tbuckley/cabot-search huggingface dataset:
Clinical experience with the new manual and automated large core biopsy systems based on a rotational cutting on a helix
Authors: J. P. Janssens, L. Rotenberg, M. Sentis, R. Schultz-Wendtland
Journal: Journal of Clinical Oncology (2007)

1550 Background: Survival from breast cancer has increased significantly in recent years mainly as a result from better imaging techniques, earlier detection and improved tissue sampling. Newer technologies should improve existing biopsies because major drawbacks, including tumor cell displacement, preclude women and physicians to biopsy suspect lesions. A new large core biopsy device with a direct frontal approach, lesser side effects, less sampling needs, lower costs and improved yields has been evaluated in clinical practice. Methods: The results of 70 subsequent transdermal biopsies with rotational cutting on a helix are evaluated with regard to quality of the sample, patient satisfaction and completeness of diagnosis. The patients with a suspect lesion in the breast are selected in an oncological practice. Malignancy was verified by subsequent excision of the lesion. Attention was given to tumor cell displacement. Benign disease was verified by the subsequent clinical course. Results: In 69 patients at least one high quality sample with an average length of 1.8 cm and 0.3 cm diameter could be obtained. One patient refused the procedure. The average number of biopsy cores needed to obtain a reliable diagnosis was 1.5 (mininum 1 - maximum 5). No complication was noted with regard to pain, hemorrhagy, infection or other wound problems. 64 patients quoted the procedure as relative pain free. In 69 patients the diagnosis was complete with regard to the diagnosis of malignancy or benign disease. No destruction, biopsy artefacts or cell displacement was noted on histopathology. In all diagnoses with malignancy the grade of the tumor could be reliably given as well as steroid receptor content and HER2 immunohistochemistry. FISH-HER2 tests were possible in all HER2 positive tumors. Automated biopsies with vacuumassistance had slightly larger samples compared to the manual technique. Conclusions: The new large core biopsy technique with a rotational cutting on a helix performs well in clinical practice. All developmental goals with regard to quality of sample, patient satisfaction and cost price per biopsy have been met. Large core biopsies are now available for a larger population of women at risk for breast cancer with less risk of complication. No significant financial relationships to disclose.
Predictive value of novel and existing activating EGFR mutations for improved survival in malignant peritoneal mesothelioma (MPM) and response to EGFR-TK inhibitors (EGFR-TKI)
Authors: J. M. Foster, R. Uppala, V. Govindarajan, J. H. Carreau, L. Stan, S. Nath, S. Poonam, Z. Galatica, B. W. Loggie
Journal: Journal of Clinical Oncology (2009)

11030 Background: MPMs are highly aggressive tumors with most patients diagnosed surviving 8–12 months. Currently there is a paucity of information about the molecular/biological perturbations involved in tumor formation. Previously we presented (at ASCO 2007) that novel EGFR-TK mutations occurred in these tumors predictive of optimal surgical cytoreduction; but the EGFR activity of these mutations was being investigated. Here we present the EGFR activity of these mutations as well as matured outcome data. Methods: Twenty-nine MPM patients were evaluated at a single tertiary center and tumors were probed for mutations in the TK domain of EGF receptor (mut+). All specimens were examined for somatic mutations by PCR amplification and confirmed by multiple independent PCRs. Twenty-five patients were treated with cytoreductive surgery (CRS) ± IPHC and clinical data including age, sex, cytoreductive score, histology, mutation, and survival was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine the time dependent activating profile of these mutations, as well as response to EGFR-TKI-inhibitor. Results: Mutations were found in 31% (9/29) of the tumors; 7 of these mutations were novel. All 7 novel mutations and L858R mutation identified were activating mutations with similar activation profiles. All mutations were responsive to EGFR-TKI treatment. Of the 25 patients managed surgically there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ have progressed and died of disease with a MFT of 22 months; while 13/18 (72%) mut- had progressive disease and 10/18 (56%) died with median TTP and survival of 12 months and14 months respectively. Estimated 3-year PFS was 70% mut+ and 25% mut- on log rank analysis p=0.099. Conclusions: This is the first report that MPM-EGFR mutations are activating mutations and responsive to EGFR-TKI-therapy. The mut+ subset has a “relative” improved outcome compared to wild type, but still developed progressive disease. TKIs may be a promising therapy in mut+ MPMs patients. Further elucidation of other molecular and pathway perturbations in this disease is necessary, as well as, validation of these results in a larger cohort. No significant financial relationships to disclose.
