-19 Acute Respiratory Distress Syndrome Is Associated with Respiratory Distress Duration before Intubation
Authors: Vasiliki S. Tsolaki, George E. Zakynthinos, Konstantinos D. Mantzarlis, Konstantina V. Deskata, Maria-Eirini E. Papadonta, Efrosini S. Gerovasileiou, Efstratios E. Manoulakas, Epaminondas Zakynthinos, Ioannis N. Pantazopoulos, Demosthenes A. Makris
Journal: American Journal of Respiratory and Critical Care Medicine (2021)