tbuckley/cabot-search huggingface dataset:
Clinical evaluation of 2-(<sup>18</sup>F) fluoro-2 deoxy-D-glucose PET/ CT in hereditary leiomyomatosis and renal cell carcinoma.
Authors: Brian Shuch, Kevin P. Asher, Clara Chen, Kelly Lin, Gennady Bratslavsky, W. Marston Linehan, Ramaprasad Srinivasan
Journal: Journal of Clinical Oncology (2013)

383 Background: 2-( 18 F) fluoro-2 deoxy-D-glucose (FDG) PET/CT is a useful tool in the staging of malignancies. In patients with kidney cancer, the role of FDG is limited in those with clear-cell histology and remains to be evaluated with other subtypes. Kidney cancer associated with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is characterized by a defect in the Krebs cycle rendering these tumors highly dependent on aerobic glycolysis (the ‘Warburg effect’) with high glucose uptake to fulfill their energy requirements; we hypothesized that FDG PET/CT may have excellent sensitivity for staging in this condition. Methods: We retrospectively reviewed patients with HLRCC kidney cancer that underwent FDG PET/CT in conjunction with anatomic imaging at our institution. The ability of FDG PET/CT to detect malignant lesions (defined using pathologic or radiologic criteria) was evaluated. Results: A total of 30 patients underwent 42 PET /CTs. Conventional imaging identified a total of 107 lesions. Both patient and lesion-based analyses were performed. A total of 90 lesions, including ten renal lesions, were classified as malignant. 76 of 80 extra-renal lesions were correctly identified as malignant by PET/CT (sensitivity, 95%, CI 88-98%). In contrast, only 4 of 10 renal lesions were correctly identified as malignant (sensitivity, 40%, CI 17-69%). 11 of 12 histologically confirmed extra-renal lesions were PET avid (sensitivity, 92%, CI-64-98%). 10 of 12 (83%) benign lesions associated with HLRCC including uterine/cutaneous leiomyomas and adrenal nodules were PET avid. In a patient based analysis, all 18 patients with extra-renal spread of kidney cancer were correctly identified (sensitivity 100%, CI 82-100%). Conclusions: FDG PET/CT is a highly sensitive diagnostic modality for identifying metastatic kidney cancer associated with HLRCC. Prospective studies evaluating the utility of PET/CT imaging to characterize response to systemic therapy are currently underway.
Lenalidomide Associated Tumor Flare Reaction Correlates with Clinical Response in Patients with Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
Authors: Taimur Sher, Mehul Patel, Amy Whitworth, Kena Miller, Laurie Musial, David Lawrence, Swaminathan Padmanabhan, Sikander Ailawadhi, Gregory Wilding, Dawn DePaolo, Naveen Bangia, Myron S. Czuczman, Paul K. Wallace, Kelvin P. Lee, Asher Chanan Khan
Journal: Blood (2008)
Disease presentation and course in patients with a high number of multiple brain metastases
Authors: C. Nieder, A. Pawinski, S. T. Astner
Journal: Journal of Clinical Oncology (2008)

13012 Background: Recent research has focused on patients with limited numbers of brain metastases and the effectiveness of intensified local treatment such as surgical resection or radiosurgery in such cohorts. Little information is available on patients which are not suitable for these approaches because the number of brain metastases is very high (defined as 10 or more for the purpose of this study). Methods: The authors performed a retrospective review of their database and identified all patients that have received whole-brain radiotherapy (WBRT) for 10 or more brain metastases from solid primary tumors. Results: The cohort consisted of 24 adult patients with a median of 14 brain metastases. The median age was 56 years and all patients had active extracranial disease (5 patients had no evidence of extracranial metastases). The presentation of brain metastases was simultaneous to first cancer diagnosis in 8 (33%) and metachronous in 16 (67%). Non-small cell lung cancer (25%), small cell lung cancer (25%) and breast cancer (21%) were the most common primary tumors. Half of the patients had KPS <70 and thus belonged to RPA class III, while the other half belonged to RPA class II. To patients failed to complete WBRT, 16 received 30 Gy in 10 fractions, and 6 higher total doses up to 50 Gy. Median survival was 2 months, maximum 14 months, and 12.5% were alive at 6 months. At least partial remission was evident on serial imaging in 8 patients (33%) and 25% had clinical symptom improvement beyond that obtained by steroids before WBRT. No prognostic parameters associated with survival were identified. No factors predictive for response were identified either. Conclusions: Patients with a large number of brain metastases have a worse outcome after WBRT (with regard to all endpoints) than previously reported for other patient cohorts. To our knowledge, this is the first report that focuses specifically on such patients. For the majority of patients with 10 or more brain metastases, short course WBRT, e.g., 20 Gy in 5 fractions, might be preferable over prolonged regimens as survival typically is very short. No significant financial relationships to disclose.
Gene-expression profiles related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells.
Authors: H. Chang, S. Y. Rha, H. Jeung, J. Ahn, J. Jung, T. Kim, H. Kwon, B. Kim, H. C. Chung
Journal: Journal of Clinical Oncology (2011)

