tbuckley/cabot-search huggingface dataset:
Pilot study of family caregiver burden in home hospice: Stress-induced immune changes.
Authors: Abdullah Ladha, Judith Salmon Kaur, Sarah Lee, Robert A. Vierkant, Wendy Kay Nevala
Journal: Journal of Clinical Oncology (2015)

9512 Background: In 2012, 1.5-1.6 million patients received hospice care in United States. The majority received care at home. Unfortunately caregiving has been reported as an independent risk factor for mortality. Caregivers of hospice patients comprise a special group, as most patients die within short time span and have diverse trajectories. Therefore, this group deserves study to confirm or negate immune dysregulation as seen in dementia caregivers. Methods: Family caregivers were enrolled after providing informed consent. Caregivers were included if they provided minimum of eight hours cares each day, for at least two weeks and had no active inflammation or infection. Participants filled a questionnaire and provided a blood sample. Samples from age and sex matched healthy control subjects were acquired from the Mayo Clinic Biobank. ELISA and flow cytometry were used to run lab tests. Paired t-tests were used to compare biomarker values in two groups. Results: Blood samples from 39 caregivers were compared with controls. The following markers were significantly higher in caregivers: IL-1 beta, IL-2, IL-12, CRP, IL-8, CXCL1, CXCL2 and CXCL3. Cell markers with higher values in caregivers were: CD4+, CD8+, CD56+16+, CD69 and CD62L. Regulatory markers like regulatory T cells and TIM-3 were also higher in caregivers. Cytokines and chemokines significantly lower in caregivers were: IL-4, CCL-7, CCL-22, CCL-4, Eotaxin (CCL-11, CCL-24, CCL-26), CX3CL1 and CXCL10. Conclusions: Hospice caregivers demonstrated an increased inflammatory state and enhanced cell mediated immune changes as compared to age-matched controls. These changes may reflect immune dysregulation and proliferation, either due to loss of regulatory markers like Eotaxins or inefficient regulatory machinery including TIM-3 and regulatory T-Cells, which is unable to suppress inflammation and potentially result in adverse caregiver health. Biomarker Paired Difference Median P-value CD16+56+ 5.5 (-1.6 , 10.6) 0.003 CD3+CD4+ 9.1 (-1.1 , 18.5) 0.001 CD3+CD8+ 8.0 (-0.2 , 15.6) 0.003 CD4+TIM3+ 3.1 (0.6 , 4.5) < 0.001 Treg 6.3 (-1.7 , 15.3) 0.005 CRP 1.2 (-0.1 , 4.3) < 0.001 Eotaxin -148.3 (-246.3 , -94.5) < 0.001 IL-2 0.3 (-1.1 , 5.8) 0.010 IL-12 5.5 (-0.6 , 17.4) 0.003
Prognostication using serum levels of components of the folate metabolic pathway in patients (PTS) treated with capecitabine for advanced colorectal cancer (ACRC)
Authors: M. D. Vincent, D. Jonker, I. Kerr, R. Goel, L. A. Martin, A. Gurjal, J. Mathews, J. Biagi, G. Knight, W. Lam
Journal: Journal of Clinical Oncology (2004)

3764 Background: Capecitabine [Xeloda (XEL)] is an oral pro-drug of 5-fluorouracil, which in turn forms a terniary complex with thymidylate synthase and reduced folate. Folate metabolism could therefore have an impact on the clinical efficacy of XEL. Players include homocysteine, which is converted to methionine in a reaction forming tetrahydrofolate in the presence of vit B12. These and other factors may play a prognostic role in pts with ACRC. Methods: A multicentre phase I/II trial of XEL 2000mg/m2 d1–14 q21d was conducted in 139 pts in one or more of the following subsets: age > 65 years (99 pts), ECOG performance status (PS) >1 (85 pts), LDH (43 pts), prior pelvic radiation (36 pts), liver enzyme abnormalities (4 pts). A substudy is reported on the prognostic significance of serum and RBC folate, vit B12, homocysteine, LDH, LDH isoenzymes, and