tbuckley/cabot-search huggingface dataset:
Scaled integration of FDA approved biosimilars: Closing the knowledge and adoption gaps.
Authors: David Michael Waterhouse, Caleb Burdette, Dan Davies, David R. Drosick, Molly Mendenhall
Journal: Journal of Clinical Oncology (2021)

15 Background: Biosimilars are clinically equivalent and highly similar to brand yet cost significantly less. Financial savings are shared by patients, practices and payers, ranging anywhere from 21-24% based on 10/01/20 ASP data from CMS. The effective conversion to biosimilar products is vitally important to total cost-of-care savings and can be achieved without negatively affecting patient outcomes. Physician understanding and confidence in biosimilar products is seen as a major conversion barrier. Methods: Interchangeability is an FDA designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician’s consent. Currently no biosimilar has that FDA approval for interchangeability. Building on previous pharmacy auto-substitution processes with therapeutic interchange, a formalized biosimilar policy and SOP was developed to automate conversion from the reference biologic product to the P&amp;T/Physician approved biosimilar. Workflow changes were instituted to alleviate the provider burden of patient-by-patient decisions and placed them with the pharmacy review team. Full staff support and understanding on biosimilar usage was endorsed through mandatory biosimilar education of physicians, advanced practice providers, pharmacists, nurses, financial navigators and prior authorization team members and tracked using meeting attendance and the online E-learning system. Patient education was verified using established teaching visits by tracking documentation in the electronic health record (EHR). Quantitative metrics and reports were developed to assist in tracking the number of unique patients receiving the brand or biosimilar agents. Billed product units per month were also tracked to facilitate auditing and assure accuracy. Baseline brand/biosimilar utilization data for Rituximab, Trastuzumab, and Bevacizumab was collected from July 1, 2019 through December 31, 2020. Results: During the baseline period of 7/01/19 – 12/31/19, biosimilar conversion ranged from 0% (trastuzumab) to 8.4% (rituximab). Following full staff education and physician consent, systematic auto-conversion to biosimilar products was initiated on January 1, 2020. Conversion rates based upon billed biosimilar units likewise improved from 11.7% (baseline) to 90.2% (2021 Q1) for rituximab, 8.4% to 87.4% for trastuzumab, and 0% to 90.0% for bevacizumab. Conclusions: Rapid and near-complete conversion from brand product to FDA approved biosimilar is feasible, measurable and can be scaled.[Table: see text]
Use of the Delphi method to develop a guideline-based geriatric oncology gap assessment.
Authors: Elana Plotkin, William Dale, Kah Poh Loh, Efrat Dotan, Peggy Burhenn, Carolyn J Presley, Ginah Nightingale, Randall A. Oyer, Pamela Ginex, Meghan Sri Karuturi, Stuart M. Lichtman, Leigh Boehmer
Journal: Journal of Clinical Oncology (2021)

