tbuckley/cabot-search huggingface dataset:
Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: Follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial.
Authors: Othman Al-Sawaf, Can Zhang, Maneesh Tandon, Arijit Sinha, Anna Maria Fink, Sandra Robrecht, Eugen Tausch, William L. Schary, Matthias Ritgen, Clemens Martin Wendtner, Karl A Kreuzer, Barbara Eichhorst, Stephan Stilgenbauer, Michael J. Hallek, Kirsten Fischer
Journal: Journal of Clinical Oncology (2020)

8027 Background: The CLL14 trial demonstrated significant improvement of progression-free survival (PFS) with fixed-duration venetoclax-obinutuzumab (VenG) as compared to chlorambucil-obinutuzumab (ClbG) in patients with previously untreated CLL and coexisting conditions. Here, we report follow-up data on safety and efficacy. Methods: Patients with previously untreated CLL and coexisting conditions were randomized 1:1 to receive 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. Primary endpoint was investigator-assessed progression-free survival. Key secondary endpoints were response rates, rates of minimal residual disease (measured every 6 months up to 5 years after last patient enrolment) and overall survival. Follow-up is ongoing but all patients are off study treatment. This trial was registered with ClinicalTrials.gov, number NCT02242942. Results: Of the 432 enrolled patients, 216 were randomly assigned to receive VenG and 216 to receive ClbG. After a median follow-up of 39.6 months (interquartile range 36.75 - 43.04), progression-free survival continued to be superior for VenG as compared to ClbG (median not reached vs 35.6 months; hazard ratio [HR] 0.31 [0.22-0.44], p &lt; 0.001). At 3 years, the estimated progression-free survival rate was 81.9% in the VenG arm and 49.5% in the ClbG arm. This benefit was consistently observed across all clinical and biological risk groups, including patients with TP53 mutation/deletion and unmutated IGHV status. Of note, PFS was also significantly longer for VenG treated patients with mutated IGHV status. Assessment of minimal residual disease 18 months after end of treatment showed that 47.2% of patients in the VenG arm had undetectable (u) uMRD ( &lt; 10 −4 ), 13% had low (L)-MRD (≥ 10 −4 and &lt; 10 −2 ) and 7.9% high (H)-MRD (≥ 10 −2 ), compared to 7.4% uMRD, 17.1% L-MRD, 26.9% H-MRD in the ClbG arm. No difference has been observed (HR 1.027, 95% CI 0.602-1.753, p = 0.921) for overall survival; median overall survival has not been reached in either group. Second primary malignancies were reported in 36 (17%) patients in the VenG arm and 22 (10.3%) in the ClbG arm. No new safety signals were observed. Conclusions: The results suggest that the superior efficacy and deep remissions after fixed-duration VenG are maintained during extended follow-up, and show the long-term benefits of 12 cycles of VenG across all known risk categories. Clinical trial information: NCT02242942 .
Patient-reported outcomes (PROs) in older adults with gastrointestinal (GI) cancer undergoing surgery.
Authors: Helen Perry Knight, Zhi Ven Fong, Carolyn L. Qian, Emilia Kaslow-Zieve, Chinenye C. Azoba, Cristina R. Ferrone, Hiroko Kunitake, Carlos Fernandez-del Castillo, Michael Lanuti, Motaz Qadan, Rocco Ricciardi, Keith D. Lillemoe, Esteban Franco-Garcia, Terrence A. O'Malley, Vicki A. Jackson, Joseph A. Greer, Areej El-Jawahri, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2020)