ECOG PS. Results: 86 pts were evaluable for homocysteine levels, 122 for LDH, and 137 for ECOG PS. High homocysteine (n=37) predicted for markedly shorter median overall survival (MS) vs normal levels (n=49). Serum folate, RBC folate, and vit B12 did not predict for survival, though high folate predicted for tumour response. High LDH (n=71) predicted for shorter MS vs normal LDH (n=51), and lower response rate. Pts with high LDH have a lower proportion of LDH isoenzyme 1 (15.1%) vs pts with normal LDH (21.5%), p<0.0001. Less LDH isoenzyme 1 depression predicted for better MS (p=0.08). ECOG PS 0 (n=52) had worse MS vs ECOG PS 1 to 2 (n=85). Pts with normal LDH and high homocysteine had a poor MS (9.4 mos), suggesting homocysteine is a more powerful prognostic factor. Conclusions: High serum homocysteine, high LDH and poor PS are poor prognostic factors in pts with ACRC treated with XEL. Accrual continues and updated results including multivariate analysis will be presented. Supported by Hoffman-La Roche Canada. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-LaRoche Canada
The driver landscape of angiosarcoma.
Authors: Sam Behjati, Patrick Tarpey, Helen Sheldon, Michael R. Stratton, Adrienne Flanagan, Andrew Futreal, Adrian L. Harris, Peter J. Campbell
Journal: Journal of Clinical Oncology (2014)

10511 Background: Angiosarcoma is an aggressive tumour of presumed vascular endothelial origin that is commonly thought to be driven by aberrant angiogenesis. The somatic alterations underpinning angiosarcoma are largely unknown and have not previously been investigated by unbiased next generation sequencing. Methods: Thirty nine primary and secondary angiosarcomas were screened by whole genome (n=3), exome (n=8), or targeted re-sequencing of 33 angiogenesis genes (n=28). Somatic alterations were identified using the analysis pipeline of the Cancer Genome Project. Results: We identified novel driver mutations in two genes, PTPRB and PLCG1, both of which function to regulate angiogenesis signalling. PTPRB mutations were identified in 10/39 (26%) tumours, comprising 11 truncating and 3 missense variants. Four cases harboured 2 different PTPRB mutations each. A single recurrent missense variant, R707Q was identified in the PLCG1 gene in (3/34) 9% of tumours. The enrichment of PTPRB and PLCG1 mutations was highly significant (q=10-9; q=2x10-6). Conclusions: The mutational profile, comprising predominantly truncating mutations, suggests that PTPRB operates as a recessive cancer gene in angiosarcoma. This proposition is consistent with the function of PTPRB as a negative regulator of vascular growth factor tyrosine kinase receptors. In contrast, PLCG1, which transduces signalling of these receptors, likely operates as a dominant cancer gene with a single recurrent missense mutation found in three cases. Molecular modelling revealed that the R707Q PLCG1mutation is predicted to lead to constitutive activation of the PLCG1 enzyme and may therefore represent an attractive therapeutic target. Combining the PTPRB and PLCG1 mutations with other driver mutations we found, shows that 15/39 (40%) tumours harbour at least 1 canonical driver mutation in angiogenesis genes, including in H/N/K-RAS (13%), PIK3CA (3%), and FLT4 (3%). Driver mutations in angiogenesis genes were not mutually exclusive and co-occurred in a single dominant tumour clone. A pertinent question that arises from our study is whether the largely disappointing results from clinical trials of anti-angiogenesis drugs in angiosarcoma are confounded by the apparent redundancy of angiogenesis driver mutations.
The impact of peri-operative chemotherapy for patients with lymph node-positive urothelial cancer.
