tbuckley/cabot-search huggingface dataset:
Poverty is not the main obstacle for quality cancer care in diagnosed cases: Experience of 520 cases from Bangladesh
Authors: E. Hoque, M. Hossain, S. Karim, R. Begum, M. Rahman
Journal: Journal of Clinical Oncology (2007)

9077 Background: Cancer management is expensive everywhere. In the developing countries poverty is always blamed for as to be the main obstacle for quality cancer care. According to WHO report (globocan) 1.295 to 1.36 million people in Bangladesh suffer from cancer. Our health care service is not extensive to diagnose all these cases. A number of diagnosed cases do not get standard specific treatment of cancer. The objective of the study is to find out the main possible reason behind it. Methods: We made a prospective analysis of pre-diagnosis and post-diagnosis expenses using hospital documents &amp; taken interview with specific questionnaire form of 520 cases regardless of age, indication and management who are treated from January 2002 to December 2005 in NICRH, City General Hospital &amp; Bangladesh Medical College Hospital. We calculated the total expenses incurred to each case before specific diagnosis (EBD). These include all investigations, and non-specific treatment costs from the onset of symptoms up to the specific diagnosis. We have estimated the total expenses after diagnosis (EAD). This includes planned specific cancer management according to diagnosis. We made a ratio in percent between them (EBD/EAD×100). Results: 219 cases (42%) spent = 100% of EAD before diagnosis. 94 cases (18%) spent = 200% of EAD before diagnosis. The more this ratio, less the quality of management they could afford. Among them 349 cases (67%) failed to complete planned management, 57 cases (11%) failed to receive any planned management. Only 114 cases (22%) completed their planned management. Queries revealed that 78% patients who failed to complete planned management is due to their financial exhaustion for high pre-diagnostic expenses. Conclusions: We conclude that poverty is not the main obstacle for quality cancer care in diagnosed cases of Bangladesh. High unnecessary pre-diagnostic expenses, which result in financial exhaustion, is one of the major obstacles for quality cancer care. Further study is required to determine how to reduce the redundant pre-diagnostic expenses &amp; find out other removable factors for quality cancer care in developing countries like Bangladesh. No significant financial relationships to disclose.
Significance of tumor biology compared to metastatic pattern (INSS 4 versus 4s) and age for prognosis of neuroblastoma less than 18 months of age
Authors: D. R. Taggart, W. B. London, M. L. Schmidt, Y. Zhang, S. G. Dubois, T. Monclair, A. D. Pearson, S. L. Cohn, K. K. Matthay
Journal: Journal of Clinical Oncology (2009)

10010 Background: Neuroblastoma is a heterogeneous disease with variability in outcome among different risk groups. Historically, INSS stage 4s neuroblastoma (age less than 12 months, stage 1 or 2 primary tumor with metastases limited to liver, skin and bone marrow) has a more favorable outcome than infant stage 4 disease. The aim was to determine if metastatic pattern (4 vs 4s) predicted favorable prognosis in infants &lt; 12 months or in toddlers aged 12–18 months when stratifying by biology. Methods: Outcome was analyzed by log rank tests and Cox models for 656 infants with stage 4s neuroblastoma and 1,019 stage 4 patients &lt; 18 months of age in the International Neuroblastoma Risk Group database (n=8,800). Prognostic factors (tumor ploidy, histology, grade, MKI, LDH, MYCN, 11q, 1p, primary site) were tested for association with age/stage subgroups (Fisher's exact test) and in Cox models. Results: MYCNamplification, 1p aberration, diploidy, and high MKI and LDH were more frequent in infant stage 4 than infant 4s tumors. The incidence of unfavorable biology was higher in toddlers aged 12–18 months, but did not differ with stage 4 vs. 4s pattern. EFS was significantly better for infants &lt;12 months with stage 4s than stage 4 (p=0.0004). EFS was similar for toddlers 12–18 months for stage 4 vs. 4s pattern (p=0.3893). Within the 717 patients with 4s pattern of metastases, age 12–18 months had worse EFS than &lt;12 months (p&lt;0.0001). After adjustment for age in 6 separate models, MYCN, 11q, 1p, MKI, and LDH were statistically significant prognostic factors. Although treatment regimens differed, EFS was similar for &lt;12 months vs. 12–18 months for MYCN not amplified patients in both 4S pattern (p=0.8469) and stage 4 (p=0.3783). Conclusions: For patients with MYCN not amplified tumors, outcome for patients 12–18 months is similar to those &lt;12 months regardless of the pattern of metastases. Tumor biology is more critical than metastatic pattern for prognosis of patients aged 12–18 months with stage 4 neuroblastoma. [Table: see text] No significant financial relationships to disclose.
Surveillance of endemic foci of tick-borne encephalitis in Finland 1995–2013: evidence of emergence of new foci
Authors: Elina Tonteri, Satu Kurkela, Suvi Timonen, Tytti Manni, Tytti Vuorinen, Markku Kuusi, Olli Vapalahti
Journal: Eurosurveillance (2015)

