tbuckley/cabot-search huggingface dataset:
My Cancer Genome: Web-based clinical decision support for genome-directed lung cancer treatment.
Authors: M. A. Levy, C. M. Lovly, L. Horn, R. Naser, W. Pao
Journal: Journal of Clinical Oncology (2011)

7576 Background: Lung cancer has traditionally been treated according to histologic subtype with a plateau in the efficacy of combination chemotherapy. Recent advances have identified oncogenic ‘driver mutations’ in lung cancer that predict response to targeted therapies. However, knowledge resources are limited regarding the clinical relevance of such mutations. Methods: We performed a literature review regarding the prevalence and clinical significance of various treatments for ~40 mutations in 10 genes (EGFR, KRAS, BRAF, NRAS, PIK3CA, MEK1, AKT1, HER2, PTEN, and ALK) for non-small cell lung cancer (NSCLC). Data from prospective and retrospective trials as well as preclinical studies was collected. Results: ~100 articles/abstracts were synthesized into the publicly available My Cancer Genome website (mycancergenome.org) which launched in Jan 2011. Content includes information about the oncogene pathway (e.g. What is EGFR?), the clinical significance of the gene for a specific type of cancer (e.g. EGFR in NSCLC), and a summary of clinically relevant data related to a particular gene mutation (e.g. EGFR Exon 19 deletion in NSCLC). Information regarding mutation directed clinical trials open for accrual both at Vanderbilt Ingram Cancer Center and worldwide is provided using a direct query of clinicaltrials.gov. This decision support tool is integrated into Vanderbilt’s electronic medical record to provide actionable decision support for mutation directed treatment prioritization and clinical trial availability. Clinicians, patients, and researchers with access to the internet can also access the website freely and directly. Conclusions: My Cancer Genome is an international resource to assist clinicians in prioritizing genome directed cancer therapies. The first implementation includes content for NSCLC. We are now expanding the content to include melanoma, breast cancer, colon cancer and other malignancies. New data will be incorporated on an ongoing basis. We welcome public/private partnerships to expand content and make this a truly global resource.
Use of exosome analysis to reveal glioma-specific genetic changes in patient serum.
Authors: B. Carter, F. Hochberg, X. Breakefield, L. Balaj, S. Sivaraman, W. Curry, S. N. Kalkanis, L. Loguidice, L. M. Russo, M. Noerhelm, J. Skog
Journal: Journal of Clinical Oncology (2011)

2061 Background: Microvesicles (including exosomes) are small lipid bilayer vesicles released from all cells into bodily fluids and have been shown to harbor both RNA and DNA from the parent cell from which they were released. Recently, a rapid method to extract high integrity RNA from serum microvesicles was developed allowing reliable assessment of their mRNA content. This allows us to gain a transcriptional profile of brain tumors without the need for invasive biopsy. Here we use serum microvesicles to examine the expression pattern of various genes in glioblastoma patients including specific mutations such as the EGFRvIII gene. Methods: Serum samples under an approved IRB protocol were collected from patients with biopsy proven glioblastoma. Microvesicles were isolated using differential ultracentrifugation. During RNA extraction a DNase step was included to remove contaminating DNA. RNA integrity was assessed using the Agilent Bioanalyzer. Isolated RNA was used for Agilent microarray analysis and qPCR based EGFRvIII mutation detection. Results: RNA with visible rRNA peaks was successfully isolated from all serum samples assessed. Microarray expression profiles of RNA isolated from serum microvesicles (exoRNA) from 8 glioblastoma (GBM) patients and 8 normal healthy controls clearly separated the two groups when used in unsupervised clustering. A distinct subset of both upregulated and downregulated genes in the glioma patients was revealed. This indicates distinct differences between the two groups and highlights the potential diagnostic relevance of RNA contained in serum microvesicles. In addition, in patients whose tumors were known to be EGFR amplified and EGFRvIII positive, we found a high rate of detection of EGFRvIII in serum microvesicle RNA (4/4) but not in controls (0/10), with 100-200 gene copies detected per ml. Conclusions: These data indicated that microvesicle RNA can reveal glioma specific genetic changes in patient serum. This may have utility in detecting brain tumors via a serum assay or analyzing specific genetic changes in a glioblastoma patient without invasive brain biopsy.
Quality-of-life results of a randomized phase III trial of four cisplatin (Cis) containing doublet combinations in stage IVB cervical carcinoma: A gynecologic oncology group (GOG) study
Authors: L. B. Wenzel, H. Huang, D. Cella, B. J. Monk, M. W. Sill, S. D. McMeekin, D. E. Cohn, L. M. Ramondetta, C. H. Boardman, J. Benda
Journal: Journal of Clinical Oncology (2008)

