tbuckley/cabot-search huggingface dataset:
The next generation of cerebrospinal fluid (CSF)-based molecular diagnostics: Improving sensitivity and actionability in breast and lung cancer patients with CNS involvement.
Authors: Veena M. Singh, Deanna M Fisher, David Berz, Robbie Schultz, Julie A Mayer, Smitha Boorgula, Minhdan Nguyen, Judy Troung, Lucia Dobrawa, Jaya Gill, Jose Arganda Carrillo, Santosh Kesari
Journal: Journal of Clinical Oncology (2020)

e14502 Background: Liquid biopsy has emerged as a minimally invasive and cost-effective strategy to assess cancer biomarkers without the risk of complications associated with surgical biopsies. Once a tumor has metastasized to the brain, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) can be found in the cerebrospinal fluid (CSF). We analyzed CSF samples from patients(pts) with primary lung or breast cancer with either brain (BM) or leptomeningeal metastases (LM). Here we report the analytical and clinical validation of Target Selector CSF assays. Validation testing included pre-analytical and analytical steps. Methods: CSF was collected prospectively from pts with a prior solid tumor diagnosis and suspected BM or LM. CTCs were captured utilizing a primary ten antibody cocktail followed by biotinylated secondary antibodies that bind selectively to CTCs followed by staining with cytokeratin (CK), CD45, streptavidin and DAPI. CTCs were captured in a microfluidic channel,classified as either CK+ or CK-. Cell-free total nucleic acids (cfTNA) was extracted from CSF supernatant and underwent both Target Selector™ single gene and next-generation sequencing (NGS) lung and breast multi-gene testing to assess for molecular alterations. For NGS, data analysis was performed using Torrent Suite with annotation and curation by Ion Reporter and Oncomine Knowledgebase Reporter software. Results: The Target Selector CTC platform assays performed on clinical samples (n = 89) resulted in clinical accuracy = 85.4%, clinical precision (intra-assay, inter-assay, inter-operator, and inter-instrument) = 100% for each measure, clinical sensitivity = 80.0%, clinical specificity = 96.6%, positive predictive value (PPV) = 98%, negative predictive value (NPV) = 70.0%, and analytical specificity = 96.0% (acceptance criteria was 95%) at a limit of detection of 2 CTCs. For molecular analyses, Target Selector™ platform assays resulted in clinical accuracy = 87.4%, clinical sensitivity = 85.2%, clinical specificity = 88.3%, PPV = 76.7%, and NPV = 93.0%. Conclusions: Target Selector is a viable, sensitive, reproducible platform for CTC detection and molecular analysis of CSF samples from patients with breast or lung cancer with CNS metastases especially as the sensitivity of CSF cytology is low and MRI findings can be equivocal. Identifying CTCs and molecular alterations can help characterize both tumor genomic evolution as well as guide treatment following cancer metastasis to the CNS.
Implementation of Symptom Care Clinic (SCC) for acute symptoms management at outpatient oncology ambulatory centers.
Authors: Han Xiao, Rosanna Fahy, Rori Salvaggio, Maryellen OSullivan, Desiree Sokoli, Cheryl Murray, Jibran Majeed, Jun J. Mao, Jeffrey S. Groeger
Journal: Journal of Clinical Oncology (2020)

2030 Background: With improved overall cancer survival, increasing number of cancer patients are undergoing active treatment. This, in return, add burden in acute symptom management related to disease and treatment. This has resulted in increasing unplanned emergency room (ER) visits and negatively impacted patients experience and health cost. We establish Symptom Care Clinic (SCC) embedded in suburban ambulatory oncology centers to reduce unplanned ER lists and to improve patient experience. Methods: Together with all stakeholders, we developed six SCCs at regional ambulatory centers in NY and NJ. Clearly defined work flow and algorithm were developed to ensure appropriate patient referral. On-site radiology and laboratory services are available. The SCCs are staffed with combination of Advanced Practice Provided (APP) and physicians or APP alone supported by on site medical oncologist or remote central Urgent Care Center Attendings. We evaluated clinic volumes, reduction ins unplanned ER visits and patient experience. Results: From October 2017 to December 2019, total of 17,542 SCC visits were documented. Total of 17,479 lab and 5,355 radiology tests as well as 3,915 infusions were performed. The top five most common laboratory tests are CBC, blood cultures, CMP, respiratory panel and urine culture. The most common symptoms are fever, nausea/vomiting/dehydration, rash and pain. Among all SCC visits during this period, 83% were discharged home and 17% were transferred to ER or hospitals. During 2019, total 10,736 SCC visits were recored, APP evaluated 73.7% of visits and physicians 16.3% with comaprable recidivism rate, 2.52% and 2.75%, respectively. Conservatively, we estimated that approximately 40% of visits would have been Er visits based on numbers of CBC and other testes performed. Qualitative feedbacks from patients indicated positive experience in convenient access, cohesive care coordination and time saving from traveling to and waiting in ER. Conclusions: We successfully implemented an effective acute symptom management system in busy ambulatory oncology centers that is patient centric. Out data showed that SCC reduced unplanned ER visits and that APP/physician model has low recidivism rate.
Evaluation of treating mild ametropic amblyopia by refractive correction alone
Authors: Long Zhao
Journal: BMJ (2013)

