tbuckley/cabot-search huggingface dataset:
Characteristics and outcomes of non-small cell lung cancer (NSCLC) patients (pts) carrying epidermal growth factor receptor (EGFR) mutations who progress after initial erlotinib (E) response
Authors: A. F. Cardona Zorrilla, T. Moran, N. Reguart, R. Porta, C. Queralt, F. Cardenal, E. Carrasco-Chaumel, B. Massuti, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2009)

8064 Background: Most NSCLC pts with EGFR mutations respond to E; however, resistance to this tyrosine kinase inhibitor (TKI) can be acquired. The resistant T790M mutation has been identified in 50% of progressing pts. We assessed pt characteristics and outcome to additional treatment in 55 EGFR mutated pts after progression to E. Results: Pts mean age was 59±12.5 years; 65% females; 94% never-smokers; 54 adenocarcinoma. 35 pts (63%) were PS ≤2; main metastasis sites were lung (39/71%), bone (21/38%) and liver (10/18%). 22 and 25 pts received E as first- or second-line treatment, respectively. Mutations in tumor were: 65% DelE19 (Δ746–750), 35% L858R mutation; with 31% and 20% serum detection respectively. For the complete cohort, overall response rate (ORR) with E was 78% and time to progression (TTP) was 11.2 months (m) (range, 4–29 m). After progressing to E, 8 pts were re-biopsied, of whom 2 had the T790M mutation; 9 had the T790M mutation in serum (16%). 49% received platinum-based chemotherapy, 14.5% E plus another agent (bevacizumab, fulvestrant, vorinostat), 25.5% single-agent chemotherapy and 11% a non-reversible TKI (HKI-272). ORR for first-line post-E treatments was 33% (CR 1/PR 9) and median TTP was 8 m (range, 4.1–11.8 m). There were no differences in TTP according to gender (p = 0.10), type of mutation (p = 0.63) or severity of skin toxicity (p = 0.16). 11 pts received a second-line post-E treatment with E plus chemotherapy, achieving an ORR of 40%. Median survival was 27 m for all 55 pts (range, 22.9–31.1 m). Conclusions: Pts with EGFR mutations present a biologically different disease which continued to be sensitive to other treatments after progressing to E. No significant financial relationships to disclose.
High dose epirubicin in refractory or relapsed non-seminomatous testicular cancer: A phase II study
Authors: A Harstrick, H J Schmoll, H Wilke, C Schöber, M Stahl, C K Wömpner, C Bokemeyer, G Dölken, K Burk, H Poliwoda
Journal: Annals of Oncology (1990)
Late-breaking abstract: Allergic sensitization to common airborne allergens among adults in urban and rural northern Vietnam: Results from a population survey
Authors: Lâm Hoàng Thi, Tuong Nguyen Van, Bo Lundbäck, Eva Rönmark
Journal: European Respiratory Journal (2011)

Background: The profile of allergic sensitization and it's association with allergic diseases varies between different areas of the world.

Objective: To study allergic sensitization and the association with asthma and allergic rhinitis in the northern part of Vietnam.

Methods: A sample of 1500 subjects, aged 21–70 years were randomly selected from all 5782 responders of a questionnaire survey performed in 2007-2008. The subjects underwent a structured interview, a skin prick test with 10 common local indoor and outdoor allergens. Further, lung function and methacholine test were performed. The questionnaire used was the GA2LEN study questionnaire which is mainly based on the ECRHS and the ARIA questionnaire with additional questions from Swedish OLIN questionnaire.

Results: Of 533 subjects attending the skin prick tests, 180 subjects (33.8%) had positive SPTs to at least one allergen. Mite and cockroach were the most common sensitizers in northern Vietnam (26.1%; 13.2%) and they strongly associated with allergic rhinitis. Young age, men sex and occupational exposure to gas, dust and fumes were risk factors for sensitization, particularly to mites and cockroach. Airway hyper-reactivity (AHR) to methacholine at doses ≤2 mg/ml was statically significant associated to multi-sensitization.

