tbuckley/cabot-search huggingface dataset:
Epigenetic alterations in inflammatory bowel disease: the complex interplay between genome-wide methylation alterations, germline variation, and gene expression
Authors: Rahul Kalla, Alex Adams, Elaine Nimmo, Nicholas Kennedy, Nicholas Ventham, Morten Vatn, Jorgen Jahnsen, Petr Ricanek, Jonas Halfvarson, Marieke Pierik, Fernando Gomollon, Ivo Gut, Mauro D'Amato, Jack Satsangi
Journal: The Lancet (2017)
Embedding palliative care into bone marrow transplantation clinic.
Authors: Danielle M Noreika, Brian Cassel, Felicia Noland, Egidio Del Fabbro
Journal: Journal of Clinical Oncology (2015)

157 Background: Stem cell/bone marrow transplantation (SC/BMT) is intensive therapy that creates the potential for a number of physical and emotional symptoms. Despite the symptom burden and support needs of these patients there are no publications describing palliative care involvement in the course of treatment. Methods: Retrospective chart review was performed on 37 patients followed over a 6-month period by a palliative care service embedded within the SC/BMT clinic. Results: 37 patients were referred by SC/BMT clinic physicians or nurses to a palliative care team embedded within the clinic (including a physician, physical therapist, and psychologist). Almost all patients were referred for symptom management rather than goals of care; only three (9%) died during the review period and for none of them was the reason for consultation goals of care/hospice referral. Patients were seen between once and eight times during the six month period by various members of the team. Most (77%) were allogenic transplant patients and most were seen within 6 months of their transplantation. The most common reasons for referral were fatigue (57%), anorexia (27%), pain (38%) and depression and/or anxiety (35%). At initial assessment the highest-rated symptoms were lack of appetite (mean 4.78, SD 3.08), fatigue (4.51 [2.59]), and diminished feeling of well-being (4.16, [2.51]). At initial assessment, 73% of patients had 3 or more different symptoms that they rated at 4+; this dropped to 39.1% at follow-up (n = 23). Of the 9 symptoms assessed at both initial and follow-up visits, 7 decreased significantly (all but fatigue and dyspnea) and none increased. For example appetite improved from 5.52 (2.98) to 3.13 (2.96); pain improved from 3.52 (2.92) to 1.78 (1.88) (n = 23, p &lt; .01). SC/BMT providers requested an expansion of the service after three months of experience. Conclusions: Patients who have undergone SC/BMT experience many physical and emotional symptoms. Palliative care embedded within the bone marrow transplant clinic can provide benefit by lessening the symptomatic burden of patients.
Standards for evaluating patient-reported outcome (PRO)-based performance measures.
Authors: Ethan M. Basch, Christine Goertz, Keri Christenson, Amaris Crawford, R. Adams Dudley, John Spertus
Journal: Journal of Clinical Oncology (2012)

45 Background: There is growing interest to use performance measures that integrate patient-reported outcomes (PROs), but there are no existing methodological standards for developing, implementing, or analyzing such measures in this context. Methods: To develop standards for evaluating PRO-based performance measures submitted to or developed by the American Medical Association-convened Physician Consortium for Performance Improvement, a multi-disciplinary expert technical panel was assembled. A systematic literature review and landscape overview were conducted to identify use cases and existing PRO standards in related contexts. Lessons learned from use cases and existing standards guided development of discrete methodological standards. Results: The systematic review identified only one use case, whereas the landscape overview identified eight. Five purposes were identified for which PROs might be measured to assess performance, including one categorized as process and four as outcome. Eight discrete methodological standards were developed which will be detailed at the meeting. Conclusions: The patient perspective is an essential but missing component of performance evaluation. When appropriately elicited, data from patients can be informative. Lack of adherence to good practices and inadequate patient input when developing measurement strategies are potential pitfalls to be avoided.
Clinical and biologic factors for immune response to sipuleucel-T (SipT) for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Mehmet Faith Hepgur, Tanya B. Dorff, Lucy Brining, Jie Cai, Jacek K. Pinski, Mary Reed, Michael Luther, Betty Chan, David I. Quinn
Journal: Journal of Clinical Oncology (2014)