A total of 102 cases (204 eyes) with mild ametropic amblyopia underwent refractive correction without any vision training. After wearing glasses, visual acuity was examined every 3 months during a follow-up period of 12 months. After wearing glasses 12 months, 201 eyes (98.53%) were treated effectively, 175 eyes (85.78%) cured basically and 3 eyes (1.47%) became invalid. The changes of visual acuity were satisfactory (P<0.01). The difference of visual acuity between every two observation timepoints were satisfactory (P<0.01). Treating mild ametropic amblyopia by refractive correction alone is both simple and effective. And it has an excellent compliance and a low cost.


Key words: 
Refractive errors; Ametropic
Clinicopathologic and protein markers distinguishing POLE and copy-number low group in endometrial cancer.
Authors: Kidong Kim, Suhyun Hwangbo, Taesung Park, Hyojin Kim, Yong Beom Kim, Jae Hong No, Dong-Hoon Suh, Ju-Hyun Kim
Journal: Journal of Clinical Oncology (2020)

e18110 Background: Requirement of DNA sequencing to diagnose POLE group is a barrier for adoption of molecular subtyping in endometrial cancer. We aimed to identify clinicopathologic and protein markers distinguishing POLE and copy-number (CN) low group in endometrial cancer. Methods: Ninety-one samples (POLE: 15, CN low 76) classified as POLE or CN low groups by integrative clustering were selected from The Cancer Genome Atlas endometrial cancer dataset. Clinicopathologic variables and normalized reverse phase protein array expression data were extracted. We first selected clinicopathologic variables associated with group (POLE vs CN low) via univariate analysis. Then, we identified protein makers using the logistic regression model with significant clinicopathologic variables as adjusting covariates. The differentially expressed proteins were selected based on q-value of the false discovery rate for multiple comparison. With various q-value cut-off ( &lt; 5%, 10%, 20%), several logistic models including differentially expressed markers were constructed by stepwise selection method using the area under curve (AUC) from 5-fold cross-validation (CV). Results: Among clinicopathologic variables, body mass index (BMI) and tumor grade were associated with group (p = 0.02 and p &lt; 0.01, respectively). Being adjusted for BMI and tumor grade, 5 proteins were associated with group in q-value cut-off of &lt; 5%. The model including clinicopathologic variables and 5 proteins identified BMI, Cyclin B1, Caspase 8, and XBP1 as markers distinguishing POLE and CN low groups. The mean of CV AUC, sensitivity and specificity of the selected model were 0.97, 0.97, and 0.60, respectively. Conclusions: BMI and expression levels of Cyclin B1, Caspase 8, XBP1 are candidate markers distinguishing POLE and CN low group. A further validation study using immunohistochemical staining is necessary to facilitate the adoption of molecular subtyping as daily practice.
CIMAC-CIDC tissue imaging harmonization.
Authors: Guray Akturk, Edwin Roger Parra Cuentas, Ana Lako, Evisa Gjini, Beatriz Sanchez Espiridion, Ignacio Ivan Wistuba, Magdalena Thurin, Stephen M. Hewitt, Scott Rodig, Jiexin Zhang, Donna S. Neuberg, J. Jack Lee, Sacha Gnjatic, Michael T. Tetzlaff
Journal: Journal of Clinical Oncology (2020)

