tbuckley/cabot-search huggingface dataset:
A phase II study of 3-week scheduling of irinotecan (I) in combination with cisplatin (P) (revised-IP) in patients with stage IIIB or IV non-small cell lung cancer (NSCLC)
Authors: H. Saito, S. Kudoh, K. Nakagawa, S. Negoro, K. Matsui, H. Senba, S. Tsukiyama, M. Takada
Journal: Journal of Clinical Oncology (2004)

7284 Background: A phase III study performed in Japan revealed the efficacy of combination therapy with I plus P given every 4 weeks (IP regimen) in patients with advanced NSCLC (Negoro et al. Br J Cancer 88:335–41, 2003). However, in that study there were considerable delays in treatment with or dose omissions of I because of leukopenia and/or diarrhea, and the dose intensity (DI) of I was only 30 mg/m2/week (range: 11.7–46.1) in contrast to the planned DI of 45 mg/m2/week. We therefore conducted a phase II study of revised-IP as a novel regimen to evaluate its response rate, safety and DI as measures of its feasibility in patients with advanced NSCLC. Methods: Eligible patients included those with histological or cytological diagnosis of NSCLC; no previous chemotherapy; age less than 75 years; and ECOG performance status of 0–1. Patients were treated intravenously with I 60 mg/m2 on days 1 and 8 and P 60 mg/m2 on day 1 every 3 weeks. Results: Of 28 patients enrolled, one patient did not receive the treatment and 27 were evaluable for response and toxicity. Baseline characteristics of the evaluable patients were as follows: median age of 63 (range 38–72); male/female, 19/8; PS 0/1, 11/16. The response rate was 30% (8 PRs) and the DI of I was 33.3 mg/m2/week (range: 9.3–40.0). The median number of cycles administered was 4 (range: 1–6). The major toxicities observed were leukopenia (grade 3: 26%, 4: 0%) and diarrhea (grade 3: 22%, 4: 0%). Other toxicities were generally mild. Conclusions: The revised-IP regimen is more feasible than the IP regimen, and its efficacy is equivalent to those of other regimens widely used. Further use of the revised-IP regimen will confirm that this regimen is useful in the treatment of advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.
Family history of breast cancer in Hodgkin disease and future risk for breast cancer.
Authors: Sarah Violet Colonna, Karen Curtin, Wendy Kohlmann, Jennifer A. Wright, Sean Tavtigian, Joshua David Schiffman
Journal: Journal of Clinical Oncology (2015)

1522 Background: Women with Hodgkin disease (HD) who undergo thoracic radiation have an extremely high risk of breast cancer (BC), up to 56x that of the average woman. The genetics underlying this increased BC risk is unclear, and we do not know if increased risk is observed in family members. We investigated BC risk among HD patients and relatives of women with HD. Methods: Using a genealogical database linked to Utah cancer data from 1966-2011, hazard ratios from Cox models were used to estimate BC risk among first-degree relatives (FDR) of women with HD. We compared female HD probands with BC (N=43) and HD probands without BC (N=837) to population controls age-matched 10:1. Results: The ‘baseline’ BC risk in FDR among BC patients in the Utah population (with no HD) is 1.8-fold (95%CI 1.7-1.8; P<0.0001). Among women with HD diagnosed before 2000 (higher radiation exposure) with subsequent BC, their FDRs are at 4-fold BC risk (95%CI 1.9-8.1; P<0.0001) compared to controls. Conversely, women with HD have markedly higher BC risk if they have FDR with BC compared to controls (HR=9.1, 95%CI 6.1-13.7; P<0.0001) and >2-fold BC risk compared to HD patients with no FDR with BC (95%CI 0.96-5.2; P=0.06). Conclusions: FDRs of women with HD and BC are at increased risk to develop BC beyond the general ~2-fold risk seen in FDRs of women with BC. Consistently, we found a very pronounced increase in BC among HD patients with FDRs with BC and 2x BC risk compared to HD patients with no BC in FDRs. This suggests an underlying genetic mechanism may predispose women with HD and their relatives to an increased risk for BC. Obtaining a BC family history at HD diagnosis may help personalize treatment around radiation therapy. Further investigation into HD treatment details related to familial and genetic for BC risk is warranted. BC risk among relatives and HD probands vs. controls. Relationship HR 95%CI P-value BC in HD probands with BC in FDR 9.2 6.1-13.7 <0.0001 FDR of HD probands with BC (before 2000) 4.0 1.9-8.1 <0.0001 FDR of HD probands with BC 3.3 1.7-6.1 0.0002 HD probands w/BC in FDR vs. HD no BC in FDR (case-case comparison) 2.3 <1.0-5.2 0.06 BC in HD probands, no BC in FDR 2.2 1.4-3.3 0.0003 FDR of BC probands (no HD) 1.8 1.7-1.8 <0.0001 FDR of HD probands with no BC 0.9 0.7-1.2 0.81
Myocardial expression of Toll‐like receptor 4 predicts the response to immunosuppressive therapy in patients with virus‐negative chronic inflammatory cardiomyopathy
Authors: Cristina Chimenti, Romina Verardo, Fernanda Scopelliti, Claudia Grande, Nicola Petrosillo, Pierluca Piselli, Ruggero De Paulis, Andrea Frustaci
Journal: European Journal of Heart Failure (2017)
Frequency of severe neutropenia occurring as an adverse events of gemcitabine plus cisplatin chemotherapy in patients with recurrent biliary tract cancer compared to those with unresectable biliary tract cancer.
Authors: Noriko Fujishiro, Shuichi Mitsunaga, Akira Shinohara, Misaki K Takeno, Hideki Funazaki, Gen Kimura, Kazuo Watanabe, Kumiko Umemoto, Mitsuhito Sasaki, Hideaki Takahashi, Hiroshi Imaoka, Yusuke Hashimoto, Izumi Ohno, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2017)

