tbuckley/cabot-search huggingface dataset:
Anthracyline (A) use among women with breast cancer (BC).
Authors: S. H. Giordano, Y. Lin, Y. Kuo, G. N. Hortobagyi, J. S. Goodwin
Journal: Journal of Clinical Oncology (2011)

1019 Background: Recent patterns of use of A vs taxane-based chemotherapy are unknown. Methods: Patients were identified from Medicare and private insurance datasets with the following criteria. 1) The 5% National Medicare file 1995−2008: Female bc treated with mastectomy or breast conserving surgery between 1/1996 and 6/2008, ³66 years, Medicare A and B coverage and no HMO, and chemotherapy 3 mo before−6 mo after surgery (n=5956). 2) Private insurance claims data: dx 4/98−6/07, female bc, age <65, breast surgery, and chemotherapy from 3 mo before −6 mo after surgery (n=25354). Patients receiving chemotherapy were classified as receiving either A-based chemotherapy (A +/− any other chemo) or taxane-based chemotherapy if codes for paclitaxel, docetaxel, or nab-paclitaxel were present with no codes for A. Chemotherapy use by year was calculated overall and by geographic area, and piecewise logistic regression analysis was used to determine changes over time. Results: 1) Medicare: A-based chemotherapy slowly increased from 1996 to 2005 (41% to 70.0% of patients) but fell sharply down to a low of 32.3% in 2008. A corresponding increase in taxane-based chemotherapy was seen, from 10.5% of patients in 2005 to 50.2% in 2008. By 2008, the majority of patients received taxane-based chemotherapy without an A. Regression analysis showed a significant increase in the use of taxane-based chemotherapy starting in the end of 2005. 2) Private insurance: Similar but less dramatic trends were seen with a fall of A chemotherapy from a peak of 86% in 2004 to 68% in 2007. Taxane-based chemotherapy increased to 28% of younger patients in 2007. While use remained stable in some states, A use declined up to 33% in other states. Analysis will be updated with the 2008−2009 private insurance data. Conclusions: Starting at the end of 2005, there has been a dramatic decline in the use of anthracyclines for women with breast cancer, with the sharpest decline among women over age 65. Anthracycline regimens are increasingly being replaced by taxane-based chemotherapy.
Catching moving targets: cancer stem cell hierarchies, therapy-resistance &amp; considerations for clinical intervention
Authors: Claudia Gasch, Brendan Ffrench, John J. O’Leary, Michael F. Gallagher
Journal: Molecular Cancer (2017)

It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.
Juan Rodés. A successful and extraordinary life of a visionary hepatologist
Authors: Albert Pares
Journal: Gut (2017)

![Graphic][1]</img> Dr Juan Rodés, architect of the Liver Unit of the Hospital Clinic of the University of Barcelona, an internationally renowned centre for research in liver disease, died in Barcelona on 10 January 2017, aged 78 years. He was one of the most inspiring and influential leaders in the field of clinical hepatology and the physician who changed modern medical practice in Spain. Juan graduated from the University of Barcelona School of Medicine, Barcelona, in 1962, and trained in Internal Medicine at the Hospital Clinic. The centre has had the privilege of having Dr Rodés as Head of Hepatology Professor of Medicine, Director and Chief Executive Officer, till his retirement. Dr Rodés and five other doctors started The Liver Unit informally in 1969 in the Catalan town of Montferri, Tarragona. Prior to this, Juan had completed a 1-year fellowship in Paris with Professor Caroli. From the beginning, each member of the … [1]: /embed/inline-graphic-1.gif
Piloting survivorship care planning with the metastatic breast cancer patient.
Authors: Elissa Thorner Bantug, Catherine Saiki, Jane Zorzi, Vered Stearns, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2016)

