tbuckley/cabot-search huggingface dataset:
One hundred years of cancer mortality in Scotland (1911-2010).
Authors: Peter Boyle, Maria Bota, Chris Robertson
Journal: Journal of Clinical Oncology (2014)

1571 Background: Mortality data by age and gender are available for Scotland for one hundred years, 1911-2010. This allows a unique insight into the changing patterns of cancer over a complete century. Methods: Bridging was established manually to ensure that each rubric contained the same cancer sites throughout the period studies. Population data were available throughout the time period. Age-standardised mortality rates per 100,000 could be calculated. It was possible to follow the observed death rates in certain cohorts of men and women born in the late 1800s and the early 1900s. Results: Data are available for 20 individual sites of cancer in addition to the combined all cancers. Notable findings include the dramatic reduction in stomach cancer, which fell in men from38 per 100,000 around 1930 to 6 per 100,000 in 2006-2010 (in women the rates fell from 30 to 4 over the same time period). Lung cancer in men fell from its peak of 80 in 1960 to 30 in 2005-2010. One quarter of men born between 1900-1910 died of lung cancer in their lifetime (over 80% of men in Scotland smoked in 1950). Breast cancer mortality in women is now lower than at any other time point during the last century. Downward trends are apparent in birth cohorts at all ages indicating that this favourable trend will continue. Colorectal cancer mortality has declined markedly in both gender groups: in men the rate fell from 39 (1930-34) to attain 15 (2006-2010). The effects of treatment advances in Testis Cancer and Hodgkin’s Lymphoma are clearly reflected in the declining mortality rate. Conclusions: These data provide insights into the changing pattern of cancer over the last century. The impact of tobacco-smoking on cancer mortality throughout the century has been dramatic although the declines in tobacco-related cancers is confirmation of the effectiveness of anti-tobacco policies. It is harder to explain the substantial declines in stomach, colorectal and breast cancer although they are very welcome.
Vorinostat (VOR) and capecitabine (CAP) in recurrent and/or metastatic squamous cell carcinoma of head and neck (RMHNSCC): A study of the Princess Margaret Phase II Consortium.
Authors: Eric Xueyu Chen, Eric Winquist, Cheryl Ho, Barbara Jennifer Gitlitz, James Ohr, Albiruni R. A. Razak, Lillian L. Siu, James A. Zwiebel, Amit M. Oza, Lisa Wang, Soo Chin, Anne Malpage, Carleen Yu, Edward Mejia, Lori Gevaudan, Prachi Mohite
Journal: Journal of Clinical Oncology (2014)

e17001 Background: VOR is a small molecule inhibitor of histone deacetylase (HDAC). Preclinical studies demonstrate that HDAC inhibition is synergistic or additive with other anti-cancer treatments such as chemotherapy and radiation. In a previous phase I dose finding study, anti-tumor activity of VOR in combination with CAP was seen in patients (pts) with advanced HNSCC. Methods: Pts with previously untreated incurable RMHNSCC and adequate organ and marrow functions were eligible. VOR was administered orally at 300 mg daily x 14 days, and CAP at 1000 mg/m2 orally twice daily x 14 days every 21 days. The primary outcome of the study was the objective response rate and it was assessed every 6 weeks. The study was of a 2-stage design, with 17 evaluable pts enrolled in Stage 1, and requiring ≥ 3 partial responses (PR) to proceed to Stage 2. Results: Twenty-one pts were enrolled. The median age was 63 years (range: 44-85), 71% pts with ECOG 0 or 1, and 76% pts were males. Prior curative therapy included chemotherapy in 62% and radiation therapy in 90% pts. A total 67 cycles of treatment were given with a median number of 2 (range: 1-10). One pt each died of respiratory failure (not related to study drugs) and small bowel obstruction (possibly related to study drugs) during study. Grade 3 adverse events at least possibly related to study drugs include: hand-foot syndrome (2 pts); and fatigue, anorexia, anemia, nausea/vomiting, hyponatremia, hypokalemia, hypocalcemia, hypophosphatemia, dehydration, leukopenia (1 pt each). Of 16 pts eligible for response assessment, 2 pts had confirmed PRs lasting 6.2 months (mos) and 7.3 mos respectively and 8 pts had stable disease as the best response lasting 1.2-3.6 mos. The estimated median progression free survival and overall survival was 2.3 mos (95% CI: 1.2 – 3.6 mos) and 10.8 mos (95% CI: 5 mos – not reached) respectively. Conclusions: Although VOR and CAP were reasonably tolerated in pts with previously untreated RMHNSCC, objective response evaluation did not meet criteria to proceed to Stage 2. VOR in combination with CAP has limited activity in RMHNSCC. Clinical trial information: NCT01267240.
Clinical Outcomes of Venetoclax Therapy in Patients with Relapsed/Refractory (r/r) Non Hodgkin Lymphomas (NHL)
Authors: Mitchell E. Hughes, Daniel J. Landsburg, Daniel J Rubin, Stephen J. Schuster, Jakub Svoboda, Donald Edward Tsai, Kyle Robinson, Saar I. Gill, Anthony R. Mato, James Nathan Gerson, Danielle Land, Brenda Shelly, Alicia McLeish, Allison Rago, Jennifer Gill, Kristy Walsh, Tanya Latorre, Jessica K. Altman, Colleen Timlin, Donna Capozzi, Sunita Dwivedy Nasta
Journal: Blood (2018)
Do special access programs facilitate off-label prescribing? The experience of enzalutamide in prostate cancer.
Authors: Nimira S. Alimohamed, Raya Leibowitz-Amit, Arnoud J. Templeton, Jo-An Seah, Francisco Emilio Vera-Badillo, Anthony M. Joshua, Jennifer J. Knox, Ian Tannock, Srikala S. Sridhar
Journal: Journal of Clinical Oncology (2014)

