tbuckley/cabot-search huggingface dataset:
Uptake and effectiveness of FOLFIRINOX for advanced pancreas cancer: A population-based study.
Authors: Safiya Karim, Jina Zhang-Salomons, James Joseph Biagi, Tim Asmis, Christopher M. Booth
Journal: Journal of Clinical Oncology (2017)

245 Background: While FOLFIRINOX is a standard treatment option for advanced pancreas cancer there is little data describing utilization and effectiveness in routine clinical practice. Here we report practice patterns and outcomes in the general population of Ontario, Canada. Methods: Using the Ontario Cancer Registry and New Drug Funding Program we identified all patients with pancreas cancer treated with palliative intent gemcitabine or FOLFIRINOX in Ontario during 2006-2014. FOLFIRINOX became available in Ontario’s single-payer health system in November 2011. Gemcitabine cases were classified as pre-FOLFIRINOX era (2006-2010) or post-FOLFIRINOX era (2011-2014). Cases treated with peri-operative chemotherapy were excluded. Comparisons of proportions between study groups were made using the chi-square test. Overall survival (OS) was measured from date of chemotherapy initiation. Results: During 2006-2014, 3826 patients in Ontario were treated with Gemcitabine (n=3042) or FOLFIRINOX (n=784) chemotherapy for advanced pancreas cancer. Uptake of FOLFIRINOX increased from 41% (206/505) of treated cases in 2012 to 56% (274/486) of treated cases in 2014. Among patients treated after 2011, median age was 69 and 63 years for Gemcitabine and FOLFIRINOX respectively (p&lt;0.001). The proportion of treated cases who received FOLFIRINOX varied considerably across geographic regions (from 26% to 58%, p&lt;0.001). Median number of FOLFIRINOX cycles delivered was 6 (median 10 cycles in pivotal RCT). Median OS of patients treated with Gemcitabine was 5.0 months in 2006-2010 and 4.8 months in 2011-2014. Median OS of FOLFIRINOX patients treated in 2011-2014 was 8.2 months (median 11.1 months in pivotal RCT). Conclusions: Use of FOLFIRINOX in the general population has increased since 2011 with a resulting decrease in use of Gemcitabine. However, outcomes achieved with FOLFIRINOX in Ontario demonstrate a substantial efficacy-effectiveness gap between survival in the pivotal clinical trial and survival in routine practice.
Readmission among patients with cancer who were discharged with hospice care.
Authors: Joanna-Grace Mayo Manzano, Andrea G. Barbo, Heather Y. Lin, Hui Zhao, Josiah Halm, Maria E. Suarez-Almazor
Journal: Journal of Clinical Oncology (2017)

46 Background: Palliative and hospice care are appropriate recommendations for patients with high symptom burden and who are at end of life. Patients with cancer who are discharged to hospice care are less likely to be readmitted and this is expected. There remains a proportion of patients however, who rescind hospice after enrolling. We sought to describe this subgroup of patients and determine their readmission rate. Methods: This is a retrospective cohort study using administrative data of adult patients discharged from a non-surgical solid tumor service at The MD Anderson Cancer Center who were discharged to hospice care. Readmission was defined as any rehospitalization after discharge regardless of timing. Descriptive statistics are presented. Results: There were 1,452 discharge encounters with a disposition of hospice in our cohort with 50 resulting in readmission (readmission rate=3.4%). The mean age of patients who were readmitted was 59 years. Majority of the readmitted patients were female (60%), had a religious affiliation (83%), were English-speaking (85%), and were from Texas (94%). 54% of the patients who were readmitted were married versus 42% who were either single, divorced, widowed or separated. 42% had Medicare insurance, 44% had private insurance, 4% were indigent, and 10% were self-pay. 75% of the patients had metastatic disease at time of first presentation at MD Anderson. Conclusions: Transitioning to hospice care is a difficult decision for most patients and caregivers. Rescinding hospice after discharge to seek acute care in the hospital potentially reflects the difficult and daunting nature of this transition. Our study provides an insight into the characteristics of patients who are readmitted after hospice care has been initiated. More analysis is needed to determine if the characteristics described are associated with readmission in this population. Other factors such as those that are related to the caregiver, the patient’s symptom burden, or the care setting, may need to be investigated as well to have a better understanding of why patients decide to rescind hospice.
Yield of active screening for tuberculosis among asylum seekers in Germany: a systematic review and meta-analysis
Authors: Kayvan Bozorgmehr, Oliver Razum, Daniel Saure, Brigitte Joggerst, Joachim Szecsenyi, Christian Stock
Journal: Eurosurveillance (2017)

