tbuckley/cabot-search huggingface dataset:
Improvement of NGS uniformity of single cell sequencing in CTCs by WGA QC and increased sequencing throughput.
Authors: Lin Ze Shiang, Kang-Yi Su, Sung-Liang Yu, Pan-Chyr Yang
Journal: Journal of Clinical Oncology (2018)

e21176 Background: As medicine advances, personalized treatment becomes a main trend of cancer control currently. Drug resistance and companion diagnosis for first or next line treatment are two important issues in cancer therapy. To improve clinical feasibility the progress of non-invasive diagnosis, particularly circulating free DNAs (cfDNAs), is very promising recently. However, assay accuracy and origins of cfDNAs certainly restrict the clinical applications of cfDNA. Signal cell analysis and circulating tumor cells (CTCs) provide a solution to overcome the limits of cfDNA-based gene test. The potential of CTCs in personalized therapy is just emerging although FDA has recognized CTC detection as one of the best and most objective means to detect tumor metastasis. However, the standardization of CTC analysis is a critical issue that should be resolved before CTC-based assays serving as a routine practice. Methods: In this study, first, IsoFlux (immunomagnetic technique) was used to enrich CTCs from peripheral blood of non small cell lung cancer (NSCLC) patients, and DEParrary was used to purify single CTC. Whole Genome Amplification (WGA) technique was applied to amplify the DNAs from a single CTC. Next, we used AmpliSeq to construct library from the single cell and measure the mutations of 50 cancer-related genes. Finally we optimized the NGS throughput of single CTC based on different WGA quality for obtaining a similar coverage and uniformity. Results: A PCR QC kit containing four different PCR sizes was used to grade the quality of WGA into four degrees, G1, G2, G3 and G4, from poor to good quality. G1 counts for one third of total 56 single CTC no matter whom CTCs come from. The averaged sequencing depth of CTCs was around 2,000 to 3,000X. The data indicated that the coverage rate of low quality WGA product (G1 and G2) is lower than that of good quality WGA (G3 and G4). If we doubled the throughput of G2, the coverage of G2 can be rescued to that of G4. Conclusions: The CTC number, even DNA amount and DNA quality are widely varied among NSCLC patients clinically, we provide a systemic standardization procedure for single cell analysis for CTC.
Reduction in therapeutic burden from use of CCP test in treatment decisions among newly diagnosed prostate cancer patients independent of Charlson Comorbidity Index.
Authors: Neal D. Shore, E. David Crawford, Matthew R. Cooperberg, Jonathan D. Tward, Rajesh R. Kaldate, Steve Stone, Michael K. Brawer
Journal: Journal of Clinical Oncology (2016)