146 Background: Emotional distress and poor symptom management are highly prevalent among patients with metastatic breast cancer (MBC). A high disease burden can further negatively impact these patients’ quality of life. To address the evolving survivorship needs in their trajectory from initial diagnosis of advanced disease to end-of-life care, patients with MBC require prompt assessment, reevaluation, and specialized support services. Limited survivorship resources are devoted to this patient population and greater attention to their needs is warranted. Methods: To address the survivorship needs of patients with MBC Johns Hopkins, we developed a new initiative designated a “Living with Breast Cancer” appointment. During this dedicated clinic encounter, a palliative care nurse practitioner works with the patient and her caregiver to develop an individualized “survivorship care plan” that describes medical and psychosocial care, symptom management, nutrition counseling, goal setting, mind/body techniques, palliative care, legacy work, pain management, health screening recommendations, family support, community referrals, and care coordination with oncology providers, among others. Patients with stable MBC are referred to this service by our medical oncology team. Patients are then asked to complete an evaluation survey (either by email or over the phone) 4-6 weeks after the appointment. Results: Since the initiation of program in March 2016, we evaluated 8 patients (3 African-Americans; 3 Caucasian; 2 Asians); mean age is 54.1 years (range, 38-75). Most patients were approximately 1-year post diagnosis of MBC (range, 1-10 years). We are currently collecting and analyzing evaluation survey results. At the time of the meeting, further demographics and evaluation results through August 2016 will be reported. Conclusions: If successful, the Living with Breast Cancer initiative may allow for more patient-centered care of individuals with MBC and their families at Johns Hopkins. The creation of an infrastructure for care coordination, survivorship support services and education aims to promote individualized services within the metastatic setting and improve the quality of life for this population.
Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker
Authors: S S Chavan, J He, R Tytarenko, S Deshpande, P Patel, M Bailey, C K Stein, O Stephens, N Weinhold, N Petty, D Steward, L Rasche, M Bauer, C Ashby, E Peterson, S Ali, J Ross, V A Miller, P Stephens, S Thanendrarajan, C Schinke, M Zangari, F van Rhee, B Barlogie, T I Mughal, F E Davies, G J Morgan, B A Walker
Journal: Blood Cancer Journal (2017)

Abstract The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C , RB1, TRAF3, BIRC3 and TP53 , and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1 , CDKN2C and TP53 where they have prognostic significance.
Overtreatment of low-risk prostate cancer in the United States: Incidence, cost, complications, and implications for the screening debate.
Authors: Ayal A. Aizer, Xiangmei Gu, Toni K. Choueiri, Neil E. Martin, Jim C. Hu, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2013)

161 Background: The National Comprehensive Cancer Network (NCCN) recommends active surveillance as the sole option for men with low-risk prostate cancer (LRPC) and a life expectancy &lt;10 years. We sought to describe the incidence, risk factors, cost, and morbidity related to overtreatment of LRPC within the United States. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare Program to identify 11,744 men ≥66 years with LRPC diagnosed from 2004-2007. Expected survival was estimated using the 2007 Social Security Life Table and was increased and decreased by 50% in men in the upper and lower quartiles of comorbidity, respectively, as specified by the NCCN. Overtreatment was definitive treatment in men with LRPC and life expectancy &lt;10 years. Costs were the amount paid by Medicare in the year following minus the year prior to diagnosis. Toxicities were defined as relevant Medicare diagnoses or interventions. Results: Of 3001 men with LRPC and a life expectancy &lt;10 years, 2011 (67%) were treated definitively. On multivariable logistic regression, men overtreated for prostate cancer were more likely to be younger (p&lt;.001), white (vs black, OR 1.44, 95% CI 1.03-2.02, p=.03), married (OR 1.30, 95% CI 1.05-1.61, p=.02), urban (trend, OR 1.40, 95% CI 0.98-2.00, p=.06), have higher Elixhauser comorbidity (p&lt;.001), and have a higher clinical stage (T2 vs T1, OR 1.57, 95% CI 1.19-2.07, p=.001) and prostate-specific antigen level (OR 1.02, 95% CI 1.02-1.02, p&lt;.001). Relative to expectant management, the mean added cost per definitive treatment was $15,308. When extrapolated nationally the cumulative net cost of overtreatment in men ≥66 years is $32 million per annum. Long-term urinary, erectile, and bowel toxicity occurred in 59.2% and 50.0%, 47.9% and 19.7%, and 7.1% and 17.8% of prostatectomy and radiation patients, respectively. Conclusions: Overtreatment of prostate cancer is partially driven by sociodemographic factors and occurs in a high percentage of men with LRPC and limited life expectancy, with marked impact on patient quality of life and health care costs. Efforts to enhance appropriate management of LRPC would reduce the harms associated with screening.
Cost effectiveness of a lung cancer screening protocol based on 3D cell cytology antecedent to helical thoracic computed tomography (CT).
Authors: T. F. Urbine
Journal: Journal of Clinical Oncology (2011)

