tbuckley/cabot-search huggingface dataset:
Identifying critical data elements for a provincial transition plan from a primary care perspective.
Authors: Stacey Hunter, Stefanie De Rossi, Angelika Gollnow, Grace Kim, Ed Kucharski, Taylor Martin, Jasmin Soobrian, Jonathan Sussman, Victoria Zwicker, Suzanne Strasberg
Journal: Journal of Clinical Oncology (2017)

54 Background: Cancer Care Ontario is the provincial government advisor on the cancer and renal systems, as well as access to care for key health services. Enhancing flow of patient information and care plans are priorities to improve continuity and quality of survivorship care. Cancer Care Ontario’s Primary and Community Care and Survivorship Programs have initiated work to identify required information that primary care providers (PCPs) should receive about a patient’s cancer care at the point of transition back to primary care. Methods: Fifteen focus groups were conducted with PCPs in Ontario using a guide to facilitate group discussions on the utility and content of transition plans. Based on the collective feedback, thematic analysis was conducted on data elements that were expressed as critical with 12 common themes identified. Transition plan materials across Ontario’s Local Health Integration Networks and relevant jurisdictions in Canada and the United States were also reviewed to abstract a list of all documented data elements. A comprehensive matrix of data elements was then created by incorporating the list of all documented data elements with the 12 common themes. Using this matrix, prevalence of data elements amongst reviewed materials was ranked by frequency. A Modified-Delphi approach was used to validate and prioritize data elements with Cancer Care Ontario provincial and regional primary care clinical leadership. Results: In total, 21 documents were reviewed and 30 standard data elements were identified and ranked by frequency. The 10 most frequent data elements were classified as required for a standard transition plan. The remaining data elements were presented to 29 Cancer Care Ontario Cancer Leads to reach consensus on a core set of data elements to be required for inclusion in a transition plan. Conclusions: Essential data elements for inclusion in a transition plan have been identified from the perspective of PCPs. Next steps include engaging patient and family advisors, oncologists, and health system administrators through a phased regional consultation process. The role of synoptic reporting for a future standard survivorship transition plan will also be explored.
The predictive value of clinical variables in patients affected with non-small-cell lung cancer (NSCLC) treated with pemetrexed (PEM) plus platinum-based regimen: A retrospective analysis.
Authors: Maria Agnese Fabbri, Luca Moscetti, Fabrizio Nelli, Teresa Gamucci, Giovanni Mansueto, Filomena Narducci, Silvia Quadrini, Isabella Sperduti, Antonio Passaro, Giuseppe Campenni, Enrico Cortesi, Olga Martelli, Sara Bianchetti, Francesco Angelini, Arianna Pellegrino, Ida Pavese, Carlo Signorelli, Enzo Maria Ruggeri
Journal: Journal of Clinical Oncology (2012)