6550 Background: There is limited data on prescribing patterns during special access programs. Enzalutamide, a novel oral anti-androgen, improves overall survival in patients with metastatic castration resistant prostate cancer (mCRPC). In the post-docetaxel setting, enzalutamide was Health Canada approved in May 2013 and publically funded in Ontario in December 2013. In the pre-docetaxel setting, data demonstrating benefit of enzalutamide (PREVAIL study) was only recently released and it is yet to be approved in this setting. Enzalutamide was provided free of charge by the manufacturer as part of a patient assistance program from June-December 2013. To understand factors influencing decision to offer enzalutamide in this program, we surveyed treating oncologists. Methods: Following ethics approval, oncologists at our institution prescribing enzalutamide completed an anonymous paper or electronic survey asking questions about the patient’s disease characteristics, prior treatments, and reasons for prescribing enzalutamide. Results: Of 193 patients enrolled, surveys were completed on all 155 patients prescribed enzalutamide by oncologists. The majority of patients had metastatic CRPC (92%), while a minority had non-metastatic CRPC (8%); 95% had progressive disease at initiation while 5% did not. Pre-docetaxel prescribing occurred in 65% of cases; with 54% of those being after PREVAIL data was released. The primary reasons for prescribing enzalutamide were data supporting its use (50%) and its availability at no charge (35%). Enzalutamide was felt to be the best choice or as good as other options by 82%; 11% stated enzalutamide would be the next line of treatment but only at the time of further disease progression; 7% stated enzalutamide would not be their next line of treatment and only prescribed it because of the program. Conclusions: During this patient access program, off-label use of enzalutamide was seen, perhaps because it is a well-tolerated hormonal agent, which may delay the need for chemotherapy. This study demonstrates that funding and accessibility issues impact prescribing practices.
Traumatic and Bloody Lumbar Puncture at Diagnosis in Children with Acute Lymphoblastic Leukemia: A St. Jude Total XV and Total XVI Cohort Study
Authors: Elena Varotto, Yinmei Zhou, Olivia Kan, John Kim Choi, Shannon Wright, Doralina Anghelescu, Yan Zheng, Scott Howard, Sima Jeha, Ching-Hon Pui, Hiroto Inaba
Journal: Blood (2018)
Importance of albumin level on outcomes of high-dose cytarabine and mitoxantrone induction therapy for AML.
Authors: Mansoor Burhani
Journal: Journal of Clinical Oncology (2014)

