tbuckley/cabot-search huggingface dataset:
Evaluation of the prostate health index (<i>phi</i>) as a novel biomarker in active surveillance of prostate cancer.
Authors: Andrew Eichholz, Frank McCarthy, Nening Dennis, Karen Thomas, Tim Howlett, Jhangir Iqbal, Jan Amin, Mildred Tan, Mausam Singhera, Elizabeth Selvadurai, Robert Anthony Huddart, David Paul Dearnaley, Chris Parker
Journal: Journal of Clinical Oncology (2014)

81 Background: Phi is calculated from serum PSA, free/total (f/t) PSA and [-2]proPSA using the Beckman Coulter assay kit, and has been approved for use in patient selection for diagnostic prostate biopsy. We hypothesized that phi might also predict outcome of active surveillance. Methods: From 2002, we have done a prospective cohort study of active surveillance for men with T1/2, Gleason &lt;= 3+4, PSA &lt; 15ng/ml prostate cancer. Serum was banked at baseline. Monitoring included 6 monthly PSA and 2-yearly repeat biopsy. Treatment was indicated for PSA velocity &gt; 1ng/ml/yr or Gleason &gt;= 4+3 on repeat biopsy. We analyzed baseline phi with respect to time to treatment. A multivariate model was fitted using total PSA, PSA velocity, PSA density, Gleason score, % biopsy cores positive, T stage, and maximum % cancer in any biopsy core. The fit of this model was then compared with the addition of % f/t PSA and phi. Results: 370 patients were evaluable with a median follow-up of 5 years. The table shows the association between baseline phiand time to treatment. On multivariate analysis, the model with % f/t PSA was a significant improvement over base model (change in fit 41.1, p&lt;0.001), and the model with % f/t PSA and phi was a significantly better fit than % f/t PSA alone (change in fit 11.1, p=0.001). Conclusions: In men with favorable risk prostate cancer, phi at diagnosis was a significant predictor of the outcome of active surveillance. The data require validation, but suggest that active surveillance is particularly attractive to men with a low phi. [Table: see text]
Emotional disclosure in home hospice cancer care: Implications for spouse caregiver bereavement.
Authors: Maija Reblin, Lee Ellington, Margaret Clayton, Michael Caserta, Dale Lund, Kathi Mooney
Journal: Journal of Clinical Oncology (2016)

54 Background: Evidence shows the benefit of positive and negative emotional disclosure for family caregivers (CG), but little is known about the impact of emotional disclosure at end of life. We assessed the effect of CG and hospice nurse disclosure during home visits on CG anxiety and depression in bereavement. Methods: As part of a larger study, nurse visits to 95 spouse CGs of cancer home hospice patients were audio recorded. An adapted Roter Interaction Analysis System was used to identify emotional disclosure: CG and nurse positive emotion (humor, gratitude), CG distress, and nurse emotional response (reassurance, validation). CGs completed demographics at hospice enrollment, and HADS anxiety scale, and Geriatric Depression Scale (GDS) at enrollment, and 2, 6 and 12 months after patient death. Growth curve analysis was conducted to predict HADS and GDS trajectories, controlling for CG gender, total talk, anxiety and depression at enrollment. Results: Average spouse CG age was 65; 60% were female and 98% were white. There were no GDS effects for CG expression of distress or nurse emotional response. Higher CG positive emotion talk predicted higher GDS at 2 months (B = .18, p &lt; .01), but a significant decline of GDS over time (B = -.08, p = .03). There were no effects for CG emotional disclosure on anxiety. However, more nurse emotional response predicted lower anxiety at 2 months (B = -.10, p = .02) which did not significantly change over time. More nurse positive emotion did not impact anxiety at 2 months, but predicted lower anxiety over time (B = -.04, p = .04). Conclusions: Emotional disclosure during cancer hospice visits was associated with spouse CG bereavement trajectories. CG positive emotion talk may signal increased potential for depression early in bereavement, but appears to lessen over time. CGs who express more positive emotion, which includes humor, gratitude and savoring the moment, may be more sensitive to loss, but appear to recover in time. Nurse expression of reassurance and validation, and of positive emotions seems to be effective in addressing and normalizing CG anxiety during bereavement. These findings have potential implications for communication interventions.
Implementing an emergency department EMR trigger tool for palliative medicine consultation and its effect on length of stay and health care costs: A retrospective study.
Authors: Dmitry Kozhevnikov, Felix Rivera, Wendy Edwards
Journal: Journal of Clinical Oncology (2016)

