tbuckley/cabot-search huggingface dataset:
Charting DNA methylation of long non-coding RNA in clear-cell renal cell carcinoma.
Authors: Gabriel Malouf, Jianping Zhang, Nizar M. Tannir, Erika Thompson, Jean-Philippe Spano, David Khayat, Xiaoping Su
Journal: Journal of Clinical Oncology (2015)

432 Background: Long non-coding RNAs (lncRNA) play a key role in regulating cell physiology through different mechanisms including the recruitment of histone-modifying enzymes. Recently, lncRNA classification of clear-cell renal cell carcinomas (cc-RCC) established four subtypes with different clinico-pathological features. However, the interplay between those lncRNA and DNA methylation patterns remains unknown. Methods: We performed a genomic analysis of GENCODE lncRNAs in cc-RCC using The Cancer Genome Atlas (TCGA) molecular RNAseq profiles of 471 primary tumors. Furthermore, we reannotated data of DNA methylation combining 27K (n=173) and 450K (n=298) Infinium arrays. We described global correlations between lncRNA expression and DNA methylation and established lncRNA methylation subtypes based on distinct signatures. In addition, we identified lncRNA regulated by DNA methylation and associated with poor outcome. Results: We identified 2,138 lncRNAs which contain promoters located in CpG islands (CGI). Out of those, 59 (2.8%) lncRNAs showed DNA methylation in both normal and cancer as compared to 1,487 (69.5%) lncRNA which were unmethylated in both of them. Importantly, 592 (27.7%) lncRNAs gained DNA methylation in ccRCC and this was associated with the repression of the expression of 70 of them. Unsupervised clustering of lncRNA using the most variable DNA methylation probes revealed three robust subtypes associated with distinct outcome. Finally, by integrating cancer subtypes data with clinical information, we identified several lncRNAs which promoter methylation was associated with patient outcome. Conclusions: Our study represents the first integrative analysis of lncRNA and DNA methylation in ccRCC and provides new insights in the role of epigenetic alterations in kidney cancer. Furthermore, we identified a subset of lncRNA regulated epigenetically which may represent potential therapeutic targets.
Estimating costs of care for patients with newly diagnosed metastatic colorectal cancer (mCRC)
Authors: L. C. Paramore, S. Thomas, K. B. Knopf, L. Cragin, K. Fraeman
Journal: Journal of Clinical Oncology (2006)

6082 Background: The cost of treatment for patients with metastatic colorectal cancer (mCRC) has become a significant component of overall cancer care due to its high incidence and the increasing duration of patient survival. This study examines the resource use patterns and costs of care for patients with incident metastatic colorectal cancer (mCRC) based on analyses of retrospective claims data from selected health plans in the United States. Methods: A case-control analysis was performed using claims data from over 70 US health plans representing 40 million lives from years 1998–2004. Incident mCRC cases were identified based on evidence of a colorectal cancer diagnosis and a metastatic disease diagnosis. Incident mCRC cases could have no other evidence of cancer in the one-year period prior to the date of their first mCRC diagnosis. Cases were matched to non-mCRC controls based on age, gender, geographic region and duration of plan enrollment. Costs were evaluated by phase of disease: diagnosis, treatment, or death phases. Ordinary least squares regressions were performed to evaluate impact of covariates in each phase. Results: Total costs in the follow-up period averaged $97,031 higher for mCRC cases (N=) than for controls. The main cost drivers for mCRC were hospitalizations ($37,369) and specialist visits ($34,582) which included chemotherapy administration. Approximately 40% of the 672 mCRC patients who qualified for the phase analysis were identified with a fatal event during follow-up. Monthly costs were similar in the diagnostic phase ($12,394) and death phase ($12,069), but were significantly lower in the treatment phase ($4,653). Both mean/median monthly costs increased over time during the study period, regardless of disease phase. Conclusion: The economic burden of mCRC is substantial for patients in commercial health plans in the U.S., and costs of care have increased substantially in recent years. Further research is needed to assess the cost impact of newer targeted therapies for the treatment of mCRC. No significant financial relationships to disclose.
Progress Toward Poliomyelitis Eradication — Nigeria, January 2018–May 2019
Authors: Usman S. Adamu, W. Roodly Archer, Fiona Braka, Eunice Damisa, Anisur Siddique, Shazad Baig, Jeffrey Higgins, Gerald Etapelong Sume, Richard Banda, Charles Kipkoech Korir, Ndadilnasiya Waziri, Saheed Gidado, Philip Bammeke, Aboyowa Edukugo, Gatei wa Nganda, Joseph C. Forbi, Cara C. Burns, Hongmei Liu, Jaume Jorba, Adeyelu Asekun, Richard Franka, Steven G.F. Wassilak, Omotayo Bolu
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The number of wild poliovirus (WPV) cases in Nigeria decreased from 1,122 in 2006 to six WPV type 1 (WPV1) in 2014 (1). During August 2014-July 2016, no WPV cases were detected; during August-September 2016, four cases were reported in Borno State. An insurgency in northeastern Nigeria had resulted in 468,800 children aged <5 years deprived of health services in Borno by 2016. Military activities in mid-2016 freed isolated families to travel to camps, where the four WPV1 cases were detected. Oral poliovirus vaccine (OPV) campaigns were intensified during August 2016-December 2017; since October 2016, no WPV has been detected (2). Vaccination activities in insurgent-held areas are conducted by security forces; however, 60,000 unvaccinated children remain in unreached settlements. Since 2018, circulating vaccine-derived poliovirus type 2 (cVDPV2) has emerged and spread from Nigeria to Niger and Cameroon; outbreak responses to date have not interrupted transmission. This report describes progress in Nigeria polio eradication activities during January 2018-May 2019 and updates the previous report (2). Interruption of cVDPV2 transmission in Nigeria will need increased efforts to improve campaign quality and include insurgent-held areas. Progress in surveillance and immunization activities will continue to be reviewed, potentially allowing certification of interruption of WPV transmission in Africa in 2020.
Retrospective analyse of grade 1 tumors in a triple-negative breast cancer cohort.
Authors: B. Lex, M. Popovich, H. Bruch, A. H. Tulusan, V. Russu
Journal: Journal of Clinical Oncology (2010)

