tbuckley/cabot-search huggingface dataset:
Evolution of sub-clinical metastases in breast cancer
Authors: P. J. Catanzaro
Journal: Journal of Clinical Oncology (2008)

12024 Some early stage breast cancer patients bear sub-clinical nodal and/or distant metastases. After primary extirpation, the proportion of failure is lower than would be expected in non-dissected axilla patients and in bone marrow biopsy positive patients. This meant that only some sub-clinical metastases progressed. Since tumor cells continually immigrate into distant or regional sites, but this stops after surgery, progression vs. extinction depends on the unlimited self renewal capability of the resident cells. In turn, this suggested a role for stem cells, specifically their number and character. The number of stem cells in a sub-clinical metastatic focus (regional or distant) can vary considerably from as few as single digits to a hundred thousand. The variation depended on both the size of the tumor at the time of metastatic transformation vs. time of surgery and on the self renewal probability of resident stem cells (Psr). The extinction probability of a single stem cell (E) depends on its Psr. Combining E with N (stem cell number) enables calculation of the probability of extinction (Pext) of a metastatic focus containing multiple stem cells. Once the focus exceeded 120 stem cells (within the clinical range of interest), progression was assured. Below that number survival or extinction of the metastatic focus depended both on Psr and N. Higher Psr and lower N results in lower Pext. It would seem that stem cell character and number determine the fate of metastatic foci. No significant financial relationships to disclose.
Circulating tumor cells (CTCs) and endothelial cells (CECs) in the diagnosis of malignant pleural mesothelioma (MPM): A single institutional prospective study
Authors: K. Yoneda, F. Tanaka, M. Hashimoto, T. Takuwa, S. Matsumoto, Y. Okumura, N. Kondo, S. Hasegawa, T. Tsujimura, K. Fukuoka, T. Nakano
Journal: Journal of Clinical Oncology (2009)

e22107 Background: Circulating tumor cell (CTC), a surrogate of distant metastasis, and circulating endothelia cell (CEC), a surrogate of angiogenesis, are potentially useful in the diagnosis of malignant tumors. Following a promising result of our preliminary study showing the diagnostic value of CTC/CEC in malignant pleural mesothelioma (MPM)(Tanaka F, et al. ASCO 2008), we conducted a prospective study. Methods: Patients (pts), who presented at our institute with suspicion or diagnosis of MPM, were eligible in the study. CTCs and CECs in peripheral blood (7.5mL and 4.0mL, respectively) were captured and quantitatively evaluated with the “CellSearch” system without knowledge of clinical characteristics of patients. Results: A total of 92 pts were enrolled into the study, and the final diagnosis was MPM in 68, other malignant tumors in 7, and non-malignant diseases in 17 pts ( Table ). CTC was positive (CTC-count, 1 or more per 7.5mL of the peripheral blood) in 35%(24/68) of MPM pts (range of CTC-count, 0–27 cells/7.5 mL). Among non-malignant pts, 3 pts (18%) showed a positive-CTC, but no patient showed 2 or more CTCs in 7.5mL of the peripheral blood. The mean CEC-count (/4.0mL) was significantly higher in MPM pts than in non-malignant pts (105.1 versus 40.2; p=0.047). When the cut-off value of CEC-count for the diagnosis of MPM was defined as 50(cells/4.0mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of malignant diseases were 66%, 70%, 93%, and 26%, respectively. There was no correlation between CTC-positivity and clinical stage of MPM pts, but was a trend of increase in the mean CEC-count along with tumor progression (mean CEC-count for stage I, II, III, and IV pts: 63.0, 82.4, 95.6, and 116.7, respectively). Conclusions: CTC and CEC are useful clinical markers in the diagnosis of MPM. [Table: see text] No significant financial relationships to disclose.
Early epirubicin (EPI)-induced myocardial dysfunction revealed by serial tissue doppler imaging (TDI): Correlation with inflammatory and oxidative stress markers
Authors: G. Mantovani, G. Mercuro, M. Dessi’, C. Madeddu, R. Serpe, E. Massa, C. Cadeddu, A. Piras
Journal: Journal of Clinical Oncology (2008)

