tbuckley/cabot-search huggingface dataset:
Effect of angiotensin system inhibitors on survival in patients receiving chemotherapy for advanced non-small cell lung cancer.
Authors: Alex R. Menter, Nikki Carroll, Thomas Delate, Mark C. Hornbrook, Lawrence H. Kushi, Lori Sakoda, Valerie S Lee, Virginia P. Quinn, John L Adams, Debra P. Ritzwoller
Journal: Journal of Clinical Oncology (2014)

8069 Background: Several retrospective studies have identified an association between angiotensin system inhibitors (ASI) and improved survival for patients with advanced stage malignancies including non-small cell lung cancer (NSCLC). We examined this association in Kaiser Permanente’s (KP’s) integrated practice settings. Methods: Data from four KP regions (Colorado, Northern California, Southern California, Northwest) contributed to the analysis. The cohort (n=2,723) included patients with stage IIIb-IV non-squamous NSCLC diagnosed between 2005 and 2011 who were treated with carboplatin and paclitaxel (CP) or CP with bevacizumab (CPB). Patients were followed from chemotherapy initiation until death, disenrollment from the health plans, or December 31, 2012. Demographic, tumor, chemotherapy, comorbidity, pharmacy, and mortality data were extracted from each region’s clinical databases. Exposure to ASI was defined as any angiotensin converting enzyme inhibitor or angiotensin receptor blocker dispensing between 30 days before to 90 days after the start of chemotherapy. Cox proportional hazard models adjusted for age, gender, weight, stage, smoking status, tumor grade, and comorbidity were used to estimate hazard ratios (HR) for overall survival (OS) comparing those who used an ASI to those who did not. Results: Of 2,277 patients treated with CP, 524 (23%) received an ASI; of 446 patients treated with CPB, 116 (26%) received an ASI. ASI patients were older and had more comorbidity. Median OS for patients receiving CP and CPB were 8.7 and 12.9 months, respectively. For CP patients with and without concomitant ASI exposure, median OS were 10.5 and 8.3 months, respectively (crude HR 0.81, 95% confidence interval (CI) 0.73-0.90). For CPB patients with and without concomitant ASI exposure, median OS was 14.9 and 12.3 months, respectively (crude HR 0.81, 95% CI 0.64-1.03). For CP and CPB patients with concomitant ASI exposure, the multivariate-adjusted HRs were 0.79 (95% CI 0.70-0.89) and 0.84 (95% CI 0.62-1.13), respectively. Conclusions: Concomitant ASI use during CP or CPB chemotherapy for NSCLC was associated with improved survival.
Largest Reported Series of Adults Who Received Treatment with Eculizumab (ECU) for Hematopoietic Cell Transplantation-Associated Thrombotic Microangiopathy (TA-TMA). a Single Center Experience
Authors: Alan P Skarbnik, Mary E Dilorenzo, Michele Simone, Scott D. Rowley, David H. Vesole, Maribel Pereiras, Tracy Andrews, Andrew L. Pecora, Michele L. Donato
Journal: Blood (2018)
Variation in the use of adjuvant chemotherapy following neoadjuvant radiotherapy and surgery for rectal cancer in a publicly-insured health care system.
Authors: Lev Bubis, Alyson L. Mahar, Vaibhav Gupta, Yunni Jeong, Laura Davis, Qing Li, Paul Jack Karanicolas, Natalie Coburn
Journal: Journal of Clinical Oncology (2018)

