tbuckley/cabot-search huggingface dataset:
Her2 expression in small bowel adenocarcinoma.
Authors: Samuel Gboyega Adediran, Usman Shah, Shereen Gheith, Pal Singh-Kahlon, Ben Fisher
Journal: Journal of Clinical Oncology (2018)

e16261 Background: The frequency of HER2 alterations in SBA varies widely in the literature but overall reported as point mutations in 9.5-12% of SBA and amplification in < 5% of SBA. Given the role of HER2 gene amplification as a potential therapeutic target in SBA, we conducted a study to evaluate the frequency of this gene amplification and the clinicopathologic features associated with this alteration in a cohort of patients diagnosed with SBA over a 15-year period. Methods: Patients diagnosed with SBA from 2002 to 2016 were identified. Records were de-identified and reviewed. Fluorescent in-situ hybridization (FISH) for HER2 and immunohistochemistry (IHC) were performed on FFPE tumor samples. Results: 53 patients with primary SBA were identified. Tissue containing tumor was available for 42 patients; 22 duodenal, 4 jejunal, 5 ileal and 11 from unspecified locations in the small bowel. 5 patients had stage I, 13 stage II, 9 stage III, 10 stage IV and 5 with unknown stage. IHC was positive in one case, equivocal in 7 cases and negative in 35 cases. FISH showed HER2 amplification in 7 of 42 (16.7%) samples. Of the 22 duodenal adenocarcinoma, 3 (13.6%) were HER2 amplified. The remaining 4 cases were from unspecified small bowel locations. Of the 29 patients with known differentiation status, 2 of 5 (40%) with HER2 amplification vs 8 of 24 (33%) with no amplification were poorly differentiated. 3 of 7 (43%) HER2 amplified vs 7 of 30 (23%) non-amplified tumors were stage IV at diagnosis. In non-metastatic disease, 1 of the 4 HER2 amplified vs 16 of the 28 unamplified tumors recurred. A year after diagnosis of metastatic disease, 3 of 3 HER2 amplified vs 1 of 7 unamplified patients were alive. Conclusions: HER2 amplification was found in 16.7% of patients with SBA. Our results showed higher frequency than previous reports and therefore might indicate a potential role for HER2 amplification screening in SBA. The sensitivity of the FISH was superior to that of IHC making the later non-suitable for screening purposes. HER2 amplification was associated with metastatic disease and poorly differentiated tumors. There was no clear association with overall survival or disease recurrence. However, the small size of the study preclude a definitive conclusion about the statistical significance of the results.
Abstract 17951: S-glutathionylation of Rac1 is a Novel Mechanism of Vascular Barrier Dysfunction in Diabetes Mellitus
Authors: Robert M Weisbrod, Di Shao, Kevin L Kot, Hannah Edenbaum, Reiko Matsui, Markus Michael Bachschmid, Naomi M Hamburg, Richard A Cohen, Jingyan Han
Journal: Circulation (2016)

Background: — Protein S-glutathionylation (Pr-SSG) is a prevalent form of oxidative modification of reactive cysteines and serves as an important mode of redox signaling. Vascular redox dysregulati...
Retrospective analysis of clinical outcome of EGFR mutated patients in a county hospital.
Authors: Srijana Rai, Hussein Hamad, Margaret Griffin Crawford, Jun Zhang
Journal: Journal of Clinical Oncology (2018)