e16572 Background: Risk of prostate cancer-specific disease progression and mortality may be assessed using the cell cycle progression (CCP) test. A large prospective registry (P1000, n=1206) recently showed that the CCP test results influence treatment decisions. Here, we assess whether the CCI, an estimate of the severity of patient comorbid conditions, was correlated with these changes in treatment decisions. Methods: The CCP test is a validated molecular assay that measures the RNA expression of 46 genes to generate a numeric CCP score. P1000 included newly diagnosed (≤6 months) patients with untreated clinically localized prostate cancer. Physicians completed a series of questionnaires to record their treatment recommendations, including initial recommendations (pre-test) and actual treatment (3-6 months of clinical follow-up). The CCI was recorded as part of the pre-test questionnaire. Changes in treatment decisions were examined with multinomial logistic regression modeling with CCI and CCP as continuous covariates along with other clinical factors. Results: The CCP score resulted in a change in actual treatment administered in 48% of patients, with treatment changes stratified by CCI in Table 1. Our analysis shows that the CCP test result is a significant covariate, while the CCI is not (univariate: p=0.0153 vs p=0.1831, multivariate: p=0.0131 vs p=0.1528). The CCI x Age interaction term is significant (p=0.0207), showing that CCI combined with age is correlated with changes in treatment. However, the CCI x CCP score (p=0.5918) and CCI x Risk Percentile (p=0.5191) interaction terms are not significant. Conclusions: The lack of univariate and multivariate statistical significance implies that changes in treatment due to the CCP test are independent of CCI. Treatment change by CCI. CCI Decrease No Change Increase Totals 0 289 (33.49%) 462 (53.53%) 112 (12.98%) 863 1 80 (37.74%) 105 (49.53%) 27 (12.74%) 212 2 24 (35.29%) 36 (52.94%) 8 (11.76%) 68 ≥3 22 (34.92%) 33 (52.38%) 8 (12.70%) 63 Total 415 636 155 1206 CMH test (row-mean scores differ): Unadjusted p=0.7933 Adjusted (risk percentiles): p=0.7546 Adjusted (AUA risk): p=0.9704
Prediction of breast cancer growth rate <i>I</i><i>n vivo</i> and its clinical implications.
Authors: Shristi Bhattarai, Sergey Klimov, Mohammed A. Aleskandarany, Helen Burrell, Anthony Wormall, Ian O. Ellis, Andrew R. Green, Remus Osan, Padmashree C.G. Rida, Emad A. Rakha, Ritu Aneja
Journal: Journal of Clinical Oncology (2018)

e12581 Background: Breast tumors have highly variable rates of growth. In vivo breast cancer growth rate is governed by number of inter-related clinicopathological and biological parameters and is strictly regulated. This study aimed to assess the molecular and clinicopathological determinants of breast cancer (BC) growth rate in vivo and its impact on outcome. Methods: The study group comprised female BC patients who had a pair of serial mammograms wherein the tumor was missed in the first screen (n = 114). Tumor volume, at both time points, along with the span between measurements were used to develop a growth rate index. A machine learning algorithm was used to determine if various combinations of biomarkers could act as a surrogate for this growth rate and was validated in a large independent validation set of 1241 BC patients. Results: Patients with missed BC at first screening showed features associated with good prognosis, when patients were stratified into the slow (59%) and fast (41%) growing based on in vivo growth rate that showed association with outcome. Using Ki67, the mitotic Index, and histological tumor size we classified patients into the in vivo growth rate groups with > 70% accuracy. Using these markers on the naïve dataset resulted in very significant survival difference (p < 0.001) between patients with fast (BCSS = 73%) and slow (BCSS = 92%) growing tumors. Conclusions: Assessment of primary tumor size, mitotic counts, and Ki67 expression can be used as a predictor of in vivo tumor growth rate. In vivo growth rate provides prognostic information and evidence-based data with relevance to medicolegal practice.
P49 Lung Adenocarcinoma with Double Heterozygote EGFR mutation and Combined Resistance: ALK Translocation and EGFR T790M
Authors: V. Denninghoff, V. Wainsztein, M.T. Cuello, G. Recondo, E. Rojas Bilbao, A. Avagnina, G. Recondo
Journal: Journal of Thoracic Oncology (2018)
Effect of H3K27 acetylation activated-long noncoding RNA CCAT1 on cell proliferation and migration by regulating SPRY4 and HOXB13 expression in esophageal squamous carcinoma cell.
Authors: Jinfei Chen, Zhi Xu, Tingting Zhao, Dongying Gu, Lingzhi Hong, Erbao Zhang
Journal: Journal of Clinical Oncology (2016)

