tbuckley/cabot-search huggingface dataset:
Minocycline to reduce chemoradiation-related fatigue in patients with non-small cell lung cancer: A phase II randomized trial.
Authors: Charles S. Cleeland, Qiuling Shi, Xin Shelley Wang, Tito R. Mendoza, Loretta A. Williams, Zhongxing X. Liao
Journal: Journal of Clinical Oncology (2016)

10017 Background: Patients with non-small cell lung cancer (NSCLC) experience substantial fatigue that may be exacerbated by inflammation-induced sickness during concurrent chemoradiation therapy (CXRT). Minocycline is a readily available, low-cost antibiotic with anti-inflammatory properties. We conducted a phase II randomized, double-blinded, placebo controlled clinical trial to investigate the effect of minocycline in reducing patient-reported symptoms during and after CXRT for NSCLC. Methods: Adults with NSCLC scheduled for CXRT at a single-institution were consented and randomized to receive either minocycline (100 mg twice daily) or placebo over the course of CXRT (6.5–7.0 weeks ±2 days). Feasibility, toxicity, and patient-reported outcome data were prospectively collected. The MD Anderson Symptom Inventory (0–10 scale) was used to assess fatigue and other symptoms weekly during CXRT and for an additional 5 weeks post-CXRT. The 12-week (±2 days) area under the curve (AUC) for fatigue was compared between the minocycline and control groups to examine minocycline’s efficacy. Results: From 01/2013–08/2015, 49 patients were enrolled and 40 (80%) were evaluable: 19 were randomized to minocycline and 21 to placebo. There were no grade 3+ study medication-related adverse events. Demographic and disease characteristics were not significantly different between groups. AUCs for fatigue over 12 weeks were 31.2±14.2 and 45.0±20.9 for the minocycline and placebo groups, respectively (P= .021). The favorable fatigue reduction in minocycline group vs placebo arm was represented by a moderate effect size (Cohen’s d =0.77). Longitudinal modelling of the entire sample revealed a significant increase in fatigue during CXRT (est = 0.18, P= .0002), a significant decrease post-CXRT (est = –0.38, P< .0001), and a significantly lower fatigue level over 12 weeks in the minocycline group (est = –0.65, P= .025). Conclusions: Minocycline during CXRT for NSCLC was feasible, had a low toxicity profile, and yielded a statistically significant positive signal in terms of patient-reported fatigue. These preliminary results are encouraging and warrant a Phase III trial to test its efficacy. Clinical trial information: NCT01636934.
Comparison of palliative care for lung cancer patients (pts) at two Veteran Affairs Medical Centers.
Authors: Sejal Kothadia, Zhen Wang, Sarah Lee, Victor Tsu-Shih Chang, Yeun-Hee Anna Park, Ellen Olson, David Klein, Andrea Nadine Leaf, Stephanie Hwa, Fengming Zhong
Journal: Journal of Clinical Oncology (2017)

e21621 Background: Palliative and end of life care is essential for lung cancer pts. We examined palliative care delivery for lung cancer pts at 2 VA medical centers. Methods: In an IRB approved protocol, we reviewed medical records of matched pts diagnosed with liver or lung cancer between 2006 and 2012 who were seen by palliative care at 2 VA medical centers (S1, S2). Veterans were compared by 1) demographics, 2) palliative interventions, and 3) outcomes: ED visit within 1 month (mo) of death, ED visit within 6 mo of death, and ICU within 30 days of death. Analyses were performed with SAS Studio Version 3.5. Results: We analyzed 69 male pts (29 at S1and 40 at S2), with a mean age of 63 and 66 years respectively. Thirty (43%) pts were Caucasian and 39 (56.5%) African American. Cancer stages were I (1%), Stage II (3%), Stage III0 (29%), Stage IV (58%), and unknown (8%). Median Karnofsky performance status was 60%. By site, differences were seen in DNR/DNI (S1, S2) [ 21 (72%), 12 (30%) p = 0.0007). For palliative care interventions, significant differences were seen in treatments for pain (S1, S2) [17 (59%), 37 (93%) p = 0.0011], constipation (S1, S2) [10 (34%), 35 (88%) p &lt; 0.0001], and dyspnea (S1, S2) [8 (28%), 29 (73%) p = 0.0003], but not for holding goals of care discussions. We observed differences between sites in evaluations by palliative social work (S1, S2) [15 (51%), 39 (98%) p &lt; 0.0001], mental health (S1, S2) [21 (88%), 10 (25%) p &lt; 0.0001], and chaplain visits (S1, S2) [ 19 (66%), 36 (90%) p = 0.0167]. Finally with outcome, there was a difference between consultations by other medical specialties (S1, S2) [ 19 (66%), 39 (98), p = 0.0005] but not for ED visits, admissions, procedures or ICU stays at the end of life . Conclusions: There are site specific differences between VA medical centers and may reflect local practice patterns, Additional sites should be studied.