Conclusions: The prevalence of allergic sensitization was 33.8% and was strongly associated with allergic rhinitis. Young subjects were at higher risk of becoming sensitized to mites, while male sex was a risk factor for sensitization to cockroach. Storage mite, house dust mite and cockroach were the most common sensitizers in both rural and urban northern Vietnam.
Survival benefit in bevacizumab-based therapy in sickle cell trait patients diagnosed with renal medullary carcinoma
Authors: E. D. Johnson, N. N. Tannir, K. A. Olejeme, C. J. Logothetis, E. Jonasch
Journal: Journal of Clinical Oncology (2009)

e16096 Background: Renal medullary carcinoma (RMC) is an epithelial malignant tumor arising from collecting duct epithelium. The tumor is almost exclusive to young black patients with the sickle cell hemoglobinopathies, primarily sickle cell trait. This is a rare and highly aggressive tumor that is shown to be most resistant to chemotherapy. In an effort to evaluate treatment outcomes, we retrospectively examined those patients diagnosed with RMC who were treated with and without bevacizumab based regimens. Methods: We reviewed the genitourinary medical oncology database at M. D. Anderson Cancer Center for patient diagnosed between 1999–2008 with histology proven RMC. Vital statistics of birth and death dates were noted. In addition, detailed chemotherapy regimen as well as medical and radiological data were also obtained. Results: All patients had metastatic disease (stage IV) to at least one distant site at presentation. Distant sites included bone, liver or lungs. A sample of five black males 5/9 (53%) were treated with therapy that included a 2 or 3 drug combinations of Adriamycin, Taxol, Gemzar, cisplatin, or Gleevac. Median survival was 12.7 months (3.2–22.2) while median age was 31 year (28–59). Only 4/9 (47%) patients received bevacizumab based therapy in a 2 or 3 drug combinations with Gemzar, Xeloda, cisplatin, or Taxol. In this group, 50% were females, median age of 36 years (33–39) and median survival of 18.5 months (15.5–22.8). Conclusions: Sickle cell trait was confirmed for all in this group diagnosed with RMC. 8/9 of these patients were black and 1/9 South-Asian. The group that received bevacizumab based therapy had a median survival of 5.8 months longer. Future studies, including genetic studies on the tumor types are essential to determining the SNP profiles of renal cell carcinoma in black patients. Furthermore, a prospective multicenter trial should be developed to evaluate the efficacy of bevacizumab based regimens in renal medullary carcinoma in this population. No significant financial relationships to disclose.
PCNA as potential marker for cervix neoplastic and preneoplastic lesions
Authors: H. Maldonado, C. Perea-Montoya, S. Cano, J. De la Cruz, A. Benitez-Galeana, E. Ruiz-Garcia, J. Silva, J. Torres- Lopez, H. Astudillo-de la Vega
Journal: Journal of Clinical Oncology (2008)

16581 Background: Proliferation Cellular Nuclear Antigen (PCNA), overexpression and correlation to the grade of squamous cell cervical carcinoma (SCC) and its precursor lesions has been demonstrated by subjective evaluation. In this study we attempted to objectively analyze PCNA expression by applying tissue microarrays (TMA) and computer-assisted image analysis (CIA) techniques. To evaluate PCNA expression as a potential marker of dysplasia and SCC by IHQ, using TMA and CIA. Methods: PCNA expression was contrasted between SCC (6 cases), low grade intraepithelial lesions (LSIL) (6 cases), high grade intraepithelial lesions (HSIL) (6 cases), and healthy controls (6 cases). Histopathological diagnosis was confirmed. TMA was prepared with two cores for each sample (Advanced Tissue Arrayer, Chemicon, USA). IHQ for PCNA was performed by the peroxidase-antiperoxidase method (anti-PCNA, FL-126, Santa Cruz Biotechnology). Images were captured and analyzed with a CIA system (Olympus, EUA). For each core with a nuclear positive reaction numerical data were obtained for: area of the epithelium, number and area of positive and negative nuclei, and intensity of the reaccion in each nuclei (RGB intensity). Results: Measurements form both cores of each sample were similar in all cases. PCNA expression was seen in 5 of 6 cases of SCC, LSIL and HSIL, and in 6 of 6 control samples. Positivity in controls was confined to the basal epithelium, while LSIL and HSIL showed positive nuclei in the superficial and/or intermedium epithelium and SCC cases had diffuse positivity. A statistically significant increase of positive nuclei was observed in HSIL, but no differences in percentage. At the same time celullar density showed a significant correlation with the grade of the lesion (r=0.711, p<0.05). No differences were observed in the mean RGB intensity. Conclusions: There are changes in the pattern of expression of PCNA in SCC, HSIL, LSIL and normal cervix. Overexpression of PCNA in high grade lesions though statistically significant appears at least in part to be related to celular density. This results differ form previously informed studies in which data are categorical and in which celullar density of the lesions has not been considered. No significant financial relationships to disclose.
Clinical significance of tumoral cells detection by immunocytochemistry in bone marrow (BM) of metastatic breast cancer (MBC) patients
Authors: A. Vincent-Salomon, J. Y. Pierga, V. Girre, V. Laurence, H. Magdelenat, M. Caly, X. Sastre-Garau, P. Pouillart, P. de Cremoux, J. P. Thiery
Journal: Journal of Clinical Oncology (2005)