5529 Background: Women with stage IVB, recurrent or persistent cancer not amenable to cure were randomized to Cis (C) plus one of the following four drugs: paclitaxel (CP, Reference Arm); vinorelbine (CV); gemcitabine (CG); or Topotecan (CT). Quality of life (QOL) was evaluated in order to determine if CV, CG, or CT was associated with less neuropathy, less pain, or better QOL relative to CP. Methods: QOL was assessed prior to randomization (baseline), prior to cycles 2 and 5, and 9 months post study entry. QOL measures included the Functional Assessment of Cancer Therapy - Cervix Trial Outcome Index (FACT-Cx TOI), the FACT/GOG-Neurotoxicity 4- item scale, and the Brief Pain Inventory 0–10 pain intensity item. Results: The study was closed in April 2007 based on a planned interim analysis on clinical endpoints. By then, 81.8% of target accrual was enrolled (N=491). There was no statistically significant difference in the completion of QOL forms between groups. Baseline scores were comparable on all measures. From pre-cycle 2 through the 9- month follow-up, there were no clinically or statistically significant differences across any of the groups in pain or QOL. Power to detect a 0.5 SD difference between groups was better than 80% pre-cycle 2, but ranged from 22–67% for the last two assessments. Women on the CG and CT regimens reported less neuropathy at the last two assessments, although the difference was not statistically significant. In general, QOL and pain improved slightly over time and neuropathy worsened, showing no indication of improving at the 9-month assessment. Conclusions: No doublet was clinically or statistically different from CP in QOL or pain. A clinical advantage to CG and CT treatment is possible with regard to neurotoxicity, but low power might contribute to a lack of statistical significance. The survival and QOL data will be fully mature in spring 2008, providing more context for interpretation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline
Metrics for measuring tumor burden: A comparison of unidimensional and volumetric measurements.
Authors: B. Zhao, D. C. Ghiorghiu, R. A. Lefkowitz, S. E. Marley, Y. Tan, M. L. Scott, H. Mann, L. H. Schwartz
Journal: Journal of Clinical Oncology (2011)

e13596 Background: Response Evaluation Criteria In Solid Tumors (RECIST) is widely used to evaluate the efficacy of anticancer therapies. However, relying upon a unidimensional length to approximate change in tumor burden may be biased. The purpose of this study was to compare tumor responses/changes assessed by volumetric and RECIST unidimensional measurements. Methods: CT scans of chest, abdomen and pelvis were acquired at 5mm slice thickness as per study protocol, from 49 patients enrolled in early phase oncology trials. Baseline and the first follow-up scans (~6 weeks) were analyzed. Tumor greatest diameter was manually measured by a radiologist and tumor volume by semi-automated computer algorithms. Results: 144 individual sites of metastatic disease were analysed, including from liver, lung and lymph nodes. As expected, the magnitude of tumor burden change was larger for volume than unidimensional measurements: 32/49 (65%) patients had an increase in tumor volume of more than 30% compared to 6/49 (12%) for unidimensional measurements. Based upon RECIST and mathematical equivalence (assuming spherical tumors) of partial response (PR) and progressive disease (PD) for volume, 9/49 (18%) patients were discordant. Out of these 9 cases, 6/9 (67%) were classified as stable disease (SD) using unidimensional measurements and PD using volume, 2/9 (22%) were classified as PD for unidimensional measurements and SD using volume, and 1/9 (11%) was classified as a PR using unidimensional measurements and SD using volume. Comparing tumor burden changes from baseline with 95% limits of agreement (derived from repeat scan reads; ECR 2011) for unidimensional measurements (-12.4, 20.4%) and volumetric measurements (-9.6, 18.0%), 20/49 (41%) patients were discordant. Out of these 20 cases, 19/20 (95%) were classified as having ‘no change’ using unidimensional and ‘change’ using volume (3/20 [15%], decrease; 16/20 [80%], increase). 1/20 (5%) patient was classified as having ‘no change’ using volume and ‘change’ (a decrease) using unidimensional measurements. Conclusions: There was some evidence to suggest that volume is more sensitive than unidimensional measurements in identifying tumor changes for individual patients.
Single-institution evaluation of intrafraction motion during frameless stereotactic radiosurgery.
Authors: Kristin Kowalchik, Siyong Kim, Christopher Serago, Ashley Smith, Stephen Ko
Journal: Journal of Clinical Oncology (2012)

