tbuckley/cabot-search huggingface dataset:
Clinical Utility of Different Approaches for Detection of Late Pseudoprogression in Glioblastoma With O-(2-[18F]Fluoroethyl)-l-Tyrosine PET
Authors: Olivia Kertels, Milena I. Mihovilovic, Thomas Linsenmann, Almuth F. Kessler, Johannes Tran-Gia, Malte Kircher, Joachim Brumberg, Camelia Maria Monoranu, Samuel Samnick, Ralf-Ingo Ernestus, Mario Löhr, Philipp T. Meyer, Constantin Lapa
Journal: Clinical Nuclear Medicine (2019)

Purpose PET/CT using O-(2-[ 18 F]fluoroethyl)- l -tyrosine ( 18 F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM). Methods Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared. Results 18 F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P &lt; 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P &gt; 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior. Conclusions Irrespective of the analytical approach, 18 F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers.
Identification of RGS5 as a tumor-associated antigen expressed in a broad range of human malignancies and recognized by antigen specific cytotoxic T cells
Authors: P. Brossart, C. Boss, K. Brauer, T. Weinschenk, L. Kanz, S. Stevanovic, H. Rammensee, F. Grünebach
Journal: Journal of Clinical Oncology (2006)

2569 Background: Identification of tumor-associated antigens (TAA) have resulted in the development of therapeutic vaccines for the treatment of cancer. We applied an integrated functional genomics approach to identify TAA in malignant tissues of patients with renal cell carcinoma (RCC). Methods: A comparative DNA chip analysis of tumor and the corresponding non-malignant tissue from patients with RCC followed by sequencing of peptides bound to the HLA-class I molecules by mass spectrometry was applied to identify novel TAA in RCC. To confirm the immunogenicity of identified epitopes cytotoxic T lymphocytes (CTL) were generated using dendritic cells (DC). Results: RGS5 was found to be overexpressed in 16 of 29 analyzed RCC (5.7–29.9 fold) as compared to non-malignant renal tissue. Two peptides derived from RGS5 binding to either HLA-A*02 or 03 were identified. RGS5 was previously shown to be expressed in pericytes and promote tumor angiogenesis. Using RT-PCR analysis we found that RGS5 is expressed on a broad variety of tumor cells including RCC, colorectal, breast and ovarian cancer, malignant melanoma and multiple myeloma as well as in acute and chronic leukemias making this protein an interesting candidate for the development of vaccination strategies to target the tumor cells and the tumor vessels. CTL that were induced using the RGS5 peptides lysed autologous DC pulsed with the cognate peptide or transfected with in vitro transcribed RGS5 RNA as well as HLA-matched tumor cell lines. The specificity and HLA restriction was confirmed using blocking monoclonal antibodies and in cold-target inhibition assays. We next utilized DC transfected with RGS5 RNA to generate specific CTL. Using this approach we confirmed the processing and presentation of the identified peptides by malignant cells. These CTL lysed tumor cells in antigen specific manner while sparing non-malignant cells. In an ongoing vaccine trial RGS5 peptides could safely be given to RCC patients resulting in the induction of peptide specific CTL responses. Conclusions: Our results demonstrate that RGS5 is a novel tumor rejection antigen expressed in a wide range of malignancies that can be applied to target malignant cells and tumor angiogenesis. [Table: see text]
The impact of sun protective behavior and vitamin D supplementation on vitamin D level in melanoma patients.
Authors: Rachit Kumar, Sarika Khanna, Patricia Reutemann, Kurt S Wenk, Suraj S. Venna, Sekwon Jang
Journal: Journal of Clinical Oncology (2012)