e15566 Background: Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. Here, we investigated the lncRNA CCAT1 in the development of esophageal squamous cell carcinoma. Methods: We investigated the lncRNA CCAT1 in the affecting cell proliferation and migration by regulating SPRY4 and HOXB13 expression in Esophageal Squamous Carcinoma Cell with a series molecular experiments. Results: In our study, we found that lncRNA CCAT1, whose expression is significantly increased and is correlated with outcomes in Esophageal Squamous Cell Carcinoma (ESCC). Consecutive experiments confirmed that H3K27-acetylation could activate expression of CCAT1. Further experiments revealed that CCAT1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. RNA-seq analysis revealed that CCAT1 knockdown preferentially affected genes that are linked to cell proliferation, cell migration and cell adhesion. Mechanistic investigations found that CCAT1 could serve as a scaffold for two distinct epigenetic modification complexes (5′domain of CCAT1 binding Polycomb Repressive Complex 2 (PRC2) while 3′domain of CCAT1 binding SUV39H1) and modulate the histone methylation of promoter of SPRY4 (sprouty RTK signaling antagonist 4) in nucleus. In cytoplasm, CCAT1 regulates HOXB13 as a molecular decoy for miR-7, a microRNA that targets both CCAT1 and HOXB13, thus facilitating cell growth and migration. Conclusions: Together, our data demonstrated the important roles of CCAT1 in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy.
Review of the impact of the treatment strategies employed at community oncology centers for patients with myelodysplastic syndrome.
Authors: Mohammad Fahad Bin Asad, Jennifer L. Cultrera, Imad Victor El-Jassous, Maen A. Hussein, Marays Veliz, Pablo Reyes, Patrick V. Acevedo, Sandeep Kumar Thaper, Vasundhara Iyengar
Journal: Journal of Clinical Oncology (2016)

e18555 Background: MDS is a heterogeneous group of clonal acquired hematologic disorders which is prevalent in the elderly population. Despite an intensive prognostic scoring system (IPSS-R) there are no distinct treatment criteria for patients. This study reviews the treatment strategies employed at community oncology centers to examine if age or IPSS-R is being utilized to risk stratify patients with MDS. Methods: Pts were selected from the six FCS practices in Central Florida . The study is retrospective, patients were identified based on a diagnosis of MDS based on the ICD9 coding from 2013 to the present. The charts of a total of 325 patients were reviewed and determined to be eligible to be included in this analysis. Treatment choices (supportive, active, and transplant) were compiled with the IPSS-R score and other criteria. The data for various lines of treatment along with the responses were analyzed. Results: 325 patients were selected based on diagnostic criteria described above. 173 patients were male and 151 were female with a median age at diagnosis of 79 years (39 to 100). The majority of patients were > / = 65 years old (N = 314). Of these elderly MDS patients in the community based setting, 6% (19 out 314) went on to undergo anti-neoplastic treatment considered “active treatment”. All others were treated with supportive care including transfusions and growth factors. There were few patients examined that were under the age of 65 (N = 11) and one of those were treatment aggressively. Of these patients 256 had criteria in which adequate IPSS-R could be quantified. 221/256 (86%) in this subset were classified as low risk (very good to good) versus 35 in the intermediate to very poor categories. Conclusions: MDS is prevalent in the aging communities of rural central Florida. Many of these patients presenting to oncologists at consider low risk and being treated with supportive care regimens. Upon Patients in the higher risk categories are getting aggressive treatment are receiving “active treatment” approximately 50% of the time. This may be related to performance status and other criteria. Further study is necessary to evaluate these confounding criteria
Clinico-epidemiologic characteristics and patterns of care in Kaposi Sarcoma: Data from a single-institution series.
Authors: Andrew Hwang, Wesley Kerr, Andrew Samir Iskandar, Stephanie Farrell, Michael Del Rosario, Steven C. Plaxe, Constantin Dasanu
Journal: Journal of Clinical Oncology (2018)

