tbuckley/cabot-search huggingface dataset:
Markers associated with circulating endothelial cells (CEC) in advanced NSCLC: Prognostic value.
Authors: A. Blasco, S. Gallach, L. Garcia, E. Jantus, R. Sirera, E. Sanmartin, N. del Pozo, R. M. Bremnes, A. Berrocal, C. Camps
Journal: Journal of Clinical Oncology (2010)

e21003 Background: Angiogenesis is a crucial step for tumor development, growth and dissemination. It is related with the migration and proliferation of endothelial cells (ECs) and endothelial progenitor cells (EPCs). The detection of circulating ECs (CECs) represents a noninvasive strategy to monitor angiogenesis. CECs are a minute subset of peripheral blood cells, characterized by the expression of several surface markers like: CD146, CD31, Tie2 and CD34 (in the case of EPCs). The aim of the study was to quantify markers associated to CECs by RT-PCR and to correlate them with clinicopathological variables, response to treatment and prognosis in advanced NSCLC patients. Methods: 53 patients with advanced-NSCLC (IIIB-IV) treated with cisplatin and docetaxel were studied. Blood samples were collected before and after 3 cycles of chemotherapy in PAXgene Blood RNA Tubes and stored at -80°C until RNA isolation. mRNA was reverse transcribed and quantification of CD146, CD31, CD34 and Tie2 genes by RT-PCR was performed using TaqMan primers/probes. Relative expression was calculated by Pfaffl formulae, using GUSB as endogenous control. Differences were considered significant at p ≤ 0.05. Results: There was no correlation between the expression of the analyzed markers and clinicopathological variables. Compared to pre-treatment levels, post-treatment CD31 and Tie2 were significantly reduced after three courses of cisplatin/docetaxel (p < 0.0001 and p = 0.003, respectively). Considering only adenocarcinomas, we found that those patients with basal low CD146 expression had significant better progression-free (p = 0.024) and overall survival (p = 0.001). Conclusions: The study of CEC-associated markers in peripheral blood showed that these can possibly be used as biomarkers of prognosis and treatment response in advanced NSCLC. No significant financial relationships to disclose.
Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to Kras mutant NSCLC reveals Gab1 assisted survival pathway post oncogene knockdown
Authors: Srikar Raman, Dhananjay Suresh, Ajit Zambre, Kristen H. Taylor, Raghuraman Kannan
Journal: Journal of Thoracic Oncology (2016)
Equivocal results of HER2 fluorescent in situ hybridization (FISH) assessment in breast cancer: Diagnostic limitations and therapeutical implications.
Authors: Marcelo Rocha De Sousa Cruz, Adriana Regina G. Ribeiro, Fábio Nasser Santos, Isabela Werneck Cunha, Vladmir C. Lima
Journal: Journal of Clinical Oncology (2012)

e11058 Background: HER2/neu status is a well established prognostic and predictive factor for breast cancer (BC) patients. However, HER2 testing remains controversial because of technical issues, lack of consensus on cut point determinations and pathology interpretation. As a result, some patients present tumors with inconclusive or equivocal tests, making the indication of anti-HER2 therapy questionable. Methods: We evaluated the incidence of inconclusive and equivocal HER2 amplification by FISH after an equivocal HER2 immunohistochemical (IHC) result in a cohort of breast cancer patients treated at a cancer center. Equivocal IHC was defined as tumor cells showing 2+ membranous immunoreactivity out of a possible 3+. Inconclusive FISH was considered when probe signs were weak and did not allow proper evaluation. Equivocal FISH was defined according to ASCO/CAP recommendation. Patients’ clinical characteristics, treatments and outcomes were evaluated. Results: From 2006 to 2011 we analyzed BC tissue samples from 404 patients that underwent HER2 FISH assessment after equivocal IHC. Gene amplification was found in 28,7% (n=116) of samples; 65,5% (n=265) showed non-amplification results. Inconclusive (n=12) plus equivocal (n=11) FISH results were found in 5,7% (n=23) of patients. In the inconclusive/equivocal FISH cohort, 78% of evaluated tissue came from breast biopsy and 22% were extracted from metastatic sites. When HER2 amplification by FISH was reclassified according to the FDA criteria (HER2/CEP17 FISH ratio above 2.0), 45% of patients previously classified as equivocal became HER2 positive. None of equivocal HER2 FISH patients received anti-HER2 therapy. Conclusions: The incidence of BC patients with equivocal HER2 FISH at our institution is similar to other large series, reflecting our adequate quality assurance methods. Anti-HER2 therapy is the backbone for HER2-positive BC patients irrespective of hormone receptor status. Further analyses using different techniques for HER2 expression and amplification status assessment are urged in order to better select patients for appropriate therapy.
Pulmonary Effects of the Cocoanut Grove Fire
Authors: Helen S. Pittman, Richard Schatzki
Journal: New England Journal of Medicine (1949)