20517 Background: Anthracycline-induced cardiotoxicity is potentially fatal and can impair patient quality of life: it increases exponentially with cumulative dose and its early detection is crucial to prevent clinical heart failure (HF). Methods: A phase II, open, non randomized trial. Inclusion criteria: patients 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥ 55%; ECOG PS 0–2, no history of cardiac disease, hypertension, diabetes mellitus and previous mediastinal irradiation. Conventional echocardiography as well as TDI with Strain (Σ) and Strain Rate (SR) (a very accurate technique in detecting minimal changes in the cardiac left ventricular (LV) function), circulating levels of biochemical markers of both myocardial damage and inflammation/oxidative stress were assessed at baseline, 24 hours and 7 days at a cumulative EPI dose of 100, 200, 300, and 400 mg/m2, respectively. Aim of the study: to detect early preclinical changes predictive of the risk for HF and compare them with biochemical/inflammatory markers. Results: 16 patients were enrolled. A significant impairment of the systolic LV function was observed at EPI 200 mg/m2: the SR peak decreased significantly (p<0.001) whereas the Σ remained unchanged. Significant changes of LV diastolic function by TDI occurred only at EPI 300 mg/m2: a decrease of conventional E/A (p=0.02), Em wave (p=0.03) and Em/Am ratio (p=0.002) without significant changes of LVEF. IL-6, sIL-6R and ROS increased, whilst GPx decreased significantly at EPI 200 mg/m2. A significant correlation (by Pearson’s t-test) between the SR peak decrease (ΔSR) at EPI 200 mg/m2, increase of IL-6/ROS (p=0.0031 and p=0.0002, respectively) and decrease of GPx (p=0.03) was observed. The multiple regression analysis showed that only ROS level was predictive of ΔSR (p=0.0167). Conclusions: Subtle cardiac abnormalities may occur at EPI doses significantly below those potentially clinically harmful. Earliest myocardial impairment affects the LV systolic rather than diastolic function and was associated with high ROS and inflammation markers. A higher sample size may allow to show the clinical meaningfulness of our study. No significant financial relationships to disclose.
Does adjuvant chemotherapy improve survival in non small cell lung cancer (NSCLC)? A pooled-analysis of 6494 patients in 12 studies, examining survival and magnitude of benefit
Authors: E. Bria, R. J. Gralla, H. Raftopoulos, G. Ferretti, A. Felici, C. Nisticò, F. Cuppone, E. Terzoli, F. Cognetti, D. Giannarelli
Journal: Journal of Clinical Oncology (2005)

7140 Background. Multiple randomized trials investigating the benefit of adjuvant chemotherapy in the post-operative setting in NSCLC have yielded conflicting results. With over 6000 patients included, we analyzed results of 12 reports over the past 10 years, in which patients received either platinum-containing chemotherapy (11 with cisplatin) or no chemotherapy. Methods. All phase III randomized trials and meta-analyses published as peer-reviewed papers or as abstracts from 1994 to 2004 were eligible. A pooled analysis was performed; event-based relative risk ratios (RR) with 95% confidence interval (CI) were derived. Primary end-points were overall survival (OS) and disease-free survival (DFS). Several sub-populations were also examined as in the table. Combined effect estimation was computed with both fixed- and random-effect model. An heterogeneity test was applied. Results. Eleven trials plus a meta-analysis (6494 patients) were gathered. When data were pooled and plotted, significant differences in favor of chemotherapy were seen in OS and DFS in the entire study population and in sub-populations; relative benefits of 6–13% and 10–11%, respectively. DFS benefits were greater than OS in all analyses. No significant heterogeneity was observed. Conclusions. Survival benefits with adjuvant chemotherapy are significant when: 1) all patients and studies are analyzed, and 2) when each sub-population (by stage, trial size, or publication/presentation type) is considered, given the limitations of pooled analysis. 3) The magnitude of benefit (RR 0.93) with this large population, and in sub-populations, appears to be smaller than generally perceived, raising issues of importance when considering the risks and benefits of treatment. No significant financial relationships to disclose.
Effect of AbGn-7, a glycotope-specific monoclonal antibody, on apoptosis in colon cancer cells and tumor growth in xenograft models
Authors: S. Lin, E. Chiang, Y. Tsai, S. Lee, B. Kuo, R. Lin
Journal: Journal of Clinical Oncology (2009)