488 Background: In patients (pts) with biliary tract cancer (BTC), relapse occurs at a high frequency even after curative resection. It remains unclear whether in pts with postoperative recurrence receiving chemotherapy, the surgery exerts any influence on the risk of development of toxicities. The aim of this study was to compare the outcomes and incidences of adverse events between recurrent BTC (rBTC) pts and unresectable BTC (uBTC) pts receiving gemcitabine plus cisplatin chemotherapy (GC). Methods: Data of pts with rBTC or uBTC receiving GC as the first-line chemotherapy were analyzed. The GC regimen consisted of gemcitabine 1000 mg/m 2 plus cisplatin 25 mg/m 2 on days 1 and 8, administered every 3 weeks. All adverse events occurring during the first 180 days of GC were evaluated according to CTCAE, version 4.0. Results: A total of 151 pts, including 55 pts with rBTC and 96 pts with uBTC, were enrolled. In regard to the baseline characteristics, no significant differences between the rBTC and uBTC groups were found in the gender distribution [male: 69% vs. 57%], age [median: 68 vs. 68], or ECOG performance status (PS) [PS0: 67%vs. 55%]. The distribution of the primary tumor site (intrahepatic bile duct [27% vs. 33%] / extrahepatic bile duct [45% vs. 20%] / gallbladder [20% vs. 44%] / ampulla [7% vs. 3%]) was unbalanced between the two groups ( p &lt; 0.01). The overall survival (OS) was significantly longer in the rBTC group than that in the uBTC group [median 15.8 months vs. 10.0 months, p = 0.02], however, there was no significant difference in the progression-free survival [median 6.8 months vs. 5.8 months] between the two groups. Grade 3-4 neutropenia was more frequent in the rBTC group [69%] as compared to that in the uBTC group [44%, p &lt; 0.01], whereas Grade 3-4 cholangitis was significantly less frequent in the rBTC [5%] group than that in the uBTC group [21%, p = 0.02]. Conclusions: The incidence of Grade 3-4 neutropenia developing during GC was significantly higher in the rBTC group as compared to that in the uBTC group.
Underwater endoscopic mucosal resection for complete R0 removal of a residual adenoma at a perforated scar in a patient with colostomy
Authors: Kazuya Hosotani, Kenichiro Imai, Kinichi Hotta, Sayo Ito, Hiroyuki Ono
Journal: Endoscopy (2017)

Endoscopic mucosal resection (EMR) of residual polyps is technically challenging, as submucosal fibrosis from the initial resection makes it difficult to lift the lesion during submucosal injection and to snare the entire tumor [1]. Endoscopic submucosal dissection (ESD) enables complete removal of such residual polyps [2] but presents some technical difficulties and is time-consuming [3].
The impact of TAS3681, a new type of androgen receptor antagonist, on aberrant AR signaling that drives tumor resistance to AR-targeted therapies by down-regulating full length and splice variant AR.
Authors: Daisuke Kajiwara, Kazuhisa Minamiguchi, Masanao Seki, Hiroya Mizutani, Keisuke Yamamura, Shigeo Okajima, Eiji Sasaki, Teruhiro Utsugi, Yoshikazu Iwasawa
Journal: Journal of Clinical Oncology (2017)

