tbuckley/cabot-search huggingface dataset:
A phase II prospective study of definitive thoracic concurrent chemoradiation followed by consolidation chemotherapy for oligometastatic non-small cell lung cancer.
Authors: Tao Li, Jiahua Lv, Liu Li, Fang Li, Yanqiong Song, Churong Li, Junchao Wang
Journal: Journal of Clinical Oncology (2015)

e19008 Background: Stage IV non-small cell lung cancer (NSCLC) carries a poor prognosis with a median survivals of 8-10 months. The standard treatment has traditionally been systemic chemotherapy and palliative radiotherapy for symptom relief. Some data has suggested that patients with oligometastatic NSCLC may benefit from aggressive thoracic radiotherapy. The aim of this study was to evaluate the efficacy and toxicity of definitive thoracic concurrent chemoradiation followed by consolidation chemotherapy in oligometastatic NSCLC. Methods: Patients with oligometastatic NSCLC, aged ≤ 75 years, and WHO performance status of 0-1 were enrolled. Oligometastatic NSCLC was defined as 5 or fewer distant metastatic lesions at diagnosis. Patients were treated with definitive thoracic radiotherapy (biological equivalent dose ≥ 60Gy) concurrent with platinum-based, two-drug chemotherapy. After concurrent chemoradiation, patients received 2-4 cycles of consolidation chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary end points were objective remission rate (ORR), overall survival (OS) and toxicity. Results: Between Jane 2008 and Jane 2013, 64 patients were enrolled. Median age was 62 years (range: 41-70 years). Median prescribed radiation dose to primary tumor was 72Gy. The median number of chemotherapy cycles was 4 (range 2-6). The confirmed ORR was 70.3% (10.9% CR and 59.4% PR). At a median follow-up of 28 months, the median PFS and OS were 14 months and 26 months, respectively. The 1-, 2-, and 3-year PFS were 56.3%, 25.6%, 7.4%, respectively. The 1-, 2-, 3-, 4-, and 5-year OS were 71.9%, 52.5%, 31.4%, 25.1% and 14.8%, respectively. Toxicities were generally mild, including grade 2/3 radiation pneumonitis (10.9%), grade 2/3 radiation esophagitis (17.2%), grade 3/4 neutropenia (39.1%), grade 3/4 thrombocytopenia (15.6%), and grade 3/4 anemia (10.9%). Conclusions: Thoracic concurrent chemoradiation followed by consolidation chemotherapy showed a promising efficacy and an acceptable tolerability profile for patients with oligometastatic NSCLC. Further larger and randomized controlled trials are warranted.
Prevalence and predictors of suicidal ideation in long-term prostate cancer survivors.
Authors: Christopher J Recklitis, Eric Zhou, Eric Zwemer, Jim C. Hu, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2013)

9529 Background: Prostate cancer (PC) is associated with an increased risk of suicide, even a decade after diagnosis. Prior research has relied largely on registry data collected at diagnosis, so little is known about the role of post-treatment functioning on the development of suicidal ideation (SI) in long-term prostate cancer survivors (PCS). To address this, our study examined the prevalence of SI, and the association with cancer therapy and post-treatment physical and emotional health in a cohort of long-term PCS. Methods: 695 PCS (5-10 years post-diagnosis) completed a mailed survey on physical and psychological functioning, including the SF-12, EPIC-26, a d epression rating scale and 8 items about SI in the prior year. Results: 12% endorsed having SI and 2% reported serious SI, plans or urges. Serious SI was more common in PCS compared to age and gender-adjusted normative data. SI was not associated with demographic variables (age, ethnicity, marital status, education, income). SI was not associated with prostate cancer stage, treatments or progression. In univariate analyses, SI was significantly associated with prostate-specific symptoms, poor physical and emotional function, a higher frequency of significant pain, and clinically significant depression (p&lt;.01). In an adjusted logistic model, depression and frequent pain remained associated with SI. Of note, 61% of PCS with SI denied a prior depression diagnosis, and 47% denied elevated current depressive symptoms. The majority of PCS with SI (97%) had a recent physician visit, and reported significant interest in receiving mental health information. Conclusions: A significant proportion of PCS report recent SI, which is associated with physical and psychological dysfunction, but not PC treatments. Depression and frequent pain, rather than PC-specific symptoms, are most important in the development of SI. While depression is strongly associated with SI, many PCS with SI have no prior or current depression, underscoring the need to evaluate SI independently. PCS with SI reported receiving regular medical care and interest in information about mental health. This emphasizes the critical role that physicians can play in identifying PCS at high risk for suicide.
Deregulation of TNFRSF18 (GITR) Through Promoter CpG Island Methylation Induces Tumor Proliferation in Multiple Myeloma
Authors: Yang Liu, Yong Zhang, Phong Quang, Hai T Ngo, Feda Azab, Abdel Kareem Azab, Brittany Morgan, Patricia Maiso, Michaela Reagan, Christopher P. Rombaoa, Antonio Sacco, Aldo M Roccaro, Ruben Carrasco, Irene M. Ghobrial
Journal: Blood (2011)
Final results of patients with metastatic renal cell carcinoma treated with MGN1601 in the ASET study.
Authors: Viktor Grünwald, Steffen Weikert, Ingo G. H. Schmidt-Wolf, Stefan Hauser, Ahmed Magheli, Matthias Schroff, Manuel Schmidt, Burghardt Wittig
Journal: Journal of Clinical Oncology (2014)

