tbuckley/cabot-search huggingface dataset:
Cognitive function and depressive symptoms in patients with newly diagnosed primary brain tumors: A potential interactive relationship.
Authors: John E. Schmidt, Dana H. Bovbjerg, Frank S. Lieberman, Catherine M Bender, Jason Weimer, Paula R Sherwood
Journal: Journal of Clinical Oncology (2014)

2095 Background: Primary Brain Tumor (PBT) and its treatment result in reduced cognitive function which significantly interferes with work, personal, and social activities. Depression is also a clinically significant problem in patients with PBT at diagnosis, during and post-treatment. Recent research in non-cancer patients with mild-cognitive impairment has found strong associations between reduced cognitive function and depression; however this association has been little researched in PBT patients. The goal of the present study was to explore the potential interactive relationship between cognitive function (psychometrically assessed) and depression in patients undergoing primary adjuvant treatment for newly diagnosed PBT. Methods: Participants included 49 patients (51% male, mean age 48.0) with glioblastoma (n=18), oligodendroglioma (n=17), and astrocytoma (n=14). All completed a pre-treatment psychological and cognitive assessment. The assessment was repeated twelve months later. Assessments included depression (CES-D), physical symptoms and interference (MDASI-BT), and cognitive function (STROOP, Digit Symbol Coding). Results: At both assessments, mean scores on Digit Symbol Coding were in the low-average to borderline range compared to WAIS-IV norms. Mean STROOP T-scores fell in the average to low-average range. No significant differences were found in physical symptom severity or interference between assessments (p’s>.05). Performance on the STROOP and Digit Symbol Coding declined significantly (rANOVA, p’s<.05). Depression scores did not change (p’s>.05). When pretreatment depression scores were included as a covariate, changes in cognitive function were no longer significant. The majority of the participants were working or in school at baseline (n=34, 70%), but were on disability or unemployed at second assessment (n=33, 67%). Conclusions: The results suggest that depressive symptoms may contribute to declines in cognitive function over time in PBT patients. It is tempting to speculate that interventions focused on improving cognitive function in these patients might be enhanced by early intervention to reduce depressive symptoms.
Association of drug exposure with clinical response and toxicities in metastatic renal cell carcinoma patients (mRCC) receiving an alternative dosing (AD) regimen of sunitinib.
Authors: Yi Ling Teo, Xiu Ping Chue, Noan-Minh Chau, Min-Han Tan, Ravindran Kanesvaran, Hwee Lin Wee, Han Kiat Ho, Alexandre Chan
Journal: Journal of Clinical Oncology (2013)

e13582 Background: An AD regimen of 37.5mg daily in repeated 4-weeks on, 2-weeks off cycle has been proposed to ameliorate frequent dose modifications due to toxicities as observed with the approved dosing regimen of sunitinib for mRCC. This study aims to determine the effect of drug exposure (sunitinib and active metabolite, SU12662) on clinical response and toxicities in patients receiving this AD regimen. Methods: All mRCC patients starting on sunitinib were invited to participate in this study. In week 4 of each cycle, toxicities were assessed and graded according to CTCAE and plasma AUC ss was quantified using high-performance liquid chromatography. Clinical response was assessed after 2 treatment cycles; and was used with drug exposure and toxicities data for dose adjustments. Statistical tests such as Mann-Whitney U were used to compare the levels between groups. Results: 24 patients with a mean age of 58.8 ± 11.2 years were recruited. Majority were males (75%) and Chinese (87.5%). Among the 17 and 14 analyzable cases for cycle 1 and 2, median total AUC ss were 2.2 and 2.1 µg•h/ml respectively. Fourteen patients completed 2 treatment cycles; 7 (50%) partial response, 4 (28.6%)stable disease and 3 (21.4%) progressive disease. A dose increment to 50mg daily was performed for a patient with disease progression. Common grade 2 and above toxicities were hypertension, hand foot syndrome (HFS) and mucositis. Higher drug exposures were observed among patients who achieved clinical responseand among those who experienced at least grade 2 toxicities. Conclusions: Drug exposure could likely be associated with clinical response and toxicities in this AD regimen. [Table: see text]
Evaluating the utility of baseline cardiac function assessment in early-stage breast cancer treatment.
Authors: Sandy Rose Truong, William Thomas Barry, Javid J. Moslehi, Emily Baker, Erica L. Mayer, Ann H. Partridge
Journal: Journal of Clinical Oncology (2014)