197 Background: The treatment of castration-resistant prostate cancer (CRPC) has changed dramatically with the use of two new therapies, enzalutamide and abiraterone, directed at the androgen receptor (AR) signaling axis. However, eventually almost all patients relapse after these agents because of acquired resistance by a variety of mechanisms such as AR overexpression, the occurrence of AR mutations, or the induction of AR splice variants that confer ligand independent AR transactivation. TAS3681 is an oral pure AR antagonist with AR down-regulating activity. In this study, we investigated the effect of TAS3681 on several issues related to resistance to current AR-targeted therapy. Methods: VCaP cells transfected with wild-type AR-expressing vector, which overexpress AR, were treated with TAS3681 in the presence of androgen. Cells were harvested and luciferase activity was determined. For the analysis of F876L mutant AR, LNCaP cells stably expressing F876L AR protein were incubated with TAS3681 in the presence of androgen. The WST-8 assay was performed to measure cell viability. Prostate cancer cells expressing AR-v7 were treated with TAS3681, and full length (FL)-AR and AR-v7 protein levels were determined by Western blot. TAS3681 was orally dosed to confirm AR down-regulation in tumor and evaluate antitumor efficacy in AR-v7 positive CRPC tumor xenograft mouse model. Results: In prostate cancer (PCa) cells which overexpress AR, in contrast to enzalutamide, TAS3681 effectively suppressed AR transactivation and cell proliferation via AR down-regulation. TAS3681 effectively antagonized F876L mutant AR which confers resistance to cell growth inhibition by enzalutamide. Moreover, TAS3681 reduced both FL-AR and AR-v7 protein level in PCa cells in vitro and in vivo, and showed strong antitumor efficacy in AR-v7 positive xenografts. Conclusions: TAS3681 disrupts the aberrant AR signaling via a novel mechanism of action: pure AR antagonism plus down-regulation of full-length and splice variant AR. These findings suggest that TAS3681 has the potential to overcome resistance to current AR pathway target drugs.
Why do breast cancer patients visit the emergency department?
Authors: Swati Kulkarni, Abdullah Nasser
Journal: Journal of Clinical Oncology (2015)

e12046 Background: Breast cancer (BC) is the second most common malignancy in cancer patients presenting to the emergency department (ED). Very few studies investigated this population’s ED utilization. Methods: In this retrospective review, 619 ED visits by 176 BC patients in Southwestern Ontario were analyzed. We identified all BC patients who presented to the ED during a one year period, and then tracked all their ED visits from the date of BC diagnosis. The median follow-up time was 2.35 years. Results: The average age of patients presenting to the ED was 61 years. Approximately half the patients presented three or more times since the date of their BC diagnosis. A third of ED visits were preceded by a chemotherapy treatment within 30 days; a majority of those visits were within 8 days of treatment. Patients who presented while on chemotherapy were younger, and more likely to be admitted. A fifth of visits resulted in an admission and the average hospitalization was 8.5 days. Pain, general weakness and shortness of breath were the most common presenting complaints. The most common ED diagnoses were pain, metastatic disease, and cellulitis. The most common discharge diagnoses were metastatic disease, febrile neutropenia, and pain. Conclusions: Better pain and symptom management in BC patients, especially those receiving chemotherapy, can significantly decrease their ED utilization and is likely to improve their quality of life.
E7080 (lenvatinib) in addition to best supportive care (BSC) versus BSC alone in third-line or greater nonsquamous, non-small cell lung cancer (NSCLC).
Authors: Libor Havel, Jong-Seok Lee, Ki Hyeong Lee, Paolo Bidoli, Joo-Hang Kim, David Ferry, Young-Chul Kim, Gyorgy Losonczy, Nicola Steele, In Sook Woo, Lea Forst, Yi Ma, Mark Joel Shelton, Fabrina Bologna, Brian Huber, Harish P. Dave
Journal: Journal of Clinical Oncology (2014)