e11091 Background: Triple-negative breast cancer (TN) is focused as a new subgroup with worse tumor biology. TN are defined to be negative for estrogen, progesteron and erbB 2-expression. About 15% of all breast cancer have TN characteristics. TN immunhistochemical cytoceratine (CK) staining offers the identification of basal like tumors inside the TN group. CK 5/14 positive tumor cells are defined as basal like carcinomas, which have a poor prognosis. The role of G1 differenciation in TN is unclear. Methods: Between 1995 and 2009 202 TN patients were treated in our institution. Median age was 56 years, the median follow-up was 57 months. 132/202 (65%) pts had G3 tumors. Nodal involvement was 40%. 7/202 (3%) patients had documented G1 differenciation. 2/7 patients recieved primary systemic therapy (PST), 1 patient adjuvant therapy. Anthracycline based PST in both patients was effective (response rate 2 and 3). 4/7 patients recivied no systemic therapy. Tumor blocks of 47 patients were tested with CK 5/14 staining. Results: 26/47 (55%) showed basal-like profile. In basal like tumors no G1 was found. Disease-free (DS) and overall survival (OS) in G1 TN tumors was 74 months, in the whole collective DS was 22 months and OS 39 months. Median proliferation index (Ki 67) in G1 tumors was lower 30%. Conclusions: Patients with good differentiated TN (G1) have lower risk of tumor relapse in comparision to G2 or G3 tumors. Good tumor response to PST and high proliferation index in the small G1 collective indicates the difference to the tumor biology in usuall G1 tumors, which express estrogen and progeteron (luminal A). Because of the small G1 number (3%) inside a small TN collective further analysis have to be done to identify the optimal therapeutic procedure for patients with this rare tumor type. No significant financial relationships to disclose.
Efficacy of ifosfamide, methotrexate, etoposide and prednisone (IMEP) chemotherapy in extranodal NK/T-cell lymphoma, nasal type
Authors: K. W. Lee, D. W. Kim, S. A. Im, T. Y. Kim, S. S. Yoon, D. S. Heo, Y. J. Bang, S. Park, B. K. Kim, N. K. Kim
Journal: Journal of Clinical Oncology (2004)