e21208 Background: Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are observed in around 15% of lung adenocarcinoma in the United States. Multiple phase III trials have shown EGFR tyrosine kinase inhibitors (TKI) to be superior to platinum-based chemotherapy for patients with metastatic EGFR mutated adenocarcinoma. We analyzed clinical outcomes of this group of patients in a community setting. Methods: We performed retrospective chart review of the patients diagnosed with metastatic lung adenocarcinoma at Harris Health District hospitals between January 2012 and December 2017. Patient characteristics, mean duration from biopsy to report of EGFR status, time to initiation of TKI and clinical outcomes were calculated. Results: We identified 213 patients with stage IV lung adenocarcinoma. Of the 151 patients tested for EGFR mutation, 52 were positive; 48% with exon 21 mutation, 46% with exon 19 deletion, 4% with exon 20 insertion and 2% with exon 18 mutation. Mean patient age was 60 years; with 71% female compared to 29% male. 42% of the EGFR positive patients were Hispanic, followed by Asian 31%, African-American 15%, White 8% and others 4%. 81% of the cohort were nonsmoker as opposed to 19% who were either active or former smoker. Mean time from biopsy to biomarker reporting was 27 days and mean time to initiation of TKI was 15 days. First line systemic therapy was Erlotinib (44%) followed by chemotherapy (36%), Afatinib (8%) and Osimertinib (2%). Three patients started TKI prior to biomarker reporting based on high clinical suspicion and later were proven to have EGFR mutation. 10% of the cohort did not receive any systemic treatment due to death prior to initial consultation. Median follow up was 20 months. Overall survival at 1 year and 2 years was 79% and 53% respectively. Median progression-free survival was 9 months. Conclusions: In our experience, median survival was comparable to other historically reported data. Although not all patients had biomarker tested, the turnaround time for results and initiation of systemic therapy were also similar.
TCT-200 Surgical Left Atrial Appendage Occlusion During Cardiac Surgery: A Systematic Review and Meta-analysis.
Authors: Varunsiri Atti, Mark Terence Mujer, Layan Elkhatib, Sowmika Rao, Deepak Asti, Nikhil Nalluri, Sunilkumar Rao, Juan Viles-Gonzalez, Varun Kumar
Journal: Journal of the American College of Cardiology (2018)
KEYNOTE-164: Pembrolizumab for patients with advanced microsatellite instability high (MSI-H) colorectal cancer.
Authors: Dung T. Le, Petr Kavan, Tae Won Kim, Matthew E. Burge, Eric Van Cutsem, Hiroki Hara, Patrick McKay Boland, Jean-Luc Van Laethem, Ravit Geva, Hiroya Taniguchi, Todd S. Crocenzi, Manish Sharma, Chloe Evelyn Atreya, Luis A. Diaz, Li Wen Liang, Patricia Marinello, Tong Dai, Bert H. O'Neil
Journal: Journal of Clinical Oncology (2018)

3514 Background: Pembrolizumab is approved for the treatment of adult and pediatric patients (pts) with previously treated MSI-H cancer regardless of tumor type or site. This approval was based in part on data from cohort A of the phase 2 KEYNOTE-164 (NCT02460198) study of pts with MSI-H CRC after ≥2 prior lines of therapy including fluoropyrimidine, oxaliplatin, and irinotecan. In addition, in Cohort B of KEYNOTE-164, we evaluated the activity of pembrolizumab in pts with metastatic MSI-H CRC treated with ≥1 prior line of therapy. Methods: KEYNOTE-164 cohort B enrolled pts with metastatic CRC, MSI-H status confirmed locally by IHC or PCR, and ≥1 prior line of therapy (fluoropyrimidine, oxaliplatin, irinotecan, or anti VEGF/EGFR). Eligible pts received pembrolizumab 200 mg Q3W for 2 years or until progression, unacceptable toxicity, or withdrawal of consent. Tumor response was assessed Q9W per RECIST v1.1 by independent review. The primary endpoint was ORR. Secondary endpoints included DOR, PFS, OS, and safety. Results: Of 63 pts enrolled, median age (range) was 59 years (23-83), and 52% were male. Pts had a median of 2 prior therapies, and 94% had ≥1 prior therapy for advanced disease. As of Sep 12, 2017, median (range) duration of follow-up was 12.6 months (0.1-15.4). ORR was 32% (95% CI, 21-45) with 2 CRs and 18 PRs. Median DOR was not reached (NR); 95% of responses were ongoing with DOR ≥6 mo in 75% of responders. Median PFS was 4.1 month (95% CI, 2.1-NR) with a 12-month PFS rate of 41%. Median OS was NR with a 12-month OS rate of 76%. Forty (64%) pts had any grade treatment-related AEs, most commonly (≥10%) fatigue (18%), hypothyroidism (16%), and hyperthyroidism (11%); 7 (11%) pts had grade 3-4 treatment-related AEs of anemia, thrombocytopenia, diarrhea, pneumatosis intestinalis, arthritis, syncope, pneumonitis, and vasculitis (n = 1 each). There were no treatment-related deaths. Twenty (32%) pts had any grade immune-mediated AEs; 2 (3%) pts had grade 3-4 immune-mediated AEs of colitis and pneumonitis (n = 1 each). Conclusions: Pembrolizumab provided durable antitumor activity with a manageable safety profile in patients with MSI-H CRC that progressed after ≥1 prior line of therapy. Clinical trial information: NCT02460198.
Role of primary tumor resection in the prognosis of patients with resectable metastatic hepatocellular carcinoma.
Authors: Kai Mao, Ruomei Wang, Qiaodong Xu, Zhiyu Xiao, Jianlong Zhang, Yingyue Liu, Jieqiong Liu
Journal: Journal of Clinical Oncology (2017)