854 Background: The efficacy of routine administration of adjuvant chemotherapy following sequential neoadjuvant chemoradiotherapy and surgery for rectal cancer is uncertain. This uncertainty may lead to practice pattern variations, with significant downstream discrepancies in oncological outcomes, patient-centered outcomes, and healthcare costs. The objective of this study, therefore, was to evaluate patient, disease, and health system factors associated with receipt of adjuvant chemotherapy following neoadjuvant radiotherapy and proctectomy. Methods: A retrospective cohort study of patients diagnosed with rectal cancer undergoing preoperative radiotherapy prior to proctectomy from January 1, 2010 to December 31, 2014 was performed using linked administrative healthcare databases. We compared the rate of chemotherapy administration (≥ 1 billing record) within 180 days of index rectal resection by healthcare administrative region in Ontario, Canada (2014 population: 13.4 million). Multivariable logistic regression models were constructed to assess patient, disease, and health system factors associated with differences in receipt of adjuvant chemotherapy. Results: We studied 1668 patients treated with preoperative radiotherapy and proctectomy, of whom 67% received chemotherapy within 180 days after surgery. The rate of adjuvant chemotherapy administration varied among health regions from 54% to 93%. On multivariable analysis, health region of residence, younger patient age, lower baseline comorbidity burden, and pathological nodal involvement were significant predictors of receipt of adjuvant chemotherapy. Conclusions: There is significant variation in receipt of adjuvant chemotherapy for patients receiving preoperative radiotherapy followed by proctectomy in Ontario. This variability is associated with patient, disease, and health system-related factors. Identifying the drivers of variability in cancer care practice may help to provide a basis for understanding and addressing discrepancies in clinical, patient-centered, and economic outcomes in healthcare systems.
Development of a mucoinert progesterone nanosuspension for safer and more effective prevention of preterm birth
Authors: Thuy Hoang, Hannah Zierden, Abhijit Date, Jairo Ortiz, Sanjeev Gumber, Nicole Anders, Ping He, James Segars, Justin Hanes, Mala Mahendroo, Laura M. Ensign
Journal: Journal of Controlled Release (2018)
Tumor cells/leukocytes ratio (TLR) in peritoneal fluids as a biomarker in patients with peritoneal metastasis of gastric cancer.
Authors: Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Shigenobu Emoto, Hiroharu Yamashita, Yasuyuki Seto, Keisuke Matsusaki, Toshiaki Watanabe
Journal: Journal of Clinical Oncology (2014)

3039 Background: Peritoneal carcinomatosis (PC) is the most frequent and life-threatening types of metastasis in patients with gastric cancer (GC). Although the presence of tumor cells in peritoneal cavity is evaluated with microscopic observation by pathologists (Cy) or detection of mRNA of tumor specific molecules, no reliable method is available to quantify the accurate frequency of tumor cells. Methods: A total of 380 samples of acsites or peritoneal lavages were recovered from 243 patients with GC and 22 patients with liver cirrhosis (LC). Peritoneal fluids were obtained by laparotomy or paracentesis, and from subcutaneous intraperitoneal access port in case of the patients who received repeated intraperitoneal (IP) chemotherapy for PC. Cells were recovered by centrifugation of peritoneal fluids and immunostained with mAbs to CD45 and to CD326 (EpCAM). Using flowcytometry, the number of CD326(+)CD45(-) and CD45(+)CD326(-) cells, which were determined as tumor cells (T) and leukocytes (L), respectively, were calculated in 104~105acquired cells, and T/L ratio (TLR) was calculated. Results: Median (M) of TLR of the GC patients with PC(+) patients was 0.19% (0%-1868.44%, n=281), which was significantly higher than those of PC(-) patients (M=0%, 0%-0.30%, n=77, p<0.001) and LC (M=0%, 0%-0.028%, n=22, p<0.001). In PC(+) patients, 168 samples which was determined as positive cytology (Cy+) showed higher TLR as compared with 113 samples with Cy (-) (M=1.33%, 0%-1868.44% vs M=0%, 0%-1.13%, p<0.0001). In 37 patients who underwent repeated IP chemotherapy, TLR was markedly decreased after chemotherapy and the response was more sensitive than the changes in Cy or mRNA of CEA. Moreover, TLR of the patients with PC(+) GC before chemotherapy was significantly associated with their outcome. Median survival times (MST) of the patients whose initial TLR were <1.0%, 1.0%~10%, <10% were 765, 394, 271 days, respectively (p<0.001). Conclusions: TLR measured with flowcytometry well reflects the relative volume of living tumor cells in peritoneal cavity and thus could be a useful biomarker to predict the prognosis as well as the effectiveness of IP chemotherapy in patients with PC.
The role of surgery in patients with primary metastatic breast cancer (PMBC) receiving monoclonal antibody treatment.
Authors: Jana Barinoff, Marcus Schmidt, Andreas Schneeweiss, Axel Hinke, Winfried Schoenegg, Tim Wohlfarth, Claudia Kiewitz, Andreas Kutscheidt, Christian Jackisch
Journal: Journal of Clinical Oncology (2014)