e18065 Background: PEM plus platinum–based regimen is a standard of care in chemonaïve advanced non-squamous NSCLC pts. This retrospective multicenter analysis was performed to evaluate the predictive value of clinical variables for PFS in an unselected population. Methods: Data were obtained by reviewing the clinical data of pts affected with advanced NSCLC treated from 2009 to 2011. 193 pts were retrieved. Main characteristics were: median age: 63 years (range 33-79); male/female (M/F): 67%/33%; ECOG PS 0-1: 97%; weight loss &gt;5%: 34%; current smoker 31%. Stage IV disease: 81% ; ≥ 1 site of metastasis: 79%. Brain metastasis: 28% of pts at diagnosis. Results: All 193 pts are evaluable for analysis. 158 pts (82%) received the cisplatin- and 35 pts (18%) the carboplatin-based regimen. Most pts received at least 2 cycles of therapy and 21% received PEM maintenance treatment. The overall disease control rate observed was 69%. (CR+PR = 44%, SD 25%). At a median follow-up of 6.7 months (range 1-22), the median PFS was 6 months (95%CI 5-7) with a 1 year-PFS rate of 16.8%. In the Cox multivariate analysis, factors found to be associated with a statistically significant longer PFS were: gender (M vs F, HR 1.68, C.I.95% 1.19-2.38; p=0.003); no. of metastatic site (&gt;1 vs 1, HR 1.6, 95%CI 1.07-2.40; p=0.02); type of response (CR/PR vs no response, HR 2.74, 95%CI 1.95-3.86; p&lt;0.0001); and maintenance treatment (no vs yes, HR 2.74, 95%CI 1.95-3.86; p=0.02). The Kaplan-Meyer analysis of 1-year PFS confirmed female gender (F vs M 24.4% vs 12.2%, log-rank p=0.01), objective response (CR/PR vs SD/PD 29.9% vs 5.2%, log-rank p&lt;0.0001), and maintenance therapy (yes vs no 30% vs 17.3%, log-rank p=0.01) as the significant clinical variables predictive of longer survival. Conclusions: According to our data only female gender, responsive disease and subsequent maintenance therapy were independent predictive factors. No difference in term of PFS outcome were found for elderly pts, presence of brain metastases and weight loss at diagnosis. Overall survival data will be presented.
Prolonged Apnea Supported by High-Frequency Noninvasive Ventilation: A Pilot Study
Authors: Adam Ogna, Maurizio Bernasconi, Bastien Belmondo, Olivier Long, Julien Simons, Nicolas Peguret, Raphaël Heinzer, Laurent P. Nicod, Jean Bourhis, Alban Lovis
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Alcohol and cardiovascular disease
Authors: Kenneth Mukamal, Mariana Lazo
Journal: BMJ (2017)

Big data puts the link between moderate drinking and lower risk under the microscope

Over four decades ago, Klatsky and his colleagues published perhaps the first carefully conducted epidemiological investigation of alcohol consumption and risk of myocardial infarction,1 a case-control study nested within the health records of the Kaiser Foundation Health Plan in California. Taking advantage of some 120 000 health plan members who completed a standardized set of over 500 individual questions, the authors identified 464 members who sustained an incident myocardial infarction at local Kaiser hospitals. They compared the alcohol consumption reported on a previous questionnaire among these members with that of two sets of controls drawn from the same source population. Among non-smokers, the odds of myocardial infarction were about twice as high among non-drinkers as among drinkers, raising the possibility that alcohol consumption could lower risk of coronary heart disease.1

In subsequent analyses of members of the Kaiser-Permanente health maintenance organization, Klatsky and colleagues went on to show that alcohol consumption has diverse associations with various forms of cardiovascular disease and its risk factors, including a roughly …
Ruxolitinib Prevents Cytokine Release Syndrome after CART Cell Therapy without Impairing the Anti-Tumor Effect in a Xenograft Model
Authors: Saad S Kenderian, Marco Ruella, Olga Shestova, Miriam Y Kim, Michael Klichinsky, Fang Chen, Natalka Kengle, Simon Francis Lacey, J. Joseph Melenhorst, Carl H June, Saar I. Gill
Journal: Blood (2016)
Pharmacogenetic study of Japanese patients with advanced nonsquamous non-small cell lung cancer treated with pemetrexed plus cisplatin.
Authors: Hisao Imai, Masakuni Serizawa, Toshiaki Takahashi, Keita Mori, Akira Ono, Hiroaki Akamatsu, Tetsuhiko Taira, Yukiko Nakamura, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Yasuhiro Koh, Masahiro Endo, Takashi Nakajima, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2013)