e15642 Background: Patients with metastatic hepatocellular carcinoma (HCC) are diagnosed more frequently because of introduction of increasingly sensitive imaging modalities. The majority of these patients die of progressive intrahepatic tumor but not due to extrahepatic metastasis. There has been little information about the role of primary tumor resection (PTR) for metastatic HCC patients with resectable primary tumor. Methods: Metastatic HCC patients recommended PTR were identified in SEER registry between 2004 and 2013. The effect of PTR on overall and cancer-specific survival (OS and CSS) using log-rank test and Cox proportional hazard regression model, as well as propensity score matching was assessed. Additionally, validation was performed in another cohort from Sun Yat-sen Memorial hospital (n = 131). Results: Overall, 529 metastatic HCC patients with resectable primary tumor were included. Of those 230 patients underwent PTR but 299 did not. The percentage of PTR among resectable metastatic HCCs increased from 38.6% in 2004 to 70.3% in 2013. PTR was associated with improved OS (hazard ratio (HR) 0.310, 95% CI 0.241-0.400, P&lt; 0.001) and CSS (HR 0.326, 95% CI 0.250-0.425, P&lt; 0.001) in the propensity score- matched patients. This improvement in outcomes remained significant after sensitivity analyses using multiple imputation. Furthermore, consistent with observations in SEER, PTR was correlated with improved OS (HR 0.496, 95% CI 0.294-0.838, P= 0.009) and CSS (HR 0.538, 95% CI 0.307-0.945, P= 0.031) in the validation cohort from Sun Yat-sen Memorial hospital. Conclusions: This study, the first population-based analysis using propensity score matching and multiple imputation, demonstrated that PTR has a favorable impact on prognosis in patients with metastatic HCC. Further prospective randomized trials is needed to conclusively determine whether metastatic HCC patients with resectable primary tumor should be offered aggressive locoregional surgery.
DLBCL in Hispanics: The University of Miami (UM) experience.
Authors: Moises Harari Turquie, Alvaro Jose Alencar
Journal: Journal of Clinical Oncology (2018)