219 Background: SipT prolongs overall survival of men with asymptomatic or minimally symptomatic mCRPC. Recently, it has been demonstrated that SipT immune parameters correlate with survival. We prospectively collected biological and inflammatory markers as part of an audit to identify possible predictors of immune response in patients (pts) receiving SipT. Methods: Circulating tumor cells (CTC), PSA, prostatic acid phosphatase (PAP), albumin (Alb), hemoglobin (Hb), serum alkaline phosphatase (SAP), LDH, C-reactive protein (CRP) and β2-microglobulin (β2m) were evaluated in reference lab before SipT. Product parameters CD54, CD54 upregulation (UPREG) and total nucleated cells (TNC) were measured by Dendreon. These datasets were analyzed using Spearman coefficients for continuous variables and the Kruskal-Wallis test for categorical variables. Results: 92 pts who received SipT were included. Median age was 69 (48-90). 43% had Gleason 8-9. 42% had ECOG Performance Status (PS) 0, 44% PS 1, and 13% PS 2. 26% had received prior chemotherapy and 18% had used opioids. 84% had bone mets, 42% had lymphadenopathy, 12% had visceral mets. Of clinical factors only PS was inversely correlated with UPREG (p=0.014) and TNC (p= 0.023). Biomarkers which significantly correlated with SipT immune parameters are shown in the Table. Age, location of mets, prior chemotherapy or opioid use did not impact the immune response to SipT Conclusions: Better product parameters correlated with good ECOG PS, lower PSA and SAP, and higher Hgb and Alb, suggesting that SipT induces a greater immune response in men with lower disease burden. The correlation of increased CD54 count with lower CRP, a surrogate for IL-6 activity, warrants investigation. [Table: see text]
Fostering patients and families during end-of-life care.
Authors: Michelle Tufaro, Jim Devries
Journal: Journal of Clinical Oncology (2014)

150 Background: Hunterdon Palliative Care Program is a service owned and run by Hunterdon Medical Center, a non-profit, Magnet-recognized, community hospital of 178 beds for the residents of Hunterdon County in New Jersey. The program strives to provide the highest quality patient and family-centered care for seriously ill and terminal patients. Our goals include respect for patient autonomy, values and personal decisions, as well as minimizing of symptom distress, optimizing supportive interventions and services for patients and their families. The individual need of each patient is determined by an interdisciplinary process that includes the ongoing clarification of goals of care. In order to achieve this we have developed several tools to capture the unique needs of each patient and encourage a daily interdisciplinary process. Methods: Three tools were developed to incorporate and utilize the expertise of each individual team member which includes physicians, nurse practitioner, social worker, chaplain and a reiki master. Results: The tools are currently being used by all in-patient palliative care patients. The psych-social-spiritual assessment and care plan sheets are completed within 24 hours of the initial consultation. The documents are placed on the chart next to the written consult. Daily rounding sheets are placed in the progress notes section of the chart. All members of the patient’s treatment team are encouraged to utilize the forms. Both the care plan note and the daily rounding sheet include a section for input from other disciplines. A hot pink strip is located at the bottom of each sheet to make it easy for others to identify forms for integration into additional patient care plans. Conclusions: The Palliative Care Program was awarded Certification by The Joint Commission, with no recommendations for improvement! The interdisciplinary approach to a patient’s end of life needs was sited as "superior" for clinical documentation with special attention to the psycho-social spiritual assessment as a “best practice” standard.
Endometrial cancer screening in patients with Lynch syndrome.
Authors: A. Bats, M. Le Frere-Belda, U. Metzger, P. Laurent-Puig, F. Lecuru
Journal: Journal of Clinical Oncology (2011)

5108 Background: Patients with Lynch syndrome are at high risk for endometrial cancer. Gynecologic screening is recommended although no screening tool has been validated. The objective of this study was to assess the diagnostic value of clinical examination, ultrasound and hysteroscopy to screen for atypical hyperplasia and cancer in women at risk for hereditary nonpolyposis colorectal cancer. Endometrial biopsy was the reference standard. Methods: Of 113 women with mismatch repair gene mutations or Amsterdam II criteria who were prospectively followed at our institution, 111 had 207 paired clinical examination-biopsy evaluations, 161 paired ultrasound-biopsy evaluations and 173 hysteroscopy-biopsy evaluations and were included in the study. Any abnormal bleeding was considered as suspicious. Transvaginal or transabdominal ultrasonographic finding was considered normal if no polyps or intrauterine abnormalities were seen and if the maximum endometrial thickness was less than 4 mm in postmenopausal women not receiving hormonal replacement therapy or less than 6 mm in other women. Hysteroscopy findings were considered as normal or suggesting abnormal or possibly malignant lesions. Endometrial biopsy results were categorized as not interpretable, normal, or showing atypical hyperplasia or cancer. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of clinical examination-ultrasound-hysteroscopy-biopsy were computed. Results: The 111 patients had a mean age of 40.6 years and a median follow-up duration of 11 months (range, 0-140 months). Cancer was diagnosed in 7 patients. There was no atypical hyperplasia. Clinical examination, ultrasonography and hysteroscopy had respectively 86%, 75% and 100% sensitivity and 99%, 55% and 100% negative predictive value, 6.59, 1.67 and 5.63 positive likelihood ratio, and 0.16, 0.45 and 0 negative likelihood ratio. No interval cancers occurred. Conclusions: Hysteroscopy had excellent diagnostic value in this study. Further studies are needed to confirm these results and to determine usefulness of screening.
Evaluation of circulating VEGF based biomarkers in INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG).
Authors: Sonia Yip, Rozelle Harvie, Andrew James Martin, Katrin Marie Sjoquist, Eric Tsobanis, Yoon-Koo Kang, Yung-Jue Bang, Thierry Alcindor, Christopher J. O'Callaghan, Margot J. Burnell, Niall C. Tebbutt, Sun Young Rha, Jeeyun Lee, Jae Yong Cho, Lara Rachel Lipton, Andrew Strickland, John Raymond Zalcberg, John Simes, David Goldstein, Nick Pavlakis
Journal: Journal of Clinical Oncology (2016)

