tbuckley/cabot-search huggingface dataset:
Breast cancer metastasis to bone: A role for Src in tumor microenvironment.
Authors: R. Singh, B. Pohorelic, A. Yang, C. Egan, A. M. Magliocco
Journal: Journal of Clinical Oncology (2011)

e11076 Background: In advaced stages, about 70% of breast cancer patients develop skeletal metastases. Recently, in vitro and bone metastasis enrichment mouse models have identified a number of factors including Src that induce breast cancer metastasis to bones. Src is over expressed in 30-75% of breast tumors. Therefore, we investigated Src mediated breast cancer metasasis to bone to- i) determine bone mediated Src activation in breast cancer; ii) investigate Src induced migration, invasion and; iii) breast cancer colony formation in bones. Methods: We have developed an in vitro breast cancer and bone cell co-culture model system to study breast-bone interactions. The human bone-derived cells are isolated from bone fragments obtained from hip and knee replacement surgeries. We co-cultured bone cells with breast cancer cells (MDA-MB 231). We employed western blotting to study bone induced Src activation, SiRNA for Src knockdown, Transwell cell migration and invasion assays and colony formation assays. Further, breast cancer cell migration, invasion and colony formation on bone cell monolayers was studied using Src SiRNA and Src inhibitors (saracatinib [AZD0530] and PP2). Human foreskin fibroblasts (HS 68) were used as controls in these experiments. Results: MDA-MB 231 cells showed higher migration (p≤0.05), invasion (p≤0.001) and colony formation (p≤0.01) on bone cell monolayers than on HS 68 monolayers. Co-culture with bone- derived cells induced Src phosphorylation at tyrosine 419 in MDA-MB 231 cells. Src knockdown and saracatinib treatments abrogated this effect in cancer cells. Pharmacologically, 1µM of saracatinib inhibited breast cancer cell migration (p≤0.001) and invasion (p≤0.01) on bone cell monolayers and increased numbers of cancer cell colonies (p≤0.001) as compared to HS 68 monolayers. PP2 (1µM) increased breast cancer cell colonies (p≤0.001) on bone cell monolayers as compared to HS 68 cells. Conclusions: Co-culture with bone-derived cells resulted in increased phosphorylation of Src on tyrosine 419 in breast cancer cells that correlated with increased cancer cell migration. Saracatinib reduced breast cancer migration and invasion but, promoted colony formation (saracatinib and PP2) on bone stroma.
Lung cancer diagnosis transformation: Aligning the people, processes, and technology sides of the learning system.
Authors: Michael Fung-Kee-Fung, Donna E. Maziak, Jason R. Pantarotto, Jennifer Smylie, Leanne Taylor, Thomas Timlin, Tiziana Cacciotti, Patrick James Villeneuve, Carole Dennie, Chantal Bornais, Jose Aquino, Paul Wheatley-Price, David J. Stewart
Journal: Journal of Clinical Oncology (2016)

50 Background: The Ottawa Hospital, serving a population of 1.2 million across a large geographic area, redesigned its regional lung cancer diagnosis and patient intake process using a systems approach. Although having a strong record of excellent coordinated care, recent challenges had created strains on delivery metrics. Prior to the implementation of the project (October 2014), it took patients a range of 15 – 225 days to get from a referral with a suspicion of lung cancer to initial treatment, with a 90 th percentile of 117 days. Methods: An innovative care platform was developed to align the people, processes and technology sides of the regional lung cancer care. It formed a basis for a “learning” system mobilizing the wider community for transformational change. We redesigned 12 main business processes facilitating accurate and timely diagnoses using the Communities of Practice approach, the Lean and Constraints methodology and the IBM business process management technology tools. In a series of rapid learning cycles, 270 technology-enabled actions were logged and resolved to support 57 process changes in workflow. The main patient value outcome was defined as improvement in the monthly proportion of patients receiving initial treatment within provincial targets and a reduction of total wait time. Results: In 14 months, the TOH Lung Cancer Transformation program yielded substantial improvement across all levels of diagnostic process including a 48% reduction in the cumulative wait times from referral to initial treatment (surgical, systemic, radiation), increased patient satisfaction with care coordination, implementation of guideline standards, efficiency gains from more intensive use of hospital resources, and sustained engagement of over 100 regional lung cancer care providers in collaborative learning and knowledge sharing across disciplinary and organizational boundaries. Conclusions: A systems approach can improve the hospital capacity to facilitate and support inter-professional and intra-professional teamwork necessary for the diagnostic process transformation.
Phase III randomized, double-blind, placebo-controlled trial of soy protein and venlafaxine for treatment of hot flashes in men with prostate cancer.
Authors: M. Vitolins, L. Griffin, W. V. Tomlinson, J. Vuky, D. B. Fried, P. T. Adams, D. Moose, B. Frizzell, J. E. Radford, T. R. C. Shah, E. G. Shaw
Journal: Journal of Clinical Oncology (2011)