The geographical risk areas for tick-borne encephalitis (TBE) in Finland remained the same until the beginning of the 21st century, but a considerable geographical expansion has been observed in the past 10 years. In order to support public health measures, the present study describes the number of laboratory-confirmed TBE cases and laboratory tests conducted and the associated trends by hospital district, with a particular emphasis on the suspected geographical risk areas. An additional investigation was conducted on 1,957 clinical serum samples throughout the country taken from patients with neurological symptoms to screen for undiagnosed TBE cases. This study identified new TBE foci in Finland, reflecting the spread of the disease into new areas. Even in the most endemic municipalities, transmission of TBE to humans occurred in very specific and often small foci. The number of antibody tests for TBE virus more than doubled (an increase by 105%) between 2007 and 2013. Analysis of the number of tests also revealed areas in which the awareness of clinicians may be suboptimal at present. However, it appears that underdiagnosis of neuroinvasive TBE is not common.
A phase I study of BMS-936558 in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, or carboplatin/paclitaxel in patients with treatment-naive, stage IIIB/IV non-small-cell lung cancer.
Authors: Scott N. Gettinger, Naiyer A. Rizvi, Frances A. Shepherd, Laura Q. Chow, Scott Andrew Laurie, David R. Spigel, Eric Sbar, Yun Shen, Julie R. Brahmer
Journal: Journal of Clinical Oncology (2012)

TPS2615 Background: Lung cancer is the leading cause of cancer-related mortality worldwide and non-small-cell lung cancer (NSCLC) accounts for ~85% of all cases. Platinum-based chemotherapy alone or in combination with bevacizumab is considered first-line standard of care for advanced NSCLC. Despite such therapy, most patients (pts) will experience disease progression within 6 months and die from their disease within 1 year. Programmed death-1 (PD-1) is a coinhibitory receptor that negatively regulates T-cell activation; PD-1 expression by tumor infiltrating lymphocytes is associated with poor prognosis in NSCLC. BMS-936558 is a fully human anti-PD-1 monoclonal antibody that blocks ligand interaction with PD-L1 and PD-L2. In a phase 1 trial, BMS-936558 had antitumor activity at doses of 1-10 mg/kg in pts with advanced tumors, and impressive tumor responses in heavily pre-treated pts with NSCLC. Here we describe a phase 1 study planned to evaluate the safety and tolerability of BMS-936558 in combination with 3 standard, platinum-based doublet chemotherapy regimens in pts with NSCLC. Methods: Treatment-naïve pts with stage IIIB/IV NSCLC will be enrolled. Treatment arms will include: A) gemcitabine 1250 mg/M 2 on day 1 (D1) and day 8 (D8)/cisplatin 75 mg/M 2 D1/BMS-936558 D1; B) pemetrexed 500 mg/M 2 D1/cisplatin 75 mg/M 2 D1/BMS-936558 D1; and C) carboplatin AUC 6 D1/paclitaxel 200 mg/M 2 D1/BMS-936558 D1. The starting dose of BMS-936558 will be 10 mg/kg for each treatment arm. A decision to de-escalate to a lower dose (2 or 0.3 mg/kg) will be guided by the number of dose-limiting toxicities reported per treatment arm. Chemotherapy will be given for 4 cycles (1 cycle = 3 weeks). BMS-936558 will be administered every 3 weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary objectives are to assess safety and tolerability by measuring the frequency of adverse events (AEs), serious AEs, and laboratory abnormalities; secondary objectives are to determine the overall response rate and disease control rates based on RECIST 1.1. As of February 1, 2012, 2 patients were enrolled.
Therapeutic inhibition of miR-375 attenuates post-myocardial infarction inflammatory response and left ventricular dysfunction via PDK-1-AKT signalling axis
Authors: Venkata N.S. Garikipati, Suresh K. Verma, Darukeshwara Jolardarashi, Zhongjian Cheng, Jessica Ibetti, Maria Cimini, Yan Tang, Mohsin Khan, Yujia Yue, Cindy Benedict, Emily Nickoloff, May M. Truongcao, Erhe Gao, Prasanna Krishnamurthy, David A. Goukassian, Walter J. Koch, Raj Kishore
Journal: Cardiovascular Research (2017)