3125 Background: The Cancer Immune Monitoring and Analysis Centers Cancer Immunology Data Commons (CIMAC-CIDC) network is a NCI Cancer Moonshots initiative to provide state-of-the-art technology and expertise for immunotherapy clinical trials. Multiplex tissue immunostaining is an integral assay provided that examines density and spatial distribution of immune cells and markers in tissues, for their prognostic or predictive value. Two approaches were evaluated for sensitivity, specificity, and reproducibility and subsequently harmonized: chromogenic-based Multiplex Immunohistochemical Consecutive Staining on Single Slide (MICSSS) and Multiplex Immunofluorescence (mIF) based tyramide signal amplification system. Methods: Harmonization was performed across CIMACs (Mount Sinai, Dana Farber Cancer Institute, MD Anderson Cancer Center) in multiple steps to prove that comparable data can be generated independent of site and platform. Goals: 1) harmonize image analysis platforms alone using tissues pre-stained with single chromogenic IHC for CD3 (membrane), Ki67 (nuclear), and CD68 (cytoplasmic), 2) compare image acquisition platforms, 3) streamline Antibody (Ab) clones and assess PD-L1 detection in relation to CLIA- assays, 4) harmonize staining protocols, image acquisition, and analysis platforms on 2 test head and neck tumor samples using MICSSS and mIF, 5) validate harmonization results with a tissue microarray on 27 tissues representing multiple tumors. For last steps, each CIMAC used their platforms for PD-L1, PD-1, CD3, CD8, and pan-cytokeratin (PanCK) staining on one of three consecutive slides from serial sections and compared densities of each marker. Results: Variables as PD-1 Ab clone, positive control reference tissues, sigma value for nuclear segmentation, and use of machine-learning based cell classifier were found to be key to produce accurate, reliable, comparable data. After visual quality control assessment and comparisons of each Region Of Interest (ROI), an overall inter-site Spearman correlation coefficient of ≥0.85 was achieved per marker within each tissue and across tissue types (expect pan-Cytokeratin, ≥0.7), with average coefficient of variation ≤0.1. Conclusions: These results show for the first time that two platforms can deliver harmonized data, despite differences in protocols, platforms, reagents, and analysis tools. Data resulting from retrospective and prospective CIMAC-CIDC analyses may be used with confidence for statistical associations with clinical parameters and outcome.
Induction bevacizumab, etoposide and cisplatin followed by whole brain radiotherapy (WBRT) versus WBRT alone in breast cancer with untreated brain metastases: Results of a randomized phase II A-PLUS trial.
Authors: Yen-Shen Lu, Ming-Shen Dai, Ling-Ming Tseng, Shin-Cheh Chen, Wei-Wu Tom Chen, Tsu-Yi Chao, Ta-Chung Chao, Yuan-Ching Chang, Chang-Fang Chiu, Chien-Ting Liu, Chingh-Hung Lin, Chun-Yu Liu, Ya-Fang Chen, Twan Ying Chang, Jyh-Cherng Yu, Kun-Ming Rau, Yao-yu Hsieh, Shih-Che Shen, Shu-Min Huang, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2020)

