tbuckley/cabot-search huggingface dataset:
Correlation of circulating miRNA levels with progression-free survival (PFS) and overall survival (OS) in early-stage lung adenocarcinoma.
Authors: Francesco Grignani, Riccardo Trombi, Sara Baglivo, Marco Gunnellini, Marinella Di Carlo, Francesca Romana Tofanetti, Annamaria Siggillino, Giulio Metro, Chiara Bennati, Lucio Cagini, Francesco Puma, Lorenza Pistola, Rita Chiari, Vienna Ludovini, Lucio Crino
Journal: Journal of Clinical Oncology (2014)

11099 Background: Surgically resected early-stage non-small lung cancer (NSCLC) display a highly variable outcome in terms of PFS and OS. Currently used clinico-pathological parameters may not precisely predict individual risk of relapse. Here, we correlated the levels of circulating miRNAs levels with PFS and OS in early stage fully resected NSCLCs. Methods: We analyzed the levels of the 84 most abundant circulating miRNAs (Qiagen PCR array) in sera from patients with stage IàIIIA resected NSCLC. All the sera were collected at the time of diagnosis. Total serum RNA was purified and miRNA levels were measured by real time PCR. Normalization was obtained by using a spike-in control miRNA and multiple endogenous unvariable control miRNAs. Results: We analyzed 94 sera, of which 44 were derived from patients who remained free of relapse for at least 2 years, while 50 sera from patients who relapsed within 2 years from the diagnosis. No significant correlation was found between miRNA levels and age, sex and smoking habits. In squamous cell lung cancer no significant correlation was found between miRNA levels and clinical outcome. Conversely, we were able to identify significant associations between the levels of a number of miRNA and PFS in samples from adenocarcinoma patients. The most significant ones were found in stage I and II patients where miR-15b levels were significantly higher in relapsed patients (p= 0.01). Also, high levels of serum miR-223 had a strong negative correlation with OS (p= 0.001). A miRNA signature could be derived which correlated with PFS with a specificity of 75% and a sensitivity of 84% (p<0.01) . The signature includes miR-15b, miR-27a, miR-106b, miR-191 and miR-223. The same miRNA signature gave similar data when OS was considered. Normalization with multiple endogenous miRNA levels was mandatory to obtain reliable statistics. Conclusions: The analysis of serum miRNA levels in resected early stage NSCLC seems to have limited usefulness as prognostic tool for early squamous cell carcinoma, whereas it may reliably predict clinical outcome in adenocarcinoma, with both high sensitivity and specificity. Prospective studies are warranted.
Parenteral hydration (PH) in advanced cancer patients: A multi-center, double-blind, placebo-controlled randomized trial.
Authors: Shalini Dalal, David Hui, Isabel Torres-Vigil, J. Lynn Palmer, Julio Allo, Susan Frisbee-Hume, Kenneth Tarleton, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

9025 Background: The vast majority of cancer patients at the end of life receive PH in hospitals and no PH in hospice. There is limited evidence supporting either practice. Our preliminary study suggested that PH (1L/day) improved dehydration symptoms (Bruera et al. JCO 2005). In this randomized controlled trial, we determined the effect of PH on symptoms associated with dehydration, quality of life and survival for patients with advanced cancer. Methods: We randomly assigned 129 cancer patients from 6 hospices to receive subcutaneous PH (normal saline 1 L/day) or placebo (normal saline 100 mL/day) daily over 4 hours. The primary outcome was change in the sum of 4 dehydration symptoms (fatigue, myoclonus, sedation and hallucinations, 0=best and 40=worst possible) between day 4 and baseline. Secondary outcomes included Edmonton Symptom Assessment Scale (ESAS), Memorial delirium assessment scale [MDAS], Nursing delirium screening scale [NuDESC], unified myoclonus rating scale [UMRS], FACIT-F, creatinine, urea, and overall survival. Intention-to-treat analysis was conducted to examine the change in each variable between baseline and day 4 or day 7. Log rank test was used for survival analysis. Results: Mean age was 67 (range 43-92), female 61%, Caucasians 60%, gastrointestinal, genitourinary and lung cancers 70%, performance status 3-4 113 (88%), with no baseline differences between the hydration (N=63) and placebo (N=66) groups. No significant differences were found between the hydration and placebo groups for the sum of 4 dehydration symptoms (-3.3 v. -2.8, p=0.77), ESAS (all non-significant), MDAS (1 vs. 3.5, p=0.084), NuDESC (0 v. 0, p=0.13) and UMRS (0 vs. 0, p=0.54). We also did not identify any group differences for day 7, except for a decrease in urea level in the hydration group (-2 vs. 2, P=0.02). Median overall survival was 21 days for PH and 15 days for placebo (p=0.83). Conclusions: PH at 1 L/day did not improve symptoms, quality of life or survival compared to placebo. Further studies are required to determine if any subgroups would benefit from PH.
Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease
Authors: Niklas Mattsson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Journal: JAMA Neurology (2017)

Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias.To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration.In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016.Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism.Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally).Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD.
Phase II randomized trial of autologous tumor lysate dendritic cell vaccine (ADC) plus best supportive care (BSC) compared with BSC, in pre-treated advanced colorectal cancer patients.
Authors: Joan Maurel, Miguel Caballero-Baños, Jordi Mila, Jaime Tabera, Sara Varea, Ramon Vilana, Luis Bianchi, Pedro Arguis, Estela Pineda, Gemma Carrera, Miriam Cuatrecasas, David Páez, Marta Martin-Richard, Mario Pagés, Juan Ramón Ayuso, Joan Cid, Miguel Lozano, Xabier Garcia-Albeniz, Antoni Castells, Ramon Vilella
Journal: Journal of Clinical Oncology (2015)

3048 Background: No treatments are available for patients (pts) with metastatic colorectal cancer (mCRC) that progresses after all approved therapies. Autologous tumor lysate dendritic cell vaccine (ADC) has T-cell stimulatory capacity and therefore potential antitumor activity. We designed a phase II randomized trial of ADC plus BSC (arm A) compared with BSC (arm B), in pre-treated mCRC patients. Methods: Pts with documented mCRC and progressive disease at least to two chemotherapy regimens and ECOG performance status (PS) of 0-2, were randomized (1:1 ratio) to arm A vs B. Stratification was done by ECOG PS (0,1 vs 2) and LDH ( < ULN vs > ULN). Arm A was administered subcutaneously days 0,10,20,40,120 and thereafter every 6 months (m) till progressive disease (PD). Radiological evaluation was planned with multidetector computed tomography (MDCT) every 2 m the first 6 m and then every 3 m till PD in both arms. Primary endpoint was progression free rate (PFR) at 4 m. Accordingly, sample size was established in 76 pts to detect differences at month 4 in the PFR of > 30% (40% in the ADC arm and 10% in BSC arm) with an a error = 0.05 and a power = 0.8. Results: From 08/2011 to 10/2013, 61 pts were screened and 52 pts were included (28 arm A and 24 arm B). An interim analysis recommended early termination for futility. Pts characteristics were well balanced between arms. No ADC-related adverse events were reported. Immunization induces an autologous tumor-specific T-cell response in 21 of 25 (84%) treated pts. Pts with evidence of a vaccine-induced, tumor-specific immune response has a markedly higher overall survival than non-responders (220 days (d) versus 113d); p = 0.026). No objective radiological response was observed in ADC arm. Median PFS and 4 m PFR in arm A was 2.7 m (95%CI 2.3-3.2m) and 15% vs 2.3 m (95%CI 2.1-2.5m) and 21% in arm B (p = 0.628). Median overall survival was 6.2m (95%CI 4.4-7.9m) in arm A vs 4.7m (95%CI 2.3-7m) in arm B (p = 0.41). Conclusions: Our trial, the first randomized clinical trial comparing ADC plus BSC vs BSC in mCRC, demonstrates that ADC generates a tumor-specific immune response, but not benefit on PFR, PFS and OS compared with BSC. Clinical trial information: NCT01413295.
Ziv-aflibercept (A) combined to FOLFIRI as first line treatment for metastatic colorectal cancer (mCRC): Interim safety and efficacy results of the phase II PULSAR trial.
Authors: Antoine Adenis, Francois Ghiringhelli, Jean Luc Raoul, Emmanuelle Tresch, Anne Thirot-Bidault, Julie Vincent, Farid El Hajbi, Mohamed Hebbar, Mohamed Bouchahda, Hajer Jarraya, Sylvaine Feutray, Eric Amela, Fredrik Laestadius, Marie-Cécile Le Deley, Sophie Taieb, Fabrice Soncin, Emmanuelle Dochy, Stephanie Clisant Delaine, Nicolas Penel, Nathalie Lassau
Journal: Journal of Clinical Oncology (2017)