Authors: Jeenan Kaiser, Haocheng Li, Richard M. Lee-Ying, Daniel Yick Chin Heng, Nimira S. Alimohamed
Journal: Journal of Clinical Oncology (2017)

388 Background: Patients with locally advanced urothelial cancer with regional lymph node involvement (LN+) have a poor prognosis. Surgical management of these patients is controversial and practice patterns vary. We evaluated the outcomes of patients with LN+ disease treated with pre-operative chemotherapy and cystectomy, cystectomy and post-operative chemotherapy, and chemotherapy alone. Methods: Patients with urothelial cancer with TxN1-3M0 disease treated with chemotherapy in Alberta from 2005 to 2015 were evaluated. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Cox regression analysis was performed to evaluate the impact of age, gender, T stage, and N stage on survival. Results: 184 patients with LN+ disease treated with chemotherapy were evaluable for outcomes; 42 underwent pre-operative chemotherapy (Group A), 92 underwent post-operative chemotherapy (Group B), and 50 received chemotherapy alone (Group C). The median age at diagnosis was 65 years (range 31-89) and most patients (83%) were male. The median follow-up time was 23.2 months. A higher T stage was seen in patients in Group A, while patients in Group C had a higher N stage. The median number of chemotherapy cycles delivered was equal in all arms at 4. Patients in Group A or B had significantly better PFS and OS compared with patients in Group C (Table). When adjusting for age, gender, T stage, and N stage, patients in Group C had significantly lower OS compared with those patients in Group A (HR 1.87, 95% CI 1.09 – 3.18, p=0.02). Conclusions: In this real-world analysis of patients with LN+ urothelial cancer, patient outcomes were improved with surgical resection of disease in combination with pre-operative chemotherapy. After chemotherapy in fit patients with LN+ disease, surgical management is a reasonable consideration. [Table: see text]
Electronic medical record as a research tool: Virtual clinical trial comparing pemetrexed and gemcitabine, both given with cisplatin, in patients with lung adenocarcinomas.
Authors: Alexander Grigorenko, Paul May, Nicholas Kastango, Howard T. Thaler, Isaac Wagner, Aryeh Caroline, Mark G. Kris, Marjorie Glass Zauderer
Journal: Journal of Clinical Oncology (2015)

8024 Background: The electronic medical record (EMR) is a tremendous research resource, but its use for exploring hypotheses has been limited by an inability to reliably and efficiently identify patient cohorts. We have created a system that uses advanced computational techniques and Memorial Sloan Kettering’s (MSK) EMR data to overcome these challenges. To validate our system, we sought to replicate a phase III clinical trial comparing cisplatin/pemetrexed (CP) to cisplatin/gemcitabine (CG) in patients with lung adenocarcinomas (Scagliotti J Clin Oncol 2008). Methods: We created a system that can identify a patient cohort by extracting structured cancer and outcomes data from the EMR, algorithmically identifying chemotherapy regimens, and using natural language processing to extract functional and smoking status from physician notes. Using the earlier clinical trial’s eligibility criteria, we identified a patient cohort and analyzed survival on an intent-to-treat basis. Our analysis relied on the extensive data warehouse of MSK’s EMR information, which contains data on the care of over a million patients since 1989. Results: Our system successfully extracted structured data, and accurately categorized treatment regimens (F-measure = 0.985), functional status (F-measure = 0.998), and smoking status (F-measure = 0.993). 281 patients were automatically identified as eligible. The median overall survival (OS) of patients with lung adenocarcinomas receiving CP and CG was 14.7 and 12.6 months with a hazard ratio (HR) of 0.69 (95% CI: 0.52 - 0.90) favoring CP. These results are similar to those of the prospective trial (Table). Conclusions: Our system replicated the results of a prospective clinical trial. Highly-accurate computational tools to extract structured and textual data from the EMR are feasible and can help address pending clinical research questions. Future steps will focus on expanding data extraction capabilities to support a broader range of hypotheses within the EMR. Metric Virtual Trial Clinical Trial OS (months; CP, CG; % difference) 14.7, 12.6; 15.4% 12.6, 10.9; 14.5% HR (95% CI) 0.69 (0.52 - 0.90) 0.81 (0.70 - 0.94)