1082 Background: Our previous study ( Clin Cancer Res. 2015;21(8):1851) demonstrated that bevacizumab preconditioning followed by etoposide and cisplatin (BEEP) is a highly effective treatment for breast cancer (BC) patients (pts) with brain metastases (BM) progressing from WBRT. We conducted a randomized phase II study A-PLUS (NCT02185352) to test whether using BEEP as an induction therapy could enhance the efficacy of WBRT and provide systemic control. Methods: BC pts with measurable BM not suitable for surgery/radiosurgery and had not received WBRT were randomized (2:1) to experimental arm: induction BEEP for 3 cycles (~2 months [ms]) followed by WBRT or control arm: upfront WBRT. The BEEP regimen consists of bevacizumab 15 mg/kg on day 1, and etoposide 70 mg/m 2 /day on days 2-4, cisplatin 70 mg/m 2 on day 2, followed by prophylaxis GCSF, every 21 days. After WBRT in both arms, pts received treatment of physician’s choice except BEEP until BM progression. Stratification was based on the Graded Prognostic Assessment score. Primary endpoint was brain-specific progression free survival (BS-PFS) based on RECIST 1.1, with a total of 108 pts, power of 0.8 at the 2-sided α level of 0.2. Results: Of 112 enrolled pts, 74 were in experimental arm and 38 in control arm. Baseline patient characteristics were generally balanced between arms. With median follow up of 28.7 ms, median BS-PFS was 8.1 vs. 6.5 ms ( p= 0.146; HR 0.71 [95% CI 0.44-1.13]), which met the primary endpoint (pre-defined α level of 0.2). Results of preplanned analysis included: 2-month brain-specific objective response rate of BEEP alone vs. WBRT was 41.9% vs. 52.6% ( p= 0.613); 8-month BS-PFS rate was 48.7% vs. 26.3% ( p= 0.027); median PFS was 6.4 vs. 4.7 ms ( p= 0.071; HR 0.67 [95% CI 0.43-1.04]), and extra-BM PFS was 7.9 vs. 5.0 ms ( p= 0.141; HR 0.71 [95% CI 0.46-1.12]). Median overall survival was 15.6 vs. 13.6 ms ( p= 0.855; HR 0.96 [95% CI 0.59-1.55]), with 31.6% of pts in control arm received BEEP regimen treatment after BM progression. The most common all-grade adverse events (AEs) in experimental arm were neutropenia (30.2%), nausea (27.9%), anemia (27.4%), and leukopenia (24.2%). Most AEs were mild to moderate in severity. Two pts discontinued BEEP treatment due to grade 4 nephrotoxicity and grade 3 infection, respectively. Conclusions: BEEP as induction treatment followed by WBRT for BC pts with BM may improve control of both BM and systemic disease. Further validation by a phase III study is necessary. Clinical trial information: NCT02185352 .
Subcutaneous daratumumab in patients with multiple myeloma who have been previously treated with intravenous daratumumab: A multicenter, randomized, phase II study (LYNX).
Authors: Nizar J. Bahlis, Jeffrey A. Zonder, Susan Wroblewski, Ming Qi, Thomas Renaud, Carolyn Chang Jackson, Thierry Facon
Journal: Journal of Clinical Oncology (2020)

TPS8553 Background: The intravenous (IV) formulation of daratumumab (DARA), a human CD38-targeted monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory multiple myeloma (RRMM) and in combination with standard-of-care regimens in RRMM or newly diagnosed MM. A subcutaneous (SC) formulation of DARA is under investigation in several ongoing studies. In the phase 3 COLUMBA study, DARA SC was shown to be non-inferior to DARA IV, demonstrating similar efficacy and pharmacokinetics, with a significantly decreased rate of infusion-related reactions and reduced administration time. The phase 2 LYNX (MMY2065) study will evaluate the efficacy and safety of retreatment with DARA. Methods: In this ongoing, multicenter, open-label, randomized phase 2 study, ~230 patients (pts) with prior exposure to DARA will be randomized 1:1 to receive carfilzomib and dexamethasone (Kd) ± DARA. Pts must have received 1 to 2 prior lines of therapy (at least one of which included DARA IV), with DARA-based therapy completed ≥3 months prior to randomization. Eligible pts have achieved a partial response or better (IMWG criteria) to DARA-based therapy, with a duration of response of ≥4 months. Pts must not have discontinued DARA due to a related adverse event or received prior treatment with carfilzomib. Pts will receive 20 mg/m 2 carfilzomib IV on Day 1 of Cycle 1, escalated to 70 mg/m 2 on Days 8 and 15; carfilzomib 70 mg/m 2 will be administered on Days 1, 8, and 15 of each 28-day cycle thereafter. Dexamethasone 40 mg will be administered (IV or PO) QW for Cycles 1-9 and then on Days 1, 8 and 15 from Cycle 10 onwards. Pts in the D-Kd group will also receive DARA SC (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. The primary endpoint is the rate of pts achieving a very good partial response or better. Secondary endpoints include overall response rate, rate of pts achieving complete response or better, progression-free survival, overall survival, overall minimal residual disease-negativity rate, time to next treatment, pharmacokinetics, and safety. Clinical trial information: NCT03871829 .
Effects of cardioprotective medications on breast cancer survival: A retrospective study from an academic center from Southern Illinois.
Authors: Manjari Rani Regmi, Priyanka Parajuli, Asad Cheema, Odalys Estefania Lara Garcia, Nitin Tandan, Ruby Maini, Hamsa Sahib, Noupama Mirihagalle, Cameron Koester, Zurain Niaz, Sabree Abedrabo, Alexander Johnson, Abdisamad M. Ibrahim, Bishal Bhandari, Kristin Delfino, Kathy Robinson, Meghna R. Desai, Abhishek Kulkarni
Journal: Journal of Clinical Oncology (2020)