THE Cocoanut Grove fire took place on November 28, 1942. In a previous report1 we described the initial pulmonary complications in the group of 39 patients admitted to the Massachusetts General Hospital. Finland2 has already published the follow-up findings in his series of 92 patients discharged from the Boston City Hospital. He found that symptoms of respiratory disease at four, nine and twenty-six months after the fire were neither frequent nor severe. Persistent cough was the most common symptom at each time period. An occasional patient later began to raise copious amounts of mucopurulent sputum (12 of the 38 patients . . .
Immunologic impact of anti-CTLA-4 therapy
Authors: P. Sharma, D. Tsavachidou, A. Kamat, D. Ng Tang, H. Chen, T. Fu, P. Troncoso, J. Wolchok, C. J. Logothetis, J. P. Allison
Journal: Journal of Clinical Oncology (2009)

3019 Background: Blockade of the T-cell inhibitory molecule known as cytotoxic T lymphocyte antigen-4 (CTLA-4) results in antitumor responses. To date, trials have been conducted with over 4,000 patients with various malignancies in the metastatic disease setting, which allow for correlation of therapy with clinical outcome but do not provide analyses of relevant biomarkers in the systemic circulation that reflect changes within the tumor microenvironment. Approximately 10% of treated patients respond to therapy. Why some patients respond while others do not remains unknown. The identification of intermediate biomarkers are essential for us to understand whether anti-CTLA-4 antibody has “hit its target” to affect human immune responses and whether these identified immune responses can serve as predictive markers of clinical outcomes. Methods: We conducted a presurgical clinical trial with anti-CTLA-4 antibody. Patients with localized bladder cancer (N=10) were given two doses of antibody prior to undergoing surgery. Immunological analyses were conducted on patients’ tissues and blood samples. Results: Expression of the inducible costimulator (ICOS) molecule was increased on CD4 T cells within tumor tissues and systemic circulation. ICOS-expressing T-cells have not previously been reported to have a role in anti-tumor responses. We showed that CD4 + ICOS hi T cells produced IFNγ and could recognize the NY-ESO-1 tumor antigen. Pre- and post-therapy CD4 T cells were analyzed by reverse-phase protein array and microRNA array, which led to the identification of signaling pathways and regulatory mechanisms that play a role in enhanced T-cell function. Furthermore, murine models confirmed our initial findings and implied a role for ICOS-expressing T-cells in antitumor responses. Finally, we extended our findings to the metastatic disease setting of melanoma patients (N=14) and our preliminary data indicate an improved survival for anti-CTLA-4 treated patients who have a sustained increase in ICOS-expressing CD4 T cells. Conclusions: Our presurgical clinical trial allowed for the correlation of data from tumor tissues with data from peripheral blood, thus identifying ICOS-expressing T-cells as a relevant biomarker that can be used to monitor patients who receive anti-CTLA-4 therapy. [Table: see text]
Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the Lung
Authors: Luisella Righi, Simona Vatrano, Federica Di Nicolantonio, Federica Massa, Giulio Rossi, Alberto Cavazza, Marco Volante, Arianna Votta, Stefania Izzo, Marco Lo Iacono, Francesco Ardissone, Massimo Di Maio, Silvia Novello, Giorgio Vittorio Scagliotti, Mauro Papotti
Journal: Journal of Thoracic Oncology (2016)
No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial
Authors: Henrik Wagner, Michael Alvarsson, Buster Mannheimer, Marie Degerblad, Claes-Göran Östenson
Journal: Diabetes Care (2016)