284 Background: Frameless stereotactic radiosurgery (SRS) is single fraction radiation therapy delivered to an intracranial lesion. Rather than with a rigid head frame, frameless SRS uses a thermoplastic mask for immobilization. The benefit of this mask includes the ability to simulate and treat the patient at different times, ease of patient set-up and improved patient comfort. Clinically, frameless SRS is used for primary brain tumors and metastatic lesions. The length of the treatments may vary based on a number of factors, including total treatment dose, number of monitor units, number and arrangement of beams, and equipment manipulations. This is a single institution review of patients treated with SRS with positional checks made before, during and at the completion of treatment to evaluate intrafraction motion. Methods: Patients were treated with SRS at Mayo Clinic Florida between 2010 and 2011. All patients were immobilized with a thermoplastic mask and treated on a Varian IX Clinac. KV Cone beam CT was taken prior to the initiation of treatment to verify the treatment position. Cone beam CT’s were also performed at the midpoint and conclusion of treatment. The same physician analyzed all cone beam CT’s. Adjustments were recorded in each dimension and analyzed to determine intrafraction motion. Results: Intrafraction motion was evaluated during six separate SRS cases. The mean displacements at mid-treatment were 0.67±0.52 mm, 0.50±0.55 mm, 0.83±0.75 mm, and 1.35±0.78 mm in the medial/lateral, superior/inferior, anterior/posterior, and vectoral direction, respectively. The mean post-treatment displacements were 0.17±0.41 mm, 0.67±0.82 mm, 0.50±0.84 mm, and 1.11±0.96 mm in the medial/lateral, superior/inferior, anterior/posterior, and vectoral direction, respectively. Estimated overall margins to accommodate intrafraction motion in 90% of patients were 2.63 mm and 2.69 mm at mid-treatment and post-treatment, respectively. Conclusions: The majority of intrafraction motion occurred during the first portion of treatment. Intrafraction motion during the course of frameless SRS treatment is not negligible and approximately a 2.5 mm margin should be taken into account during the planning process.
The effect of stress on efficacy of dendritic cell therapy for esophageal squamous cell carcinoma.
Authors: Yasunori Akutsu, Wei Qin, Kentaro Murakami, Isamu Hoshino, Naoyuki Hanari, Takanori Nishimori, Mikito Mori, Yuka Isozaki, Takeshi Toyozumi, Xin Hu, HIroshi Suito, Naoki Akanuma, Masahiko Takahashi, Hisahiro Matsubara
Journal: Journal of Clinical Oncology (2014)

69 Background: Recently, abscopal effect, by which systemic anti-tumor effect by local radiation therapy (RT) was elicited, has been reported. This phenomenon was thought to be mediated by stress protein gp96, a key molecule in antigen-presenting. We tested the enhancement of dendritic cell (DC) therapy by various stress, such as radiation or modulated electro-hyperthermia (mEHT) in DC therapy for squamous cell carcinoma (SCC). Methods: Mouse SCC cells, SCCVII, were inoculated into the left femur (primary tumor) of C3H/He mice subcutaneously, and also similarly inoculated into non-treated chest subcutaneous tissue (secondary tumor). Only the primary tumor was exposed to 4 or 10 Gy of RT or 5-10 watts of mEHT. Then DCs was injected only into the primary tumor. Following that, tumor volumes of the primary and secondary tumor were measured. Next, the population of immune-related T-cells in tumor-draining lymph nodes (TDLN) and gp96 expression in the primary tumor were evaluated. Results: With intratumoral injection of DCs and RT, primary tumor growth was markedly suppressed. Furthermore, secondary tumor growth was also suppressed. On the other hand, the combination of DCs and mEHT could inhibit tumor growth at both the primary and the secondary tumor. As for the population of T-cells, the population of CD3+, CD 4+ and CD 8+T-cells in the TDLN was markedly elevated and that of FoxP3 was reduced my mEHT. Gp96 expression, a stress protein, was strongly enhanced after RT and mEHT. Conclusions: Stress, such as RT or hyperthermia can enhance the efficacy of DC therapy and can induce a strong antitumor effect by stimulating the expression of stress protein, gp96. These combination therapies can be a strong systemic immunotherapy for esophageal SCC.
Predictive effect of phosphoglycerate kinase 1 as a disease progressive marker after EGFR-TKI treatment in NSCLC patients.
Authors: L. Yan, C. Zhou
Journal: Journal of Clinical Oncology (2010)

