tbuckley/cabot-search huggingface dataset:
Possible clinical implication of serum testosterone surge caused by the GnRH antagonist degarelix.
Authors: Gaku Arai, Kojiro Nishio, Ryo Sato, Makoto Kawaguchi, Keisuke Suzuki, Toshiyuki Iwahata, Yuko Sadaoka, Shigeyuki Ota, Masashi Iijima, Takeshi Shin, Yoshio Ashizawa, Yoshitomo Kobori, Hiroshi Yagi, Shigehiro Soh, Hiroshi Okada
Journal: Journal of Clinical Oncology (2014)

e16097 Background: Degarelix directly blocks GnRH receptors, therefore, it is believed to produce a rapid decline of serum testosterone level without an initial surge in leutenizing hormone (LH), follicule stimulating hormone (FSH) and testosterone(T) seen in LHRH agonists. However, hormonal change caused by Degarelix in ultra-acute phase is unknown. We investigated the change of serum levels of LH, FSH and testosterone within 24hours of administration of Degarelix. Methods: Eleven patients (median age 74 years old; range 63-74), with a histologic diagnosis of advanced prostate cancer and without pretreatment by androgen deprivation therapy, were involved. Serum levels of LH, FSH and T were measured at 0, 1, 3, 6, 9, 12, 24 hours and1 month after injection of Degarelix. Serum prostate-specific antigen (PSA) level was also measured at baseline and 1 month after treatment. Results: The median serum PSA level before treatment was 378ng/ml (15.9-7187). The median baseline serum levels of LH, FSH and T were 7.6mIU/ml (2.9-17), 10.6mIU/ml (2.4-32) and 390ng/dL (206-697), respectively. Those at 24hr were 0.7mIU/ml (0.01-2), 6.6mIU/ml (1.4-18.6) and 50ng/ml (8-95). Although, serum levels of LH and T declined rapidly, serum levels of FSH declined more slowly. In 5 patients, serum levels of T at 24hr were below the castration level (<50ng/dL). T surge (an elevation of serum level of T within first 3hr) was observed in 6 patients. In 9 patients, hormonal levels at 1 month after treatment were available. In 7 of 9 patients, serum levels of T were below the castration level. Four patients showed T surge and 5 did not show this phenomenon. In four of 5 patients without T surge, serum levels of PSA declined to 96% in average at 1 month. In contrast, only one of 4 patients with T surge showed 92% reduction of serum levels of PSA, in the rest of 3 patients PSA reduction was only 67% in average. Conclusions: Degarelix suppresses serum levels of and Testosterone rapidly. Testosterone surge could be a possible predictor of effectiveness of Degarelix on prostate cancer.
Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure
Authors: Joel L. Berry, Wuqiang Zhu, Yao Liang Tang, Prasanna Krishnamurthy, Ying Ge, John P. Cooke, Yabing Chen, Daniel J. Garry, Huang-Tian Yang, Namakkal Soorapan Rajasekaran, Walter J. Koch, Song Li, Keitaro Domae, Gangjian Qin, Ke Cheng, Timothy J. Kamp, Lei Ye, Shijun Hu, Brenda M. Ogle, Jack M. Rogers, E. Dale Abel, Michael E. Davis, Sumanth D. Prabhu, Ronglih Liao, William T. Pu, Yibin Wang, Peipei Ping, Nenad Bursac, Gordana Vunjak-Novakovic, Joseph C. Wu, Roberto Bolli, Philippe Menasché, Jianyi Zhang
Journal: Circulation Research (2019)

On March 1 and 2, 2018, the National Institutes of Health 2018 Progenitor Cell Translational Consortium, Cardiovascular Bioengineering Symposium, was held at the University of Alabama at Birmingham. Convergence of life sciences and engineering to advance the understanding and treatment of heart failure was the theme of the meeting. Over 150 attendees were present, and >40 scientists presented their latest work on engineering human functional myocardium for disease modeling, drug development, and heart failure research. The scientists, engineers, and physicians in the field of cardiovascular sciences met and discussed the most recent advances in their work and proposed future strategies for overcoming the major roadblocks of cardiovascular bioengineering and therapy. Particular emphasis was given for manipulation and using of stem/progenitor cells, biomaterials, and methods to provide molecular, chemical, and mechanical cues to cells to influence their identity and fate in vitro and in vivo. Collectively, these works are profoundly impacting and progressing toward deciphering the mechanisms and developing novel treatments for left ventricular dysfunction of failing hearts. Here, we present some important perspectives that emerged from this meeting.
Microsatellite Instability as an Emerging Biomarker for Checkpoint Inhibitor Response in Advanced Prostate Cancer
Authors: Zachery R. Reichert, Joshua Urrutia, Joshi J. Alumkal
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
The use of whole-genome sequencing in therapeutic for decision making in patients with advanced malignancies.
Authors: Howard John Lim, Yaoqing Shen, Janessa J. Laskin, Karen A. Gelmon, Daniel John Renouf, Sophie Sun, Stephen Yip, David Huntsman, Anna Tinker, Cheryl Ho, Stephen K. L. Chia, Yvonne Li, Katayoon Kasaian, Peter Eirew, Sreeja Leelakumari, Samuel Aparicio, Yussanne Ma, Steven Jones, Marco Marra
Journal: Journal of Clinical Oncology (2014)