236 Background: Older adults are more likely to be diagnosed with cancer than their younger counterparts. Because the underlying health status of older adults with cancer is generally heterogeneous, geriatric assessment (GA) is helpful for uncovering age-related vulnerabilities and guiding subsequent care planning. GA provides multidimensional, multidisciplinary evaluations of pertinent health domains. When used to evaluate an older adult with cancer prior to initiating therapy, GA and screening tools can help oncologists differentiate between fit and frail patients and tailor their treatment accordingly. Methods: The Association of Community Cancer Centers (ACCC) conducted a 4-round Delphi method to achieve expert consensus (≥75%) related to 9 domains of geriatric oncology care from a multidisciplinary perspective. A survey was conducted with 70 international clinicians working in geriatric oncology to assess perspectives on guideline-recommended GA tools in clinical practice. Facilitator led focus groups were conducted to review the results in a large group format and come to consensus. Aggregated results were shared back with the group to ensure effective capture of group discussion regarding validated clinical practice tools to include as resources in the gap assessment instrument. Results: A 32 question geriatric oncology gap assessment was developed in an online survey platform. This tool was beta tested by 30 individuals at cancer programs of various types and regions across the US. A final version was published and made accessible for multidisciplinary teams to self-assess care delivery for older adults with cancer in 9 domains: Functional Status; Cognition; Comorbidities; Decision Making: Screening, Life Expectancy, Chemo Toxicity; Pharmacy/Medication Management; Psychological Health; Nutrition; Patient Goals and Needs; and Communication and Workforce Training. Within each domain, respondents select the level (see Table) that most closely represents the practice(s) at their institution. A personalized report is generated. Sample Question. Conclusions: The ACCC geriatric oncology gap assessment offers cancer programs a validated way to evaluate care delivery for older adults with cancer. To optimize workflow, cancer programs should consider utilizing gap assessment results to develop and advance scalable quality improvement programs at their institution, taking into consideration resource level and infrastructure.[Table: see text]
P14.04 Detection of circulating tumor cells in cerebrospinal fluid for patients with suspected breast cancer leptomeningeal metastases. A prospective study
Authors: A Darlix, S Pouderoux, S Thezenas, A Bievelez, W Jacot, L Cayrefourcq, C Leaha, C Alix-Panabières
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Breast cancer (BC) is the most frequent cause of leptomeningeal metastases (LM). LM diagnosis is confirmed by the detection of tumor cells in the cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, even with optimal CSF sample volume and time to the analysis, the sensitivity of this technique is low, demanding repeated samples. Here, we aimed to evaluate the value of circulating tumor cell (CTC) detection in CSF using the CellSearch® system for LM diagnosis. MATERIAL AND METHODS This prospective, monocentric study included adult BC patients with suspected LM (clinical and/or radiological signs). CSF samples from 1–3 lumbar puncture(s) were analyzed: protein level, conventional cytology (60 drops), and CTC detection with the CellSearch® system (60 drops, first lumbar puncture only). Sensitivity (Se) and specificity (Sp) were calculated, using the results of the conventional cytology as the gold-standard. RESULTS Forty-nine eligible patients were included (Jan 2017-Jan 2020): median age 51.8, 95.9% women, 20.4% HER2+ BC, 93.8% previously diagnosed with metastatic BC, 89.8% with clinical symptoms. Among them, 40 were evaluable (CTC detection failure: n=8, eligibility criteria failure: n=1). Median sample volume was 3.0 mL for conventional cytology samples (median time to analysis: 22min) and 3.3 mL for CTC samples. Of the 40 evaluable patients, 18 had a positive cytology (on CSF sample n=°1/n°2: n=16/n=2) and were therefore diagnosed with LM using the gold-standard method. Protein level was elevated in 88.2% of these patients, compared with 45.1% of patients with negative CSF cytology (p=0.005). CTCs were detected in these 18 patients (median 5824 CTCs, range 93-45052). CTCs were also detected in 5/22 patients with a negative cytology (median 2 CTCs, range 1–44). Among them, one patient (44 CTCs) was diagnosed with a cytologically-proven LM 9 months later, while there was no further argument for LM in the other 4 patients’ history (1–3 CTC), who died of the extra-cerebral disease after a median time of 5.2 months (range 0.9–25.9). The detection of at least one CTC in CSF was associated with a Se of 100.0% (IC95% 82.4–100) and a Spe of 77.3% (IC95% 64.3–90.3) for the diagnosis of LM. CONCLUSION CTCs were detected with the CellSearch® system in all patients diagnosed with a cytologically-proven LM, as well as in a few patients without a cytological confirmation of LM. The prognosis of these patients with CSF cytology-/CTCs+ needs to be further investigated in a larger cohort.
Trends in total and out-of-pocket cost of cancer care around the first year of diagnosis for the four most common cancers among privately insured nonelderly adults: 2009-2016.
Authors: Ya-Chen T. Shih, Ying Xu, Cathy Bradley, Sharon H. Giordano, James C. Yao, K. Robin Yabroff
Journal: Journal of Clinical Oncology (2021)