Clinical factors to predict the absence of benefit of surgery in patients operated for colorectal liver metastases.
Authors: Ali Bohlok, Héloïse Tessely, Emiko Naets, Fikri Bouazza, Desislava Germanova, Jean-Luc Van Laethem, Alain Hendlisz, Valerio Lucidi, Vincent Donckier
Journal: Journal of Clinical Oncology (2018)

e15613 Background: A substantial proportion of patients undergoing colorectal liver metastases (CRLM) resection with curative-intent will rapidly recur, emphasizing the need to improve the current selection process for surgery. This study’s aim is to validate clinicopathologic prognostic factors as biomarkers accurate enough to identify patients unlikely to benefit from resection and who should be spared surgery. Methods: A prospective database of patients having undergone hepatectomy for CRLM between 2005 and 2017 was analysed. Within this population, we compared early relapsers (ER), defined as patients with unresectable recurrence ≤1 year (yr) postoperatively and long-term survivors (LTS), defined as patients without recurrence ≥5 yrs after the first hepatectomy. In the entire population and in the 2 subgroups, we analysed potential predictive factors, using uni- and multivariate analysis. Results: In the total population (N = 357), 5 and 10-year disease-free survival (DFS) and overall survival (OS) are 26 and 21.5% and 44 and 25% respectively. In univariate analysis, Fong’s Clinical Risk Score (CRS) > 2, mutated-KRAS, major hepatectomy and positive resection margins are significant poor prognostic factors for DFS and OS. In multivariate analysis only mutated-KRAS remains a significant poor prognostic factor for DFS (HR = 1,5 Ci:1,06-2,12 p = 0,02) and OS (HR = 1,8 Ci:1,19-2,70 p = 0,005). Comparing the 2 subgroups ER-group (77 pts) and LTS-group (64 pts), representing respectively 21 and 18% of the entire population, the univariate analysis showed significantly more synchronous CRLM, multiple metastases, mutated-KRAS and CRS > 2 in the ER group. Of note, 25% of LTS had CRS > 2. In multivariate analysis, only multiple metastases remain statistically significant (p = 0.016). Conclusions: Preoperative clinical factors are unable to discriminate the patients unlikely to benefit from surgery for CRLM. This strongly underlines the need to identify markers of tumor biology for better treatment personalization .
Impact of venous thromboembolism among hospitalized pancreatic cancer patients: Results from national inpatient sample.
