tbuckley/cabot-search huggingface dataset:
To study the gene expression profile of advanced gall bladder cancer.
Authors: Arvind Kumar, Nitin Mathur, Lata Rani, Arpit Jain, Ritu Gupta, Venkateswaran KUMAR Iyer, N. K. Shukla, Sujoy Pal, Sanjay Thulkar, Durai Sundar, Mohsin Maqbool, Atul Sharma
Journal: Journal of Clinical Oncology (2014)

e15099 Background: Gall bladder cancer (GBC) have predilection for female sex, specific geographical areas, prior history of gall stone disease and carries worse prognosis. The reason for this is not known. Majority of cases present in advanced and incurable stage. Little is known about genetics of gall bladder cancer. Methods: Aims and objective: To study the gene expression profile of advanced gall bladder cancer by gene based Microarray. Material and methods: Microarray was done on 12 advanced GBC and 4 cases of chronic cholecystitis by single colour cRNA based microarray technique (8X60Kformat; Agilent Technologies, USA). Results: A total of 1307 genes out of 18240 differentially expressed genes satisfied P value of <0.05 as per unpaired t- test with a fold change cut off ± 2. Of 1307 genes, 535 genes were significantly upregulated and 772 genes were significantly downregulated in advanced GBC in comparison to chronic cholecystitis samples. Among these, genes involved in Biological process, Cellular component, Molecular function were 55.03%, 31.48% and 13.49% respectively. The pathway analysis tool demonstrated that a total of 27 pathways were significantly affected by the differentially regulated genes. The important pathway which were affected were cell cycle, DNA replication, Gastric cancer network, integrated cancer pathway, superoxide radicals degradation, oxidative stress, RB in cancer, protein signaling and selenium pathway. Important upregulated genes were CDK2, CCNB1, CDC20, CDC45, MDM2, Skp2, BCL2A1, CASP8, BIRC5, MCM4, POLE CDC45, RCF-4 and IGF2BP3 and important down regulated genes were TNF, SMOC-2, ANGPT1, FGF2, TNF, RB and TGFbeta3. Conclusions: The above results if refined meticulously can give answer to some hitherto unanswered questions in GBC in a better way.
Randomized phase II trial of irofulven (IROF)/prednisone (P), IROF/capecitabine (C)/P or mitoxantrone (M)/P in docetaxel-pretreated hormone refractory prostate cancer (HRPC) patients (pts)
Authors: L. Hart, T. Ciuleanu, J. Hainsworth, S. Oudard, E. R. Berger, J. Alexandre, K. N. Chi, D. Ruether, J. R. MacDonald, E. Cvitkovic
Journal: Journal of Clinical Oncology (2006)