167 Background: Several studies have shown that palliative medicine consultation can improve multiple patient-centered outcomes, especially when provided early. Our goal is to show that our electronic health record (EHR) trigger tool is a cost-effective way for hospitals to identify patients who may benefit from early consultation, improving outcomes such as hospital length of stay and facilitating appropriate disposition for patients with metastatic cancer. Methods: Retrospective chart review of 721 patients at an urban community hospital who were identified by a trigger system integrated into the Emergency Department (ED) EHR. Patients who met criteria for a palliative consultation as determined by ED physicians at the time of inpatient admission were tracked by the palliative medicine department as part of a pilot phase. Those that were triggered and received usual care made up the control group. The intervention group was made up of patients who were triggered and seen in consultation. Results: Patients who were seen within 3 days of trigger were found to have a mean length of stay of 7.57 days, while those seen after 3 days had a mean length of stay 10.61 days. Patients who were triggered for metastatic cancer were found to have differences in final disposition between the two groups. Discharge to subacute rehabilitation facilities (SAR) in these patients decreased from 24% in the control group to 12% in the intervention group, while use of home hospice more than doubled to 11%. The percentage of these patients dying in the hospital decreased from 18% to 12%. Conclusions: Our study showed that earlier consultation was associated with shorter hospital length of stays if patients were seen within 3 days of being flagged as having palliative care needs in the ED. We also found that our EHR trigger doubled home hospice utilization in patients with metastatic cancer, decreased the proportion of discharges to SAR, and decreased in-hospital death in these patients.
Classification of a VUS in <i>MLH1</i> using a combination of family segregation studies and protein biochemistry.
Authors: Kevin M. Zbuk, Kathleen Bell, Anna Zhou, Alba Guarne, Melyssa Aronson, Jordan Lerner-Ellis, Aaron Pollett, Laura Palma, George Chong
Journal: Journal of Clinical Oncology (2013)

342 Background: The identification of variants of unknown clinical significance (VUS) presents a challenge for diagnostic laboratories and clinicians working with families with Lynch syndrome (LS). Although a variety of strategies exist to attempt clarification, data from multiple sources is often required before a VUS is re-classified to pathogenic or benign. Methods: We report on the investigation of 2 families with a variant in the MMR gene MLH1, c.2038T&gt;C (p.Cys680Arg). In addition to segregation analysis, and review of published literature, the c-terminal domain of MLH1was cloned, the p.Cys680Arg variant was generated using site-directed mutagenesis and protein expression was induced. In addition, this point mutation was modelled onto the crystal structure of the dimerization domain of MLH1. Results: Both families fit Amsterdam criteria for a diagnosis of LS. All available tumours exhibited MLH1 deficiency and microsatellite instability and all living affected individuals available were positive for MLH1 p.Cys680Arg variant. Protein studies confirmed that p.Cys680 resides in a tight hydrophobic cavity and the p.Cys680Arg mutation disrupts the folding of the C-terminal domain of MLH1. In two families this variant segregated with disease in a total of 12 individuals (&gt;10 meiosis and &gt;1000:1 odds in favor of linkage) and 3 had an MLH1 deficient tumour, supporting a pathogenic role for this variant. Inspection of the crystal structure of MLH1 suggested that the Cys680Arg mutation should severely alter the folding of the dimerization domain. As opposed to the dimerization domain of MLH1 that can be readily produced recombinantly and is stable in solution, the same domain of MLH1 encoding the Cys680Arg mutation was expressed as inclusion bodies, confirming that this mutation causes misfolding of the dimerization domain of MLH1. Conclusions: Our data confirms that the p.Cys680Arg mutation destabilizes the dimerization domain of MLH1, and presumably the DNA mismatch repair proficiency of individuals carrying this mutation. Based on this evidence and family history data, the MLH1 C680R missense variant is classified as pathogenic. This approach may prove useful in the classification of other variants.
Prophylactic mastectomy: The role of risk aversion.
Authors: Laura Kruper, Meghana Bhatt, Karin London, Katherine Henderson, Courtney Vito, John H. Yim, Steven L. Chen
Journal: Journal of Clinical Oncology (2012)