6685 Background: Although most patients diagnosed with extranodal NK/T-cell lymphoma, nasal type (ENNKTL) have localized disease, radiation therapy alone is not satisfactory because of frequent systemic failure. Also, when compared with B-cell lymphomas, ENNKTL have poor response to conventional doxorubicin-based chemotherapy. Therefore, more effective chemotherapeutic regimens are required. Methods: Patients with histologically confirmed ENNKTL were included. All patients received IMEP chemotherapy as first-line treatment (ifosfamide 1.5 g/m2 i.v. with mesna supplement on days 1–3; methotrexate 30 mg/m2 i.v. push on days 3 and 10; etoposide 100 mg/m2 i.v. on days 1–3; and prednisone 120 mg p.o. on days 1–5). Radiation therapy was used only in patients of Ann Arbor stage I or II developing local failure. Results: Since June 2001, 21 ENNKTL patients were enrolled. Of these patients, 15 patients had nasal localization (Ann Arbor stage I or II) and 6 patients had extranasal or disseminated disease. Median follow-up duration was 9.9 (3.5∼30.0) months. Overall complete remission (CR) rate was 66.7%. Among patients with nasal localization (stage I or II), 11 had CR (84.6%). Of these patients with CR, 3 patients (27.3%) developed recurrence, but this was successfully controlled with additional radiotherapy. However, patients with extranasal or disseminated disease had poor response (CR: 20.0%). Conclusions: IMEP regimen in patients with ENNKTL was effective as first-line therapy, especially in the cases with nasal localization. No significant financial relationships to disclose.
Age-specific prognostic factors in patients treated surgically for pulmonary metastases of colorectal cancer: A multi-institutional cumulative follow-up study.
Authors: Sayumi Nakao, Michio Itabashi, Mamiko Ubukata, Yoshiko Bamba, Tomoichiro Hirosawa, Shimpei Ogawa, Shingo Kameoka, Kenichi Sugihara
Journal: Journal of Clinical Oncology (2015)

773 Background: The aim of this study was to investigate the age-specific prognostic factors for overall survival (OS) and disease-free interval (DFI) after pulmonary metastasectomy for colorectal cancer (CRC). Methods: We performed a retrospective analysis of 1,179 patients who underwent lung resection for colorectal metastases from 2001 to 2012 in 109 affiliated institutions of the Japanese Society for Cancer of the Colon and Rectum study group. The patients were divided into three groups by the age at pulmonary resection: Group A (GA) comprised of 396 patients who underwent lung resection under the age of 60 years old; Group B (GB) comprised of 604 patients who underwent lung resection between the ages of 61 and 74 years old; Group C (GC) comprised of 179 patients who underwent lung resection over the age of 75 years old. We used the Cox proportional hazard regression to identify independent prognostic factors for OS and DFI. Results: Median OS times after pulmonary resection were 45 months, 43 months, and 43 months for GA, GB, and GC, respectively. Two-year and 5-year overall survival rates were 73% and 54% for GA, 77% and 63% for GB, and 82% and 68% for GC, respectively. The independent unfavorable prognostic factors were recurrence after pulmonary resection (p&lt;0.0001) in GA, detection of liver metastases before lung resection (p=0.0126), a high level of carcinoembryonic antigen (p=0.0003), and recurrence after pulmonary resection (p&lt;0.0001) in GB, and recurrence after pulmonary resection (p&lt;0.0001) in GC. Median DFI times were 11 months in all groups. The independent unfavorable prognostic factor was a removal of mediastinal lymph node (p=0.0335) in GB. Conclusions: Elder patients (GC) showed nearly the same OS rate compared with non-elder patients (GB), while younger patients (GA) showed poor OS rate. Recurrence after pulmonary resection revealed to be a poor prognostic factor in all groups.
Intermittent erlotinib (ERL) in combination with pemetrexed (PEM): Phase I schedules designed to achieve pharmacodynamic separation
Authors: A. M. Davies, C. Ho, L. Beckett, D. H. Lau, S. Scudder, P. N. Lara, N. Perkins, D. R. Gandara
Journal: Journal of Clinical Oncology (2008)