e19025 Background: Vitamin D (VitD) is synthesized in the skin as a result of exposure to sunlight and its deficiency is common in the general population as well as in cancer patients. Sun protection is strongly recommended for patients after a melanoma diagnosis. We conducted a pilot study to assess the prevalence of VitD deficiency and the impact of both sun protective behavior and VitD supplementation on VitD levels in melanoma patients Methods: Adult patients with AJCC Stage 0-III melanoma were recruited from the Washington Cancer Institute between July 2011 and January 2012. Subjects completed a questionnaire asking about oral VitD supplementation and sun protective behaviors. VitD deficiency was defined by a 25-hydroxyvitamin D (25(OH)D) level less than 30ng/mL. Pearson Chi-square test and multivariate logistic regression were used to determine predictors of VitD deficiency. Results: A total of 49 participants (20 males, 29 females) completed the questionnaire and provided a blood sample for 25(OH)D determinations. Median age was 52 years (23-82), and most (n=48, 98%) were Caucasian. The majority had either stage 0 (n= 13, 27%) or 1 (n=29, 59%) melanoma. Twenty-six (53%) reported regular use of VitD supplements, and the majority reported sun protective behaviors (n=36, 73%). The prevalence of VitD deficiency was 46% (n=23). VitD deficiency was more common in patients who were not taking VitD supplementation (73% vs. 26%, p&lt;0.01). Other associations include: (1) BMI&gt;25 vs. BMI ≤25 (57% vs. 33%, p=0.10); (2) winter vs. summer months(54% vs. 40%, p=0.34); (3) those who practiced sun protective behavior vs. not (50% vs. 38%, p=0.48). On multivariate analysis, the use or non-use of VitD supplementation remained the only significant predictor of VitD deficiency (OR=0.11, p&lt;0.01). Conclusions: VitD deficiency is common in melanoma patients especially in those who are not on VitD supplementation.
Swallowing function for patients treated on E2399: A phase II trial of function preservation with induction paclitaxel/carboplatin followed by radiation plus weekly paclitaxel
Authors: B. A. Murphy, K. Smith, A. Cmelak, A. Forastiere
Journal: Journal of Clinical Oncology (2006)

5524 ECOG 2399 is a phase II organ preservation study using induction chemotherapy followed by concomitant chemoradiation in unresectable patients with squamous cancer of the larynx or oropharynx. A correlative study was undertaken to assess acute and long-term swallowing. Methods: Swallow evaluations were done at baseline, 3, 12 and 24 months posttreatment. Self-report measures consisted of the PSS-HN and FACT-HN. Objective measures include the Modified Barium Swallow (MBS) scored using a physiologic measure, the Dysphagia Outcome Severity Scale (D) and a functional measure, the Functional Communication Measure (F). Both D and F are graded on a 7-point scale (7 = normal through 1 = absent swallow/unable to take p.o). Results: The number of evaluable D and F assessments at each time point: baseline 97/99, 3 months 72/73, 12 months 40/41, 24 months 24/26. The scores presented in the table are expressed in percentages. Conclusions: The majority of patients presented with objective abnormalities on MBS, but swallow function remained largely intact. At 3 months, swallowing was markedly impaired (severe 18 and 24%, moderate 20 and 21%). By 12 months, swallowing had improved for most patients; however, a significant percentage of patients had persistent mild deficits (5–6). Severe swallowing abnormalities were found in less than 10% of patients at 12 and 24 months. Sponsored, in part, by Bristol-Myers-Squibb. [Table: see text] [Table: see text]
Association of Renal Scarring With Number of Febrile Urinary Tract Infections in Children
Authors: Nader Shaikh, Mary Ann Haralam, Marcia Kurs-Lasky, Alejandro Hoberman
Journal: JAMA Pediatrics (2019)