5 Background: To provide a comprehensive evaluation of the trends in treatment pattern, total and out-of-pocket (OOP) costs of cancer care for in the period between 2-month before and 12-month after cancer diagnosis for the privately insured non-elderly adults diagnosed with female breast, colorectal, lung, or prostate cancer. These four cancers represent the four most prevalent cancers in the United States and the 14-month duration captures the most expensive care phase in the cost trajectory of cancer. Methods: We constructed incident cohorts using claims data from the Health Care Cost Institute between 2009 and 2016. We identified treatment modality (cancer-related surgery, systemic therapy, radiation, and other hospitalizations) and calculated associated total and OOP (sum of deductible, coinsurance, and copayment) costs from payment variables. For each cancer, we examined healthcare utilization and cost trends based on the year of diagnosis and conducted logistic regressions to assess the trend in utilization and generalized linear models to evaluate the trend in costs. All estimates are reported in 2020 US dollars. Results: The cohorts consisted of 105,255 breast, 23,571 colorectal, 11,321 lung, and 59,197 prostate cancer patients. Between 2009 and 2016, use of systemic therapy and radiation significantly increased, except for lung cancer. Cancer surgeries significantly increased for breast and colorectal cancer but decreased for prostate cancer, whereas hospitalizations for reasons other than cancer declined for all cancers (p &lt; 0.001). Costs increased for nearly all treatment modalities except for systemic therapy in colorectal and radiation in prostate cancer. Total mean costs per patient had the largest increase in breast cancer (29%, $109,544 to $140,743), followed by lung (11%) and prostate (4%) cancer. Cost increase in colorectal cancer was not statistically significant (P = 0.089). Similar trends were found in median costs. Although not every cancer had significant increase in total costs over time, OOP costs increased &gt; 15% for all cancers, with deductibles accounting for an increasingly proportion. Conclusions: Rising costs of cancer treatments, compounded with increasing cost-sharing increased OOP costs for privately insured, non-elderly cancer patients. Policy initiatives to mitigate financial hardship should consider cost containment as well as insurance reform.
Poloxamer 188 vs Placebo for Painful Vaso-occlusive Episodes in Children and Adults With Sickle Cell Disease
Authors: Marcel J. H. Kenter, Adam F. Cohen
Journal: JAMA (2021)

To the Editor In their recent study,1 Dr Casella and colleagues found no significant difference between poloxamer 188 and placebo for management of painful vaso-occlusive episodes in children and adults with sickle cell disease (SCD).
ACE: a probabilistic model for characterizing gene-level essentiality in CRISPR screens
Authors: Elizabeth R. Hutton, Christopher R. Vakoc, Adam Siepel
Journal: Genome biology (2021)

Abstract High-throughput CRISPR-Cas9 knockout screens are widely used to evaluate gene essentiality in cancer research. Here we introduce a probabilistic modeling framework, Analysis of CRISPR-based Essentiality (ACE), that accounts for multiple sources of variation in CRISPR-Cas9 screens and enables new statistical tests for essentiality. We show using simulations that ACE is effective at predicting both absolute and differential essentiality. When applied to publicly available data, ACE identifies known and novel candidates for genotype-specific essentiality, including RNA m 6 -A methyltransferases that exhibit enhanced essentiality in the presence of inactivating TP53 mutations. ACE provides a robust framework for identifying genes responsive to subtype-specific therapeutic targeting.
Diameter of surgical versus endoscopic ultrasound-guided gastrojejunostomy: that much wider after all is said and done?
Authors: Giuseppe Vanella, Domenico Tamburrino, Francesco Vito Mandarino, Michiel Bronswijk, Schalk Van der Merwe, Massimo Falconi, Paolo Giorgio Arcidiacono
Journal: Endoscopy (2021)