1097 Background: Apart from the individual palliative need, the beneficial effect of surgically removing the primary tumor in PMBC on long-term outcomes, as suggested by retrospective series and meta-analyses, remains controversial. A cohort of 2,401 patients (pts) with metastatic breast cancer from two prospective non-interventional studies (NIS), enrolled between 2000 and 2011, was screened with respect to this question. Methods: One study investigated trastuzumab therapy for HER2+ metastatic breast cancer in addition to mainly 1st line chemotherapy. The second NIS observed bevacizumab therapy for mostly HER2– disease additional to chemotherapy as 1st line treatment. Progression-free survival (PFS) was defined as the time from start of antibody therapy to disease progression or death; overall survival (OS) was defined as the time from start of targeted therapy to death of any cause. Results: 570 (24%) pts had PMBC, and valid information on primary tumor surgery was available for 568. Out of these, 426 (75%) underwent local surgery (LS). The LS group was characterized by less overall metastatic burden (20% vs. 39% with ≥3 sites involved) and a lower proportion of T4 tumors (26% vs. 52%). No major differences were observed with respect to age, hormone receptor and HER2 status, visceral disease, prior palliative treatment and performance status. Numerically, the LS group showed a slightly favorable PFS (medians: 13.6 vs. 11.8 months; p=0.18) and OS (34.1 vs. 31.7; p=0.23). However, in multivariate analysis including all other univariately significant parameters (age, hormone receptor status, visceral disease, number of involved sites, performance status), no trend for better outcome after surgery remained observable, neither for PFS (hazard ratio 0.99; p=0.92) nor OS (0.95; p=0.71). Conclusions: In PMBC pts treated with modern targeted therapies, our findings confirm the recent preliminary results from two randomized studies with no survival advantage for LS shown in the overall pt population. However, further analyses are warranted to define specific risk groups, which may benefit from surgical removal of the primaries.
Role of the EphA4 and EphA7 genes in mediating the growth and aggressiveness of medulloblastoma tumors in the Smo/Smo medulloblastoma mouse model.
Authors: Nimrah A Baig, Olga Rodriguez, Elena Pasquale, Anatoly Dritschilo, Maria Donoghue, Olga Timofeeva, Christopher Albanese, Sana D Karam
Journal: Journal of Clinical Oncology (2014)

e22137 Background: Eph/ephrin signaling in numerous cancer systems promotes aspects of tumorigenesis, including proliferation, migration, and angiogenesis. Few studies, however, have investigated the role of Eph/ephrin signaling in medulloblastoma, an aggressive primitive neuroectodermal tumor originating from granule neuron precursors in the cerebellum. Here, we evaluated the effects of EphA4, EphA7, and ephrinA5 silencing on the radiographic tumor growth and development of medulloblastoma in vivo. Methods: We used the Smo/Smo transgenic mouse model bred to a doubly transgenic EphA4/EphA7 mouse model to evaluate the roles of EphA4 and EphA7 on medulloblastoma tumor growth. We similarly analyzed the effect of knockdown of ephrinA5, a high affinity binding ligand to both EphA4 and EphA7, on radiographic tumor development and progression. In the Smo/Smo model, regulation under the NeuroD2 promoter allows constitutive activation of Smoothened, a G protein-coupled receptor in the Sonic Hedgehog signaling pathway, in granule neuron precursors. EphA4 is expressed on Purkinje cells, while EphA7 and ephrinA5 expression are mostly limited to granule cells. Protein expression in tumor tissue dissected from mice with altered EphA4/EphA7 gene expression in the Smo/Smo transgenic animals was analyzed by Western blotting. Results: Serial MRI images of a total of 40 mice showed accelerated tumor onset and growth in mice with altered EphA4/EphA7 gene expression. Analysis of protein expression in tumor tissue dissected from mice with altered EphA4/EphA7 gene expression in the Smo/Smo transgenic animals showed corresponding changes in the expression of cyclinD1, PCNA, phospho-Akt, phospho-Erk, and Pax6, as well as changes in PARP cleavage. Analysis of approximately 50 MRI images from Smo/Smo mice bred to the ephrinA5 ligand showed no consistent effect on growth or progression of tumors. Conclusions: Knockdown of EphA4 and EphA7 genes results in radiographic acceleration of medulloblastoma tumor growth and progression in vivo.
Characterization of Pathogenic Variants and Clinical Phenotypes in 117 Japanese Fanconi Anemia Patients
Authors: Minako Mori, Asuka Hira, Kenichi Yoshida, Hideki Muramatsu, Yusuke Okuno, Michiko Anmae, Kazuo Tamura, Jun Yasuda, Tomoo Osumi, Yasushi Noguchi, Souichi Adachi, Hiroshi Kawabata, Akifumi Takaori-Kondo, Seiji Kojima, Seishi Ogawa, Hiromasa Yabe, Miharu Yabe, Minoru Takata
Journal: Blood (2018)
Differential diagnosis challenges, treatment patterns, and adverse outcomes for a rare head and neck neoplasm: A global systematic review of cervical sympathetic chain schwannomas.
Authors: Maryam Navaie, Leighla A. Sharghi, Michael A. Keefe, Benjamin A. Howie, Soojin Cho-Reyes, Gavin Setzen
Journal: Journal of Clinical Oncology (2014)