9027 Background: Hot flashes (HFs) occur in approximately 2/3 of androgen-deprived men. There is limited data on treatment from prospective intervention studies. Methods: Eligible androgen-deprived men were randomly assigned to 1 of 4 daily regimens (2x2 factorial design) for 12 weeks: placebo pill and casein protein (P), soy protein and placebo pill (S), venlafaxine (Effexor) and Casein Protein (E), or soy plus venlafaxine (SE). The primary endpoint was hot flash symptom severity score (HFSSS), defined as number x severity of hot flashes. The secondary endpoint was quality of life (QoL), assessed using the FACT-P. Results: 120 men aged 46-91 (median 69 years) participated. Most were Caucasian (78%) and overweight obese (83%). Groups were similar at baseline (BL). Treatment compliance was 88%. Toxicity was minimal. All groups showed a reduction in HFSSS, but there were no significant differences between groups (Table). QoL did not change significantly over time and did not differ between groups. Conclusions: In androgen-deprived men, neither venlafaxine nor soy protein had a significant effect on HFSSS or QoL, in contrast to findings from Quella et al (1999), which reported a 54% decrease in HF score in men taking venlafaxine. Supported by CCOP Research Base Grant 5 U10 CA081851-11. Least squares estimates (SE). Outcome Visit P (N = 30) S (N = 30) E (N = 30) SE (N = 30) P value HFSSS (%BL) Week 4 80.5 (12.9) 75.4 (13.6) 75.0 (14.3) 63.1 (13.6) 0.789 Week 8 58.8 (13.2) 73.9 (14.0) 67.8 (14.7) 66.8 (14.2) 0.873 Week 12 45.2 (13.8) 68.9 (14.4) 64.9 (15.2) 72.2 (15.3) 0.477 FACT-P Baseline 111.5 (4.0) 115.7 (4.0) 119.5 (4.1) 119.6 (4.1) 0.474 Week 12 110.6 (4.2) 120.0 (4.3) 116.2 (4.4) 120.1 (4.4) 0.239
Evaluating abiraterone responses in African Americans with metastatic CRPC.
Authors: Michael D. Stolten, Elisa M. Ledet, Jeffrey R. Guccione, Allison H. Feibus, Brian E. Lewis, Jonathan L. Silberstein, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2016)

244 Background: A disparity between African American (AA) and other racial groups is documented in prostate cancer incidence and mortality. For metastatic CRPC, abiraterone (Abi) showed improvement in overall survival and gained FDA approval. However, Phase III trials enrolled mostly Caucasian (CA) patients. Documentation of Abi response rates in AA men is scant. Further characterization of Abi responses in AA men was the objective of this study. Methods: Age at diagnosis, prior enzalutamide (Enza) and/or docetaxel (Doc), and duration of Abi treatment were assessed. Baseline values at Abi initiation for alkaline phosphatase (ALP), hemoglobin (Hgb), and lactate dehydrogenase (LDH) were recorded. PSA values at baseline and throughout treatment were also logged. The velocity of PSA decline was determined by the PSA half-life (PSAHL) based on time to nadir. PCWG2 criteria were used to define PSA response and progression. Results: This was a single institution, retrospective cohort of 103 patients with mCRPC treated with Abi (n = 24 AA; n = 79 CA). Median age at diagnosis was 61.8 years and 62.4 years for AA and CA respectively. Prior Enza/Doc was 4.2%/33.3% for AA and 6.3%/29.1% for CA. Median duration of Abi therapy in AA was 207 days and 253 days for CA; neither median age or duration were statistically distinct. Median AA baseline ALP, Hgb, LDH, and PSA was 136 (range (r) = 59-653), 11.8 (r = 8.9-15.4), 256 (r = 157-401), and 59.9 (r = 4.8-1658) respectively. Median CA baseline ALP, Hgb, LDH, and PSA were 88 (r = 51-1600), 12.4 (r = 8.4-15.0), 204 (r = 100-528), and 40.6 (r = 2.5-2890) respectively. The difference in baseline lab values between AA and CA were insignificant. No statistical difference was seen in median PSAHL (AA = 55 days; CA = 64 days), or PSA decline of &gt; 30% (AA = 50%; CA = 52%), &gt; 50% (AA = 46%; CA = 39%), or &gt; 90% (AA = 21%; CA = 14%). Finally, neither the median time to nadir (AA = 119 days; CA = 137 days) or progression (AA = 157 days; CA = 131 days) were significantly different. Conclusions: Comparison between AA men and CA men in mCRPC patients being treated with Abi showed no statistical difference in response rates, duration of response, or time to progression. Prospective, multi-institutional studies are needed to further assess these findings.
In vitro and in vivo studies of human lymphocytes genetically engineered to express T cell receptors that recognize a p53 antigenic epitope
Authors: M. R. Theoret, C. J. Cohen, M. E. Dudley, R. A. Morgan, S. A. Rosenberg
Journal: Journal of Clinical Oncology (2008)