6590 Background: Cardiotoxicity is a rare complication of anthracycline or trastuzumab-based therapy for patients with early-stage breast cancer. Screening echocardiogram (ECHO) and radionuclide ventriculogram (RVG) are often performed prior to administration of these agents to evaluate cardiac function. Only limited evidence for the clinical utility of these screening tests is available. We sought to determine the role of baseline cardiac imaging in treatment planning in asymptomatic patients without prior cardiac problems. Methods: Early-stage breast cancer patients diagnosed from 2006 to 2011 (n=1067) with a baseline ECHO/RVG were identified in a single institution prospective registry. Chart review was performed to obtain pre- and post-ECHO/RVG treatment plans, baseline ECHO/RVG results, and cardiac risk factors. A total of 600 patients had available medical records, as well as no prior chemotherapy, radiation therapy, or cardiac history or complaints. ECHO/RVG abnormalities were defined as ejection fraction (EF) <55%, valvular disease, left ventricular hypertrophy, and diastolic dysfunction. Results: Among 600 eligible patients, average age was 48 (range 23-80); 79% of treatment plans included anthracycline, 34% included trastuzumab, 16% both. Abnormal ECHO/RVG results were observed in 13 of the 600 patients (2.2%, 1.2%-3.7%), including 9 with baseline EF <55%. There were no detected changes in treatment plans (e.g., switching to a less cardiotoxic agent) in any of these patients, although 2 were recommended to undergo more frequent cardiac function monitoring in follow-up. There were no statistically significant differences in age, race, menopausal status, smoking history, alcohol use, BMI, or medical comorbidities (hypertension, diabetes, or hyperlipidemia) between patients with abnormal and normal ECHO/RVG results. Conclusions: Baseline screening ECHO/RVG rarely yields an abnormality that prompts change in anthracycline and/or trastuzumab-based treatment plan. Further investigation should include determination of the utility of baseline screening ECHO/RVG among patients who develop cardiac problems during or following breast cancer treatment.
Association of chromosome 17 copy number instability with favorable prognosis in nonsurgically treated gastroesophageal adenocarinoma and impaired response to trastuzumab.
Authors: Neal Spada, Jacqueline Birkness, Sanja Dacic, James D. Luketich, Katie Sue Nason, Weijing Sun, Jon M. Davison
Journal: Journal of Clinical Oncology (2017)