Whereas retrospective literature confirms the comparable clinical success of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) and surgical gastrojejunostomy (SGJ) [1] [2], no head-to-head comparison exists of their caliber and long-term patency.
Neuroimaging and biomarker evidence of neurodegeneration in asthma
Authors: Melissa A. Rosenkranz, Douglas C. Dean, Barbara B. Bendlin, Nizar N. Jarjour, Stephane Esnault, Henrik Zetterberg, Amanda Heslegrave, Michael D. Evans, Richard J. Davidson, William W. Busse
Journal: Journal of Allergy and Clinical Immunology (2021)
Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models
Authors: Marcel André Schneider, Laura Heeb, Michal Mateusz Beffinger, Stanislav Pantelyushin, Michael Linecker, Lilian Roth, Kuno Lehmann, Udo Ungethüm, Sebastian Kobold, Rolf Graf, Maries van den Broek, Johannes vom Berg, Anurag Gupta, Pierre-Alain Clavien
Journal: Science Translational Medicine (2021)

Serotonin dampens tumor-specific immunity in pancreatic and colorectal cancer mouse models.
Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab
Authors: C. Cattaneo, V. Cancelli, L. Imberti, K. Dobbs, A. Sottini, C. Pagani, A. Belotti, A. Re, A. Anastasia, V. Quaresima, A. Tucci, J. A. Chiorini, H. C. Su, J. I. Cohen, P. D. Burbelo, G. Rossi, L. D. Notarangelo
Journal: Blood Cancer Journal (2021)

Abstract The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.
Kidney toxicity of the BRAF-kinase inhibitor vemurafenib is driven by off-target ferrochelatase inhibition
Authors: Yuntao Bai, Ji Young Kim, Bijay Bisunke, Laura A. Jayne, Josie A. Silvaroli, Michael S. Balzer, Megha Gandhi, Kevin M. Huang, Veronika Sander, Jason Prosek, Rachel E. Cianciolo, Sharyn D. Baker, Alex Sparreboom, Kenar D. Jhaveri, Katalin Susztak, Amandeep Bajwa, Navjot Singh Pabla
Journal: Kidney International (2021)
Reply to: When adopting Global Lung Function Initiative reference values, can we also adapt them to a local context as needed?
Authors: Sanja Stanojevic, Brendan Cooper, Nicole Filipow, Jane Kirkby, Gregg Ruppel, Irene Steenbruggen, Bruce Thompson, Graham Hall
Journal: European Respiratory Journal (2021)

<b>Global Lung Function Initiative reference equations help to standardise interpretation of pulmonary function tests; however, there is a need to balance precision and generalisability with the uncertainty of interpretation</b>https://bit.ly/3iheRFv
The influence of the gut microbiome on BCG-induced trained immunity
Authors: Martin Stražar, Vera P. Mourits, Valerie A. C. M. Koeken, L. Charlotte J. de Bree, Simone J. C. F. M. Moorlag, Leo A. B. Joosten, Reinout van Crevel, Hera Vlamakis, Mihai G. Netea, Ramnik J. Xavier
Journal: Genome biology (2021)

The bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome is increasingly recognized as an important modulator of vaccine responses and immunity in general, its potential role in BCG-induced protection is largely unknown.
Feasibility and preliminary effectiveness of a cancer survivorship care delivery intervention.
Authors: Sarah A. Birken, Alexandra Peluso, Cheyenne Wagi, Stacy Wentworth, Kathryn E. Weaver
Journal: Journal of Clinical Oncology (2021)