8043 Background: Lenvatinib (E7080; LEN) is an oral, tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT, and PDGFRβ with evidence of antitumor activity in a broad range of solid tumors. Currently there is an unmet medical need for treatments in third-line or greater NSCLC patients (pts). Methods: This study was a double-blind, placebo-controlled, multicenter, randomized Phase II study of LEN 24 mg PO once daily + BSC vs. placebo (PBO) + BSC (2:1 randomization). Pts with nonsquamous NSCLC who had failed ≥ 2 two systemic anticancer regimens were enrolled. Prior erlotinib or gefitinib was required for pts with known EGFR-activating mutations. The primary endpoint was overall survival (OS). Progression free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were based on investigator assessment. Efficacy endpoints were estimated via Kaplan-Meier. Results: 135 pts enrolled in the study. Per protocol, the study was unblinded and analyzed after 90 deaths. 76% received ≥ 3 prior anti-cancer regimens and 85% received prior erlotinib or gefitinib (similar rates in each arm). A summary of efficacy and safety is presented by study arm (Table). In a post hoc analysis, a similar treatment effect was observed among subjects with wild-type EGFR. Conclusions: LEN in addition to BSC demonstrated a clinically meaningful improvement in both OS and PFS (~ 3 months) in heavily pretreated patients with NSCLC, including those who received prior EGFR inhibitors. LEN was generally well-tolerated, with an AE profile consistent with observed LEN monotherapy studies. These data warrant additional evaluation of LEN in this population. Clinical trial information: NCT01529112. Median value or percentage LEN + BSC (n=89) PBO + BSC (n=46) P value OS, wks (95% CI) 38.4 (26.57, 47.86) N=58 events 24.1 (15.29, 36.43) N=37 events p = 0.065 PFS, weeks (95% CI) 20.9 (15.86, 23.86) N=73 events 7.9 (7.43, 8.14) N=45 events p < 0.001 ORR 10.1% 2.2% 0.1635 DCR 42.7% 19.6% 0.0079 Treatment duration (days) 113 58 Not compared (NC) Serious adverse events (AEs) 52% 46% NC Grade 3/grade 4 AEs: Hypertension Dyspnea Pneumonia 69% 17% 9% 9% 50% 0% 13% 6.5% NC Study discontinuation due to AE 24.7% 17.4% NC
Kansas cancer survivors: An opportunity for lifestyle modification targeting primary and secondary cancer prevention.
Authors: Jennifer R. Klemp, Mickey H.C. Wu, Julie Sergeant
Journal: Journal of Clinical Oncology (2017)

233 Background: Cancer survivors are at increased risk for cancer recurrence and new primary cancer, and engage in lifestyle behaviors that can adversely affect risk and quality of life. Primary care physicians and oncologists are in a position to refer patients to evidence-based interventions for primary and secondary cancer prevention. This study aims to gain an understanding into the diagnostic characteristics of cancer survivors and lifestyle behaviors between persons ever diagnosed and never diagnosed with cancer in Kansas. Methods: Data from Kansas Cancer Registry (KCR) was used to examine the diagnostic characteristics by cancer status: cancer survivor (diagnosed and alive) or non-survivors (diagnosed and deceased). Group differences in selected characteristics were evaluated by t-tests and chi-square tests. Logistic regression was applied to assess the odds of being a survivor based on stage of diagnosis. The 2014 Kansas Behavioral Risk Factor Surveillance System (KS-BRFSS) data was used to compare health risk behaviors, health status, and health care access between persons ever diagnosed and never diagnosed with cancer. Distributions of both groups were evaluated by linear and logistic regression to produce adjusted percentages. Results: Significant group differences were observed between cancer survivors and non-survivors.The odds of being a non-survivor were 11.6 times greater for those initially diagnosed at a distant stage compared to those diagnosed with localized disease. Survivors were significantly more likely to be older, female, and retired; and were significantly more likely to be current smokers, physically inactive, and emotionally unhealthy. Conclusions: Cancer survivors are now living longer with and through their disease, but in our study reported an increase in unhealthy behaviors compared with those never diagnosed with cancer. Results from this study indicate the need of survivor health education and access to care, and provider continuing education (for both primary care physicians and oncologists), targeting lifestyle behaviors associated with cancer and chronic disease management.
Contents, Vol. 41, 1984
Authors: Harold Levitan, Robert C. Smith, G.C. Lyketsos, A. Karabetsos, J. Jordanoglou, T. Liokis, A. Armagianidis, C.G. Lyketsos, Nancy L. Hutner, Steven E. Locke, Reinhold Schwarz, Siegfried Geyer, James Georgas, Eliza Giakoumaki, Nikos Georgoulias, Eugene Koumandakis, Dionysios Kaskarelis
Journal: Psychotherapy and Psychosomatics (1984)
HER2 expression on circulating tumor cells (CTC) in patients with early HER2-positive breast cancer: Results of the German SUCCESS B trial.
Authors: Bernadette Anna Sophia Jaeger, Brigitte Kathrin Rack, Julia Katharina Neugebauer, Ulrich Andergassen, Carola Anna Melcher, Doraid Mouarrawy, Gabriele Ziemendorff, Michael Clemens, Ekkehard von Abel, Georg Heinrich, Katharina Schueller, Andreas Schneeweiss, Werner Lichtenegger, Matthias W. Beckmann, Klaus Pantel, Harald Leo Sommer, Klaus Friese, Wolfgang Janni
Journal: Journal of Clinical Oncology (2012)