39 Background: The rate of women undergoing contralateral prophylactic mastectomy (CPM) has increased significantly over the past decade. Large population studies have examined factors associated with the use of CPM. We studied the factors associated with CPM within our institution. Methods: A 30-question validated survey was mailed to all patients who underwent mastectomy from 1972 to 2011 and are currently receiving treatment or surveillance at our institution. Responses were analyzed to determine the factors predictive of CPM. Multivariate logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for possible associations between exposures (including age at surgery, marital status, education, race, family history of breast cancer, and BRCA genetic mutation (BRCA mutation) and likelihood of CPM. Results: 368 of 691 surveys were returned. Younger age was statistically significantly associated with increased likelihood of CPM (p-trend &lt; 0.001). Caucasian patients were 4 times as likely to undergo CPM compared to non-Caucasian patients (OR 3.95, 95%CI=1.89-8.23). Patients with a family history of breast cancer were 3 times as likely to undergo CPM as compared with those with no family history (OR 3.38, 95%CI=1.4-8.16). Married patients were also 3 times as likely to undergo CPM compared with unmarried patients (OR 3.00, 95%CI=1.39-6.52). Reporting a BRCA mutation was highly correlated with younger age, positive family history, higher level of education and marital status. Conclusions: When faced with the decision of whether to undergo a CPM, patients must assess both objective future risks and subjective feelings about those risks. These results suggest that the decision to undergo CPM is associated with known risk factors for the development of contralateral cancer such as younger age and positive breast cancer family history. In addition, multiple demographic factors including Caucasian race and married status increased the likelihood of choosing CPM. This may relate to social support as well socioeconomic status. Further exploration into societal factors that impact CPM use is warranted.
The lipid metabolome of kidney cancer.
Authors: Saby George, Kyoung-Soo Choi, Jeff C. Miecznikowski, Roberto Pili, A. Latif Kazim
Journal: Journal of Clinical Oncology (2012)

16 Background: The commonest type of kidney cancer is CCRCC. Kidney cancer is 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. 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. The XCMS data was converted to log2 ratios (normal/tumor) in order to utilize the paired aspect of this data: each patient’s disease tissue was analyzed in conjunction with corresponding normal tissue. Significance was determined by controlling the family wise error rate (FWER) at 0.05 using a Bonferroni adjustment. All computations were performed using the R statistical software and the “limma” package. 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. Controlling FWER at 0.05 using a Bonferroni scheme, we found eight statistically significant lipids. Preliminary attempts to identify the analytes included use of METLIN (Scripps Center for Metabolomics) and HMDB (Human metabolome database, Genome Alberta and Genome Canada) databases. The identified metabolites included phosphatidylcholines, cholesterol esters and triglycerides, as well as other lipid species. Conclusions: The lipid metabolomic profile varied significantly between CCRCC and control. Further studies are underway to confirm the identities and significance of the lipid species in detail.
Frequency of recurrence in early breast cancer and association of known prognostic factors with relapse and time to relapse in a tertiary care hospital in Pakistan.
Authors: N. A. Zahid, S. Tabassum, R. Soomro, B. Soomro, N. Faridi
Journal: Journal of Clinical Oncology (2011)