All asylum seekers in Germany undergo upon-entry screening for tuberculosis TB, but comprehensive evidence on the yield is lacking. We compared the national estimates with the international literature in a systematic review and meta-analysis of studies reporting the yield of TB, defined as the fraction of active TB cases detected among asylum seekers screened in Germany upon entry. We searched 11 national and international databases for empirical studies and the internet for grey literature published in English or German without restrictions on publication time. Among 1,253 screened articles, we identified six articles reporting the yield of active TB based on German data, ranging from 0.72 (95% confidence interval (CI): 0.45–1.10) to 6.41 (95% CI: 4.19–9.37) per 1,000 asylum seekers. The pooled estimate across all studies was 3.47 (95% CI: 1.78–5.73; I 2 = 94.9%; p &lt; 0.0001) per 1,000 asylum seekers. This estimate was in line with international evidence (I 2 = 0%; p for heterogeneity 0.55). The meta-analysis of available international estimates resulted in a pooled yield of 3.04 (95% CI: 2.24–3.96) per 1,000. This study provides an estimate across several German federal states for the yield of TB screening in asylum seekers. Further research is needed to develop more targeted screening programmes.
CD30 expression in non-small cell lung cancer with and without <i>ALK</i> gene rearrangement.
Authors: Yan Feng, Snehal Dabir, Eugen C. Minca, Christopher Lanigan, Raymond R. Tubbs, Afshin Dowlati
Journal: Journal of Clinical Oncology (2014)

e22146 Background: 3-5% Non-Small Cell Lung Cancer (NSCLC) harbors ALK gene translocation (ALK(+)) for which targeted ALK inhibitor has greater efficacy and tolerance than cytotoxic chemotherapy. However, resistance to ALK inhibition inevitably occurs and new therapeutic targets are urgently needed in this unique patient population. Interestingly, CD30, a TNF receptor super family member, is commonly expressed in anaplastic large cell lymphoma which is another malignancy associated with ALK gene arrangement in a majority of cases. Targetable CD30 could represent a new therapeutic target in ALK(+) NSCLC. CD30 expression has been observed in a study of 875 multiple types of non-lymphomatous malignancies (3-33%), including one case with small cell lung cancer (4%). The expression of CD30 in NSCLC, especially in ALK(+) NSCLC, is largely unknown. Methods: CD30 expression in the NSCLC cell lines A549, H358, H1666 and H1299 (none containing ALK gene translocation) was tested by western blot, flow cytometry and confocal microscopy using CD30 antibody (Novus biologicals, NBP1 – 72175). We also examined a total of 21 ALK(+) NSCLC and 17 ALK(-) NSCLC patients whose formalin fixed paraffin embedded tumor were available for CD30 immunohistochemistry staining using CD30 antibody (DAKO, M075101, clone Ber-H2) on Ventana Medical Systems Benchmark Ultra Automated Immunostainer (Tucson, AZ). CD30 IHC positive is defined as staining in ≥ 10% tumor cells. Results: CD30 expression was detected at a similar level in all four different NSCLC cell lines by western blot. The CD30 staining in A549 and H1299 was mainly membranous, as demonstrated by confocal microscope and the flow cytometry analysis. We did not detect any CD30 expression by IHC in all 21 ALK(+) and 17 ALK(-) NSCLC tumors. Conclusions: Our in vitro studies showed positive CD30 expression in four different NSCLC cell lines, but no significant CD30 expression was detected by IHC in both ALK(+) and ALK(-) NSCLC tumors. CD30 is unlikely a treatment target in NSCLC with or without ALK gene rearrangement.
The Schedule Dependent Combination of Bortezomib (Bor) with Rituximab (R), Cyclophosphamide (C) and Prednisone (P) Produces Minimal Toxicity, Even at Relatively High Doses of Proteasome Inhibitor, in Patients with Relapsed/Refractory Indolent B-Cell Lymphomproliferative Disorders.
Authors: John Gerecitano, Carol Portlock, Ariela Noy, Paul Hamlin, Craig Moskowitz, David Straus, Steven M. Horwitz, Maria Lia Palomba, Otilia-Liana Dumitrescu, Jennifer Pappanicholaou, Ellen Neylon, Rachel Hamelers, Andrew Zelenetz, Thomas J. Myers, Anthony L. Boral, Owen A. O’Connor
Journal: Blood (2006)
Manipulating the local tumor microenvironment with vaccinia virus expressing costimulatory molecules for the treatment of melanoma
Authors: C. S. Hesdorffer, H. Hoerig, G. Deraffele, J. Mitcham, D. Moroziewicz, K. Hurst-Wicker, J. Di Vito, M. Vuolo, T. Schuetz, H. L. Kaufman
Journal: Journal of Clinical Oncology (2004)