e15590 Background: MGN1601 is a fixed combination of allogeneic tumor cells modified via MIDGE vectors to express IL-7, GM-CSF, CD80, and CD154 plus the DNA-based immunomodulator dSLIM. In the ASET trial heavily pre-treated patients with metastatic renal cell carcinoma (mRCC) were enrolled to assess safety, immunological effects and clinical efficacy of this cell-based therapeutic cancer vaccine. Methods: The ASET study is a multicenter, single-arm phase I/II study with a treatment phase of 8 intradermal vaccinations over 12 weeks. Following evaluation, patients with at least disease stabilization entered an extension phase (EP, 5 vaccinations over 120 weeks). Overall, 19 patients were included and received at least one MGN1601 injection (ITT); the majority (N=17) had ≥3 lines of previous therapy. Results: Ten patients of 19 completed the treatment phase per-protocol (PP); 9 discontinued the study due to early progression of disease (PD) or rapid deterioration. Overall, 109 adverse events were documented (grade 1-2: 81.6%) of which only 10 (9.2%) were related to MGN1601. No MGN1601-related serious adverse event was reported. Immunological analyses of patients' PBMCs via LTT and ELISpot assay confirmed an improved cellular immune function during MGN1601 treatment. Two patients achieved disease control (PR, SD) after 12 treatment weeks and continued in the extension phase: One patient had PD after 60 weeks, the other remains in sustained PR after completion of the EP. Median OS was 24.8 weeks in the ITT population and 115.3 weeks in the PP population with 2 patients still alive at week 120. Univariate analysis of pre-treatment characteristics revealed absolute lymphocyte counts, neutrophil to lymphocyte ratios, platelets, MSKCC score, and liver metastasis as putative predictive factors of longer overall survival. Conclusions: MGN1601 administration was safe and feasible. MGN1601 improved cellular immune function and showed clinical activity in a heavily pretreated RCC population. These results warrant further study in a larger, controlled clinical trial. Baseline biomarkers and factors may allow identifying patients more likely to benefit from this innovative vaccination approach. Clinical trial information: NCT01265368.
Multiparametric quantitative functional MRI for assessing early changes in volumetric functional tumor burden in hepatocellular carcinoma treated by intra-arterial therapies.
Authors: Vivek Gowdra Halappa, Susanne Bonekamp, Celia Pamela Corona Villalobos, David Cosgrove, Luis A. Diaz, Timothy M Pawlik, Jean-Francois Geschwind, Ihab R. Kamel
Journal: Journal of Clinical Oncology (2012)

