tbuckley/cabot-search huggingface dataset:
Patients with advanced NSCLC presenting to medical oncologists through the inpatient vs. outpatient departments.
Authors: Joanna Gotfrit, Glenwood D. Goss, Scott Andrew Laurie, Garth Andrew Nicholas, Tinghua Zhang, Paul Wheatley-Price
Journal: Journal of Clinical Oncology (2016)

e20518 Background: Most newly diagnosed advanced NSCLC patients have an initial medical oncology consult as an outpatient. Sometimes, the initial referral occurs as an inpatient. We explored differences among NSCLC patients presenting to medical oncology while hospitalized versus as outpatients. Methods: With ethics approval, we performed a retrospective analysis of all stage IIIB and IV NSCLC patients at our institution whose initial medical oncology consult was from 2009 to 2012. Demographics, treatment and survival data were collected. Results: In total, 637 patients were included: 514 outpatients and 123 inpatients. Baseline demographics are shown in the Table. Among outpatients, 55% received systemic therapy compared to only 21% of inpatients. Among these treated patients, inpatients were more likely to be younger (81% vs. 70% <70 years, p=0.04), have PS 3-4 (38% vs. 5%, p<0.001), have ≥5% weight loss (54% vs. 42%, p=0.01), anemia (19% vs. 4%, p=0.001), leukocytosis (38% vs. 32%, p=0.001), thrombocytosis (27 vs. 23%, p=0.001), renal dysfunction (12% vs. 5%, p=0.01) and more rapid onset of symptoms (27% vs. 6% for <2 weeks, 35% vs. 11% for 2-6 weeks; p<0.001). Of note, inpatients who received systemic therapy were more likely to have a complete or partial response (42% vs. 26%, p=0.007), however had a shorter median OS than treated outpatients (8.4 vs. 10.5 months, p=0.003). Conclusions: Patients presenting to medical oncologists through the inpatient department were more unwell with more clinically aggressive disease. Unsurprisingly, fewer received systemic therapy, but among those who did, they were more likely to respond and their OS began to approach that of the outpatient cohort. Systemic therapy should therefore be a consideration in selected hospitalized patients with advanced NSCLC. Demographic Overall (n=637) Outpatients (n=514) Inpatients (n=123) P value Median age (range) 67 (23-90) 68 (35-90) 65 (23-85) 0.75 Female (%) 47 56 44 0.017 PS 3-4 (%) 31 22 74 <0.001 Weight loss ≥5% (%) 50 49 56 <0.001 Anemia (%) 9 5 23 <0.001 Leukocytosis (%) 40 35 61 <0.001 Thrombocytosis (%) 26 25 39 0.20 Renal dysfunction (%) 9 7 14 0.019 Nonsquamous histology (%) 77 78 76 0.63
Ginsenoside Rg3 to regulate the EMT induced by TGF-in gastric cancer.
Authors: Lianjun Zhao, Qing Lv, Qiuping Xv, Jie Shao, Shu Su, Fanyan Meng, Jia Wei, Baorui Liu, Xiaoping Qian, Lixia Yu, Zhengyun Zou
Journal: Journal of Clinical Oncology (2017)

e23200 Background: To discuss the regulate effect of Ginsenoside Rg3 during the TGF-β1 induced EMT in human gastric cancer SNU-601 cell line. Methods: In the first part of our experiment, ninety-nine patients who were diagnosed as gastric cancer were admitted to this study eventually. The Luminex® xMAP technology was used to measure the plasma levels of TGF-β1. In the second part, human gastric cancer SNU-601 cell line were cultured normally. Inverted microscope was used to observe morphological changes. The cell relative growth rate of proliferation was analyzed by MTT assay. Wound-healing assay and transwell invasion assay were carried out to predict the capacity of Ginsenoside Rg3 in inhibiting migration and invasion. Western Blot was performed to analyze the influence of Ginsenoside Rg3 and TGF-β1 on the protein expression of E-cadherin and Vimentin. Results: The plasma cytokine levels of TGF-β1 were associated with vessel invasion, peritoneal involvement, TNM stage, T stage, N stage in gastric cancer patients. In Vitro Study, TGF-β1 stimulated epithelial-mesenchymal transition in SNU-601 cell lines. Ginsenoside Rg3 inhibited the TGF-β1 induced morphological changes, cell proliferation increase, cell migration and cell invasion. Ginsenoside Rg3 markedly increased expression of the epithelial marker E-cadherin, and repressed the upregulation and expression of the mesenchymal marker Vimentin during the TGF-β1 induced EMT in SNU-601 cell line. Conclusions: The plasma cytokine levels of TGF-β1 were associated with vessel invasion, peritoneal involvement, tumor stage in gastric cancer patients. TGF-β1 stimulated biological malignant behavior through EMT in gastric cancer. Ginsenoside Rg3 could inhibit the EMT induced by TGF-β1 in SNU-601 cell lines.
P01.025 MiRNA-181d expression significantly affects treatment responses to carmustinewafer implantation
Authors: C Sippl, R Ketter, L Bohr, J Oertel, S Urbschat
Journal: Neuro-Oncology (2018)