e13585 Background: HHV-8 is the etiologic agent forKaposi sarcoma (KS) and several other neoplasms. Clinicopathologic characteristics in KS patients at the time of diagnosis may differ based on T-cell CD4+ (CD4) counts. Methods: With IRB approval, we conducted a retrospective analysis of all consecutive patients with KS treated at our institution from 2007-2017. Clinico-epidemiologic data, therapy and information on clinical course were collected. Statistical analysis: Significance of associations was assessed via Fishers' exact test. Two-sample t-tests with homoscedastic variance were used to compare the CD4 counts and viral load in patients with mucosal versus skin-only involvement. Results: We identified 27 patients with KS (n = 27). The mean age at diagnosis was 48 years; 92% (25/27) patients were male; 84% (21/27) were HIV positive. 25.9% (7/27) patients had mucosal involvement. Patients with mucosal involvement had a mean CD4 count of 83 cells/mm3 (95% confidence interval [CI] 27-139) as opposed to 381 cells/mm3(95% CI 282-480)in patients with skin-only involvement (t = 3.3, p = 0.005). All HIV-infected patients received antiretroviral therapy. 48.1% (13/27) KS patients were observed without treatment (other than antiretrovirals), 7.4% (2/27) underwent surgical resection of lesions, 18.5% (5/27) received local radiotherapy, and 25.9% (7/27) received liposomal doxorubicin. There were 3 deaths in KS patients with mucosal involvement and 4 deaths in KS with skin-only involvement (unrelated to KS). Mean time to death in deceased KS patients with mucosal involvement was 571 days. Castleman’s disease was identified in 7.4% (2/27) KS patients. We found no cases of body cavity lymphoma in our cohort. Conclusions: In patients with KS, mucosal involvement was found to be associated with a significantly lower CD4 count at the time of diagnosis compared to patients with skin-only KS. Survival was compromised in the former patient cohort. Final statistical analysis, including survival analysis, and significance are to be discussed.
Lanreotide depot/autogel before, during, and after peptide receptor radionuclide therapy (PRRT) in advanced neuroendocrine tumors (NETs): Data from the PRELUDE study.
Authors: Vikas Prasad, Raj Srirajaskanthan, Christos Toumpanakis, Chiara Maria Grana, Sergio Baldari, Tahir Shah, Angela Lamarca, Frédéric Courbon, Klemens Scheidhauer, Eric Baudin, Xuan Mai Truong Thanh, Aude Houchard, Lisa Bodei
Journal: Journal of Clinical Oncology (2018)

e16167 Background: PRRT, licensed for gastroenteropancreatic (GEP) NETs, has been used with somatostatin analogs such as lanreotide depot (LAN). PRELUDE is the first retrospective study to describe use of LAN with PRRT (LAN–PRRT) in advanced NETs. Methods: PRELUDE was an international, retrospective, non-comparative analysis of medical records of patients receiving LAN with 177Lu-DOTATATE/DOTATOC, and 12 mo LAN only follow-up. Key inclusion criteria: metastatic/locally advanced, grade 1/2, somatostatin receptor positive GEP or lung NET, progressive disease (PD) in the year prior to LAN–PRRT start, ≥1 LAN injection 8 wks before the 1st LAN–PRRT cycle, continuous LAN use during LAN–PRRT, cumulative PRRT activity ≥500 mCi. Primary endpoint: progression-free survival (PFS) rate from day 1 of 1st cycle to the end of the last LAN–PRRT cycle (RECISTv1.1, centrally assessed). Secondary endpoints included best overall response (OR; RECISTv1.1), objective response rate (ORR), change from baseline in diarrhea and flushing. Safety included incidence of nephro, hemato and hepatotoxicity; vomiting during infusion. Results: Enrollment was terminated early (insufficient recruitment). Of 40 patients enrolled, 39 had GEP NET (incl.; ileum 33.3%, unknown origin 25.6%, right colon 20.5%, pancreas 10.3%); one had lung NET (full analysis set: GEP NET n = 23, lung NET n = 1). Most patients with GEP NET had Ki67 > 2–≤20% (53.1%), global overall Krenning score (centrally assessed) grade 4 (70.4%), received 4 (17/23 patients) LAN–PRRT cycles, and 120mg LAN (18/23) last dose before PRRT. Median (range) LAN exposure: 37.0 (13.2, 90.0) mo overall; 12.6 (6.1, 32.5) mo during LAN only follow-up. PFS rate [95% CI]: 91.7% [53.9–98.8]. Best OR (GEP NET): 34.8% partial response, 60.9% stable disease, 4.3% PD. ORR at time of last LAN–PRRT cycle [95% CI]: 27.3% [13.2; 48.2]. Most patients with GEP NET had stable/improved diarrhea (15/15) and flushing (13/14). Few toxicities reported; no safety issues identified. Conclusions: Effectiveness data were encouraging in this selected population. In clinical practice, LAN use is considered before, during, and after PRRT. Clinical trial information: NCT02788578.
Towards national systems for continuous surveillance of antimicrobial resistance: Lessons from tuberculosis
Authors: Amitabh B. Suthar, Patrick K. Moonan, Heather L. Alexander
Journal: PLoS Medicine (2018)