50 Background: We evaluated the cytotoxic effects of combining of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, with taxanes in human gastric cancer cell lines, and evaluated the pre-treatment difference of gene profile to identify genes that could potentially mediate the cytotoxic response. Methods: Twenty-five gastric cancer cell lines with 22K gene expression data were treated with SAHA and paclitaxel or docetaxel, and the synergistic interaction between the drugs was evaluated in vitro using the combination index (CI) method. We performed significance analysis of microarray (SAM) to identify chemosensitivity-related genes in gastric cancer cell lines that were concomitantly treated with SAHA and taxane. We generated a correlation-matrix between gene expression and CI values to identify genes whose expression correlated with a combined effect of taxanes and SAHA. Results: Taxane and SAHA combination had a synergistic cytotoxic effect against taxane-resistant gastric cancer cells. We selected 49 chemosensitivity-related genes, which were commonly identified in paclitaxel and docetaxel combined with SAHA, via SAM analysis. Among them, nine common genes (SLIT2, REEP2, EFEMP2, CDC42SE1, FSD1, POU1F1, ZNF79, ETNK1, and DOCK5) were extracted from the subsequent correlation-matrix analysis. Conclusions: Taxane and SAHA combination could be efficacious for the treatment of gastric cancer. The genes which were related with the synergistic response to taxane and SAHA could serve as surrogate biomarkers to predict the therapeutic response in gastric cancer patients. We are researching to determine the expression of the nine genes in malignant human gastric cancer tissue and to correlate them with clinical information. No significant financial relationships to disclose.
A phase II trial of weekly nab-paclitaxel with GM-CSF as chemoimmunotherapy for platinum-resistant epithelial ovarian cancer.
Authors: R. E. Swensen, J. Childs, D. Higgins, T. Gooley, B. A. Goff, P. A. Fintak, B. Buening, M. L. Disis
Journal: Journal of Clinical Oncology (2011)

5020 Background: Ovarian cancer patients who mount an anti-tumor immune response enjoy a prolonged survival, suggesting that augmenting anti-tumor immunity may be therapeutic. We hypothesized that weekly nab paclitaxel (nabP) followed by the immune stimulant, GM-CSF may enhance anti tumor immunity and prolong time to progression (TTP). Methods: Eligible subjects had platinum resistant ovarian, primary peritoneal or fallopian tube cancer, and an elevated CA125. Conditional power estimate after 11 subjects showed 22 subjects had 80% power to show an improved response rate (RR) if the true RR is 35%. Study end points were RR and TTP. Progression (DP) was doubling of CA125 above the nadir. Complete response (CR) was a decline of CA125 below institutional normal. Partial response (PR) was a decline of >50% from baseline. Stable disease (SD) was all other scenarios. Subjects received nabP, 100mg/m2 days 1,8,15 followed by GM-CSF (Leukine) 250mcg days 16-26 of a 28 day cycle until progression or 6 cycles were complete. Responding subjects received up to 6 more cycles of GM-CSF on days 14-28. Results: 20 subjects received at least one dose of study medications, 16 have completed the study. Median age was 62 (30-91) and had a median of 3 (1-13) prior regimens. Among those completing the study, the median TTP was 110 days vs. 269 days on the prior platinum regimen. 6/16 (37%) had a PR and 2/16 (13%) had a CR. Subjects with a response had a median TTP of 140 days. Toxicities were manageable. 3 subjects went off nabP due to progressive sensory neuropathy. 3 subjects had grade 3 neutropenia requiring dose delay and reduction. 3 subjects experienced grade 3 lymphopenia. One episode of grade 3 fatigue, hypokalemia, and anemia each occurred. One subject was hospitalized for bowel obstruction, another with bowel obstruction, esophagitis and hypoxia due to pleural effusion. Two subjects died while on study, one of a pulmonary embolism, another at home unattended, cause unknown. Conclusions: Weekly nabP with GM-CSF has manageable toxicity and induces a high response rate in patients with platinum resistant ovarian cancer, however this regimen does not prolong the TTP beyond the TTP observed in the prior platinum regimen.
Population pharmacokinetic (PK) analysis of lanreotide autogel/depot in the treatment of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs): Pooled analysis of four clinical trials.
Authors: Nuria Buil-Bruna, Maria Jesus Garrido, Marion Dehez, Amandine Manon, Thi Xuan Quyen Nguyen, Edda L. Gomez-Panzani, Inaki F Troconiz
Journal: Journal of Clinical Oncology (2015)