OBJECTIVE There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes. RESEARCH DESIGN AND METHODS Subjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0–12 min) and second-phase (12–120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control. RESULTS A total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43–82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results. CONCLUSIONS This study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.
Anti-tumor activity of mTOR inhibitor temsirolimus for relapsed mantle cell lymphoma: A phase II trial in the North Central Cancer Treatment Group
Authors: S. M. Ansell, S. M. Geyer, P. J. Kurtin, D. J. Inwards, S. H. Kaufmann, P. J. Flynn, R. F. Morton, R. F. Luyun, S. R. Dakhil, H. Gross, T. E. Witzig
Journal: Journal of Clinical Oncology (2006)

7532 Background: Mantle Cell Lymphoma (MCL) is characterized by t(11;14) resulting in over expression of cyclin D1, a member of the phosphatidylinosital 3-kinase (PI3K) pathway. Temsirolimus is a novel inhibitor of the mammalian target of rapamycin (mTOR) kinase. Previous studies with weekly temsirolimus at a dose of 250mg demonstrated a 38% overall response rate in 35 patients (JCO 23 (23); 5347–56, 2005). Thrombocytopenia was frequently observed and was dose limiting. The current study tested whether low-doses (25mg) of temsirolimus could produce a similar overall response rate (ORR) with less toxicity. Methods: Eligible patients had biopsy proven cyclin D1 positive MCL and had relapsed or were refractory to therapy. Patients received temsirolimus 25mg IV weekly as a single agent. Patients were restaged after 1 cycle (4 doses), after 3 cycles, and every 3 cycles thereafter. Patients with a tumor response after 6 cycles were eligible to continue drug for a total of 12 or 2 cycles after complete remission (CR) and then were observed without maintenance. The goal was to achieve an ORR of at least 20%. Results: Twenty-nine patients were enrolled between March and August 2005. Twenty-two patients have completed therapy. One patient with a major protocol violation on cycle-1 and one ineligible patient were excluded, leaving 27 evaluable patients. The ORR was 41% (11/27), with 1 CR and 10 PRs. Early evaluation of TTP showed a median of 5.5 months (95% CI: 3.3–7.7) and the duration of response for the 11 responders was 6.2 months (95% CI: 3.6 to not yet reached). These results compare favorably with the 6.5 months and 6.9 months, respectively, found in previous trials that used 250 mg. The median dose delivered per month was 80 mg (range, 10–100 mg). Sixteen (59%) of patients required a dose reduction. The median time on treatment was 4.4 months (95% CI, 3.3–7.7). The incidence of grade 3 and 4 thrombocytopenia was 12% and 0%, respectively. One patient experienced grade 5 infection without neutropenia, which was considered unrelated to CCI-779. Conclusions: Single agent CCI-779 at a dose of 25mg has anti-tumor activity in relapsed MCL similar to the 250 mg dose. This study indicates that combinations of temsirolimus with other agents should be feasible. [Table: see text]
Diptheria toxin-interleukin 3 fusion protein therapy of patients with elderly or relapsed/refractory acute myeloid leukemia (AML)
Authors: A. E. Frankel, M. A. Weir, P. D. Hall, D. E. Hogge, D. A. Rizzieri
Journal: Journal of Clinical Oncology (2006)