64 Background: The INTEGRATE study evaluated activity of regorafinib (REG) v placebo (PBO) in 147 eligible patients with refractory AOGC. REG was highly effective in prolonging progression free survival (PFS). Differences between regions (i.e. Australia New Zealand/Canada (ANZ/CAN) vs Korea) were found in the magnitude of effect, but REG was effective across all regions and subgroups. We report on an exploratory analysis of VEGF biomarkers to identify predictive/prognostic markers. Methods: Protein biomarkers IL8, VEGF-A,-B,-C-D, soluble(s)VEGFR-1,-2-3 were analysed in plasma at baseline (BL) by multiplex immunoassays (Bio-Plex,BioRad) or ELISA (Abnova). Spearman statistics were used to quantify correlations between markers. Wilcoxon Rank-Sum tests were used to compare markers across regions. The prognostic and predictive value of markers was determined using cox proportional hazards analysis of PFS. Results: There were moderate-to-strong correlations between BL levels of IL8 and VEGF-C (ρ = 0.68), IL8 and VEGF-D (ρ = 0.66), VEGF-A and VEGF-C (ρ = 0.68), VEGF-A and sVEGFR-1 (ρ = 0.54); and a modest negative correlation between VEGF-D and sVEGRF-1 (ρ = -0.33). The regions differed according to BL levels of: VEGF-A (higher in ANZ/CAN; p = 0.0015), VEGF-B (higher in Korea; p = 0.0003), VEGF-D (higher in Korea; p &lt;.0001), and sVEGFR-1 (higher in ANZ/CAN; p &lt;.0001). Adjusting for treatment group, there were statistically significant negative associations between PFS and BL IL8 (p = 0.047), VEGF-A (p = 0.037) and sVEGFR-1 (p = 0.045). There was no convincing statistical evidence that any BL plasma biomarker modified the effect of REG. The effect of region on effectiveness of REG was maintained when evaluated in conjunction with BL biomarkers individually and in combination. Conclusions: Highplasma IL8, VEGF-A and sVEGFR-1 may be adverse prognostic factors. A predictive VEGF blood based biomarker remains elusive. A broader biomarker study including markers beyond the VEGF axis and tissue based markers is ongoing. Clinical trial information: ACTRN12612000239864.
Cord Blood as a Very Valuable Source of Neonatal Cells but Embryonic-Like Nature Reevaluated
Authors: Anja Buchheiser, Stefanie Liedtke, Amelie Pia Houben, Simon Waclawczyk, Milaid Stephan, Teja Falk Radke, Peter Wernet, Gesine Koegler
Journal: Blood (2008)
Comprehensive protein profiling with iTRAQ-based LC-MS/MS to identify proteins associated with doxorubicin and docetaxel resistance in human breast cancers.
Authors: S. Lee, J. R. Lim, T. Guo, A. L. Wong, S. Tan, W. Yeo, H. Yap, S. Sze, B. C. Goh
Journal: Journal of Clinical Oncology (2010)

