tbuckley/cabot-search huggingface dataset:
Improving hepatitis B screening prior to rituximab at a multispecialty urban hospital.
Authors: Lakshminarayanan Nandagopal, Ravi Kumar Paluri, Barbara Gleaton, Diego Alonso De Idiaquez, Lisle Nabell
Journal: Journal of Clinical Oncology (2017)

176 Background: Rituximab(R) is a novel anti-CD20 monoclonal antibody used in multiple hematologic and rheumatologic diseases. Patients who are hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive are at risk for hepatitis-B reactivation with R-based treatments. Therefore, the VA’s medication use evaluation tracker recommends serological testing for HBsAg, HBsAb and HBcAb within 6 months prior to initiating R. We conducted a PDSA cycle to improve Hepatitis-B serological testing in patients receiving R at Birmingham VA medical center (BVAMC). Methods: For baseline evaluation, patients at BVAMC who were treated with R between 2004- march 2014 were retrospectively evaluated for HBV serology results 6 months prior to first treatment. Presence of all 4- HBsAg, HBsAb and HBcAb (IgM and total) was complete; absence of all 4 was ‘not done’ with remaining being incomplete. After conducting a RCA, 3 pharmacy-based interventions were implemented- 1) pharmacy education; 2) pharmacist autonomy to order hepatitis B serology eliminating physician dependence; 3) pharmacy reminders to health care providers to order HBV serology. We aimed to improve ‘complete’ screening rates to &gt; 90% in the post-intervention period (april 2014-sep 2016). Results: In the pre-intervention group (n = 162), majority (81%) had hematologic indications and complete testing was performed in 38%, reminder being incomplete (13%) or not done (49%). Post-intervention (n = 86), majority (54%) had rheumatologic indications with complete testing in 71%, incomplete in 15% and not done in 14%. No Hepatitis B reactivations were identified in either study periods. Conclusions: Pre-intervention, ‘complete’ testing was performed in only one-third of patients and our intervention was effective in almost doubling screening rates. We also demonstrate increasing use of Rituximab in non-hematologic conditions and with second-generation anti-CD20 Ofatumumab and Obinutuzumab also requiring similar testing; our study could standardize Hep-B screening for these agents. A second PDSA cycle with a reflex ‘forcing-function’ EMR-based tool to decrease reliance on human factors is planned to meet the study goal of &gt; 90%.
The lipid metabolome of clear cell renal cell carcinoma (CCRCC).
Authors: Saby George, Kyoung-Soo Choi, Roberto Pili, Abdul Latif Kazim
Journal: Journal of Clinical Oncology (2012)

10609 Background: The commonest type of kidney cancer is CCRCC. Treatment approaches mostly target aberrant vasculature. However, kidney cancer is also known to accumulate lipids and a detailed knowledge of the lipid species present in these tumors could lead to a better understanding of the underlying aberrant metabolic pathways and suggest possible treatment strategies. Lipidomics is an emerging field driven by rapid advances in mass spectrometry (MS), and is widely used to discover biomarkers. We attempt to identify the lipidomic profile of CCRCC using a liquid chromatography MS-based approach (LC-MS). Methods: We utilized 6 fresh frozen representative samples of CCRCC and matching non-tumor areas of kidney from nephrectomy samples. Lipids and other non-polar cellular constituents were extracted from both CCRCC and control tissues by methyl-t-butyl ether /methanol. LC-MS based lipid profiling was performed on a Waters Q-ToF Premier MS coupled with Ultra Performance LC. The peak detection and alignment across all chromatograms were performed using the XCMS software (v 1.14.1, Scripps Center for Metabolomics). Statistical comparisons of the intensities of aligned peaks were performed using the XCMS-built-in Welch's t-test. Results: The outcome of XCMS was converted to a table that contains fold change, p-value and mass to charge ratio (m/z) for each peak, its corresponding retention time, and the integrated peak intensities from all samples. 224 peaks out of 1419 differed between CCRCC and the control group, with p &lt;0.05, calculated by XCMS. About an equal number of analytes increased or decreased in CCRCC compared with control samples. Preliminary attempts to identify the analytes included use of METLIN (Scripps Center for Metabolomics) and HMDB (Human metabolome database, Genome Alberta &amp; Genome Canada) databases. Many of the hits identified phosphatidylcholines, phosphatidylethanolamines, triacylglycerols and diacylglycerols, as well as other lipid species. Conclusions: The lipid metabolomic profile varied significantly between CCRCC and control. Further studies are required to confirm the identities of the lipid species contributing to this variation by obtaining structural information using tandem MS (LC-MS/MS).
Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy
Authors: Maryam Hussain, Loïc Borcard, Kevin P. Walsh, Maria Pena Rodriguez, Christoph Mueller, Brian S. Kim, Masato Kubo, David Artis, Mario Noti
Journal: Journal of Allergy and Clinical Immunology (2017)
Pneumocystis Jirovecii pneumonia (PJP) in metastatic breast cancer (MBC) patients (pts) treated with mTOR inhibitor everolimus (EVE) and exemestane (AI).
Authors: Geoffrey Watson, Giuseppe Gullo, Alessandra Zacchia, Daniele Zanoni, John Crown
Journal: Journal of Clinical Oncology (2015)