Standard therapeutic protocols for glioblastoma, the most aggressive type of brain cancer, include surgery followed by chemoradiotherapy. Additionally, carmustine-eluting wafers can be implanted locally into the resection cavity. Objective: This study evaluated micro RNA (miRNA)-181d as a prognostic marker of responses to carmustine wafer implantation. Eighty glioblastoma patients (40/group) were included in a matched pair analysis. One group (carmustine wafer group) received concomitant chemoradiotherapy with carmustine wafer implantation (Stupp protocol). The second group (control group) received only concomitant chemoradiotherapy. All tumor specimens were subjected to evaluations of miRNA-181d expression, results were correlated with further individual clinical data. A TCGA dataset of 149 patients was used as an independent cohort to validate the results. Results: Patients in the carmustine wafer group with low miRNA-181d expression had significantly longer overall (hazard ratio [HR], 35.03, [95% CI: 3.50–350.23], p =0.002) and progression-free survival (HR, 20.23, [95% confidence interval (CI): 2.19–186.86], p = 0.008) than patients of the same group with a high miRNA-181d expression. These correlations were not observed in the control group. The non-significance in the control group was confirmed in the independent TCGA dataset. The carmustine wafer group patients with low miRNA-181d expression also had a significantly longer progression-free (p = 0.049) and overall survival (p = 0.034), compared with control group patients. Gross total resection correlated significantly with longer overall survival (p = 0.023). MiRNA-181d expression significantly affects treatment responses to carmustine wafer implantation.
Cancer expression quantitative trait loci (eQTLs) can be determined from heterogeneous tumor gene expression data by modeling variation in tumor purity
Authors: Paul Geeleher, Aritro Nath, Fan Wang, Zhenyu Zhang, Alvaro N. Barbeira, Jessica Fessler, Robert L. Grossman, Cathal Seoighe, R. Stephanie Huang
Journal: Genome biology (2018)

Expression quantitative trait loci (eQTLs) identified using tumor gene expression data could affect gene expression in cancer cells, tumor-associated normal cells, or both. Here, we have demonstrated a method to identify eQTLs affecting expression in cancer cells by modeling the statistical interaction between genotype and tumor purity. Only one third of breast cancer risk variants, identified as eQTLs from a conventional analysis, could be confidently attributed to cancer cells. The remaining variants could affect cells of the tumor microenvironment, such as immune cells and fibroblasts. Deconvolution of tumor eQTLs will help determine how inherited polymorphisms influence cancer risk, development, and treatment response.
Abstract 14136: Effectiveness of Adaptive Servo-Ventillation for the Prevention of Atrial fibrillation Recurrence after Radiofrequency Catheter Ablation
Authors: Keijiro Nakamura, Koji Kumagai, Takehito Sasaki, Naofumi Tsukada, Yohsuke Nakatani, Mamoru Hayano, Suguru Nishiuchi, Kohki Nakamura, Kenichi Kaseno, Shigeto Naito, Shigeru Ohshima
Journal: Circulation (2012)

Bachground: Early recurrence of atrial fibrillation (AF) after successful pulmonary vein electrical isolation (PVI) is indicated as a predictor of late recurrence, the prevention of early recurrence by aggressive intervention improves AF outcome. A novel respiration device called adaptive servo-ventilation (ASV) has been developed for central sleep apnea, ASV therapy improves heart failure and cardiac function. The aim of the present study was to investigate the efficacy of ASV therapy during a short period for preventing AF recurrence after catheter ablation. Methods: This study consisted of consecutive 112 AF patients (mean age: 64.3±8.1, 87 male, paroxysmal: n=42, persistent: n=37, long-standing: n=33). All patients underwent an overnight full polysomnography and circumferential PVI guided by CARTO system. 56 patients were randomly received ASV therapy (ASV group) with agreement by informed consent at overnight during 3 days after ablation procedure, 4 rejected patients with poor compliance after first...
PSA doubling time (PSADT) ≤6 months to identify a subgroup of men with biochemically-recurrent prostate cancer (BRPC) after prostatectomy (RP) at highest risk of distant metastasis (dMET).
Authors: Daniel L. Suzman, Jennifer Cullen, Bruce J. Trock, Yongmei Chen, Inger L. Rosner, Zhaoyong Feng, Emmanuel S. Antonarakis, Misop Han, Alan W. Partin, Lauren Hurwitz, Huai-Ching Kuo, David G. McLeod, Mario A. Eisenberger
Journal: Journal of Clinical Oncology (2016)