3032 Background: T cell adoptive immunotherapy can mediate objective cancer regression in patients with invasive melanoma. To extend T cell based therapies to patients with common epithelial cancers, the tumor associated antigen (TAA) p53 has been extensively studied in animal models and humans. We investigated tumor recognition in vitro and in vivo by normal lymphocytes gene modified to express an anti-p53 T cell receptor (TCR). Methods: A MSGV1 retroviral construct encoding an HLA-A2.1 restricted p53:264–272 specific α/β TCR (p53:264 TCR), derived from HLA-A2.1 transgenic mice, was used to optimize transduction (Td) of activated peripheral blood lymphocytes (PBL). A panel of well-characterized tumor cell lines with known HLA-A type and p53 gene sequences including the NCI-60 lines were used to test the recognition by p53:264 TCR Td PBL. Results: After Td optimization, expression of the p53:264 TCR was routinely achieved in > 80% of T cells. A panel of tumor cell lines including breast, colon, lung, renal, liver, ovarian, melanoma, central nervous system, and hematopoietic cancers were recognized by p53:264 TCR Td T cells irrespective of the level of p53 expression determined by FACS or western blot. Although this casts doubt on p53 as an ideal TAA based on the concept that p53 overexpression creates a therapeutic window for immune discrimination of tumor from normal cells, with few exceptions a panel of normal cells was ignored by p53:264 TCR Td PBL. We developed a method to expand p53:264 TCR Td PBL up to 1000 fold in vitro and a pilot clinical trial was conducted in metastatic cancer patients with breast, melanoma, esophageal, bile duct, small bowel, and parotid gland tumors. Eleven patients received lymphodepleting conditioning chemotherapy, p53:264 TCR Td PBL, and high dose interleukin-2, and no toxicity attributable to the Td PBL was observed. One patient achieved a partial response in all sites of disease including lung nodules and a hilar lymph node. Conclusions: Lymphocytes transduced with genes encoding anti-p53 TCR can recognize a wide array of cancer cell lines but recognition does not correlate with p53 gene expression. Adoptive immunotherapy clinical studies are underway using these gene-modified cells. No significant financial relationships to disclose.
Optimal prophylactic method of venous thromboembolism for gastrectomy in Korean patients: A prospective randomized trial.
Authors: Kyo Young Song
Journal: Journal of Clinical Oncology (2015)

TPS229 Background: Whereas routine prophylaxis for venous thromboembolism (VTE) is frequently utilized in the West, Asian physicians employ it much less often, based on its recorded rarity amongst their patients. This trial is to examine the incidence of VTE and to determine the optimal method of thromboembolic prophylaxis following gastrectomy for cancer. Methods: In this prospective randomized trial, patients will be assigned to either an intermittent pneumatic compression (IPC) only or an IPC plus enoxaparin. The primary end point of this study is to determine the VTE incidence rate within 30 days of surgery. A history with physical examinations for VTE and a serum d-dimer test is scheduled on postoperative days (POD) 0, 1, 4, and 7. Duplex ultrasonography (DUS) was performed as an objective test for deep vein thrombosis at POD 4. The number of patients to be randomized was calculated to be 682. Clinical trial information: NCT01448746.
Active surveillance: How to measure, manage, and improve.
Authors: Franklin Gaylis, Edward Cohen, Renee Calabrese, Hillary Prime, Paul Dato, Christopher J. Kane
Journal: Journal of Clinical Oncology (2016)