Authors: Ramesh Kumar Pandey, Sushil Ghimire, Rashmi Dhital, Sirjana Basnet Pandey, Dilli Ram Poudel
Journal: Journal of Clinical Oncology (2018)

e16224 Background: Venous thromboembolism (VTE) among malignancies is common and is associated with worse in-hospital outcomes. We aimed to study prevalence of VTE and its impact among hospitalized patients with pancreatic cancer (PC). Methods: We used the National Inpatient Sample (NIS) database from 2001 to 2013 to identify adults (≥18 yrs) with PC as well as presence of VTE using ICD-9 codes and compared demographic characteristics and in-hospital outcomes between PC with and without VTE. Regression analysis was used to calculate odds of association. Results: 85,228 (8.43%) of a total of 1,010,562 hospitalized pancreatic cancer patients had associated VTE. Demographic characteristics including age, race, gender and comorbidity index are shown in the table. PC patients withVTE had a longer mean length of stay (LOS) (8.42 vs 6.99 days, OR 1.7, (CI 1.4 – 2.0), p < 0.001), higher average cost of hospitalization ($18115 vs $14859, OR 1.3 (CI 1.2 – 1.4), p < 0.001) and significantly higher inpatient mortality (12.5 % vs 9.5%, OR 1.4 (CI 1.3 – 1.43), p < 0.001). Factors associated with higher odds of VTE were female sex, African-American race, higher comorbidity index and use of chemotherapy on multivariate analysis. Interestingly, advancing age and smoking were associated with lower odds of occurrence of VTE. Conclusions: VTE in PC is associated with increased mortality, longer hospitalization and higher cost. Effective intervention to reduce the VTE among the PC patients could improve in-hospital outcomes. VTE No VTE DVT PE Age (yrs) 67.19 68.19 67.51 66.92 Female (%) 50.53 50.67 50.05 49.39 Race Caucasian 74.46 74.6 73.66 75.53 African American 14.56 12.21 14.39 15.28 Others 10.97 13.18 11.95 9.20 Charlson comorbidity Index (%) 2 13.45 20.72 3 9.49 15.18 ≥4 77.06 64.09 Mean LOS (days) 8.42 6.99 8.64 7.93 Mortality 12.5% 9.5% 11.36% 15.89% Cost of hospital stay ($) 18114.76 14858.8 17976.15 17717 Factors associated with VTE: Multivariate regression, OR (CI) Smoking Chemo Age Female Race Charlson Comorbidity Index AA Others 3 ≥4 0.83 (0.79 – 0.87) 1.36 (1.26- 1.46) 0.995 (0.993 – 0.996) 1.05 (1.01- 1.09) 1.15 (1.08 – 1.21) 0.81 (0.76 – 0.87) 1.02 (0.95 – 1.10, p 0.588) 1.89 (1.79 – 2.00)
Practice transformation: Early impact of OCM on hospital admissions.
Authors: Molly Mendenhall, Brian Bourbeau, Karyn M. Dyehouse, Andrew S Guinigundo, Teresa Meyer-Smith, David Michael Waterhouse
Journal: Journal of Clinical Oncology (2018)

30 Background: The purpose of the Oncology Care Model is to improve quality and reduce cost through practice transformation. A foundational tenant is to reduce avoidable ER visits and hospitalizations. In anticipation of being an OCM participant, we instituted a multidimensional campaign designed to meet these objectives. Methods: Prior Actions: Established phone triage unit. After-hours and weekend call. Instituted weekend urgent care. Year One: Improved education provided by nurse navigators and APPs prior to start of treatment (OCM Treatment Planning visit). Implemented triage pathways: 38 symptom and 27 follow-up pathways (modified COME HOME, Barbara McAneny, M.D.). Proactive symptoms follow-up calls to help circumvent emergent admissions. Increased APP staffing to provide blocked time slots for same day patient visits w/o schedule disruptions. Initiated “Call Us Early – Call Us First” campaign. Incorporated verbal and/or written instructions at all patient touch points, emphasizing patient’s responsibility to call before going to the emergency room. Results: Based on data from the Chronic Condition Warehouse, as provided by CMS, we were successful at reducing the acute care admissions rate by 16 percent. Conclusions: By implementing a cost efficient, reproducible, and scalable campaign targeting ER avoidance and hospitalizations, we were able to decrease hospital admissions. Reported Medicare savings amounted to nearly $798,000 in inpatient cost per quarter over 1,600 patients.[Table: see text]
TCT-844 Long term risk for major bleeding and ischemic events after PCI with implantation of everolimus-eluting stents: A Pooled-level Analysis of 8,020 Patients
Authors: Sabato Sorrentino, Bimmer Claessen, Usman Baber, Lijuan Jenny Wang, Mitchell Krucoff, Ken Kozuma, Junbo Ge, Ashok Seth, Raj Makkar, Sripal Bangalore, Deepak Bhatt, Dominick Angiolillo, Shigeru Saito, Franz-Josef Neumann, James Hermiller, Marco Valgimigli, Roxana Mehran
Journal: Journal of the American College of Cardiology (2018)
Cryocompression for enhanced limb hypothermia in preventing paclitaxel-induced peripheral neuropathy.
