tbuckley/cabot-search huggingface dataset:
A phase II, open-label study of ramucirumab (IMC-1121B), an IgG1 fully human monoclonal antibody (MAb) targeting VEGFR-2, in combination with paclitaxel and carboplatin as first-line therapy in patients (pts) with stage IIIb/IV non-small cell lung cancer (NSCLC).
Authors: D. R. Camidge, M. S. Ballas, S. Dubey, M. Haigentz, P. J. Rosen, J. F. Spicer, H. J. West, G. D. Shah, H. Youssoufian, A. C. Mita
Journal: Journal of Clinical Oncology (2010)

7588 Background: VEGF-mediated angiogenesis contributes to NSCLC pathogenesis. Ramucirumab is a recombinant human MAb that binds the extracellular domain of the vascular endothelial growth factor receptor 2 (VEGFR-2) and inhibits cancer growth in diverse preclinical models. Methods: Approximately 40 pts with advanced NSCLC (stage IIIB not suitable for locoregional therapy or stage IV) are planned for enrollment. Squamous histology and treated brain metastases are allowed. Exclusion criteria include prior bevacizumab, blood vessel invasion, intratumor cavitation, and recent gross hemoptysis. Pts receive ramucirumab 10 mg/kg, paclitaxel 200 mg/m2, and carboplatin AUC = 6 on Day 1 of each 3-week cycle for up to 6 cycles, followed by maintenance ramucirumab. Tumor evaluations occur every 6 weeks. The primary endpoint is progression free survival at 6 months; secondary/exploratory endpoints include safety, objective response rate (ORR), pharmacokinetic/pharmacodynamic profiles, and immunogenicity. Results: 31 pts have been enrolled to date, 22 are evaluable for safety (7M:15F; median age 59 [37-79]). None had squamous histology and 1 had treated brain metastases. 1 pt discontinued due to an adverse event (AE) (pneumothorax) and 2 pts reported serious AEs possibly related to ramucirumab: G4 febrile neutropenia and G2 pneumothorax. 15 pts are evaluable for best response. 10 of 15 pts had an objective response (1 complete response, 9 partial responses: ORR = 67%). 50% of responses have been confirmed, and in all cases, where repeat scans are available, initial response was confirmed. 5 of 15 pts had SD, 4 with tumor shrinkage. Preliminary median PFS is 5.7 m (95% CI: 5.62-5.75), with 14 of the 15 pts still on therapy as of December 4, 2009. Conclusions: Ramucirumab in combination with paclitaxel and carboplatin is well tolerated in NSCLC pts. Preliminary results do not highlight any unusual safety concerns. Preliminary efficacy data are encouraging. Updated safety and efficacy data and the relevance of pharmacodynamic markers to outcomes will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems ImClone Systems ImClone Systems
Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy.
Authors: G A Fyfe, R I Fisher, S A Rosenberg, M Sznol, D R Parkinson, A C Louie
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.8.2410 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8708739 Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy. G A FyfexG A FyfeSearch for articles by this author , R I FisherxR I FisherSearch for articles by this author , S A RosenbergxS A RosenbergSearch for articles by this author , M SznolxM SznolSearch for articles by this author , D R ParkinsonxD R ParkinsonSearch for articles by this author , A C LouiexA C LouieSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.8.2410 PDF "Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy.." Journal of Clinical Oncology, 14(8), pp. 2410–2411© 1996 by American Society of Clinical Oncology
A patient with complex multiple genomic<i>ALK</i>alterations
Authors: Xin Liu, Shawn J Rice, Carlos A Jamis-Dow, Catherine Abendroth, Siraj Ali, Salah Almokadem, Chandra P Belani
Journal: Thorax (2016)

Lung cancer is a disease with a heterogeneous complement of mutations.1 Although point mutations and deletions are among the most common types of mutations in lung cancer, translocations in the ALK gene, which occur in approximately 5% of lung adenocarcinomas, exist predominantly in non-smokers. ALK translocations gained notoriety recently because they are targets for the kinase inhibitor crizotinib (Xalkori).1 Crizotinib has exhibited profound efficacy and has obtained FDA (United States Food and Drug Administration) approval for use in patients with non-small cell lung cancer (NSCLC) with ALK translocation, as determined by a break-apart fluorescent in situ hybridisation (FISH) assay.2 Here we report a case where a patient with a complicated ALK genotype, including an EML4-ALK variant 5a/b translocation and ALK tandem duplication with response to crizotinib treatment.