137 Background: Active surveillance (AS) is an important strategy to limit the overtreatment of low risk prostate cancer (PCa). A best practice was established for AS inclusion criteria and follow-up, aimed to measure past AS adoption rates, institute the best practice, then measure AS adoption. Methods: Patient biopsy and treatment data was retrieved from an integrated EMR (Allscripts). AS adoption rates were calculated using 4 methods: 1) All newly diagnosed PCa patients; 2) Newly diagnosed PCa patients treated at Genesis Healthcare Partners (GHP); 3) Patients eligible for AS treatment according to the National Comprehensive Cancer Network (NCCN) (very low risk and low risk categories) guidelines and treated at GHP; and 4) Patients eligible for AS treatment according to the UCSD/GHP best practice and treated at GHP, according to the following inclusion criteria: Stage T1c; PSA Density (PSAD) &lt; 0.15 ng/mL/cc and absolute PSA level &lt; 10 ng/mL; Gleason ≤6; ≤3 cores (+); No individual core with &gt;50% involvement. Between 2013 and 2014, GHP physicians underwent an educational training program on the UCSD/GHP best practice. Comparative report cards on AS adoption were sent to all physicians. Results: See Table. Conclusions: AS adoption improved in those patients considered most eligible (according to evidence based guidelines) for AS following institution of an educational program and comparative reporting in a community practice. Selection criteria appear to significantly impact AS adoption rates. [Table: see text]
Prognostic impact of discordance/concordance of triple-receptor expression between primary tumor and metastasis in patients with metastatic breast cancer
Authors: K. Broglio, S. L. Moulder, L. Hsu, S. Kau, L. Pusztai, W. F. Symmans, G. N. Hortobagyi, A. M. Gonzalez-Angulo, C. Liedtke
Journal: Journal of Clinical Oncology (2008)

1001 Background: Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 expression and carries an unfavorable prognosis. It has been hypothesized that expression status of these three features might change during disease course. Methods: We studied discordance of triple receptor status between primary tumor (T) and metastasis (M) in 789 patients who were diagnosed with metastatic breast cancer. ER, PR and HER2 status were determined by immunohistochemistry and/or fluorescence-in-vitro hybridization. Expression status for ER, PR and HER2 in both T and M was known in 228 (28.9%), 218 (27.6%) and 528 (70.0%) cases, respectively. Cases with TNBC were compared to cases expressing at least one receptor. Discordance was correlated to clinical/pathological parameters, site of recurrence and overall survival (OS). Results: Discordance rates for ER, PR, HER2, and TNBC are given (Table). Loss of receptor expression occurred more often than gain thereof. Discordance of ER, PR or HER2 expression was not associated with size, stage or histologic grade of the primary tumor. HER2 concordance was associated with bone as opposed to visceral/soft tissue recurrence. For both ER and PR, positivity in both T and M was associated with better OS compared to negative expression in at least one. HER2 discordance was associated with better OS compared to patients with HER2 concordance (p = 0.029). Patients with TNBC discordance had worse OS compared to patients with TNBC concordance (p = 0.002). After adjustment for clinical/pathological parameters, these associations remained independent. Conclusions: Discordance in triple-receptor expression between primary tumor and metastasis carries a worse prognosis compared to concordance. N Percent ER discordance 42 18.4 PR discordance 87 40.3 HER2 discordance 72 13.6 TN discordance 55 23.8 No significant financial relationships to disclose.
Impact of care at NCI comprehensive cancer centers (NCICCC) on outcomes in children, adolescents, and young adults (AYA) with central nervous system tumors (CNSt).
Authors: Julie Anna Wolfson, Can-Lan Sun, Tongjun Kang, Smita Bhatia
Journal: Journal of Clinical Oncology (2013)