e19050 Background: Pemetrexed (PEM) inhibits multiple enzymes in the folate (F) pathway. Several studies show that genetic polymorphisms in these enzymes influence the efficacy and toxicity of PEM. We aimed to investigate the relationship between genetic polymorphisms associated with the F pathway and clinical outcomes of Japanese patients with advanced non-squamous non-small cell lung cancer (NSQ-NSCLC) treated with PEM plus cisplatin (CIS). Methods: We analyzed 38 polymorphisms in 15 genes associated with the F pathway in NSQ-NSCLC patients treated with PEM plus CIS: ABCC11, ADA, ATIC, CBS, DHFR, ERCC1, FPGS, GGH, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS. These polymorphisms were compared with clinical outcomes such as response, toxicity, and progression-free survival (PFS) using Pearson’s χ 2 test and the log-rank test. Results: All 56 patients were Japanese, with a median age of 62 years; 57.1% were male, 96.4% had an Eastern Cooperative Oncology Group Performance Status of 0–1, 96.4% had stage IV disease, and 94.6% had adenocarcinoma. The response rate, disease control rate, and median PFS were 32.2%, 78.6%, and 4.7 months, respectively. Of the 38 polymorphisms tested, none were associated with response or toxicity, but 2 single nucleotide polymorphisms (SNPs) (in the gamma-glutamyl hydrolase [GGH 452C&gt;T] and methionine synthase [MTR 2756A&gt;G] genes) were significantly associated with PFS. Patients harboring the GGH-C452C variant had significantly longer PFS (5.6 vs 2.8 months; p &lt; 0.0001) than those with the C452T or T452T variants. Further, patients harboring the MTR-A2756A variant had significantly longer PFS (5.3 vs 3.7 months; p = 0.036) than those with the A2756G variant. In addition, among patients with the GGH-C452C variant, those harboring the MTR-A2756A variant had significantly longer PFS (5.9 vs 4.3 months; p = 0.044) than those with the A2756G variant. Conclusions: SNPs in GGH and MTR seem to predict differences in PFS in NSQ-NSCLC patients treated with PEM plus CIS, and a combination of these 2 SNPs may predict differences in PFS more accurately. These results should be validated in larger, adequately designed prospective studies.
Validation of GEMCaP as a DNA based biomarker to predict disease recurrence in patients undergoing prostatectomy for prostate cancer.
Authors: Hao Gia Nguyen, Christopher Welty, Karla Lindquist, Vy Ngo, Elizabeth Gilbert, Henrik Bengtsson, Cristina Magi-Galluzzi, Jerome Jean-Gilles, Jorge Yao, Matthew R. Cooperberg, Edward M. Messing, Eric A. Klein, Peter Carroll, Pamela Paris
Journal: Journal of Clinical Oncology (2017)

58 Background: There are currently no validated DNA based biomarkers available for routine clinical use to predict prostate cancer recurrence after prostatectomy. The Genomic Evaluators of Metastatic Cancer of the Prostate (GEMCaP) assay is a tumor genotype using copy number for a set of genomic loci. We aim to validate the GEMCaP assay using an external cohort of intermediate and high risk patients. Methods: We randomly identified 203 patients who had undergone radical prostatectomy at the Cleveland Clinic (CC) and University of Rochester (UR) from 2000-2005. DNA from macrodissected cancer tissues were subjected to high resolution array comparative genomic hybridization (aCGH) using Agilent’s oligonucleotide microarray platform. A high GEMCaP score was defined as &gt; 20% of the genomic loci exhibiting copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and risk of biochemical recurrence in univariate and multivariate analyses adjusted for the CAPRA-S score. The outcome was biochemical failure defined as PSA &gt; 0.2. Results: We report the results from 140 patients, with sufficient DNA and acceptable aCGH, 54 from the CC cohort and 86 from the UR cohort. Median time to recurrence was 45.3 months and median follow-up among those who did not recur was 120.2 months. Based on the CAPRA-S score, 39.3% were low-risk, 42.2% were intermediate-risk and 18.5% were high-risk. 30.7% of the cohort had a high GEMCAP score ( ≥ 20%). A high GEMCaP score was associated with higher risk of biochemical recurrence (HR 2.69, 95%CI 1.51-4.77) and remained associated with biochemical recurrence after adjusting for the CAPRA-S score (HR 1.91, 95% CI 1.05-3.48). The C-index for GEMCaP alone was 0.64, and improved when combined with CAPRA-S (C-index = 0.76). Conclusions: In this validation study, a high GEMCaP score was associated with biochemical recurrence in two external cohorts. This remained true after adjusting for clinical and pathologic factors as accounted for by the CAPRA-S score. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify prostate cancer patients for early adjuvant therapy.
Materials for Microfluidic Immunoassays: A Review
Authors: Lei Mou, Xingyu Jiang
Journal: Advanced Healthcare Materials (2017)