61 Background: Chromosomal instability (CIN), defined as cell to cell variation in copy number, is a feature of solid tumors that has been shown in experimental systems to result in aneuploidy, DNA damage, changes in gene expression, and genetically heterogeneous cell populations. In esophageal adenocarcinoma, chromosome 17 (Chr17) aneusomy is associated with heterogeneous HER2 amplification, a marker of poor prognosis (Yoon et al., J Clin Oncol 2012), but the association between CIN, HER2 amplification and clinical outcome has not been well studied. Methods: We retrospectively analyzed individual cell Chr17 centromere counts in 348 gastroesophageal adenocarcinomas that were tested for HER2 amplification. As an estimate of Chr17 CIN (CIN-17), we calculated the percentage of cells with centromere counts differing from the mode (modal centromere deviation, MCD, Roylance et al. Cancer Epidemiol Biomarkers Prev, 2011). We analyzed the association of CIN-17 with Chr17 aneusomy, HER2 amplification, pathologic tumor characteristics and clinical outcome. Results: Using pre-established cutoffs, we found CIN-17 (MCD &gt; 30%) in 45% (158/348) and extreme CIN-17 (MCD &gt; 45%) in 28% (99/348) of cases. Compared to CIN-17 negative tumors, CIN-17 positive tumors were more likely to be polysomic (77% vs 0.5%, P &lt; 0.001) and Lauren intestinal type (84% vs 70%, P = 0.005). HER2 amplification was detected in 23% (80/348) of tumors, but there was no association with CIN-17 (P = 0.493). In patients who received pharmacologic therapy (n = 77), there was a 58% reduction in overall mortality associated with extreme CIN-17 (HR = 0.42, 0.25-0.72) independent of age, stage and addition of trastuzumab. Addition of trastuzumab to pharmacologic therapy showed a trend toward improved clinical outcome only in the subgroup without extreme CIN (n = 50, HR = 0.37, 0.13-1.06). CIN-17 was not associated with differences in patient survival after surgical resection. Conclusions: In this retrospective study, extreme CIN-17 was a favorable prognostic factor in patients who receive chemotherapy but could impair response to trastuzumab. These findings warrant further study.
Do CT perfusion measures predict early clinical response in patients with advanced renal cell carcinoma?
Authors: Alice C. Fan, Aya Kino, Heiko Schmiedeskamp, Vandana Sundaram, Sandy Srinivas, Viola Chen, Yori Imae, Manisha Desai, Aya Kamaya
Journal: Journal of Clinical Oncology (2017)

496 Background: We need biomarkers of response to guide treatment decisions in RCC. Our pilot study uses perfusion CT to assess early changes in tumor vascularity in response to targeted therapies. We will determine if perfusion CT measurements can help predict response to therapy after 1 week of treatment in patients with metastatic RCC. Methods: Nine patients with metastatic renal cell carcinoma treated with targeted therapy have been enrolled to date. CT perfusion measures were collected: (1) prior to treatment, (2) 7-10 days after start of treatment, and (3) 12 weeks after start of treatment. At each time point, 5 measures were analyzed: (1) blood volume (BV), (2) blood flow (BF), (3) mean transit time (MTT), (4) flow extraction product (FEP), and (5) tumor size. Clinical response was determined based on RECIST criteria. Univariate and multivariate logistic regression analyses were conducted to determine the association of the CT perfusion measures and clinical response. The relationship between clinical response and individual measure at each time point, change in each measure at each time point, and the rate of change over the measure across all time points (slope) were evaluated in each patient. Results: We found that two blood volume measurements are associated with outcome. 5/9 (56%) patients had stable disease and 4/9 (44%) had progressive disease. Decrease in blood volume from time prior to treatment to 7-10 days after start of treatment was significantly associated with decreased odds of having stable disease (OR 0.63 (0.4-0.99), p=0.04). When examining the rate of change, the slope of blood volume was significantly associated with decreased odds of having stable disease (OR 0.52 (0.27-1.01), p=0.05). Univariable logistic regression for each individual CT measure, FEP prior to treatment (OR 1.07 (0.99-1.15), p=0.08) and 12 weeks after treatment (OR 1.13 (0.99-1.29), p=0.06) were not significantly associated with stable disease. Conclusions: Changes in blood volume including absolute difference as well as rate of change of blood volume were statistically significantly different between patients with stable disease versus progressive disease. Clinical trial information: NCT01926990.
A phase II trial of cabozantinib (Cabo) in patients (pts) with castrate-resistant prostate cancer (CRPC) metastatic to bone (NCT01428219).
Authors: Petros Grivas, Stephanie Daignault, Kathleen A. Cooney, Jon Jacobson, Corrie Yablon, Brian Dale Ross, Thomas L Chenevert, Craig J Galbán, Alnawaz Rehemtulla, Evan T. Keller, Priya Kunju, Rohit Mehra, June Escara-Wilke, Greg Shelley, Kenneth James Pienta, Maha Hussain, David C. Smith
Journal: Journal of Clinical Oncology (2013)