11026 Background: We used information obtained from whole genome and transcriptome sequencing to aid in therapeutic decision-making in patients (pts) with advanced cancers. Methods: Eligible pts with incurable cancers with limited or no standard options, had several samples analyzed: a fresh tumor biopsy; a blood sample for normal comparison; and archival tumor tissue when available. Samples underwent both the Ion Torrent AmpliSeq cancer panel analysis and comprehensive DNA (80X) and RNA sequencing followed by in-depth bioinformatic analysis to identify somatic mutations, copy number alterations, structural rearrangements, and corresponding gene expression changes that may be cancer “drivers” or provide informative/diagnosticor actionable targets. Aberrant pathways were matched to drug databases and manual literature reviews were performed to identify drugs that may be useful or potentially contraindicated. A report was generated and discussed in a multidisciplinary team. Results: Between July 2012 - January 2014, 65 pts had consented (including 4 pediatrics cases) and 56 have been sequenced: 18 breast, 8 lung; 4 colorectal, 3 squamous, 3 adrenal; 2 pancreas; 2 sarcomas, 2 neurofibroma, 2 mesothelioma, and 1 of each of nasopharynx, primary unknown, CLL-peripheral mantle cell, parotid, anal, appendix, peripheral T-cell, prostate, ovary, endometrial, glioma, and leiomyoma. The median number of lines of chemo prior to sequencing was 3. The AmpliSeq panel only yielded actionable targets in 40% of cases. The full genomic data was more comprehensive about driver pathways and was informative in 70% of cases. Clinical data is available on 30 pts. In 21 pts data was actionable. In 3 pts, the diagnosis was changed and 9 pts died before the results could be used. Treatments were delivered based on the results in 8 pts, 6 (75%) of these pts derived clinical benefit from treatment based on genomic therapy. Conclusions: Whole genome sequencing based therapeutic decision-making in the management of advanced cancer is feasible. The information is more comprehensive than panels and yields clinically actionable data not identified by panel sequencing. Further studies are needed to determine the utility of this technology.
The prognostic significance of vasohibin-1 expression in patients with prostate cancer.
Authors: Takeo Kosaka, Yasumasa Miyazaki, Akira Miyajima, Ryuichi Mizuno, Shuji Mikami, Tatsuaki Daimon, Eiji Kikuchi, Ken Nakagawa, Yasufumi Sato, Mototsugu Oya
Journal: Journal of Clinical Oncology (2014)

e16063 Background: The development and establishment of blood supply play an important role in the growth of prostate cancer cells. Although several parameters evaluating tumor angiogenesis have been investigated in prostate cancer, it has not been fully characterized yet that those parameters reflects the activity of tumor angiogenesis. Recently we isolated a novel angiogenic molecule Vasohibin-1(VASH1) that is specifically expressed in activated vascular endothelial cells (ECs). The aim of this study was to assess the prognostic value of VASH1 expression in prostate cancer (PCa). Methods: We retrospectively analyzed the clinical records of 167 patients with PCa. We immunohistochemically examined the accomplished microvessels positive for anti-CD34 as MVD and the microvessels with activated ECs positive for VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinico-pathological parameters. Results: Forty-eight patients experienced biochemical PSA recurrence during follow-up. Although CD34 staining of vascular endothelial cells in benign prostatic tissue adjacent to cancerous tissue was positiven, VASH1 staining of vascular endothelial cells was negative or negligible. VASH1 was restricted to ECs of blood vessels in the tumor stroma. VASH1 density was significantly associated with pathological T stage (p=0.005), Gleason score (GS) (p<0.001) and MVD (p<0.001). Using Spearman’s correlation coefﬁcient test, we detected a significant positive correlation between MVD and VASH1 density in microvessels in the tumor (ρ = 0.504, P < 0.001). The 5-year PSA recurrence-free survival rate was 66.1% in patients with higher VASH1 density (≥12/mm2) and 81.0% in patients with lower VASH1 density (<12/mm2) respectively (P<0.001). Multivariate analysis revealed that high VASH1 density was an independent prognostic indicator of tumor recurrence (P= 0.007, HR = 2.950). Conclusions: VASH1 density represents a clinically relevant predictor of patient prognosis in PCa. The results suggest that VASH1 density can be a new biomarker that would provide additional prognostic information concerning PCa.
CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in patients with stage I diffuse large B-cell lymphoma.
Authors: Xiaohui He, Bo Jia, Yuankai Shi
Journal: Journal of Clinical Oncology (2014)