4114 Background: Hepatocellular carcinoma (HCC) is the most common primary malignant disease of the liver. Intra-arterial therapy (IAT) has been shown to improve survival and is commonly used in unresectable HCC. Assessing response to IAT as early as possible using objective criteria is paramount for clinical care. The purpose of this study was to evaluate volumetric diffusion weighted (DWI) and contrast Enhanced MR imaging (CE-MRI) changes for assessing early treatment response to IAT in hepatocellular carcinoma. Methods: This study included 177 lesions of HCC in 107 patients (85 Male, mean age 64 years) with BCLC A (19) B (44) C (36) D (8) treated by IAT. All patients had pre-IAT and 3-4 weeks follow up MRI with DWI and CE-MR. Tumors were segmented using semi automated software to provide volumetric functional analysis of DWI and CE- MRI as well as percent tumor burden. Statistical analyses include paired t-test, Kaplan-Meier curves, log rank test and multivariate analysis with cox model. Results: There was significant increase in volumetric ADC and significant decrease in volumetric arterial (AE) and venous (VE) enhancement after IAT. Patients with tumor burden of &lt; 10% had improved survival compared to patients with high tumor burden of &gt;10% (log rank p &lt;.008 ) This survival benefit was larger among patients with tumor burden of &lt; 10% who demonstrated an increase in volumetric ADC (&gt;20%. Overall survival (OS) 33.5 mo) and decrease in volumetric VE (&gt;50% OS 35.2 mo) compared to patients with high tumor burden &gt;10% who no favorable response in ADC ( OS 14.1 mo) or VE (OS 16.5 mo) (Log rank p &lt; .001) . In multivariate analysis factors associated with favorable prognosis were: increased ADC, (Hazard Ratio (HR) = 0.44, 95% CI =0.24 - 0.80) decreased VE, (HR = 0.43, 95% CI = 0.22 - 0.84) and BCLC A and B (HR = 0.31, 95% CI =0.18 - 0.54). Conclusions: Volumetric functional analysis of DWI and CE-MR are reliable imaging biomarkers of treatment response and tumor necrosis were able to differentiate responders and non responders. Early assessment of treatment response by volumetric functional MRI predicts prognosis in patients undergoing IAT in HCC.
Protein activation mapping and exploratory predictive markers for pCR in triple-negative breast cancer patients treated with neratinib in the I-SPY 2 TRIAL.
Authors: Julia Dianne Wulfkuhle, Christina Yau, Denise M Wolf, Rosa Isela Gallagher, Jianghong Deng, Lamorna Brown Swigart, Gillian Hirst, Minetta C. Liu, John W. Park, Laura Esserman, Donald A. Berry, Laura van't Veer, Emanuel Petricoin
Journal: Journal of Clinical Oncology (2015)

1085 Background: In the I-SPY 2 trial, the pan-ERBB inhibitor, neratinib (N) arm was open to all HR/HER2 subtypes but graduated in the HR-/HER2+ signature. Exploratory analysis of protein signaling was performed to identify biomarker candidates correlated with pCR in the TN population. We evaluated 110 key signaling proteins using reverse phase protein microarray (RPPA) data from pre-treatment LCM purified tumor epithelium. Methods: Of 59 TN patients, 49 (N: 30, concurrent controls: 19) had RPPA and pCR data. RPPA data was correlated to pCR in both the treated and untreated patients using parametric (t-test) or non-parametric (Wilcoxon) statistical analysis, depending on data distribution. Only analytes whose levels were associated with response in the N but not the control arm were selected for further analysis. Markers are analyzed individually; p-values are descriptive and were not corrected for multiple comparisons. ROC analysis identified an optimal cut point and pCR rates of biomarker positive patients were assessed using that cut point. Results: Out of 110 analytes analyzed, only activation of HER2 Y1248, p = 0.03; EGFR Y1173, p = 0.009; were found to be positive predictors of pCR, and 3 proteins, TIE2 Y992, p = 0.02; LC3B, p = 0.02, and A-RAF S299, p = 0.0008, were found to be negative predictors of pCR. pCR rates in the biomarker positive group of 62.5% (10/16), 66% (11/16), 55%(10,/18), 67% (12/17). 61% (11/18) were determined for phospho- HER2, EGFR, TIE2, A-RAF and total LC3B, respectively, compared to a pCR rate of 40% ffor the IHC/FISH-based TN subgroup where RPPA data were available. Conclusions: Our sample size is too small to draw definitive conclusions. However, activation of HER2-EGFR in HER2- tumors may identify patients who respond to N. Low levels of activated A-RAF and LC3B also correlated with response. The results imply that there is a subset TN patients that paradoxically exhibit HER family signaling activation and may achieve clinical benefit with N. These findings merit future consideration as we develop trials for patients with suboptimal response to neoadjuvant therapy where biomarkers could be used as the basis for treatment reassignment. Clinical trial information: NCT01042379.
Anticoagulation Clinic Protocol and Electronic Medical Records in Patients Treated with Warfarin: Do They Increase the Likelihood of Achieving Therapeutic INR?
Authors: Urmeel H Patel, Liya Galooshian, Franklin Fontem, Nadine Kalavazoff, Jordan Klein, Patience Agbonavbare, Yijin Wert, Pramil Cheriyath
Journal: Blood (2014)
Hospital treatment patterns and survival for metastatic colorectal cancer.
Authors: Robert Wallace Krell, Scott E. Regenbogen, Mousumi Banerjee, Sandra L. Wong
Journal: Journal of Clinical Oncology (2015)