TPS5094 Background: MET overexpression predicts prostate cancer invasion and bone metastasis; inhibition of MET/VEGF pathways has synergistic activity in CRPC (Knudsen et al. Adv Cancer Res 2004; Aftab et al. Clin Transl Oncol 2011). Cabo is a small molecule that inhibits multiple receptor tyrosine kinases, including MET and VEGFR2. A phase II randomized discontinuation trial of Cabo showed clinical activity in CRPC, including reduction of soft tissue lesions, prolongation of progression-free survival (PFS), resolution of bone scans, and reductions in bone turnover markers, pain and narcotic use (Smith et al, JCO 2013). To further define the activity of Cabo in pts with CRPC and bone metastases, we launched a phase II trial to characterize the effects of Cabo on bone metabolism and tumor activity in prostate cancer bone lesions. We hypothesize that the clinical activity of Cabo correlates with measurable pharmacodynamic effects on bone micro-environment. Methods: After informed consent, chemotherapy-naive pts with progressive CRPC and bone metastases accessible to CT-guided biopsy, adequate performance status/organ function, are treated with Cabo 60 mg once daily. Primary endpoint: proportion of pts progression-free (PF) at 12 weeks. Secondary endpoints: safety, PFS, response proportion/duration, PSA response, PSA time-to-progression. A Simon's two-stage mini-max design permits early termination after the first 27 evaluable pts in case of unfavorable results. Alternatively, up to 46 evaluable pts will be accrued. Cabo would not be of interest if the 12-week PF proportion is &lt;0.45; it would be of definite clinical interest if the 12-week PF proportion is &gt;0.65 (5% type I error, 85% power). Perfusion/diffusion-weighted MRI (parametric response maps) and bone lesion biopsies are required at baseline and 6 weeks after starting Cabo. Doxycycline is administered prior to bone biopsy for bone labeling. Bone cores are sent for dynamic histomorphometry and immunohistochemistry (phospho-MET/MET, phospho-VEGFR2/VEGFR2, phospho-Akt/Akt). Serum is collected at several time-points to measure markers of bone metabolism. 13 of 27 first-stage pts have been enrolled and started Cabo. Clinical trial information: NCT01428219.
Sequencing cell free DNA in patients receiving selective internal radiation therapy for colorectal liver metastases.
Authors: Helen Winter, P Kaisaki, Rebecca Carter, Anthony Cutts, Tessa Greenhalgh, Anna Schuh, Ricky A. Sharma, Jenny C Taylor
Journal: Journal of Clinical Oncology (2017)

646 Background: Tumour heterogeneity is a key determinants of cancer resistance. Serial sampling of cell free (cf)DNA may detect evolving somatic mutations. Monitoring cancers after therapies e.g. selective internal radiation therapy (SIRT) require new biomarkers as RECIST imaging was developed to assess response to chemotherapy and may not reflect tumour changes due to new therapeutic strategies. The utility of cfDNA to detect recurrence and predict response is emerging. The objective of this study was to sequence serial cfDNA samples from patients with liver predominant metastatic disease receiving SIRT, and explore the feasibility of using this method to detect evolution of somatic mutations after high dose radiation. Methods: A prospective imaging biomarker study was performed in patients with colorectal liver metastases (CRLM) receiving SIRT. Plasma was extracted and frozen within 4 hours at 3 time points: baseline, 4 and 10 weeks after SIRT. Ion Torrent Amplicon sequencing was performed using cancer hotspot panel v.2. Sequencing of primary tumours was obtained by pyrosequencing. Results: Twenty-four patients with CRLM were recruited from March – Dec 2015, and 18 had cfDNA extracted for sequencing at a minimum of two time points. Ion Torrent amplicon sequencing of baseline cfDNA showed high concordance with formalin-fixed paraffin-embedded (FFPE) tumour samples. Serial cfDNA sequencing in a patient with partial response by imaging, detected 22% KRAS G12C mutation at baseline, which decreased to 1.5% by 4 weeks, then was undetectable 10 weeks after SIRT. Sequencing of another patient’s cfDNA revealed persistence of KRAS G13D and a truncating APCmutation at both 4 and 10 weeks after SIRT, consistent with the patient’s progressive disease. Conclusions: Cell-free DNA is emerging as a biomarker in colorectal cancer. Our measurements of mutational status in baseline cfDNA and FFPE samples show high concordance. This study reports that serial cfDNA sequencing detects changes in mutational status and specific mutations following high dose radiation to the liver. This adds to the evidence of cfDNA as a tool to detect evolution of somatic mutations following therapy.
5-fluorouracil, oxaliplatin and dasatinib (FOLFOX-D) for previously untreated metastatic pancreatic adenocarcinoma.
Authors: Thomas J. George, Long H. Dang, Karen Colleen Daily, Jason Scott Starr, Hiral D. Parekh, Alison Marguerite Ivey, Daniel Delitto, Carmen Joseph Allegra, Steven J. Hughes, Xiaomin Lu, Margaret A. McEwan, Jessica L Cioffi, Jose Gilberto Trevino
Journal: Journal of Clinical Oncology (2017)