159 Background: Older adults with GI cancer often experience poor surgical outcomes, yet little is known about their PROs, such as physical function, quality of life (QOL), and physical and psychological symptom burden. Methods: As part of a randomized trial of perioperative geriatric care, we prospectively enrolled adults age ≥65 with GI cancer planning to undergo surgical resection. We asked patients preoperatively to self-report their physical function (activities of daily living [ADLs] and instrumental ADLs [IADLs]), QOL (EORTC QLQ-C30), symptom burden (Edmonton Symptom Assessment System [ESAS], scores &gt; 3 considered moderate/severe [mod/sev]), depression symptoms (Geriatric Depression Scale [GDS], scores &gt; 4 represent a positive screen for depression), and comorbidities. We used regression models to explore relationships among PROs and clinical outcomes (receiving planned surgery, postoperative complications [Clavien-Dindo], hospital readmissions within 90 days, and survival). Results: From 9/2016 - 4/2019, we enrolled 160 of 221 (72.4%) patients approached (median age: 72, range: 65-92). At baseline, most (53.1%) reported at least one comorbidity and required assistance with ADLs (94.8%) and IADLs (52.3%). Patients reported an average of 2.56 mod/sev ESAS symptoms, and 27.7% screened positive for depression. For surgical outcomes, 137 patients (85.6%) underwent planned surgery, and 99 (72.2%) of these had at least one postoperative complication. Greater independence with ADLs was associated with undergoing planned surgery (OR = 1.21, P = .02), lower risk of complications (OR = 0.81, P &lt; .01), and improved survival (HR = 0.87, P = .02), but not readmissions. Greater independence with IADLs was associated with undergoing planned surgery (OR = 1.30, P = .03) and improved survival (HR = 0.73, P &lt; .01), but not other outcomes. Higher baseline QOL was only associated with lower risk of postoperative complications (OR = 0.97, P = .04). Higher depression scores were only associated with worse survival (HR = 1.13, P = .02). Higher baseline symptom burden predicted for shorter time to readmission (HR = 1.13, p = .03). Patient-reported number of comorbidities was associated with shorter time to readmission (HR = 1.49, p = .03) and higher risk of complications (OR = 1.70, P = .03). Conclusions: Older adults with GI cancer often have baseline functional limitations and a high symptom burden, all of which are associated with worse clinical outcomes. Future work should study whether addressing preoperative PROs could improve older patients’ surgical outcomes. Clinical trial information: NCT02810652 .
Clinical evaluation and performance of QIAGEN Clinical Insight Interpret (QCI-I) as a reporting tool for a comprehensive cancer panel (TSO 500).
Authors: Nikhil Shri Sahajpal, Ashis Mondal, Meenakshi Ahluwalia, Vamsi Kota, Allan Njoroge Njau, Nwogbo Okechukwu, Ravindra Kohle
Journal: Journal of Clinical Oncology (2020)

e14048 Background: The rapid adoption of next-generation sequencing (NGS) methods into clinical diagnostic laboratories have revolutionized the field of genetic testing. To interpret the exhaustive NGS data, bioinformatics has become an inevitable component of any laboratory implementing a clinical NGS test. However, there is an unmet need for accurate, efficient and standardized variant interpretation for actionable insights. In this effort, AMP/ASCO/CAP released a joint consensus recommendation proposing a four-tiered system to categorize somatic alterations based on their clinical significance in cancer diagnosis, prognosis, or therapeutics for standardization of interpretation and reporting of results among laboratories. Thus, the aim of the study was to assess and validate QIAGEN Clinical Insight (QCI) Interpret software for clinical laboratory test interpretation. Methods: 67 malignant cases (myeloid neoplasm and lung) were analyzed using the TSO-500 NGS assay and secondary analysis platform (Illumina, San Diego, CA). The data was uploaded and analyzed using QCI Interpret. Patient case draft reports were produced using a TS0-500 customizable workflow with automated variant filtering, and variant classifications. Results: Data analysis on 67 cases resulted in a total of 251 alterations (SNVs and Indels). A total of 77 and 174 alterations were reported as pathogenic/ likely pathogenic into tier based classification by the QCI Interpret for myeloid and lung malignancies, respectively. For myeloid malignancies, the QCI Interpret was able to detect accurately all the clinically relevant variants and listed them into appropriate tier-based classification compared to the expertly reported alterations. For lung malignancies, 16 alteration were classified in tier 1, 96 alteration in tier 2, 61 alteration in tier 3, and 1 alteration in tier 4. The QCI interpret was able to detect 100% of the alterations being validated, and reported them into tier based classification. Conclusions: Systematic evaluation of an automated classification based on AMP/ASCO/CAP using an up to date knowledge base is critical to accurately classify actionable mutations and detect emerging relevant mutations. The QCI Interpret seems to be a critical bioinformatics tool that adheres to the AMP/ASCO/CAP classification system and incorporates TMB and MSI values from the TSO500 assay, which can be used across clinical laboratories for accurate, efficient and standardized variant interpretation for actionable insights.
Using a tele-oncology service provides a direct benefit to patients and caregivers in rural communities in the Intermountain West.
Authors: Derrick S. Haslem, Zachary Reese, Kimberlee Emfield, David Michael Gill, Ryan Eldredge Wilcox, Terence Duane Rhodes, Brian P. Tudor
Journal: Journal of Clinical Oncology (2020)