e15118 Background: While clinical benefit against colorectal cancer has been observed with therapeutic monoclonal antibodies such as bevacizumab, cetuximab and panituzumab, the death rate of advanced colorectal cancer remains high that warrants further development of more potent therapeutics. Methods: A cell-based immunization approach was used to generate monoclonal antibodies against targets expressed on human colorectal cancer cells. A chimeric monoclonal antibody, AbGn-7, was selected and evaluated for the potential clinical use to treat colorectal cancer. Results: Expression of AbGn-7 antigen: Carbohydrate competition assay demonstrated that AbGn-7 recognizes a Lewis-A-like carbohydrate antigen (AbGn-7 antigen). Immunohistochemical studies showed that AbGn-7 antigen is expressed in colorectal cancer tissue. No significant binding could be detected in non-tumor tissues except in the epithelia of GI track. Effector function of AbGn-7: AbGn-7 triggered dose-dependent apoptosis in COLO 205 colon cancer cell. In addition, AbGn-7 elicited potent complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) in a dose-dependent manner. Molecular mechanism of apoptosis induced by AbGn-7: Tunel assay, PARP cleavage assay as well as caspase inhibitor studies demonstrated that AbGn-7 induced apoptosis in COLO 205 colon cancer cells via a caspase-independent pathway. Xenograft study: AbGn-7 alone, or in combination with 5FU-Leucovorin, effectively inhibited the growth of COLO 205 xenograft in SCID mice and prolonged their survival. Conclusions: The results of the present study suggest that AbGn-7 is a potential candidate for effective treatment of colorectal cancer. [Table: see text]
Localization of yttrium 90 ibritumomab tiuxetan (<sup>90</sup>Y IT) in patients with CD20 + non-Hodgkin’s lymphoma (NHL)
Authors: S. A. Jacobs, S. A. Swerdlow, N. Avril, N. Vidnovic, K. A. Foon, A. M. Harrison, K. S. McCarty
Journal: Journal of Clinical Oncology (2005)

2547 Background: Yttrium-90 ibritumomab tiuxetan (90Y IT, Zevalin) is effective treatment for relapsed or refractory low-grade, follicular, or transformed B-cell NHL although affected lymph nodes may not visualize on pre-treatment imaging with indium-111 IT. Our aims were to assess cellular localization, determine spatial distribution of 90Y IT, and correlate the density of 90Y IT with treatment response. Methods: To evaluate cellular localization and spatial distribution of 90Y IT in nodal tissue and bone marrow, we performed autoradiography on tissues sampled after therapy. Eligible patients had CD20+ NHL, a bulky peripheral lymph node, positive bone marrow biopsy, and were scheduled for 90 Y IT as part of their treatment plan. Histologic classifications included follicular (n = 2), mantle cell (n = 1) and small lymphocytic (n = 1) lymphomas. PET-CT scans were performed prior to 90 Y IT administration and at 12 weeks. Bone marrow, lymph node, and blood samples were taken 4 days after 15 MBq/kg 90Y IT administration and processed for histology, scintillation counting, and microscopic autoradiography. Results: Clear pericellular localization of labeled IT to lymphoma cells was observed in the involved areas of lymph node and bone marrow, with absence of significant localization in histologically normal sections of bone marrow. However, spatial distribution of grains was not uniform throughout affected lymph nodes and varied with each patient. The 90 Y IT binding in the affected lymph node sampled appeared to correlate with response on PET-CT imaging with 1 complete response, 1 partial response and 1 non-response and 1 too early to evaluate. Conclusions: 90 Y IT localizes to the surface membrane of CD 20+ lymphoma cells in affected lymph nodes and bone marrow. Spatial distribution of bound 90 Y IT in the nodal tissue is not uniform. Work is in progress to determine if non-uniform distribution is biologically significant and to estimate the radiation dose delivered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioGen IDEC BioGen IDEC
Abstract 357: A glial origin for medulloblastoma and inhibition of MYCN stabilization.
Authors: Sara Bolin, Jasmine Lau, Vasil Savov, Justin Chen, Anders I. Persson, Sanna-Maria Hede, William A. Weiss, Fredrik J. Swartling
Journal: Cancer Research (2013)