14513 Background: IROF, a semisynthetic derivative of the natural product illudin S, is a novel DNA binding agent. IROF alone or in combination has shown activity in phase I-II trials in HRPC, notably with IROF/C (Cvitkovic et al, ASCO 2004). Methods: Pts with histologically-proven metastatic HRPC who progressed (RECIST or PSA) during prior docetaxel or within 3 months of discontinuing treatment, with adequate hematologic and organ functions and KPS ≥70% were stratified by pain and randomized to one of three treatments: Arm A: IROF (0.45 mg/kg, day 1 and 8 q3weeks [w]) and P (10 mg po daily); Arm B: IROF (0.4 mg/kg day 1 and 15), C(2000 mg/m 2 day 1–15 q4w) and P; or Arm C: M (12 mg/m 2 q3w) and P. Primary endpoint was TTP (RECIST, PSA or clinical progression); secondary endpoints included PSA response (≥50% decrease for ≥4 w), pain response, and toxicity; 135 pts are planned in a 2:2:1 ratio. The study was powered to detect a difference in TTP of 1.5 vs 3 months. Results: As of Dec 2005, 78 pts were randomized and treated with ≥ 5 months follow-up (A/B/C: 31/31/16). Median age (A/B/C) 69/70/61, KPS ≥80% 24/28/9, median baseline PSA ng/mL 90/147/235, disease related pain at baseline 61%/58%/63%; other characteristics, including metastatic site distribution, were similar between arms. Safety: 65 pts were evaluated for safety. Median cycles/Pt (A, B, C) 3/2/2; grade 3/4 toxicities (% pts A, B, C): asthenia (4%, 16%, 0%), vomiting (0%, 12%, 0%) and diarrhea (4%, 8%, 0%). The most common grade 3/4 laboratory abnormalities were neutropenia (10%, 6%, 31%) and thrombocytopenia (15%, 12%, 0%). Conclusion: IROF in combination with P and, in particular, C/P shows improved activity and acceptable tolerance compared to M/P in docetaxel-resistant HRPC. Patient accrual is complete as of Jan 2006, and final results will be presented. [Table: see text] [Table: see text]
Clinical outcomes in t(11;14) multiple myeloma.
Authors: Muhamad Alhaj Moustafa, S. Vincent Rajkumar, Angela Dispenzieri, Martha Lacy, Morie A. Gertz, Francis Buadi, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Yi Lisa Hwa, John Anthony Lust, Ronald S. Go, Robert A. Kyle, Shaji Kumar
Journal: Journal of Clinical Oncology (2015)

8592 Background: Chromosomal translocations involving the immunoglobulin heavy chain region on chromosome 14 are common abnormalities in multiple myeloma (MM); with translocation t(11;14) being the most common (15-20%). Our study focuses on the outcomes of this group and response to different therapies. Methods: We identified 254 patients with MM, who had fluorescence in situ hybridization (FISH) performed between 2004 and 2012 for MM and had t(11;14) abnormality. We included 199 patients who had FISH studies before MM diagnosis or within 2 years of diagnosis. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: The median age at diagnosis was 63 years (range, 22-95) and 129 (65%) were male. The estimated median follow up for the whole cohort was 69 months; 100 (50%) patients are alive. The PFS for the whole cohort was 15 months (95% CI; 11, 18) and the OS was 68 months (95% CI; 54, 88). Twenty-seven (14%) patients received conventional therapies for induction, whereas 172 (86%) received novel agents (116 IMiDs, 33 proteasome inhibitors, 23 both); 115 had stem cell transplant (SCT). Partial response (PR) or a better response to induction was seen in 55%. Median OS was similar for patients receiving conventional drugs or novel agents for initial therapy; 68 months vs. 70.5 months, p= 0.53. Median OS for those receiving an SCT was 72 months compared with 35 months for the remainder. The median OS for 33 patients with a 17p deletion was 26 months vs. 73 months for the remainder, p< 0.01. The OS for the 91 patients diagnosed before 2009 was similar to the 108 patients diagnosed later; p= 0.2. Conclusions: The median survival of patients with t(11;14) abnormality is 5-6 years, and does not appear to have changed significantly within the last decade.
A phase 1b study of the anticancer stem cell agent demcizumab (DEM), pemetrexed (PEM), and carboplatin (CARBO) in pts with first-line nonsquamous NSCLC.
Authors: Mark James McKeage, Dusan Kotasek, Ben Markman, Manuel Hidalgo, Michael Millward, Michael B. Jameson, Dean Laurence Harris, Robert J. Stagg, Jakob Dupont, Brett Gordon Maxwell Hughes
Journal: Journal of Clinical Oncology (2014)