e11582 Background: The mTOR inhibitor EVE has been shown to augment the clinical activity of AI in MBC. Interstitial pneumonitis (IP) - presumed to be drug-induced - occurs in up to 20% of pts receiving EVE in MBC. The mTOR inhibitors as a class are immunosuppressive, and tacrolimus and EVE have been used to prevent rejection following organ transplants. PJP is a very rare complication of MBC therapy, usually seen only in pts receiving corticosteroids. A single case-report of PJP associated with EVE in MBC has been reported. We report the first series of PJP in pts treated with EVE/AI for MBC. Methods: We conducted a retrospective review of all MBC pts treated with EVE/AI at our institution and analyzed the cases who had a respiratory adverse event of any grade and a concomitant diagnosis of PJP. Results: Fifty-one pts received EVE/AI for MBC between September 2012 and December 2014. Five pts (9.8%) had a diagnosis of PJP while on EVE/AI. One non-EVE/AI MBC pt, who was receiving frequent steroids with weekly paclitaxel, was also diagnosed with PJP during this time. All the PJP cases were diagnosed based on clinical presentation and pulmonary infiltrates, and were confirmed by positive Polymerase Chain Reaction of the broncho-alveolar lavage fluid for PJ DNA. PJP pts characteristics were as follows: mean age: 71.6yrs (range 70-74), median exposure to EVE before PJP: 14 weeks (range 10-50), long-term/concomitant steroids: 1 pt. At PJP diagnosis 4 pts had normal leukocytes and lymphocyte count, 1 pt had G1 lymphopenia. None of the 5 pts had received chemotherapy or radiotherapy to the thorax in the preceding 12 months. No other additional risk factors of PJP were identified. All pts required hospitalization and received therapeutic IV co-trimoxazole. Conclusions: (1) PJP can complicate EVE/AI therapy for MBC. (2) A causative role for mTOR-induced immunosuppression is plausible and seems likely. (3) PJP may be underdiagnosed in this setting and should be considered in pts developing respiratory symptoms during EVE/AI therapy. (4) Some cases of presumed EVE/AI drug-induced IP may be caused by PJP. (5) If this observation is confirmed PJP prophylaxis should be considered.
Is adjuvant therapy for older patients with node (+) early breast cancer cost-effective?
Authors: A. Naeim, E. Keeler
Journal: Journal of Clinical Oncology (2004)

865 Background: To evaluate if adjuvant treatment for early-stage node (+) breast cancer with hormone therapy, chemotherapy, or combination therapy is cost-effective in older patients. Methods: A decision-analysis model for 65, 75, and 85 year-old female breast cancer patients using life tables. Both estrogen receptor (ER) (−) and (+) patients were considered. Treatment benefits were derived primarily from Early Breast Cancer Trialists' Collaborative Group meta-analyses. The cost of treatment in dollars and impact of quality of life was examined. Scenarios were used when treatment benefit was uncertain. The incremental cost-effectiveness of different treatment strategies were then compared and mapped graphically. Results: Adjuvant therapy is cost-effective in 65 year-old women with early breast cancer. In a 75 year-old ER (+) patient, hormone therapy is cost-effective, $10,965/QALY, but chemotherapy was only cost-effective, $27,406/QALY, only if one assumed it was as efficacious as in a 65 year-old woman. In a 75 year-old ER (−) patient, chemotherapy was cost-effective at $42,605 only with the same assumption. In an 85 year-old ER (+) patient, hormone therapy was cost-effective, $26,463/QALY, if efficacy is not age-sensitive, but chemotherapy was not cost-effective for ER(+) or ER(−) patients. Conclusions: Treatment decisions for older breast cancer patients suffer from the lack of sufficient clinical trial data. Decision analytic models can set bounds for the benefit of adjuvant breast cancer treatment and reveal the assumptions underlying different recommendations. No significant financial relationships to disclose.
Abstract 268: Transforming Growth Factor-β1 Increases Resistance of Fibroblasts to Apoptotic Cell Death
Authors: Ulugbek Negmadjanov, Zarko Godic, Mahek Mirza, Larisa Emelyanova, Farhan Rizvi, Ekhson Holmuhamedov, Arshad Jahangir
Journal: Circulation Research (2014)