737 Background: A is approved in combination with FOLFIRI (A-FOLFIRI) for the treatment of mCRC patients (pts) previously treated with oxaliplatin. PULSAR trial (NCT02173990) aims to measure the activity A-FOLFIRI as 1 st -line mCRC treatment. Key secondary objectives are safety, as well as circulating biomarkers and dynamic contrast-enhanced ultrasound measurements as PFS prognosticators. We present here interim analysis of safety and activity. Methods: Pts received A (4 mg/kg I.V.) every 2 weeks in combination with FOLFIRI (Irinotecan: 180 mg/m 2 , leucovorin: 200 mg/m 2 , Bolus FU: 400 mg/m 2 , infusional FU: 2400 mg/m 2 over 46hrs). The primary endpoint is 10-month [m] PFS (RECIST 1.1). The target sample size is 72 pts for the following assumptions: P0 = 0.40, P1 = 0.55, α = β = 0.1. Results: Among the first 30 recruited mCRC pts with unresectable metastases (mets), 29 received at least 1 cycle of A-FOLFIRI. 30, 23, and 28 pts were evaluable for survival (intent-to-treat), tumor response, and safety, respectively. Median age was 61.5 (45-82), 70% pts were men. ECOG PS was 0, 1, and 2, in 47%, 43%, and 10% of the pts. 6/30 pts received previous adjuvant chemotherapy. 22/30 pts presented with synchronous mets. 26/30 pts presented with liver mets. Median treatment duration was 6.3m (0.5-24.3) and pts (n = 29) received a median number of 10 cycles (1-37) of A and of 11 cycles (1-43) of FOLFIRI. Median follow-up was 7.2m (1.6-23.9). The 10-m PFS was 59.9% [95%-CI: 37.5-76.5]. Median PFS was 12.9m (95% CI: 6.1-…). 12-m OS rate was 73.7% (95% CI: 48.3-87.9). 5 pts died from PD, and 1 from treatment-related toxicity (colon perforation). 27/28 pts presented at least one severe Adverse Event (AE). Most frequent severe AE (related or not) were hypertension (43%), neutropenia (29%), diarrhea (18%), alkaline phosphatase increase (18%), fatigue (18%), GGT increase (14%), and weight loss (14%). Conclusions: A-FOLFIRI seems promising in 1 st line setting mCRC, with respect to PFS. Due to high rates of severe AEs, dose modifications have to be proceeded in a coming protocol amendment. Funded by Sanofi. Clinical trial information: NCT02173990.
Risk factors and prevalence of cognitive deficits in women with gynecologic malignancies.
Authors: Anne Van Arsdale, Gurpreet Kaur, June YiJuan Hou, Merieme Klobocista, Mendel Goldfinger, Gary L. Goldberg, Mark H. Einstein, Nicole Nevadunsky
Journal: Journal of Clinical Oncology (2014)

9601 Background: Cognitive impairment has implications in counseling, treatment, and survivorship for women with gynecologic malignancies. The purpose of our study was to evaluate prevalence and risk factors associated with cognitive impairment. Methods: After IRB approval, 165 women at an urban ambulatory facility were queried using a Montreal Cognitive Assessment (MOCA), Depression Scale, Wong-Baker pain scale, and neuropathy scale. The association of cognitive deficit with age, education, race/ethnicity, disease site, stage, treatment, pain, neuropathy, anxiety and depression was evaluated. Results: Mean MOCA score was 24.1 (range 13-30.) 24% of patients had MOCA scores less than 22. Low scores (<22) were associated with older age, non-white race/ethnicity, lower education level, uterine cancer, and pain > 5 (p<0.05). There was a trend toward lower scores for with chemotherapy and radiation treatment (p=0.10). Low cognition scores were not associated with pain medication use. Conclusions: There was a high prevalence of cognitive deficits in women with gynecologic malignancies. Further research is needed to evaluate the impact of deficits on treatment adherence and outcomes. Variable Normal cognition (≥22) Low cognition (<22) p-value Age at diagnosis (years -mean) 56.7 (12.6) 63.2 (11.6) 0.005 Time since diagnosis (weeks - median) 129 108 0.36 (Wilcoxon – skewed distribution) Ethnic background African American 26 (63.4) 15 (36.6) 0.02 Hispanic 28 (68.3) 13 (31.7) White 67 (87.0) 10 (13.0) Other 4 (80.0) 1 (20.0) Education Middle school or less 4 (40.0) 6 (60.0) 0.004 Any HS 38 (69.1) 17 (30.9) College and higher 82 (83.7) 16 (16.3) Disease site Uterus 67 (70.5) 28 (29.5) 0.012 (Fisher Exact) Ovary/fallopian tube/PP 44 (89.8) 5 (10.2) Cervix 10 (83.3) 2 (16.7) Vulva 4 (50.0) 4 (50.0) Stage I/II 82 (78.1) 23 (21.9) 0.53 III/IV 33 (73.3) 12 (26.7) Treatment variables No further treatment (surgery only) 60 (79.0) 16 (21.0) 0.10 RT only 3 (50.0) 3 (50.0) Chemo only 38 (82.6) 8 (17.4) Both chemo/RT 22 (64.7) 12 (35.3) Pain <5 106 (79.7) 27 (20.3) 0.03 ≥5 19 (61.3) 12 (38.7) Taking pain medications No 92 (78.6) 25 (21.4) 0.22 Yes 32 (69.6) 14 (30.4)
Ofatumumab Plus Ifosfamide/Etoposide (OIE) Followed By Autologous Stem Cell Transplantation (ASCT) in Patients with b-Cell Non-Hodgkin's Lymphomas (NHL)
Authors: Issa F. Khouri, Francesco Turturro, Denái R. Milton, Martin Korbling, Barry I Samuels, Elias J. Jabbour, Celina Ledesma, Rosamar B Valverde, Hui Gao, Michelle A Fanale, Luis E. Fayad, Loretta J. Nastoupil, James M Reuben, Alison M Gulbis
Journal: Blood (2016)
Plasmacytoma: 10 years experience at a tertiary care center in India.
Authors: Saphalta Baghmar, Vinod Raina, Atul Sharma, Lalit Kumar
Journal: Journal of Clinical Oncology (2012)