Although prior studies have suggested that the risk of renal scarring gradually increases with each febrile urinary tract infection (UTI), recent and detailed data are lacking.To evaluate how the risk of renal scarring is associated with the number of febrile UTIs.A post hoc analysis was performed from June 2018 to April 2019 of data collected in the context of 2 multicenter prospective studies (RIVUR [Randomized Intervention for Children With Vesicoureteral Reflux], conducted from June 2007 to June 2013, and CUTIE [Careful Urinary Tract Infection Evaluation], conducted from May 2008 to October 2013), of children with a first UTI without baseline renal abnormalities who were followed up for 2 years for febrile recurrences.Number of known febrile UTIs.Renal scarring was defined as decreased uptake of tracer associated with the loss of contours or cortical thinning on a technetium 99m dimercaptosuccinic acid renal scan obtained at study exit or approximately 4 months after the last febrile UTI.A total of 345 children were included (307 girls and 38 boys; mean [SD] age, 19.4 [18.2] months; 221 with vesicoureteral reflux and 124 without vesicoureteral reflux). The incidence of renal scarring was 2.8% (95% CI, 1.2%-5.8%) after 1 febrile UTI, 25.7% (95% CI, 12.5%-43.3%) after 2 febrile UTIs, and 28.6% (95% CI, 8.4%-58.1%) after 3 or more febrile UTIs. The odds of renal scarring after a second febrile infection were 11.8 (95% CI, 4.1-34.4) times greater than after a single febrile infection, and the odds of renal scarring after 3 or more febrile infections were 13.7 (95% CI, 3.4-54.4) times greater than after a single febrile infection.Although relatively few children have 2 febrile UTIs, those who do have a substantially higher risk of renal scarring compared with children with a single febrile UTI. This finding suggests that research should focus on the identification of biomarkers that could noninvasively identify children at risk for subsequent febrile infections. More research is also needed to understand the molecular basis of the increased risk of renal scarring among children with recurrent febrile UTIs.
Protein Kinase Cι and Wnt/β-Catenin Signaling: Alternative Pathways to Kras/Trp53-Driven Lung Adenocarcinoma
Authors: Ning Yin, Yi Liu, Andras Khoor, Xue Wang, E. Aubrey Thompson, Michael Leitges, Verline Justilien, Capella Weems, Nicole R. Murray, Alan P. Fields
Journal: Cancer Cell (2019)
The Current Genomic Landscape of Western South America: Andes, Amazonia, and Pacific Coast
Authors: Chiara Barbieri, Rodrigo Barquera, Leonardo Arias, José R Sandoval, Oscar Acosta, Camilo Zurita, Abraham Aguilar-Campos, Ana M Tito-Álvarez, Ricardo Serrano-Osuna, Russell D Gray, Fabrizio Mafessoni, Paul Heggarty, Kentaro K Shimizu, Ricardo Fujita, Mark Stoneking, Irina Pugach, Lars Fehren-Schmitz
Journal: Molecular Biology and Evolution (2019)

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis.
Desmoid tumor (DT): Clinical and treatment characteristics and quality of life (QoL) in a large cohort from a referral center.
Authors: Ulrich Ronellenfitsch, Bea Wiedemann, Franka Menge, Jens Jakob, Ralph Hohenberger, Bernd Kasper, Peter Hohenberger
Journal: Journal of Clinical Oncology (2013)

10566 Background: Due to its low incidence, evidence regarding DT is scarce, and consensus on recommended treatment is difficult to achieve. This study systematically assesses clinical presentation, treatment characteristics and QoL in a large cohort of DT patients (pts). Methods: Demographic and clinical variables were retrieved from a database of 224 pts with histologically confirmed DT presenting to our referral center from 10/04-7/12. For a subset of 46 pts, QoL was assessed with the SF-12 questionnaire. The distribution of variables in the entire pt population and clinically relevant subgroups was calculated and compared with appropriate statistics (t-test, nonparametric tests). Denominators varied due to non-availability of variables for some pts. Results: 153 (68.3%) pts were female. Mean age at first diagnosis was 36.9 (3-73) yrs. Primary tumor site was limb/intraabdominal/rectus abdominis/trunk in 40/43/43/66 (21/22/22/35%) of 192 pts. 65/108 (60%) pts recalled a trauma or medical intervention at the DT site. 38/43 (88%) pts with rectus abdominis DT were female, and 31/38 (82%) had previous pregnancies, median time to DT diagnosis after end of pregnancy was 17 months. Primary therapy was resection/imatinib/tamoxifen/watchful waiting in 136/9/8/7 (83/6/5/4%) pts. Resection was R0/R1/R2 in 47/66/22 (35/49/16%) pts. After R0/R1 resection, DT recurred in 46% and 62% resp. after a median of 356/334 days. Physical/mental SF-12 summary scores were 39.2/40.8, 41.5/45.4, and 48.0/44.5 in pts with limb, intraabdominal, and trunk DT and 38.6/42.6 and 43.3/42.5 in pts with and without recurrence (reference population score 50; all p&gt;0.05 for subgroup comparisons). Five women delivered a healthy child in parallel to clinically existent DT. 56% of our patients are alive with disease, whereas 44% have no evidence of disease. Conclusions: In 83% of DT pts, resection is the first treatment step and is R0 only in one third. 60% of the pts recall trauma/medical intervention at the DT site. Rectus abdominis DT occur after a median of 1.5 yrs after pregnancy. Despite the fact that 56% of our pts live with disease, their QoL is only slightly decreased, with lowest values for physical QoL in pts with recurrence.
Activity of <i>nab</i>-paclitaxel (<i>nab</i>-P) monotherapy in heavily pretreated pancreatic cancer (aPDAC) patients (pts): A multicenter retrospective analysis.
Authors: Vanja Vaccaro, Emilio Bria, Michele Reni, Isabella Sperduti, Alain Gelibter, Carmen Nuzzo, Angela Torsello, Carlo Garufi, Eleonora Lucchini, Melissa Frizziero, Davide Melisi, Carmen Belli, Stefano Cereda, Giampaolo Tortora, Francesco Cognetti, Michele Milella
Journal: Journal of Clinical Oncology (2013)