397 Background: Lanreotide Autogel (Depot in US) has been shown in clinical trials to have antitumor effects and control symptoms associated with hormone hypersecretion in GEP NET patients. Objectives: To describe the PK of Lanreotide 60, 90, or 120 mg SC injections every 4 weeks in GEP NET patients, to quantify inter-patient variability (IPV) and to identify PK impacting patient characteristics. Methods: 1,541 serum concentrations were obtained from 290 patients and analysed simultaneously using the population approach with the software NONMEM version 7.2. The covariates evaluated included demographics, renal and hepatic function markers, and disease related information. Results: Serum profiles were described with a one-compartment disposition model and with an absorption process characterized by two parallel absorption pathways following first and zero order kinetics. The estimated apparent volume of distribution was 18.3 L. The estimated apparent total serum clearance for a typical 74 kg patient was 513 L/day. No covariate tested showed a statistically significant effect on the PK profile except body weight, which showed a moderate effect on clearance (clearance increased by 25% as weight increased by 30%). However, when comparing a subject with low weight (51 kg) to a subject with high weight (104 kg), their PK profiles were similar with a great degree of overlapping. Therefore, this weight effect on clearance was not considered clinically relevant. The magnitude of IPV was low for clearance (27%) and moderate for absorption constant (61%). However due to the lack of PK timepoints around the C max , a higher IPV was observed for volume of distribution (150%). Mean (SD) derived parameters AUC and C max at steady-state were respectively 239 (64.8) ng.day/mL and 13.9 (7.44) ng/mL, showing moderate IPV in the PK profile. Conclusions: The PK of lanreotide Autogel/Depot was well characterized in GEP NET patients using two mechanisms of absorption. The IPVof the PK of lanreotide was moderate. Among all the patients characteristics tested, none were found clinically relevant to a potential dose adjustment in clinical practice.
Prognostic value of chromosomal imbalancies and the colon gene expression signatures in rectal cancer.
Authors: Jerome Doyen, Eric Letouze, Pascale Romestaing, Olivier Chapet, Jean-Pierre Gérard
Journal: Journal of Clinical Oncology (2012)