e18573 Background: To evaluate the clinical features, diagnoses, prognostic factors, progression to MM of the patients of solitary plasmacytoma (SP) treated at AIIMS in last 10 years(2001-2010). Methods: From 2001-2010, we identified 57 patients with SP. OS, EFS, progression to myeloma were calculated using the Kaplan-Meier method and log rank test. Results: Out of 57 patients; 48 patients were evaluable. The M:F ratio was 3.5:1 with the median age of 49 years. The primary site was osseous(SBP) in 49 patients, extramedullary(EMP) in 8; 5 lesions were located in the upper respiratory passages, ie nasal cavity and maxillary sinus and rest of the 3 were one each in bronchus, gluteal region and intracranial. 43.8% of the lesions involved the vertebral column. The thoracic spine was the single most commonly involved site (12/57 patients). Out of 25 patients with lesions in vertebral column, 12 presented with paraparesis. Monoclonal protein was present in 48% patients and Urine M- Band in additional 2 patients. Treatment consisted of RT [45 Gy (8-50 Gy)] alone in 27, excision in 2 and excision and RT(n=9) and combined modality(n=10). The median follow-up was 28 months(range 3-160 months). Local control was achieved in 41(85%) while progressive disease was seen in 4. Serum M protein became undetectable after treatment in 60% patients. 17(41%) patients progressed to MM after initial response. The median duration of progression to MM was 21 months. Even though there was a trend towards a better EFS and OS for EMP than SBP, in univariate analysis this was not statistically significant. Patients having vertebral lesion showed trend towards progression to MM (p=.057). 5 yr EFS &amp; OS were 44.4% and 89 % respectively. Median EFS and OS were 38 and 122 months respectively. 5 yr survival rate in patients who developed MM and those who did not were 81% and 100% respectively. None of the baseline characteristics were predictive of survival. Conclusions: Out of 1129 patients of plasma cell dyscrasias registered between 2001-2010; 5% were of SP. Bone was the most common site. Attainment of local control is the predictor of significant EFS (p&lt;0.0001) and OS (p&lt;0.05). Progression to MM is the commonest pattern of failure. Vertebrae involvement was predictor for disease progression to MM.
Computing by Robust Transience: How the Fronto-Parietal Network Performs Sequential, Category-Based Decisions
Authors: Warasinee Chaisangmongkon, Sruthi K. Swaminathan, David J. Freedman, Xiao-Jing Wang
Journal: Neuron (2017)

