tbuckley/cabot-search huggingface dataset:
Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous Glucose Monitoring
Authors: Richard M. Bergenstal, Roy W. Beck, Kelly L. Close, George Grunberger, David B. Sacks, Aaron Kowalski, Adam S. Brown, Lutz Heinemann, Grazia Aleppo, Donna B. Ryan, Tonya D. Riddlesworth, William T. Cefalu
Journal: Diabetes Care (2018)

While A1C is well established as an important risk marker for diabetes complications, with the increasing use of continuous glucose monitoring (CGM) to help facilitate safe and effective diabetes management, it is important to understand how CGM metrics, such as mean glucose, and A1C correlate. Estimated A1C (eA1C) is a measure converting the mean glucose from CGM or self-monitored blood glucose readings, using a formula derived from glucose readings from a population of individuals, into an estimate of a simultaneously measured laboratory A1C. Many patients and clinicians find the eA1C to be a helpful educational tool, but others are often confused or even frustrated if the eA1C and laboratory-measured A1C do not agree. In the U.S., the Food and Drug Administration determined that the nomenclature of eA1C needed to change. This led the authors to work toward a multipart solution to facilitate the retention of such a metric, which includes renaming the eA1C the glucose management indicator (GMI) and generating a new formula for converting CGM-derived mean glucose to GMI based on recent clinical trials using the most accurate CGM systems available. The final aspect of ensuring a smooth transition from the old eA1C to the new GMI is providing new CGM analyses and explanations to further understand how to interpret GMI and use it most effectively in clinical practice. This Perspective will address why a new name for eA1C was needed, why GMI was selected as the new name, how GMI is calculated, and how to understand and explain GMI if one chooses to use GMI as a tool in diabetes education or management.
E2 to enhance the ability of doxorubicin to disturb iron homeostasis, induce cell cycle arrest and apoptosis in breast and ovarian cancer cell lines.
Authors: Khuloud Bajbouj, Jasmin Shafarin, Mawieh Hamad
Journal: Journal of Clinical Oncology (2018)

e24225 Background: Doxorubicin (Dox) remains a gold standard of leukemia treatment and some solid tumors. Dox precipitates some of its anti-cancer effects by disrupting iron metabolism, an effect that drives generation of reactive oxygen species and oxidative stress. Estrogen (E2, 17-β estradiol) has been shown to disrupt intracellular iron metabolism, induce oxidative stress and cause membrane damage in target cells. The aim of our study is to assess whether treating cancer cells with E2 prior to Dox could further disturb iron metabolism, induce stronger oxidative stress responses and enhance apoptosis. Methods: Cell count, viability, and apoptosis were evaluated in MCF-7, SKOV-3, MDA-MB-231 and Hep-G2 cells treated with 20 nM E2 for 48 h prior to treatment with 1ug/ml Dox for 24 or 48 h. The expression of iron regulatory proteins (hepcidin, ferroportin, and transferrin receptors 1 and 2) and cell cycle regulatory proteins was also assessed in treated cells. Results: A significant increase in ferroportin and ferritin expression was observed in MCF-7 cells treated with E2+Dox as compared with cells receiving Dox alone. Although hepcidin synthesis was reduced in E2+Dox-treated MCF-7 cells, its levels were similar to that in Dox alone-treated cells. E2+Dox treatment led to a significant decrease in cell count and viability in MCF-7, SKOV-3 and MDA-MB-231 cells as compared with that in Dox or E2 alone treated cells. Cell cycle arrest at the G1 phase was more significant in those cells receiving E2+Dox treatment as compared with those receiving Dox or E2 alone. Furthermore, levels of apoptosis were significantly higher in E2+Dox treated these cells in comparison with similar cultures receiving Dox or E2 alone. Hep-G2 cells treated with E2+Dox showed reduced cell count and viability, cell cycle arrest and apoptosis at levels that were statistically similar to Dox alone treated cells. Conclusions: These findings suggest that sensitizing epithelia-derived cancers with E2 prior to Dox further disrupts intracellular iron metabolism and enhances cell cycle arrest and apoptosis.
Immunotherapy efficacy and toxicity in a real-world elderly population.
Authors: Joobin Sattar, Baskoro Kartolo, Wilma M Hopman, Joshua Matthew Lakoff, Tara D. Baetz
Journal: Journal of Clinical Oncology (2018)

