tbuckley/cabot-search huggingface dataset:
miRNA expression profiles in high-grade prostatic intraepithelial neoplasia.
Authors: Okyaz Eminaga, Fabian Woetzel, Jochen Fries, Susanne Neiss, Michaela Heitmann, Udo Engelmann, Axel Heidenreich, Ute Warnecke-Eberz
Journal: Journal of Clinical Oncology (2016)

45 Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is widely believed to be a precursor of prostate cancer (PCa). However, little is known about the expression of miRNAs variations in HGPIN compared to normal tissues and PCa. Methods: The expression data of 1054 miRNAs from TCGA were applied to identify relevant miRNAs associated with tumor progression (i.e., miR-98-5p, miR-183-5p, 345-5p, miR-143 miR-210-3p and miR-378-3p). miRNA were isolated by miRNeasy FFPE kit (Qiagen, Hilden, Germany) from paraffin-embedded tissues (FFPE) of prostate specimens with PCa, HGPIN and normal tissues. Early-stage PCa was defined as PCa with pT2 tumor stage, Gleason score &lt;=7a (3+4) and PSA level &lt;10 ng/ml. Quantitative miRNA expression data were acquired and analyzed using a real-time TaqMan-based PCR with the ABI Prism 7900HT (Life Technologies, Darmstadt, Germany). ANOVA analysis were performed to evaluate the expression of miRNAs between HGPIN, Normal and PCa tissues. All statistical analysis was performed using SPSS (IBM, Armonk, USA). P values were adjusted using the false discovery rate for multiple comparisons. The small nuclear U6 RNA was used as an endogenous control. Results: The expression of miR-143-3p, miR-210-3p and miR-345-5p and miR-98-5-p were varied between normal tissue, HGPIN and early-stage PCa. Interestingly, decrease in expression of miR-143.-3p, miR-98-5p and miR-210-3p was associated with tumor development (Normal tissues &gt; HGPIN &gt; early-stage PCa) (FDR&lt;0.001). Furthermore, overexpression of miR-345-5p was observed in normal tissues compared to HGPIN and early-stage PCa, which both showed similar expression level of miR-345-5p. No significant differences in expression of miR-375, miR-183-5p and miR-378-3p were observed between HGPIN and PCa. These miRNAs were interacted with genes related to HIF-1 signaling pathway, p53 signaling pathway, androgen receptor signaling pathway, intrinsic apoptotic signaling pathway, RNA transcription, homologous recombination and non-homologous end-joining. Conclusions: HGPIN shows an altered expression of miRNAs interact with genes related to hypoxia, androgen receptor signaling pathway, cell cycle and epigenetic regulation.
Task implementation and top-down control in continuous search
Authors: Wolfgang Prinz
Journal: Behavioral and Brain Sciences (2017)

Abstract Evidence from continuous search suggests that targets are detected by default, whereas distractors are processed in considerable depth. These observations shed light on task implementation and top-down control. Task implementation builds on forming dynamic distractor models, based on continuous integration of distractor-related information. Top-down control builds on using these models for testing upcoming stimulus information.
Comparison of a large NGS panel to hot-spot testing and small panels for the ability to accurately stratify advanced colorectal cancer patients to appropriate treatment pathways.
Authors: Stephen Lyle, Winslow Powers, Jia Xu, Claudia S. Huettner, Meaghan Russell, Alexei Protopopov
Journal: Journal of Clinical Oncology (2016)