6581 Background: Despite evidence that multimodality therapy (surgery and multi-agent chemotherapy) improves survival for patients with metastatic colorectal cancer (CRC), there is broad variation in its use across hospitals. It is unclear whether survival differences across hospitals reflect differences in hospital quality or their treatment choices. We assessed survival for patients with metastatic CRC based upon their treatment and the hospitals treating them. Methods: We assessed patients with metastatic CRC in the 2003-06 National Cancer Data Base (N = 53,884 patients in 1019 hospitals). We compared survival across hospitals based on their adjusted relative utilization of cancer treatments (primary and distant site surgery, chemotherapy, or palliative care). Then, to assess the influence of different treatment patterns on survival, we compared outcomes for patients who received similar treatments across hospitals. Results: Compared to hospitals with low multimodality treatment utilization, patients in hospitals with high utilization were more likely to receive multi-agent chemotherapy (51.0% vs 32.1%, p < 0.001), primary site resection (66.3% vs 62.3%, p < 0.001), metastatic site resection (32.0% vs 10.0%, p < 0.001), or palliative care (9.1% vs 6.9%, p = 0.014), and had longer median survival (15.2 vs 12.4 months, p < 0.001). The observed survival differences across hospitals were eliminated once patients were stratified by treatment modality (adjusted HR for treatment in a high-utilization hospital 1.02 [0.98-1.07]). For example, there were minimal differences in median survival between high and low utilization hospitals for patients treated with multimodality therapy (30.7 vs 29.1 months, p = 0.31), chemotherapy only (12.1 vs 12.6 months, p = 0.04) or palliative care (7.8 vs 7.8 months p = 0.24). Conclusions: There is broad variation in hospital treatment utilization for patients with metastatic CRC. Survival differences across hospitals are minimal, however, when patients receive similar treatments. Higher survival in hospitals with high treatment utilization likely reflects their willingness to utilize cancer treatments, include palliative care, rather than other features of their overall quality of care.
ICORG 10-14: Neo-AEGIS: A randomized clinical trial of neoadjuvant and adjuvant chemotherapy (modified MAGIC regimen) versus neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the esophagus and esophagogastric junction.
Authors: Niamh Keegan, Fionnuala Keane, Sinead Cuffe, Moya Cunningham, Narayanasamy Ravi, Geraldine Lee, M. John Kennedy, William Grogan, Brian O'Neill, Derek G. Power, Gregory Leonard, Maccon M. Keane, Cormac Small, Imelda Parker, Brian Moulton, Seamus O'Reilly, John Vincent Reynolds
Journal: Journal of Clinical Oncology (2014)

TPS4145 Background: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the esophagus and junction (AEG). The MAGIC and CROSS regimens were superior to surgery only in randomized controlled trials (RCTs) that included AEG but were not powered on this cohort, and no completed RCT has directly compared neoadjuvant chemotherapy and chemoradiation. This trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these Level I regimens. Methods: This open label, phase III RCT randomizes patients in a 1:1 fashion to receive either pre and postoperative chemotherapy as per the MAGIC regimen [Etoposide, Cisplatin, Fluorouracil (Capecitabine)] or neoadjuvant chemoradiation as per the CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 15% difference in 3 year overall survival, power at 80%, two-sided alpha level of 0.05, requiring 366 subjects over a five year period, with analysis performed one year after last subject recruited. Eligibility includes: AEG, types I, II, and III, staged (CT-PET and EUS) as cT2-3, N0-3, M0 and surgically resectable, with good performance status and no major co-morbidities. The primary endpoint is overall survival, with a minimum 3 year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumor regression grade, operative in-hospital complications, and health-related quality of life. Pre-treatment bio-resourcing of tumor and blood will enable correlative translational studies. Conduct to Date: The trial activated in February 2013 at the national center in Ireland, 35 patients are randomized to date. Other centers in Ireland and Europe will commence in 2014. Clinical trial information: NCT01726452.
Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits
Authors: Felix Grassmann, Christina Kiel, Martina E. Zimmermann, Mathias Gorski, Veronika Grassmann, Klaus Stark, Iris M. Heid, Bernhard H. F. Weber
Journal: Genome Medicine (2017)