e14153 Background: Cancer treatment is becoming more complex, necessitating subspecialty expertise and multidisciplinary approaches to treatment planning. Simultaneously, there is increasing demand to provide care as close to home as possible. Oncology services are in high demand with a geographical mismatch between where oncologists work and where patients live. Traditionally, patients have been required to travel long distances to seek care outside of their communities resulting in increased financial expense and emotional distress caused by leaving the comforts of their support system. Leveraging existing technologies, most of modern cancer care, including infusions can be delivered through a coordinated effort from consulting/ordering oncologists, onsite administrators, physicians, nurses and ancillary staff. Methods: Using a secure video-conferencing platform, Intermountain Healthcare has implemented 5 tele-oncology clinics (Site A- Sevier, UT; B- Cassia, ID; C- Teton, ID; D- Uintah Basin, UT, E- Star Valley, WY) in rural communities of Utah, Idaho and Wyoming. Patients are referred to the clinic by local providers. With the assistance of a nurse navigator, oncologists meet with patients via video conference for initial consults, follow-up, supportive care, survivorship care and systemic treatment including chemotherapy, immunotherapy, and targeted therapy. Standard NCCN/ASCO guidelines are followed in the treatment strategies for these patients. Care is taken to ensure any treatment that can safely be delivered in the local facility/community is coordinated to take place there. Based on distances from the rural facility to nearest tertiary cancer center, we calculated the mileage avoided and hours traveled avoided by using tele-oncology. Results: Since 2017, the tele-oncology service has managed 269 unique patients (A- 200; B- 21, C- 22, D- 18, E- 8) with 1,237 total tele-oncology visits (A- 1,068; B- 69; C- 39; D- 32; E- 29). In total, there were 397,326 driving miles avoided (A- 326,808; B- 26,358; C- 22,932; D- 9,280; E- 11,948). Travel hours avoided in total were 6,062 hours (A- 4,989; B- 380; C- 341; D- 155; E- 197). Conclusions: Intermountain Healthcare’s tele-oncology program benefits patients and communities by easing travel burden and improving quality of life by making cancer care more convenient and providing the care closer to home. Work is ongoing to prospectively evaluate the effects on the communities in addition to cancer related outcomes.
Engaging patients on tumor boards: A multi-stakeholder perspective study.
Authors: Kelly M Smith, Mary A Hill, Kelly Rosendall, Maen Farha
Journal: Journal of Clinical Oncology (2020)

e19243 Background: Patient and family-centered care (PFCC) is grounded in the concepts of dignity and respect, information sharing, and active participation and collaboration in their health care. Efforts to engage patients and family members as part of the healthcare team as part of robust multidisciplinary breast cancer care (MBCC), including in multidisciplinary tumor boards, is an extension of PFCC for breast cancer care. Our team explored multi-stakeholder perspectives of engaging patients as partners on a virtual multidisciplinary tumor board (MTB) using an mHealth application. Methods: We conducted a prospective cohort study employing semi-structured interviews and focus group methodology to explore stakeholder (patients with Stage 0-III breast cancer, family members/caregivers, clinicians, and tumor board staff) perspectives of engaging patients in a virtual MTB. Interviews and focus groups were audiotaped, transcribed, and analyzed using concurrent content analysis to identify common themes. Recruitment continued until saturation of themes was achieved. Results: We conducted 22 interviews and 5 focus groups with 49 participants. Patients and family members reported discomfort with idea of engaging in MTB discussions about their cancer. Disease burden, limited understanding of medical terminology, and not wanting to be a part of the early discussions about their disease (e.g., being overwhelmed, need to trust clinician’s advice) were commonly reported. Clinicians and staff also reported concerns about patient engagement in MTB. Clinicians reported that it may change the candor of the discussions at MTB and obfuscate the problems/issues if they needed to modify their language to accommodate patients’ sensitivities. Clinicians and staff were also concerned about patient’s perception of discordance within the MTB clinician members and how to explain this uncertainty to patients. Staff concerns centered around the use of medical terminology which may create anxiety and result in patient misunderstanding. Conclusions: Clinicians, staff, patients and family members were overwhelmingly concerned about adding patients to the MTB. Engaging patients in the frank and candid early treatment planning discussions may need further evaluation in a clinical environment and among different patient cohorts.
Abstract 211: Enteral Feeding Shortly After Cardiac Arrest Treated With Veno-Arterial Extra Corporeal Membrane Oxygenation and Therapeutic Hypothermia is Safe and Feasible
Authors: Alejandra Gutierrez, Claire Carlson, Demetris Yannopoulos, Jason A Bartos
Journal: Circulation (2019)