e15137 Background: Immunotherapy has emerged as an effective treatment option for the management of advanced cancers. However, the immune system modulation of this class of medication can cause immune related adverse events (irAEs). In this study, we explored the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and irAE in the context of real-world management of solid cancers. Methods: This retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined 'Elderly' as age ≥75. We collected treatment responses, efficacy, and irAEs as study outcomes. All statistical analyses were conducted under SPSS IBM for Windows version 24.0. Results: Our study (N = 78) had 29 (37%) patients age < 65, 26 (33%) patients age 65-74, and 29 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age < 65, age 64-74, age ≥75 groups respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28-43.9, 95% CI) and 17 months (0-36.9, 95% CI) in the age < 65 and age 64-74 groups respectively, and it has not been reached in the age > 75 (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups. Conclusions: Elderly patients are able to tolerate and gain significant benefit from immunotherapy at least as much as or even more than younger patients. The toxicity of the single agent immunotherapy is mild in this population, and the treatment is well-tolerated. Future studies in evaluating aging and combination immunotherapy would be required.
Apalutamide + abiraterone + leuprolide with stereotactic, ultra-hypofractionated radiation (AASUR) in very high risk prostate cancer (PCa).
Authors: Sean Matthew McBride, Michael J. Zelefsky, Daniel Eidelberg Spratt, Marisa Kollmeier, Susan F. Slovin, Jahan Aghalar, Jason W.D. Hearn, Robert Benjamin Den, Curtiland Deville, Karen Borofsky, Han Xiao, Wassim Abida, Howard I. Scher, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2018)

TPS5100 Background: Radiotherapy and long course (18-28 months) androgen deprivation therapy (ADT) is a current standard of care in very high risk PCa; however, biochemical failure remains frequent. We hypothesize that stereotactic, hypofractionated radiotherapy (SBRT) delivered with a total of 6 months of apalutamide, abiraterone (Abi), and leuprolide will result in a superior 3-year rate of biochemical control compared to the historical control of conventionally fractionated radiation therapy (42-48 treatments) and long term ADT in pts with very high risk PCa (Gleason 9-10 or 2 high risk features or > 4 Gleason 8 cores ). The regimen, if proven in a phase 3 setting, would enable very high risk PCa pts to receive curative therapy with potentially decreased morbidity compared with extended androgen ablation. Methods: We present a single arm, phase 2 trial to determine the efficacy of anti-androgen therapy combined with SBRT in very high risk PCa, with the proportion of pts who have had biochemical failure (nadir+2) by 36-months post completion of anti-androgen therapy as the primary endpoint. Eligible pts will receive 6 months of leuprolide, abi, and apalutamide to begin 3 months prior to SBRT with continuation 3 months post-SBRT. Pts will be assessed every 4 weeks (±1 week) (cycle = 28 days) throughout study treatment, and at least once during SBRT. A prostate biopsy will be required prior to the start of SBRT; 2 additional biopsies (at 24 months and, if applicable, metastatic progression) will be performed; partial exome analyses using the MSKCC genomic platform (IMPACT) will be performed on all biopsies; additional correlatives include circulating tumor cell evaluation and cell-free DNA measurement pre and post treatment. Interim analysis will ensure early trial termination should toxicities exceed historical controls. 32 of planned 58 pts have been enrolled. The trial is open at 5 sites and managed by the Prostate Cancer Clinical Trials Consortium and funded by Janssen. Clinical trial information: NCT02772588.
Doxorubicin plus dacarbazine (DoDa), doxorubicin plus ifosfamide (DI) or doxorubicin alone (Do) as first line treatment for advanced leiomyosarcoma (LMS): A retrospective study from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG).
Authors: Lorenzo D'Ambrosio, Nathan Touati, Jean-Yves Blay, Giovanni Grignani, Ronan Flippot, Anna Malgorzata Czarnecka, Sophie Piperno-Neumann, Javier Martin Broto, Roberta Sanfilippo, Daniela Katz, Florence Duffaud, Bruno Vincenzi, Bernd Kasper, Daniel P. Stark, Filomena Mazzeo, Armin Tuchscherer, Saskia Litiere, Ward Sents, Hans Gelderblom, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2018)

