tbuckley/cabot-search huggingface dataset:
North American (NA) subgroup results from VELOUR: Ziv-aflibercept versus placebo plus FOLFIRI in mCRC that is resistant to or has progressed after an oxaliplatin-containing regimen.
Authors: Edith P. Mitchell, Michael J. Guarino, Michael L. Andria, Pankaj Bhargava, Jeffrey J. Kirshner
Journal: Journal of Clinical Oncology (2013)

e14528 Background: Ziv-aflibercept (known outside the US as aflibercept) is a multiple angiogenic factor inhibitor that prevents VEGF-A, VEGF-B, and PlGF from binding their receptors. Ziv-aflibercept in combination with FOLFIRI was FDA approved for metastatic colorectal cancer (mCRC) patients who are resistant to or have progressed following an oxaliplatin-containing regimen. Approval was based on the multinational phase 3 VELOUR trial (N=1226) showing statistically significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) with ziv-aflibercept/FOLFIRI. Detailed analyses of the NA subgroup are presented here. Methods: Patients were randomized 1:1 to ziv-aflibercept 4 mg/kg + FOLFIRI or placebo (pbo) + FOLFIRI q2wks. Patients had ECOG PS ≤2 and 1 prior oxaliplatin-based regimen; prior bevacizumab was allowed. Primary endpoint was OS. NA analysis was prespecified but not powered to compare within or between subgroups. Results: NA patients (n=138) were randomized to ziv-aflibercept/FOLFIRI (n=63) or pbo/FOLFIRI (n=75). Baseline characteristics were similar in both arms (ziv-aflibercept: median age 61 y; 60% male; 96% PS 0-1; 56% &gt;1 metastatic organ; 74% prior bevacizumab) and were similar to the worldwide population. Median OS for ziv-aflibercept vs pbo was 17.94 vs 12.88 mos; median PFS was 6.01 vs 4.17 mos; ORR was 12% vs 9%. On average, patients received more cycles (median 8.5 vs 7.0), had longer duration of exposure (median 20 vs 14 wks), and more treatment modifications with ziv-aflibercept vs pbo. Most severe AEs (grade ≥3) with ziv-aflibercept were grade 3, including hypertension, venous thromboembolic events, proteinuria, diarrhea, fatigue/asthenia, infection, stomatitis/ulceration, and neutropenia; there were few grade 4 AEs. Conclusions: Ziv-aflibercept/FOLFIRI in mCRC patients previously treated with an oxaliplatin-based regimen showed improvements in OS, PFS, and ORR with an acceptable safety profile. NA results are consistent with the VELOUR worldwide population. Clinical trial information: NCT00561470.
The importance of caregivers in improving the care of geriatric oncology patients.
Authors: Vicky Bhagat, Benjamin Isaiah, Maria Soriano-Pisaturo, Ponnandai Somasundar
Journal: Journal of Clinical Oncology (2014)

223 Background: Geriatric patients with cancer have special needs. The diagnosis of cancer is stressful for patients and their caregivers. A new age of medicine has emerged to facilitate caregivers in aiding elderly oncology patients through oncology programs. Many caregivers need support themselves. The purpose of this study is to evaluate our geriatric oncology program’s effectiveness and to demonstrate specific factors that caregivers believe have the greatest positive impact. The aim is to determine different interventions that can be implemented to help caregivers of geriatric oncology patients. Methods: This is a qualitative study that used a questionnaire completed by caregivers of patients enrolled in a geriatric oncology program directed towards easing the stressors encountered when caring for patients. Caregivers rated the effectiveness of the program by responding to 12 statements and 2 open-ended questions via telephone. Results: There were 94 patients in the program from November 2012 to November 2013. After excluding patients that did not meet criteria 71 caregivers were available. Analysis of results from 37 out of 71 caregivers enrolled identified six areas that the program most helped them with: time management of caregivers (82.8%), delivery of decision-making information (97.3%), resources available to caregivers and patients (88.23%), establishing goals of care (94.59%), and pain control for patients (100%). 83.78% of respondents agreed that the well-being and quality of their life improved with the program. Analysis on the patient survey conducted for the same time period also showed significant improvement. Conclusions: Caregivers play a vital role in cancer management of geriatric patients. In order to help both the patients and their caregivers, programs have emerged focusing on the teamwork of social workers, clinicians, and counselors. Caregivers express that this approach helps them effectively provide care to patients, and helps them get through this stressful period. The specific areas found to be most positively impacted by this type of organized program are what oncology departments may focus on in order to improve quality of life for caregivers which may ultimately improve the patient’s care.
<i>MGMT</i> methylation status may predict survival in elderly patients with newly diagnosed glioblastoma (GBM)
Authors: E. R. Gerstner, S. Yip, D. L. Wang, D. N. Louis, A. J. Iafrate, T. T. Batchelor
Journal: Journal of Clinical Oncology (2009)