Conventional immunoassays suffer from at least one of these following limitations: long processing time, high costs, poor user‐friendliness, technical complexity, poor sensitivity and specificity. Microfluidics, a technology characterized by the engineered manipulation of fluids in channels with characteristic lengthscale of tens of micrometers, has shown considerable promise for improving immunoassays that could overcome these limitations in medical diagnostics and biology research. The combination of microfluidics and immunoassay can detect biomarkers with faster assay time, reduced volumes of reagents, lower power requirements, and higher levels of integration and automation compared to traditional approaches. This review focuses on the materials‐related aspects of the recent advances in microfluidics‐based immunoassays for point‐of‐care (POC) diagnostics of biomarkers. We compare the materials for microfluidic chips fabrication in five aspects: fabrication, integration, function, modification and cost, and describe their advantages and drawbacks. In addition, we review materials for modifying antibodies to improve the performance of the reaction of immunoassay. We also review the state of the art in microfluidic immunoassays POC platforms, from the laboratory to routine clinical practice, and also commercial products in the market. Finally, we discuss the current challenges and future developments in microfluidic immunoassays.
A proposal for a novel and simple TNM staging for gastric cancer.
Authors: Taeil Son, Jiyu Sun, Hyoung-Il Kim, Jong Won Kim, Jae-Ho Cheong, Seung Ho Choi, Sung Hoon Noh, Yanghee Woo, Yuman Fong, Sohee Park, Woo Jin Hyung
Journal: Journal of Clinical Oncology (2017)

21 Background: Current TNM staging system for gastric cancer has controversies regarding N classification. We aimed to develop a simple and novel TNM staging system for gastric cancer by re-grouping N classification. Methods: We retrospectively reviewed 14260 patients treated for gastric cancer. To develop simple combinations of TNM staging with similar weighted value between T and N classification, N classification was restructured with different cutoffs. The optimal cutoffs for the number of metastatic lymph node which maximize the x 2 statistic of log-rank test for survival differences among patients were selected. C-statistic was used to compare the discriminating performance of the proposed N classification with the current N classification in the TNM staging system. We performed validation with 2 external datasets from a hospital in Korea (n = 1500) and SEER (n = 11324). Results: We identified the new cutoffs of N classification as 1~4, 5~10, 11~24, and 25 or more for N1, N2, N3a, and N3b, respectively. We found survival of the new N3b classification was similar to M1, regardless of T classification. Thus, we stratified these groups of N3b and M1 disease as stage IV, simultaneously. Our new TNM staging had similar weighted value between T and N classification resulting in simple combinations. (Table) Survival curves of subgroups in the new TNM staging had higher x 2 value than current staging system (x 2 : 8239 vs. 7023, respectively) and homogeneity among subgroups in the same stage increased. However, C-statistics (0.801, 95%CI: 0.795, 0.807) of new model showed similar discrimination power than that (0.797, 95%CI: 0.791, 0.803) in 7th TNM staging system. C-statistics were also similar in other hospital in Korea (0.805 vs. 0.802, respectively) and SEER database (0.709 vs. 0.706, respectively). Conclusions: This novel staging system by recalculating cut-offs of N classification provides exceptionally simple and practical way to stratify substages in TNM staging for gastric cancer. [Table: see text]
10-year remission rates following rituximab (R) and FND chemotherapy (fludarabine, mitoxantrone, dexamethasone) with interferon (IFN) maintenance in indolent lymphoma: Results of a randomized study.
Authors: Loretta J. Nastoupil, Sattva Swarup Neelapu, Felipe Samaniego, Fredrick B. Hagemeister, Jorge Enrique Romaguera, Larry W. Kwak, Michael Wang, Luis Fayad, Michelle A. Fanale, Yasuhiro Oki, Jason R. Westin, Maria Alma Rodriguez, Fernando Cabanillas, Peter McLaughlin, Nathan Hale Fowler
Journal: Journal of Clinical Oncology (2014)