e17020 Background: To systematically evaluate the global literature to determine differences in the differential diagnosis approach, treatment practice patterns, and surgical outcomes of cervical sympathetic chain schwannomas (CSCS), a rare and benign head and neck neoplasm. Methods: Using Medline, EMBASE, and Cochrane databases, a systematic literature review identified 89 CSCS case reports or series from 1997 to 2013. The majority of cases were treated internationally (82%), predominantly in Asia (50%) and Europe (27%). Data on diagnosis and surgical treatment approach relative to outcomes were extracted by independent reviewers with high inter-rater reliability (κ=.79). Descriptive statistics, bivariate analyses, and comparative Z-tests were performed with p<0.05 denoting statistical significance. Results: On average, patients were 42.6 years old (SD=13.3) and had a 2 - 4 cm (52.7%) or >4 cm (43.2%) neck tumor. Nearly 70% of cases were asymptomatic. Pre-surgical diagnosis relied on CT (63.4%), MRI (59.8%) or both (20%), supplemented by cytology (47.6%). U.S.-treated cases were significantly more likely to receive MRI than internationally-treated cases, but less likely to have cytology/histopathology (p<0.05). Pre-surgical diagnosis accuracy was only 11% as confirmed by post-surgical histopathology. Extracapsular (complete) resection of the tumor with nerve sacrifice vs. an intracapsular approach with nerve preservation was the most common treatment (87.6%), irrespective of tumor size and treatment country. Adverse events (AEs) including Horner’s syndrome (89.9%), First Bite syndrome (21.1%) or both (15.7%) were significantly more prevalent with >4 cm tumor size and extracapsular resection (p<0.05). AEs persisted in 81.8% of cases at follow-up (mean: 28.8 months, SD:27.1). Conclusions: Globally, variations in diagnostic approach and treatment impacted patient outcomes. Given the typical CSCS patient is young and asymptomatic and the likelihood of persistent morbidity is high with aggressive surgery typical for malignant neoplasms, less invasive approaches to managing CSCS are warranted.
Differential action of angiotensin II on inward rectifier K^+ currents in atrial myocytes isolated from WKY rats and SHRs
Authors: K Sonoyama, Junichiro Miake, Yasutaka Yamamoto, Toshihiro Hamada, Kazuhide Ogino, Osamu Igawa, Ichiro Hisatome, Chiaki Shigemasa
Journal: Circulation (2006)
Adjuvant treatment modalities and outcomes in locally advanced rectal cancers without neoadjuvant treatment.
Authors: Neda Nikolic, Vladimir Nikolic, Davorin Z. Radosavljevic, Zorica Tomasevic, Nemanja Stanic, Suzana Rundic-Stojanovic, Jelena Spasic, Srdjan Nikolic
Journal: Journal of Clinical Oncology (2014)

e14622 Background: Treatment of locally advanced rectal cancer (LARC) has shifted to preoperative application of radiotherapy (RT) or combined chemo-radiotherapy (CRT). In patients with LARC without neoadjuvant treatment adjuvant RT with or without chemotherapy (CT) is mainstay of treatment. Methods: A cohort of 98 LARC patients (T3/T4) were treated postoperatively at single institution and prospectively followed. None of the patients received any neoadjuvant treatment before curative resection of the primary tumor. All patients were considered candidates for postoperative CRT based on a post operative pathology stage. Among them 28 patients refused postoperative RT and were treated with adjuvant CT. A matched pair analysis was performed by comparing the study group with control group which consisted of patients who received postoperative CRT. Matching was carried out for age, gender, T and N stage. Follow up data included recurrence rate, disease free survival and overall survival. The data was obtained from the hospital charts and analyzed with SPSS version 20. Results: A total of 56 patients were identified: median age 67 (range 44-78), 64% male, adjuvant CT: capecitabine 60%, 5FU 40%. In the median follow up of 50 months, 24 patients (43%) experienced recurrence of the disease: 14(25%) in the CRT group, 10(18%) in CT group, with no statistically significant differences between the two groups (p 0.280). Deaths occurred in 37% of all patients, without significant differences between the two groups (p 0,408). Conclusions: The outcomes of our patients were good after radical surgery and adjuvant CT. In this study we found no significant differences in outcomes between adjuvant CT vs CRT group in LARC patients operated for cure. Results of our study have to be interpreted taking into account limited number of patients, retrospective analysis of prospectively conducted observational study and not randomized design. Patients Relapse of disease 2-year recurrence rate 4-year recurrence rate mMdian DFS (months) Deaths 2-year survival rate 4-year survival rate Median OS (months) With RT 28 14 (25%) 64% 50% 43 12 89% 60% 51 Without RT 28 10 (18%) 67% 62% 53 9 89% 68% 58
Neoadjuvant treatment of soft tissue sarcoma: A single center experience.
Authors: Daniela Greto, Domenico Campanacci, Giovanni Beltrami, Ilaria Furfaro, Fiammetta Meacci, Laura Trombetta, Anna Mancuso, Rodolfo Capanna, Lorenzo Livi
Journal: Journal of Clinical Oncology (2014)