Treatment of cancer patients with ex vivo anti-CD3-activated killer cells and interleukin-2.
Authors: B D Curti, D L Longo, A C Ochoa, K C Conlon, J W Smith, W G Alvord, S P Creekmore, R G Fenton, B L Gause, J Holmlund
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study describes the physiologic and biologic effects resulting from the adoptive transfer of ex vivo anti-CD3-stimulated T-killer cells (T-AK) to patients with advanced cancer in combination with interleukin-2 (IL-2). METHODS Autologous peripheral-blood mononuclear cells were obtained by leukapheresis and stimulated ex vivo with anti-CD3. The stimulated cells were reinfused at one of three dose levels on the next day (5 x 10(9), 7.5 x 10(9), and 1 x 10(10)). Cell administration was followed by IL-2 given by bolus and continuous infusion (1.5 x 10(6) U/m2 and 3.0 x 10(6) U/m2, respectively) for 7 days, or continuous infusion alone (3.0 x 10(6) U/m2) for 14 days. RESULTS Pronounced leukocytosis and atypical lymphocytosis were observed with individual values as high as 80,000 and 50,000 cells/microL, respectively. The other major clinical sequelae included a marked lactic acidosis with bicarbonate levels as low as 4.0 mmol/L in some patients, and prolongation of the prothrombin time (PT) and partial thromboplastin time (PTT) due to decreases in clotting factors VII, IX, and X. Antithrombin III levels were also reduced. Hypotension associated with increased serum nitrate and neopterin levels was observed. These toxicities were accompanied by increases in hepatocellular enzymes and creatinine previously described with IL-2. These events occurred at a time when the number of circulating T-AK cells reached their peak. The amount of bolus IL-2 correlated with increases in WBC count (P = .0311), atypical lymphocytes (P = .0241), PT (P = .0006), and PTT (P = .0122). CONCLUSION Substantial in vivo expansion of activated T lymphocytes was induced by a protocol combining ex vivo activation of peripheral-blood cells with anti-CD3 antibody followed by adoptive transfer and IL-2 administration. The synchronous expansion of these T cells superimposed on diminished liver and kidney function from IL-2 can cause profound but reversible metabolic changes.
Ectopic Expression of Guanylyl Cyclase C in CD34<sup>+</sup> Progenitor Cells in Peripheral Blood
Authors: Tracy A. Fava, Rodwige Desnoyers, Stephanie Schulz, Jason Park, David Weinberg, Edith Mitchell, Scott A. Waldman
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To examine the utility of guanylyl cyclase C (GC-C)–specific nested reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating tumor cells in patients with colorectal cancer. PATIENTS AND METHODS: Peripheral-blood mononuclear cells from 24 patients with Dukes’ stage D colorectal cancer were analyzed by GC-C-specific nested RT-PCR using 1 μg of total RNA. Peripheral-blood mononuclear cells from 20 healthy volunteers served as controls. Additionally, peripheral-blood CD34 + progenitor cells were assayed for the expression of both GC-C and other epithelial cell–specific markers. RESULTS: GC-C mRNA was detected in blood mononuclear cells from all 24 patients with colorectal cancer and all healthy volunteers. These unexpected positive results reflected low-level ectopic transcription of GC-C in CD34 + progenitor cells. Moreover, CD34 + progenitor cells expressed other epithelial cell–specific markers, including prostate-specific antigen, prostate-specific membrane antigen, carcinoembryonic antigen, CK-19, CK-20, mucin 1, and GA733.2. Limiting the quantity of mononuclear cell total RNA analyzed to ≤ 0.8 μg eliminated detection of GC-C and other tissue-specific transcripts in blood of healthy volunteers. However, under the same conditions, GC-C mRNA was detected in mononuclear cells from all 24 patients with metastatic colorectal cancer. Using 0.5 μg of total RNA and GC-C–specific primers, nested RT-PCR detected a single human colon carcinoma cell (approximately 20 to 200 GC-C transcripts/cell) in 10 6 to 10 7 mononuclear blood cells. CONCLUSION: These data suggest that GC-C may be useful for detecting circulating colorectal cancer cells. They also demonstrate that CD34 + cells are a source of ectopically expressed epithelial cell–specific markers and that CD34 + cells may contribute to the high false-positive rate generally observed when those markers are used to detect rare circulating metastatic cancer cells by RT-PCR.