e18108 Background: Currently, EGFR-TKIs such as gefitinib and erlotinib have been confirmed as effective treatments for second-line therapy of advanced NSCLC patients. However, most patients would face acquired resistance after one or two year treatment. Radiographic examination and clinical symptoms are the most common methods to detect disease progress, however, which lack sensitivity and specificity and lead to missing the best time point to change treatment. In the previous research, we found PGK1 was highly expressed in the patients with progressive disease after EGFR-TKI treatments. In this study, we detected PGK1 before and at the time of progression disease in advanced NSCLC patients with EGFR-TKIs treatment, and investigated its predictive effect to disease progression of EGFR-TKIs treatment. Methods: PGK1 in the serum was measured by a highly sensitive immunoassay method before and at the time of progression disease in advanced NSCLC patients with EGFR-TKIs treatment. Results: 39 patients were enrolled with a median age of 67 years old, stage IIIB/IV: 5/34, Male/Female:17/22, ECOG PS 0-1/2-3: 30/9. The response rate was 25.6% and median progression free time was 6.1 months. Serum PGK1 levels were significantly higher in the patients at progression disease after EGFR-TKI treatments than that at the baseline (0.483 ± 0.033 ng/mL vs 0.29 ± 0.012 ng/mL, p < 0.01). Conclusions: PGK1 might be a new serum biomarker to be more sensitive and specific to early detection of disease progress after EGFR-TKI treatment in advanced NSCLC. No significant financial relationships to disclose.
Early radiotherapy versus late radiotherapy after incomplete transarterial chemoembolization in hepatocellular carcinoma.
Authors: Mi Sun Kim, Do Young Kim, Kwang-Hyub Han, Jong Yun Won, Do Yun Lee, Jinsil Seong
Journal: Journal of Clinical Oncology (2015)

459 Background: To investigate the efficacy of early RT (ERT) in comparison to late RT (LRT) in HCC patients after incomplete TACE. Methods: Between January 2006 and December 2011, 99 BCLC B and C stage HCC patients were reviewed. We defined ERT as curative aimed additional RT after the first TACE, and LRT was defined as salvage aimed additional RT for recurrent or re-growing remnant tumors after repeated TACE. The median prescribed dose was 45 Gy (range, 21.6 Gy–60 Gy) given in daily dose of 1.8 Gy–3 Gy. Three-dimensional conformal RT or intensity modulated RT was used for all patients. The in-field tumor response rate (IFTR) was evaluated using the modified response evaluation criteria in solid tumors. Results: Fifty eight (58.6%) patients received ERT and 41 (41.4%) patients received LRT. All patients had BCLC B-C stage HCC and the characteristics between two groups were not different significantly. However, vessel invasion was observed more often in the LRT group (p=0.039). The median interval between last TACE and RT was 2weeks in the ERT group, and 4 weeks in the LRT group. The IFTR at one month and three months were significantly higher in the ERT group. The one-year in-field progression-free survival rates were 79.5% and 45.9% in the ERT and LRT groups, respectively (p=0.007).The one-year overall survival rates were 75.9% and 48.8% in the ERT and LRT groups, respectively (p = 0.01). In the multivariate analysis, vessel invasion and treatment group (ERT vs.LRT) were independent predictor of OS (p=0.039 and p=0.035). PVTT and treatment group (ERT vs.LRT) showed correlation with IFPFS in the multivariate analysis (p=0.002 and p=0.01). Conclusions: While this finding may reflect differences in biological characteristics between the two groups, ERT within 2weeks after incomplete TACE should be considered.
Neurotoxicity of intra-CSF liposomal cytarabine in the treatment of leptomeningeal metastases.
Authors: M. C. Chamberlain, S. K. Johnston
Journal: Journal of Clinical Oncology (2011)