In a Perspective on the research article from Jacobson and colleagues, Amitabh Suthar and colleagues from the Centers for Disease Control and Prevention discuss the importance of and considerations for developing real-time and large-scale reporting systems for tracking and controlling antimicrobial resistance.
Global Cancer Institute multidisciplinary tumor boards as a tool to improve patterns of clinical practice for breast and gynecologic cancer in resource-limited settings.
Authors: Jessica St. Louis, Alexandra Bukowski, Angelica Noguelra Rodrigues, Joel Moreno, Mayra Ferreyra, Andre Lopes, Frances De La Serna, Chakou Halfani Tindwa, Obayedullah Baki Mollah, Cynthia Villarreal-Garza, Carlos Duarte, Vahagn Hambardzumyan, Pamela Salman, Tannia Soria, Paul E. Goss
Journal: Journal of Clinical Oncology (2017)

6556 Background: Multidisciplinary tumor boards (MTBs) are commonly practiced in high-income countries (HICs) to ensure adherence to guidelines through a team approach to patient care. The Global Cancer Institute (GCI) established online MTBs in 2012 to facilitate live telemedicine discussions of breast and gynecologic case scenarios between specialists in low- and middle-income countries (LMICs) and expert specialists in HICs. GCI MTBs aim to improve clinical knowledge and patterns of practice for specialists in LMICs through an interactive online forum. Methods: In each monthly MTB, three patient case scenarios are presented by specialists in LMICs for live discussion with an expert panel of specialists based in HICs. Guideline or clinical trial-based discussions are held for each case scenario. Best practices for clinical care in limited resource settings are also discussed. Links to clinical practice guidelines, clinical trials, and resources are provided to all MTB attendees. For educational purposes, each MTB is live streamed and uploaded to a private YouTube channel for viewing by community oncologists and trainees worldwide. Results: The GCI MTBs program has recruited over 500 LMIC participants from 48 hospitals in 24 countries across Latin America, Eastern Europe, Africa, and Asia. 17 expert breast cancer specialists and 13 expert gynecologic cancer specialists provide multidisciplinary guidance. To date, 130 breast cancer case scenarios and 80 gynecologic cancer case scenarios have been presented. For breast MTBs, 73% of case scenarios were invasive ductal carcinomas. Common subtypes presented were ER/PR+ (63%), HER2+ (30%), and triple negative disease (28%). 56 cases involved advanced disease management (43%). For gynecologic MTBs, common gynecologic cancer case scenarios were cervical (74%) and ovarian (15%). 37 cases involved advanced disease management (46%). Conclusions: GCI MTBs are a useful educational tool for specialists in LMICs to improve patterns of clinical practice and engage in multidisciplinary discussions. GCI continues to expand its MTBs to cancer facilities in LMICs.
Burden of Illness and Economic Model for Patients With Nonalcoholic Steatohepatitis in the United States
Authors: Zobair M. Younossi, Radhika Tampi, Massoom Priyadarshini, Fatema Nader, Issah M. Younossi, Andrei Racila
Journal: Hepatology (2018)