Abstract 3346: The ketone body β-hydroxybutyrate increases radiosensitivity in glioma cell lines in vitro
Authors: Alex P. Rossi, Eric C. Woolf, Kenneth S. Brooks, Marshall J. Fairres, Adrienne C. Scheck
Journal: Cancer Research (2015)

Abstract Glioblastoma (GB) is the most common and aggressive primary malignant brain tumor. Despite aggressive treatment, including maximum surgical resection followed by both chemotherapy and radiotherapy, median survival for patients remains at approximately 1.5 years after diagnosis. Recent preclinical studies examining the potential of the ketogenic diet (KD) as an adjuvant therapy for the treatment of malignant gliomas demonstrated that animals fed a KD and treated with chemotherapy or radiation survived significantly longer than those treated with chemotherapy or radiation and fed a standard diet. One of the key results of the KD is an increase in the blood level of the ketone body β-hydroxybutyrate (BHB). To more fully examine the mechanism through which the KD potentiates radiation, we examined the potential of BHB to increase radiosensitivity in mouse glioma cells in vitro. Plating cells in 10mM BHB followed by treatment for 2 weeks following radiation prevented colony formation in both the control and the radiation groups. We therefore assessed the effect of pretreatment with 5mM or 10mM BHB alone prior to radiation with 4 Gy. A statistically significant change in survival was observed when cultures were pre-treated with 10mM BHB for 24 hours prior to irradiation but not with 5mM BHB. However, significant changes in clonogenic survival were observed with a dose of 5mM BHB when cells were treated for 7 days post irradiation, starting 24 hours after irradiation. The effect of BHB on cell growth was then assessed using live cell counts. Both 5mM and 10mM BHB were effective in significantly reducing the cell number by 192 hours post plating. Growth was similarly affected by 10mM BHB or 2 Gy of radiation alone; however, when 10mM BHB was added to 2 Gy of radiation there was a very strong potentiating effect. These data suggest that BHB is an effective radiosensitizer for mouse glioma cells when used alone. In addition, they provide evidence that the extended survival seen in our in vivo mouse model of glioma when radiation is used in addition to the ketogenic diet may be modulated, to a large extent, by blood ketone levels. Whether this is due to differences in radiation-induced DNA damage, DNA repair or changes in the growth rate of the tumor cells is currently under investigation. Citation Format: Alex P. Rossi, Eric C. Woolf, Kenneth S. Brooks, Marshall J. Fairres, Adrienne C. Scheck. The ketone body β-hydroxybutyrate increases radiosensitivity in glioma cell lines in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3346. doi:10.1158/1538-7445.AM2015-3346
Third-generation drugs in the chemoradiation of stage III non-small cell lung cancer (NSCLC): A meta-analysis of efficacy and toxicity parameters
Authors: A. Aydiner, G. Can
Journal: Journal of Clinical Oncology (2009)

7536 Background: The role of third generation drugs (paclitaxel, docetaxel, gemcitabine and vinorelbine) in the chemoradiotherapy to maximize survival and decrease toxicity in NSCLC is unclear. We performed a meta-analysis of published randomized controlled trials (RCT) comparing third generation drugs. Methods: We searched MEDLINE, EMBASE, CENTRAL, proceedings of ASCO and other Cancer Congresses to December 08 for RCTs comparing chemoradiation treatment (CRT) including any type of third generation drugs in stage III NSCLC patients who had not been treated surgically. Standard meta-analysis techniques, using random effects model, were used to compare study arms with regards