510 Background: It is well established that KRAS mutations confer resistance to anti-EGFR therapy for colorectal cancer patients. More recently, other RAS mutations (NRAS and BRAF) have been determined to cause similar resistance and treatment guidelines are changing to incorporate testing of these genes as well. In addition, evidence suggests that mutations outside of hot-spot regions (Codons 12 &amp; 13 of KRAS and NRAS; BRAF V600E) can also mediate therapeutic response. Recent data also suggest that other genes are relevant for treatment planning. We evaluated the ability of a 415 gene panel, CancerPlex, to accurately stratify colorectal cancer patients to appropriate treatment pathways compared to single gene “hot-spot” testing and small gene panels ( ≤ 50 genes). Methods: 70 colorectal cancer samples were analyzed by a large NGS panel of 415 genes that includes full-gene sequencing for SNPs, short insertions and deletions, and CNVs. All actionable mutations for each patient were recorded. We calculated relative frequencies of variants present in key oncogenic drivers to compare the effectiveness of current single gene testing with data obtained using a large panel. Testing was performed in a CLIA-certified laboratory (KEW Group Inc, Cambridge, MA). Results: 40% of samples contained a KRAS hot-spot mutation. When expanded to NRAS and BRAF hot-spots, an additional 8% of patients were identified as resistant to anti-EGFR therapy. An additional 15% of clinically significant variants were captured by full-gene sequencing of these 3 genes. Thus, &gt; 25% of mutations lie outside traditional hot-spot regions. The majority of BRAF mutations were not V600E. The 415 gene panel identified clinically significant driver mutations in 99% of patients, while in smaller panels missed a significant number of actionable changes. In very few patients were actionable changes limited to KRAS, NRAS and BRAF hot-spots. Conclusions: Hot-spot testing and small gene panels can miss clinically significant genomic alterations. The detection of mutations outside of small panels and hot-spots may lead to more appropriate and successful treatment of colorectal cancers.
A population-based study of cardiovascular (CV) mortality among patients with prostate cancer (PCa) treated with radical external beam radiation therapy (EBRT) with and without adjuvant androgen deprivation therapy (ADT) at a provincial cancer agency.
Authors: J. O. Kim, M. Vaid, S. Tyldesley, R. Woods, T. Pickles
Journal: Journal of Clinical Oncology (2010)

4656 Background: There are conflicting studies of the impact of ADT on CV mortality among PCa patients receiving curative intent EBRT. D’Amico et al suggested that men > 65 yrs are at increased risk of CV mortality with ADT. We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT, and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by duration of ADT using competing risk analysis and Fine and Gray multivariant analysis. 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: We identified 5,948 PCa patients treated with radical intent EBRT, of which 1,933 were treated without ADT, 674 received ADT for ≤6 mo and 3,341 received > 6 mo of ADT. The cumulative CV mortality at 7 yrs was 2.6% [95%CI 1.9 to 3.5%], 2.1% [1.2 to 3.5%], and 1.4 [1.0 to 2.0%] for patients with no ADT, ≤ 6 mo NADT and > 6 mo ADT respectively (Gray's p=0.002). Baseline CVS disease and risk factors were more prevalent in the no ADT group compared to the > 6 month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT, rather than effect of ADT itself. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Ferring Pharma, sanofi-aventis AstraZeneca, Ferring Pharma, sanofi-aventis Abbott Laboratories
Process of standardizing time to follow-up when initiating oral chemotherapy.
Authors: Meghan Shea, Donna Giampietro, Inga Tolin Lennes, Theresa Margaret McDonnell, Nie Bohlen
Journal: Journal of Clinical Oncology (2014)

95 Background: With the explosion of oral chemotherapy agents, cancer care is shifting from the hospital to the home. The many safeguards developed for parenteral chemotherapy have not translated to oral chemotherapy. Patients are responsible for adherence to complex medication regimens while managing the side effects of chemotherapy at home. Many clinicians at Massachusetts General Hospital (MGH) improvise systems to monitor patients on oral agents, and practices remain varied. The 2013 American Society of Clinical Oncology/Oncology Nursing Society (ASCO/ONS) addressed standards for safe administration and management of oral chemotherapy, which served as the framework for improving follow up care at MGH. Methods: Theclinicians in the thoracic and gastroenterology disease centers were surveyed and selected standardization for the first follow up appointment after initiation of oral chemotherapy as a safety initiative. The team, which consisted of the thoracic clinicians, delineated a process map from writing the prescription for erlotinib or crizotinib to the follow up appointment, as well as identified barriers to ensuring a standardized time for follow up. A second survey established a consensus of a 28 day ceiling for time to first follow up for both oral agents. The aim was for 95% of patients to be seen within 28 days of initiating oral chemotherapy. An education campaign for providers regarding the standardized algorithm for time to follow up and a text template to incorporate in the clinic note was instituted. Results: Prior toan intervention, patients initiated on erlotinib or crizotinib were seen in follow up within 19 days (on average), and 82% reached the aim of within 28 days. A time frame for return to follow up was established as well as required documentation for initiation of each drug. Conclusions: The process of implementing standardized drug specific time to follow up highlighted a number of key lessons. It is crucial to evaluate and measure the current process prior to developing interventions. Support of local leadership and “buy in” from all clinicians and staff is essential to the success of the intervention. Additionally, a regular setting to discuss and present updates on the process improvement is vital.
Novel tool utilized as a trigger for advance care planning in hospitalized oncology patients.
Authors: Nicole Lincoln, Sandhya Rao, Diane Sarnacki, Alexandra Dobie, Karla Damus, Gretchen Gignac
Journal: Journal of Clinical Oncology (2016)