Decision making involves dynamic interplay between internal judgements and external perception, which has been investigated in delayed match-to-category (DMC) experiments. Our analysis of neural recordings shows that, during DMC tasks, LIP and PFC neurons demonstrate mixed, time-varying, and heterogeneous selectivity, but previous theoretical work has not established the link between these neural characteristics and population-level computations. We trained a recurrent network model to perform DMC tasks and found that the model can remarkably reproduce key features of neuronal selectivity at the single-neuron and population levels. Analysis of the trained networks elucidates that robust transient trajectories of the neural population are the key driver of sequential categorical decisions. The directions of trajectories are governed by network self-organized connectivity, defining a "neural landscape" consisting of a task-tailored arrangement of slow states and dynamical tunnels. With this model, we can identify functionally relevant circuit motifs and generalize the framework to solve other categorization tasks.
Abiraterone plus prednisone alone or with dasatinib in chemotherapy-naive metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Tanya B. Dorff, Susan G. Groshen, David I. Quinn, Amir Goldkorn, Cynthia L. Martel, Jacek K. Pinski, Peter Kuhn, Mitchell E. Gross
Journal: Journal of Clinical Oncology (2014)

TPS5108 Background: Skeletal complications dominate the morbidity of disease progression for men with mCRPC and resistance eventually emerges to all known androgen suppression therapies. Abiraterone acetate (AA) was approved by the FDA for mCRPC based on a survival advantage as well as delay in skeletal-related events, however resistance ultimately develops. Src kinases are involved in androgen receptor phosphorylation, and may represent one resistance pathway. Src kinases also mediate osteoclast-osteoblast interactions, and inhibition has been associated with reduction in bone metastasis formation. Dasatinib is an oral multi-targeted kinase inhibitor with strong Src inhibition. Based on these properties, we hypothesized that the combination of abiraterone plus dasatinib would delay the time to disease progression in mCRPC. The two agents have been combined at full doses in a phase I trial without dose-limiting toxicity. Methods: Design: randomized, phase II. Treatment: Arm A=AA 1000 mg PO daily, prednisone 5mg PO bid. Arm B=same plus dasatinib 100 mg PO daily. Eligibility criteria: mCRPC without prior chemotherapy treatment. Endpoint: disease progression. Assessment, including PSA, will be defined by PCWG2 criteria but patients will be encouraged to stay on study therapy until radiographic progression. Statistics: Rather than binomial testing, we will compare the probability of remaining progression-free at 12 and 24 weeks in Arm A vs Arm B using actual follow-up on a continuous scale. Correlatives: circulating tumor cells will be captured and analyzed using the hi-definition technology (Kuhn laboratory, Scripps) and protein changes will be evaluated in the samples (Gross laboratory, USC) at baseline, 4 weeks, and at progression. Biomarkers examined will be chosen to reflect acquired/somatic changes associated with therapeutic response to androgen or Src-kinase directed therapies. Progress: 21 of 96 planned subjects have been accrued. Clinical trial information: NCT01685125.
Impact of robotic-assisted approach on lymphadenectomy for colorectal cancer.
Authors: Reza Gamagami, Paul Kozak, Venkata R. Kakarla
Journal: Journal of Clinical Oncology (2017)

787 Background: In most recent years, robotic assisted laparoscopic surgery (RALS) has proven to be a viable alternative to laparoscopic and traditional open surgery for colorectal cancer. Obtaining the adequate number of lymph nodes is not only essential for accurate staging, but also impacts both prognosis and the need for adjuvant chemotherapy. To date, the efficacy of lymph node harvest for RALS is not well studied or established. The aim of our study is to analyze the impact of RALS on lymphadenectomy for colorectal cancer. Methods: We performed a retrospective review of patients who underwent curative resections for colorectal cancer over a five-year period at a single institution by a single surgeon. Resections were classified as right-sided, sigmoid, or rectal, and subdivided into robotic and non-robotic surgery groups. The demographic data and histopathology were obtained, with an emphasis on the number lymph nodes harvested (LNH) during resections. Emergencies and non-curative resections were excluded. Results: Between January 2010 and December 2015, 136 patients with colorectal cancer underwent curative resections. Sixty-four underwent right-sided resections (28 laparoscopic, 36 robotic). Twenty-five underwent sigmoid resections (11 laparoscopic, 14 robotic), and 47 underwent rectal resections (15 open, 32 robotic). There was no significant difference in age, sex, BMI and ASA scores between the cohorts examined. The mean number of LNH with RALS was significantly higher in all three groups (right-sided—24 vs. 15 ( p= .0001), sigmoid—16 vs. 12 ( p= .046), rectal—19 vs. 4 ( p= .0016)). There was no difference in the rate of adequate lymph node extraction for staging purpose, i.e., 12 lymph nodes in all three groups. Conclusions: Robotic-assisted laparoscopic surgery is associated with a statistically significant increase in lymph node harvest for right-sided, sigmoid and rectal resections for malignancy. Future studies with larger sample sizes are necessary to validate these findings.