tbuckley/cabot-search huggingface dataset:
Diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the evaluation of hypermetabolic lymphadenopathy mediastinum lower, posterior, and middle, detected by PET-CT with 18F-FDG (PET) (APOGEE Study).
Authors: Dominique Bechade, Carine A. Bellera, Coralie Cantarel, Isabelle Soubeyran, Marc Debled, Francois Chomy, Guilhem Roubaud, Marianne Fonck, Anne Laure Cazeau
Journal: Journal of Clinical Oncology (2020)

798 Background: In the context of a new cancer or relapse, the high sensitivity (Se) (95-100%) of PET-CT with 18F-FDG can lead to the demonstration of hypermetabolic mediastinal adenopathies. Its lower specificity (Sp) (89%) can require histological examination. We report the results of a prospective, single-center study evaluating the diagnostic performance of EUS-FNA in this indication. Methods: Prospective single-center study featuring patients in whom PET had revealed hypermetabolic mediastinal lymphadenopathy requiring diagnostic certainty. All EUS-FNA were performed with a 19-gauge needle (EchoTip, Cook Endoscopy). Main objective: To evaluate the diagnostic performance in terms of Se and Sp of EUS-FNA in the characterization of hypermetabolic mediastinal adenopathies in PET in the context of a new cancer or relapse. Secondary objectives: To evaluate the negative predictive value (NPV) of the EUS-FNA and to evaluate the percentage of surgical diagnostic procedures avoided. The standard technique was a thoraco-abdominopelvic CT scan at 6 months and at 12 months. Results: 52 patients were eligible and evaluable for the primary endpoint. The most common primary cancers were mammary (17.3%) and bronchial (13.5%). The lymph nodes were analyzed as malignant in 44.2% of cases, benign in 50% of cases and atypical or suspicious in 3.8% of cases. The malignant lymph nodes were metastatic for breast cancer in 21.7% of cases, bronchial cancer in 17.4% of cases, colorectal cancer in 17.4% of cases and prostate cancer in 13% of cases. The Se of the EUS-FNA was 92% (95% CI 0.74-0.99) and the Sp 100%. NPV was 87% (95% CI: 0.59-0.98). A diagnostic surgical procedure was necessary in 2% of the cases. PET and EUS-FNA often allowed the modification of the therapeutic strategy. Conclusions: When a confirmed diagnosis is required, the diagnostic accuracy of the minimally invasive procedure of EUS-FNA, is sufficiently robust to avoid a surgical diagnosis technique. The combination of PET and EUS-FNA may alter the therapeutic strategy that would have been considered after PET alone. Clinical trial information: NCT01892501.
A retrospective multicenter study evaluating the efficacy and safety of irinotecan in patients with advanced gastric cancer: Analysis of albumin-bilirubin (ALBI) grade.
Authors: Iori Motoo, Yoshito Komatsu, Satoshi Yuki, Shintaro Nakano, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Tetsuhito Muranaka, Kentaro Sawada, Takayuki Ando, Takuto Miyagishima, Kazuaki Harada, Yoshimitsu Kobayashi, Kazuteru Hatanaka, Atsushi Ishiguro, Aya Tanimoto, Takuya Honda, Masayoshi Dazai, Takahide Sasaki, Naoya Sakamoto
Journal: Journal of Clinical Oncology (2020)

415 Background: It is important to predict prognosis and risk of adverse events in patients with advanced gastric cancer receiving chemotherapy. Albumin-bilirubin (ALBI) grade is recently used as liver function assessment and prognosticator in hepatocellular carcinoma. Irinotecan is metabolized in the liver, so ALBI score may be useful for predicting irinotecan efficacy and safety. Methods: We conducted a retrospective multicenter study and investigated association between efficacy and ALBI grade in patients who received irinotecan monotherapy between January 2010 and December 2017. All patients had to receive fluoropyrimidine and platinum as prior therapy. The ALBI score is calculated by the equation: ALBI score = (log 10 bilirubin [µmol/L] × 0.66) + (albumin [g/L] × −0.0852). As a result, ALBI grades 1, 2, and 3 were developed as follows: ALBI score ≤ −2.60 (ALBI grade 1), &gt; −2.60 to ≤ −1.39 (ALBI grade 2), and &gt; −1.39 (ALBI grade 3). Results: The number of patients with ALBI grade 1/2/3 is 100/68/5. In ALBI 1/2-3 patients, performance status 0/1/≥2 was 37/57/6 and 17/43/14, treatment line 2 nd /3 rd or later was 58/42 and 21/53, HER2 positive/negative 