2544 Background: Delta-like ligand 4 (DLL4) activates the Notch pathway and is important for cancer stem cell (CSC) survival. DEM is a humanized IgG2 anti-DLL4 antibody that has been shown to inhibit tumor growth, decrease CSC frequency & cause dysfunctional sprouting of new vessels resulting in an antiangiogenic effect in human tumor xenograft models. Methods: Pts received DEM (2.5, 5 or 7.5 mg/kg), PEM 500 mg/m2 & CARBO (AUC = 6) every 3 weeks followed by maintenance DEM or PEM (7.5 mg/kg cohort) every 3 weeks until progression. The objectives were to determine the MTD, safety, efficacy, immunogenicity, pharmacokinetics & biomarkers of Notch signaling. Results: Thirty-two pts were enrolled; 6 received 2.5 mg/kg, 20 received 5 mg/kg & 6 received 7.5 mg/kg of DEM. Related AEs in > 20% of pts were: nausea (53%), fatigue (47%), hypertension (41%), vomiting (34%), edema (28%), neutropenia (25%), & increased B-type natriuretic peptide (BNP) (22%). Increased BNP values are an early indicator of the cardiac effects of DEM & mildly elevated values are being used to initiate cardioprotective therapy with an ACE inhibitor or carvedilol. Two pts receiving 5 mg/kg developed reversible pulmonary hypertension & heart failure on days 167 and 183, respectively. As a result, DEM treatment was limited to 63 days in subsequent cohorts. One of 28 (4%) evaluable pts had a RECIST CR, 12 (43%) had a PR and 11 had SD. The Kaplan Meier estimated median progression free survivals for the 2.5, 5 and 7.5 mg/kg pts were 4.8, 5.3 and 4.4 months, respectively. Five pts who discontinued the study for a reason other than progression (3 continued to receive CARBO & PEM off-study) were progression-free through Day 223+, 243+, 457+, 497+, 680+ and a sixth pt (who continued to receive CARBO & PEM off-study) progressed at Day 850. Conclusions: DEM, CARBO & PEM was generally well tolerated with nausea, fatigue & hypertension being the most common drug related toxicities. The duration of DEM therapy is being limited to 63 days due to cardiopulmonary toxicity which was observed following more prolonged administration. Encouraging early clinical activity has been observed. Enrollment is ongoing and updated results will be presented. Clinical trial information: NCT01189968.
Final Journey: A reference booklet for families of dying patients.
Authors: Finly Zachariah, Stefanie Mooney, Chandana Banerjee, Sorin Buga, Bonnie Freeman
Journal: Journal of Clinical Oncology (2017)

189 Background: Family members will carry the memory of the death of their loved-one with them for the rest of their lives. If they perceive their loved-one suffered as they died there is a risk they will develop Post Traumatic Stress Disorder or other psychological dysfunctions. It is crucial the family be educated and holistically supported during the dying process. Health care providers and care givers require information that will enable them to act as patient advocates and work effectively with families toward the common goal of a peaceful death. Resources that provide basic explanations, suggestions for care, open communication, and prepare families and care givers about the dying process are essential. Methods: Final Journey is a patient and family centric booklet developed based on the CARES tool, which is a guide to help medical teams better care for the dying and their family. CARES stands for comfort, airway, restlessness and delirium, emotional and spiritual support, and self-care. Final Journey details in each section what patients and families may experience, helps families understand what constitutes suffering, and suggests what families can do to help their loved ones. Results: There is a need for education tools that are easily understood, pertinent, and made accessible to help improve the dying experience for all parties involved. Final Journey helps assure families are informed and more emotionally prepared. Furthermore, the booklet expands the available resources available to medical providers, allowing them to more effectively address the challenges of caring for the dying. Final Journey will be available as a free download from the Department of Supportive Care Medicine website. Conclusions: We anticipate utilization of the Final Journey booklet will improve knowledge and understanding for health care providers, care givers, and families regarding a normal dying process and how to distinguish this from suffering, provide them suggestions on how to offer support and comfort during the dying process, promote communication between health care providers, care givers, and families of dying patients and supply resources and information on the importance of self-care when working with a dying patient.
Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records
Authors: Steven Bell, Marina Daskalopoulou, Eleni Rapsomaniki, Julie George, Annie Britton, Martin Bobak, Juan P Casas, Caroline E Dale, Spiros Denaxas, Anoop D Shah, Harry Hemingway
Journal: BMJ (2017)

