tbuckley/cabot-search huggingface dataset:
Safety and efficacy outcomes for patients ages 65 and older treated with dose-dense chemotherapy for epithelial ovarian cancer.
Authors: Eleonora Teplinsky, Haven Lindsay Caldwell, Nina Kohn, Kit Cheng, Mark Allan Hoffman, Lisa A. Dos Santos, Antoinette Sakaris, Karin Shih, John L. Lovecchio, Jill Suzanne Whyte, Andrew Menzin, Veena S. John
Journal: Journal of Clinical Oncology (2017)

e17058 Background: Dose-dense chemotherapy is increasingly more utilized in the adjuvant treatment of patients (pts) with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC), as compared to the conventional q3 week chemotherapy regimen. The safety and tolerability of the dose-dense regimen in pts ≥65 yrs old has not been well studied. We performed a retrospective analysis of pts with stage II-IV EOC treated at our institution with either regimen. Methods: We identified pts with stage II-IV EOC treated at Northwell Health from 2010-2015 who received adjuvant chemotherapy with the dose-dense (carboplatin q3 weeks/weekly paclitaxel) or the conventional (carboplatin and paclitaxel q3 weeks) regimen. Pts who received IP chemotherapy were excluded. Demographics, adverse events (AEs), dose delays/reductions and efficacy outcomes were evaluated. Results: 38 pts received conventional chemotherapy (median age 68 yrs) and 29 pts received dose-dense chemotherapy (median age 61 yrs). There were no differences in the frequency of grade ≥3 hematologic toxicities b/w the two arms. There were no differences in delayed or missed doses between the two arms but a higher proportion of dose reductions in the dose-dense arm ( P= 0.0472). Among pts treated in the dose-dense arm, 87.5% of women &lt; 65 yrs old had at least one grade ≥3 AE when compared to 38.5% of women ≥ 65 yrs old ( P= 0.0161). There were no differences in dose delays, dose reductions, or missed doses when compared by age in the dose-dense arm. In the dose-dense arm, stage III-IV pts &lt; 65 yrs old had a median time to progression (TTP) of 13.0 mo (95% CI, 6.7-13.8) and a median overall survival (OS) of 48.3 months (95% CI, 11.5-48.3). Pts ≥ 65 yrs old had a median TTP of 10.9 mo (95% CI, 8.7-12.7) and median OS of 35.9 mo (95% CI, 30.8-not reached). There was no difference in TTP ( P= 0.2154) or OS ( P= 0.9260) between the two cohorts. Conclusions: Our institutional experience of administering dose-dense adjuvant chemotherapy to women with EOC suggests that this regimen is likely safe in women ≥ 65 yrs old, with similar efficacy outcomes and should be considered for this population. Further study with larger sample sizes and in prospective trials is warranted.
Use of FDA-approved vs. lab-developed tests in advanced non-small cell lung cancer.
Authors: Celine Audibert, Michael Shea, Daniel Glass, Marina Kozak, Alexis Caze, Ryan Hohman, Jeff Allen, Ellen V. Sigal, Jonathan Leff
Journal: Journal of Clinical Oncology (2016)

e20532 Background: Molecular testing is central to the management of many cancers. We measured the extent to which FDA-approved and lab-developed tests (LDTs) are used in stage IV adenocarcinoma non-small cell lung cancer (NSCLC) patients, with a focus on EGFR mutations and ALKrearrangements. Methods: A retrospective chart review of NSCLC patients was conducted between April and September of 2015. A representative sample of US oncologists was asked to complete an online form containing fields for anonymized patient information, including year of diagnosis, whether molecular testing was performed, and if so, which markers were tested, type of test used, and test location. 8,129 NSCLC-treating oncologists in the US were invited to participate in the study. Oncologists were eligible to participate if they personally managed at least 5 NSCLC patients per month, and diagnosed at least one NSCLC patients in the past 12 months Results: Information on 765 patient records was obtained from the 153 physicians who met eligibility criteria. Histological subtype split was as follows: 76% of patients had adenocarcinoma, 19% had squamous cell carcinoma and 5% had other types. Among the 579 patients with adenocarcinoma, 95% and 84% were tested for EGFR mutations and ALK-rearrangements, respectively. Sample was further reduced to only include patients for which the type of test was known, and whose diagnostic was performed after FDA approval of the relevant test (May 14, 2013 for EGFR and August 26, 2011 for ALK), resulting in 424 patients for EGFR, and 399 for ALK. 87% of adenocarcinoma patients were tested with non-FDA-approved tests for EGFR, and 49% for ALK. Conclusions: This study highlights the prevalence of non-FDA-approved testing in the treatment of lung cancer. Further evaluation of the comparability of approved and unapproved tests currently being used interchangeably is needed to mitigate uncharacterized variability between tests. Type of test performed. FDA-Approved LDT EGFR 55 (13%) 369 (87%) ALK 204 (51%) 195 (49%)
Relationship between diagnostic interval and pancreatic ductal adenocarcinoma (PDAC) resectability: A single-center retrospective analysis.
Authors: Amar Deshwar, Deirdre Torto, Elizabeth Sugar, Daniel A. Laheru, Mark Yarchoan
Journal: Journal of Clinical Oncology (2017)