14/86 and 16/58, respectively. In ALBI 1/2-3 patients, median PFS was 3.3 and 2.3 months (HR = 0.684, P = 0.018) and median OS was 11.7 and 6.7 months (HR = 0.492, P &lt; 0.001), respectively. In ALBI 1/2-3 patients, median treatment cycle which was 6 and 4 ( P = 0.09) and RDI were significantly different was, and RDI was 0.80 vs 0.70( P = 0.027), respectively.Hematological AEs were observed in 88% and 87% ( P = 1.000), severe hematological AEs (≥G3) were 41% and 58%( P = 0.040). Non-hematological AEs were 87% and 86%( P = 1.000), severe non-hematological AEs (≥G3) were 11% and 18% ( P = 0.257), respectively. Severe AEs in more than 5% patients were leukopenia (12% and 18%), neutropenia (23% and 28%), anemia (16% and 31%), and anorexia (2% and 10%).In multivariate analysis, ALBI grade was associated with shorter OS (ALBI 1 and 2-3: HR 1.773 95%C.I. 1.184-2.654, p = 0.005). Conclusions: ALBI grade might be both prognostic factor and risk factor in treatment with irinotecan monotherapy for patients with AGC.
Novel cancer stem cell model for human solid tumors: Molecular profiling and tumorigenicity of tumor cell clones expressing developmental markers
Authors: Tatyana Ignatova, Raisa Krutilina, Arindam Chatterjee, Galina Dulatova, Christopher Duntsch, Valery Kukekov
Journal: Cancer Research (2008)

5427  The cancer stem cell (CSC) model relies on the existence of a rare subset of cells in a total tumor cell population. They exhibit an exclusive competence for tumor recapitulation in xenograft models and the ability to self-renew analogous to adult organ stem cells resulting in inevitable tumor growth and metastasis. In order to evaluate novel therapeutic treatments against metastatic disease of most solid tumors, as the principal cause of mortality, and to enhance our understanding of the mechanisms driving tumor growth and metastasis, several CSC models have been recently proposed. Here, we established a novel CSC model to dissect heterogeneity of human solid tumors, including glioblastomas, breast cancer and bone sarcomas based on CSCs expressing developmental markers. Single cell suspensions prepared from cell lines, tissues of surgically removed primary tumors, metastatic lesions or xenografts grown in nude mice were analyzed by using the original reporter constructs or flow cytometry for the expression of different developmental markers specific for stem cells in embryonic settings and adult somatic tissues. The markers which showed interclonal heterogeneity for their expression in cell subsets isolated from tumor cell lines and clinical specimens were used for further cloning and clone enrichment by cell sorting. The resulted independent clonal cell subsets were tested for tumorigenicity in nude mice and for molecular profiling by real-time PCR, microarrays, flow cytometry and Western blottings. Eventually, this study allowed us to dissect cancer cell populations for subsets with the highest potential in orthotopic or ectopic engraftment and distant metastasis. At this end, the best ability to engraft in vivo was observed for clonal subsets selected from breast cancer line MDA-MB-231 based on their ability to maintain the reporter fluorescent constructs, as well as to express differentially several markers including CD44high and CD24low. Orthotopic and ectopic tumor xenografts originated from such clonal subsets were able to recapitulate the initial tumor cell population heterogeneity. Several types of cells differing for their potential to maintain the expression of reporter constructs and to express differentially the stem cell developmental markers persisted in xenografts resulted from multiple rounds of orthotopic grafting in nude mice. Their cells exhibited the increased proficiency for tumor and metastases formation. The molecular profiles of clonal xenografts suggested the mechanisms that underlie tumor heterogeneity and metastasis based on CSCs and their progeny. These findings validate our novel CSC model for human solid tumors. They suggest the persistence of rare tumor cells competent to maintain the expression of specific developmental markers which may be not associated with adult tumor tissue specificity.
A phase II study of niraparib in combination with EGFR inhibitor panitumumab in patients with advanced colorectal cancer.