to treatment response, survival and toxicity data. For treatment response odds ratio (OR), to reach complete response and overall response were calculated. For survival data, hazard ratios (HR) and confidence intervals (CI) of individual studies were calculated based on survival curves-published in the manuscript (Parmar MKB, 1998). Basically two types of comparisons were performed: (1) subgroups defined by the type of CRTs, (2) subgroups defined by the type of drugs administered. Results: We found 18 RCTs including 2725 patients. Concurrent CRT was superior to the pool of other types of CRT (overall survival [OAS] HR 0.76, 95%CI 0.6–0.96, p=0.021) and sequential CRT (OAS HR 0.59, 95%CI 0.39–0.88, p=0.01). CRT with paclitaxel was superior to CRT without paclitaxel or with another type of third generation drug with regard to complete response (OR 1.93, 95%CI 1.02–3.67, p=0.044), with no significant difference in OAS (HR 0.94, 95%CI 0.56–1.57, p=0.799). CRT with paclitaxel was less toxic to CRTs without paclitaxel or with another type of third generation drug with regard to the incidence of grade III and IV anemia (OR 0.1, 95%CI 0.03–0.36, p&lt;0.001) and febrile neutropenia (OR 0.22, 95%CI 0.1–0.49, p&lt;0.001). Conclusions: Paclitaxel has less haematologic toxicity when compared with the other drugs without any significant survival difference. No significant financial relationships to disclose.
Comparison of three different methods for the detection of human papillomavirus infected in cervical lesions
Authors: W. Ahn, J. Shin, D. Park, S. Lee, L. Wen, K. Kim, Y. Kim
Journal: Journal of Clinical Oncology (2009)

e22166 Background: Several techniques are in use for HPV DNA detection: Hybrid Capture II R (HCII R ) assay, PCR-based DNA microarray and Luminex-based assay. This study was aimed to examine the performances of three validated HPV assays. We compared the concordance between the three methods for detecting HPV in cervical specimen. Methods: Cervical samples of 189 Korean women (21∼77 ages, average 41.2 age) were tested for HPV detection in this study. We examined the performances of three validated HPV assays according to each method's instructions : 1) Hybrid Capture II R (HCII R ) assay (HCII R ; Digene Corporation, USA) was used to test for detection of 18 types of HPV (high-risk types: HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and low-risk types types: HPV 6, 11, 42, 43, 44). 2) HPV DNA Chip, PCR-based DNA microarray system (MyGene Co., Seoul, South Korea) was used to test for genotyping of 24 types of HPV: 15 types of high-risk types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and 9 types of low-risk types (HPV6, 11, 34, 40, 42, 43, 44, 54, 70). 3) Luminex-based HPV test (YBT, Seoul, Korea) was performed for genotyping 26 types of HPV including 15 high-risk HPV types (HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68) and 11 low-risk types (HPV-6, 11, 34, 40, 42, 43, 44, 54, 55, 67, 70). Results: We compared HPV detection results obtained by the HC II assay with those from the Luminex assay. 51 cases were discordant: 29 samples were HC II negative/Luminex positive and 22 samples were HCII positive/Luminex negative. We also compared HPV detection results obtained by the DNA chip assay with those from the Luminex assay. 37 cases were discordant: 5 samples were DNA chip negative/Luminex positive and 32 samples were DNA chip positive/Luminex negative. Conclusions: The distribution of the HPV detection results obtained for 91 samples using three different methods suggested that the results of DNA chip assay are more often discordant (17.9% instead of 5.1% for Luminex assay and 5.1% for the HC II assay). No significant financial relationships to disclose.