6569 Background: To target myleoid leukemic stem cells in relapsed/refractory patients, we produced a recombinant protein composed of the catalytic and translocation domains of diphtheria toxin (DT 388 ) fused to human interleukin 3 (IL3). DT 388 IL3 binds to IL3 receptors on leukemic progenitors; the toxin is internalized and enzymatically inactivates protein synthesis leading to programmed cell death. We prepared a clinical batch of DT 388 IL3 and obtained FDA approval for a phase I study. Patients and Methods: Relapsed/refractory or elderly (≥70 years) AML patients with normal organ function and low anti-DT antibody titers were consented and given 15 minute infusions of DT 388 IL3 on a M-W-F for two weeks schedule. Premedication was hydrocortisone, acetaminophen, and diphenhydramine. Inter-patient dose escalation was done. Five patients at 4 ug/kg, 6 patients at 5.32 ug/kg, and 2 patients at 7.07 ug/kg received all 6 planned doses. Results: Eighteen patients have been treated as of 1/06. Median age was 58 years (25–81). There were 9 males and 9 females. One patient had de novo AML; 7 patients were in second relapse; 6 patients were in third relapse and 4 patients had refractory AML. One patient each received an autologous stem cell transplant (SCT), and an allogeneic SCT. Cytogenetics were unfavorable in 3, intermediate in 10 and not done in 5 patients. One patient each had MDS-related AML and treatment-related AML. Drug-related side effects were mild and transient including grade 3 fever, grade 2 hypotension, chills and hypoalbuminemia. Responses seen to date have been transient including a reduction in bone marrow blast index (% cellularity × fraction blasts) of pretreatment 40%, 70%, 36% and 40% converting to 8%, 4%, 4% and 4% on day 15. Conclusions: The preliminary data suggests mild toxicity with biological activity. Dose escalation is planned as per protocol. No significant financial relationships to disclose.
Can Oncotype DX recurrence score (RS) be used in luminal A and luminal B breast cancer patients (pts) to predict the likely benefit of chemotherapy? A retrospective study in the Spanish population.
Authors: Laura García-Estevez, Ana C Contreras, Isabel Calvo, Maria Fernandez Abad, Juan J de la Cruz, Sofia Perea, Ana Suárez, Fernando López-Ríos, Manuel Hidalgo
Journal: Journal of Clinical Oncology (2012)

e11006 Background: The 2011 St Gallen guidelines recommend the use of Ki67 as a surrogate marker for luminal A and Luminal B breast cancer subtypes. Pts with luminal B subtypes should be considered for adjuvant chemotherapy. The guidelines also recognize the Oncotype DX RS as a predictor of chemotherapy benefit. The aim of this study is to assess the distribution of the RS in luminal A and luminal B breast cancer subtypes as defined by Ki67. Methods: Data from 91 pts with invasive breast cancer for which Oncotype DX results and pathology data were available. Pathological assessment was evaluated by the same pathologist. Estrogen (ER) and progesterone (PR) receptor was assessed by immunostaining (cut-off 10% nuclear staining). Ki67 was assessed by IHC [high (≥14%) and low (&lt; 14%)]. Grading was performed by using Nottingham grading system. Results: Median age: 50 years (range: 35-78); premenopausal status: 49 pts (53.8%). Median tumor size: 1.5 cm (0, 3-6); Median of Ki 67 index: 15. 5 (range: 3-63); Median ER: 93 (35-100) and PR: 85(0-100). Sixty nine pts (75.8%) had negative-lymph nodes. RS was low in 56 (61. 5%) cases, intermediate in 24 (26. 4%), and high in 11 (12. 1%). The median RS was 16 (range 3-55). Forty six (51%) tumors were classified as luminal B (according to high Ki 67) and 38 (41.7%) as Luminal A. In the Luminal B group RS was low in 28 (61%) pts, intermediate in 10 (22%) and high in 8 (17%) while in the Luminal A group 23 (61%) had low RS; 13 (34%) intermediate and 2 (5%) high RS. RS changed the first treatment recommendation in 23 (50%) cases of Luminal B subtype vs. 10 (26%) cases in Luminal A subtype (p=0.013). Conclusions: Although based in a small case series, the results show that a substantial number (61%) pts with Luminal B breast cancer subtype had a low RS, therefore preserving them from adjuvant chemotherapy treatment. In addition, 5% of patients with Luminal A breast cancer had a high RS and thereby likely to benefit from chemotherapy. The wide range of RS in both Luminal B and Luminal A breast cancer subtypes confirm the important role of Oncotype DX in treatment decision- making.
Safety Profile of Bortezomib Impacts Survival in Light Chain Amyloidosis
Authors: Zoé Van de Wyngaert, Greg Vanoutryve, Guillemette Fouquet, Stéphanie Guidez, Charles Herbaux, Helene Demarquette, Loic Renaud, Louis Terriou, Marie Pierre Noel, Marie Odile Petillon, Bénédicte Hivert, Matthieu Wemeau, David Launay, Nicolas Lamblin, Eric Hachulla, Thierry Facon, Xavier Leleu
Journal: Blood (2014)
Improving the efficiency and effectiveness of clinical research regulatory review processes: Lessons from the Six Sigma Body of Knowledge
Authors: D. C. Stahl, C. J. Song, R. A. Figlin
Journal: Journal of Clinical Oncology (2009)