e19526 Background: Diffuse large B cell lymphoma (DLBCL) has subtypes with different biological features and outcomes. Cell of origin classification (COO) represents 2 biologic entities - germinal center (GCB) and non-germinal center (non-GCB) B-cell like. Double hit (DH) and double expressor (DE) DLBCL are subtypes with inferior outcomes. Retrospective review SCHOLAR-1 emphasized the poor prognosis of primary refractory DLBCL (PRD) [Blood 130:1800, 2017]. DLBCL also carries a risk of central nervous system (CNS) recurrence stratified by the CNS international prognostic index (CNS-IPI) [J Clin Oncol 34:3150, 2016]. UM has a strategic location in the United States with a Hispanic population of approximately 68% versus 18% in the USA according to 2016 Census. The objective of this study was to evaluate potential biologic variations in Hispanics. Methods: Retrospective chart review of patients with treated at UM between 2015-2016. Patient characteristics, treatment information, and tumor biologic information were collected. Patients were divided as Hispanic and non-Hispanic. Results: A total of 66 patients met inclusion criteria. Median age was 62, 75% with advanced stage, 36 Hispanic (55%), 30 non-Hispanic (50%). Median follow-up was 15 months. Non-GCB was more common (n = 45, 68%) with similar proportion between Hispanics and non-Hispanics. DH/DE status could be evaluated on 59 cases. Nearly one quarter was DE (n = 14, 24%) and 7 DH (12%), also with similar proportion between groups. Twelve patients had PRD. Median CNS-IPI was 3 (low 3, 21 %; intermediate 7, 50 %; high 4, 29%). Fourteen patients received CNS prophylaxis, 4/14 DE, 2/7 DH, with no CNS recurrence. Progression was noted in 31 (47%, median time to recurrence 10.3 months). Conclusions: The greater proportion of Hispanics in our population did not reflect in difference in characteristics or outcomes compared to the literature. COO distribution, DE phenotype, CNS-IPI, PRD, disease recurrence rates were within published data suggesting no effect from ethnicity in these biologic features. The 12% DH was higher than expected but similar incidence in Hispanics and non-Hispanics. Hispanic ethnicity appears not to play a role in the biology of DLBCL.
Surveillance after curative resection of pancreatic ductal adenocarcinoma: A multicenter survey in Germany.
Authors: Thomas Jens Ettrich, Lucas-Alexander Schulte, Lukas Perkhofer, Natalie Eitel, Andreas W. Berger, Melanie Guethle, Thomas Seufferlein
Journal: Journal of Clinical Oncology (2016)

e15713 Background: 80% of patients with pancreatic ductal adenocarcinoma (PDAC) relapse within 5 years after surgery. Surveillance may be helpful for early detection of relapse. However, there are no evidence-based or consensus-based guidelines for surveillance strategies. In the absence of guidelines and given that there is a plethora of means of surveillance after surgery for PDAC we aimed at establishing the most frequently used means in Germany and to assess, how these means are judged in terms of effectiveness. In particular we were interested whether high-level surveillance including frequent imaging is superior to anamnesis and physical examination. Methods: Questionnaire-based online survey among various German institutions experienced in the surveillance of patients after PDAC surgery. The questionnaire included 25 items regarding the institutions, their surveillance algorithms including the most frequently used means for surveillance after PDAC surgery and their evaluation regarding the effectiveness of these measures. Results: In total 161 institutions replied. 29% of the institutions were certified PDAC centers of the German Cancer Society, 25% were University Hospitals and 10% private practices. 96% of all institutions performed a surveillance and nearly half of them for 5 years. In 82,4% of all institutions surveillance procedures exceed only laboratory testing during adjuvant chemotherapy. These measures includes imaging (CT, MRI) in 63,7% of patients at 3 months. After termination of adjuvant chemotherapy 76,5% of institutions performed CT/MRI scan, 72,3% used abdominal ultrasound and 92,9% employed CA19-9. For relapse diagnosis imaging techniques and CA19.9 levels were the most common. However, anamnesis was useful for detection of relapse in a high number of patients (60-80%) too. Conclusions: Here we present an overview of the broad spectrum of surveillance strategies used in Germany. Adjuvant therapy and surveillance strategies are commonly used after R0/R1 resection in PDAC patients. In conclusion there is no standardized surveillance strategy throughout Germany, but standard procedures like regular anamnesis seem to be of value to detect a relapse.
Subsite study of salivary gland malignancies treated with neutron radiotherapy provides better information for patient selection.
Authors: Dorothy Chilambe Lombe
Journal: Journal of Clinical Oncology (2016)