e21175 Background: Breast cancer is the most prevalent cancer in women and a leading cause of cancer-related death. Following surgery and initial treatment, recurrence remains a risk for all patients with breast cancer. Methods: This is a cross sectional study. Complete data of 300 patients treated for early breast cancer during 2004-2008 at Oncology Dept, LNH was analysed. Out of these 300 patients, 76 patients had relapsed. Data were collected on SPSS version 17, and analyzed. Variables were age, tumor size, nodal status, tumor grade, hormonal status and her 2 neu status, taxanes versus non taxanes treatment, use of trastuzumab and hormonal treatment. Early relapse was defined as in less than 2 years and relapse after 2 or more years was taken as late relapse. Results: 300 patients were analyzed. Mean age of our patients were 47.6 ± 11.2 years. Out of these 300, 73 patients relapsed (24.7%). 44 patients (58%) relapsed in less than 2 years, and 33 patients (42%) relapsed after 2 years. Risk factors associated with relapse included tumor size, nodal status, grade and hormone receptor status. There was significant association between hormonal status and time to relapse ((P 0.001). We did not find any significant association in over all relapse rate, and different immunohistochemical subtypes but on analyses of time to relapse, early relapse was higher in triple negatives and her 2 neu positive group (P 0.001). There was a trend towards increased incidence of visceral and brain metastases in early relapse and of bone metastases in late relapse. Patients who relapsed early (< 2 years) had median survival of 1 year while those who relapsed after 2 years had median survival of 4 years. Conclusions: We found strong association of ER/PR status only with time to relapse in carcinoma breast. Early relapse was higher in triple negatives and her 2 neu positive group with shorter median survival in early relapse.
Developing a culture of safety in systemic cancer treatment at the system level.
Authors: Sherrie Hertz, Leonard Kaizer, Monika K. Krzyzanowska, Vicky Simanovski, Kathy Vu
Journal: Journal of Clinical Oncology (2013)

230 Background: Chemotherapy ordering, preparation and delivery involve multiple providers and complex systems where high impact errors may occur. Cancer Care Ontario, a provincial agency responsible for continually improving cancer services in Ontario, Canada employs a comprehensive systematic approach to build a culture of safety for systemic treatment. Methods: A comprehensive strategy is applied at 77 systemic treatment hospitals in the Province. A multi-pronged approach is used that includes: 1) system planning, organization and funding, 2) engagement of health care providers working at the regional and local levels, 3) guidelines implementation and, 4) quality measurement. Results: Institutions are organized into regional networks, according to four levels of service complexity based on quality standards, planning, funding, coordination and health human resources. A customized, system-wide incident reporting system is available. Quality improvement is undertaken in several ways. Regional clinical and administrative leaders foster engagement with local providers and work is facilitated by a provincial multidisciplinary community of practice, an annual Safety Symposium, and local improvement projects with funding support. In this way, collaborative sharing and learning occurs across the Province. Comprehensive evidence-based guidelines have been produced addressing safe labeling, administration, handling and the use of computerized prescriber order entry systems. Routine performance management together with guideline concordance measurement, public reporting, planning for improvement and re-evaluation strategies, has produced system improvements. Conclusions: A comprehensive, evidence-based and systematically applied approach to providing systemic cancer treatment can produce a culture of safety that is coordinated and standardized across multiple providers and provider sites.
Development and validation of a prognostic nomogram for progression-free and overall survival in patients with advanced renal cell carcinoma (aRCC) treated with pazopanib.
Authors: Michael W. Kattan, Cora N. Sternberg, Faisal Mehmud, Kamalnayan Bhatt, Debasis Chakrabarti, Lauren McCann, Robert John Motzer
Journal: Journal of Clinical Oncology (2014)