11574 Background: LMS is one of the most common soft tissue sarcoma histotypes that may arise in any site of the body. In advanced disease, first line treatment is still based on Do alone or in combination. Previous retrospective data suggested limited activity of ifosfamide (Sleijfer 2010), whereas Da showed interesting results in limited series. DoDa, DI and Do regimens were retrospectively evaluated as first line treatment in advanced LMS. Methods: Inclusion criteria: confirmed histological diagnosis, treatment between 1/2010 and 12/2015, measurable disease (RECIST 1.1), ECOG performance status (PS) ≤2, age ≥18 years, no major comorbidities. Endpoints: progression-free survival (PFS), overall survival (OS), overall response rate (ORR), toxic death (TD) rate. Results: 303 patients, 87 males (29%), median age 58 (range 20-87), were enrolled from 18 EORTC STBSG sites and were distributed as follows: 117 DoDa (39%), 71 DI (23%), 115 Do (38%). No significant differences were detected between treatment arms in terms of dose reductions > 10%, delays > 72h, G-CSF use, or TD. Median PFS was 9.4 (95% CI 6.1-9.7), 6.8 (4.5-9.5), 5.4 months (3.8-6.8), and ORR was 36.8%, 21.5%, and 25.9%, for DoDa, DI and Do, respectively. When attempting to adjust for lack of randomization by balancing baseline characteristics among arms, a non-significant trend for PFS and ORR in favor of DoDa was observed. Shorter median follow-up was observed in DoDa (32 months; IQR 23-47) compared to DI (50; 37-73) and Do arms (46; 31-58), weakening a direct comparison of OS. Subsequent treatments were well balanced across arms. Conclusions: To our knowledge, this is the largest retrospective study on the first line treatment of advanced LMS. Acknowledging the limitations of such retrospective analysis and the unbalanced follow up, DoDa may favorably compare with both DI and Do showing interesting activity in advanced LMS in terms of both ORR and PFS similar to previous single center-based experiences. Consistency of both DI and Do arms outcomes with EORTC 62012 trial results increases the reliability of these results.
Association of single nucleotide polymorphisms (SNPs) in TPD52 gene with response to treatment with enzalutamide (ENZA) in men with metastatic castration refractory prostate cancer (mCRPC).
Authors: Neeraj Agarwal, Hannelore Heemers, James M. Farnham, Shiven B. Patel, David Michael Gill, Sumati Gupta, Craig Teerlink, Robert A Stephenson, Anitha Alex, Lisa A Cannon-Albright
Journal: Journal of Clinical Oncology (2016)

5066 Background: Germline variations in genes encoding proteins that contribute to androgen receptor (AR)’s transcriptional output may be associated with response to AR antagonists in men with mCRPC, serve as prognostic and predictive biomarkers, and guide towards more individualized therapy. Methods: 3152 single nucleotide polymorphisms (SNPs) from the Illumina OmniExpress genotyping platform within the boundaries of 253 genes encoding proteins that contribute to AR’s transcriptional output, and may be associated with response to novel AR antagonists, were investigated for association with time to treatment failure (TTF) in 43 Caucasian men with mCRPC, treated with ENZA. Cox proportional hazard analysis was employed using Gleason score as a covariate and assessing each SNP under an additive genetic model in which the number of minor alleles contributes increasing risk (or protection). Results: Four SNPs in the TPD52 gene showed evidence of association with time to TTF on ENZA, controlling for Gleason Score (p < .0007) (Table). Dysregulation of oncogenic TPD52 by genomic amplification and androgen induction have been reported in association with progression of mCRPC (Rubin MA et al, Cancer Research 2004). Conclusions: To our knowledge, this is the first report on investigation of possible associations of germline DNA variants with TTF on ENZA. Although the sample size is small and the results should be considered preliminary, they represent an important step forward. These results are being validated in a larger cohort. gene chromosome SNP bp position p value #Cases (median TTF, months) 0 Rare 1 Rare 2 Rare TPD52 8 rs1025187 80981317 0.000921 26(7.0) 16(2.0) 1(1.0) TPD52 8 rs16907441 80993478 0.001458 29(7.0) 13(2.0) 1(1.0) TPD52 8 rs6473202 81036045 0.001458 34(7.0) 8(2.0) 1(1.0) TPD52 8 rs4740122 81068774 0.001911 34(7.0) 8(2.0) 1(1.0) *Equal contribution from authors Neeraj Agarwal, Hannelore Heemers and James M. Farnham.
Abstract 18064: Lipid Reduction Measurements in a Veteran Population - Implications for Genetic Modeling in the Million Veteran Program
Authors: Derek Klarin, Yuk-Lam Ho, David R Gagnon, Jacqueline Honerlaw, Jason L Vassy, Deepak Voora, Tim Assimes, Daniel J Rader, William Boden, Scott Damrauer, Pradeep Natarajan, Sekar Kathiresan, Christopher J O’Donnell, J. Michael Gaziano, Kelly Cho, Philip S Tsao, Peter W Wilson
Journal: Circulation (2016)