e21521 Background: The aim of this study is to evaluate disease free survival (DFS), overall survival (OS) and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma. Methods: Data of 38 consecutive patients affected by soft tissue sarcoma were retrospectively analyzed. Six (15.8%) patients were treated only with neoadjuvant radiotherapy (NRT), thirty-two (84.2%) high grade disease with neoadjuvant chemo-radiation therapy (NCRT) with the schedule: epirubicine (60 mg/m2 Day 1-2) and ifosfamide (1800 mg/m2 Day 1-5) administered every 28 days. Surgery was performed within 4-6 weeks after the completion of neoadjuvant treatment. Results: Median follow up was4.9 years (range: 1-13.7 years). All patients received preoperative external beam radiotherapy. The most part of patients (84.2%) underwent a neoadjuvant chemotherapy treatment associated with radiotherapy. After neoadjuvant treatment the majority of patients underwent wide excision (32 out of 38) and 5 patients had a marginal surgery, only one patient underwent amputation. Local recurrence was observed only in 2 patients (5.2%). 14 (36.8 %) patients experienced metastatic relapse. At the time of our analysis 13 patients (34.2%) were dead due to metastatic spread of the disease. In our series disease free survival (DFS) in relation to distant metastases (DM) showed a significant result for lower limbs involvement ( p=0.038) and marginal excision (p=0.024) predicted a worst DFS, histology resulted statistically significant but it was not evaluable the risk for specific histology due to the low number of events in the different subtypes. Conclusions: Results obtained from our study are encouraging about the feasibility and efficacy of preoperative RT, considering results in terms of local control, limbs sparing and safety. The use of preoperative chemotherapy did not result in a gain in clinical outcome.
Systemic mastocytosis manifested as chronic urinary symptoms for decades: A case report.
Authors: Aarati Poudel
Journal: Journal of Clinical Oncology (2014)

e18028 Background: Systemic mastocytosis is characterized by abnormal growth and accumulation of mast cells in various organs including skin, bone marrow, and viscera. Gastrointestinal symptoms and pruritis are the common manifestations in this disease and can significantly impair quality of life. Chronic urinary symptoms as the only presenting feature in indolent systemic mastocytosis have not been reported in the literature previously. Methods: In this report, we discuss the case of a 57 year old female patient with urinary symptoms of urgency, hesitancy and discomfort for a decade. With numerous empiric treatments, she had remained undiagnosed. She was incidentally found to have patches of mast cells with abundant eosinophils on a biopsy from distal ascending colon during routine colonoscopy. This led to further digging into the history and ultimately cystoscopy with biopsy. Histology revealed dense infiltrates of mast cell aggregates found in tryptase-stained biopsy sections. Bone marrow biopsy showed multiple focal infiltrates of eosinophilia and less than 5 % spindle shaped mast cells (CD 117 and tryptase positive). The mast cells were CD25 positive by immunohistochemistry and c-KIT D816V mutation testing was positive. Laboratory study revealed a normal white blood cell count with eosinophilia and an elevated serum tryptase level of 74 μg/l. Diagnosis of indolent systemic mastocytosis was made. The patient subsequently was put on antihistamine, which significantly improved her symptoms. Results: This case is the first reported case with chronic bladder symptoms as the only manifestation of systemic mastocytosis. Conclusions: Physicians should be aware of chronic bladder symptoms as a manifestation of systemic mastocytosis.
Abstract 17951: Body Fat and Cellular Aging: Important Players in Cardiac Aging
Authors: Vivian J Chow, Hannah H Chew, Jia-ing Wong, Ru San Tan, Woon-Puay Koh, Ren-Wei Wang, Michael Fenech, Caroline Bull, Louis L Teo, Jian-min Yuan, Angela S Koh
Journal: Circulation (2017)

Introduction: Telomere length (TL), a marker of cellular aging, has been linked to cardiovascular disease (CVD). Recent studies suggest that obesity (as defined by body-mass index (BMI) may induce ...