e16534 Background: Despite decades of progress in treatment and prevention, lung cancer mortality remains frustratingly high. Better survival prognosis for early stage cases, along with the occult nature that keeps lung cancer hidden from clinical observation in those early stages have combined to make early detection an appealing public health strategy. The National Lung Screening Trial (NLST) provides the first conclusive evidence that lung cancer screening with helical computed tomography (CT) can produce a significant mortality reduction for a high-risk population cohort. Because improved clinical outcomes are discounted by factors of test uncertainty, test cost, and the effects of elective radiation exposure, we sought to explore the value of preceding the CT exam with a non-invasive, highly specific and sensitive diagnostic test. Methods: Using a disease progression model based upon clinical evidence from published studies, we simulate a 15 year probabilistic experience for a high-risk patient cohort under the proposed protocol of pretesting followed by CT exam if positive, and periodic retesting if negative. The pretest is based upon the LuCED technology (Lung Cancer Evaluation Device) that compares patient cells from expectorate sputum to 3D morphometric biosignatures from a cancerous cell line. Results: The introduction of the LuCED technology to the screening protocol for a high-risk patient population resulted in increased early detection of stage I and Stage II NSCLC, reduced overall false positive and false negative detection rates, reduced unnecessary post-CT procedures and morbidity, and increased the number of life years saved by the program. The cost effectiveness ratio (CER) of this protocol ranged from $17,800 to $74,900 per life year saved with variation dependent on sensitivity, specificity and disease prevalence assumptions. Conclusions: The introduction of LuCED technology to the standard screening protocol for a high-risk population is comparable to other national cancer screening protocols such as breast and colorectal cancers in terms of CER.
Quercetin inhibits the akt pathway, leading to suppression of survival and induction of apoptosis in cancer cells
Authors: Nicholas Gulati, David Harter, Dhimant Desai, Shantu Amin, Raj Murali, Meena Jhanwar-Uniyal
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2281 

The tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) gene maps to chromosome 10q23.3 and encodes dual specificity phosphatase. The PTEN gene is mutated in 40-50% of patients with brain tumors, especially glioblastomas. PTEN exerts its effects, in part, via inhibition of the antiapoptotic protein kinase B(Akt). The Akt pathway is a cell survival pathway. We evaluated the effects of quercetin (3,3’,4’,5,7-pentahydroxyflavone), a bioflavonoid found in apples, red wine, and tea, on the Akt pathway. We treated BRCA1 mutant HCC1937 breast cancer cells, which have a homozygous deletion of the PTEN gene and an activated Akt pathway, with quercetin (25 μM). The vehicle-treated control had activated levels of Akt at the Ser473 site. Treatment with quercetin for 0.5, 1, and 3 hr completely suppressed Akt phosphorylation at Ser473. The PI3K/Akt inhibitor, LY 294002 ([2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one];10 μM), also suppressed the Akt pathway as evidenced by a reduction of Akt phosphorylation at Ser473, after treatment of the HCC1937 cells for 0.5, 1, and 3 hr. Chemical structural analysis revealed that both quercetin and LY 294002 are members of the benzopyranone class of compounds. To investigate the specificity of quercetin, we used the T47D breast cancer cell line, with an intact PTEN gene. Treatment of the T47D cells for 30 min. with epidermal growth factor (EGF) induced Akt phosphorylation at Ser473. EGF-induced Akt phosphorylation at Ser473 was suppressed by pretreatment of the cells for 3 hr with quercetin (25 μM) or LY 294002 (10 μM). Cells treated with quercetin and LY294002 displayed an apoptotic phenotype. Both quercetin and LY294002 stimulated the MAPK pathway. Our results demonstrate that pharmacologically safe doses of quercetin inhibit the Akt pathway, leading to suppression of cancer cell survival. This finding provides a molecular basis for designing treatment for patients with an activated PI3K/Akt pathway and provides a model to investigate natural compounds for anti-cancer activity.
The effect of gaps in chemotherapy on survival in patients with high-risk stage II and stage III colon cancer.
Authors: Yvonne Sada, Zhigang Duan, Hashem El-Serag, Jessica Davila
Journal: Journal of Clinical Oncology (2012)

180 Background: Current guidelines recommend six months of chemotherapy (CT) for stage III colon cancer and consideration for high-risk stage II colon cancer. No previous studies have examined the impact of CT gaps on survival. This retrospective study examines determinants of CT gaps and the effect of gaps on survival. Methods: Using national Surveillance, Epidemiology, and End Results registry-Medicare linked data, high-risk stage II and stage III colon cancer patients diagnosed between 2000-2007 who received surgery and CT were identified. CT duration and gaps were calculated. CT gap was defined as 30 to 90 days between two CT claims. Data on demographics, clinical factors (comorbidity, tumor grade), and treatment factors (time to CT initiation, toxicity, hospitalization) were collected. Multivariable regression was used to examine factors associated with gaps. Cox proportional hazards analysis examined the effect of gaps on risk of mortality. Results: 7,371 patients were identified. Median age was 75 (IQR: 71-79); 47% were male. Among all patients, 1,803 (24%) had a gap. 2,674 patients (36%) received 5 to 7 months of CT, of which 469 (18%) had a gap. Multivariable regression analysis showed that patients who were black (OR 1.3, 95% CI: 1.1-1.7), stage III (1.2, 1.0-1.3), had toxicity (1.3, 1.1-1.4), or had 3 to 4 months of CT (vs. 5-7 months, 2.6, 2.3-3.0) were more likely to have a gap, while patients with a more recent diagnosis in 2007(vs. 2000, 0.6, 0.5-0.8) were less likely to have a gap. 3-year cancer-specific survival was the same in all patients with CT gaps compared with no gaps (80%, 95% CI: 78%-82% vs. 81%, 95% CI: 80%-82%). Cox proportional hazard models showed that patients with gaps did not have increased risk of mortality (HR 0.99, 0.89-1.1) adjusting for patient and clinical factors. Among those who received 5 to 7 months of CT, 3-year survival was 8% lower in patients with gaps compared to those with no gaps (80%, 95% CI: 75%-83% vs. 88%, 95% CI: 87%-90%). Conclusions: Nearly 25% of high-risk stage II and III patients who received CT had a gap. CT gaps were associated with worse survival in patients who received 5 to 7 months of CT. Interventions to improve CT toxicity management and reduce gaps are needed to maximize the benefit of CT.
Quantitative image analysis of VEGF expression on a breast cancer tissue microarray
Authors: S. Ghosh, M. P. Zerkowski, M. M. Abu-Khalaf, R. L. Camp, D. L. Rimm, G. G. Chung
Journal: Journal of Clinical Oncology (2005)