7504 Background: The local tumor site possesses a number of suppressive factors that may limit therapeutic responses following vaccination. Therefore, we hypothesized that delivery of a vaccinia virus expressing costimulatory molecules directly into the tumor environment would improve local and systemic anti-tumor immunity. Methods: We conducted two Phase I clinical trials in 25 patients with metastatic melanoma, one using vaccinia virus expressing B7.1for monthly direct intra-lesional vaccination and one using vaccinia virus expressing three costimulatory molecules: B7.1, ICAM-1, and LFA-3 using a similar design. Patients were evaluated for toxicity and local responses by blood chemistry, measurement of injected lesions, and FNA for tumor antigen expression. Systemic immunity was assessed in all patients against vaccinia virus, and in HLA-A2 patients (9/25) using A2-restricted gp100 and MART-1 epitopes by IFN-γ ELISPOT assay. Results: 25 patients with melanoma were sequentially enrolled in the two clinical trials (mean age 57.1 years). Toxicity was minimal with three reports of vitiligo and several grade I/II local reactions. All patients developed anti-vaccinia antibody titers, and several patients had evidence of vaccinia-specific T-cell responses. Systemic immunity was documented by an increase in gp100- and MART-1-specific T-cells following vaccination. Overall, 12/25 (48%) of the patients exhibited an objective clinical response in the index lesion. Furthermore, 8/25 (32%) of the patients demonstrated responses of distant disease, including two patients with a complete response for 22+ and 43+ months. Conclusions: These results demonstrate that local vaccination with vaccinia virus expressing human costimulatory molecules was well tolerated and induced local tumor regression in nearly half of vaccinated patients. The use of poxviruses to deliver costimulatory molecules to the tumor microenvironment appears to be a powerful method for inducing local anti-tumor responses. Further studies are needed to determine the full potential for the translation of local vaccination into systemic immunity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Therion Biologics Corp.
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy
Authors: Roland Seiler, Hussam Al Deen Ashab, Nicholas Erho, Bas W.G. van Rhijn, Brian Winters, James Douglas, Kim E. Van Kessel, Elisabeth E. Fransen van de Putte, Matthew Sommerlad, Natalie Q. Wang, Voleak Choeurng, Ewan A. Gibb, Beatrix Palmer-Aronsten, Lucia L. Lam, Christine Buerki, Elai Davicioni, Gottfrid Sjödahl, Jordan Kardos, Katherine A. Hoadley, Seth P. Lerner, David J. McConkey, Woonyoung Choi, William Y. Kim, Bernhard Kiss, George N. Thalmann, Tilman Todenhöfer, Simon J. Crabb, Scott North, Ellen C. Zwarthoff, Joost L. Boormans, Jonathan Wright, Marc Dall’Era, Michiel S. van der Heijden, Peter C. Black
Journal: European Urology (2017)
Are inter-country variations in the use of expensive oncology products (EOP) partly responsible for differing cancer treatment outcomes?
Authors: E. M. Wilson, J. P. Crown
Journal: Journal of Clinical Oncology (2004)