Increased miR-375 levels has been implicated in rodent models of myocardial infarction (MI) and with patients with heart failure. However, no prior study had established a therapeutic role of miR-375 in ischemic myocardium. Therefore, we assessed whether inhibition of MI-induced miR-375 by LNA anti-miR-375 can improve recovery after acute MI. Ten weeks old mice were treated with either control or LNA anti miR-375 after induction of MI by LAD ligation. The inflammatory response, cardiomyocyte apoptosis, capillary density and left ventricular (LV) functional, and structural remodelling changes were evaluated. Anti-miR-375 therapy significantly decreased inflammatory response and reduced cardiomyocyte apoptosis in the ischemic myocardium and significantly improved LV function and neovascularization and reduced infarct size. Repression of miR-375 led to the activation of 3-phosphoinositide-dependent protein kinase 1 (PDK-1) and increased AKT phosphorylation on Thr-308 in experimental hearts. In corroboration with our in vivo findings, our in vitro studies demonstrated that knockdown of miR-375 in macrophages modulated their phenotype, enhanced PDK-1 levels, and reduced pro-inflammatory cytokines expression following LPS challenge. Further, miR-375 levels were elevated in failing human heart tissue. Taken together, our studies demonstrate that anti-miR-375 therapy reduced inflammatory response, decreased cardiomyocyte death, improved LV function, and enhanced angiogenesis by targeting multiple cell types mediated at least in part through PDK-1/AKT signalling mechanisms.
Phase I trial of dose escalated whole liver irradiation (WLRT) with hepatic arterial (HA) fluorodeoxyuridine (FUDR)/leucovorin (LV)/streptozotocin (STZ) chemotherapy followed by chemoembolization with mitomycin C (MMC) for patients with neuroendocrine hepatic metastases.
Authors: Mark Shilkrut, Matthew J Schipper, William D. Ensminger, Edgar Ben-Josef, Theodore Steven Lawrence, Mary Uan-Sian Feng
Journal: Journal of Clinical Oncology (2012)

e14603 Background: Phase I trial combining HA chemotherapy, chemoembolization and dose-escalated WLRT was conducted to determine if the maximum safe dose of 32 Gy in 2 Gy fractions could be delivered to patients (pts) with neuroendocrine (NE) hepatic metastases. Methods: Pts with symptomatic liver metastases from NE tumors who failed somatostatin analog therapy were eligible. HA FUDR (3 mg/m 2 /d) and LV (300 mg/m 2 /d) were given for 12 days; STZ (500 mg/m 2 /d) was given on days 5,8,10. Concurrent WLRT was prescribed in 2 Gy/day with doses escalated from 24 Gy to 32 Gy using the time-to-event continual reassessment method for dose allocation with a target rate of dose-limiting grade ≥3 radiation-induced liver disease (RILD) of 10%. 8 weeks later, for patients without RILD and other grade ≥4 toxicities, 72-h infusion with HA FUDR (3 mg/m 2 /d) and LV (300 mg/m 2 /d) was given, followed by chemoembolization with mitomycin C (20 mg) and polyvinyl alcohol. Results: 19 pts were enrolled in the trial, 11 pts completed the entire protocol. 7 pts received 24 Gy, 2 - 26 Gy, 1 - 28 Gy, 2 - 30 Gy and 6 - 32 Gy. One pt stopped at 14 Gy because of STZ-induced grade 4 renal failure. No pts developed RILD at any dose level; 4 - had grade 3-4 increased liver function tests, 4 - had other grade 4 toxicities during or after the first part of the treatment; 1 - had other grade 4 toxicity during the second part. Posterior estimates of probabilities of RILD were all &lt;10% (table). Three pts (14%) had partial response, 16 (84%) - stable disease. Median freedom from local progression for all pts was 35.3 (9.3-58.9) months. Conclusions: The study showed that chemotherapy can be safely combined with a full dose of WLRT and subsequent chemoembolization without producing RILD. [Table: see text]
The use of the internet for medical information and a needs assessment for a web based educational resource: A survey of Canadian medical oncology trainees and training program directors
Authors: L. Horn, S. Berry, J. Chung, S. Vijayaratnam, S. Verma
Journal: Journal of Clinical Oncology (2007)