465 Background: Some studies have suggested colon and rectal cancer as two different entities when considering DNA mutations or chromosomal imbalances. We therefore wondered if two colon gene expression signatures could predict specific survival. We also tested the influence of chromosomal imbalancies on prognosis in rectal cancer. Methods: Between 1998-2001 a series of 94 patients (pts) with rectal adenocarcinoma (T1-2-3 M0) were treated with preoperative radiotherapy (RT) with or without concurrent chemotherapy (CT) (78 pts) or with curative RT alone using contact X Ray therapy (CXRT) (18 pts). High-throughput analysis of genomic imbalancies and DNA expression were performed within the frame of the Carte d’Identité des Tumeurs (CIT) programme of Ligue du Cancer- France. Biostatistical analysis were performed and correlated with metastasis-free survival (MFS) and specific survival (SS). Coloprint and Oncotype DX colon signatures were tested on this cohort. Results: The median survival of the 96 patients was 105 months. The overall specific survival rate at 8 years was 75% for the preoperative group and 65 % for the RT alone group. Overall the rate of distant metastases was 30 % at 8 years (26 pts). A validated biopsy specimen was analysed in 67 pts for DNA expression and for genomic imbalances. Deletion of 8p and 1p36-35 correlated with MFS (p=0.001 and p=0.02 respectively) and SS (p=0.0002 and p=0.008 respectively). Multivariate analysis identified -8p as an independent prognostic factor of MFS (p=0.004) and SS (p=0.003). Validation of this deletion on an independent cohort is on-going. Regarding mRNA profile analysis, no stable consensus could identify clusters that accurately separate patients of bad and good SS or MFS, whatever the method used (28 methods of clustering). Coloprint signature could discriminate patients with the worst prognosis (SS: p&lt;0.05) whereas Oncotype DX colon signature did not (SS: p=0.4). Conclusions: By analysing this series of patients from a single center we have been able for the first time in rectal cancer to identify -8p as an independent prognostic factor of MFS and SS. mRNA analysis suggest that colon and rectal cancer may not always share the same DNA expression profile.
<i>Paulinia</i> <i>cupana</i> (Guarana) for the treatment of cancer-related fatigue in patients undergoing radiation therapy or chemotherapy: A meta-analysis of three clinical trials.
Authors: A. Del Giglio, D. d. I. G. Cubero, A. Serpa, R. P. Riechelmann, M. P. O. Campos
Journal: Journal of Clinical Oncology (2011)

e19706 Background: For cancer patients undergoing radiation therapy (RT) or systemic chemotherapy (CHT), cancer-related fatigue (CRF) is a common problem that can negatively impact in their quality of life. Guarana (Paullinia cupana) is a plant native to the Amazon basin that has been used as a stimulant since pre-Columbian times. We wanted to evaluate the effectiveness of guarana extract on fatigue in patients undergoing either CHT or RT in three randomized placebo controlled with crossover trials. Methods: 137 cancer patients (85% with breast cancer) undergoing either CHT (101) or RT (36) were randomized to receive either placebo or guarana. In all three studies, guarana was given as an unmanipulated dry extract at a dose of 75 mg PO QD in the first two studies or 50 mg PO BID in the third study. Patients were crossed over to the other experimental arm, and fatigue was evaluated with the Chalder Scale in all three studies. Results: Guarana significantly improved the Chalder Scale Global Scores (-0.75; 95% CI: -1.03 to -0.47; p < 0.00001; heterogeneity p = 0.07 ); Physical Fatigue Scores (-0.73; 95% CI: -1.01 to -0.45; p < 0.00001; heterogeneity p < 0.001) and Mental Fatigue Scores (-0.94; 95% CI: -1.12 to -0.76; p <0.00001; heterogeneity p = 0.97). Guarana did not produce any CTCAE grades 3 or 4 toxicities in any of the studies. Conclusions: Dry guarana extract is an effective, cheap and non-toxic alternative for the treatment of fatigue in cancer patients undergoing oncologic treatment. We believe that Guaraná's positive effects in mental fatigue were very consistent and significant and warrant further investigation.
Outcome of patients with micropapillary bladder cancer treated with neoadjuvant therapy and radical cystectomy.
Authors: Daniel Levi Willis, Mario Fernandez, Rian J. Dickstein, Sahil Parikh, Arlene O. Siefker-Radtke, Charles Guo, Bogdan Czerniak, Jay Bakul Shah, Louis L. Pisters, H. Barton Grossman, Colin P.N. Dinney, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2013)