8032 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) given concurrently with chemotherapy do not improve patient outcomes compared with chemotherapy alone in advanced non-small cell lung cancer (NSCLC). We hypothesized that pharmacodynamic separation (PDS) by intermittent delivery of EGFR-TKI with chemotherapy would increase efficacy by overcoming proposed antagonism, and tested this concept with docetaxel/ERL (Davies, Clin Lung Cancer 2007). Here we report experience with two schedules of intermittent ERL in combination with PEM. Methods: Two dose escalating phase I trials (Arm A and Arm B) were conducted simultaneously. PEM was given every 21 days in both arms (500 mg/m2 IV). Arm A: ERL was given weekly days 2, 9, 16 (800–1400 mg). Arm B: ERL was given days 2–16 (150–250 mg). Dose limiting toxicity (DLT) was defined as: gr 4 platelets, gr 3 platelets with bleeding, febrile neutropenia, gr 3 ANC with infection, or any ≥ gr 3 non-heme toxicity. Results: 42 patients with advanced solid tumors were treated, including 16 NSCLC. Characteristics: Age range 29–77; Sex: 19 M; KPS ≥90/<90 = 27/15; Median cycles: 2. Treatment was well tolerated. Planned dose escalation has been completed without reaching the MTD. DLTs included gr 3 infection/fever (ARM A: 500/1200) and gr 3 infection/neutropenia (ARM B: 500/150). Gr 1/2 acneform rash: 65%. There were 6 partial responses (4 lung, 1 H&N, 1 breast) and 16 stable disease. 4 NSCLC patients remained on therapy for 9, 16, 16, and 22 cycles. Conclusions: 1. We report the first clinical trial to test intermittent ERL plus PEM to achieve PDS and overcome hypothesized antagonism. 2. PEM 500 mg/m2 and weekly erlotinib 1400 mg (ARM A) or PEM 500 mg/m2 and erlotinib 250 mg day 2–16 (ARM B) are feasible and well tolerated. 3. Efficacy of Arm B regimen is being examined in a randomized phase II trial for second-line NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OSI Oncology Eli Lilly, Genentech Genentech Eli Lilly
Combining plasma TGF-β1 and lung dosimetric factor to predict radiation-induced lung toxicity in patients with non-small cell lung cancer: A combined analysis from Beijing and Michigan
Authors: L. Wang, L. Zhao, W. Ji, X. Wang, X. Zhu, J. A. Hayman, G. P. Kalemkerian, D. Brenner, T. S. Lawrence, F. Kong
Journal: Journal of Clinical Oncology (2008)

7548 Background: We hypothesized that the radiation induced elevation of transforming growth factor β1 (TGF-β1) during radiation therapy (RT) correlates with radiation-induced lung toxicity (RILT) in non-small cell lung cancer (NSCLC) and combined consideration of TGF-β1 and lung dosimetric parameters will be more accurate in predicting RILT. Methods: This study was approved by both institutional boards of University of Michigan Medical Center (UMMC-26 patients) and Peking Union Medical College Cancer Hospital (PUMC-139 patients). Eligible patients included stage I-III NSCLC treated with fractionated RT with or without chemotherapy. Platelet- poor plasma was obtained pre-RT and at 4–5 weeks (40–50 Gy) during-RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was ≥ grade 2 radiation pneumonitis or fibrosis. Logistic regression and Chi-square were used for statistical analysis. Results: A total of 165 protocol patients enrolled from Feb 2004 to Apr 2007. The median radiation dose was 60 Gy and the median mean lung dose (MLD) was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. In the multivariate analysis, TGF-β1 ratio (during-RT/pre-RT) was the only factor that significantly correlated with the risk of RILT (P = 0.044). The incidence of RILT was 46.2% in patients with TGF-β1 ratio >1 versus 7.9% in patients with TGF-β1 ratio ≤ 1 (P < 0.001). As regarding to lung dosimetric consideration, the incidence of RILT was 42.9% if mean lung dose (MLD) > 20Gy versus 17.4% if MLD ≤ 20 Gy (P = 0.035). The incidence of RILT was 4.3% in patients with none of the two negative factors, versus 47.4% in those with one negative factor and 66.7% in those with both the two negative factors (P < 0.001). Conclusions: Radiation induced elevation in plasma TGF-β1 level during RT is predictive of RILT. The addition of MLD may improve the accuracy of prediction. Studies with larger number of cases are warranted to validate such promising findings. No significant financial relationships to disclose.
Challenges in economic outcomes research.
Authors: J R Cook
Journal: Hepatology (1999)

In light of current pressures to limit health care expenditures, economic evaluations will continue to be conducted to help assess the value of new therapies or treatment programs. Although guidelines for the conduct of economic evaluations have been proposed, it is unlikely that a standard/common methodology will (or should) be used. Consequently, it is important that the reader/reviewer of such analyses be aware of the potential challenges or difficulties when evaluating these assessments. While not providing a comprehensive list of these challenges, it is hoped that this article will serve to bring awareness to some of these challenges in the design, analysis and interpretation of these evaluations.
Evaluation of nitinol stent placement complications for palliation of malignant dysphagia
Authors: E. Alach, E. Troncoso, A. Barbero, A. Mainella, M. Lavezzaro, G. Zapata, S. Bonicatto
Journal: Journal of Clinical Oncology (2006)