8528 Background: Between 1997-2002, we conducted a randomized trial for patients (pts) with previously untreated stage IV small lymphocyctic (SLL), marginal zone (MZL), or follicular lymphoma (FL), with the primary aim to compare concurrent FND+R versus sequential FND followed by R. This is the final analysis with mature data. Methods: Patients were randomized to 6 doses of R given during the first 5 of 8 courses of FND, or monthly during IFN maintenance following FND. We now report response rates, progression free survival (PFS), overall survival (OS), and adverse events (AE) including secondary malignancy with nearly 12 years of follow up. Results: Of the 157 pts, 18% had SLL, 11% MZL, and the remaining 71% had FL. 80 pts received concurrent FND+R, 77 sequential. Pts on the 2 arms were comparable in terms of prognostic features (FLIPI components). Median age for all pts was 54 years, 54% were female, 90% had bone marrow involvement, 80% had intermediate or high FLIPI score, 68% had high tumor burden. With a median follow up of 11.8 years, response rates, PFS, and OS were similar between the two groups and are included in the table below. Most AEs were hematologic, grade ≥3 neutropenia in 76%, thrombocytopenia 24%, and anemia in 13%. There was slightly more neutropenia with FND+R, but no excess infection or neutropenic fever. Non-hematologic AEs were mostly grade 1/2: 46% fatigue, 33% nausea, 31% alopecia, 18% neuropathy, and 18% infection (8% grade ≥3 infection). Six pts (4%) developed MDS/AML. Conclusions: With mature data, this large frontline study of FND with either concurrent or sequential R, and IFN maintenance in advanced stage indolent lymphoma demonstrated high complete response rates, robust PFS and OS. Determining the curative potential for this highly effective therapy will require further follow up. Concerns about tolerability and the incidence of secondary malignancy may impact treatment decisions. Clinical trial information: NCT00577993. All patients N=157 FND+R N=80 FND->R N=77 CR/CRu 90% 93% 87% 10-yr PFS estimates 55% 53% 56% Median OS 10-yr OS estimates Events NR 76% 63 NR 74% 35 NR 78% 28
The impact of lymph node ratio (LNR) on the prognosis of colorectal cancer.
Authors: Bernadette Hanley, Brian Richard Bird, Jo O' Keeffe, Conleth G. Murphy
Journal: Journal of Clinical Oncology (2014)