6083 Background: There are stubborn, unexplained international differences in treatment outcome for cancer patients.While some of these differences might be explicable on the basis of stage at diagnosis, or methodology of national tumour registry data collection, we hypothesise that some component might be due to international differentials in access to/use of EOPs between different countries eg docetaxel and trastuzumab had relatively delayed introduction in the UK (which has relatively poor breast cancer survival) compared to the US Methods: We have analysed the use of EOPs, using data provided by International Medical Statistics (London). The data base mainly reflects hospital (in- and out-patient) usage. We constructed a per capita relative scale of hospital-based drug use for the following drugs and countries: US, UK, Finland (Fn), Germany (G), France (Fr), Italy (I), Spain(S); trastuzumab (H), carboplatin (C), capecitabine (X), gemcitabine(G), filgrastim (N), paclitaxel (P), docetaxel (D) pamidronate+zoledronate (PZ) Results: Drug use by nation (2002) was in the following order (kg/million population): D:US 289, Fr 131, I 117, S 88,Fn 86,Ger 43,UK 30. P:US 499,S 380,Fr 306,I 284,Fn 262,Ger 149,UK 84 C:US 1013,Fr 801,Fn 709,S 692,I 592,UK 492,G 467; H:US 237, S 137, I 108, Fr 101, Fn 82, Ger 48,UK 44. G:I 7073,Fr 3978,US 3757,UK 3183,Fn 2636,Ger 2313, S 1443 N:I 12,US 5,S 4,Fr 3,Fn 2,UK 1,Ger 1X:Fr 22509,UK14709,I 14309,US 7245,Ger 5130,S 4296,Fn 2867 PZ:US 319,I 301,UK 243,Fr 171,S 163,G 133,Fn 128. By assigning a descending point scale per country based on its place in each drug category, the following index of EOP use was obtained. (1) US (2)Fr (3)I (4)S (5)UK,Fn (6)Ger. Conclusions: There are gross variations in the use of EOP between countries. These data probably understate the use of EOP in the US, where much oncology drug administration takes place in private offices. For 5/6 parenteral drugs studied, the US is the leading user. The low use of C in the US might be influenced by re-imbursement practices. Higher drug use in the US may partly explain the generally superior results of cancer treatment in that country. No significant financial relationships to disclose.
Resection after chemotherapy (CT) with irinotecan (CPT) for initially unresectable liver metastasis (LM) from colorectal cancer (CRC)
Authors: G. Pascal, B. Nordlinger, J.-Y. Douillard, M. Rivoire, M. Ducreux, M.-C. Clavero-Fabri, J.-L. Raoul, C. Oprea, E. Magherini, R. Adam
Journal: Journal of Clinical Oncology (2004)

3692 Background: Surgical resection of LM is the only treatment able to offer long term survival (30–35% at 5 years); however most LM are initially unresectable. Methods: The aim of this retrospective study was to evaluate the outcome of patients (pts) from 14 centers, with LM initially considered unresectable by each investigator and subsequently submitted to liver resection after treatment with CPT. Results: Data were available for 56 pts resected between July 1996 and May 2002. Pts characteristics: male/female: 29/27; median age: 56[34–76]; primary tumor: colon/junction/rectum: 32/17/7; median diameter of LM (mm): 44[21–188]; diameter of the largest LM>3 cm: 76%; median number (nb) of LM: 5[1–10]; nb of pts with>3LM: 66%; extrahepatic sites: 16%; prior CT for metastatic setting: 21 pts (5 pts with 2 or 3 lines CT before CPT). CPT based regimens included: combination with 5FU/AF 42 pts, with oxaliplatin and 5FU/AF 7 pts, with other 2 pts, monotherapy 5 pts. The primary endpoint was the median overall survival (OS), the 1-year (1y) and 2-year (2y) survival rate (SR). Median nb of cycles before surgery: 8[1–43]. LM surgery type: one stage hepatectomy: 50 pts (44 pts with major resection), two stage hepatectomy: 6 pts (all with major resection). All pts were resected and 42 pts (75%) had R0 resection. After a median follow-up (FU) of 15 months, the median OS after surgery was of 34.2 months (38.7 for pts with R0 resection), the 1y SR was 83% and 2y SR of 60%. After a median FU of 23.1 months, the median OS after CT with CPT was 42.1 months (45.4 for pts with R0 resection), the 1y SR was 92% and 2y SR 69%. 41 pts (73%) relapsed and 14 pts underwent a surgical intervention for recurrence (hepatic or extrahepatic). Morbidity rate was 37% (local and general postsurgical complications). Postoperative mortality (≤ 2 months) was 3% and was not related to the treatment. Conclusions: CT with CPT allows some unresectable pts to be further resected of their LM. R0 resection could be achieved in 75% of pts.The survival of these pts compares similarly to that of primarily resected pts. These results must be confirmed by a prospective on-going study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Laboratoires Aventis
The effect of BMI-1 inhibition on brain cancer stem cells.
Authors: Monal Mehta, Atif J. Khan, Hatem E. Sabaawy, Bruce George Haffty
Journal: Journal of Clinical Oncology (2012)