Single-agent docetaxel (TXT) as first-line treatment in metastatic breast cancer (MBC)
Authors: D. Guarneri, R. Ratti, A. Venturino, G. Addamo, Z. Coccorullo, G. Colloca, E. Campora
Journal: Journal of Clinical Oncology (2007)

11515 Background: Historically anthracyclines have been considered the most active agents in metastatic breast cancer (MBC). Docetaxel (TXT) has challenged this belief. Aims: Evaluate response rates, toxicity and time to progression in patients with MBC receiving single agent TXT as first line treatment. Methods: MBC patients received first line single agent treatment according to one of the following schedules: TXT 35 mg/m2 iv weekly for 6 wks q 8 wks (Group 1) or TXT 100 mg/m2 iv day 1 q 3 weeks (Group 2). Adjuvant chemotherapy was FAC (600,50,600) day 1 q 21 days for 6 courses in all cases so treated. Results: Conclusions: It appears that results with single agent TXT obtained in clinical practice are comparable to those reported in Phase II-III trials (Group 1 and Group 2, respectively ) using the same regimens. [Table: see text] No significant financial relationships to disclose.
The risks of debilitating falls (DFs) in patients (pts) with cancer: The Manitoba experience.
Authors: Joel Roger Gingerich, Pascal J Lambert, Marshall W. Pitz, Paul Joseph Daeninck, Malcolm Doupe
Journal: Journal of Clinical Oncology (2014)

6588 Background: Falls and fall-related injuries are significant pt safety challenges. We sought to identify if cancer pts were at greater risk of DFs. Methods: Using a retrospective population-based study design, we linked the Manitoba Cancer Registry with health care use records from Manitoba, Canada. Our study cohort consists of all adult community-dwelling pts with a first cancer diagnosis between April 1, 2003 and March 31, 2008, matched by age and gender to three cancer-free controls. DFs were defined as falls requiring hospitalization (ICD billing codes) between the time of cancer diagnosis and Dec 31, 2009. Regression models using death as a competing risk were used to compare DFs separately for those <65, 65-79 and 80+. Each model was adjusted for individual year of age, sex, medication use, neighborhood income, previous falls and co-morbidities. Results were expressed using sub-hazard ratios (SHR). Results: 27,164 cancer pts were matched to 83,928 controls; 50% of the overall cohort was female, with a median age of 68 years. For each group, the median length of follow-up ranged from 1.6 and 3.7 years and decreased with age. DFs occurred in 866 cancer pts (3.2%) vs. 2883 (3.4%) controls. Without adjustment, short-term (<1 year) DF risk was greater in cancer versus control pts (Table 1). For all pts except those 80+ this increased risk was explained by study covariates. Adjusted long-term (>1 year) DF rates were statistically lower in cancer pts 65+ years old vs. controls. The SHRs for death in cancer pts compared to controls during <1 and >1 years were: <65, 104.4 and 20.6 (p<.001); 65-79, 41.2 and 7.7 (p<.001); 80+, 26.6 and 3.7 (p<.001). Conclusions: In this population-based study, cancer pts were at increased risk of DFs compared to matched controls during the 1st year after diagnosis. The risk disappeared after adjusting for confounding factors except in those > 80. After 1 year of follow-up, cancer pts no longer had a higher risk of falls in part due to their higher risk of death. Subhazard ratios for cancer versus cancer-free cohorts. Age < 1 year of follow-up >1 year of follow-up Unadjusted Adjusted Unadjusted Adjusted <65 2.005 t 0.943 1.137 0.892 65–79 1.547 t 0.996 0.869 0.652 t 80+ 1.774 t 1.440 * 0.520 t 0.466 t t < 0.001;* < 0.05.