17022 Background: Medical Oncology trainees develop their skills and knowledge through formal educational sessions, independent learning and clinical rotations. The internet serves as a source of up to date information and a potential educatinal resource. Despite the existence of many websites with oncology related information, there has not been a comprehensive assessment of how medical oncology trainees and program directors use the internet to meet educational objectivs. Method: In the first phase of developing a new educational website (OncologyEducation.com), we surveyed medical oncology trainees and program directors from training programs across Canada to assess how they accessed the internet to determine the elements they considered essential for a trainee-oriented site. Results: 12 out of 13 Canadian medical oncology training programs participated in our survey. A total of 12 program directors and 23 trainees responsed to our survey for a 74.5% response rate. 71.4% of respondents spend up to 10 hours per week on the internet for work related reasons. Pubmed and UptoDate were the most frequently visited sites. Respondents reported using the internet for email (97.1%), answering clinical questions (88.6%), accessing practice guidelines (80%), and literature updates (71.4%). Respondents expressed a need for an educational website stressing the following content: (1) Key updates by disease sites (2) Access to pivotal journal articles (3) Access to upcoming conferences/information (4) Links to other medical sites/medical oncology sites (5) Fellowship Opportunities. Conclusion: The internet is an important resource for supplementing the training of medical oncology trainees. The development of an educational website based on the needs assessed in this survey is warranted. Upon development of the website it will be evaluated for effectiveness and impact on oncology training and clinical practice. No significant financial relationships to disclose.
Development of a novel immunotherapy for muscle invasive bladder cancer (MIBC).
Authors: Irina Y. Tcherepanova, Bradley C. Leibovich, Jacoba Slagter-Jager, Patrick Dillon, Shawn Michael Leland, Lance A Mynderse, Brian Addis Costello, Charles A. Nicolette
Journal: Journal of Clinical Oncology (2017)

402 Background: AGS-003 is an autologous tumor RNA-loaded dendritic cell-based immunotherapy being tested in advanced renal cell carcinoma (RCC) patients. The immunologic specificity for the patient’s own tumor is achieved using amplified tumor RNA electroporated into monocyte derived dendritic cells. To produce AGS-003 for RCC patients the RNA is amplified from a 100 mg primary tumor sample obtained via nephrectomy. In this non treatment study we evaluated the feasibility of RNA amplification from MIBC tissue acquired by transurethral resection of bladder tumor (TURBT). Methods: MIBC tissue was obtained via TURBT. Following draining of the irrigant used during the TURBT procedure, tissue was placed into an RNA preservative solution to prevent RNA degradation until processing. Methods developed for the amplification of RCC tumor RNA and RNA quality testing were applied to the RNA extracted from the MIBC specimens. Results: This work demonstrated that the methods developed for the amplification and testing of RNA from RCC can be successfully employed for the amplification of RNA from MIBC specimens collected by TURBT. Results demonstrated that the total RNA yields obtained from bladder tissue exceed that of similar masses of primary RCC tumors. This finding enabled the reduction in the amount of starting material from 100 mg to 50 mg of bladder tissue. The amount of amplified RNA produced from the lower bladder cancer masses were sufficient to support the production of immunotherapy at full scale (17 doses average). Conclusions: These data demonstrate the feasibility of RNA extraction and amplification from muscle invasive bladder cancer tissue and supports our planned phase II clinical study. [Table: see text]
Retrospective analysis of breast cancer patients in an Asian-majority community clinic.
Authors: Adriana Hu, Yi-Kong Keung, Ryan A Lau, Lap-Woon Keung, Eddie Hu
Journal: Journal of Clinical Oncology (2013)