e13023 Background: Methylation of the MGMT gene promoter is associated with prolonged survival and response to temozolomide in GBM &lt; 70. However, it is unclear if MGMT is a useful prognostic biomarker in the elderly GBM population who traditionally are viewed as less responsive to treatment. Methods: We retrospectively reviewed MGMT promoter methylation status and clinical characteristics in patients 70 years or older with newly diagnosed GBM undergoing resection at our institution from 1998–2008. MGMT analysis was performed by extracting tumor genomic DNA for bisulfite conversion. MGMT methylation specific PCR (MSP) was then performed using PCR primer sets specific for methylated and unmethylated MGMT promoter sequence. The logrank test was used to compare mPFS and mOS in patients who had methylated (ME) MGMT vs. unmethylated (UN) MGMT. Results: Thirty-four patients were included in the analysis. Twenty patients (59%) were ME while 14 (41%) were UN. Patients were treated with multimodality treatment (radiation + chemotherapy), radiation alone, or chemotherapy alone. ME was associated with a significantly prolonged mPFS and mOS as noted in the table below which also summarizes the characteristics of the study population. Conclusions: MGMT methylation status is associated with prolonged PFS and OS in elderly patients with newly diagnosed GBM. Knowledge of MGMT status may help improve prognostication in this patient population. [Table: see text] [Table: see text]
Phase III double-blinded, placebo-controlled study of MABp1 for improving survival in metastatic colorectal cancer.
Authors: Sanjay Goel, Lucjan Wyrwicz, Minsig Choi, Andrew L. Coveler, Antonio Ucar, Alexander Ward Brown, Tomasz Sarosiek, Lucas Wong, Michael Stecher, George A. Fisher, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2016)

TPS784 Background: Interleukin 1 alpha (IL-1a) is a pro-inflammatory cytokine that initiates and propagates sterile inflammatory responses. IL-1a is present on the surface of tumors, and released from necrotic cells within the microenvironment, where it upregulates MMPs, VEGF, chemotactic cytokines, and IL-6 contributing to tumor growth and infiltration of the microenvironment by T-regulatory cells and tumor associated macrophages. IL-1a is also found on the surface of platelets and activates vascular endothelium allowing for circulating tumor cells to establish new areas of metastasis. Specific blockade of IL-1a with the true human IgG1k antibody MABp1, is expected to deprive the tumor of its ability to grow, spread, and evade immune surveillance. A phase I/II study showed radiographic evidence of tumor response in mCRC patients, as well as clinically meaningful improvement in cancer associated symptoms, with no significant toxicity. In the context of this therapy, the improvement in key cancer symptoms, including reversal of lean body mass loss, fatigue, and anorexia, is the direct result of an anti-neoplastic effect and is expected to correlate with an overall survival benefit. Methods: This “Phase III Study of MABp1 in Patients With Advanced Colorectal Cancer (XCITE)” is a global study of 600 patients, ECOG-PS 0-2, metastatic CRC refractory to oxaliplatin, irinotecan, fluoropyrimidine, and EGFR-inhibitors if KRAS wildtype. Patients are randomized 2:1 to receive MABp1 7.5 mg/kg iv every two weeks plus best supportive care (BSC) versus placebo (iv Q2 week) plus BSC. BSC does not include any other therapy with proven anti-cancer activity. The primary endpoint is OS, with secondary endpoints of PFS, ORR, change in lean body mass, and QoL. Patients continue on trial until clinical or radiographic progression as defined by the immune related response criteria (irRC). The study is powered to show a clinically meaningful improvement in OS, evaluated by log-rank test with a one-sided alpha of 0.025. As of September 2015, enrollment is currently underway in the United States and Europe, and results of the first interim analysis are expected in 2016. [NCT01767857]. Clinical trial information: NCT01767857.
Profound T Cell Depletion Does Not Eradicate CMV Specific CD8 T Cells Responsible for Protective Immunity to CMV after T Cell Depleted Allogeneic Stem Cell Transplantation.
Authors: Pim L.J. van der Heiden, Jayant S. Kalpoe, Wilmy M.E. Haarman, Sonja M. Opdam, Roelof Willemze, J.H. Frederik Falkenburg, Erik W.A. Marijt
Journal: Blood (2006)
A Comprehensive Study of Chromosome 13 Abnormalities (Δ 13) in Multiple Myeloma Using High-Throughput, Array-Based Methods.
Authors: Angela S. Baker, Tammy Price-Troska, Michael L. Bittner, Scott A. Van Wier, Rachel Rempel, Gregory J. Ahmann, Tyler S. Pidgeon, Spyro Mousses, Bernie Futscher, Rafael D. Fonseca, John D. Carpten
Journal: Blood (2004)
Erythroid response to lenalidomide (LEN) + recombinant erythropoietin (EPO) and endogenous serum EPO concentration in MDS cytokine-failures
Authors: J. E. Lancet, J. Yu, H. Saba, R. Lush, M. Schmidt, K. Wride, R. Knight, A. F. List
Journal: Journal of Clinical Oncology (2008)