e15738 Background: PDAC often presents with nonspecific symptoms and the workup for suspected PDAC is not standardized. While surgery remains the only curative therapy, only 20% of PDAC is resectable due to local extension or metastasis. We examined the relationship between diagnostic interval of PDAC and surgical resectability. Methods: We performed a retrospective chart review of patients evaluated for PDAC at the Center for Pancreas Cancer at Johns Hopkins in 2014. Data were collected on the patient, diagnostic, and treatment time intervals (defined as days between first symptoms to medical presentation, presentation to diagnosis, and diagnosis to treatment), diagnostic tests performed, and the type of initial treatment. Asymptomatic patients diagnosed incidentally, or those for whom initial medical presentation was unclear, were excluded from our analysis. Results: Of 453 charts reviewed, 116 patients met our inclusion criteria. The median patient interval was 14 days (IQR 6-30), the median diagnostic interval was 22 days (IQR 8-46), and the median treatment interval was 26 days (IQR 15-35). The median number of diagnostic tests performed was 8 (IQR 6-11). At the time of diagnosis, 7 patients (6%) had stage 1, 53 (46%) had stage 2, 24 (21%) had stage 3, and 32 (28%) had stage 4 disease. A total of 38 patients (33%) received upfront surgery for treatment of PDAC and 78 (67%) received nonsurgical treatment. Non-white individuals had lower odds of receiving surgery (Adjusted Odds Ratio [aOR]: 0.09, 95% Confidence Interval [CI]: 0.01, 0.74, p = 0.024). After adjusting for age, sex, race and diagnostic clinic, the odds of receiving surgery significantly increased for individuals with a patient interval of 1 month or less (aOR: 3.47, 95% CI: 1.003, 12.0, p = 0.010) and with a diagnostic interval of 2 months or less (aOR: 15.3, 95% CI: 1.90, 122, p = 0.019). Conclusions: A patient interval of less than 1 month and a diagnostic interval less than 2 months for symptomatic PDAC were associated with an increased probability of upfront surgical treatment. These data indicate that extended intervals prior to PDAC diagnosis may reduce the odds of obtaining a potentially curative treatment.
Abstract P320: Dairy Consumption and Risk of Stroke: A Systematic Review and Dose-response Meta-analysis of Prospective Cohort Studies
Authors: Janette de Goede, Johanna M. Geleijnse, An Pan, Lieke Gijsbers, Sabita Soedamah-Muthu
Journal: Circulation (2016)

Introduction: A higher milk consumption may be associated with a lower stroke risk. We conducted a comprehensive systematic review and dose-response meta-analysis of milk and other dairy products with stroke risk. Hypothesis: We assessed the hypothesis that milk and possibly other types of dairy consumption were inversely associated with stroke risk. Methods: Through a systematic literature search prospective cohort studies of dairy foods and incident stroke in stroke-free adults were identified. Random-effects meta-analyses with summarized dose-response data were performed taking into account sources of heterogeneity and spline models were used to systematically investigate nonlinearity of the associations. Results: We included 17 studies with 10-26 years of follow-up that included 675,389 individuals and 28,912 stroke events. An increment of 200 gram of daily milk intake was associated with a 7% lower risk of stroke (RR 0.93; 95% CI 0.88-0.97; P=0.003; I2=85%). RRs were 0.82 (95% CI 0.75-0.90) in East Asian and 0.98 (95% CI 0.96-1.01) in Western countries (median intakes 38 and 266 g/d respectively) with moderate heterogeneity within the continents. Cheese intake was marginally inversely associated with stroke risk (RR 0.97; 95% CI 0.94-1.01 per 40 g/d). Risk reductions were maximal around 125 g/d for milk and from 25 g/d onwards for cheese. Based on a limited number of studies, low-fat milk was inversely and high-fat milk directly associated with stroke risk. No associations were found for yogurt, butter or total dairy. Conclusions: Milk and cheese consumption were inversely associated with stroke risk. Future epidemiological studies should provide more details about dairy types, including fat content. In addition, the role of dairy in Asian populations deserves further attention.
Apatinib in combination with hypofractionation radiotherapy in bone metastatic prostate cancer: Results from a pilot, multicenter study.
Authors: Ming Zeng, Feng Zhao, Wei Tian
Journal: Journal of Clinical Oncology (2017)