Abstract The origin of MYCN-driven medulloblastoma, a poor-prognosis childhood brain tumor is not known. We recently showed that MYCN could generate tumors with high penetrance from a glutamate transporter (GLT1) promoter in a transgenic model (GTML) of medulloblastoma. By using Rosa26-lsl-LacZ reporters we also showed that GLT1-positive neural stem cells (NSCs) from normal brain represent putative cells of tumor origin. GTML mice generate aggressive MYCN-driven medulloblastoma 2-3 months after birth. BrdU-labeling of 3-week-old GTML mice detected significantly more proliferation in thalamic forebrain cells and of BrdU/BLBP-double positive Bergmann glia in the cerebellum as compared to corresponding normal brain. Retroviral tagging with the RCAS/tv-a system marked BLBP- or GFAP-positive tumor initiating cells and expression analysis could further determine genetic profiles of tumor origin. Interestingly, MYCN levels and early proliferation of brain tumors could be reduced by specific inhibition of CDK2 or by using the bromodomain inhibitor JQ1. Both treatment strategies induced tumor cell senescence as seen by SA-beta-gal activity and by downregulated Lamin B1. Our results propose a radial glial or a Bergmann glial origin for MYCN-driven medulloblastoma and further suggest ways to inhibit tumor growth by repressing MYCN stabilization. Citation Format: Sara Bolin, Jasmine Lau, Vasil Savov, Justin Chen, Anders I. Persson, Sanna-Maria Hede, William A. Weiss, Fredrik J. Swartling. A glial origin for medulloblastoma and inhibition of MYCN stabilization. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 357. doi:10.1158/1538-7445.AM2013-357
Patient surveillance following curative-intent treatment for breast carcinoma: Current practice patterns.
Authors: J. A. Margenthaler, E. Allam, L. Chen, K. S. Virgo, U. Kulkarni, A. Patel, F. E. Johnson
Journal: Journal of Clinical Oncology (2010)

9110 Background: Although the management of potentially curable breast cancer is well standardized, the optimal regimen to monitor patients after initial therapy is less clear. The purpose of the current study was to determine how physicians monitor their patients after curative-intent treatment for breast cancer. Methods: A custom-designed survey instrument with four idealized patient vignettes (TNM stages 0 - III) was emailed to the 3245 members of the American Society of Clinical Oncology (ASCO) who identified themselves as having breast cancer as a major focus of their practice. Respondents were asked how they use 12 specific follow-up modalities during years 1 to 5 for each vignette. Mean, median, standard deviation, and range of the intensity of use for each modality was calculated for the 4 vignettes. Results: Of the 3245 ASCO members surveyed, 1012 (31%) responded. Of these, 812 were evaluable and included in the analysis. Respondents included 72.6% medical oncologists, 14.6% surgeons, 11.6% radiation oncologists, and 1.2% other. The percentage of their practice devoted to breast cancer patients was >50% for 47.9% of respondents, 26-50% for 21.6%, 11-25% for 22.7%, and ≤10% for 7.9%. Office visit, mammogram, complete blood count, and liver function tests were the most commonly recommended methods of surveillance. There was marked variation in the follow-up intensity. For example, office visit was used 4.1 ± 2.2 times in year 1 following curative treatment of a Stage III breast cancer. The corresponding median and range were 4 and 1-12. Similar variation was observed for all modalities. Conclusions: This is the largest survey of its kind to date. The intensity of post-treatment surveillance performed by ASCO members caring for patients with breast cancer varies markedly. The lack of consensus is likely due to multiple factors, including the limited evidence supporting any particular strategy. No significant financial relationships to disclose.
Transcatheter Closure versus Medical Therapy of Patent Foramen Ovale and Presumed Paradoxical Thromboemboli
Authors: P Khairy, CP O'Donnell, MJ Landazberg
Journal: Annals of Internal Medicine (2003)