Introduction: Cardiac injury results in the death of cardiac myocytes and subsequent scar formation through extracellular matrix (ECM) deposition by fibroblasts (FB) and myofibroblasts (myoFB). Excessive fibrosis results in pathological scarring that predisposes to arrhythmogenesis and heart failure, particularly in the elderly. Strategies to limit adverse ECM remodeling are urgently needed to curtail the growing epidemic of atrial fibrillation and heart failure in the aging population. Persistence of myoFB and resistance to apoptotic cell death has been proposed to underlie the mechanism of excessive fibrosis, yet is not fully characterized. Methods: Cultured NIH/3T3 cells (control and TGF-β1 treated) have been challenged with activators of extrinsic (FAS-Ligand, 1 μg/mL) or intrinsic (Thapsigargin 10 μM and Staurosporine 5 μM) apoptotic pathways and Caspase-3 activity was measured in cellular lysate. Results: FAS-L exposure induced ~40-fold suppression of Caspase-3 activity in TGF-β1 treated cells as compared with control (17±12 vs 686±5 nmol AMC/min/106 cells, respectively). Similarly, Staurosporine activated Caspase-3 in TGF-β1 treated cells ~3-fold (171±38 vs 536±29 nmol AMC/min/106 cells), and Thapsigargin ~10-fold (73±33 vs 742±8 nmol AMC/min/106 cells). Conclusion: TGF-β1 treatment increased the sensitivity of NIH/3T3 cells toward extrinsic and intrinsic apoptotic stimuli. Although, TGF-β1 treatment increased overall resistance of NIH/3T3 cells to apoptosis, the responsiveness of cells to extrinsic vs intrinsic pathways was differentially affected. This data support the hypothesis that persistence of myoFB results in pathological scarring.
Association between the expression of hormone receptors and HER2/Neu in early breast cancer and overweight or obesity.
Authors: Eduardo Richardet, Martin Eduardo Richardet, Matias Molina, Matias Nicolas Cortes, Romina Brombin, Aldo Alejandro Riso, Pablo Companys, Luciana Paola Acosta, Patricia Hernandez
Journal: Journal of Clinical Oncology (2014)

e11552 Background: In this paper we evaluate the association between overweight and obesity in patients with early-stage Breast Cancer in our population, and the presence of hormone receptors and Her 2 Neu. Methods: It is a retrospective study. A medical chart of 284 patients with early-stage Breast Cancer treated in our institution from 2005 to 2012 were evaluated. Obesity was defined as BMI greater than 30, overweight as a BMI between 25 and 29, and normal weight BMI since 18 to 24. Results: The median age was 62, 23 years. Follow-up was 53 months. The average BMI was 25.92. 39% of patients had normal weight, 36% overweight and 24% obesity. 78% of patients had positive hormone receptors, 14.78% were Her 2 neu positive and 11% triple negative. In this study we found a statistically significant association between patients with obesity or overweight and the presence of hormone receptor-positive (p = 0.001) and Her 2 Neu positive (p = 0.001). Conclusions: In our population, obesity / overweight were significantly associated with the presence of hormone receptors and Her 2 Neu in early breast cancer.
Phase II study of DHA-paclitaxel (TXP) as first line chemotherapy in patients with hormone refractory prostate cancer (HRPC)
Authors: R. Bellet, M. Carducci, D. Petrylak, B. Kasimis, D. Irwin, M. Modiano, R. Mansour, R. Axelrod, M. Doukas
Journal: Journal of Clinical Oncology (2004)