7031 Background: LEN promotes erythropoiesis in a subset of lower risk MDS pts who fail EPO treatment (tx) [N Eng J Med 2005;352:549]. We reported that LEN acts to relieve suppression of the EPO-R signal in non-del(5q) MDS progenitors. We hypothesized that erythroid response (HI-E) to LEN is influenced by endogenous EPO level and can be augmented by combined tx (CT) with EPO in pts with low serum EPO (sEPO) concentration. To evaluate the potential benefit of CT, the effect of sEPO level, and the effects of LEN pharmacokinetics (PK) on cytopenias, we performed a two-stage PK and efficacy study. Methods: Eligible pts had transfusion-dependent (TD), Low/Int-1 IPSS MDS who failed prior treatment with EPO. In the 1st stage pts received LEN monotherapy (MT) at 10mg/d [n=25] or 15mg/d [n=15]. Single dose [n=12] and steady state [n=24] PK were evaluated on days -7 and +14 at the 10mg LEN dose. After 16 wks of MT, erythroid non-responders (NR) and minor (MiE) responders (IWG 2000) were offered CT with epoetin alpha 40,000U/wk for 8 wks. Results: Among 39 pts, median age is 72 years; 7 pts had del(5q). HI-E response to LEN-MT was 36% (n=14) [10mg, 36%; 15mg, 36%] with 13 major (Ma) [del(5q), n=6] and 1 MiE. 18 pts received CT at wk16 with 5(28%) HI-E (3Ma, 2MiE) [10mg, 10%; 15 mg, 50%]. Mean baseline sEPO was higher in HI-E responders vs. NR to LEN-MT [1177 vs.530 mU/ml], whereas in CT responders, mean wk 16 sEPO was lower [339 vs. 1116 mU/ml]. Similarly, HI-E response rate to CT was higher in pts with sEPO <500 mU/ml (4/12, 33% vs. 1/6, 17%). LEN AUC was higher in pts with reduced creatinine clearance (30–49 mL/min, n=2: 955+49; vs. >50 mL/min, n=22: 558±166). There was no difference in AUC or Cmax by magnitude of change in ANC or platelet count in the first month of tx. However, mean AUC inversely correlated with time to >50% reduction in platelet count (ANOVA, P = 0.04). Conclusions: These data suggest that HI-E response to LEN in TD-cytokine failures is sEPO-dependent, yielding a higher response rate to LEN-MT in pts with appropriate sEPO elevation, whereas addition of EPO may improve response in pts with low EPO production. The benefit of CT with LEN+EPO will be investigated in a phase III intergroup study (E2905) in pts who failed primary EPO tx or have a poor cytokine response profile. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Celgene, Pharmion Celgene Pharmion
SWI/SNF Protein SMARCD2 Orchestrates Transcriptional Networks Controlling Hematopoiesis and Neutrophil Granulocytes in Humans, Mice and Zebrafish
Authors: Maximilian Witzel, Daniel Petersheim, Yanxin Fan, Ehsan Bahrami, Tomas Racek, Meino Rohlfs, Jacek Puchalka, Christian Mertes, Julien Gagneur, Christoph Ziegenhain, Wolfgang Enard, Asbjorg Stray-Pedersen, Peter D Arkwright, Miguel R Abboud, Vahid Pazhakh, Graham J Lieschke, Peter K Krawitz, Maik Dahlhoff, Marlon R Schneider, Eckhard Wolf, Hans-Peter Horny, Heinrich Schmidt, Alejandro A Schäffer, Christoph Klein
Journal: Blood (2016)
Prediction of risk for prostate cancer in histopathologically negative biopsies by multigene epigenetic assay.
Authors: Leander Van Neste, Wim Van Criekinge, Olivier Thas, Joseph Bigley, Grant Duncan Stewart, David James Harrison
Journal: Journal of Clinical Oncology (2013)