e17566 Background: Parotid gland malignancies are very rare and constitute less than 1% of all cancers. Fast neutrons are effective in controlling locally advanced salivary gland malignancies, though their use has often been associated with high expense of facilities and high toxicity rates. Most investigators have studied salivary gland malignancies as a cluster despite their variable location in the head and neck region due to the paucity of patients. For radiotherapy this can be undesirable as the organs at risk may vary per sub-site. The outcomes of treatment of salivary gland malignancies of the sub-site parotid with neutron radiotherapy were then studied in an attempt to refine patient selection for this modality. Methods: Records of patients with unresectable parotid gland malignancies treated with neutron radiotherapy at Tygerberg Hospital/iThemba Laboratory for Accelerator Based Sciences (LABS) in Cape Town between January 1991 and December 2012 were reviewed. Twenty-two patients were eligible for statistical analysis. All patients but 1 received 20.4 Gy for 4 – 5 weeks. Treatment planning was 3D conformal. Results: Median time to local control was 4 months. Locoregional control at 2 years was 80% (CI 41-95) and at 5-, 10- and 15- years was 69%(CI 30 -89). Overall survival at 2 years was 40% (CI 18 – 61) and at 5-, 10- and 15- years was 35% (CI 14 – 56). Unresectable disease had a significant negative influence on survival compared to macroscopic residual p = 0.02, HR 6.7 (CI 1.23 – 36.30) where as inoperable disease did not p = 0.81, HR 1.2 (CI 0.18 - 9.1) . The severe toxicity rate (CTCAE grade 3 and above) was 9%. Conclusions: Subsite study does reveal different outcomes when compared to global studies. The locoregional control outcomes of treatment of sub-site parotid trend are better but overall survival is poorer. The toxicity rate appears to be lower for this sub-site study than for global studies. Neutron radiotherapy for sub-site parotid is both efficacious and safe.
Identification of druggable targets in high-grade epithelial ovarian cancer (EOC) using next generation sequencing (NGS)–based molecular diagnostic.
Authors: Jean-Louis Merlin, Shuhui Chen, Julia Salleron, Elisa Cavazza, Catherine Barlier, Celine Gavoille, Pierre Filhine-Tresarrieu, Alexandre Harle
Journal: Journal of Clinical Oncology (2016)

e17076 Background: Despite the great histological and molecular heterogeneity, the clinical management of EOC remains univocal. Additionally to conventional histological prognostic markers and oncogenetic investigations, molecular diagnostic was performed using NGS to identify
Identification of biomarkers to predict response to single-agent platinum chemotherapy in metastatic triple-negative breast cancer (mTNBC): Correlative studies from TBCRC009.
Authors: Steven J. Isakoff, Lei He, Erica L. Mayer, Paul E. Goss, Tiffany A. Traina, Lisa A. Carey, Karen Krag, Minetta C. Liu, Hope S. Rugo, Vered Stearns, Steven E. Come, Paula D. Ryan, Dianne M. Finkelstein, Anne-Renee Hartman, Judy Ellen Garber, Kirsten Timms, Eric P. Winer, Leif W. Ellisen
Journal: Journal of Clinical Oncology (2014)