Introduction: The 2013 ACC/AHA guidelines on the Treatment of Blood Cholesterol to Reduce Cardiovascular Risk presented a new statin algorithm to guide the selection of a statin agent and dosage ba...
Influence of ADIPOQ rs266729 G/C gene polymorphism on serum adiponectin and correlation with metabolic syndrome in colorecatal cancer patients.
Authors: Rosa Divella, Antonella Daniele, Raffaele DeLuca, Porzia Casamassima, Eufemia Savino, Rosanna Maci, Eleonora Montenegro, Cosimo Caliandro, Eustachio Ruggeri, Francesco Giotta, Gennaro Gadaleta-Caldarola, Ivan Lolli, Antonio Mazzocca, Michele Simone, Ines Abbate
Journal: Journal of Clinical Oncology (2016)

e23280 Background: Adiponectin (APN), the product of the ADIPOQ gene, is sited on chromosome 3q27, which is linked to a susceptibility locus for metabolic syndrome (MetS). MetS is associated with an increased risk of colon cancer and APN displays beneficial antineoplastic effects. In fact, decreased APN serum levels correlate with tumor development and progression. The APN rs266729 gene polymorphism is significantly associated with low APN levels and is thought to be linked to susceptibility to cancer. Here, we investigate the influence of APN rs266729 G/C polymorphism on APN circulating levels in colorectal cancer patients (CRC) with and without MetS. Methods: Blood samples from 85 CRC patients 40 women and 45 men with and without MetS, were genotyped for APN rs266729 G/C polymorphism by TETRA ARMS PCR and ELISA assay was used to measure APN serum levels. Biochemical and anthropometric parameters of MetS were also obtained. Results: We found that CRC patients (N = 51) with genotype rs266729G/C or carriers of G allele were associated with a significantly increased risk of MetS development (OR = 2.93) compared to those with CC genotype (N = 34). Also, CG/GG genotypes were associated with significantly lower serum APN levels in comparison to CC genotype (P = 0.034) and that APN levels decreased in relation to BMI increases (P = 0.001). Conclusions: Our findings show that APN rs266729 G/C polymorphism is associated with lower APN levels in CRC patients, suggesting that decreased APN circulating levels may be a determinant risk factor for CRC in Mets patients.
Octogenarians with colorectal cancer: Clinical characteristics and therapy in a single institution experience.
Authors: Elizabeth Inga Saavedra, Jose Ramon Rodríguez, Estefania Casaut, Veronica Serrano, Alba Gonzalez-Haba, Maria Fernanda Martinez, Esperanza Blanco, Jacobo Gomez-Ulla Astray
Journal: Journal of Clinical Oncology (2018)