Introduction: Literature regarding the timing and safety of enteral feeding after cardiac arrest treated with therapeutic hypothermia and veno-arterial extra corporeal membrane oxygenation (VA-ECMO) is lacking. Aim: To describe the safety and feasibility of early enteral feeding in adult patients presenting with refractory out-of-hospital cardiac arrest treated with VA ECMO and therapeutic hypothermia. Methods: We performed a retrospective analysis of the enteral feeding patterns for patients admitted through the University of Minnesota ECPR program for refractory ventricular tachycardia or fibrillation (VT/VF). Outcomes were compared in patients with early enteral feeding initiation (within 2 days of admission) versus those with delayed enteral feeding (&gt;2 days after admission). Results: The study included 108 consecutive patients (age 56.3+/-12.2 years, 78% male) admitted to the CICU between December 2015 and February 2019. Average CPR duration was 62.8+/-15.3min. Enteral feeding was initiated in 68(62.9%) of the sample. Enteral feeding was not started in patients expected to die within 48 hours of ICU admission. All patients underwent therapeutic hypothermia and 97.2% received neuromuscular blockade. Time to enteral feeding initiation ranged from 1 to 11 days post admission. Patients who had enteral feeding started within the first two days (43%) had similar rates of feeding interruption, (with 40% of cases in the setting of a surgical procedure or family request), gut ischemia, ileus and ventilator associated pneumonia (Table 1). Mortality and neurologic outcomes were not affected by timing of enteral feeding initiation. Conclusion: Initiation of enteral feeding within the first two days of presentation was not associated with adverse outcomes in patients with refractory cardiac arrest treated with prolonged CPR, VA ECMO, and therapeutic hypothermia.
Hepatobiliary tumors in adolescents and young adults: Site, age and gender distribution.
Authors: Evelyn Wong, Wei Lin Goh, Jiancheng Hong, Victoria Wong, Daniel Quah, Yee Pin Tan, Yung Ying Tan, Jason Yongsheng Chan, Nagavalli Somasundaram, Mohamad Farid Rin Harunal Rashid, Eileen Yi Ling Poon
Journal: Journal of Clinical Oncology (2020)