e18009 Background: Thousands of Americans are affected by acute myeloid leukemia (AML) with various factors affecting outcome. This study examines a patient's outcome as compared to nutritional status prior to treatment using albumin results. In this study, patients received a high dose cytarabine and mitoxantrone induction regimen, and the results are examined to see whether the albumin counts had any effect on treatment by examining short term (response rates) and long term (overall and relapse free survival) efficacy. Methods: Ninety patients were treated with a high dose cytarabine and mitoxantrone regimen from 2008-2012. Two doses of cytarabine were given over 3 hours 12 hours apart (hour 0 and 12) followed by one dose of mitoxantrone over one hour (hour 15) on days 1 and 5. Before treatment began, the albumin count for each of the patients was recorded. The outcome data was collected and analyzed. Results: Of the 90 patients, 43 had low albumin levels, and 47 had normal albumin levels. The definitions of low and normal albumin counts are based on the commonly used values of <3.5 g/dL as low and >3.5 g/dL as normal (g/dL= grams/deciliter). Below are the results for complete remission (CR) rate, relapse rate, median relapse free survival (RFS), and median overall survival (OS). Conclusions: Patients with a normal albumin level are more likely to achieve a response to induction chemotherapy when using high dose cytarabine and mitoxantrone induction. However, there does not appear to be a correlation between albumin levels and long term outcomes. Overall Normal albumin Low albumin CR rate 63% 70% 56% Relapse rate 37% 41% 31% Median RFS 10.4 months 10.1 months 10.9 months Median OS 10.6 months 11.3 months 9.3 months
The association among information provision, experience with medical team, HRQOL, and unmet needs for personalized health management program in cancer survivors.
Authors: Jin-Ah Sim, Young Ho Yun
Journal: Journal of Clinical Oncology (2014)

e17521 Background: Web-based tailored health management program can have a significant health impact to cancer survivors. Three parts – health information provision, personal experience with medical team, and health-related quality of life (HRQOL) – were examined to see the relationship with unmet needs for personalized health management program in a Korean sample of diverse cancer survivors. Methods: In this cross-sectional study, we analyzed health program needs from 625 cancer survivors in two hospitals’ cancer registries in Korea. Multivariate logistic regression model was conducted to identify factors related with unmet needs for web-based tailored health management system. Through multivariate logistic regression model, each factor’s (cancer care information medical experience, HRQOL) association with the unmet needs for tailored health management program was found. Results: Cancer patients who had higher income (aOR=1.57; 95% CI, 1.02 to 2.41) and education (aOR=3.42; 95% CI, 2.18 to 5.36) showed more needs for the tailored healthcare program. Other than these two socio-economic status (SES) factors, following cancer survivors responded a high prevalence of unmet personalized health management program needs : for those who already have been received enough information about things patients can do to help themselves (aOR=1.69; 95% CI, 1.08 to 2.65), and wished to receive more information (aOR=2.06; 95% CI, 1.28 to 3.30) reported the big necessity of the tailored health management program. Moreover, participants who have cognitive functioning problems (aOR=2.87; 95% CI, 1.38 to 5.96) and have appetite loss (aOR=2.87; 95% CI, 1.38 to 5.96) also replied that they need tailored healthcare program. Conclusions: These results implicate that providing web-based personalized health management program, which considers cancer patients needs and access to health information with HRQOL, is critical in managing health for cancer survivors.
Circulating tumor cell capture in hepatocellular carcinoma (HCC).
Authors: Holly Rochefort, Anthony B. El-Khoueiry, Christina Ann To, Yucheng Xu, Tong Xu, Denice Tsao-Wei, Susan G. Groshen, Jenny Wei, Niloofar Kossari, Sophoclis Alexopoulos, Amir Goldkorn
Journal: Journal of Clinical Oncology (2014)

e22033 Background: Circulating tumor cells (CTC) have been associated with outcome in epithelial malignancies, but conventional immunoaffinity capture has not been amenable to HCC given the rare expression of epithelial cell adhesion molecules in this malignancy. Here, we used a parylene-C slot microfilter to capture and characterize CTCs based on size and deformability in HCC patients (pts) initiating therapy. Methods: Pts were enrolled in 3 cohorts: Cohort 1 (C1): advanced disease (BCLC B and C), planned systemic therapy; cohort 2 (C2): (BCLC A and B), planned chemoembolization; cohort 3 (C3): within Milan criteria, listed for liver transplant. At baseline and subsequent time points, 7.5ml of blood was drawn for microfilter CTC enrichment and immunofluorescent staining for 4',6-Diamidino-2-Phenylindole (DAPI nuclear stain), cytokeratin, alpha-fetoprotein (AFP), and Erk 1/2. Microfilter-captured cells were imaged on a Zeiss Axiozoom multispectral microscope, and merged and tiled images were assessed for stain-positive cells. Results: 83 pts have been enrolled (C1: 33 pts, C2: 26 pts, C3: 24 pts). Demographically the 3 cohorts were similar: 80% male, median age 62, 52% Hispanic, 24% Caucasian, 22% Asian and 2% other. 64% of pts had viral hepatitis and 65% had Child Pugh A cirrhosis. C1 had portal vein invasion (PVI) and extrahepatic spread in 33% and 52% of pts respectively, and median baseline serum AFP was 303 (median AFP was 44 for all 3 cohorts). Baseline CTCs were detected in 75% of pts across all cohorts (median 3, range 0-1154): C1: 1(0-28); C2: 5(0-1154); C3: 6(0-224). Baseline CTC counts were inversely related to BCLC stage, PVI and serum AFP (p values <0.001, 0.016, and 0.026 respectively). At first subsequent collection, CTCs increased in 50% of C1 pts, 60% of C2 and 61% of C3; CTCs decreased in 30% of C1, 20% of C2, and 33% of C3. Conclusions: CTCs were successfully captured from a majority of HCC pts across the spectrum of disease. The association between lower baseline CTC count and advanced disease is unexpected, and molecular characterization of CTCs has been undertaken in a subset of pts. Additional follow-up and analysis are ongoing to identify associations between CTCs (baseline and changes from baseline) and disease outcomes (progression, survival).
Clinical significance of serum macrophage migration inhibitory factor (MIF) level in breast cancer.
Authors: Rumeysa Ciftci, Faruk Tas, Ece Aksit, Sezai Vatansever, Senem Karabulut, Fatma Sen, Ibrahim Yildiz, Serkan Keskin, Hamza Ugur Bozbey, Leyla Kilic, Ceren Tilgen Yasasever, Didem Tastekin
Journal: Journal of Clinical Oncology (2014)