22 Background: Study Purpose: reduce inpatient oncology readmissions; determine if there is a need to standardize trigger for Advance Care Planning in the inpatient oncology population. Methods: Investigational Quality Improvement Study January-June 2014. Retrospective chart review of oncology readmissions on the BMC Hematology and Oncology service during a 6 month period, January-June 2013 (N = 68). Data abstracted included: demographics (age, race/ethnicity, primary language, education, marital status, ECOG); type and stage of cancer; type of consults (palliative, spiritual, social services, integrative, PT/OT, hospice, visiting nurse). Developed a Severity of Illness Scale for use in the oncology inpatient patients at BMC. Results: Mortality rate within 1 year of discharge: 32.8% (non-elective readmissions) 19/58; mean days to death from readmission discharge: 65 days (range 0-252); 84.2% of those who died had metastatic cancer in index admission; only 37% ever had a palliative care consult placed (all on readmit); only 17% had a documented EOL discussion on index admission; 38.5% of patients had lung CA (22% of all non-elective readmissions). Conclusions: (1) There is a need to standardize triggers to goals of care discussions and access to Palliative Care in the Hematology/Oncology Inpatient Population at this Institution. (2) Readmissions may be reduced with better Advance Care Planning. (3) There is a communication gap amongst interdisciplinary teams in regards to Advance Care Planning at this institution. Currently IRB Approval for use of novel severity of illness scale on a maximum 450 patient sample (current N = 300) at daily rounds administered in all inpatients admitted to the Hematology/Oncology Service January 4, 2016-June 30, 2016. Preliminary data shows 25-30% of study sample scoring in for Advance Care Planning with a score of greater than or equal to 4 on novel tool (BMC Cancer Care Severity Of Illness Tool).
Characteristics and outcomes of advanced cancer patients admitted to an acute palliative care unit (PCU) with severe dyspnea receiving high flow oxygen (HFO).
Authors: Marvin Omar Delgado-Guay, Alfredo Rodriguez-Nunez, Oluwatobi O Adegboyega, Amy Newton, Maria Gabriela Hernandez-Azmitia, Minjeong Park, David Hui, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

247 Background: Dyspnea is very complex and distressing symptom in patients with advanced cancer. The therapeutic goal of its symptomatic management is to relieve the patient’s breathlessness sensation. Limited literature has addressed the characteristics and clinical outcomes of advanced cancer patients with severe dyspnea receiving HFO admitted to PCU. Methods: We reviewed the records of 101 advanced cancer patients with dyspnea receiving HFO and 110 matched PCU inpatients with dyspnea receiving regular O 2 flow (NoHFO) between January 1 to December 31, 2012. Demographics, frequency and intensity of symptoms at PCU admission and follow-up, and outcomes were recorded. Results: Median age: 60 years, range (51, 69). 56% were Male. White(71%), Hispanic(13%), African American(10%), Asian (4%). Primary cancer: Lung (27%), Gastrointestinal (19%), Hematological (18%), Breast (13%), Gynecological (6%). Dyspnea was present in all cases and it was related mainly to: lung involvement by cancer (53%), pneumonia (40%), Congestive Heart Failure (6%), COPD (8%). ECOG: 4. No significant difference in age, ethnicity and type of cancer, ECOG, and possible cause of dyspnea among both groups. HFO and NoHFO were started the same day of admission. Median ESAS symptoms (Interquartile range: IQR) for HFO was Pain 4.5 (2, 7) vs. 5 (3, 7) for NoHFO, p = 0.1423; fatigue [7(5, 8) vs. 7 (5, 8), p = 0.450]; depression [3 (1, 5) vs. 3.5 (2, 5), p = 0.81]; anxiety 7 (4, 9) vs. 6 (3, 8), p = 0.01; dyspnea [7.5( 6, 9) vs. 5 (3, 8), p &lt; 0.0001]. Memorial Delirium Scale 5 (2, 15) vs. 7(2, 15), p = 0.77). Morphine Equivalent Daily Dose: 48 (36, 120) vs. 55 (30, 120), p = 0.72. The median difference among first and follow up ESAS was Pain 0 (-3, 1) vs. -1(-2, 1), p = 0.62; fatigue[(-2, 1) vs. 0 (-2, 0), p = 0.63]; depression [0 (-1, 1) vs. 0 (-1, 2), p = 0.93]; anxiety [0 (-2, 2) vs. 0 (-2, 2), p = 0.94; dyspnea [0( -1, 1) vs. -1 (-2, 1), p = 0.18]. Memorial Delirium Scale 0 (-1.5, 5.5) vs. 0 (-2, 3), p = 0.21).The median time (IQR) from HFO started to discharge was 10 days (6, 15) vs. 8.5 (5, 14) days for NoHFO, p = 0.07). The median time(IQR) from HFO started to Death was 10.5 (7, 19) vs. 13.5 (7, 26) days for NoHFO, p = 0.18. 77/101(76%) HFO patients vs. 56/110 (51%) NoHFO died at the hospital, p = 0.002. 24/101(23%) HFO patients were discharged alive weaned off HFO. The Odd ratio for hospital death in patients with HFO vs. NoHFO was 4.83 (95% CI: 1.72 – 13.59), p = 0.003. Conclusions: Severe dyspnea is significant at the end of life of advanced cancer patients. Patients with HFO require similar MEDD than NoHFO patients. Inpatient mortality is higher in patients with HFO. More research is needed.
Risk Factors for Silent Cerebral Infarcts in a Pediatric Sickle Cell Anemia (SCA) Cohort
Authors: Francoise Bernaudin, Suzanne Verlhac, Annie Kamdem, Cécile Arnaud, Lena Coïc, Emmanuelle Lesprit, Isabelle Hau, Philippe Reinert, Christophe Delacourt
Journal: Blood (2008)
Repeated dose samarium 153 lexidronam in patients with prostate cancer bone metastases
Authors: A. O. Sartor, R. Reid, C. Higano, D. Bushnell, D. Quick
Journal: Journal of Clinical Oncology (2005)