e14595 Background: The American Joint Committee on Cancer (AJCC) uses the number of positive lymph nodes removed as one of their staging criteria for colorectal cancer. However, in recent years, many studies have shown lymph node ratio (LNR; ratio of positive lymph nodes to the total number dissected) to be a more significant prognostic factor. Methods: We performed a retrospective study of all patients diagnosed with node-positive colorectal cancer in a single institution between January 1, 2000 and December 31, 2011. End points were overall survival (OS) and disease-free survival (DFS). Patients were stratified into LNR groups 1 (LNR≤0.11), 2 (0.11<LNR≤0.27), and 3 (LNR>0.27). Results: 172 patients met the inclusion criteria (109 colon, 63 rectal). In the colon cancer patients, 5-year OS decreased significantly (p<0.05) with increasing LNR: 75.8% (LNR1), 62.5% (LNR2) and 41% (LNR3). Similarly, 5-year DFS decreased significantly (p<0.05) from 75.5% (LNR1) to 38.8% (LNR3). Conversely, in the rectal cancer patients, 5-year OS increased from 41.7% (LNR1) to 74.4% (LNR3) and 5-year DFS increased from 34.9% (LNR1) to 54.1% (LNR3). 25% of the rectal cancer patients received neoadjuvant chemoradiation. When the pN1a group of colorectal cancer patients was divided into low- and high-risk LNR groups, 5-year OS was 78% within the lower LNR group and 43% within the higher LNR group. Conclusions: LNR is a useful prognostic indicator for colon cancer patients; however, further research is required to examine the trend shown in rectal cancer patients. A proportion received neoadjuvant chemoradiation which may confuse results. Given the small numbers, this may be a statistical anomaly. LNR also identifies heterogeneity within the current staging system and provides additional prognostic classification, as demonstrated in our pN1a patients.
sVEGFR2 and circulating tumor cells to predict for the efficacy of pazopanib in neuroendocrine tumors (NETs): PAZONET subgroup analysis.
Authors: Enrique Grande, Oriol Casanovas, Julie Earl, Daniel E. Castellano, Rocio Garcia-Carbonero, Alex Teule, Ignacio Duran, Jose Fuster, Isabel Sevilla, Pilar Escudero, Javier Sastre, Jesús García-Donas, Luis Ortega, Juan Jose Diez, Ainara Soria Rivas, Jaume Capdevila
Journal: Journal of Clinical Oncology (2013)

4140 Background: The PAZONET trial (Grande et al, ESMO 2012) performed by the GETNE group analyzed the efficacy and safety of the use of pazopanib (800 mg/qd) in patients (pts) with progressive metastatic NETs that had been previously treated with other novel targeted agents. Here we report on the relationship between clinical outcome and circulating and tumor-related biomarkers. Methods: Kaplan-Meier analysis was used to correlate progression-free survival (PFS) with: blood circulating markers at baseline and after 12 weeks of treatment (VEGF-A and sVEGFR2 circulating plasma, Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC)), tumor functional status, Ki67, concomitant somatostatin analogues (SSA), chromogranin A (CgA) and primary tumor location. Results: 44 pts were enrolled, 42 were evaluable for response. sVEGFR2 decreased after 12 weeks of treatment (median decrease 20%, p&lt;0.0001) and the duration of treatment with pazopanib was associated with a decrease in sVEGFR2 (p=0.0046). Pts with a decrease in sVEGFR2 of &gt;20% and &lt;=20% had a median progression-free survival (mPFS) of 12.6 and 9.1 months (mo) respectively (p=0.067). Pts with and without CTC at baseline had a mPFS of 5.8 and 9.1 mo respectively (p=0.12). VEGFA and CEC were not found to predict PFS. mPFS in the intention to treat population was 10.0 mo (95% CI 4.3-15.6). Significant differences in mPFS were found in concomitant SSA treatment (11.9 mo [10.6-13.2]) vs. pazopanib alone (4.8 mo [3.0-6.6]) (p=0.007); decrease of CgA (3.4 mo [0.0-6.8]) vs no decrease (11.2 mo [8.4-14.1]) (p=0.024) and pancreatic (12.8 mo [11.0-14.6]) vs gastrointestinal (10.0 mo [4.9-15.1]) vs other primary tumors (3.4 mo [0.0-7.0]). No differences in mPFS were seen in functioning (10.0 mo) and non-functioning tumors (9.3 mo) and Ki67 status (&lt; 2% 10.0 mo, 3-10% 10.8 mo or &gt;10% 4.1 mo). Conclusions: sVEGFR2 and baseline CTC are promising predictive biomarkers for pazopanib in NETs. The updated results confirm the efficacy of pazopanib as a sequencing treatment of pts with progressive NETs, particularly in those with pancreatic primary tumors. The combination of pazopanib and SSA seems to be synergistic. Clinical trial information: NCT01280201.