405 Background: Pazopanib, an oral multikinase inhibitor, demonstrated noninferiority to sunitinib in patients with aRCC in COMPARZ (NCT00720941), a randomized, phase III trial (NEJM 2013;369:722). The purpose of this study was to develop and validate prognostic nomograms based on outcome data from COMPARZ for predicting the probability of 12-month progression-free survival (PFS) and 30-month overall survival (OS) for aRCC patients who received pazopanib. Methods: Statistical modeling was performed on a dataset consisting of 557 patients from the pazopanib arm of COMPARZ. A Cox proportional hazards regression model was fit using predictors thought to be prognostic. These predictors included neutrophil count, platelet count, LDH, and alkaline phosphatase, all relative to ULN; calcium; albumin; hemoglobin; Karnofsky score; months from diagnosis to treatment; number of metastatic sites; and presence of lung, liver, and bone metastases. Data from patients on the sunitinib arm of COMPARZ and the pazopanib arm of the VEG105192 trial (NCT00334282; J Clin Oncol 2010;28:1061) were used for validation. Missing values were imputed using chained equations. For validation with the VEG105192 dataset, bootstrap-corrected estimates of discrimination and calibration were calculated following 1000 resamples. The Cox model was plotted as a nomogram. Results: Prognostic nomograms were developed and validated for predicting the probability of 12-month PFS and 30-month OS in aRCC patients based on a Cox regression model. Calibration plots suggested reasonable correspondence between predicted probabilities and actual proportions of PFS and OS. The concordance index for 12-month PFS was 0.636 with sunitinib patients and 0.635 for pazopanib patients; the concordance index was 0.692 for 30-month OS (sunitinib patients). When examining the PFS and OS nomograms, albumin, calcium, and LDH levels appeared to be the most influential predictors of outcome. Conclusions: The nomograms predict, with reasonable accuracy, treatment outcomes in patients with aRCC receiving pazopanib, based on their baseline clinical characteristics.
FDG-PET as predictor of outcome in diffuse large B-cell lymphoma (DLBCL): First analysis of “indeterminate” reports
Authors: A. Thomas, R. Gingrich, B. J. Smith, L. S. Jacobus, T. M. Habermann, B. K. Link
Journal: Journal of Clinical Oncology (2008)

8510 Background: Studies to date establishing the predictive value of FDG-PET scans after primary therapy for DLBCL have utilized Nuclear Medicine specialists to score these images as “negative” or “positive”. In practice however, there are indeterminate scans where the report is neither clearly positive nor clearly negative. We evaluate the predictive value of FDG-PET reports, including indeterminate ones, following curative intent therapy in DLBCL. Methods: Consecutive, newly diagnosed patients (pts) > 18 yo with systemic DLBCL from 9/02-12/05 were prospectively offered enrollment in the University of Iowa/Mayo Lymphoma SPORE registry. Available FDG-PET reports obtained 3–8 weeks after primary therapy were analyzed. FDG-PET reports (de-identified) were separately interpreted as positive, negative or indeterminate by three medical oncologists (AT, RG, BL) blinded to other clinical information. Reports were labeled positive or negative if all three interpreters independently agreed. All others were considered indeterminate. Event-free survival (EFS) and overall survival (OS) using the combination of restaging FDG-PET interpretation and initial R-IPI score were calculated. Results: 139 pts were evaluated. Median follow-up was 31 months. 21% of reports were indeterminate. EFS at 2 and 3 years by FDG- PET interpretation is reported in the table. NPV of a negative FDG-PET report at three years was 80%. OS at 3 years for the negative, indeterminate, and positive groups was 86%, 82%,and 51% respectively (p <0.0001). Among pts with a positive FDG-PET report 2 year OS by Very Good, Good and Poor R-IPI was 80%, 63% and 30% respectively (p=0.027) Conclusions: This is the largest analysis to date describing the predictive value of restaging FDG-PET reports in pts with DLBCL. Indeterminate reports predict outcomes more similar to negative than positive reports, and were notable for later events. Pre-therapy R-IPI score enhanced predictive value of FDG-PET reports. EFS by FDG-PET Interpretation and R-IPI score FDG-PET Report Indeterminate (N=29) Negative (N=78) 2-year EFS (95% CI) 80% (62–93) 86% (78–94) 3-year EFS (95% CI) 61% (44–84) 80% (71–89) R-IPI subset Very Good (N=1) Good (N=15) Poor (N=13) Very Good (N=14) Good (N=35) Poor (N=29) 2-year EFS (95% CI) 100% 87% (71–100) 62% (40–95) 100% 86% (75–98) 79% (66–96) 3-year EFS (95% CI) 100% 74% (52–100) 40% (16–85) 100% 76% (63–92) 75% (61–93) p-value for R-IPI within PET Result 0.087 0.081 No significant financial relationships to disclose.