Abstract 67: Cardiac Arrest and Surgical Case Volume, Household Income and Availability of Trauma and Cardiac Surgery Are Associated with Higher Risk-Standardized Survival After Cardiac Arrest Among University Hospital Consortium Institutions in 2012
Authors: Michael C Kurz, John P Donnelly, Henry E Wang
Journal: Circulation (2014)

Objective: Wide variation exists in cardiac arrest survival. Historically cardiac arrest research has focused upon clinical pre-arrest and intra-arrest factors to explain this variation in outcomes. In-hospital post-arrest care is increasingly recognized as an important aspect of survival. We sought to identify hospital characteristics associated with improved cardiac arrest survival. Methods: We examined all participating hospitals in the University Hospital Consortium (UHC) clinical database with more than 25 adult cardiac arrests in 2012. Cases were identified using International Classification of Diseases, 9th Edition, code 427.5 (cardiac arrest) or 99.60 (CPR), excluding prisoners, pregnant patients, transfers, and hospice patients. We estimated hospital-specific risk-standardized survival rates (RSSRs) using hierarchical logistic regression, adjusting for individual risk of mortality. Institutions in the highest RSSR quartile were compared with those in the lowest three quartiles using Pearson chi-square tests of association. Results: UHC institutions admitted 3,686,296 patients in 2012, of which 33,700 patients experienced cardiac arrest. Overall survival was 42.3% (95% CI 41.8-42.9) with median RSSR of 42.7% (IQR 35.5-50.8). Hospitals in the highest quartile of RSSR had higher cardiac arrest volume (median 193 vs. 150, p-value 0.019), higher annual surgical operation volume (21,177 vs. 14,122, 0.007), cared for patients from catchment areas with higher household income ($60,753 vs. $56,424, 0.027), and were more likely to be a trauma (79% vs 59%, 0.024) or cardiac surgery center (91% vs 70%, 0.007). In addition, hospital size (477 vs 415 beds, 0.060) and teaching status (77% vs. 62%, 0.067) demonstrated a trend toward association with higher RSSR. Conclusion: Among hospitals in the UHC, those with higher cardiac arrest and surgical case volume, patient household income, and availability of trauma and cardiac surgery were associated with improved RSSR.
Population pharmacokinetic modeling for intravenous temsirolimus and sirolimus metabolite in subjects with various solid tumors
Authors: D. Sonnichsen, S. Liao, A. Berkenblit, J. Boni
Journal: Journal of Clinical Oncology (2009)

2522 Background: Temsirolimus (TEMSR) is an mTOR inhibitor approved for treatment of patients with advanced renal cell carcinoma, and under development for relapsed/refractory mantle cell lymphoma (MCL). In MCL, TEMSR showed a dose-related increase in median progression-free survival [4.8 vs. 3.4 mo] and objective response rate [22% vs 6%] for 175 mg x 3 wks then 75 or 25 mg weekly regimens (175/75-mg and 175/25-mg), respectively. We aim to characterize the population pharmacokinetic exposure, covariate influence, and differences afforded by these regimens. Methods: Nonlinear mixed-effects models of TEMSR and sirolimus (SIR; major active metabolite) blood concentrations were defined in healthy subjects and patients. Modeling for TEMSR employed a 4-compartment model with saturable distribution to red cells and peripheral tissue, and modeling for SIR utilized a linear 2- compartment model with factor for dose. Covariates included demographic factors, clinical labs, and disease condition. Following validation, simulations with variability were used to evaluate effects of covariates on exposure. Results: Final datasets comprised 1342 observations from 150 subjects (TEMSR) and 1648 observations from 279 subjects (SIR). In a typical patient (56-year-old male weighing 76.5 kg), disease affected TEMSR clearance (62.4 L/h in MCL, 92.1 L/h in breast cancer vs. 112 L/h for other subjects). Dose, single vs. multiple, and body weight affected SIR apparent clearance. Simulations for the 175/75-mg regimen indicate that significant covariates yield only modest differences on blood exposures. For MCL (175/75-mg regimen), TEMSR C max (week 3) was 2574 ng/mL and SIR C trough (week 6) was 10.7 ng/mL. AUC for the 75-mg maintenance arm was ∼2.3-fold (TEMSR) and ∼3.5-fold higher (SIR) than respective values of the 25-mg arm. Correlation of average AUC to clinical response was not apparent. Conclusions: No significant differential effects were observed for age, gender, race, or hepatic and renal laboratory measures. Covariates of disease, while significant, have only modest effects on the exposure profile. Higher clinical responses observed with the 175/75-mg regimen as compared with the 175/25-mg regimen may critically derive from differences in exposure. [Table: see text]