14120 Background: Over 50% of patients (pts) with obstructive carcinoma are inoperable at the time of the diagnosis and only 18% of them survive beyond a year. Palliative treatment must be quickly effective, safe, well tolerated and focused to relieve symptoms, improving the nutritional state and quality of life. The objective of the study was to investigate the clinical effectiveness and complications of palliative treatment with esophageal stent placement. Methods: Descriptive and prospective study about functionality of nitinol autoexpandible stent was carried out. Evaluable pts included those with confirmed histological diagnosis of inoperable or unresectable esophageal cancer, with some clinical contraindication due to risk or personal rejection. An immediate post placement follow-up was performed after 24hours, 7 and 30 days, to evaluate the stent proper location, its permeability as well as its degree of expansion, presence of epigastric or precordial pain, reflux and degree of dysphagia. Results: From August/02 to September/05 stent was placed in 20 people, 9 women and 11 men, mean age 67.8 (range: 42–85). The autoexpandible stent placement was achieved in 100% of pts (3 = gastric carcinoma and 17 = esophagus carcinoma). Histological diagnosis was epidermoid (11 pts) and adenocarcinoma (9 pts). Inoperable malignant stricture was as follows: lower third: 11 pts (55%), middle third: 9 pts (45%). A second stent was required in 2 pts. Median time of hospitalization was 48 hours.Immediate complications appeared in 12 pts: pain 3 (15%), vomiting 3 (15%), pneumonia 2 (10%), cough 1 (5%), pyrosis 1 (5%). After 24 hour control: pain 2(10%), respiratory complications 2 (10%). The delayed ones were as follows: level 4 dysphagia 2 (10%), pain 8 (40%), reflux 5 (25%). No mortality related to stent placement was observed. Dysphagia was perceptibly reduced, from 3.0 to 1, (p &lt; 0,005). Conclusion: The nitinol stent is easy to place, it provides effective palliation of malignant esophageal obstruction with short hospitalization time and low risk of serious complications. No significant financial relationships to disclose.
A gene expression profile of BRCAness that correlates with responsiveness to platinum and PARP inhibitors.
Authors: P. Konstantinopoulos, D. Spentzos, B. Karlan, T. Taniguchi, E. Fountzilas, N. Francoeur, D. A. Levine, S. A. Cannistra
Journal: Journal of Clinical Oncology (2010)

5004 Background: PARP inhibitors have been evaluated in patients with germline BRCA 1/2 mutations with impressive results. In addition to patients with germline BRCA 1/2 mutations, it has been suggested that PARP inhibition might also be a useful therapeutic strategy for the treatment of some patients with sporadic cancers. In order to better identify such patients, we defined a gene expression profile of “BRCAness” that correlates with responsiveness to platinum and PARP inhibitors. Methods: A publicly available microarray dataset including 61 patients with epithelial ovarian cancer with either sporadic disease or BRCA 1/2 mutations was used for development of the profile. Correlation with platinum responsiveness was assessed in platinum sensitive and resistant tumor biopsy specimens from 6 patients with BRCA germline mutations. Association with PARP inhibitor responsiveness and with radiation-induced RAD51 foci formation (a surrogate of homologous recombination) was assessed in Capan-1 cell line clones. The BRCAness profile was validated in 70 patients (35 patients who had been sequenced and known to be wildtype for BRCA 1/2, and 35 patients enriched for sporadic disease based on negative family history) in order to assess its association with outcome. Results: The BRCAness profile accurately predicted platinum responsiveness and mutation status in 8 out of 10 patient-derived tumor specimens, and between PARP-inhibitor sensitivity and resistance in 4 out of 4 Capan-1 clones. When applied to the 70 patients with sporadic disease, patients with BRCA-like (BL) profile had improved disease-free survival (34 months versus 15 months, log-rank p = 0.013) and overall survival (72 months versus 41 months, log-rank p = 0.006) compared to non-BRCA-like (NBL) patients, respectively. BRCAness profile maintained independent prognostic value in multivariate analysis, controlling for known clinical prognostic factors. Conclusions: The BRCAness profile correlates with responsiveness to platinum and PARP inhibitors and identifies a subset of sporadic patients with improved outcome. Use of this profile may ultimately permit identification of sporadic EOC patients who may benefit from PARP inhibitor therapy. No significant financial relationships to disclose.