2062 Background: Treatment of leptomeningeal metastasis (LMD) remains challenging due to advanced systemic disease at presentation and limited treatment options. Methods: All patients underwent standard pre-treatment LMD assessment including CSF assessment (cytology or flow cytometry), brain and spine MR imaging, and radioisotope CSF flow study. Liposomal cytarabine was administered intraventricularly (n=80) or intralumbar (n=40) at 50mg every 2-weeks x4 and then every 4-weeks x6 in responding patients. Dexamethasone (4mg orally twice per day x5days) was co-administered with each liposomal cytarabine treatment. Patients were seen with each liposomal cytarabine treatment and assessed for toxicity. Results: 120 adult patients (median age 51 years [range 33-68]) with LMD were treated with liposomal cytarabine. Liposomal cytarabine Common Toxicity Criteria > Grade 3 neurotoxicity was seen in 62 cycles (11.9%) in 28 patients (23.3%). Toxicity included bacterial meningitis (3.75% ventricular: 0% lumbar); chemical meningitis (17.5%:15%); communicating hydrocephalus (3.75%: 5%); conus medullaris/cauda equina syndrome (5%:5%); decreased visual acuity (5%:2.5%); encephalopathy (5%: 5%); leukoencephalopathy (7.5%: 2.5%); myelopathy (2.5%: 2.5%); radiculopathy (1.25%: 5%); and seizures (1.25%: 2.5%). Distribution of toxicity was similar regardless of route of administration (ventricular vs. lumbar). Toxicities were transient in 38 episodes (61.3%) and permanent in 24 (38.7%; 17 patients). There were no treatment-related deaths however 20 treatment-related toxicities (32.2%) required hospitalization. Conclusions: Liposomal cytarabine is mostly well tolerated however a subset of patients (14%) not easily identified pre-treatment develop serious treatment-related neurological complications that may be persistent and impact quality of life.
The SUCCESS-Trial: Toxicity analysis of a phase III study evaluating the role of docetaxel and gemcitabine in the adjuvant therapy of breast cancer patients
Authors: W. J. Janni, E. Genss, H. L. Sommer, B. K. Rack, A. Schneeweiβ, M. Rezai, J. Hilfrich, A. Schneider, W. Lichtenegger, M. W. Beckmann
Journal: Journal of Clinical Oncology (2008)

551 Background: In several randomized trials, taxane-containing regimens have demonstrated superiority compared to mere anthracycline-containing schedules for the adjuvant treatment of patients with early breast cancer. Given an array of novel drugs, continued improvements in the adjuvant setting may further reduce breast cancer mortality in future. Methods: The SUCCESS-Study is an open-label randomized controlled, phase III study comparing the disease-free survival after randomization in patients treated with 3 cycles of epirubicin (100 mg/m²)-fluorouracil (500)-cyclophosphamide (500, FEC)-chemotherapy, followed by 3 cycles of docetaxel (100 mg/mg², D) versus 3 cycles of FEC, followed by 3 cycles of gemcitabine (1,000mg/m² d1,8)-docetaxel (75 mg/m²)(DG). Complete, monitored toxicity data of 2,691 pts were available for this analysis. Results: Cytostatic treatment was prematurely stopped in 119 pts (4.4%) receiving FEC-DG and in 103 pts (3.8%) with FEC-D (p=0.21). Dose reduction >20% (3.97% vs. 2.90%) and postponement of treatment cycles >7die (22.85% vs 14.19%) was rare, but more frequent in the FEC-DG arm (both p<0.001). G-CSF support was applied in 850 (29.2%) vs. 602 pts (20.7%, p<0.001). Toxicities NCI grade > 2 which occurred with incidence > 1% or significantly different in the two arms are depicted in Table 1. Afebrile and febrile neutropenia and anemia did not differ between the two arms, but thrombocytopenia was more frequent in FEC-DG (1.7%, p=0.007). Hand-foot syndrome and neuropathy was more frequent in the FEC-D arm (p=0.09 and p=0.02, respectively). Conclusions: Severe adverse effects were rare in both treatment arms. The addition of gemcitabine to FEC-D adjuvant chemotherapy increases toxicity moderately. These findings will have to be interpreted in the context of survival outcome results. Grade 3-4 NCI Toxicities Toxicity FEC-DG (%) FEC-D (%) p-value Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection) (ANC =38.5 degrees C) 2.91 4.02 0.99 Thrombocytopenia 1.73 0.41 0.007 SGPT (ALT) (serum glutamic pyruvic transaminase) elevation 4.71 1.91 0.0004 Vomiting 3.81 3.95 0.99 Stomatitis/pharyngitis (oral/pharyngeal mucositis) 1.66 1.77 0.99 Diarrhea 2.84 2.65 0.99 Fatigue 2.77 3.13 0.95 Thrombosis/embolism 1.66 1.97 0.94 Neuropathy 0.62 1.91 0.023 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Chugai, Lilly Oncology, sanofi-aventis Chugai, Lilly Oncology, sanofi-aventis