4657 Background: DHA-paclitaxel (Taxoprexin) is a covalent conjugate of paclitaxel and docosahexaenoic acid that has greater tumor specificity in pre-clinical models than paclitaxel. The conjugate accumulates in tumor tissue where it is cleaved to paclitaxel. The objective of this multi-center study was to evaluate the efficacy and tolerability of TXP as first line therapy in patients with HRPC. Methods: Thirty-six patients, median age 70y (range 56–86) PS 0 (12), PS 1 (24) with advanced HRPC and no previous cytotoxic treatment were enrolled. Patients were required to have adequate renal, hepatic and bone marrow function and measurable disease. TXP was administered iv over 2 hours q21 days at one of two doses, 1100 mg/m2 (14), 900 mg/m2 (22) . Results: Fifty-one courses (mean 3.6) were administered at 1100 mg/m2 and 65 courses (mean 2.9) at 900 mg/m2. Neutropenia was the primary toxicity and was dose limiting: 12 of 14 (86%) patients treated at 1100 mg/m2 had grade 3/4 neutropenia vs. 9 of 22 (41%) at 900 mg/m2. Thirty-two patients were evaluable for response: at 900 mg/m2, PR 1/19 (5%), SD 8/19 (42%) PSA 1/19 (5%); at 1100 mg/m2, PR 2/13 (15%), SD 7/13 (54%), PSA 1/13 (7%). Median survival is 17.5 months. Conclusions: The combination of objective responses and lengthy survival suggests that TXP is active in the treatment of patients with HRPC. (Supported by American Regent.) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Luitpold Pharmaceuticals, Inc. Protarga, Inc.
Adjuvant chemotherapy in lymph node positive bladder cancer
Authors: O. N. Gofrit, W. M. Stadler, K. C. Zorn, J. Silvestre, A. L. Shalhav, G. P. Zagaja, G. D. Steinberg
Journal: Journal of Clinical Oncology (2007)

15526 Background: Lymph node-positive bladder cancer is a systemic disease in the majority of patients. Prescribing adjuvant chemotherapy shortly after surgery, when tumor burden is low seems reasonable, yet there is no proof that this treatment strategy improves survival. In this retrospective study, we compared the outcomes of patients with microscopic lymph node positive bladder cancer (pN1 or pN2) treated with radical cystectomy followed by adjuvant chemotherapy and those who declined chemotherapy. Methods: Sixty-seven patients with lymph node positive bladder cancer (pN1 in 26 patients and pN2 in 41) who underwent radical cystectomy between April 1995 and April 2005 were reviewed. Combined adjuvant chemotherapy (gemcitabine and cisplatin in most patients) was given to 35 patients (52%), but deferred by 32 (48%). The two groups were similar in performance status, postoperative complication rate and N stage but deferring patients were on average 4 years older and had a more advanced T stage. Results: Adjuvant chemotherapy was well tolerated with 28/35 patients (80%) completed all 4 cycles. Median overall survival of patients given adjuvant chemotherapy was 48 months compared to 8 months for deferring patients (hazard ratio 0.13, 95% CI 0.04–0.4, p&lt;0.0001). Multivariate age adjusted analysis showed that adjuvant chemotherapy was an independent factor affecting overall survivals (hazard ratio 0.2, p&lt;0.0001). Subgroup analysis demonstrated that chemotherapy provided survival benefit for patients with pN2 disease but not for patients with pN1 disease (p=0.0001 and p=0.235 respectively). Conclusions: This retrospective real-life study supports the use of adjuvant chemotherapy after radical cystectomy in patients with node positive bladder cancer, especially when more than one lymph node is involved. No significant financial relationships to disclose.
Delivery of cancer care to inmates of correctional facilities through telemedicine
Authors: L. J. Lyckholm, D. Justis
Journal: Journal of Clinical Oncology (2004)

8142 Background: Provision of hematology/oncology and palliative care to inmates in correctional facilities is challenging for oncologists, facility healthcare providers and patients. Necessary consultation may not be readily available to the inmate population due to multiple barriers, including distance, expense, safety and inability of inmates to travel due to illness. Methods: Using real-time videoconferencing, with clear audio and video connections, we are making symptom management, surveillance and chemotherapy follow-up visits by telemedicine, reducing the expense of security personnel and travel to tertiary care centers from correctional facilities. Most importantly, we are able to minimize discomfort for the inmate with cancer, who must endure long distance travel, wear shackles for prolonged periods and undergo possible embarrassment of being seen in public in shackles and prison garb. So far, we have seen patients with acute leukemia, lung cancer and deep venous thrombosis secondary to a hypercoagulable state. Results: We are able to examine the patient, evaluate symptoms, answer questions, and discuss management with the facility providers. Our interventions have resulted in closer and more frequent evaluation than if the patient were being seen in the clinic. The patients are appreciative of the telemedicine visits, and it appears that their needs and concerns receive more consideration because of heightened visibility. Facility providers are also appreciative of the chance to discuss the patients' case and ask questions of specialists in real time. Communication and staff education, especially in issues of palliative care are enhanced, as well as education of oncology fellows in this special form of care delivery. Laboratory and radiographic studies may be done locally and reviewed at the time of the visit. Conclusions: Telemedicine provides safe, timely, cost-conscious, and comfortable evaluation and management when the patient does not need to be seen in person or receive therapy in the clinic. We next plan to survey inmates, guards and providers, as well as evaluate cost in personnel and travel time to quantify our findings. No significant financial relationships to disclose.
Qualitative themes underlying potentially avoidable terminal oncology ICU hospitalizations.
Authors: Robert Michael Daly, Andrew Hantel, Blase N. Polite
Journal: Journal of Clinical Oncology (2017)