4635 Background: Prospective randomized multi-center studies have demonstrated safety/efficacy of single 1.0 mCi/kg doses of 153Sm-EDTMP in relieving pain/reducing opioid use in patients (pts) with symptomatic bone metastases. Toxicity was restricted to reversible sdecreases in white blood cells (WBCs) and platelets (PLTs). Less data exist on safety profiles of repeated dose radiopharmaceuticals. Methods: We prospectively investigated safety of multiple dose 153Sm-EDTMP in two separate clinical setting of pts with bone metastases: a) symptomatic patients (primarily hormone-refractory prostate cancer) received multiple doses of 1.0 mCi/kg based on symptom recurrence and normalized WBC and PLT counts, and b) hormone-sensitive stage chemotherapy naive D2 prostate cancer patients received multiple higher doses at fixed intervals in combination with hormone therapy. Results: Repeat doses (range 2–11 doses/patient) at 1 mCi/kg were given to 54 pts. The mean WBC nadir (% baseline) was 3.6±1.1 (49%), 3.6±1.1 (54%), and 3.5±0.9 (57%) for pts administered 1, 2, or ≥3 doses (respectively). Mean PLT nadir (and % baseline) was 129±37 (50%), 105±49 (48%), and 93±38 (50%). No grade 4 PLT or grade 4 WBC toxicities were noted. At the higher fixed interval dose of 2.0 mCi/kg/dose q 12 weeks (four planned cycles), 2/6 hormone sensitive D2 pts were unable to receive fourth cycles due to persistently low PLTs. An additional group (6 pts) with D2 prostate cancer planned to receive 3 doses at 2.0 mCi/kg/dose q 16 weeks. The three planned doses were completed in 5/6 pts. At this dose/schedule, the mean WBC nadir (and % baseline) was 2.5±0.5 (46%), 2.4±0.5 (52%), and 2.5±0.7 (57%) for pts administered 1, 2, or 3 doses. The mean PLT nadir (and % baseline) was 113±69 (47%), 110±45 (60%), and 102±21 (52%). Time to nadir was 5–6 weeks for both WBC and PLTs. No grade 3–4 PLT toxicities were observed but 5/6 pts had grade 3 WBC decreases. No grade 4 WBC decreases were noted. Conclusions: These data indicate that multiple doses of 1 mCi/kg of Samarium-153-lexidronam can be safely administered to pts provided normal WBCs and PLTs are present at dosing. For fixed interval dosing, we conclude that 2.0 mCi/Kg/dose q 16 weeks X 3 is safe in chemotherapy-naïve D2 prostate cancer pts. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytogen Cytogen
Reducing breast cancer chemotherapy treatment delays by improving the transition from surgical to medical oncology.
Authors: Katya Losk, Sarah Kadish, Mehra Golshan, Nancy Lin, Judith Hirshfield-Bartek, Linda Cutone, Craig A. Bunnell, Saul Weingart
Journal: Journal of Clinical Oncology (2013)