e16587 Background: In patients with BRPC after RP, PSADT is the strongest determinant of metastasis-free and overall survival. Prior reports defined 4 broad PSADT subgroups that predicted MFS and OS (<3, 3-9, 9-15, >15 mo). Prostate cancer specific survival impacts OS when PSADT ≤9 mo. Treatment and clinical trials are often offered to these patients, but risk of dMET remains heterogeneous. We combined two large BRPC databases to further evaluate PSADT cut-points that may sub-stratify risk of dMET in patients with PSADT ≤9 mo and potential PSA thresholds associated with dMET. Methods: Of 31,296 men with RP from 1989-2014 found in the CPDR and Johns Hopkins, those with BRPC with PSADT ≤9 mo and no prior androgen deprivation were eligible for analysis. PSADT was categorized as ≤3.0, 3.01-6.0, and 6.01-9.0 mo. MFS was modeled with Kaplan Meier (KM) curves and multivariable Cox proportional hazards analysis. The most proximal PSA value within 12 mo prior to dMET was evaluated. Results: Of 2,289 men with BRPC and no other treatment until metastasis, 373 (16.3%; median follow-up 10 yrs) had PSADT ≤9 mo and 181 (48.5%) developed dMET. Shorter PSADT was strongly associated with increased 3- and 5-yr dMET risk (p<0.0001), with risk doubled between PSADT 3.01-6 v. 6.01-9 mo, and nearly tripled for <3 mo (Table). Among all patients with PSADT ≤9 mo, 52% of metastases developed at PSA ≤ 10 ng/mL. Conclusions: Data from these two large cohorts of men with BRPC suggest that men with PSADT ≤6 months and PSA of ≥10 ng/mL portend high risk of dMET, with implications for patient counseling and clinical trial design. Absolute PSA as a trigger for treatment may be a potential endpoint that requires prospective validation. PSADT (mo) N (%) Comparison between PSADT groups 3-Year dMET risk (95% CI) 5-Year dMET risk (95% CI) HR (95% CI)* 6.01-9 151 (40.5) vs. 3.01-6 p=0.0006 14.4% (0.1- 21.5) 26.6% (19.6- 35.5) 1 3.01-6 153 (41.0) vs.≤ 3.0 p=0.86 39.5% (31.8- 48.2) 50.6% (42.0- 59.9) 1.9 (1.3- 2.6) [p = 0.0005] ≤3 69 (18.5) vs.6.01-9 p<.0001 60.2% (48.3- 72.4) 64.4% (52.3- 76.4) 2.4 (1.6- 3.7) [p<0.0001] *Adjusted for age at RP, race, pathologic Gleason and margin status.
Anxiety and patients: Perspectives on surveillance and adjuvant therapy in renal cell carcinoma.
Authors: Dena Battle, Hans J. Hammers, Eric Jonasch, Ithaar Derweesh, Daniel J. George, Axel Bex, Borje Ljungberg, Michael D. Staehler
Journal: Journal of Clinical Oncology (2018)