e13543 Background: Glioblastoma (GBM) is the most frequent and deadly brain cancer. Despite tolerance doses of radiation, control of tumor growth within the brain remains a formidable failure. Since the identification of brain cancer stem cells (BCSCs), efforts are underway to target the pathways regulating these cells. The role of Bmi-1 (B-cell specific MMLV insertion site-1), a polycomb member of chromatin-remodeling complex, in BCSCs self-renewal was elucidated. Here we utilize shRNA targeting or pharmacological inhibition of Bmi-1 in GBM cell lines and primary cells as a radiosensitizer to examine the effects of combination therapy on cell death and BCSCs differentiation. Methods: Cells were pre-treated with a Bmi-1 inhibitor before being irradiated. Serial neurosphere assay, a measure of self-renewal potential, was employed to study the effects of radiation, Bmi-1 inhibition, or the combination on BCSCs. The efficacy of this combination on cell death was assessed with MTT and clonogenic assays. Next, the abilities of the inhibitor and radiation to induce differentiation in GBM cell lines and primary cells were quantified. Further, by utilizing a novel zebrafish orthotropic xenograft model, small molecules targeting Bmi-1 and other BCSC pathways can be identified, and used to predict response to combination therapies. Results: Targeting of Bmi-1 in combination with radiation, specifically as a radiosensitizer, induced significant cell death in GBM cells, and was five-fold more effective than radiation only. Importantly, the neurosphere forming ability of BCSCs was severely compromised when the cells were treated with the combination, indicating a potent effect on the stem cell constituency. These effects may be due to loss of BCSC self-renewal potential, increased differentiation, and/or apoptosis as cells treated with the combination exhibited decreased expression of neural stem cell markers and abnormal phenotypes compared to single treatment. Conclusions: Targeting of Bmi-1 may eliminate the subpopulation of radioresistant BCSCs. Bmi-1 inhibition when combined with radiotherapy might provide an effective therapy for GBM patients specifically through its effect on BCSCs by affecting their survival, proliferation, and stem cell features.
Measurement of health literacy to advance global health research: a study based on Demographic and Health Surveys in 14 sub-Saharan countries
Authors: Heather McClintock, Sarah Schrauben, Ashley Andrews, Douglas Wiebe
Journal: The Lancet Global Health (2017)

BackgroundEducation and literacy are key determinants of health, but these do not ensure health literacy. A definition of health literacy from the US Institute of Medicine (IOM) is widely accepted, but there is no consensus on the traits by which health literacy can be measured. Some questions in Demographic and Health Surveys (DHS) represent domains of health literacy as defined by the IOM (ie, the capacity to interpret, obtain, and understand health information; and the ability to make appropriate health decisions), and could be a valuable untapped resource for the measurement of health literacy. Building on pilot work in Zambia, we aimed to derive a measure of health literacy from information recorded in the DHS that aligned with the IOM definition.MethodsWe accessed data from surveys conducted between 2006 and 2015 in 14 sub-Saharan African countries: Cameroon, Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Côte d'Ivoire, Lesotho, Rwanda, Niger, Namibia, Sierra Leone, Swaziland, Togo, and Zambia. Surveys were the same in all countries, but translated to local languages as appropriate. We used factor analysis to extract one measure of health literacy and assessed its reliability and validity. We reclassified the continuous measure into tertiles and collapsed observations in the lower two groups to derive a dichotomous indicator. We then used χ2 tests to assess whether the prevalence of (high) health literacy varied by demographics and country, accounting for sample weights.FindingsWe included 259 684 survey respondents aged 15–49 years. We identified eight survey questions that corresponded to elements of the four domains of IOM-defined health literacy. The questions addressed school and reading comprehension (capacity to interpret); reading magazines or listening to the radio or TV (capacity to obtain); learning family planning information (capacity to understand); and knowledge of a place to get an HIV test or acquire condoms (make appropriate health decisions). The derived continuous measure of health literacy demonstrated internal consistency (Cronbach's α = 0·72), and good content validity. Using the dichotomous indicator, overall prevalence of health literacy was 35·2% (95%CI 34·9–36·6%). Health literacy varied by sex (women 34·1% vs men 39·2%, p<0·001) and education level (primary education or less 8·9%, some secondary education 69·4%, and completed secondary education or higher 84·4%, p<0·001). Health literacy also varied greatly between countries, from 8·5% in Niger to 63·9% in Namibia (p<0·001)InterpretationOur study derives a robust indicator of IOM-defined health literacy in a large population in sub-Saharan Africa. Researchers could use this indicator with DHS datasets to measure health literacy in other countries, and ultimately examine how health literacy relates to health behaviour and outcomes, including for HIV/AIDS and domestic violence.FundingNone.
Erratum: impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: Results of a European concerted action (Journal of Hepatology (1998) 29 (173-83))
Authors: C. Brechot, F. Jaffredo, D. Lagorce, G. Gerken, K. Meyer zum Buschenfeld, A. Papakonstontinou, S. Hadziyannis, R. Romeo, M. Colombo, J. Rodes, J. Bruix, R. Williams, N. Naoumov
Journal: Journal of Hepatology (1998)