<h3>Abstract</h3> <h3>Objectives</h3> To investigate the association between alcohol consumption and cardiovascular disease at higher resolution by examining the initial lifetime presentation of 12 cardiac, cerebrovascular, abdominal, or peripheral vascular diseases among five categories of consumption. <h3>Design</h3> Population based cohort study of linked electronic health records covering primary care, hospital admissions, and mortality in 1997-2010 (median follow-up six years). <h3>Setting</h3> CALIBER (ClinicAl research using LInked Bespoke studies and Electronic health Records). <h3>Participants</h3> 1 937 360 adults (51% women), aged ≥30 who were free from cardiovascular disease at baseline. <h3>Main outcome measures</h3> 12 common symptomatic manifestations of cardiovascular disease, including chronic stable angina, unstable angina, acute myocardial infarction, unheralded coronary heart disease death, heart failure, sudden coronary death/cardiac arrest, transient ischaemic attack, ischaemic stroke, intracerebral and subarachnoid haemorrhage, peripheral arterial disease, and abdominal aortic aneurysm. <h3>Results</h3> 114 859 individuals received an incident cardiovascular diagnosis during follow-up. Non-drinking was associated with an increased risk of unstable angina (hazard ratio 1.33, 95% confidence interval 1.21 to 1.45), myocardial infarction (1.32, 1.24 to1.41), unheralded coronary death (1.56, 1.38 to 1.76), heart failure (1.24, 1.11 to 1.38), ischaemic stroke (1.12, 1.01 to 1.24), peripheral arterial disease (1.22, 1.13 to 1.32), and abdominal aortic aneurysm (1.32, 1.17 to 1.49) compared with moderate drinking (consumption within contemporaneous UK weekly/daily guidelines of 21/3 and 14/2 units for men and women, respectively). Heavy drinking (exceeding guidelines) conferred an increased risk of presenting with unheralded coronary death (1.21, 1.08 to 1.35), heart failure (1.22, 1.08 to 1.37), cardiac arrest (1.50, 1.26 to 1.77), transient ischaemic attack (1.11, 1.02 to 1.37), ischaemic stroke (1.33, 1.09 to 1.63), intracerebral haemorrhage (1.37, 1.16 to 1.62), and peripheral arterial disease (1.35; 1.23 to 1.48), but a lower risk of myocardial infarction (0.88, 0.79 to 1.00) or stable angina (0.93, 0.86 to 1.00). <h3>Conclusions</h3> Heterogeneous associations exist between level of alcohol consumption and the initial presentation of cardiovascular diseases. This has implications for counselling patients, public health communication, and clinical research, suggesting a more nuanced approach to the role of alcohol in prevention of cardiovascular disease is necessary. <h3>Registration</h3> clinicaltrails.gov (NCT01864031).
Panobinostat plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma who received prior bortezomib and IMiDs: A predefined subgroup analysis of PANORAMA 1.
Authors: Jesus F. San Miguel, Vania T.M. Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A. Dimopoulos, Ashraf Elghandour, Wieslaw W. Jedrzejczak, Andreas Guenther, Thanyaphong Na Nakorn, Noppadol Siritanaratkul, Robert L. Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae Hoon Lee, Hermann Einsele, Monika Sopala, Bourras-Rezki Bengoudifa, Claudia Corrado, Paul G. Richardson
Journal: Journal of Clinical Oncology (2015)