e15057 Background: No standard treatment exists in pretreated aPDAC pts, who have already received available active drugs. nab-P has shown to improve survival in combination with GEM in first line and to be active in GEM-resistant aPDAC pts. Methods: aPDAC pts who received off-label single agent nab-P (125 or 100 mg/m 2 over 30 minutes on days 1, 8, and 15 of a 28- day cycle) as 2 nd or further line of treatment for metastatic disease in three Italian centers were retrospectively reviewed. Results: 29 pts were identified (M/F: 16/13; median age: 66 yrs, range: 39-83); &gt;50% of pts had an ECOG PS 2; median number of previous treatment lines: 2 (range 1-5); 7 pts had received Folfirinox as first line. nab-P starting dose was 125 mg/m2 in 5 pts and 100 mg/m2 in the others. A median of 2 cycles (range 1-10) were administered. Two partial responses (44 and 46-wk duration) were observed; 4 pts had stable disease SD (9, 16, 23, 28-wk duration, respectively); 5 pt are presently not evaluable. Median and mean progression free survival (PFS) were 8 (95% CI: 5-11) and 13 (95% CI: 7-18) wks, respectively; median and mean overall survival (OS) were 13 (95% CI: 9-17) and 25 (95% CI: 15-35) wks, respectively. Three- and 6-month PFS rates were 33% and 15%, respectively; 6- and 12-month OS rates were 36% and 22%, respectively. Toxicity was mild with G4 neutropenia in 1 pt and G3 neuropathy in 1 pts. With at least 10 out of 29 pts free from progression at 3 months (3-month PFS rate: 35%), our results satisfy the following post-hoc statistical hypothesis: p0: 15%, p1: 35%, a: 5%, 1-b: 80%, according to A’Hern exact single stage phase II design. Conclusions: nab-P is well tolerated and moderately active, even in heavily pretreated aPDAC pts. Further analyses are warranted, especially to identify the small proportion of pts who derive exceptionally prolonged benefit from nab-P monotherapy.
Palatability Can Drive Feeding Independent of AgRP Neurons
Authors: Raphaël G.P. Denis, Aurélie Joly-Amado, Emily Webber, Fanny Langlet, Marie Schaeffer, Stéphanie L. Padilla, Céline Cansell, Bénédicte Dehouck, Julien Castel, Anne-Sophie Delbès, Sarah Martinez, Amélie Lacombe, Claude Rouch, Nadim Kassis, Jean-Alain Fehrentz, Jean Martinez, Pascal Verdié, Thomas S. Hnasko, Richard D. Palmiter, Michael J. Krashes, Ali D. Güler, Christophe Magnan, Serge Luquet
Journal: Cell Metabolism (2017)
A phase I study of the pan-Bcl2 family inhibitor GX15–070, administered as a 3-hour weekly infusion in patients with refractory solid tumors or lymphomas
Authors: K. Firozvi, J. Hwang, N. Hansen, S. Malik, M. Maclean, L. Siu, J. L. Marshall, D. Mendelson, J. Kuruvilla
Journal: Journal of Clinical Oncology (2006)