101 Background: ICU admissions in the last 30 days of life is a quality measure endorsed by the National Quality Forum. Our prior research has demonstrated that nearly half of terminal oncology ICU hospitalizations are potentially avoidable. Methods: This was a retrospective care series of patients cared for in an academic medical center’s ambulatory oncology practice who died in an ICU during July 1, 2012 to June 30, 2013. Using a standardized assessment tool, an oncologist, intensivist, and hospitalist reviewed each patient’s electronic health record from 3 months prior to hospitalization until death and made a clinical determination of avoidability. Two investigators, blinded to the specialty of the reviewer, used a grounded theory approach to extract clinical themes associated with avoidability from the reviewers’ assessments. Results: The primary themes for avoidability identified and percent by specialty were as follows: failure to initiate appropriate advance care planning in the outpatient setting (68% oncologists, 55% intensivists, 65% hospitalists), failure to integrate understanding of limited prognosis from underlying cancer within the context of acute hospitalization (23% oncologists, 24% intensivists, 26% hospitalists), failure of clinical management (6% oncologists, 21% intensivists, 6% hospitalists), failure to recognize futility of outside hospital transfer (3% oncologists, 0% intensivists, 0% hospitalists), and failure of care coordination (0% oncologists, 0% intensivists, 3% hospitalists). A failure to educate and integrate surrogates into timely medical decision making was a prominent secondary theme for oncologists (22%), intensivists (18%), and hospitalists (29%). Conclusions: The themes identified suggest potential interventions to prevent avoidable terminal oncology ICU hospitalizations, including improved advance care planning in the outpatient setting, inpatient multidisciplinary communication to gain a better understanding of the patient’s underlying malignancy within the context of the acute hospitalization and prevent failures in clinical management, and better education and integration of surrogates in medical decision making.
Gene expression profile signature (DecisionDx-Melanoma) to predict visceral metastatic risk in patients with stage I and stage II cutaneous melanoma.
Authors: Navneet Dhillon, Anna R Rogers, Keith A. Delman, Derek Maetzold, Kristen M. Oelschlager, Stephen Lyle, Gilchrist L. Jackson, Anthony Greisinger, Douglas Parker, Robert W. Cook, David H. Lawson
Journal: Journal of Clinical Oncology (2012)

8543 Background: The current AJCC TNM staging system has poor specificity for predicting visceral metastatic risk in patients diagnosed with stage I or stage II cutaneous melanoma. We, therefore, developed a gene expression profile signature (GEP) following in silico investigation of previously published microarray analyses. Methods: 60 formalin fixed paraffin embedded primary cutaneous melanoma samples from patients with stage I or II cutaneous melanoma with at least a follow up period of at least 6 years were macrodissected and analyzed blindly. RNA was isolated, converted to cDNA and RT-PCR was performed to assess the expression of the gene set. Expression data and biostatistical analysis was performed using GeNorm and JMP Genomics (SAS) Predictive modeling included Radial Basis Machine (RBM) and Partition Tree Analysis (PTA) Metastasis-free survival (MFS) was assessed using Kaplan-Meier analysis. The following clinical data was retrieved from medical records: survival, metastases, types of metastases. 20 out of 60 patients had developed visceral metastases in the follow up period. Results: GEP was developed following multiple analytical approaches.Two types of signatures emerged: Low risk (Class 1) and High risk (Class 2). Without optimizing for sensitivity, the analyses of the 60 sample cohort by radial basis machine (RBM) resulted in 92% ROC (met. accuracy = 90%, non-met. accuracy = 85%), while partition tree analysis (PTA) yielded 99% ROC (met. accuracy = 100%, non-met. accuracy = 95%). RBM classification showed 6-year MFS rates of 97% for Class 1 and 19% for predicted Class 2 of metastasis (median MFS = NR and 5.6 yrs, resp., P&lt;0.0001 Log-Rank respectively). PTA showed 6-year MFS rates of 100% for predicted Class 1 and 14% for Class 2 of metastasis (median MFS = NR and 5.4 yrs, resp., P&lt;0.0001 Log-Rank respectively). Conclusions: This study shows that DecisionDx-Melanoma GEP signature can provide excellent accuracy in predicting metastatic risk in stage I and II cutaneous melanoma.To our knowledge, the GEP provides the most accurate predictor to date for development of visceral metastases in patients with Stage I and II cutaneous melanoma.