e12540 Background: Cardiovascular disease is one of the leading causes of deaths in breast cancer patients. Pre-existing cardiac conditions and cardiovascular risks associated with chemotherapy affect the overall mortality of these patients. Cardio protective medications like beta-blocker, ACEIs, ARBs, statin, and potassium-sparing diuretics have shown to increase the survival odds. In our study, we investigated the survival of breast cancer patients who were on cardio protective medications. Methods: Our retrospective cohort study included breast cancer patients from Simmons Cancer Institute, Springfield, Illinois from January 1 st , 2014 to December 31 st , 2017. The first step comprised of screening patients using ICD code of breast cancer. Next, a retrospective chart review led to selecting eligible patients with biopsy proven breast cancer diagnosis within the aforementioned dates. We excluded patients who were diagnosed outside the give time frame. Data on age, gender, medical comorbidities, medications, and survival status were also collected. Comparisons between categorical variables were compared with the Chi-Squared test. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival are assessed with Cox proportional hazards regression analyses. Results: Screening using ICD codes resulted in 1618 patients. Of those, 478 had biopsy proven diagnosis within the dates mentioned. 301 out of 478 patients were on some kind of cardio protective medication (88 on beta-blockers, 73 on ACEIs, 41 on ARBs, 87 on statins, and 12 on potassium sparing diuretics). We looked into survival analysis in patients on different cardioprotective medications. ARBs and potassium sparing diuretics showed increased likelihood of survival as the hazard ratio (HR) was found to be 0.512 (95% Cl: 0.068-3.832, p-value:0.0919) and HR 0.390 (95% CI: 0.130-1.66, p-value:0.514) respectively. In contrast, other cardio protective medications showed decreased trends for survival. The HR of beta blocker was 1.734 (95% CI: 0.508-5.919, p-value: 0.379) and of ACEIs was 1.350 (95% CI: 0.395-4.613, p-value: 0.632). Similarly, statins had a hazard ratio of 1.534 (95% CI: 0.512- 4.594, p-value:0. 444). Conclusions: We found that the cardio protective medications showed no statistically significant difference in survival in breast cancer patients. Given the smaller sample size and single center study, further multi-center clinical trial is warranted to establish a stronger association.
Patterns of use of medical cannabis in a community oncology clinic.
Authors: Deepti Behl, Stacy D. D'Andre, Carol Parise
Journal: Journal of Clinical Oncology (2020)

e24111 Background: Despite the fact that cannabis is still illegal in some states, two-thirds of all patients with cancer may have used cannabis at some point in their life to alleviate anorexia, nausea, chronic pain, and/or insomnia. Cannabis remains a Schedule 1 drug on the federal list with drugs such as heroin and LSD, which limits the ability to conduct quality clinical trials. This purpose of this study was to assess the prevalence, reasons for use, methods of use, and perceived benefits of medical cannabis in an adult community oncology clinic. Methods: Patients completed a questionnaire when they checked in for their appointment at the outpatient oncology clinic at Sutter Medical Center, Sacramento. Patients who used marijuana were asked questions regarding the mode of ingestion, perceived benefits, types of underlying cancer, and estimated monthly cost. Results: Of the 775 patients who completed the study to date, 129 men (29.3%) and 54 women (70.1%) responded that they used medical cannabis. Approximately 72% were white, 29.3% had breast cancer, and 13% had lung cancer. 39% percent had a diagnosis of metastatic cancer and 44% were undergoing chemotherapy. The most often stated reasons for use were pain (45%), sleep (43%), nausea (38%); and anxiety/mood (38%). Over 50% reported use of oils and tinctures and 44% used edibles. A smaller percentage preferred vaping (26%) or smoking (30%). Topical use was preferred by fewer patients (17%). Over 58% of patients stated they used more than one method. Most patients felt that use of cannabis helped alleviate symptoms. Marked improvement was reported by 40% patients; moderate improvement by another 41%. Only 13% users stated that they noted little to no improvement. The majority of patients (66%) spent $100 or less per month on marijuana whereas 22% spent between $100 and$200 per month. Conclusions: Medical cannabis is used by approximately one-fourth of all patients in an urban community cancer center in Northern California and the majority reported that cannabis provided improvements in symptoms associated with cancer and its treatment. Further research regarding mechanism of actions and associated risks is warranted.