e13038 Background: Proteins are the actual effectors in cells, and protein profiling of cancers treated with chemotherapy may identify biomarkers that predict drug response. Methods: Breast cancer patients received doxorubicin (n=48) or docetaxel (n=50); serial tumor biopsies were obtained at baseline (T1) and 3 weeks after chemotherapy (T2) for protein expression profiling using the iTRAQ (isobaric tag for relative and absolute quantitation)-based electrospray ionization liquid chromatography tandem mass spectrometry (ESI LC-MS/MS); chemotherapy response was defined as ≥25% tumor reduction after one cycle. Protein expression were compared between responders and non-responders to either drug (n=29 vs. 19 for doxorubicin, n=28 vs. 22 for docetaxel) by analyzing pooled samples. Results: At baseline, levels of desmoyokin and cathepsin D were quantitatively higher in sensitive tumors to doxorubicin (2.4 fold) and docetaxel (2.74 fold) respectively. Using a differential expression threshold of ≤0.67 and ≥1.5 for chemotherapy-induced protein expression changes (T2/T1), changes in the levels of 13 proteins were significantly different between doxorubicin responders and non-responders, and include proteins involved in inflammation, integrin and FAS signaling. Changes in the levels of 20 proteins were different between docetaxel responders and non-responders, including proteins involved in p38 MAP kinase pathway. After treatment, doxorubicin non-responders increased levels of tenascin, thrombospondin-1, collagen α1 and fibronectin-1 by ≥2 fold, while docetaxel non-responders increased levels of apolipoprotein A1, carbonic anhydrase 2, thrombospondin-1, and prolargin by ≥1.5 fold. Interestingly, many of these are extracellular matrix proteins, which have been implicated in cancer proliferation and invasion as well as drug resistance. Conclusions: Comprehensive proteomic profiling using iTRAQ-LC-MS/MS provided insights into proteins and pathways that associate with chemotherapy response. In particular, proteins mediating stromal function appear to be important, and should be studied further for biological significance. No significant financial relationships to disclose.
Patient-reported distress symptoms in patients undergoing palliative radiotherapy.
Authors: Megan Single, Laeticia Hollant, Katherine Gaines, Bridget Smart, Jacob Habboush, Heather Biers, Atiya Day, Robert Clell Miller, Laura Vallow, Katherine S. Tzou
Journal: Journal of Clinical Oncology (2015)

75 Background: The focus of palliative radiotherapy (RT) is on improving quality of life (QOL) for patients with serious illnesses by eliminating or decreasing physical symptoms. The importance of assessing distress levels in palliative care patients is recognized due to the relevance of QOL, as treatment is given to provide symptom-relief rather than curative results. We sought to identify the most common causes of patient reported distress during palliative RT. Methods: Retrospective review was performed for patients who received palliative RT from 11/1/2012 to 6/4/2015 for various types of metastatic cancer at our institution. All patients completed a Patient Reported Distress (PRD) questionnaire with 30 specific questions and an overall distress thermometer prior to beginning treatment. The PRD survey quantified 30 areas of current concern ranging in patient-reported values from 1 to 5 in addition to a linear analog measure from 0 to 10 of overall reported distress in the last month. Results: Completed PRD surveys were available for a total of 297 patients, 149 (50.2%) female and 148 (49.8%) male. All patients were undergoing external beam radiation therapy for treatment of metastatic disease. 49 (16%) received chemotherapy and 46 (9%) underwent surgery. Overall distress ranged from 0 to 10, with a median of 5.0. The mean distress scores for the top five concerns ranged from 1.4 to 2.7. Top distresses were “Fatigue” (2.7), “Pain that affects daily functioning” (2.6), “How will I feel during treatment” (2.5), “Sleep difficulties” (2.4), and “Out of pocket medical costs” (2.3). Least troubling symptoms were “Transportation” (1.4), “A loved one relying on me for their physical care” (1.5), “My job” (1.5), “Housing during treatment” (1.5), “Spirituality” (1.5), and “Anger” (1.5). Conclusions: Patients demonstrated concern for distress related to interruption of activities of normal life, such as tiredness and insomnia, pain, and overall burdens from treatment. Medical costs were also a major concern. Importantly, housing and transportation were not issues in the current study but could be of concern in other regions. Providers should be aware that patients’ primary concerns may not be directly related to the symptom being palliated.
Association of diabetes mellitus with increased mortality in patients receiving curative surgery for colon cancer.
Authors: Kuo-Hsing Chen, Yu Yun Shao, Yi-Chun Yeh, Wen-Yi Shau, Raymond Nienchen Kuo, Zhong-Zhe Lin, Ho-Min Chen, Kun-Huei Yeh, Ann-Lii Cheng, Mei-Shu Lai
Journal: Journal of Clinical Oncology (2013)