e17554 Background: The duration and complexity of regulatory review processes are increasingly associated with the slow pace and high cost of clinical trials. To evaluate and minimize the impact of these factors, City of Hope (COH), a NCI-designated Comprehensive Cancer Center, developed a strategic initiative to improve the efficiency and effectiveness of its clinical research review processes. The ongoing initiative is supported by Six Sigma-based techniques for problem identification and process optimization that have been successfully applied in other industries. Methods: The Six Sigma process improvement methodology known as DMAIC (Define, Measure, Analyze, Improve, and Control) was applied to five different clinical trial submission types (new study submissions, amendments, continuations, internal adverse events, external adverse events) reviewed by the COH Institutional Review Board (IRB), Cancer Protocol Review and Monitoring Committee (CPRMC), and Data and Safety Monitoring Board (DSMB). A consistent set of metrics and expectations were created for each review process to evaluate pre-review queue times, review process durations, submissions returned for corrections, and submissions returned with conditional approvals. Results: Over 7,900 submissions received during a 15 month period were evaluated quarterly to identify opportunities for improvement and the effects of previously implemented solutions. Multiple root causes for submission defects and delays were identified, including: (1) staffing and training deficiencies, (2) suboptimal workload distribution, (3) unclear policies and processes, (4) submission standardization opportunities, and (5) workflow automation and other information technology opportunities. Ongoing remediation efforts have yielded substantial improvements. Conclusions: Although Six Sigma process improvement techniques were originally developed for manufacturing applications, they can be applied in a clinical research setting to improve regulatory review processes. The methodology was most effectively introduced incrementally via application to specific problems rather than a traditional top-down implementation. Support provided by NCI P30 CA33572. No significant financial relationships to disclose.
Bowel dysfunction-related needs assessment in colorectal cancer survivors.
Authors: Virginia Sun, David D. Smith, Lily L. Lai, Carrie Chong, Marcia Grant
Journal: Journal of Clinical Oncology (2015)

715 Background: Bowel dysfunction is common following treatment for colorectal cancer (CRC), with substantial impact on survivors’ quality of life (QOL). There are few evidence-based protocols to support positive adjustments to bowel function changes. The purpose of this study was to assess CRC survivors’ bowel dysfunction related information needs following surgery. Methods: CRC survivors who were within 1-3 months post-resection (n=37) completed questionnaires on bowel function, fecal incontinence specific QOL, and bowel dysfunction needs. Six randomly selected participants were interviewed to further explore unmet needs. Quantitative data were summarized using descriptive statistics for all subscales and individual items. Qualitative data were interpreted through content analysis methods. Results: The mean number of daily bowel movements was 5.5 (range 2-10). Many survivors reported incomplete bowel evacuation (66%) and increased urgency/frequency (75%). More problems were reported on the impact of diet on function (X=12, SD=3.2) and urgency/soilage (X=13.5, SD=4.5). Lower QOL scores were observed for the impact of dysfunction on lifestyle (X=2.7, SD=1.0) and coping behavior (X=2.7, SD=0.9). Survivors reported unmet information needs for the following: 1) managing bowel dysfunction in an emergency; 2) type of foods that are helpful or not helpful with bowel function; and 3) talking to others who share the same experience. The majority (75%) desired to participate in a rehabilitation program, and preferred to receive content before treatments or discharge from hospital following surgery. Conclusions: CRC survivors report unmet bowel dysfunction related needs, and desire more information and strategies to help with managing changes to their bowel patterns. Evidence-based interventions that are timely and personalized are needed to support long-term, positive adjustments following treatment.