Authors: Raghav Sundar, Aishwarya Bandla, Stacey Tan, Nesaretnam Barr Kumarakulasinghe, Yiqing Huang, Sally Ang, Zarinah Hairom, Joline Si Jing Lim, Alvin Seng Cheong Wong, Gloria HJ Chan, Natalie Ngoi, Emily Ang, Amanda Chan, Soo-Chin Lee, Nitish Thakor, Einar Wilder-Smith
Journal: Journal of Clinical Oncology (2018)

10095 Background: Severe peripheral neuropathy is a common dose-limiting toxicity of paclitaxel chemotherapy, with no effective treatment. We have previously described the role of continuous-flow hypothermia in reducing neurotoxicity caused by paclitaxel. We hypothesized that cryocompression (addition of pressure to hypothermia) may enhance depth of cooling and improve efficacy. Methods: A proof-of-concept study was conducted in cancer patients receiving taxane chemotherapy. Each subject underwent four-limb cryocompression with each chemotherapy infusion (3 hours) for a maximum of 12 cycles. Cryocompression was administered at 16°C and cyclic pressure (5-15 mmHg). Skin surface temperature and tolerance scores were recorded. Neuropathy was assessed using nerve conduction studies (NCS) conducted before (NCSpre), after completion (NCSpost) and 3-months post chemotherapy (NCS3m). Results: In total, thirteen patients underwent 142 cycles of cryocompression concomitant with chemotherapy. Mean skin temperature reduction of 3.8 ± 1.7°C was achieved and was well tolerated. Only 1 out of 13 patients required an intra-cycle temperature increase, with no early termination of cryocompression in any subject. NCS analysis showed significant preservation of motor amplitudes at NCS3m compared to baseline (common peroneal nerve below fibula head stimulation: 12.7 ± 25.6 %; p = 0.013; tibial nerve abductor hallucis stimulation: 8.8 ± 22.9%; p = 0.005). Sensory nerve amplitudes showed a reduction at NCSpost compared to baseline but continued to be preserved at NCS3m (% change from baseline: (NCSpost) -28.1 ± 21.9 %; (NCS3m) -26.7 ± 19.0 %). Crycompression did not significantly affect taxane-induced changes in nerve velocities. Conclusions: Cryocompression is well tolerated and results in preservation of neuron function, as measured by gold-standard NCS. When compared to our previously reported continuous-flow hypothermia (21°C) cohort, cryocompression permitted delivery of lower temperatures with similar tolerability, potentially leading to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are ongoing. Clinical trial information: NCT03299582.
Detection of clinically-actionable alterations as hallmarks of <i>de novo</i> small cell prostate cancer.