95 Background: Many men are biopsied for suspicion of prostate cancer (PCa), often based on a serum PSA test, while cancer is missed in up to 30% of the cases due to sampling errors, leading to uncertainty of diagnosis. The diagnostic process is further complicated due to the fear of overtreatment of insignificant PCa. The multi-center MATLOC (Methylation Analysis To Locate Occult Cancer) study confirmed that epigenetic silencing of key genes is a significant predictor of those men with a histologically negative biopsy whose tumor is missed by the biopsy procedure. The epigenetic profile of GSTP1, APC and RASSF1,determined on collected prostatic tissue, resulted in a negative predictive value (NPV) of 90%, identifying a large proportion of men that could forgo repeat biopsy. In current clinical practice, risk factors are intuitively combined to determine the risk that cancer is missed and the need for rebiopsy. Methods: PCa risk factors age, PSA (&gt; 10 ng/mL), DRE (suspicious) and histopathology (HGPIN or atypical cells) were combined with an epigenetic profile to construct a comprehensive metric that improves PCa risk assessment after a negative biopsy. Logistic regression models were fit on a subset of MATLOC with a complete panel of risk factors (n = 391, n cases = 71, prevalence = 18%). These models were subjected to 10-fold cross validation to assess clinical performance. Results: DNA methylation was the strongest predictor (Youden’s J = 0.303) that PCa was missed by biopsy, while PSA was the lowest performing individual marker (J = 0.083). Combinations of risk factors were evaluated, however, only a model including epigenetic profiling and histology of the initial biopsy could improve upon the results of epigenetics alone (J = 0.361). Cross validation resulted in a sensitivity of 74%, a specificity of 63% and a NPV of 91%. Conclusions: Epigenetic profiling is a significant predictor for PCa risk, especially to identify those men who should (not) undergo a repeat biopsy following a negative initial biopsy. An integrated risk management approach that combines epigenetics with other risk factors, most notably histopathology of the cancer-negative initial biopsy, resulted in an improved prediction for the presence of PCa.
Splenectomy as a diagnostic method in lymphoma-associated hemophagocytic lymphohistiocytosis of unknown origin
Authors: J Ma, Z Jiang, T Ding, H Xu, J Song, J Zhang, Y Xie, W Wang
Journal: Blood Cancer Journal (2017)

Splenectomy as a diagnostic method in lymphoma-associated hemophagocytic lymphohistiocytosis of unknown origin
Impact of breast cancer and BRCA mutations on thoughts and feelings of future pregnancies.
Authors: Ashley Henriksen Woodson, Kimberly I. Muse, Michelle Jackson, Banu Arun, Jennifer Keating Litton
Journal: Journal of Clinical Oncology (2012)