10540 Background: Recent reports showed a discrepancy in the Her2-status of metastases or minimal residual disease in blood and bone marrow compared to the primary tumor in patients with breast cancer. The Her2-status of CTC was prospectively evaluated in the German multicenter SUCCESS B study. Methods: The SUCCESS B trial is a randomized Phase III study comparing FEC-Docetaxel (Doc) vs. FEC-Docetaxel-Gemcitabine (Doc-G) as well as Her2 targeted therapy with Trastuzumab as adjuvant treatment in patients with early, Her2 positive, node positive or high risk node negative primary breast cancer. As part of the translational research program, 23ml of peripheral blood were drawn before adjuvant chemotherapy. In 638 samples CTC and Her2-status were assessed using the CellSearch System (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for Her2 phenotyping. Cutoff for CTC-positivity was ≥1 CTC and for Her2 ≥1 CTC with strong Her2-staining (+++). Results: 40.2% of pts (n=257) were positive for CTC (mean 4.52; range 0-1689). The number of detected CTC was distributed as follows: 1 CTC (n=112; 43.6%), 2 CTC (n=65; 25.3%), 3 CTC (n=36; 14.0%), 4 CTC (n=12; 4.7%) and ≥5 CTC (n=31; 12.1%). Her2 status on CTC was negative or weak in 12.5% (n=32) and 8.9% (n=23) of CTC positive patients respectively and therefore categorized as Her2 negative. In 21.4% (n=55) we detected moderate and in 57.2% (n=147) strong Her2-staining of ≥1 CTC per sample. Therefore 57.2% of CTC-positive samples were diagnosed as Her2 positive and 21.4% as questionable. No association was found between the detection of CTC or the Her2-status on CTC with tumor size, histopathological grading, hormone receptor status or axillary lymph node involvement. Conclusions: The data of this trial confirms the frequent discordance of Her2 expression on CTC compared to the primary tumor. Survival data within the Success B trial will give further insight into the tumor biology of Her2 positive disease and the role of the Her2-status on CTC to predict treatment efficacy.
Effect of GDC-0449, a hedgehog (Hh) pathway inhibitor, on tumor activity and on erlotinib and cisplatin in a xenograft model of non-small cell lung cancer (NSCLC) with activated Hh pathway.
Authors: Aamir Ahmad, Fazlul H. Sarkar, Main Maitah, Shadan Ali, Seema Sethi, Amro Aboukameel, Shirish M. Gadgeel
Journal: Journal of Clinical Oncology (2012)

e21057 Background: We have previously shown that chronic exposure of A549 NSCLC cell line to TGF-β1 can induce epithelial-mesenchymal transition (EMT) and can make these cell lines (A549-M) resistant to erlotinib, an EGFR inhibitor and cisplatin. EMT in A549-M cells was associated with significant activation of signaling through the Hh pathway. We therefore evaluated the activity of GDC-0449, an inhibitor of the Hh pathway, and assessed its activity in combination with erlotinib and cisplatin in A549-M cells both in vitro and in vivo. Methods: We assessed the effects of GDC-0449 (20 nM) on clonogenic growth (colony formation assay), cell motility (wound healing assay) and invasion (matrigel assay) in A549-M cells, and also assessed the activity of GDC-0449 in combination with erlotinib and cisplatin both in vitro (MTT assay) and in an experimental lung metastasis animal model in vivo by injecting A549-M cells through tail vein. Results: A549-M cells showed significantly higher rate of clonogenic growth, cell motility and invasion in vitro and a greater propensity to form metastases in vivo compared to parental A549 cells, and also showed higher resistance to erlotinib and cisplatin. A549-M cells showed higher mRNA levels of Shh (sonic hedgehog, a ligand of the Hh pathway) and ZEB1 and reduced levels of E-cadherin than A549 cells. GDC-0449 significantly reduced growth of A-549-M cell in vitro but had no effect on A-549 cells. GDC-0449 also reduced clonogenic growth, cell motility and invasion of A549-M cells. Pre-treatment with GDC-0449 significantly enhanced the activity of erlotinib (5 and 10 mM) and cisplatin (1mM-10mM) in A549-M cells (p &lt; 0.05) but not in A-549 cells. GDC-0449 reduced the number of lung metastases in the xenograft model and enhanced the activity of erlotinib and cisplatin in this model. Conclusions: This data suggests that the EMT phenotype in NSCLC may be associated with the activation of the Hh signaling pathway. It also suggests that GDC-0449 has anti-tumor activity against NSCLC with activated Hh pathway, and can enhance the effects of erlotinib and cisplatin in such tumors.