4571 Background: Until recently there has been no approved adjuvant therapy (AT) for renal cell carcinoma (RCC). Surveillance after nephrectomy is carried out with various modalities without clear recommendations from guidelines. In the S-TRAC trial, sunitinib improved disease-free survival (DFS) for high risk RCC patients (pts). Overall survival (OS) data is immature. Data on pts perception of AT vs surveillance are missing. The purpose of this study was to assess pts anxiety and perspectives regarding AT vs surveillance in RCC. Methods: We conducted a survey-monkey survey in n = 450 pts with RCC. The survey was promoted via kccure.org, Facebook and smartpatients.com. Questions focused on pts attitude towards AT. Results: Baseline pts characteristics include: median age 55.6 years (17-82 years); 56.4% female; 73.6% post-nephrectomy, 22.0% post-partial nephrectomy; 76.4% clear cell; 39.1% pts with RCC recurrence; 35.3% receiving systemic therapy for RCC. Median NCCN distress score was 6.39 in the majority of the pts. Main drivers of anxiety were cancer recurrence (74.4%), fear of the loss of renal function (38.7%), contrast media harming the kidney (27.1%) and exposure to radiation (20.7%). No differences in anxiety levels ranged between stage, age, gender, and type of surgery. Systemic therapy increased NCCN distress score (6.87, p < 0.0001). 63.1% of pts would use AT if it prolonged OS; 60.1% if AT prolonged DFS; 42.7% if AT demonstrated acceptable toxicity; 36.7% if guaranteed insurance coverage and efficacy. Use of systemic therapy correlated with a wish for a prolonged OS (p < 0.0001). Pts on systemic therapy had a significant higher acceptance of toxicity (p < 0.0001). Conclusions: Anxiety is a key driver for pts decisions and is unrelated to stage. Most pts are willing to use AT based on DFS benefits alone and place lower emphasis on toxicity. These data provide an important perspective on pts perceptions with RCC and the need for pts education on risks of AT.
Phase I/II study of niraparib plus pembrolizumab in patients with triple-negative breast cancer or recurrent ovarian cancer (KEYNOTE-162).
Authors: Panagiotis Konstantinopoulos, Kathleen N. Moore, Jasgit C. Sachdev, Monica M. Mita, Shaveta Vinayak, Shelly Marie Seward, Vassiliki Karantza, Gursel Aktan, Andrew Ferguson, Dmitri Bobilev, Ursula A. Matulonis
Journal: Journal of Clinical Oncology (2016)

TPS5599 Background: Homologous recombination defects are common in triple-negative breast cancer and high-grade serous ovarian cancer. Both niraparib, a highly selective inhibitor of PARP1/2, and pembrolizumab, a monoclonal antibody that blocks binding of the immune checkpoint receptor programmed death-1 (PD-1) to its ligands (PD-L1/2) and alleviates negative regulation of immune responses to cancer cells, have demonstrated single-agent antitumor activity in patients with breast or ovarian cancer. Combinations of PARP inhibitors with immune checkpoint inhibitors have shown synergistic effects in preclinical tumor models, suggesting that co-treatment with these drugs may improve clinical efficacy compared with monotherapy. This multicenter, open-label phase 1/2 study is evaluating niraparib plus pembrolizumab in metastatic triple-negative breast cancer and advanced ovarian cancer. Methods: Eligible patients have triple-negative breast cancer and ≤ 3 lines of prior chemotherapy ( ≤ 2 lines for the phase 2 portion) in the metastatic setting or recurrent, platinum-resistant ovarian cancer and ≤ 4 lines of prior chemotherapy ( ≤ 3 lines for the phase 2 portion) for advanced disease. Patients must have measurable lesions per RECIST v1.1 and no prior treatment with a PARP inhibitor or an anti-PD-1 or anti-PD-L1/2 agent. The phase 1 portion is enrolling ≈18 patients to identify the recommended phase 2 dose (RP2D) and schedule of niraparib (starting dose: 200 mg orally once daily) combined with pembrolizumab (200 mg IV on day 1 of 21-day cycles). The phase 2 portion will enroll patients with triple-negative breast cancer or ovarian cancer (≈48 of each) to receive the RP2D and schedule of niraparib plus pembrolizumab. Tumors will be assessed per RECIST v1.1 and immune-related RECIST (irRECIST), a modified version to assess responses to immunotherapies. The primary endpoint of the phase 2 portion is objective response rate (ORR) per RECIST v1.1. Secondary endpoints are ORR per irRECIST; duration of response, disease control rate, and progression-free survival per RECIST and irRECIST; and overall survival. Niraparib pharmacokinetics and biomarkers will be investigated. Clinical trial information: NCT02657889.
Oral Contraceptive Progestin and Estrogen Use and Increases in Breast, Ovarian, and Endometrial Cancers—Reply
Authors: Kara A. Michels, Britton Trabert
Journal: JAMA Oncology (2018)

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Estimating the optimal rate of adjuvant chemotherapy utilization in stage III colon cancer.
Authors: Safiya Karim, Kelly Brennan, Yingwei Peng, William J. Mackillop, Christopher M. Booth
Journal: Journal of Clinical Oncology (2017)