38 Background: Many women diagnosed with premenopausal breast cancer are concerned with treatment-related infertility. Identifying a BRCA mutation associated with hereditary breast and ovarian cancer may affect attitudes regarding future childbearing. We evaluated attitudes regarding the impact of cancer or potentially being a BRCA mutation carrier on future childbearing. Methods: Women with childbearing potential were invited to participate in an IRB-approved questionnaire study administered prior to genetic counseling and after results disclosure, if applicable. Women were provided a series of 15 statements and asked to rate how often they thought about the impact of cancer or of having a BRCA mutation on the ability to conceive or carry a pregnancy on a 4-point scale ranging from not at all to often. Descriptive statistics were used. Results: We received 148 pre-questionnaires and 114 post-questionnaires. Thirteen women tested positive for a BRCA 1 mutation and 5 with a BRCA 2 mutation. The mean age was 35 (range 20-45) with 71% having breast cancer. The majority (62%) had at least 1 biological child prior to diagnosis and 45% desired a future child. Across 15 statements, 57% of women did not have any thoughts or feelings about the impact of cancer or a BRCA mutation on a future pregnancy at initial visit. Across the same 15 statements, 52% of women who tested positive for a BRCA mutation changed their answer from the pre-questionnaire to post-questionnaire. Of these women, 70% thought about the impact more often than they reported initially. When compared to women who tested negative for a BRCA mutation (n=78), only 40% of women changed their answer choice, with 54% thinking about the impact less often. Conclusions: Women testing positive for a BRCA mutation were more likely to have an increase in thoughts and feelings regarding the impact of cancer or of being a BRCA mutation carrier on the ability to have a future pregnancy, while women who tested negative showed a decrease. Therefore, women with a BRCA mutation may be influenced in their decisions regarding future childbearing.
Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO)
Authors: Riccardo Soffietti, Ufuk Abacioglu, Brigitta Baumert, Stephanie E. Combs, Sara Kinhult, Johan M. Kros, Christine Marosi, Philippe Metellus, Alexander Radbruch, Salvador S. Villa Freixa, Michael Brada, Carmine M. Carapella, Matthias Preusser, Emilie Le Rhun, Roberta Rudà, Joerg C. Tonn, Damien C. Weber, Michael Weller
Journal: Neuro-Oncology (2016)

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care.
Patient-reported satisfaction with symptom control during lanreotide autogel/depot (LAN) treatment for carcinoid syndrome (CS) in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients: Symnet, a large multinational, cross-sectional, observational study.
Authors: Philippe B. Ruszniewski, Martyn E Caplin, Juan W. Valle, Catherine Lombard Bohas, Pascal Maisonobe, Philippe Atlan
Journal: Journal of Clinical Oncology (2014)

273^ Background: Somatostatin analogs are used to reduce the incidence and severity of symptoms of CS in GEP-NET patients. How this impacts on patients’ satisfaction needs further investigation. Methods: At routine clinic visit, GEP-NET patients with CS-related diarrhea and &gt; 3 months LAN treatment completed questionnaires (including Likert scales) on satisfaction with diarrhea control (primary endpoint) and other symptoms following treatment. Investigators also recorded, based on chart reviews, demographic parameters, disease history, diarrhea characteristics and symptom changes for analysis of predictive factors for satisfaction. NCT01234168. Results: Of the study population (n=273), 56% were male, 57% were aged &gt;60 yrs, mean time since diagnosis was 4.4 yrs, 66% had small bowel primary tumor, and 80% had liver metastases. Within the prior 3 mo, 66% had surgery and 23% other anti-tumor therapy. Mean LAN treatment duration was 21.7 mo and median dose on visit day 120 mg/mo. The study showed most patients (76%) were “completely” or “rather satisfied” with their diarrhea control. Similar satisfaction (73%) with flushing control was also reported. Most patients (79%) reported an overall improvement in their diarrhea with LAN treatment, and more had no or mild impact on daily activities during treatment (75%) than before (33%). Investigators identified a clinically relevant decrease in daily stool frequency from treatment initiation to current visit (median of 4 to 2). Furthermore, statistically significant decreases (McNemar paired tests, p&lt;0.001) were seen in no. of patients with urgency (73-41%), leakage (21-9%), and associated pain (37-14%). Baseline stool leakage and localization of primary outside small bowel were factors associated with satisfaction with diarrhea control. Conclusions: Patient-reported information indicates that LAN-treated GEP-NET patients achieve good and sustained control of CS symptoms. Analyses of predictive factors could help identify patients who may benefit the most of LAN. Clinical trial information: NCT01234168.