TPS517 Background: Systemic chemotherapy for pancreatic adenocarcinoma improves survival and cancer related symptoms. Most targeted agents combined with gemcitabine have consistently failed to demonstrate clinical benefits. Src is overexpressed in pancreatic cancer and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the pancreatic cancer phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This is a multicenter phase II trial to determine activity and toxicity of FOLFOX + D in previously untreated metastatic pancreatic adenocarcinoma. Eligible pts must have at least 1 measurable target lesion by RECIST, ECOG PS 0-2, normal QTc and adequate organ function. Pts received standard cycles of mFOLFOX6 repeated q14d with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints included progression-free survival (primary; PFS), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those demonstrating durable disease control or exceptional response. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months. NCT01652976. Results: Enrollment continues on this prospective phase II study with 38 of 42 evaluable patients. There are no unexpected toxicities noted thus far. Clinical trial information: NCT01652976. [Table: see text]
Adverse Effects of Statins
Authors: Larry B. Goldstein
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of baseline plasma biomarker signature with survival in advanced NSCLC patients on linifanib.
Authors: Evelyn Mary McKeegan, Arunava Chakravartty, Peter J Ansell, Gerard Davis, Gong Chen, Sabrina Chan, Raj Chandran, Angel DeGuzman, Susan Gawel, Barry Dowell, Anahita Bhathena, Mark D. McKee, Justin L. Ricker, Dawn M. Carlson, Viswanath Devanarayan
Journal: Journal of Clinical Oncology (2012)

e13583 Background: Linifanib is a potent and selective VEGF and PDGF receptor inhibitor that has activity in unselected, advanced NSCLC patients (pts) both as monotherapy in the relapsed setting and with carboplatin (C) and paclitaxel (P) in the first-line setting. A baseline plasma biomarker signature identifying NSCLC pts most sensitive to linifanib is needed. Methods: An exploratory retrospective analysis of four randomized clinical trials including linifanib or other treatments in relapsed NSCLC was conducted. Evaluable baseline plasma samples were obtained from 116 pts who received linifanib and 71 pts on other treatments. A signature combining established tumor markers (carcinoembryonic antigen [CEA] and fragments of cytokeratin 19 [CYFRA 21-1]) was derived using a sequential BATTing approach. The signature was then tested across a randomized trial of CP + placebo, linifanib 7.5 mg, or linifanib 12.5 mg in first-line advanced, non-squamous NSCLC. Results: In 2/3L NSCLC, the signature was associated with improvement in survival on linifanib monotherapy (HR=0.51 vs. signature negative; P=0.0017), but no improvement in survival on other treatments (P=0.87). In the first-line setting with CP, the signature was associated with significant PFS improvement with linifanib and a trend towards significant overall survival improvement at high dose (Table). Conclusions: A baseline plasma biomarker signature is associated with improved survival in advanced NSCLC patients on linifanib. Incorporation of this signature should be considered in any further investigation of linifanib in NSCLC. [Table: see text]