399 Background: Diabetes mellitus (DM) is associated with increased risk of colon cancer and has potential impact on its prognosis. This study aimed to investigate the association between DM and the prognosis of patients with early colon cancer who underwent curative surgery. Methods: We established the patient cohort of the study by searching the database of the population-based Taiwan National Cancer Registry. All patients who had newly diagnosed stage I or II colon cancer from 2004 to 2007 and underwent surgical resection with uninvolved surgical margins were enrolled. Information of DM, anti-DM medication, and other comorbidities was retrieved from the database of National Health Insurance, Taiwan. Colon cancer-specific survival (CSS) and overall survival (OS) were compared between patients with and without DM. The Cox proportional hazard model was used to estimate the adjusted hazard ratio (HR) of clinicopathologic variables in multivariate analysis. Results: A total of 5,525 patients were identified; 1,009 of them (18.9%) had DM and 4,325 of them (81.1%) had no DM. Patients with DM had an older median age at diagnosis (69.9 y vs. 66.8 y, p &lt; 0.001), similar initial stage and grade, fewer adjuvant chemotherapy (26.5% vs. 31.2%, p = 0.003). Patients with DM had significantly poorer CSS and OS than patients without DM (Table). In multivariate analysis adjusting for age, gender, stage, adjuvant chemotherapy and comorbidities, DM remained an independent prognostic factor for poorer OS (adjusted HR: 1.45, p &lt; 0.001). Among patients with DM, patients who used insulin had significantly poorer CSS and OS than patients who did not (5-year CSS: 79.5% vs. 85.5%, p = 0.047; 5-year OS: 50.9% vs. 70.4%, p &lt; 0.001). Conclusions: In patients receiving curative surgery for early colon cancer, patients with DM had poorer OS than patients without DM. [Table: see text]
Derivation, Characterization, and In Vitro Differentiation of Canine Embryonic Stem Cells.
Authors: Aravind Ramakrishnan, Brian Hayes, Sara R. Fagerlie, Szczepan Baran, Michael Harkey, Lynn Graf, Merav Bar, Ausra Bendoraite, Muneesh Tewari, Beverly Torok-Storb
Journal: Blood (2007)
Phase II study of monthly pasireotide LAR (SOM230C) for recurrent or progressive meningioma.
Authors: A. D. Norden, S. Hammond, J. Drappatz, S. Phuphanich, D. A. Reardon, E. Wong, S. R. Plotkin, G. J. Lesser, J. J. Raizer, T. Batchelor, E. C. Quant, R. Beroukhim, T. J. Kaley, A. Muzikansky, A. S. Ciampa, L. M. Doherty, K. H. Smith, M. Gerard, C. Sceppa, P. Y. Wen
Journal: Journal of Clinical Oncology (2011)

2040 Background: Patients with recurrent or progressive meningiomas who have exhausted surgical and radiation options have limited remaining treatment choices. Somatostatin receptors are expressed in nearly 90% of meningiomas, and somatostatin inhibits meningioma growth in vitro. The somatostatin analog octreotide had promising results in a pilot clinical study. Pasireotide LAR is a long-acting somatostatin analog that has higher binding affinity for most somatostatin receptor subtypes than octreotide. Methods: This is an open label, single arm phase II trial of monthly pasireotide LAR 60 mg intramuscularly in patients with recurrent or progressive intracranial meningioma. Treatment cycles are 28 days. Treatment continues until progressive disease or unacceptable toxicity. Restaging MRIs are performed every 3 cycles and response is assessed using Macdonald criteria. Octreotide scans are performed in all patients at baseline. Results: Twenty-six participants have been accrued, 17 (65%) of whom have atypical/malignant meningiomas, median age 56 (range 36-74), 11 men (42%), median KPS 85 (range 60-100), and 22 (85%) with previous radiation therapy. Twenty-two tumors (85%) show at least intermediate octreotide uptake. There are no radiographic responses. Of 22 evaluable patients, 16 (73%) achieved stable disease. Median PFS overall is 20 weeks (95% CI: 9-21) and PFS6 29% (benign meningiomas - median PFS 27 weeks [95% CI: 8-not yet reached], PFS6 50%; atypical/malignant meningiomas - median PFS 16 weeks [95% CI: 8-20], PFS6 20%). Toxicity has been mild except for grade 3 hyperglycemia in 5 (19%) patients, grade 4 hyperglycemia in 1 (4%) patient, and grade 3 lipase in 2 (8%) patients. Conclusions: Pasireotide LAR is a well-tolerated somatostatin analog that is under investigation for heavily pre-treated, recurrent meningiomas. Updated results will be presented at the meeting.