Authors: Gillian Rae Vandekerkhove, Edmund Chedgy, Cameron Herberts, Matti Annala, Ladan Fazli, Himisha Beltran, Kim N. Chi, Alexander William Wyatt
Journal: Journal of Clinical Oncology (2018)

e17072 Background: Small cell prostatic carcinoma (SCPC) is a rare but often fatal disease. SCPC is commonly seen after treatment with androgen deprivation therapy, however, primary de novo SCPC can occur and accounts for < 0.1% of prostate cancer (PC) diagnoses. We sought to review the clinicopathological, genomic, and transcriptomic landscape of a cohort of patients diagnosed with de novo SCPC. Methods: We identified 18 British Columbian patients diagnosed with de novo SCPC since 2004, all of whom received platinum-based chemotherapy as their initial PC treatment. Archival diagnostic tissue underwent comprehensive histopathological analysis and nucleic acid extraction. DNA was analysed using a custom panel of 73 PC genes, as well as whole exome sequencing in select patients. RNA was analysed using the NanoString nCounter Analysis System. Results: 17 patients had tissue available for molecular analysis; 55% with pure SCPC and 45% SCPC admixed with adenocarcinoma. Median overall survival was 28.3 months, with 4 patients alive at last follow-up. 13/17 patients harboured TP53 alterations, and one case of MDM2 amplification. Alteration of RB1 was observed in > 50% of the cohort. 5/15 patients harboured deleterious mutations in DNA repair genes (BRCA1/2, ATM, MSH2/6). The median overall survival for DNA repair deficient patients was 40 months, compared to 14 for the rest of the cohort, with similar frequencies of metastatic disease at diagnosis (3/5 vs 12/18). No AR mutations or amplifications were identified. Likewise, RNA expression profiles (11/18 patients) revealed lower expression of AR and AR-related genes and higher expression of neuroendocrine-related genes (SYP, MYCN) in pure de novo SCPC as compared to SCPC admixed with adenocarcinoma. FOXA1 forkhead domain mutations were identified in 4 patients, and in 2 patients, fusions of ETS genes to AR regulated promoters. Conclusions: De novo SCPC has a high rate of TP53 and RB1 alteration, features also typical of treatment-emergent SCPC. The observation of FOXA1 mutations and ETS fusions in pure de novo SCPC provides evidence for an AR-positive ancestor. Frequent DNA repair alterations indicate an actionable pathway, which may be associated with de novo SCPC development.
Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition
Authors: Hu Huang, Seung-Hwan Lee, Inês Sousa-Lima, Sang Soo Kim, Won Min Hwang, Yossi Dagon, Won-Mo Yang, Sungman Cho, Min-Cheol Kang, Ji A. Seo, Munehiko Shibata, Hyunsoo Cho, Getachew Debas Belew, Jinhyuk Bhin, Bhavna N. Desai, Min Jeong Ryu, Minho Shong, Peixin Li, Hua Meng, Byung-Hong Chung, Daehee Hwang, Min Seon Kim, Kyong Soo Park, Maria Paula Macedo, Morris White, John Jones, Young-Bum Kim
Journal: Journal of Clinical Investigation (2018)

Obesity is a major risk factor for developing nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common form of chronic liver disease and is closely associated with insulin resistance, ultimately leading to cirrhosis and hepatocellular carcinoma. However, knowledge of the intracellular regulators of obesity-linked fatty liver disease remains incomplete. Here we showed that hepatic Rho-kinase 1 (ROCK1) drives obesity-induced steatosis in mice through stimulation of de novo lipogenesis. Mice lacking ROCK1 in the liver were resistant to diet-induced obesity owing to increased energy expenditure and thermogenic gene expression. Constitutive expression of hepatic ROCK1 was sufficient to promote adiposity, insulin resistance, and hepatic lipid accumulation in mice fed a high-fat diet. Correspondingly, liver-specific ROCK1 deletion prevented the development of severe hepatic steatosis and reduced hyperglycemia in obese diabetic (ob/ob) mice. Of pathophysiological significance, hepatic ROCK1 was markedly upregulated in humans with fatty liver disease and correlated with risk factors clustering around NAFLD and insulin resistance. Mechanistically, we found that hepatic ROCK1 suppresses AMPK activity and a ROCK1/AMPK pathway is necessary to mediate cannabinoid-induced lipogenesis in the liver. Furthermore, treatment with metformin, the most widely used antidiabetes drug, reduced hepatic lipid accumulation by inactivating ROCK1, resulting in activation of AMPK downstream signaling. Taken together, our findings establish a ROCK1/AMPK signaling axis that regulates de novo lipogenesis, providing a unique target for treating obesity-related metabolic disorders such as NAFLD.