702 Background: Level of circulating Tumoral Cells (TC) have been recently shown to predict survival in MBC (Cristofanilli, M, NEJM, 2004, 351, 781). We have previously shown that the detection of TC in BM defined moreaccurately the outcome than TC in in the Peripheral Blood (PB) in non metastatic patients (Pierga, JY, Clin Cancer Res, 2004). Material and Methods: We have retrospectively analysed prognostic value of immunocytochemical (ICC) detection of TC in BM of 122 MBC patients. Cytospun Ficoll fractions of BM aspirations were obtained from 11/98 to 12/01 before treatment with chemotherapy. The pancytokeratin monoclonal antibody A45-B/B3 was used. Immunostained cells were detected by a manual analysis and an automated cellular imaging system (ACIS). 3.106 mononuclear cells were screened per patient. Results: Median follow-up was 38 months. Median overall survival was 22 months. Median age was 53 years (34–78). Eighty percent of the patients (97) received first line chemotherapy for MBC. TC were detected in BM of 12 patients (10%) by conventional cytology and in 86 pts (70.5%) by ICC. Median number of TC was 9 (1–3000). Incidence of TC was non significantly higher in lobular (19 pts) compared to ductal carcinomas (84% vs 66%, p=0.1). TC detection in BM was highly associated with clinical or radiological bone metastasis (p=0.0001). Adverse prognostic factors for overall survival were hormonal receptor negativity (p=0.005) and more than one line of chemotherapy (p=0.005). Presence of TC in BM was not associated with a poorer survival rate (median 20 vs 28 months, logrank test, p= 0.39), neither was presence of TC in cluster. Conclusion: We did not find a prognostic value of TC detection by ICC in BM of stage IV breast cancer patients. This could be related to bone metastasis contamination. Circulating TC could be a more efficient tool to evaluate prognostic and monitor tumor response at this stage of the disease. No significant financial relationships to disclose.
P-093 HER2 protein over-expression in early stage gastric cancer: correlation with clinicopathological features and survival
Authors: T. Yavuzsen, N. Demir, U. Oflazoglu, N. Kazaz, I. Somali, T. Unek, O. Sagol, S. Sarioglu, K. Atila, I. Oztop
Journal: Annals of Oncology (2015)
Messenger RNA vaccination in NSCLC: Findings from a phase I/IIa clinical trial.
Authors: M. Sebastian, L. von Boehmer, A. Zippelius, F. Mayer, M. Reck, D. Atanackovic, M. Thomas, F. Schneller, J. Stoehlmacher, E. Goekkurt, H. Bernhard, A. Groeschel, R. Bals, S. Schmidt, B. Scheel, S. D. Koch, T. Lander, K. Kallen, A. Knuth
Journal: Journal of Clinical Oncology (2011)

2584 Background: CV9201 is a therapeutic cancer vaccine for non small cell lung cancer (NSCLC) based on a novel vaccination technology using self-adjuvanted mRNA molecules. It comprises five mRNAs encoding NSCLC associated tumor antigens (NY-ESO1, Mage-C1, Mage-C2, Survivin, 5T4). Here, we report interim results of a phase I/IIa trial with CV9201 in stage IIIb/IV NSCLC patients that responded or stabilized after first line (chemo-) radiotherapy. Primary endpoint was assessment of safety and tolerability of CV9201 and secondary endpoints were evaluation of induction of immune response and assessment of anti-tumor activity. Methods: Patients were vaccinated intra-dermally up to five times in max. 15 weeks. Blood samples were taken before the first vaccination and two weeks after the 3rd and 5th vaccination. 3 patients were vaccinated in the phase I part of the study at each of three different dose levels (400µg, 800µg and 1600µg total mRNA administered). Enrollment was then expanded at the highest dose level within the phase IIa part. Peripheral blood mononuclear cells were analyzed for induction of effector and memory T cell subsets, B cells and CD4+CD25++ T regulatory cells during the course of vaccination. Antigen-specific B and T-cell responses against all antigens were analyzed by IgM and IgG ELISA, IFN-g ELISPOT, ICS and tetramer analysis. Results: Phase I safety analysis showed mainly treatment related grade 1 injection site reactions and grade 2 fever. Neither dose-limiting toxicity nor vaccine-related serious adverse events were reported. B-cell frequency increased and a significant (P< 0.004) shift from IgD+CD38+/- naïve B-cells towards IgD+CD38++ germinal center founder B-cells by > 2 fold was detected in 50% of 16 intermediate analyzed patients after 3 vaccinations. T-cell population shifted from effector to memory subtype 2 weeks after the final vaccination. Antigen-specific B cell, CD4+ and CD8+ T cell responses were detected during and after vaccination with CV9201. Conclusions: The interim analysis indicated that vaccination with CV9201 was safe and well tolerated by the study participants. Moreover, CV9201 led to an adaptive immune activation, and detectable antigen-specific humoral and cellular immune responses.
Time-dependent patterns of recurrence after early stage breast cancer: Preliminary observations and methodological issues
Authors: J. J. Dignam, V. M. Dukic, S. J. Anderson, E. P. Mamounas, J. H. Jeong, J. P. Costantino
Journal: Journal of Clinical Oncology (2007)