6591 Background: Identifying optimal chemotherapy utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of adjuvant chemotherapy (ACT) for stage III colon cancer. Methods: The Ontario Cancer Registry was linked to electronic chemotherapy records to identify ACT utilization among a random 25% sample of patients with stage III colon cancer diagnosed during 2002-2008 in Ontario, Canada. We explored whether hospital factors (teaching status, regional cancer centre, medical oncologist on-site) were associated with ACT rates. The benchmark population included hospitals with the highest ACT rates that accounted for 10% of the patient population. Hospital ACT rates were adjusted for case mix in a multi-level model accounting for random variation at the hospital level. A Monte Carlo simulation was used to estimate the proportion of observed ACT rate variation that could be due to chance alone. Results: The study population included 2,801patients with stage III colon cancer; ACT was delivered to 66% (1861/2801) of patients. There was no difference in hospital ACT rate by teaching status (64% academic vs 67% non-academic, p = 0.107), comprehensive cancer centre status (65% cancer centre vs 67% non-cancer centre, p = 0.362), or having medical oncology on site (67% on site vs 66% not on site, p = 0.840). After excluding hospitals that had case volumes less than 10 (N = 150), unadjusted ACT rates varied across hospitals (range 44% to 91%, p = 0.017). The unadjusted benchmark ACT rate was 81% (95%CI 76%-86%); utilization rate in non-benchmark hospitals was 65% (95%CI 63%-66%). When using adjusted ACT rates in a multi-level model significant variation remained across hospitals (p &lt; 0.001). The adjusted benchmark ACT rate was 74% (95%CI 63%-83%); non-benchmark hospital ACT rate was 65% (95%CI 53%-75%). The simulation analysis suggested that the non-random component of ACT rate variation across hospitals was 1.5%. Conclusions: There is significant variation in ACT rates across hospitals in routine practice. The estimated benchmark ACT rate is 74%. However, simulation analyses suggest that most of the variation in ACT utilization across hospitals may be due to chance alone.
TCT-435 The outcomes of Bicuspid Aortic Valve Patients Undergoing Surgical versus transcatheter aortic valve replacement
Authors: Mohamad Soud, Yasser Al-khadra, Homam Moussa Pacha, Fahed Darmoch, Amr Idris, Ziad SayedAhmad, Amir Kaki, Amjad kabach, Abdulah Alrifai, Zaher Fanari, M Chadi Alraies
Journal: Journal of the American College of Cardiology (2018)
The open, multicenters, double-arms, randomized, parallel controlled clinical trial of lobaplatin or gemcitabine combined with docetaxel as second-line therapy for advanced osteosarcoma-the effectiveness and safety analysis.
Authors: Yuanjue Sun, Yang Yao, Zhengdong Cai, Xiuchun Yu, Sujia Wu, Zhaoming Ye, Yingqi Hua, Shui'er Zheng, Guojing Chen, Yongcheng Hu, Yong Zhou, Zhen Wang
Journal: Journal of Clinical Oncology (2017)

e22506 Background: to study the progression free survival (PFS), objective response rate (ORR), overall survival (OS) and safety of lobaplatin or gemcitabine combined with docetaxel as second-line therapy for advanced osteosarcoma. Methods: the NO. of clinical trial was HNCA001,a total of 15 cases were enrolled into experiment group adopted lobaplatin combined with docetaxel,and 14 into control group received gemcitabine combined with docetaxel.The trial concluded screening, treatment and follow-up periods.21 dyas as one treatment period,they got drugs at the first day,and were evaluated the effects per two periods, treated at most 6 periods. Results: The baseline characteristics of two groups were no ststistical differences(diastolic blood pressure excluded) (P &gt; 0.05).The PFS rates of 2,4 and 6 periods in experiment group were 87.50%、87.50% and 70.00%,83.33%,27.78% and 0 in control group,middle PFS more than 12 months in experiment group and 3.20 months in control group;while there was no statistical difference of PFS rates(χ 2 = 2.42,P = 0.1194).The survival rates of 2,4 and 6 periods in experiment group were 100.00%,83.33% and 83.33%,83.33%,83.33% and 0 in control group,the middle OS more than 12 months in the two groups, there was no statistical difference of survival rates (χ 2 = 0.65,P = 0.4196).The ORR was 6.67% in experiment group and 0 in control group(P = 1.0000).There were no adverse events occurring in the two groups. Conclusions: There is negative results of the trial,most reason may be the samples are greatly less;the next step is samples expanded and follow-up extended for the priority of lobaplatin or gemcitabine combined with docetaxel as second-Line therapy for advanced osteosarcoma. Clinical trial information: NCT02099396.