Astrocyte Elevated Gene-1 Regulates Macrophage Activation in Hepatocellular Carcinogenesis
Authors: Chadia L. Robertson, Rachel G. Mendoza, Nidhi Jariwala, Mikhail Dozmorov, Nitai D. Mukhopadhyay, Mark A. Subler, Jolene J. Windle, Zhao Lai, Paul B. Fisher, Shobha Ghosh, Devanand Sarkar
Journal: Cancer Research (2018)

Chronic inflammation is a known hallmark of cancer and is central to the onset and progression of hepatocellular carcinoma (HCC). Hepatic macrophages play a critical role in the inflammatory process leading to HCC. The oncogene Astrocyte elevated gene-1 (
A phase Ib/II study of cancer stemness inhibitor napabucasin (BB608) combined with weekly paclitaxel in platinum-resistant ovarian cancer.
Authors: Agustin A. Garcia, John L. Hays, Gregory Michael Cote, Carlos Becerra, Adrian Langleben, Susie K Lau, Lynda D. Roman, Colleen Catherine McCormick, Donald A. Richards, Fadi S. Braiteh, Habte Aragaw Yimer, Stephen Lane Richey, William Jeffery Edenfield, Kimiko Kossler, Stephanie Hume, Youzhi Li, Matthew Hitron, Chiang Li
Journal: Journal of Clinical Oncology (2016)

5578 Background: Napabucasin (BBI-608, BB608) is a first-in-class cancer stemness inhibitor targeting the STAT3 pathway that has shown potent synergistic anti-tumor activity with paclitaxel in vivo. In a dose escalation study, BB608 plus weekly paclitaxel was well tolerated in patients (pts) with advanced solid tumors. RP2D expansion included accrual of pts with platinum resistant ovarian cancer (PROC). Methods: Pts with advanced epithelial ovarian, fallopian, or peritoneal cancer who have progressed on a prior taxane-based regimen and who were platinum resistant or refractory were enrolled. BB608 240-480 mg twice daily was administered orally with paclitaxel 80 mg/m2 IV weekly 3 of every 4 weeks. A sample size of 40 set the bounds of the 90% CI at ±10% to 14%, assuming a disease control rate (DCR) of 60% to 80%. DCR is the proportion with stable disease (SD) at least 8 weeks or ,partial (PR) or complete response (CR) per RECIST 1.1. Results: 56 pts were enrolled after a median 4 prior lines of therapy, including prior taxanes (92% paclitaxel only, 4% docetaxel only, 4% both). Treatment was tolerated without dose-limiting toxicity or unexpected adverse events (AE). Grade 3 AE included rapidly-reversible diarrhea (18%), vomiting (7%), abdominal pain (7%), nausea (5%), dehydration and fatigue ( < 4% each). 80% of pts with grade 3 AE continued study at a reduced dose. In evaluable pts (n = 40), DCR was 68%, tumor regression occurred in 40%, and ORR (PR+CR) was 25%, including 1 with CR. Prior to being evaluated, 2 pts withdrew due to neuropathy, 6 for other AE, 5 for deterioration, 2 for noncompliance, and 1 for MI (unrelated). In the intent to treat (ITT) pts (n = 56), DCR was 48%, ORR was 18%, median progression free survival was 15 weeks and median overall survival was 38 weeks. In pts with up to 2 prior lines of therapy (n = 11), ORR was 45%. Conclusions: BB608 can be safely combined with weekly paclitaxel with acceptable tolerability in pts with heavily pretreated PROC who have progressed on prior taxane-based regimens. Complete and partial response, durable disease control, and prolonged progression free survival and overall survival have been observed in this population, warranting further clinical study. Clinical trial information: NCT01325441.