318 Background: Micropapillary bladder cancer (MPBC) is an uncommon and aggressive variant of urothelial carcinoma for which the role of neoadjuvant chemotherapy (NAC) is not well-defined. Here we report a retrospective analysis of patients with MPBC undergoing radical cystectomy (RC) with and without NAC. Methods: An IRB-approved review of our radical cystectomy database demonstrated 159 patients with a preoperative diagnosis of MPBC. Of these, 131 patients presented with surgically resectable (≤cT4aN0M0) disease and form the basis of this report. Disease-specific (DSS) and overall survival (OS) were estimated using the Kaplan-Meier estimator and compared by log-rank test. Results: The clinical stage breakdown was cT1:50; cT2:66; cT3:15; and cT4a:0. NAC was administered to 61 patients (47%) with 78% receiving cisplatin-based regimens. Patients were more likely to receive NAC if they presented with cT3 disease, hydronephrosis, or lymphovascular invasion (LVI) in the transurethral resection (TUR) specimen. After a median follow-up of 44 mo., 50% of patients recurred and 41% died of disease, resulting in a 5-year estimated DSS of 58.4% for all 131 patients. Survival analysis was performed for comparable groups according to our established risk factors. For the low risk patients (i.e. cT1-T2, no hydronephrosis, and no LVI) RC upfront (n=47) resulted in a 73% 5-yr DSS compared to 83% with NAC (n=19) (p=0.47). In the high-risk group (cT3 or cT2 with LVI and/or hydronephrosis), 41 patients were treated initially with NAC and 5-yr DSS was 40%, which was similar (p=0.74) to the 31% 5-yr DSS for those treated with RC upfront (n=20). The most important overall prognostic factor was pathologic downstaging to pT0, pTa, or pTis at cystectomy (seen in 52% after NAC and 19% after TUR alone) which conferred a significant survival advantage (5-yr DSS 93% vs. 40% in those not downstaged; p&lt;0.001). Conclusions: Despite incorporation of a multimodal treatment strategy, patients with MPBC and high risk features (LVI, hydronephrosis and/or cT3 stage) have poor outcomes. Further studies are necessary to define the optimal treatment strategy in this challenging subset of patients with urothelial cancer.
Clinical outcome of preoperative breast MRI for early-stage breast cancer.
Authors: Shadi E. Hamdan, Leslie A. Martin, Rajitha Sunkara
Journal: Journal of Clinical Oncology (2012)

42 Background: Preoperative breast magnetic resonance imaging MRI is used in clinical practice to improve oncologic outcome of breast cancer. Concerns over increased rate of unnecessary mastectomies and additional biopsies have been raised. The purpose of our study is to review the outcome of preoperative breast MRI at our institution. Methods: The current study is a retrospective review of 215 patients with early stage breast cancer who underwent definitive surgery. Breast MRI is being used at our institution within the context of multidisciplinary approach. Patients who had complete clinical, radiologic, and pathological data available were identified and formed the basis of this analysis. Results: 215 patients were diagnosed with breast cancer stage I-II in the period of 2006-2012 and had complete data for review. 92 patients out of 215 (43%) had breast MRI prior to definitive surgery. both groups were different in regard of age. Rate of breast conservative surgery, mastectomies, and re-excision for positive margins was similar in both groups. 6 patients out of 12 patients who had breast MRI and underwent bilateral mastectomies were found to have abnormal pathological findings (DCIS 3, LCIS 1, invasive ductal carcinoma 1, and focal epithelial atypia 1). Time from first diagnostic procedure to definitive surgery was similar in both groups (29 days vs. 27.5 days). 38 (41%) patients out of 92 who had breast MRI underwent additional breast biopsies for suspicious lesions with only 8 (21%) patients found to have abnormal pathological findings. Conclusions: Use of breast MRI prior to definitive surgery for early stage breast cancer was associated with increased rate of additional biopsies for suspicious lesions with no favorable effect on re-excision rate. [Table: see text]
Cross-sectional comparisons of patient-reported disease control, disease severity and symptom frequency in children with atopic dermatitis
Authors: J. Chang, W.B. Bilker, O. Hoffstad, D.J. Margolis
Journal: British Journal of Dermatology (2017)

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that commonly affects children. Research in AD has utilized an increasing variety of scoring measures to monitor disease, and this lack of standardization has been cited as an obstacle to evidence-based decision making. The Harmonizing Outcome Measures for Eczema (HOME) initiative aims to establish consensus on a core set of outcome measures for AD and currently recommends the Patient-Oriented Eczema Measure (POEM) for recording patient-reported outcomes.

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