e16523 Background: To study safety and efficacy of apatinib, a vascular endothelial growth factor receptor-2 (VEGF2) inhibitor, in combination with radiotherapy in patients with bone metastatic prostate cancer (BMPC), based on potential synergistic antitumor activities of apatinib and Radiation Therapy (RT). Methods: In a dose escalation study, 18 patients (6/cohort) received apatinib at 250 mg every other day, 250 mg or 500 mg daily. The 250 mg daily cohort was expanded to 19 patients in combination with RT (6 Gy/fraction, 5 fraction in total), comparing with the RT alone cohort with 10 patients. Evaluations included adverse events (AEs), prostate specific antigen (PSA) levels, radiographic evaluation and pain relief. Results: In the dose escalation patients, common apatinib-related AEs (arAEs) were fatigue (11, 61%), anorexia 10, 55%), hand foot syndrome (9, 50%), proteinuria (8, 44%), and HTN (8, 44%). Grade 3 arAEs included HTN, proteinuria, and liver dysfunction. No treatment-related death occurred. In the apatinib plus RT cohort, AEs were increased comparing to either apatinib alone or RT alone; The combination cohort showed improvement in pain control. Conclusions: In BMPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity, consistent with previous reports in patients with other tumors. Apatinib at dose of 250mg daily combining with RT improved pain control while the overall AEs were manageable. Further studies are needed in large sample size trials. Clinical trial information: NCT02998242.
IGFBP-7 to confer resistance to the epidermal growth factor receptor tyrosine kinase inhibitor.
Authors: Shang-Gin Wu, Tzu-Hua Chang, Yih-Leong Chang, Meng-Feng Tsai, Chong-Jen Yu, Jin-Yuan Shih
Journal: Journal of Clinical Oncology (2017)

e20572 Background: Lung cancer is a leading cause of cancer death worldwide. The EGFR mutation-positive patients of lung adenocarcinoma had dramatic response to EGFR tyrosine kinase inhibitors (TKIs). However, acquired drug resistance developed invariably after one year treatment course of EGFR TKI. IGFBP-7, a secreted 31 kDa protein, exhibits low affinity for IGF but binds strongly to insulin. No previous studies had been mentioned the correlation between the protein and acquired EGFR TKI resistance. Methods: cDNA microarray was used to screen differentially expressed genes between EGFR TKI-sensitive (PC9 and HCC827) and acquired EGFR TKIs-resistance cell lines (PC9/gef and HCC827/gef). The expression levels of the screened genes were validated by RT -PCR and Western blot analysis. Molecular manipulations (silencing or overexpression) were performed to investigate the effects of IGFBP-7 on gefitinib resistance in vitro. In addition, clinical specimens were collected to validate the imact of IGFBP-7 on the efficacy of EGFR TKI treatment . Results: IGFBP-7 is over-expressed in gefitinib-resistant cells. The IGFBP-7 mRNA expression in the malignant pleural effusion of patients with acquired resistance to EGFR TKI was significant higher than that in the treatment-naïve patients. Knockdown IGFBP-7 reverses gefitinib resistance in PC9/gef cells. Knockdown IGFBP-7 could increase gefetinib induced-apoptosis through the regulation of BIM. IGFBP-7 affected the mechanism of EGFR TKI resistance resulted from inhibition of IGF-IR.. In clinical practice, low IGFBP-7 serum level is associated with longer progression free survival (PFS) of EGFR TKI as the first line treatment. Furthermore, lower IGFBP-7 level of resected tumor predicts a longer 5-year tumor relapse-free survival. Positive IGFBP-7 immunoihistochemical stain could predict a shorter PFS of the first-line EGFR TKI treatment. Conclusions: IGFBP-7 confers resistance to the EGFR TKI and may be a target for future treatment investigation.
Mass spectrometry-based identification of VHL-regulated N-glycosylated membrane proteins in renal cell carcinoma
Authors: Gunther Boysen, Bernd Wollscheid, Damaris Bausch-Fluck, Kirsten Struckmann, Peter Schraml, Wilhelm Krek, Holger Moch
Journal: Cancer Research (2007)