e19513 Background: The role of rituximab in combination with CHOP-like chemotherapy regimens in patients with stage I diffuse large-B cell lymphoma (DLBCL) remains to be defined.We aimed to compare CHOP-like chemotherapy and rituximab (R-CHOP) with CHOP-like chemotherapy alone in these patients. We also evaluated whether chemotherapy followed by involved-field radiotherapy (IFRT) could improve outcome compared with chemotherapy alone of stage I DLBCL patients. Methods: Between 2003 and 2009, 140 previously untreated patients with stage I DLBCL treated in Cancer Institute and Hospital, Chinese Academy of Medical Sciences were included in this study. Seventy-eight patients were treated by R-CHOP regimen and 62 patients received CHOP-like chemotherapy alone. Ninety-one patients received additional radiotherapy at the end of chemotherapy. Results: Complete remission (CR) rate was 77% both in patients received R-CHOP and CHOP-like chemotherapy. After a median follow-up of 55 months, patients received R-CHOP chemotherapy had similar 5-year progression-free survival(PFS)(76% vs 85%; log-rank P=0.215) and 5-year overall survival (90% vs 96%; log-rank P=0.175)compared with those with CHOP-like chemotherapy alone. All stage I (86% vs 71%; log-rank P=0.005) and non-bulky stage I (85% vs 71%; log-rank P=0.009)DLBCL patients who received radiotherapy had significantly increased 5-year PFScompared with those who had chemotherapy alone. Subgroup analysis showed that both in favorable subgroup (ie, IPI=0, no bulk) (82% vs 88%; log-rank P=0.628)and less-favorable subgroup (ie, IPI≥1, or bulk, or both) (69% vs 83%; log-rank P=0.138), patients received R-CHOP chemotherapy were not associated with superior 5-year progression-free survival(PFS)rates compared with those with CHOP-like chemotherapy alone. Conclusions: These results suggest that CHOP-like chemotherapy alone could be as effective as R-CHOP chemotherapy and additional radiotherapy is necessary for stage I or stage I non-bulky DLBCL patients.
Body mass index, comorbidities, and hormonal factors in relation to meningioma in an ethnically diverse population: the Multiethnic Cohort
Authors: Ivo S Muskens, Anna H Wu, Jacqueline Porcel, Iona Cheng, Loïc Le Marchand, Joseph L Wiemels, Veronica Wendy Setiawan
Journal: Neuro-Oncology (2019)

Meningioma is the most common intracranial tumor in the US and its etiology remains poorly understood. Meningioma has been predominantly studied among white populations. The aim of this study was to evaluate the associations of anthropometric, comorbidity, and hormonal factors with meningioma in an ethnically diverse population.A nested case-control analysis was performed within the Multiethnic Cohort (MEC). Meningioma cases were identified via linkage with Medicare and the California Office of Statewide Health Planning and Development Hospital Discharge data and were matched to up to 10 controls. Anthropometric, comorbidities, physical activity level, and hormonal factors at baseline based on questionnaires were evaluated for association with meningioma.A total of 894 cases and 8918 matched controls were included in this study. Increasing body mass index (BMI) (P-trend = 0.041) and weight increases since age 21 (P-trend = 0.0052) were positively associated with meningioma. Hormonal factors including oral contraceptive use (odds ratio [OR]: 1.24; 95% CI: 1.01-1.51) and estrogen hormonal therapy use (per 5 years, OR: 1.07; 95% CI: 1.01-1.15) were associated with meningioma risk. Hypertension was positively associated with meningioma (OR: 1.26; 95% CI: 1.09-1.47), with individuals who reported a history of both hypertension and diabetes showing a stronger association (OR: 1.54; 95% CI: 1.17-2.03). The tests for heterogeneity across race/ethnicity were not statistically significant (P heterogeneity ≥ 0.17); however, the association of BMI with meningioma was mainly observed in Japanese Americans (P-trend = 0.0036) and hypertension in Japanese Americans (OR: 1.63; 95% CI: 1.17-2.27) and Native Hawaiians (OR: 1.86; 95% CI: 1.02-3.40).Obesity, hormonal factors, and hypertension were associated with meningioma in an ethnically diverse population.
Survival improvements associated with access to biologic agents: Results from the South Australian (SA) Metastatic Colorectal (mCRC) Registry.
Authors: Michail Charakidis, Timothy Jay Price, Carol Beeke, Robert Padbury, David Roder, Amanda Rose Townsend, Guy Maddern, Amitesh Chandra Roy, Scott Carruthers, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2014)