19 Background: A large and rapidly increasing number of US cancer survivors who have completed active treatment continue to seek oncology care. Low-risk survivors who continue to seek oncology care incur greater costs but experience worse care quality and outcomes than those who seek primary care. In this study, we assessed the feasibility and preliminary effectiveness of START (Supporting Transitions AfteR Treatment), a theory-driven, stakeholder-engaged intervention intended to improve the transition of low-risk survivors to primary care. Methods: To pilot START, beginning in August 2020, we engaged oncology providers (n = 5) and staff (n = 4) at a small community affiliate of our academic comprehensive cancer center. We worked with a nurse navigator, office manager, and physician champion to refine START’s content and delivery to accommodate the needs of a busy community cancer center. We queried electronic health records (EHRs) to assess the feasibility of identifying low-risk survivors and measuring key outcomes (i.e., receipt of recommended health maintenance services). In a formal meeting, we introduced providers to START and helped them to identify survivors whom they agreed should be transitioned to primary care. Front desk staff flagged these survivors to remind providers to transition them in upcoming appointments. Beginning in July 2021, we will conduct in-depth, semi-structured interviews with oncology providers and staff and survivors regarding their perspectives on START’s acceptability, appropriateness, and feasibility. Results: We successfully identified survivors using EHRs and engaged the nurse navigator and providers in identifying the subset of survivors whom they deemed eligible for transitioning to primary care. Preliminary results indicate that START helped providers to transition eligible survivors to primary care. We have successfully engaged cancer center data managers in measuring relevant outcomes using EHRs. Informal provider and staff feedback suggests that START is an acceptable, appropriate, and feasible approach to transitioning survivors. Conclusions: At the conference, we will report on oncology provider and staff and survivor perceptions of START’s acceptability, appropriateness, and feasibility for improving survivorship care delivery and preliminary findings regarding START’s effectiveness in increasing survivors’ receipt of recommended health maintenance services. Findings will be used to refine START and form the basis of a clinical trial to evaluate its effectiveness in improving survivorship outcomes.
OS03.3.A Characterization of long-term metabolic changes of irradiated brain metastases using serial dynamic FET PET imaging
Authors: N Galldiks, G Stoffels, J Werner, E K Bauer, C Baues, E Celik, M I Ruge, G R Fink, K Langen, P Lohmann
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In the present study, we characterized the long-term metabolic changes of brain metastases irradiated with stereotactic radiosurgery (SRS) by sequential dynamic PET imaging using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). We hypothesized that this approach is of considerable clinical value to diagnose delayed radiation-induced changes. MATERIAL AND METHODS From 2010–2021, we retrospectively identified patients with brain metastases from solid extracranial primary tumors who (i) were treated with SRS with or without concurrent immunotherapy using checkpoint inhibitors, (ii) had equivocal or progressive MRI findings after SRS, and (iii) subsequently underwent at least two additional dynamic FET PET scans during follow-up for long-term evaluation. Mean tumor-to-brain ratios (TBR) and the dynamic FET PET parameter time-to-peak were obtained. Diagnostic performances were calculated using receiver operating characteristic curve analyses. Diagnoses were confirmed histologically or clinicoradiologically. RESULTS We identified 36 patients with 98 FET PET scans (median number, 3; range, 2–6). Concurrent to SRS, 8 patients (22%) were treated with checkpoint inhibitors. Following SRS, suspicious MRI findings occurred after a median time of 11 months (range, 2–64 months). Subsequently, FET PET scans were acquired over a median period of 13 months (range, 5–60 months). The overall median follow-up time was 26 months (range, 8–101 months). Twenty-one patients (58%) had delayed radiation-induced changes. TBRs calculated from the last available FET PET scan showed the highest accuracy (92%) to identify delayed radiation-induced changes (threshold, 1.95; P&amp;lt;0.001). CONCLUSION FET PET has a high diagnostic accuracy for characterizing the long-term changes of irradiated brain metastases.
Glutamine anaplerosis is required for amino acid biosynthesis in human meningiomas
Authors: Omkar B Ijare, Shashank Hambarde, Fabio Henrique Brasil da Costa, Sophie Lopez, Martyn A Sharpe, Santosh A Helekar, Gilbert Hangel, Wolfgang Bogner, Georg Widhalm, Robert M Bachoo, David S Baskin, Kumar Pichumani
Journal: Neuro-Oncology (2021)

We postulate that meningiomas undergo distinct metabolic reprogramming in tumorigenesis and unraveling their metabolic phenotypes provide new therapeutic insights. Glutamine catabolism is key to the growth and proliferation of tumors. Here, we investigated the metabolomics of freshly resected meningiomas and glutamine metabolism in patient-derived meningioma cells.