e16651 Background: Hepatobiliary cancer is one of the common cancers within Asia with 80% of global cases occurring in the continent alone. Currently little is known about the incidence of hepatobiliary cancer in the Adolescent and Young Adults (AYA). In this population, hepatobiliary cancer may present in an insidious manner due to low suspicion and management may result in a higher likelihood of survivors with long-term treatment-related toxicities. We aim to highlight the clinicopathological features and treatment outcomes in this age-group in an Asian high-volume tertiary cancer institution. Methods: Patients diagnosed between the age of 16-39 with hepatobiliary cancers between 1st January 2015 to 31st December 2019 in a single-centre institution in Singapore were included in this study. Results: There was a total of 84 AYA patients with hepatobiliary tumours who were referred to our institution. Median age of diagnosis was 35 years old (n = 84). 32 patients (38.1%) had hepatocellular carcinoma, 22 patients (26.2%) had biliary tract tumours, 11 patients (13.1%) had neuroendocrine cancers while 19 patients (22.6%) had other tumour types (Figure 1). Male incidence was highest in all hepatobiliary AYAs (n = 56, 66.7%, p = 0.002) and hepatocellular carcinomas (n = 25, 78.1%, p = 0.001) (Table). 65 patients (77.4%) remain alive as of 31 st December 2019. Conclusions: Patterns of hepatobiliary incidence differ between sexes. In the young AYA population, hepatocellular precursor cells may have sex-specific features affecting malignant potentials. More studies should be done to further elucidate the genomic and epidemiology of hepatobiliary tumours in the younger population of patients to better outcomes in this population. [Table: see text]
Performance of a guideline-recommended algorithm for prognostication of poor neurological outcome after cardiac arrest
Authors: Marion Moseby-Knappe, Erik Westhall, Sofia Backman, Niklas Mattsson-Carlgren, Irina Dragancea, Anna Lybeck, Hans Friberg, Pascal Stammet, Gisela Lilja, Janneke Horn, Jesper Kjaergaard, Christian Rylander, Christian Hassager, Susann Ullén, Niklas Nielsen, Tobias Cronberg
Journal: Intensive Care Medicine (2020)

To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM).Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72-96 h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3-5. Variations of the ERC/ESICM algorithm were explored within the same cohort.The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1-44.7) and 100% specificity (95% CI 98.8-100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7-48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8-100) remaining.The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6-42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies.
DREAMM-2: Assessing efficacy via indirect comparison of single-agent belantamab mafodotin versus selinexor plus dexamethasone combination in anti-CD38 exposed relapsed/refractory multiple myeloma (RRMM).
Authors: Rakesh Popat, Attaya Suvannasankha, Venediktos Kapetanakis, Thibaud Prawitz, Grammati Sarri, Rachel Hughes, Feng Wang, Cosima Hogea, Shannon Allen Ferrante, Jenny Willson
Journal: Journal of Clinical Oncology (2020)

e20527 Background: Single-agent belantamab mafodotin (GSK2857916) is a first-in-class immunoconjugate targeting B-cell maturation antigen that demonstrated deep and durable responses in heavily pretreated patients with RRMM in the pivotal DREAMM-2 study (NCT03525678; Lancet Oncol 2020). Methods: DREAMM-2 included patients with late-line RRMM treated with ≥3 prior lines of therapy, refractory to an immunomodulatory agent and a proteasome inhibitor, with prior exposure to an anti-CD38 antibody. Evidence from Phase II/III trials in a similar patient population was systematically identified following PRISMA guidelines. Based on the specificity of the DREAMM-2 population, selinexor plus low-dose dexamethasone (sel+dex) was identified as the only feasible comparator (STORM Part 2, NCT02336815). Matching-adjusted indirect comparisons (MAIC) were used to investigate the efficacy of single-agent belantamab mafodotin vs. sel+dex. Populations were matched for all clinically validated effect modifiers and prognostic factors with available data. MAIC were performed for overall response rate (ORR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS), as per NICE guidelines. Results: Single-agent belantamab mafodotin was more efficacious than sel+dex in terms of OS and DoR (Table). Results for ORR, TTR, and PFS showed no statistical difference between the two regimens. Conclusions: MAIC of single-agent belantamab mafodotin vs. sel+dex in this patient population with RRMM showed significantly improved efficacy on OS and DoR for belantamab mafodotin. Further validation is required owing to limited data availability. Additional safety analyses will further inform comparisons of the two. Clinical trial information: NCT03525678; NCT02336815. Funding: GlaxoSmithKline (207145). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. [Table: see text]
Doctors, patients, and the drug industry: Partners, friends, or foes?
Authors: Gottlieb Scott
Journal: BMJ (2009)

药品企业、学者、医疗专家和患者之间的关系一直以来都不被人看好，这些群体都希望能改善彼此间的关系。皇家外科学院本周提出了42条建议，旨在促进各方和药品企业建立更有成效的关系。这里我们列出有关药品企业和医生与患者之间应该具有什么理想关系的5种观点以及需要采取的相应措施。