e17616 Background: Survival of mCRC has improved greatly over the last decade, in part due to access to anti-VEGF and anti-EGFR agents. Clinical trials now report median overall survival (OS) of 24 months or more. In Australia access to these agents was delayed until 2009 and thus we have the potential to assess the impact of these therapies when comparing two time cohorts based on this change in accessibility. Methods: We explored the SA mCRC registry to assess if there were any differences in patient characteristics, treatment received and outcomes based on diagnosis in two time cohorts; 1/2/2006 to 31/5/09 (A) versus 1/6/09 to31/12/12 (B) . KM was used for survival outcomes. Results: 2,864 patients were available for this analysis, 1,446 (A) and 1,418 (B). 60.6% and 56.5% respectively received chemotherapy in the cohorts. Patient characteristics (A) v (B) as follows; Med age 73.4yrs v 71.2 yrs, any biological drug use through lines of therapy 13.2% v 27.1%, KRAS determination 22.8% v 52.4% (MT 38.5% v 40.7%), clinical trial 12.4% v 6.6%, liver surgery 9.3% v 9.2%. Lines of therapy beyond first line is as follows; secpnd-line 60.3% v 50.3%, third-line 18.9% v 31.6%. Avastin use is as follows (A) v (B); first-line 8.8% v 37.4%, second-line 7.7% v 12.2%. Anti-EGFR therapy; second/third-line 28.4% v 13.3%. The OS for whole group was 12.9 mths (A) v 19.6 mths (B). For patients receiving only systemic therapy (chemotherapy and/or biological) OS was (A) 11.8 mths v (B) 16 mths (p=<0.0001). For patients having systemic therapy and including surgery OS was (A) 13.7 mths v (B) 20.4 mths (p=0.007). Liver surgery patients had same median OS of 66.7 mths in both cohorts (p=0.3). Conclusions: The expected increase in use of bevacizumab is seen although only 37.4% of first line chemotherapy protocols incorporated this drug even after subsidised access. This is relatively low and potentially reflects real world practice where co-morbidities, primary in-situ and age have an impact. Overall survival has improved over time likely reflecting access to the newer targeted drugs.
FLT3-ITD Mutations Are Prevalent and Significantly Impact Outcome after Intensive Therapy in Elderly Adults with Acute Myeloid Leukemia (AML): Analysis of the North American Intergroup E2906 Phase III Trial in Patients Age ≥60 Years
Authors: James M. Foran, Zhuoxin Sun, Elisabeth Paietta, Janis Racevskis, David F. Claxton, Hillard M Lazarus, Daniel A. Arber, Jacob M. Rowe, John Godwin, Yanming Zhang, Martin S. Tallman, Mark R. Litzow, Keith W. Pratz, Selina Luger
Journal: Blood (2018)
DS-3201, a Potent EZH1/2 Dual Inhibitor, Demonstrates Antitumor Activity Against Non-Hodgkin Lymphoma (NHL) Regardless of EZH2 Mutation
Authors: Daisuke Honma, Emi Nosaka, Machiko Shiroishi, Yoshimi Takata, Yasuhiro Hama, Yuka Yamamoto, Nobuaki Adachi, Dai Maruyama, Kensei Tobinai, Takashi Ishida, Shigeru Kusumoto, Kenji Ishitsuka, Yoshitaka Imaizumi, Shogo Takeuchi, Kunihiro Tsukasaki, Tomoyuki Fujioka, Jun Watanabe, Osamu Kanno, Eiji Kumazawa, Sumiaki Fujitani, Kazushi Araki, Kosaku Fujiwara
Journal: Blood (2018)
Enhancing pathway adherence in a quality initiative for breast cancer.
Authors: Johnathan M. Lancaster, Karen K. Fields, Douglas D. Letson, Lisa DeMaria, John W. Peabody
Journal: Journal of Clinical Oncology (2014)