536 Background: For patients with lymph node-negative (n0) breast cancer, benefit from adjuvant therapy is established. However, absolute gains are smaller than in node-positive disease and thus more selective use is warranted, prompting development of risk profiling to identify those most (or least) likely to benefit. In addition to defining risk based on recurrence-free status to specific time landmarks, examination of the magnitude and changes in the risk (hazard) of failure over time may be informative. We investigate recurrence hazards in n0 breast cancer. Methods: In a cohort of 9,279 participants from 5 NSABP randomized trials (accrual 1982–1998) investigating cytotoxic chemotherapy (CTX) and tamoxifen (TAM) for n0 breast cancer, we examine recurrence-free survival curves and recurrence hazards over time. The latter presents analytic challenges, because empirical (i.e., nonparametric) estimates are too unstable to provide reliable inference on patterns and do not incorporate covariates, while traditional semi-parametric (i.e., Cox) and parametric survival models are too restrictive to permit hazard changes. We apply flexible extensions of these models to examine and compare time-varying hazard profiles. Results: In patients undergoing surgery only, distinctive recurrence risk patterns between estrogen receptor (ER)-negative (-) and ER- positive (+) patients emerge. We observe an earlier, larger hazard peak in ER- patients, but a more persistent hazard in ER+ patients and a crossover (hazard for ER+ &gt; ER-) occurring around 48 months. Under adjuvant treatment (CTX in ER- and TAM or TAM+CTX in ER+), magnitudes of failure hazards are reduced but other inter-relationships are largely maintained. For example, while TAM decreases the early hazard in ER+ patients to a level comparable to CTX treated ER- disease, in later follow-up (&gt;5 years) the ER+ hazard again exceeds that of ER- patients. Adding CTX to TAM results in hazard reductions in both early and later periods. Conclusions: Examination of recurrence hazards over time with our models reveals changes in risk that may have biologic and therapeutic strategy relevance. The proposed analytic approaches address shortcomings of standard methods and will be developed further. No significant financial relationships to disclose.
A Phase IIa trial of weekly EPO906 in patients with hormone-refractory prostate cancer (HPRC)
Authors: A. Hussain, R. S. Dipaola, A. D. Baron, C. S. Higano, N. S. Tchekmediyan, J. A. Miller, J. D. Rothermel
Journal: Journal of Clinical Oncology (2004)