Authors: Olatunji B. Alese, Walid Labib Shaib, Mehmet Akce, Christina Wu, Gregory B. Lesinski, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2020)

TPS269 Background: Panitumumab (Pmab) is a recombinant monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR), and is indicated for metastatic colorectal carcinoma (mCRC). EGFR inhibition induces synthetic lethality with poly ADP ribose polymerase inhibitors (PARPi) by attenuating DNA repair pathways. This susceptibility to PARPi-induced cell death by EGFR inhibition is associated with deficient Non-homologous end joining (NHEJ), and Homologous recombination (HR) mediated DNA repair and persistence of DNA damage. Furthermore, efficacy of PARPi (such as niraparib) is highly correlated with platinum sensitivity. Cancer cell sensitivity and resistance to both PARPi and platinum have been associated with loss and restoration of HR DNA repair, indicating similar mechanisms of anticancer activity and resistance. Platinum sensitivity in CRC could therefore predict for anticancer properties of PARPi when utilized in the setting of synthetic lethality. Combining PARP and EGFR inhibition has the potential to confer synergistic benefit, while ameliorating resistance mechanism to PARPi. This study aims to evaluate the activity of the combination of niraparib and Pmab in RAS wildtype (WT) mCRC. Methods: Eligible patients for the trial include advanced, RAS WT mCRC who have been intolerant of, progressed on, or failed at least one line of systemic chemotherapy. Those currently on first line oxaliplatin-containing regimen are allowed on the trial if they have remained stable or better (PR or CR) for at least 4 months on that line of treatment, and are being considered for maintenance therapy as standard of care. Patients must also be 18 years old, ECOG PS 0-1 and measurable disease per RECIST 1.1. A safety run-in cohort of 6 eligible patients, and additional 20 patients with the same inclusion criteria will be enrolled. Pmab dose - 6 mg/kg IV on days 1 &amp; 15 of each 28-day cycle; Niraparib - 200mg or 300mg (based on body weight and platelet count) orally continuously. Primary endpoint: clinical benefit rate (CR +PR + SD). Biomarker analysis includes skin biopsies evaluated for p-Caspace-3, PARP, p-MAPK, Ki-67, and p27. The study was activated in Sept. 2019. Clinical trial information: NCT03983993.
Improved efficacy to cytotoxic agents chemotherapy after immune checkpoint inhibitors exposure in metastatic gastric cancer.
Authors: Tamotsu Sagawa, Yasushi Sato, Kyoko Hamaguchi, Masahiro Hirakawa, Hiroyuki Nagashima, Eriko Waga, Koshi Fujikawa, Yasuo Takahashi
Journal: Journal of Clinical Oncology (2020)

297 Background: An association between improved responses to chemotherapy after exposure to vaccine-based immunotherapy has been previously reported in other cancers. However, it is unclear whether the chemotherapy response improves after exposure to immunotherapy, such as immune checkpoint inhibitors (ICIs). The objective of this retrospective study was to evaluate whether chemotherapy (4th-line) would yield improved efficacy when given after exposure to anti-PD-1 antibody in metastatic gastric cancer (mGC). Methods: We investigated retrospectively clinical characteristics at baseline of mGC patients who received chemotherapy after progression of anti-PD-1 antibody (Nivolumab) between February 2018 and July 2019. Anti-PD-1 antibody was adapted as third-line therapy. Inclusion criteria for the analysis reported herein: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received chemotherapy including 5-fluoropyrimidines (5-FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, DCR by RECIST version 1.1, PFS, and OS. Results: Out of 27 treated with anti-PD-1 antibody, 10 patients were evaluable for responses and eligible to be included in this analysis. Patient characteristics were as follows: median age (range), 72 (50-88) years; male/female, 8/2; ECOG PS (0/1/2), 4/5/1; HER2 (+/-), 5/5; histology (differentiated/undifferentiated), 5/5; metastatic lesions (LN/peritoneum/liver/lung), 5/3/1/3; number of metastatic sites (1/≥2), 5/5; number of prior CTx regimens (3/4/5), 10/0/0; median period (range) from first line CTx, 18.8 (7.9-47.1) months; and CTx regimens (CPT-11/PTX/S-1+Oxaliplatin), 7/2/1; Among the 10 patients, 1 achieved a partial response, giving an ORR of 10.0%. Six patients had stable disease and three had progressive disease. The DCR was 70%. Median PFS and OS were 5.5M and 8.5M, respectively. These were no new irAEs appeared during CTx. Conclusions: In mGC patients, our study demonstrated that increased efficacy to cytotoxic agents chemotherapy given after exposure to ICI was higher as compared to our historical data from the pre-anti-PD1 era. Updated results will be presented.