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease. Our aim was to estimate the total economic burden of NASH and advanced NASH in the United States. We constructed lifetime Markov models for all stages of NASH and a separate model to specifically identify the increased burden of advanced NASH (fibrosis stage >3). The models comprised patients aged 18+, who moved through seven different health states. We used a lifetime horizon with 1-year cycles for each transition. Cohort size was estimated using US population data, and prevalence and incidence rates were obtained from the literature. Transition probabilities between states were derived from meta-analyses. Costs included inpatient, outpatient, professional services, emergency department, and drug costs, which were obtained from the Center for Medicare and Medicaid Services Fee Schedule 2017 and published data. All future costs were discounted at an annual rate of 3%. Our models estimated that there are 6.65 million adults (18+ years old) with NASH in the United States and that there were 232,000 incident cases in 2017. Lifetime costs of all NASH patients in the United States in 2017 will be $222.6 billion, and the cost of the advanced NASH population will be $95.4 billion. Conclusion: NASH, especially advanced NASH, is associated with high lifetime economic burden; in the absence of treatment, the total direct costs of illness for these patients will continue to grow, and these costs would be even greater if the societal costs are included.
A randomized phase II clinical trial of a fasting-mimic diet prior to chemotherapy to evaluate the impact on toxicity and efficacy.
Authors: Tanya B. Dorff, Mahshid Shelechi, Irene Kang, Todd E Morgan, Susan G. Groshen, Sriram Yennu, Agustin A. Garcia, David I. Quinn, Valter Longo
Journal: Journal of Clinical Oncology (2018)

TPS10132 Background: Chemotherapy toxicity impacts dose intensity as well as temporarily deteriorating quality of life; some toxicity can be permanent, such as neuropathy. We previously demonstrated that fasting induces Differential Stress Resistance and hypothesized that fasting may protect normal host cells from chemotherapy toxicity, while potentially sensitizing cancer cells to chemotherapy. A low calorie, low protein fasting-mimicking diet (FMD) may be more acceptable than pure fasting. We are studying whether FMD will reduce chemotherapy toxicity and/or enhance efficacy. Changes in glucose and insulin‐like growth factor 1 (IGF1) may mediate or be biomarkers for the protective effects of fasting and will be studied in the trial population. Methods: Randomized phase II in 2 parallel cohorts (Prostate, n = 60, Breast n = 60). Treatment: Arm A = restricted diet consumed 3 days prior to and 24 hours after chemotherapy for 4 cycles. Arm B = regular diet. Eligibility: breast cancer with AC or TC in neoadjuvant setting, prostate cancer treated with Docetaxel, up-front or for mCRPC. BMI > 18.5. Exclusion: Diabetes Mellitus. Endpoints: Primary: Grade 2+ non-hematologic symptomatic toxicities experienced during 4 courses; additionally, radiographic (RECIST) response and PSA changes. Secondary: toxicity (all grade 2-4 events, dose reductions/delays) and efficacy (pathologic response for breast cancer, PSA/RECIST response for prostate cancer). Biomarker: plasma insulin, glucose, IGF1 and IGF binding protein (IGFBP) at baseline, and each cycle. Statistics: Proportion of patients with grade 2-4 symptomatic toxicities will be compared between treatment arms using stratified Mantel-Haenszel test; p-value ≤ 0.20 indicates the diet intervention is promising. With 60 patients in each cohort there is 88% power; initial analyses will evaluate breast/prostate cancer separately, yielding standard error no more than +/- 0.18 for estimates of the difference in the proportions of patients who experience a specific toxicity (or the composite). Quality of life will be assessed with SWOG questionnaire on day 1 of each chemotherapy cycle. Progress: 70 of 120 planned subjects have been accrued. Clinical trial information: NCT01802346.