Paradoxical thromboembolism through a patent foramen ovale may be an important mechanism of cryptogenic stroke. This review shows that transcatheter closure of a patent foramen ovale is associated ...
Combination with zoledronic acid (ZA) and sunitinib (SU) to reduce severity of osteolytic lesions in bone metatstases.
Authors: C. Schem, D. O. Bauerschlag, A. Lorenzen, S. Tiwari, H. Kalthoff, C. C. Glueer, W. Jonat
Journal: Journal of Clinical Oncology (2010)

1089 Background: Skeletal metastases are observed frequently in patients with breast cancer (BC). High osteoclast activity with bone resorption is a feature of most bone metastases. Bisphosphonates are established as the main treatment. The treatment delays the rate at which skeletal-related events occur and with regards to study results provide a DFS benefit to patients with early BC. This opens the possibility of new preventive treatment regimens that could interfere with the tumor cell-osteoclast interaction. SU is an oral multitarget TKI that demonstrated anti-angiogenesis activity. In this study the preventive potential of a SU and ZA combination is tested in a mouse xenograft model of breast cancer bone metastases. Methods: DsRed2-labelled bone-metastatic MDA-MB231 cells were injected into the left ventricle of nude mice. One group of mice (n=10 each) was treated with 40mg/kg SU (orally/daily), another group were treated with ZA at 20ug/kg/week, starting one day before injection of tumor cells. A third group was given the combination of SU and ZA and the fourth group was injected with vehicle control only. Tumor development was monitored by measuring fluorescent signals in vivo and x-ray measurements. Osteolytic lesions were monitored by optical imaging using near infrared bone mineral binding dyes Osteosense 680 and Bonetag injected i.p. Results: Nonradiographic detection of metastatic lesions correspond to metastatic lesions as confirmed by x-ray measurements (mm2). Numbers of lesions as analyzed by x-ray and immunohistochemistry are significantly less after 6 weeks of treatment with the combination of SU and ZA compared to monotherapy. The preventive protocol with ZA and SU does not increase survival. Conclusions: In this model of bone metastases, combination treatment with ZA and SU resulted in a significant reduction in the extent of osteolytic skeletal lesions in bone as compared to zoledronic acid treatment alone. The near infrared bone mineral binding dyes may be a future alternative to x-ray measurements in assessing osteoblastic and osteolytic lesions in bone metastases and gives insights into disease biology. No significant financial relationships to disclose.
640. AdCD40L Immunostimulatory Gene Therapy in Combination with Cyclophosphamide Prolongs 6-Months Survival in a Phase I/II Trial for Malignant Melanoma
Journal: Molecular Therapy (2014)

AdCD40L Immunostimulatory Gene Therapy in Combination with Cyclophosphamide Prolongs 6-Months Survival in a Phase I/II Trial for Malignant Melanoma
Surgical specimen handling for conjunctival melanoma: Implications for local control, tumor thickness, and sentinel lymph node biopsy
Authors: B. Esmaeli, R. Banay, H. Diwan
Journal: Journal of Clinical Oncology (2005)

7564 Background: To evaluate conjunctival melanoma surgical specimens for their ability to provide reliable information about margins of resection and tumor thickness. Methods: The excisional biopsy specimens for 23 patients with a diagnosis of bulbar or palpebral conjunctival melanoma, treated at the University of Texas M. D. Anderson Cancer Center between January of 2000 and June 2004, were reviewed. The ability to evaluate margins of resection and tumor thickness were specifically studied in these specimens. Results: Five out of the 23 specimens were found to have been cut tangentially; thus eliminating the possibility of tumor thickness determination. In all 23 specimens, the margins of resection were positive on the original biopsy specimen and in each case additional surgery was required after the initial excision and upon subsequent referral to our hospital. Conclusions: Tangential cutting of the conjunctival specimens is a frequently encountered problem and may eliminate the pathologist’s ability to comment on tumor thickness. The majority of excisional biopsies for suspected conjunctival melanoma are indeed found to have positive margins. Tumor thickness has been shown to be one of the most important predictors for regional lymph node metastasis and survival for conjunctival melanomas. With the advent of sentinel lymph node biopsy as an optional staging procedure, loss of ability to comment on tumor thickness eliminates appropriate patient selection for this procedure. Careful orientation of the biopsy specimens for suspected conjunctival melanoma is crucial to allow for adequate assessment of tumor thickness and margins of resection. No significant financial relationships to disclose.