Positron emission tomography/computed tomography to improve staging and restaging in Merkel cell carcinoma.
Authors: Elena B. Hawryluk, Kevin N. O'Regan, Niall Sheehy, Ye Guo, Andrew Dorosario, Chris Sakellis, Heather A. Jacene, Linda C Wang
Journal: Journal of Clinical Oncology (2012)

8552 Background: Merkel cell carcinoma (MCC) is a rare (~1,500 cases per year) and highly aggressive (33% mortality) cutaneous neuroendocrine carcinoma that occurs in older white patients on the UV-exposed skin of the head, neck, and extremities. As a patient’s stage at presentation is a strong predictor of survival, and there is a high propensity for locoregional recurrence and distant progression, imaging remains crucial for initial and subsequent management. There is, however, no consensus on the timing or method of imaging for MCC. Methods: We retrospectively reviewed 270 2-fluoro-[ 18 F]-deoxy-2-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans performed in 97 patients at the Dana-Farber/Brigham and Women’s Cancer Center from August 2003 to December 2010. Results: The mean SUVmax was 6.5 for primary tumors, 6.4 for regional lymph nodes, 7.2 for distant metastases (all sites), 8.0 for bone/bone marrow metastases, and 9.4 for non-regional metastases in those patients with no identified primary. PET/CT imaging performed for initial management tended to upstage patients with more advanced disease (50% of stage IIIB patients). Metastases to bone/bone marrow (12 patients, 38%) was the 2nd most common site of distant spread after non-regional lymph nodes (19 patients, 59%), followed by skin (8 patients, 25%), liver (6 patients, 19%), lung/pleura (5 patients, 16%), adrenal (3 patients, 9%), muscle (3 patients, 9%), pancreas (2 patients, 6%), and peritoneum (1 patient, 3%). In 10 of 12 patients, PET identified bone/bone marrow metastases that were not seen on CT imaging, which resulted in either upstaging or initiation of more targeted palliative therapy. Conclusions: Added value of PET over CT, such as in the detection of bone/bone marrow metastases, may lead to more accurate staging, and thus prognostication, as well as earlier detection of relapse and initiation of salvage treatment. Its use should be considered in the staging and restaging of MCC.
Prognostic significance of hypervolemic or euvolemic hyponatremia in patients with lymphoma, breast, lung, or colorectal cancer.
Authors: Jorge J. Castillo, Ilya G. Glezerman, Susan H. Boklage, Joseph A. Chiodo, Beni A. Tidwell, Lois E. Lamerato, Kathy L. Schulman
Journal: Journal of Clinical Oncology (2015)

e17554 Background: It has been suggested that hyponatremia (HN) may be a negative prognostic factor in patients with cancer but its impact has been assessed only for select cancers in specific clinical settings, e.g., upon hospitalization. We examined the impact of HN after initial cancer diagnosis on overall survival (OS) in 4 types of cancer. Methods: This retrospective cohort analysis combined electronic medical record information with data from tumor registries and administrative databases from two healthcare systems. Adults diagnosed with incident invasive lymphoma (LYM), breast (BC), lung (LC), or colorectal cancer (CRC) between 2002 and 2010 were selected if they also had ≥ 1 administration of chemo or radiation therapy ≤ 6 months from diagnosis and met continuous enrollment thresholds. Patients were followed from the date of diagnosis until death, clinical trial entry, onset of a new primary cancer, study end, or cessation of enrollment. Patients were excluded if they experienced ≥ 1 postindex episode of hypovolemic HN. Kaplan-Meier curves and two-tailed log-rank test compared OS in patients who never developed HN vs those experiencing ≥ 1 episodes after diagnosis (with HN defined as serum sodium ≤ 135 mEq/L). A Cox proportional hazards model assessed the importance of HN as a time varying covariate on OS. Results: In total, 1758 patients were selected into the study (71% female, mean [SD] age 60 [13] years, 79% White). Mean (SD) follow-up was 3.1 (2.7) years. Of the sample, 48% had BC, 28% LC, 13% CRC, and 11% LYM; 22% of patients had distant metastasis at diagnosis. Five-year OS was 69% (17% in LC, 68% in CRC, 82% in LYM, and 94% in BC). Hazard ratio (HR, 95% CI) for OS in HN group was 2.7 (2.2–3.4; P < 0.0001) after controlling for age, gender, race, income, cancer type, data source, diagnosis year, cancer stage, and performance status at diagnosis. HR in cancer specific models for OS in HN group were 2.4 in CRC (1.3–4.7; P < 0.01), 2.4 in LC (1.8–3.2; P < 0.0001), 3.7 in BC (1.9–7.2; P = 0.0001), and 4.5 in LYM (1.8–11.5; P < 0.01). Conclusions: The occurrence of hypervolemic or euvolemic HN after cancer diagnosis is associated with poorer survival in patients with BC, LC, LYM, and CRC.