e11556 Background: The macrophage migration inhibitory factor (MIF) is overexpressed and associated with increased invasiveness of breast cancer (BC) both in vitro and in vivo. The objective of this study was to determine the clinical significance of the serum MIF levels in BC patients. Methods: We enrolled 96 female patients with histopathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum MIF levels were measured by ELISA method and compared with 28 healthy controls. Results: The median age at diagnosis was 48 (range: 29-80) years. Thirty-nine percent of the patients had metastatic disease. The rates of patients with estrogen receptor positive, HER2 positive and triple negative disease were 71%, 32% and 8%, respectively. CT response rate of patients with locally advanced or metastatic disease was 78%. The mean serum MIF level of BC patients was significantly higher than controls (10.7 vs 5.49 ng/ml, p<0.001). The serum levels of MIF were higher among younger patients (p=0.053) and T1 tumors than others (p=0.032). However, there was no significant difference according to other clinicopathological/laboratory parameters or CT response. Serum MIF level did not have a significant impact on overall survival in both univariate (p=0.36) and multivariate analysis (p=0.32). ROC analysis showed that serum MIF level with a cut-off level of 1.1275 ng/ml has diagnostic value for BC (sensitivity: 97%, specifity: 71%). Conclusions: Serum MIF level is elevated and has diagnostic value in BC patients. However, it has no prognostic or predictive role for CT response.
Looking forward: Will the fudge on equity sustain the NHS into the next millennium?
Authors: N. Mays, J. Keen
Journal: BMJ (1998)

The NHS was established as a compromise between key parties; it allowed those patients who could afford it to have access to both private health care and the NHS and it permitted consultants to have access to income from private practice while working in the NHS. This safety valve for excess demand was developed contrary to the founding principles of equity, but it has been a feature of health care in the United Kingdom ever since; it allows more affluent patients to circumvent the periodic funding crises in the NHS while maintaining their support for health care funded by taxes. However, the share of total healthcare spending contributed by the private sector has risen steadily. This trend has led some commentators to argue that the NHS is not sustainable, primarily because funding through taxation will lead to an increasing gap between the demand for and supply of health care. Alternatives to the NHS would involve requiring a larger private contribution to the costs of health care but such systems require complex regulation and seem to produce inequities that reveal the specific interests of their proponents. In contrast, expanding the funding of the NHS in line with increases in the gross national product is affordable and broadly equitable.

Whether the UK compromise between public and private interests will be sustained cannot be predicted. Recent developments suggest that major change may occur unintentionally through the cumulative effects of small or unplanned changes, or both, or result from applying policy thinking from other fields of welfare, such as social security reform.

#### Summary points

The advent of the NHS did not lead to the abolition of private finance for or the private provision of health care in the United Kingdom

Shares of total healthcare spending and healthcare provision contributed by the private sector have risen steadily …
Screening and 6-month surveillance interval ultrasonography in early detection of cholangiocarcinoma in an endemic area.
Authors: Prakongboon Sungkasubun, Surachate Siripongsakul, Kunlayanee Akkarachinorate, Sirachat Vidhyarkorn, Akeanong Worakitsitisatorn, Tanachai Leelapisut, Thaniya Sricharunrat, Rawisak Chanwat, Chairat Bunchaliew, Pittayapoom Pattaranuthaporn
Journal: Journal of Clinical Oncology (2014)