6637 Background: Clinical pathways are associated with improved outcomes and reduced health care costs. However, physician adherence to clinical pathways remains a challenge for cancer centers across the country. Moffitt Cancer Center (MCC) has developed and implemented clinical pathways across disease-focused programs. We performed a series of measurements of adherence to evidence-based clinical pathways, which included subsequent educational feedback on performance. Methods: Using Clinical Performance and Value (CPV®) vignettes, a validated in silicosimulation measurement tool, we evaluated breast cancer clinical pathway adherence every 4 months. 18 providers completed two BC cases each at months 1, 5 and 9. For each case completed, an overall CPV score was generated with scores calculated as a percentage of the items that the physician correctly completed against all necessary elements of care for that case. Clinicians then received confidential individualized feedback for each case, with quantitative feedback benchmarked to their peers and qualitative individual feedback with suggestions on how they could improve pathway adherence. Results: At baseline, measurement revealed wide variance levels of adherence to pathways across the clinician cohort. With serial measurement and feedback, mean CPV scores increased significantly from 55.4% at round 1 to 68.8% at round 3 (p <0.01). Particular categories of pathway compliance also improved after the three rounds. Chemotherapy pathway compliance increased from 40% to 65%; appropriate diagnostic work up from 31 to 93% and surgery pathway compliance from 69% to 86%. Conclusions: We found that adherence to clinical pathways can be improved with a serial measurement and feedback tool. Future studies will link these changes to utilization and costs. Consistent feedback at the individual and group level engages and aligns providers around pathways and common practice standards. Breast pathway adherence improvement over time, by treatment category. Round 1 (M1) Round 2 (M5) Round 3 (M9) Surgery 69% 57% 86% Work-up of the axilla 31% 31% 93% Radiation therapy 83% 83% 77% Chemotherapy 40% 50% 65% Hormonal 79% 64% 100%
Geographic variation in high-risk uterine cancer histology and access to care.
Authors: Kemi Morenikeji Doll, Ke Meng, Ethan M Basch, Paola A. Gehrig, Laura Jean Havrilesky, Wendy R. Brewster, Anne-Marie Meyer
Journal: Journal of Clinical Oncology (2014)

e16546 Background: Race has been associated with high-risk uterine cancer (UC) histology, but other risk factors, including age, health service utilization, and low socioeconomic status (SES), are not well characterized. The objective of this study was to evaluate the demographic risk factors and geographic distribution of patients with high-risk (HR) histology in North Carolina (NC) and the proximity to a gynecologic oncologist. Methods: We identified a patient cohort of incident UC cases in NC from the NC Central Cancer Registry between 2003-2010 and linked clinical and demographic factors with SES and geographic data from the US Census. Referral care regions were defined in accordance with NC AHEC (Area Health Education Center) clusters. HR histology was defined as all non-endometrioid types. Multiple logistic regression was used to model demographic and geographic relationships to HR histology. Results: Of 14,562 gynecologic cancer patients identified, 7,216 had UC. The cohort was 79% White (n=5677), 17% Black (n=1261), 1% Hispanic (n=102), and 4% Other/Missing (n=176) and 28% (1996) were ≥ 70 years old. Age-adjusted incidence by AHEC region ranged from 21.6 to 26.4 cases/100,000 person-yr. There were 13% (940) patients with HR histology. Black race (OR 2.97, 2.6-3.5), age ≥ 70 (OR 1.76, 1.4-2.2), and low SES (6K-39K) status (OR 1.22, 1.0-1.4) were all independently associated with HR histology. Of the 9 AHEC regions, 4 had significantly increased odds of high-risk histology (Charlotte OR 1.4(1.2,1.7), Eastern OR 1.3(1.1-1.7), Area L OR 1.6 (1.2-2.2), Southern OR 1.4 (1.1-1.8)), of which three have ≤ 1 practicing gynecologic oncologist. After adjusting for demographic covariates, geographic area was no longer independently associated with HR histology. Conclusions: Low SES, black race, and age ≥ 70 are all independently associated with HR uterine cancer histology. Patients with HR histology are not evenly distributed throughout the state. Most regions with a higher proportion of patients with HR histology have little to no access to a gynecologic oncologist within their region. Identification of at-risk regions could provide target populations for improved referral care model systems.
Biodegradable wafers releasing Temozolomide and Carmustine for the treatment of brain cancer
Authors: Tovi Shapira-Furman, Riccardo Serra, Noah Gorelick, Marisol Doglioli, Valentina Tagliaferri, Arba Cecia, Michael Peters, Awanish Kumar, Yakir Rottenberg, Robert Langer, Henry Brem, Betty Tyler, Abraham J. Domb
Journal: Journal of Controlled Release (2018)