9534 Background: Angiogenesis is essential for breast cancer progression and is regulated in part by vascular endothelial growth factor (VEGF). VEGF, the most potent endothelial cell mitogen and regulator of vascular permeability, is the target for numerous biologic therapies in breast cancer and other malignancies. Using a large cohort breast cancer tissue miccroarray (TMA), we analyzed the expression and subcellular localization of VEGF and correlated its expression with clinico-pathologic variables. Methods: Our TMA consisted of 659 cases of primary breast cancers, nearly equally divided between node negative and node positive cancers. We used our automated quantitative image analysis software (AQUA) which uses a modified immuno-histochemistry technique with fluorochromes. Primary antibody was polyclonal VEGF (Santa Cruz, Carpinteria, CA). Survival curves and cutpoint analysis were determined with X-tile, our recently developed software for determination of optimal cutpoints. Chi-square and multivariate analysis were performed with Statview software (version 5.0.1; SAS Institute Inc., Cary, NC). Results: VEGF stained predominantly in the membrane/cytoplasm and was overexpressed in tumors versus adjacent stroma. Using total expression within the tumor, high expressers consistently had worse 20 year disease-specific survival. X-tile however divided the population optimally into the top 23% versus the remaining 77% (Monte Carlo P value 0.0040). Using this cutpoint, high VEGF expression was associated positively with Her2/neu and inversely with ER/PR. On multivariate analysis, only tumor size, nodal status, and VEGF expression retained independent prognostic significance. Conclusions: VEGF expression was higher in tumors versus stroma. It was associated with other biomarkers of poor prognosis, and with worse 20 years disease-specific survival in our breast cancer cohort. No significant financial relationships to disclose.
Ovarian preservation in premenopausal patients with early stage endometrial cancer: A multicenter retrospective matched cohort study.
Authors: T. S. Lee, S. J. Seong, J. W. Kim, J. M. Lee, H. S. Ryu
Journal: Journal of Clinical Oncology (2011)

5106 Background: Bilateral oophorectomy is a recommended procedure irrespective of patient age during the treatment of endometrial cancer. However, the benefits of oophorectomy in this setting are unknown. We examined the safety of ovarian preservation in young women with endometrial cancer who underwent hysterectomy. Methods: A database which included 1032 endometrial cancer patients who underwent hysterectomy from 14 tertiary hospitals was used. Premenopausal patients diagnosed with stage Ia to IIb endometrioid adenocarcinoma who had undergone ovary-preserving surgery were matched to control group who had undergone bilateral salpingo-oophorectomy (1:1) based on 3 variables: age; stage; grade. The recurrence and long-term survival rates were compared. Results: The 114 pairs of study subjects were included. Mean patient age at the time of surgery was 41.5±7.2 years (range 25-51). Median duration of follow-up was 43.0 ±37.1 months. Overall 4 recurrences (4/228, 1.8%) and 5 deaths (5/228, 2.2%) were detected. Two recurrences and 4 deaths were identified in ovary-preserving group. One patient had metachronous ovarian malignancy at the saved ovary after 1 year of surgery. Two of the 4 deaths were unrelated to recurrence. In the control group, two recurrences and 1 disease related death were identified. We found no significant difference in recurrence-free survival or overall survival between two groups in Kaplan-Meier analysis (p=0.949, 0.235, respectively). Conclusions: The risk for adnexal malignancy in saved ovary in endometrial cancer patient is still present, but ovarian preservation does not seem to adversely impact on survival. In young women, ovary-saving surgery may be feasible in early stage endometrial cancer.
Systemic Ceramide Accumulation Causes Dysregulated Hematopoiesis
Authors: Shaalee Dworski, Alexandra Berger, Makoto Yoshimitsu, Abdulfatah Alayoubi, Bryan Au, Mathilde Exertier, Jessa Forster, Caren Furlonger, James C Wang, Toshihiro Takenaka, Christopher J. Paige, Jeffrey A. Medin
Journal: Blood (2012)