8526 Background: Panobinostat (PAN) is a potent pan-deacetylase inhibitor (pan-DACi) that targets key biological aberrations in multiple myeloma (MM), including epigenetics and protein metabolism. PAN + bortezomib (BTZ) and dexamethasone (Dex; PAN-BTZ-Dex) led to a clinically relevant and statistically significant increase in progression-free survival (PFS) of ≈4 months compared with placebo + BTZ and Dex (Pbo-BTZ-Dex) in patients (pts) with relapsed or relapsed and refractory MM in the PANORAMA 1 phase 3 clinical trial. Methods: The study design was described previously (San-Miguel. Lancet Oncol. 2014;15:1195-206). For this subanalysis, pts who received prior BTZ and IMiDs (lenalidomide or thalidomide) were analyzed for outcomes and safety. Results: A total of 193 pts (25%) received prior BTZ and IMiDs (PAN-BTZ-Dex [n = 94] or Pbo-BTZ-Dex [n = 99]). Median PFS as determined by investigator assessment for the PAN arm was 10.6 mo (95% CI, 7.6-13.8) vs 5.8 mo (95% CI, 4.4-7.1) for the Pbo arm (HR 0.56 [95% CI, 0.39-0.80]; P = .0011). Most (76%) received ≥ 2 prior lines and the difference in median PFS increased in these pts: PAN arm (n = 73): 12.5 mo (95% CI, 7.3-14.0); Pbo arm (n = 74): 4.7 mo (95% CI, 3.7-6.1; HR 0.47 [95% CI, 0.32-0.72]; P = .0003). For all pts who received prior BTZ and IMiDs, overall response rate was 58.5% (95% CI, 47.9%-68.6%) vs 41.4% (95% CI, 31.6%-51.8%; P = .0179) and ≥ near complete response rate was 22.3% (95% CI, 14.4%-32.1%) vs 9.1% (95% CI, 4.2%-16.6%) in the PAN and Pbo arms, respectively. Common grade 3/4 adverse events and laboratory abnormalities in each arm included thrombocytopenia (68.5% vs 48.0%), lymphopenia (50.0% vs 46.5%), neutropenia (35.9% vs 17.2%), diarrhea (30.4 vs 13.1%), and asthenia/fatigue (25.0% vs 12.1%). The percentage of on-treatment deaths in each arm was similar (6.4% vs 5.1%). Conclusions: PAN-BTZ-Dex demonstrated efficacy, with an increased median PFS of 4.8 months among MM pts who received prior BTZ and IMiDs, a population with a clear unmet need. The safety profile is consistent with that in the overall PANORAMA 1 population, although on-treatment deaths were similar. Clinical trial information: NCT01023308.
Outcomes of adjuvant ACT vs. TC chemotherapy in older women with breast cancer.
Authors: Sarah Schellhorn Mougalian, Jessica B. Long, Jane Hall, Kerin B. Adelson, Maysa M. Abu-Khalaf, Lajos Pusztai, Cary Philip Gross
Journal: Journal of Clinical Oncology (2015)

1009 Background: Chemotherapy with both anthracyclines and taxanes sequentially or concurrently (ACT) has improved survival in breast cancer. A regimen containing docetaxel and cyclophosphamide (TC) was developed to avoid cardiac side effects, which are of particular concern in older women. The efficacy of ACT vs. TC is under investigation in NSABP B-49, but results are not yet available. We examined temporal trends and clinical associations with ACT vs. TC use in clinical practice in older women and compared the overall survival of patients receiving adjuvant ACT vs. TC. Methods: We used the SEER-Medicare database for women over 65 diagnosed 2004-2009. Women were classified by regimen received: ACT, TC, and other (including anthracycline without taxane and cyclophosphamide, methotrexate, and 5-fluorouracil). We excluded women who received trastuzumab. We used chi-square and logistic regression to identify factors associated with ACT vs. TC receipt and Cox proportional hazards models to assess survival differences by treatment. Results: We identified a total of 4391 patients: 1577 (36%) received ACT, 1174 (22%) received TC, and 1640 received other regimens. Use of ACT decreased from 26% in 2004 to 21% in 2009, whereas use of TC increased from 1% to 43% in the same period. Receipt of ACT vs. TC was associated with younger age; fewer comorbidities; lack of history of coronary artery disease, diabetes, or atrial fibrillation; higher stage and lymph node involvement; and living in the Northeast United States (as compared to the West or South). Five-year overall survival (OS) estimates were 81% for patients receiving ACT and 86% for patients receiving TC (p = .21); 3-year unadjusted survival for stage III patients was 87% for ACT and 79% for TC (0.002). The adjusted Cox proportional hazard ratio for all patients, adjusted for stage, comorbidities, and other significant associations, was 1.10 (95% CI 0.64-1.91). The hazard ratio for ACT vs. TC was not significant for stage I/II patients, but for stage III patients was 0.59 (95% CI 0.40-0.89). Conclusions: TC has become a common choice for adjuvant chemotherapy among older patients. In all patients, 5-year OS was similar between groups, but OS may be higher for patients with stage III disease receiving ACT.
Intermediate-term outcomes from the DISSRM registry: A prospective analysis of active surveillance in patients with small renal masses.
Authors: Ridwan Alam, Hiten D. Patel, Mark F. Riffon, Bruce J. Trock, Akachimere Uzosike, Peter Chang, Andrew J. Wagner, James M. McKiernan, Mohamad Allaf, Phillip M. Pierorazio
Journal: Journal of Clinical Oncology (2017)