2250   Loss of von Hippel-Lindau (VHL) tumor suppressor gene function in clear-cell RCC (ccRCC), the most common subtype of RCC, activates tumor progressing pathways that are not yet completely understood. Proteins of the cell membrane are mainly responsible for invasive and metastatic processes thus representing potential molecular anti- cancer drug targets. The aim of this study is to identify such cellular membrane proteins that are highly expressed in VHL negative RCC.  Glycosylated cell membrane proteins labelled with biotin hydrazid and enriched using streptavidin- coated sepharose were isolated from VHL null 786-O or 786-O transfectants expressing isoforms VHL19 and VHL30. LC-MS/MS was used to identify and compare isolated proteins qualitatively and quantitatively.  Labeling and enrichment of glycosylated cell membrane proteins was highly specific. Classification of identified proteins revealed different functions, e.g. nutrient transport, cell adhesion, cell growth, and signaling. Normal kidney proteins, e.g. kidney cadherin as well as RCC-specific proteins, e.g. NY-REN 47 were also identified.  Using a proteomic- based approach, we identified glycosylated membrane proteins that may represent potential biomarkers for RCC. The biological and clinical significance of these proteins in ccRCC are further investigated.
Phase 1b/2 study of olaratumab plus gemcitabine and docetaxel for the treatment of advanced soft tissue sarcoma (STS) (ANNOUNCE 2): Phase 1b results.
Authors: Victor Manuel Villalobos, Andres Redondo, Brian Andrew Van Tine, Gary K. Schwartz, Mark Andrew Dickson, Bartosz Chmielowski, Patrick Peterson, Damien Cronier, Jennifer A. Wright, Steven Attia
Journal: Journal of Clinical Oncology (2018)

11542 Background: Olaratumab (O) is an antibody against platelet-derived growth factor receptor alpha. In a randomized phase 2 study, O in combination with doxorubicin (dox) demonstrated a significant improvement of overall survival (OS) over dox alone in patients (pts) with advanced STS. Here we report the safety, tolerability and recommended phase 2 dose (RPTD) of O plus gemcitabine (G) and docetaxel (D) (O + G/D). Methods: This dose-escalation study enrolled pts with advanced/metastatic STS, ≤2 prior lines of systemic therapy, no prior G, D or O, and ECOG PS 0-1. Pts received O on Days 1 and 8 at 15 mg/kg (cohort 1) or 20 mg/kg (cohort 2) with G (900 mg/m2 Days 1 and 8) and D (75 mg/m2 Day 8) on a 21-day cycle. The primary objective was to determine the RPTD of O + G/D, with a dose-limiting toxicity (DLT) occurring in Cycle 1 at a rate below 33%. Secondary objectives included safety and pharmacokinetics (PK). Results: 54 pts (cohort 1/2 = 21/33) received at least one dose of treatment. No DLT occurred in cohort 1. In cohort 2, 5 pts (15.2%) experienced 6 DLTs (ALT increase, bacteremia, neutropenia [2 pts], and thrombocytopenia [2pts]). Treatment-related adverse events (TRAEs) reported for cohorts 1 and 2 included all grades (90.5% and 93.9%), Gr 3 (14.3% and 42.4%), Gr 4 (0 and 18.2%), and serious AEs (9.5% and 15.2%), respectively. Common TRAEs (all grades, Gr ≥3) occurring in ≥ 25% of pts were fatigue (66.7%, 11.1%), anemia (61.1%, 18.5%), thrombocytopenia (35.2%, 18.5%), nausea (29.6%, 0%) and diarrhea (27.8%, 3.7%). 1 pt discontinued due to a study-related AE of fatigue (cohort 1). Following 2 deaths unrelated to study treatment, cohort 2 was expanded to 33 pts. The PK profile of O + G/D was similar to that of O in combination with other chemotherapies. Conclusions: Both dose levels were tolerated with a higher incidence for known toxicities of G/D in cohort 2. Based on safety and exposure-response analyses across O studies, the RPTD for O + G/D is 20 mg/kg at Days 1 and 8 in Cycle 1, followed by 15 mg/kg at Days 1 and 8 thereafter. The randomized, double-blinded phase 2 part of the study is enrolling and will compare OS of pts with STS receiving G/D + O vs G/D + placebo (ANNOUNCE 2). Clinical trial information: NCT02659020.
An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 study of palbociclib (an oral CDK4/6 inhibitor) plus cetuximab in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).
Authors: Bhumsuk Keam, Makoto Tahara, Jin-Ching Lin, Assuntina Gesualda Sacco, Bohuslav Melichar, Tara Baney, Justin Hoffman, Diane Dan Wang, Shaw Ling Wang, Jean-Francois Martini, Holger C. Thurm, Douglas Adkins
Journal: Journal of Clinical Oncology (2016)