Exercise Training in Patients With Chronic Heart Failure and Atrial Fibrillation
Authors: Nancy Luo, Peter Merrill, Kishan S. Parikh, David J. Whellan, Ileana L. Piña, Mona Fiuzat, William E. Kraus, Dalane W. Kitzman, Steven J. Keteyian, Christopher M. O’Connor, Robert J. Mentz
Journal: Journal of the American College of Cardiology (2017)
BH3 profiling as a predictive biomarker for response to cytarabine-based treatment of acute myelogenous leukemia.
Authors: William E. Pierceall, Nicole E. Carlson, David J. Richard, Xuelin Huang, Michael Elaschoff, Marina Konopleva, Steven Mitchell Kornblau, Michael H. Cardone, Michael Andreeff
Journal: Journal of Clinical Oncology (2013)

7022 Background: Acute myelogenous leukemia (AML) is the most frequently diagnosed of the leukemias with approximately 13,000 new cases per year in the U.S. Although intense therapeutic discovery efforts have been directed towards AML, cytarabine-based treatment remains unchanged as the standard-of-care (SOC). As patient response to SOC is variable, segregating patients based on biomarker-driven predicted response may lead to improved clinical outcomes. One personalized diagnostic approach that may provide actionable information in patient management is BH3 profiling, a surrogate functional biomarker assay that assesses cell mitochondrial response to pro-apoptotic signaling. Methods: Blinded to outcomes, we profiled an AML cohort (n=63) treated with cytarabine-based therapy using a panel of BH3 peptides with response as a primary endpoint. Peripheral blood mononuclear cell (PBMC) or bone marrow aspirate (BM) specimens were obtained from newly diagnosed AML patients and viably preserved. Specimens were assayed by flow cytometry following cell permeabilization and incubation with potentiometric JC-1 mitochondrial dye and individual BH3 peptides. Results: Mann-Whitney analysis indicates BH3 profiling biomarkers are correlated with response to induction therapy. Among BH3 peptides, BIM was highly significant (p=2X10 -6 ; CI[0.73,0.94]) with a notable sensitivity/specificity profile (AUC=0.84; p=2X10 -10 ). Multivariate analysis indicates improved profiles for BIM + patient age (AUC=0.89; CI[0.81,0.97])and BIM + patient age +cytogenetic status (AUC=0.91; CI[0.83,0.98]). When patients were stratified by cytogenetic status, BIM was significant for both intermediate (p=0.0017; AUC=0.88; CI[0.71,1.04]) and unfavorable (p=0.016; AUC=0.80; CI[0.60,1.00]), demonstrating that the predictive power of the assay is independent of cytogenetics. Conclusions: Here, BH3 profiling predicts patient response to cytarabine-based treatment regimens with accuracies of 90%. Thus, patients may potentially benefit from being given alternate therapies while at the same time spared the toxicities, cost, and time lost associated with a therapy less likely to exhibit response.