e12502 Background: Incidence of breast cancer in Asian countries is about one third to one half of that of the US. Asian immigrants have a higher risk of developing breast cancer in the US presumably by adopting more westernized lifestyles. We conduct a retrospective analysis of breast cancer patients (pts) in an Asian-majority community in Southern California. Methods: Unselected consecutive female breast cancer pts were studied. Clinical data were review and statistical analysis was conducted by SPSS 16.0. Results: 501 pts, 334 Asians (incl. Chinese 84%) and 167 non-Asians (incl. Caucasian 47% and Hispanic 45%) were studied. Conclusions: This study raised several intriguing findings: 1. Asian pts are significantly younger and have lower BMI than non-Asians. 2. Asian pts are more likely to undergo mastectomy than breast conserving surgery. 3. Asian pts tend to have denser breasts which may potentially limit the sensitivity of mammogram. Since the ratio of DCIS to invasive cancer is comparable between Asian and non-Asian pts in this study, mammogram is probably effective in detecting early cancer in Asians. 4. Significantly fewer Asian pts are diagnosed by screening mammogram. It is probably due to lower utilization of mammogram in the Asian population. 5. BRCA1/2 mutation is not significantly different between Asians and non-Asians. Due to inherent limitations of retrospective study, these findings need to be confirmed in a larger prospective study. [Table: see text]
Comparative genomics of pulmonary and extrapulmonary small cell carcinoma.
Authors: Gabriel Sica, Krisztina Hanley, Scott Newman, Marina Mosunjac, Anthony Martinez, Erica Han, Guojing Zhang, Suresh S. Ramalingam, Fadlo Raja Khuri, Michael R. Rossi, Taofeek Kunle Owonikoko
Journal: Journal of Clinical Oncology (2015)

e18547 Comparative genomics of pulmonary and extrapulmonary small cell carcinoma Background: Biology of small cell lung cancer (SCLC) is poorly understood in part due to limited opportunities for investigation. We explored whether genomic characteristics of small cell arising from different organ sites will elucidate the biology of this fatal disease. Methods: We employed archival tissue samples of small cell cancers arising from the lung, bladder, genital tract and anorectal region. Total RNA was isolated from FFPE specimens using the QIAGEN miRNeasy FFPE kit. RNA-Seq library was generated using NuGen Ovation® kit by AKESOgen (AKESOgen Inc., Norcross, GA). Paired end (100x100) sequencing was performed using an Illumina HISeq2000 instrument. Data quality was assessed on a minimum of 50 million reads per sample using HTQC and FastQC tools. FASTQ reads were aligned to the human reference build 37/hg19 using TopHat alignment. Gene fusions were identified using TopHat Fusion and differential gene expression was performed with CuffDiff. Results: We employed 19 cases of small cell carcinoma arising from the lung (5 cases), bladder (3 cases), genital tract (9 cases) and anorectal region (2 cases). See Table 1 Conclusions: Similarities and differences in genetic aberrations in small cell carcinoma arising from pulmonary and extra pulmonary sites provide a unique opportunity to study SCLC biology. Published Data Combined Lung Studies (n=169) ESCL (n=5) ESCG (n=9) ESCBL (n=3) ESCAR (n=2) Emory Combined (n=19) Gene Mut % Mut % Mut % Mut % Mut % TP53 85% 40% 22% 100% 0% 37% RB1 47% 60% 0% 0% 0% 16% LRP1B 21% 0% 0% 0% 0% 0% KMT2B (MLL2) 10% 0% 11% 0% 0% 5% SLIT2 10% 0% 0% 0% 0% 0% EPHA7 7% 0% 0% 0% 0% 0% CREBBP 5% 0% 0% 33% 0% 5% EP300 5% 20% 33% 33% 0% 26% PTEN 5% 0% 22% 0% 0% 11% SPEN 5% 0% 0% 0% 0% 0% KMT2A (MLL1) 4% 0% 11% 33% 0% 11% KMT2D (MLL3) 4% 20% 22% 33% 0% 21% KIT 4% 20% 0% 33% 0% 11% NOTCH3 4% 0% 0% 33% 0% 5% EGFR 4% 20% 0% 0% 0% 5% KDM6A 4% 0% 0% 0% 0% 0% BRCA2 3% 0% 0% 0% 0% 0% CSF1R 3% 60% 0% 0% 50% 21% KRAS 3% 0% 0% 0% 0% 0% NF1 3% 0% 11% 0% 0% 5% PIK3CA 3% 0% 0% 0% 0% 0% SMARCA4 3% 0% 0% 0% 0% 0% CTNNB1 2% 0% 0% 0% 0% 0% TSC1 1% 0% 0% 0% 0% 0% ESCL: Emory SCLC; ESCG: Emory Genital Tract Small Cell; ESCBL: Emory Bladder Small Cell Cancer; ESCAR: Emory Anorectal Small Cell Cancer