430 Background: Active surveillance is an alternative to primary intervention aimed at reducing the overtreatment of small renal masses, defined as solid renal masses ≤4.0 cm (clinical stage T1a). Methods: Since 2009, the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry prospectively enrolled 615 patients with small renal masses who chose to undergo primary intervention or active surveillance. Intervention was recommended to patients for masses with an elevated growth rate (&gt;0.5 cm/year) or increased tumor diameter (&gt;4.0 cm). Primary outcomes were cancer-specific survival and overall survival; secondary outcomes included progression-free survival. Progression was strictly defined as growth rate &gt;0.5 cm/year, greatest tumor diameter &gt;4.0 cm, metastatic disease, or elective crossover. Outcomes were evaluated using Kaplan-Meier survival analysis and comparisons were performed using the log-rank test. Results: Of the 615 enrolled patients, 298 (48.5%) chose primary intervention and 317 (51.5%) chose active surveillance. From the active surveillance cohort, 45 (14.2%) patients underwent delayed intervention. Median follow-up time for the entire registry was 2.9 years, with 203 (33.0%) patients followed for 5 years or more. At baseline, patients who chose active surveillance were older (p &lt; 0.001) and had higher comorbidity status (p &lt; 0.001) than those who chose primary intervention. There was no difference in cancer-specific survival at 7 years between primary intervention and active surveillance (99.0% vs. 100%, respectively, p = 0.3). However, overall survival was higher in patients with primary intervention when compared to active surveillance at 5 years (93.0% vs. 80.2%, respectively) and 7 years (91.7% vs. 65.9%, respectively, p = 0.002). The 5-year and 7-year progression-free survival rate in the active surveillance cohort was 76.7% and 48.4%, respectively. Conclusions: In the intermediate-term, active surveillance appears to be as safe as primary intervention for carefully selected patients with small renal masses. As the registry matures, further studies will elucidate the effectiveness of active surveillance in the long-term. Clinical trial information: NCT02346435.
Weekend emergency surgery is no riskier than operations during week, study finds
Authors: Nigel Hawkes
Journal: BMJ (2017)

Deaths in patients who have emergency surgery at the weekend are no more likely than in those whose operations take place on weekdays, a study in Scotland has found.1

In contrast with earlier studies that have shown a “weekend effect” among patients having elective surgery, the team, led by Michael Gillies, consultant anaesthetist at Edinburgh Royal Infirmary, found no evidence of higher short term or long term deaths in emergency patients operated on at the weekend.

In the British Journal of Surgery the team reported a cohort study looking at patients who had emergency general surgery in Scotland from 2005 to 2007.1 Data from Information Services Scotland identified 50 844 patients who had general surgical procedures, of whom 31 499 had their operation on a weekday (defined as Monday to Thursday) and 19 345 on a Friday, Saturday, or Sunday. The patients …