Real-world outcomes for metastatic non-small cell lung cancer patients treated with checkpoint inhibitor immunotherapy in Canada.
Authors: Dimas Yusuf, Jenny J. Ko, Hyokeun Cho, Corey Sheremeto, Ying Wang, Rosalyn A. Juergens, Peter Michael Ellis, Alkarim Billawala, Amin Kay, Swati Kulkarni, Tarek A. Elfiki, Rasna Gupta, Krista Naccarato, Alex Pennetti, Devalben Patel, Elliot Charles Smith, Ryan Walton, Manjusha Hurry, Geoffrey Liu, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2020)

54 Background: The majority of patients with non-small cell lung cancer (NSCLC) are diagnosed with incurable, metastatic disease. Immunotherapy (IO) agents have improved overall, long term survival. There is a need to better understand how these drugs are utilized and perform in the real world to further inform physicians and policymakers. Methods: In this retrospective study, we analyzed characteristics, treatment patterns, and outcomes of patients with metastatic NSCLC treated with checkpoint inhibitors nivolumab or pembrolizumab at five Canadian cancer centres, with a focus on patients who received these treatments in the 2nd (2L) or 3rd line (3L) setting. We excluded patients who were in blinded clinical trials, exposed to multiple IO drugs, or who had tumors with EGFR or ALK mutations. Primary endpoints were overall survival (OS) and progression free survival (PFS) from start of IO. Secondary endpoints included immune-related toxicities. Results: Across all sites, we screened 322 patients and included 230 who met criteria: 49 (21%) from Alberta; 60 (26%) from British Columbia; and 121 (53%) from Ontario. Patients were diagnosed with metastatic NSCLC from 2009 to 2018, but the majority were diagnosed after 2015. Median age at diagnosis was 66.6 years, 54% were female, and 86% were either current or former smokers and 67% had stage IV disease. About 88% received nivolumab; 87% (n=200) received IO in 2L (n=111) or 3L (n=89). The median OS from start of IO was 10.9 (8.7–15.6) months, and were similar for 2L vs 3L (9.3 vs 12.0 months, p = 0.2). Median PFS was 5.7 (4.4–8.1) months. Pneumonitis was the most frequently reported toxicity affecting 7% of patients. Thyroiditis was reported in 4%; colitis, while dermatitis and hepatitis were each reported in 3%, and nephritis in 1%. Conclusions: In the real world, IO for advanced NSCLC was well-tolerated and had outcomes that were comparable to landmark clinical trials.
Abstract 11922: Perioperative Myocardial Injury After Non-Cardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Gabriel Redel-Traub, Anais Hausvater, Andrew Armanious, Joseph Nicholson, Jeffrey Berger, Nathaniel Smilowitz
Journal: Circulation (2018)

Background: Myocardial injury after non-cardiac surgery (MINS) is a major perioperative complication of non-cardiac surgery and is associated with increased risk for morbidity and mortality. The pu...
Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder
Authors: Sarah E. Wakeman, Marc R. Larochelle, Omid Ameli, Christine E. Chaisson, Jeffrey Thomas McPheeters, William H. Crown, Francisca Azocar, Darshak M. Sanghavi
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Although clinical trials demonstrate the superior effectiveness of medication for opioid use disorder (MOUD) compared with nonpharmacologic treatment, national data on the comparative effectiveness of real-world treatment pathways are lacking. <h3>Objective</h3> To examine associations between opioid use disorder (OUD) treatment pathways and overdose and opioid-related acute care use as proxies for OUD recurrence. <h3>Design, Setting, and Participants</h3> This retrospective comparative effectiveness research study assessed deidentified claims from the OptumLabs Data Warehouse from individuals aged 16 years or older with OUD and commercial or Medicare Advantage coverage. Opioid use disorder was identified based on 1 or more inpatient or 2 or more outpatient claims for OUD diagnosis codes within 3 months of each other; 1 or more claims for OUD plus diagnosis codes for opioid-related overdose, injection-related infection, or inpatient detoxification or residential services; or MOUD claims between January 1, 2015, and September 30, 2017. Data analysis was performed from April 1, 2018, to June 30, 2019. <h3>Exposures</h3> One of 6 mutually exclusive treatment pathways, including (1) no