Age-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits. For each of 60 complex diseases/traits with publicly available genome-wide significant association data, the lead genetic variant per independent locus was extracted and a genetic score was calculated for each disease/trait as the weighted sum of risk alleles. The association with AMD was estimated based on 16,144 AMD cases and 17,832 controls using logistic regression. Of the respective disease/trait variance, the 60 genetic scores explained on average 4.8% (0.27–20.69%) and 16 of them were found to be significantly associated with AMD (Q-values < 0.01, p values from < 1.0 × 10–16 to 1.9 × 10–3). Notably, an increased risk for AMD was associated with reduced risk for cardiovascular diseases, increased risk for autoimmune diseases, higher HDL and lower LDL levels in serum, lower bone-mineral density as well as an increased risk for skin cancer. By restricting the analysis to 1824 variants initially used to compute the 60 genetic scores, we identified 28 novel AMD risk variants (Q-values < 0.01, p values from 1.1 × 10–7 to 3.0 × 10–4), known to be involved in cardiovascular disorders, lipid metabolism, autoimmune diseases, anthropomorphic traits, ocular disorders, and neurological diseases. The latter variants represent 20 novel AMD-associated, pleiotropic loci. Genes in the novel loci reinforce previous findings strongly implicating the complement system in AMD pathogenesis. We demonstrate a substantial overlap of the genetics of several complex diseases/traits with AMD and provide statistically significant evidence for an additional 20 loci associated with AMD. This highlights the possibility that so far unrelated pathologies may have disease pathways in common.
A phase II study of pazopanib in children, adolescents, and young adults with refractory solid tumors.
Authors: Alice Lee, Julia Glade Bender, Brenda Weigel, Elizabeth Fox, Anne C. Huff, Hiroomi Tada, Susan M. Blaney, Peter Langmuir
Journal: Journal of Clinical Oncology (2015)

TPS10081 Background: Pazopanib (VOTRIENT; GlaxoSmithKline) is an angiogenesis inhibitor targeting VEGFR-1, -2, and -3; PDGFR-α and -β; and c-Kit, and is indicated for the treatment of adults with advanced RCC and advanced soft tissue sarcoma. Data from adults with sarcoma support the study of soft tissue and bone sarcomas, as well as embryonal tumors, in pediatric subjects. The current Phase II study undertaken by the Children’s Oncology Group (COG-ADVL1322/ VEG116731) was preceded by a Phase I trial of pazopanib tablets and powder for oral suspension (PfOS) in children (N = 51). The maximum tolerated dose (MTD) for tablets was 450 mg/m2/dose and 160 mg/m2/dose for the PfOS, with two dose-limiting toxicities (DLTs) seen at 225 mg/m2 of the PfOS. Hematologic and non-hematologic toxicities were generally mild. One subject each with hepatoblastoma or desmoplastic small round cell tumor had a partial response; 8 had stable disease ( ≥ 6 cycles); 7 of these had sarcoma (Glade Bender; J. Clin. Oncol. 2013; 31:3034). Given these findings, this Phase II trial will further evaluate efficacy, safety, pharmacokinetics, and pharmacodynamics in children. Methods: This is a multi-center study of pazopanib in US and Canadian subjects age 1 to 18 years with solid tumors relapsed or refractory to prior therapy. Tumor types include rhabdomyosarcoma, non-rhabdomyosarcomatous soft tissue sarcoma, Ewing sarcoma, osteosarcoma, neuroblastoma, and hepatoblastoma. Subjects will be stratified by tumor type, and the response rate to pazopanib will be assessed for each of the six disease strata using a two-stage design. Pazopanib will be administered orally once daily as a tablet at 450 mg/m2 or as PfOS at 225 mg/m2. The phase I PfOS MTD of 160 mg/m2 may result in suboptimal exposure. Given that the toxicity at 225mg/m2 was isolated and reversible, the first 6 patients receiving PfOS will be dosed at 225 mg/m2 and assessed for first-cycle DLTs and PK. The study will also evaluate pazopanib pharmacokinetics and toxicity in this pediatric population and will assess the relationship between efficacy and levels of cytokines and angiogenic factors, and VEGF and KDR polymorphisms. Four of 77 subjects have been enrolled. (NCT01956669) Study funded by GSK. Clinical trial information: NCT01956669.