123 Background: AYA (15-39yo) have not seen the same survival improvement as younger cancer patients with similar diagnoses (dx), leaving an AYA Gap. Treatment on pediatric trials is associated with superior survival in 15-21yo. However, impact of care at NCICCC for complex diseases with poor prognosis that require evidence-based care available at NCICCC (e.g. CNSt), remain unstudied. Methods: We constructed a cohort of 560 children (0-14yo) and 785 AYA with newly-dx CNSt, reported to the LA County (LAC) cancer registry between 1998 and 2008. While 82% of children (0-14y) and 65% of young AYA (15-18y) were treated at one of 3 NCICCC or 3 COG sites in LAC, only 17% of older AYA (19-39y) were treated at one of 3 NCICCC. We sought to determine the impact of NCICCC/COG on overall survival (OS) and barriers to access to care at NCICCC/COG in AYA with CNSt. Since distance to NCICCC/COG could serve as a barrier to accessing care, Geographic Information Systems were used to derive distance between patient’s residence to the nearest NCICCC/COG. Results: OS rates were uniformly good for children and AYA with grade 1 CNSt (96 vs. 89% at 5y, p=0.2) and uniformly poor for children and AYA with grade 3/4 CNSt (43 vs. 43% at 5y, p=0.6). Among patients with WHO grade 2 CNSt, AYA had worse outcome (HR=1.9, p&lt;0.01) after adjustment for race/ ethnicity, SES, and gender. This difference in outcome between AYA and children was abrogated by care at NCICCC (HR 1.4, p=0.2). Furthermore, patients cared at non-NCICCC saw worse outcome (HR=1.6, p=0.04). Compared with children, young AYA (15-18yo) were less likely to receive care at NCICCC (OR=0.3, p=0.02); race/ ethnicity, SES and distance to NCICCC did not influence care at NCICCC. Among older AYA (19-39yo), low SES (OR 0.4, p=0.01), public/ no insurance (OR 0.3, p&lt;0.01) and longer distance to NCICCC (5-12mi: OR=0.3 , p&lt;0.01; &gt;12mi OR 0.5 , p=0.05) reduced likelihood to receive care at NCICCC. Conclusions: Population-based data reveal that receipt of care at NCICCC abrogates the inferior outcome in AYA with WHO grade 2 CNSt. Young AYA are less likely to use NCICCC than children, as are older AYA with low SES, public/ no insurance, or living &gt; 5 miles from an NCICCC.
Bing-Neel Syndrome at Diagnosis of Waldenstrom: An Extremely Rare Case Report
Authors: Dionisios Stoumbos, Ioannis Patsias, Evaggelos Asmanis, Evangelia Eleni Christaki, Katsiva Vailiki, Anna Tasidou, Marie-Christine Kyrtsonis, Panagiotis Repousis, Maria Kotsopoulou
Journal: Blood (2015)
Predictors of quality of life (QOL) and mental health (MH) in caregivers of patients with advanced cancer.
Authors: D. Wadhwa, D. Burman, N. Swami, C. Zimmermann
Journal: Journal of Clinical Oncology (2011)

9110 Background: Growing demands on caregivers (CG) of patients with advanced cancer create a pressing need to understand the factors that impact on CG well-being. This study evaluates CG and patient characteristics that predict caregiver QOL and MH. Methods: Patients with metastatic gastrointestinal, genitourinary, breast, lung, or gynaecologic malignancy, and their CG, were recruited from 24 medical oncology clinics. Measures included the Caregiver QOL-Cancer scale (CQOLC), SF-36 v2 (CG mental and physical health), and FACT-G (patient QOL). The influence of socio-demographic and medical factors on CG QOL and MH were assessed using univariate linear regression. Multivariate analysis (backwards method) was used to determine independent predictors. Results: Of 191 CG, 65% were female and the median age was 57 years. The majority were a spouse/partner (84%) and/or lived with the patient (90%); 20% reported having a chronic illness/disability, and 25% stated they had a recent change in work situation. CG spent a mean of 3.5 hours per day directly caring for the patient. Independent predictors of better CG QOL and CG mental health are shown in the table. Conclusions: CG QOL is associated with better patient physical well-being, better CG MH and not caring for others in addition to the patient. CG MH was worse for females, those with a change in work situation and longer caregiving hours, and worse patient emotional well-being. These factors should be considered when developing interventions for caregiver support. Multivariate predictors of CG QOL and MH (n = 191). CG QOL (CQOLC) Adjusted R2 = 0.456 CG MH (SF-36 v2 MCS) Adjusted R2 = 0.193 Predictors* CG predictors Patient predictors CG predictors Patient predictors β SE P β SE P β SE P β SE P Female sex - - - -5.72 1.9 0.003 Caring for others (other than patient) -6.21 2.3 0.007 - - Change in work situation - - - -8.36 2.0 <0.001 Hours/day spent care-giving - - - -0.39 0.2 0.01 SF-36 v2 mental component summary (MCS) 0.76 0.1 <0.001 FACT-G Physical well-being 0.57 0.2 0.004 - - - Emotional well-being - - - 0.71 0.2 <0.001 *Patient and CG age, patient income, and patient ECOG score were also included in initial model.
Simultaneous Measurement of Thrombin Generation and Fibrin Formation in Whole Blood Applying Continuous Flow Is Predictive for the Amount of Blood Loss during/after Cardiothoracic Surgery
Authors: Leonie Pelkmans, Anne Bouwhuis, Evelien Schurgers, Theo Lindhout, Dana Huskens, Coenraad Hemker, Marcus Lancé, Bas De Laat, Hilde Kelchtermans
Journal: Blood (2014)