51 Background: Delayed chemotherapy is associated with adverse clinical outcomes for breast cancer patients. Few studies have examined the processes of care within administrative staff and providers’ control that might affect the timeliness of breast cancer care. Coordinating transitions of care from surgical to medical oncology to eliminate variation is essential in ensuring timely chemotherapy for patients after surgery. This study evaluated the time of transition from surgery to medical oncology when administrative change of practice was implemented. Methods: We studied 192 consecutive breast cancer patients who received adjuvant chemotherapy. The interval between last definitive surgery and initiation of chemotherapy was calculated by integrating billing and scheduling data. Using process improvement methods a multidisciplinary team identified the opportunity to reduce delays in care coordination by scheduling the surgery, surgical post-op appointment, and medical oncology follow-up appointments simultaneously. Furthermore, responsibility for scheduling the medical oncology follow-up appointment was shifted and standardized from medical to surgical oncology administrative staff. Criteria for acceptable timeliness of appointments and escalation pathways for when provider availability was limited were established. The intervention targeted patients whose initial consultation with a breast surgeon and medical oncologist occurred on the same day, the standard practice at our institution. Results: Implementation of the interventions decreased the time from surgery to chemotherapy by six days. The standard deviation also declined, suggesting that the intervention reduced process variability. Conclusions: Standardizing administrative practices between breast surgery and medical oncology has led to a significant decrease in the time from last definitive surgery to initiation of chemotherapy and in the variability of that delay. [Table: see text]
242PD Subgroup analysis of Asian men in the PREVAIL trial of enzalutamide (ENZA) in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC)
Authors: C.-S. Kim, Y.D. Choi, S.E. Lee, H.M. Lee, T. Ueda, J. Yonese, T. Fukagai, E. Chiong, W. Lau, S. Abhyankar, A. Theeuwes, B. Tombal, T.M. Beer, G. Kimura
Journal: Annals of Oncology (2015)
Effect of caloric restriction on the efficacy of radiation in both hormone-sensitive and hormone-resistant prostate cancers.
Authors: Matthew Joseph Schiewer, Robert Scott Gitman, Edouard John Trabulsi, Taziana DeAngelis, William Kevin Kelly, Leonard G. Gomella, Karen E. Knudsen, Adam Dicker, Nicole Lynn Simone
Journal: Journal of Clinical Oncology (2016)

16 Background: Locally advanced prostate cancers (LAPC) are aggressive, have poor prognosis, and are associated with high recurrence rates and conversion to castrate resistance. The molecular underpinnings of LAPC are being investigated to identify novel therapeutics. Animal models have shown that caloric restriction (CR) can potentially prevent the initiation of prostate cancer. We propose that CR may be used as a novel therapeutic intervention to enhance outcomes of radiation treatment by altering the molecular profile of prostate tumors. Methods: To assess the effect of CR with radiation in vivo, 6 week old male nude mice were injected with LNCaP (hormone sensitive, N = 60) or PC3 (hormone refractory, N = 60) tumor cells. Once tumors were palpable, mice were randomized to be treated with one of 4 conditions: ad libitum (AL) diet, 8Gy of radiation (RT), 30% reduction in caloric intake (CR), or CR+RT. Results: After PC3 tumor injection, compared with AL, the mice had a 22% reduction in tumor size with radiation, 77% with CR (p &lt; 0.01) and an 80% reduction with CR+RT (p &lt; 0.01). After LNCaP tumor injection, compared with ad libitum, the mice had a 49% reduction in tumor size with CR and a 55% reduction with CR+RT (p &lt; 0.01). Tissue evaluation of mice treated with CR or CR+RT from both the LNCaP and PC3 models revealed decreased proliferation via Ki-67 and increased apoptosis with cleaved caspase-3 levels. Furthermore we establish significant changes of the pro-inflammatory IGF-1R pathway hypothesized to play in intricate roll in prostate cancer; down regulation of serum IGF-1R, IRS-1, PI3K, pAKT, and IGF-1:IGF-BP3. Conclusions: For the first time, we have shown that the efficacy of radiation can be increased by decreasing calories by 30% in both hormone-sensitive and hormone-refractory prostate cancer models. Future clinical trials should consider the innovative use of CR to augment standard cancer therapy as it has the potential to change the biology of tumors and enhance the opportunity for clinical benefit.