TPS6102 Background: SCCHN is the sixth most common cancer worldwide. Current second-line treatments for human papillomavirus (HPV)–negative, R/M SCCHN have marginal effectiveness and significant toxicity. Therefore, improved treatment options are needed. Inhibition of the cyclin D1/cyclin-dependent kinase (CDK)4/Rb axis using the selective CDK4/6 inhibitor palbociclib (PAL) represents a rational treatment approach for patients (pts) with incurable, cetuximab-naive, HPV-negative SCCHN because loss of RB1 is infrequent but loss of CDKN2A expression or amplification of CCND1 occurs in most cases; the majority of a large cell line panel responded at low nanomolar concentrations of PAL; and PAL exhibited significant single-agent activity in a series of HNSCC patient-derived xenograft (PDX) models. A combinatorial approach with the epidermal growth factor receptor (EGFR) inhibitor cetuximab may further enhance antitumor effects because EGFR overexpression is considered an important driver in SCCHN pathogenesis; EGFR inhibition demonstrated strong synergy in combination with PAL in vitro; and PAL plus cetuximab showed significant antitumor activity in an HNSCC PDX model. A phase 1 trial established the safety of combining PAL with cetuximab in pts with incurable SCCHN, with a decrease in tumor target lesions observed in approximately 50% of pts (Michel, ASCO 2015, Abs: 6043). Methods: Patients with HPV-negative, cetuximab-naive R/M SCCHN after failure of 1 platinum-containing regimen will be randomized 1:1 to receive either 125 mg PAL orally daily for 21 days followed by a 7-day break in combination with weekly cetuximab (initial dose, 400 mg/m2 followed by 250 mg/m2) or placebo plus the same regimen of cetuximab. The primary objective is to compare overall survival for both treatment arms. Secondary and exploratory objectives include evaluation of progression-free survival, PK/PD relationships, patient-reported outcome measures, and biomarker analyses. Clinical trial information: NCT02499120.
Abstract 20530: Do Screening Electrocardiograms in a Tertiary Bariatric Program Alter Patient Management? A Retrospective Cohort Study
Authors: Daniel Goubran, Tyler James, Aun Yeong Chong, Benjamin Hibbert, Robert Dent, Judy Shiau, Derek Y So
Journal: Circulation (2016)

Background: In tertiary bariatric programs, screening ECGs are routinely conducted. Objectives: To document common ECG changes in this population and evaluate whether screening ECGs delay or alter ...
A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of TAB008 and bevacizumab in healthy volunteers.
Authors: Jacqueline M Liu, Xinghe Wang, Jin Wang, Lu Qi, Zejuan Wang, Xisheng Liu
Journal: Journal of Clinical Oncology (2018)

e14504 Background: This study compared the pharmacokinetic (PK) profiles of the biosimilar TAB008 with bevacizumab (EU) in healthy adult males. Methods: A randomized, double-blind, single-dose study in which healthy male subjects aged 18 to 45years, and body mass index 19-28kg/m2, were randomized to receive 1 mg/kg of TAB008 (n = 49) or bevacizumab (EU) (n = 50) over a 90 minute infusion. The subjects were followed for 99days after drug administration. Primary endpoints were area under the serum concentration–time curve from time 0 to time of last quantifiable concentration (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-inf), and the maximum observed serum concentration (Cmax). Secondary endpoints included safety and immunogenicity. Results: The 2 groups of test subjects were well matched with regards to all demographic and baseline characteristics. The treatment-group ratios of LS geometric means for the 3 primary PK parameters were fully contained within the bioequivalence limits of 80.00% to 125.00% (90% CI: 103.66% to 118.33% for Cmax, 94.32% to 111.72% for AUC0-t, and 94.69% to 112.23% for AUC0-∞). Treatment-emergent adverse events (TEAEs) were reported in 25 (51.0%) subjects in the TAB008 group and 22 (44%) subjects in the Bevacizumab (EU) group; drug related TEAEs were reported in 19 (38%) subjects in both groups. NCI-CTCAE Grade 3 TEAEs were reported in 1 (2.0%) subject in the TAB008 group, and 3 (6.0%) subjects in the BevACIZUMAB(EU) group; there were no Grade 4 or 5 TEAEs. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies were detected in the TAB008 group, one subject in the bevacizumab (EU) group developed anti-drug antibody. Conclusions: This study demonstrated the PK similarity of TAB008 to bevacizumab (EU). Safety and tolerability were comparable between treatments, and no subject developed binding or neutralizing anti-drug antibodies to TAB008. Clinical trial information: CTR20160522.