1020 Background: TNBC has a poor prognosis compared to other BC subtypes and lacks therapeutic targets. We previously reported TBCRC009, a multicenter single-arm phase II study of single-agent platinum in 86 patients (pts) with mTNBC: the objective response rate (ORR) was 25.6% overall and 54.5% vs. 19.7% (p=0.02) in BRCA1/2 carriers (n=11) vs. non-carriers (n=66). Six long-term responders remain disease free at median follow up of ~4 yrs. Here we explored biomarkers of response to platinum in TBCRC009. Methods: Participants had measurable disease, available archival tumor, ≤1 prior metastatic therapy, and no prior platinum chemotherapy. By physician choice, pts received cisplatin 75mg/m2or carboplatin AUC=6 every 21 days. Co-primary endpoints were: 1) ORR and 2) p63/p73 expression by RT-PCR as a predictor of response. Tumor-based exploratory studies included: gene expression (GE) profiling, PIK3CA and p53 mutational status, and homologous recombination deficiency (HRD) assays correlating with BRCA1/2 inactivation. Results: Among 61 pts evaluable for co-primary endpoint 2, 28 (46%) had the pre-specified p63/p73 ratio ≥2, which did not predict response to platinum (ORR 18% vs. 27% in p63/p73 ≥2 vs. <2, respectively, p=0.54). 36/54 pts (67%) had p53 mutations, and 9/55 pts (16%) had PIK3CA mutations, but neither correlated with ORR. PAM50 analysis from global GE profiling identified 60% (32/53) basal-like tumors, which showed a higher ORR that did not reach significance (28% vs. 10% in basal vs non-basal, p=0.17). All HRD assays, including Loss Of Heterozygosity (LOH), Telomere Allelic Imbalance (TAI), and Large-scale State Transition (LST), scored higher in BRCA1/2 carriers than non-carriers, and in responders than non-responders among the small group of 22 non-carriers with available tissue (HRD-LST responders vs. nonresponders, p=0.0016). Conclusions: Single-agent platinum is effective in both BRCA1/2-associated and sporadic mTNBC. Although established biomarkers failed to predict responses, HRD assays may identify sporadic TNBC tumors that are BRCA1/2-like and responsive to platinum chemotherapy. Clinical trial information: NCT00483223.
Effect of VERU-111, a novel oral inhibitor of α and β tubulin, on tumor growth in the human castration-resistant prostate cancer model 22Rv1.
Authors: Mark Christopher Markowski, Robert H. Getzenberg, Mitchell S. Steiner, Nilofer Saba Azad, Stephanie Gaillard, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2018)

e17003 Background: VERU-111 is a novel, oral α and β tubulin inhibitor that blocks tubulin polymerization and is not a substrate for multi-drug resistance mechanisms. In xenograft models of taxane responsive and resistant cancers, VERU-111 results in almost complete tumor inhibition at ≤20 mg/kg orally dosed infrequently as 1/week. VERU-111 and docetaxel were tested in the human PCa model, 22Rv1 which expresses androgen receptor splice variants, including AR-V7, and is resistant to abiraterone and enzalutamide. Methods: Human 22Rv1 cells were grown and implanted into SCID mice. When tumors reached 150-200 mm3, the animals were randomized into 4 groups (n = 10 per group): PO vehicle; PO VERU-111 -5 or 20 mg/kg; or IP docetaxel 10 mg/kg 3X per week. Animal weights and tumor volumes were measured 2X week and tumor weights determined at study end. Animals were removed from study when the tumor volume exceeded 2000 mm3 or upon treatment for 28 days. Results: VERU-111 (PO 5 and 20 mg/kg) significantly reduced tumors by 31% (p = 0.049) and 49% (p = 0.010), respectively, compared to vehicle. Administration of 10 mg/kg docetaxel IP resulted in a nonsignificant 25% reduction in tumor size (p = 0.10). With respect to relative toxicity, mice treated with oral VERU-111 either significantly gained (5 mg/kg) or maintained their weight (20 mg/kg) whereas the animals treated with docetaxel lost weight (p = 0.013). There was a significant difference in weight between all animals treated with VERU-111 and the docetaxel-treated animals (p = 0.014). Conclusions: VERU-111 is an orally administered inhibitor of α and β tubulin with significant preclinical activity against PCa and other tumors. In the human PCa model 22Rv1, VERU-111 was associated with a statistically significant reduction in tumor volumes and was well tolerated. In comparison, IP docetaxel did not significantly reduce tumor volumes and resulted in notable toxicity. A phase 1/2 trial to test VERU-111 in PCa and other taxane sensitive neoplasms is soon to be initiated. Treatment Group Median (mg) P-value Placebo 1085.15 VERU-111 5 mg/kg (PO) 753.8 0.049 VERU-111 20 mg/kg (PO) 556.5 0.010 Docetaxel 10 mg/kg (IP) 811.5 0.099