treatment, (2) inpatient detoxification or residential services, (3) intensive behavioral health, (4) buprenorphine or methadone, (5) naltrexone, and (6) nonintensive behavioral health. <h3>Main Outcomes and Measures</h3> Opioid-related overdose or serious acute care use during 3 and 12 months after initial treatment. <h3>Results</h3> A total of 40 885 individuals with OUD (mean [SD] age, 47.73 [17.25] years; 22 172 [54.2%] male; 30 332 [74.2%] white) were identified. For OUD treatment, 24 258 (59.3%) received nonintensive behavioral health, 6455 (15.8%) received inpatient detoxification or residential services, 5123 (12.5%) received MOUD treatment with buprenorphine or methadone, 1970 (4.8%) received intensive behavioral health, and 963 (2.4%) received MOUD treatment with naltrexone. During 3-month follow-up, 707 participants (1.7%) experienced an overdose, and 773 (1.9%) had serious opioid-related acute care use. Only treatment with buprenorphine or methadone was associated with a reduced risk of overdose during 3-month (adjusted hazard ratio [AHR], 0.24; 95% CI, 0.14-0.41) and 12-month (AHR, 0.41; 95% CI, 0.31-0.55) follow-up. Treatment with buprenorphine or methadone was also associated with reduction in serious opioid-related acute care use during 3-month (AHR, 0.68; 95% CI, 0.47-0.99) and 12-month (AHR, 0.74; 95% CI, 0.58-0.95) follow-up. <h3>Conclusions and Relevance</h3> Treatment with buprenorphine or methadone was associated with reductions in overdose and serious opioid-related acute care use compared with other treatments. Strategies to address the underuse of MOUD are needed.
Comparison of the clinical features, treatment patterns, and tumor mutations of patients with intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma.
Authors: Leon Pappas, Stephanie Reyes, Aishwarya Lanka, Rachna T. Shroff, Tri Minh Le, Osama E. Rahma, Andrea Grace Bocobo, Mitesh J. Borad, Thomas DeLeon, Kabir Mody, Marc Thomas Roth, Mary Linton Bounetheau Peters, Laura Williams Goff, Kylie Boyhen, Christine VanCott, Nora Horick, Andrew X. Zhu, Milind M. Javle, Robin Kate Kelley, Lipika Goyal
Journal: Journal of Clinical Oncology (2020)

580 Background: Though studies indicate that the genomic profiles of ICC and ECC are distinct, the clinical features that differentiate them still remain to be well characterized. The purpose of this study was to further analyze these differences and patient treatment patterns in a multi-center cohort. Methods: A retrospective chart review was performed at 8 institutions on patients (pts) with ICC or ECC diagnosed after June 2009. Data on demographics, risk factors, treatments, pathology and overall survival (OS) were collected. Tumor genotyping results from CLIA-certified tissue assays were analyzed. Fisher’s exact, Wilcoxon rank sum and log-rank tests were used to compare sub-groups. Results: In a database of 737 pts with cholangiocarcinoma, 538(73%) had ICC and 199(27%) had ECC. Pts with ICC more often presented in later stages, had tumors &gt; 5cm at resection (p &lt; 0.0001) and had metastases to the liver, lymph nodes, lung and/or bone (p &lt; 0.01). Pts with ICC more often received liver directed therapy, targeted therapy and multiple lines of systemic therapy and they more often enrolled in a clinical trial (all p &lt; 0.01). Pts with ECC were more likely to be male, undergo surgery, receive adjuvant chemotherapy and/or chemoradiation (all p &lt; 0.05). Mutation profiling performed in 381 (52%) pts (ICC/ECC = 301/80) showed that pts with ICC were more likely to have IDH1 mutations and FGFR2 fusions, whereas pts with ECC were more likely to have KRAS, APC, SMAD4, WNT, TGFb and TP53 mutations (all &lt; 0.05). Factors that did not differ significantly between pts with ICC and ECC include race, rates of primary sclerosing cholangitis, median diagnosis CA19-9 levels and R1 resection rate. Median OS from diagnosis was 18.9 months in ICC and 17.3 months in ECC (p = 0.8471). Conclusions: While pts with ICC and ECC have some similarities in their clinical features, differences in metastases patterns and molecular profiling significantly impact their management such that pts with ICC receive more liver-directed therapy, targeted therapy and more lines of systemic therapy. Further prospective studies are needed as referral patterns to tertiary care centers may have impacted these results.