4563 Background: Single-agent taxanes have demonstrated clinical activity in HPRC; however, the median duration of response is relatively short. The epothilone EPO906 is a potent microtubule stabilizer that is not a substrate for multidrug-resistance protein and has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and refractory tumors. Thus, EPO906 may be an appropriate alternative to taxane therapy in patients (pts) with HRPC. In a phase IIa study, we investigated the safety and efficacy of weekly EPO906 in these pts. Methods: Pts with histologically proven disease with documented metastases or prostate-specific antigen (PSA) progression > 20 ng/mL were enrolled. Pts could have received ≤ 1 prior chemotherapy regimen for hormone-resistant disease. Pts were maintained on androgen ablation therapy or had undergone an orchiectomy. EPO906 2.5 mg/m2 was administered via a 5-min IV infusion once weekly for 3 wks followed by 1 wk of rest for 6 cycles. Results: A total of 37 pts with a median age of 68 yrs (range, 52 - 82 yrs) were enrolled, 95% had a performance status of ≤ 1. Twenty-nine pts had received prior chemotherapy. Pts received a median of 3 cycles (range, 1 - 12) of EPO906. EPO906 was well tolerated; the most common adverse events were gastrointestinal. Grade (gr) 3 or 4 diarrhea, fatigue, dehydration, abdominal pain, and vomiting were reported in 7 (19%), 5 (14%), 3 (8%), 2 (5%), and 2 (5%) pts, respectively. Gr 2 diarrhea was reported in 7 (19%) pts. Gr 1 and 2 peripheral neuropathy was reported in 5 (14%) and 2 (5%) pts, respectively. Five pts withdrew because of adverse events, although only 1 pt discontinued for a clinically significant adverse event (gr 3 diarrhea). Gr ≤ 2 anemia was reported in 7 (19%) pts; there were no reports of neutropenia or thrombocytopenia of any grade. By PSA assessment, 8 (22%) had a PR, 6 (16%) had SD, and 16 (43%) had PD. PSA values were not available for 7 pts. By tumor assessment, there were 4 PR out of 20 pts with measurable disease. Two pts are ongoing. Conclusions: Weekly EPO906 was generally well tolerated and active in pretreated pts with HRPC. Future studies will determine the role of this agent in the treatment of prostate cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp. ICPME; Novartis Pharmaceuticals Corp. Novartis Pharmaceuticals Corp. Genentech Novartis
Pilot trial of 5-FU/oxaliplatin (CIFOX) for patients with metastatic colorectal cancer who progressed on 5-FU/LV/CPT-11 (IFL)
Authors: A. Aparicio, S. Iqbal, D. Yang, S. Groshen, D. Park, A. Garcia, H. J. Lenz
Journal: Journal of Clinical Oncology (2004)

3773 Background: 5-FU/oxaliplatin is approved for the treatment of metastatic colorectal in patients who have progressed on IFL. In September 2001, we began accruing patients to a pilot trial combining 5-FU and oxaliplatin for patients who had progressed on IFL. The primary goal of the trial is to assess both the intratumoral gene expression and the genomic polymorphisms relationship to clinical outcome and toxicity. We are updating the previously reported results (Padmanabhan et al; Proc ASCO 2002). Methods: Patients received continuous infusion 5-FU 200 mg/m2/d for 10 weeks followed by a 2 week break and oxaliplatin 130 mg/m2 every 3 weeks (CIFOX). Response was assessed every 6 weeks. Chemotherapy was administered until progression of disease or intolerance. This study is designed to accrue 200 patients. Results: As of December 2003, 168 patients have been accrued; median age 60 years (range 25 - 87), 81 (48%) females, 87(52%) males; 27(16%) Asian, 7(4%) African American, 113(67%) Caucasian, 21(13%) Hispanic; 101(60%) colon cancer, 67(40%) rectal cancer; all patients had prior chemotherapy, 50 (30%) had prior radiation. Of the 149 evaluable patients, responses (by RECIST) were as follows: 23(15%) partial response, 71(48%) stable disease and 55(37%) progressive disease. The median number of cycles received was 4 (range 1–20). Grade 3–4 hematologic toxicity was reported in 4(3%) and 86(59%) had grade 3–4 non-hematologic toxicity. The most common grade 3–4 toxicities were gastrointestinal (diarrhea/vomiting/nausea/anorexia/stomatitis/pharyngitis), constitutional symptoms (fatigue), neurologic (neuropathy-sensory/neuropathy-motor), and pain (abdominal pain/cramping/headache). To date, 119 patients have progressed and 117 have died. The median overall survival is 9.0 (95% CI: 7.3, 10.0) months, median progression-free survival of is 4.0 (95% CI: 3.4, 4.6) months. Conclusions: 5-FU/oxaliplatin (CIFOX) is an effective and well tolerated second line regimen for metastatic colorectal cancer. Assessment of the molecular correlates is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Sanofi
A first-in-class, first-in-human phase I study of enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus, administered intravenously in patients with metastatic epithelial tumors.
Authors: Emiliano Calvo, Marta Gil-Martin, Jean-Pascal H. Machiels, Sylvie Rottey, Antonio Cubillo, Ramon Salazar, Feby Ingriani Mardjuadi, Karen Paula Geboes, Christopher Ellis, John William Beadle, Christine Blanc
Journal: Journal of Clinical Oncology (2014)

3103 Background: Enadenotucirev (E) is an Ad11/Ad3 group B adenovirus, selective for killing cancer cells with little or no activity expected in normal tissue. E shows a broad anti-tumor activity in preclinical models. Methods: Main objectives of this study were to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD) of E delivered intravenously (IV) on Day (D) 1, 3 and 5 as single cycle and to recommend a dose for phase 2 (DP2). Once determined, DP2 was confirmed with up to 4 repeat cycles. A