4091 Background: Very high incidence rates of cholangiocarcinoma have been reported in Southeast Asia, especially in the north and northeastern parts of Thailand where the prevalence of this cancer is the highest in the world. Ban Luang district of Nan province in the northern Thailand is known to have a very high mortality rate from cholangiocarcinoma. Objectives: To ascertain the prevalence of cholangiocarcinoma in Ban Luang districtof Nan province and to implement a screening and surveillance program to identify early-stage cases for better treatment outcome. Methods: A 5-year prospective cohort study was conducted in Thai individuals, aged 30-60 years, in Ban Luang district. The initial cholangiocarcinoma screening program included blood testing, stool examination and ultrasonography every 6 months. Results: During the first 2 years, from 6,327 targeted participants, screening with abdominal ultrasonography could be completed in 4,337 subjects (68.5%). Cholangiocarcinoma was diagnosed in 22 cases from 4 repeated ultrasonography, 16 of which were in the curative and resectable stages. The prevalence of cholangiocarcinoma was 8 cases (184.5:100,000) and the average 6-month incidence was 4.7 cases (108.4:100,000).The 2-year survival was observed in 19 of 22 cases(86.4%) and the 2-year progression- or recurrence-free survival was found in 13 of 22 cases(59.1%). Conclusions: The high prevalence of cholangiocarcinoma in Ban Luang district was confirmed through this population-based study, with satisfactory results from ultrasonography-based screening and surveillance program. Early-stage cholangiocarcinoma cases were uncovered leading to better prognosis.
Abstract 13096: Role of Endogenous Bone Marrow-Derived Stem Cells and Its Pharmacological Modulation in Pulmonary Arterial Hypertension in Mice: A New Mechanism of Action in Bosentan Therapy
Authors: Taichi Kato, Hirofumi Sawada, Junko Maruyama, Takao Deguchi, Yukiko Ikeyama, Hiroyuki Ohashi, Shoichiro Otsuki, Noriko Yodoya, Masahiro Masuya, Hideto Shimpo, Kazuo Maruyama, Yoshihiro Komada, Yoshihide Mitani
Journal: Circulation (2012)

Background: Bone marrow(BM)-derived stem cells were reported to play an important role in various physiological and pathological conditions of vessels. We investigated whether endothelin receptor a...
Molecular characterization of renal medullary carcinoma (RMC).
Authors: Jianjun Gao, Hui Yao, Xiaoping Su, Priya Rao, Padmanee Sharma, Jose A. Karam, Christopher G. Wood, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2014)

4586 Background: RMC is a rare and highly aggressive malignancy that affects primarily young individuals with sickle cell trait. RMC usually presents at advanced stages and is universally fatal with a median survival of <12 months despite chemotherapy and targeted therapy. Molecular insights of RMC are needed for identification of potential therapeutic targets. Methods: We performed whole-exome sequencing using the Illumina platform on RMC tumor tissues from 11 patients for somatic mutational analysis. We also performed Affymetrix microarray and Ingenuity pathway analyses to identify genes that are differentially expressed. In addition, reverse phase protein arrays (RPPA) were carried out to identify differentially expressed proteins. Molecular changes were compared and correlated at DNA, RNA, and protein levels to identify genes and signaling pathways that may play important roles in RMC pathogenesis and serve as potential therapeutic targets in RMC. Results: Exome sequencing identified 981 genes that were mutated in 1 tumor; 87 genes mutated in 2 tumors; 10 genes mutated in 3 tumors; 1 gene mutated in 4 tumors; 4 genes mutated in 5 tumors; and 1 gene mutated in 6 tumors. Microarray analysis indicated mRNA expression levels of a total of 2166 genes were changed ≥ 2 fold with p-value <0.05 in RMC tumors. RPPA data showed that protein expression levels of a total of 60 genes were changed ≥1.4 fold with p<0.05. Further correlation analyses demonstrated genes involved in signaling pathways such as PI3 kinase (PIK3C2G), cell cycle control (CDC25D and CDC73), and histone synthesis (HIST2H3D) are significantly changed at DNA, mRNA, and protein levels. Conclusions: Our data suggest that genes in at least 3 signaling pathways may be important for RMC pathogenesis and may have therapeutic relevance for future targeting.
Generation of Memory Stem T Cells Specific for Tumor Antigens and Resistant to Inhibitory Signals By Genome Editing
Authors: Beatrice Claudia Cianciotti, Alessia Potenza, Valentina Vavassori, Zulma Magnani, Luigi Naldini, Fabio Ciceri, Pietro Genovese, Eliana Ruggiero, Chiara Bonini
Journal: Blood (2018)