e22036 Background: As the population ages, octogenarians are becoming the fastest growing patient demographic for colorectal cancer (CRC). Treatment of the elderly with CRC has, therefore, become an important issue. Methods: We performed a retrospective observational study of all octogenarians (≥80 years) with CRC referred to Medical Oncology during 5 years (2012-2016) and followed until December 2017. Clinicopathological data collected included age, gender, stage, and treatment including surgery, radiation or chemotherapy (CT). Results: Octogenarians were a 19% of all patients (pts) with CRC. Our study cohort was 141 pts, 80(57%) men and 61(43%) women. The median age was 84 years (80-94); 8(6%) were aged 90 years or more. There was no difference in performance status (PS) between genders with PS 0-1 in 75%, PS 2 in 18% and PS 3-4 in 7%. In 64% of patients Charlson Comorbidity Index score was significantly lower ( < 3) The tumor was located in the rectum, left colon and right colon in 19%, 39% and 42% of cases. Stage at diagnosis included IV (n = 48), III (n = 51), II (n = 28) and I (n = 14). For stage IV 35/48 pts(72%) received CT: 28 capecitabine (cape) monotherapy, 3 capeox (cape and oxaliplatin) and 4 oral tegafur-uracil, at first line. 12%(25) had second-line treatment (3 cape, 5 capeox, 3 cape-irinotecan and 1 tegafur-uracil); 6 pts had 3 lines. Median overall survival (OS) for those with stage IV who received CT was 526 days (347-704) versus 234 days(27-509) for best supportive care (p < 0.05). For stage III 40/51 pts(78%) received adjuvant CT: 33 cape, 1 capeox and 6 oral tegafur-uracil. OS for who received CT was 1512 days (1244-1780) compared to 846 days who did not (638-1054). To date, 74 pts died (52%), most of them at hospital (51%). Median follow-up was 1137 days (36 months). Stage IV pts had an expected OS of 453 days, stage III 1430 days and stage II pts 1715 days. (p < 0.05). Conclusions: Management of cancer in the elderly is challenging. CT had significant benefit for OS in octogenarians with stage III and IV. The most significant factors for OS were stage at diagnosis and treatment. We need more studies to determine the appropriate management in this population.
Does clinical stage predict pathologic stage in pancreatic adenocarcinoma?
Authors: Gyulnara G. Kasumova, Mariam F. Eskander, Andrea J. Bullock, Benjamin L. Schlechter, Rebecca A. Miksad, Sing Chau Ng, Robert Najarian, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2016)

4118 Background: When faced with a diagnosis of pancreatic cancer, patients and providers rely upon stage of disease to formulate a treatment plan. The possibility of undertreatment of early-stage patients has been raised. We performed a large national retrospective analysis to evaluate the consistency between clinical and pathologic staging. Methods: National Cancer Data Base was queried for pancreatic adenocarcinoma 2004-2013. Those who underwent resection with or without chemotherapy and had defined AJCC clinical and pathologic stages were included for analysis. Clinical and pathologic stages were compared; if pathologic>clinical stage defined as up-staged; if clinical>pathologic defined as down-staged. Characteristics were compared by χ2. Cochran-Armitage trend test used to evaluate trends in consistency of staging over time. Results: In 22,076 patients, clinical and pathologic stages were consistent 64.4% of the time. 68.8% of those down-staged received neoadjuvant therapy. Patients younger than 65 were more likely to be down-staged (56.0 vs 44.0%) while those older were up-staged (57.6 vs 42.4%) (p<0.0001). Private insurance holders were more likely to be down-staged (45.1%) vs those with Medicare were up-staged (56.4%) or have consistent staging (50.9%) (p<0.0001). Majority were treated at academic vs community centers (58.9 vs 41.1%) with down-staging more frequent at academic centers (67.8 vs 32.3%, p<0.0001). Over time, consistency between clinical and pathologic staging has declined (p<0.0001), with more patients being up-staged (p<0.0001). Conclusions: Our ability to accurately predict clinical stage of pancreatic cancer has not improved over time. An increased proportion of patients are upstaged based on resection pathology. The so-called “national failure to operate” may in part be a reflection of this poor correlation and underlying advanced disease. Better prognostic tools and novel treatment strategies including neoadjuvant treatment may be warranted. TREATMENT Consistent STAGING N (%) p-value UP-stage DOWN-stage Total Surgery First 12267 (86.3) 6051 (91.3) 388 (31.2) 18706 (84.7) <0.0001 Neoadjuvant 1939 (13.7) 576 (8.7) 855 (68.8) 3370 (15.3) Total 14206 (64.4) 6627 (30.0) 1243 (5.6) 22076 (100.0)
TCT-327 Single-center experience on percutaneous rheolytic thrombectomy in patients with pulmonary embolism at high risk or intermediate-high risk
Authors: Ozgur Akbal, None Cihangir Kaymaz, Aykun Hakgor, Seda Tanyeri, Hacer Tokgoz, Berhan Keskin, None Ali Karagoz, Sevim Turkday, None Ibrahim Tanboga, None Cem Doğan, Rezzan Deniz Acar, None Zübeyde Bayram, Nihal Ozdemir
Journal: Journal of the American College of Cardiology (2018)