3081 Background: GX15–070 is an antagonist of the BH3-binding groove of the bcl-2 family of anti apoptotic proteins. GX15–070 activates apoptosis in vitro and exhibits clinical activity in chronic lymphocytic leukemia (O’Brien et al, ASH 2005) with a recommended phase II dose of 28 mg/m 2 every 3 weeks with DLT of grade 3 infusional CNS toxicities. Methods: In a standard titration design, 4 cohorts of 3 patients (pt) were treated with 5mg/m 2 - 14 mg/m 2 IV infused over 3 hours, weekly. Each cycle of therapy consisted of 4 weekly infusions. Pharmacokinetics (PK) and pharmacodynamic (PD) response based on plasma oligonucleosomal DNA levels were evaluated. Results: N=15 pts were treated. Median age was 58 (range 24–71). Median number of prior regimens was 4 (range 1–11). A total of 105 infusions (26 cycles) was administered. GX15–070 underwent first order elimination kinetics with a short initial distribution phase (α t 1/2 =0.6 h), followed by a longer elimination γphase (t 1/2 =43.8 h). At the 14 mg/m 2 dose level, median C max and AUC values were 98 ng/ml and 276 ng.hr/ml, respectively. The coefficient of variation was low at 38%. Adverse events have mostly been observed during or shortly after the infusion and have been transient. The most common pertain to the central nervous and gastro-intestinal system (drowsiness, euphoria, ataxia, and abdominal pain). Most toxicities were mild to moderate, with the exception of grade 3 pain experienced by 2/2 pts with Hodgkin’s disease, that resolved rapidly but resulted in treatment discontinuation in 1 patient. One episode of Grade 3 infusional CNS toxicity was reported at 14 mg/m 2 requiring the inclusion of 6 patients with no further DLT. No neutropenia, thrombocytopenia or lymphopenia have been reported. The MTD has not been reached. Mean increase in plasma oligonucleosomal DNA was 36 fold (range 0–182 fold) over baseline. Best response to treatment to date : SD ≥ 8 weeks (4); PD (5); too early (6). Conclusion: Weekly GX15–070 as been well tolerated at doses showing biological activity. Dose escalation will be pursued up to 28 mg/m 2 weekly. No significant financial relationships to disclose.
Cost of palliative external beam radiotherapy (EBRT) utilization for bone metastases secondary to prostate cancer (PC).
Authors: Nancy A. Nickman, Xiangyang Ye, David K Gaffney, Reed B. Barney, Joseph E. Biskupiak, Gary J. Okano, Vinson C. Lee, Jorge Arellano
Journal: Journal of Clinical Oncology (2013)

e16091 Background: Evaluations of palliative EBRT costs for patients with bone metastases are limited. The objective of this study was to summarize documentation of usual care patterns and episode costs of EBRT to bone in deceased men with metastatic PC treated in a United States specialty cancer hospital. Methods: An Electronic Health Record (EHR)-based retrospective review was used to identify deceased PC (ICD-9 185.xx) patients ≥18 years of age with bone metastases (ICD-9 198.5) treated between 1995 and 2012 with EBRT for metastasis and pain management. Variables of interest encompassed patient-specific demographic and clinical characteristics, including length and number of EBRT treatments and total cost of EBRT usage (standardized to 2011$US).Common Procedural Terminology (CPT) codes related to EBRT and hospital assigned visit numbers were used in an algorithm to identify EBRT episodes of care (defined as all billed professional and technical EBRT services provided between initial and final evaluation by radiation oncologist). Bootstrapping (percentile method) was used to approximate the 95% confidence interval for final EBRT cost estimates. Results: A cohort of 176 men were identified; 19 (10.8%) had metastases in &gt;1 site, and an average (±SD) Charlson Comorbidity Index of 6.4 ± 3.9 at metastasis diagnosis (excluding cancer). An average of 5.1 ± 4.6 years elapsed between PC and bone metastasis diagnoses. Prior to bone metastasis diagnosis, patient-reported symptoms included bone pain (54%). All men received at least 1 episode of EBRT, and 89 (50.6%) received &gt;1 episode (range 1-6, median = 2). The length of first episode of EBRT ranged from 1 - 44 calendar days (average ± SD, 13.4 ± 8.4), with an average cost totaling $7,084 ± $4,028. Approximately 70% of costs were attributable to hospital (technical) charges and 30% to physician (professional) charges. Bootstrapping resulted in a 95% confidence interval of total cost between $6,641 and $7,527. Conclusions: Results suggest thatpalliative EBRT may constitute a significant burden in time and healthcare system costs.