A 70-year-old female patient with complaints of progressive dyspnoea underwent a chest CT scan, which revealed a 6 cm spiculated mass with extrinsic compression of the trachea and the right main stem bronchus. PET-CT (positron emission tomography-CT) scan confirmed the findings of the CT scan and the mass was metabolically active, and there was presence of metastases in the lymph nodes. Histological evaluation along with immunostaining revealed primary lung adenocarcinoma. An MRI of the brain revealed nodular intraparenchymal metastatic deposits in the left cerebellar hemisphere, left inferior cerebellar vermus and the left superior parietal cortex. The patient received palliative radiation to the lung mass and gamma knife treatment for the brain metastasis. Genetic profiling performed on …
Fertility in young patients treated with chemotherapy for Hodgkin’s disease (HD): Long-term results
Authors: S. Viviani, V. Bonfante, G. Ragni, G. Bonadonna, P. Valagussa, A. M. Gianni
Journal: Journal of Clinical Oncology (2005)

6578 Background: Due to improved lymphoma cure rates, long-term toxicity, including iathrogenic sterility, is of great concern. We thus evaluated the fertility of patients (pts) treated for HD at the Istituto Nazionale Tumori of Milan from 1990 to 2001 with three different chemotherapy (CT) regimens +/- radiotherapy excluding pelvic nodes. Material and Methods: The case series included 191 pts (73 males,118 females), median age 27 years (range 18–45), in long-lasting complete remission after three different CT regimens: 119 pts received 4–6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine); 48 pts were given 6–8 cycles of VEBEP (VP16, epirubicin, bleomycin, cyclophosphamide, prednisone) and 25 pts were treated with sequential CT including intermediate-high doses of epirubicin, vincristine, prednisone, cyclophosphamide and etoposide for a 3 months period. Fertility was evaluated by semen analysis and conceptions in males and by history of menstrual cycles and pregnancies in females. WHO criteria were used to classify normospermia, azoospermia, abnormal semen (all sperm abnormalities but azoospermia), amenorrhea and normorrhea. Results: Males: after ABVD we observed permanent azoospermia in 6%, abnormal semen in 70% and normal semen in 24%; 30% of pts fathered. After VEBEP we documented permanent azoospermia in 35%, abnormal semen in 46% and normal semen in 19%; 27% of pts fathered. After sequential CT permanent azoospermia occurred in 33% and abnormal semen in 67%; 11% of pts fathered. Females: definitive amenorrhea was documented in 2% after ABVD, 17% after VEBEP and 6% after sequential CT; all pts who became amenorrheic were aged > 30 years at treatment. Pregnancies occurred in 38%, 21% and 25% in each treatment group respectively. Conclusions: Long-term results confirm that ABVD spares fertility in the majority of cases. Regimens containing alkylating agents, like VEBEP or sequential CT, induce sterility in less than 20% of women, but in a large fraction of male pts. Therefore pretreatment cryopreservation of semen should be offered to all males. No significant financial relationships to disclose.
Cancer Patient Survival: Surveillance, Epidemiology, and End Results Program, 1973–79
Authors: L G Ries, E S Pollack, J L Young
Journal: JNCI Journal of the National Cancer Institute (1983)

Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used in the evaluation of cancer patient survival experience for almost 10% of the U.S. population. This first report contains actuarial (life table) survival analysis on 368,263 patients with first primary cancer diagnosed in 1973-79 from nine SEER areas: the entire States of Connecticut, Iowa, New Mexico, Utah, and Hawaii and the metropolitan areas of Atlanta, Detroit, San Francisco, and Seattle. Both observed and relative survival rates were shown for whites and blacks, sex, age, primary site, and time period (each yr, 1973-78). The largest racial difference in survival was for cancer of the corpus uteri: 87% 5-year relative survival rate for white females versus only 54% for black females. Survival rates varied considerably by primary site. For most sites, as age increased the relative and observed survival rates decreased. Analysis of relative survival rates by ech year of diagnosis, 1973-78, and for each year following diagnosis suggested increasing rates for cancers of the colon, lung, and prostate gland, whereas there were no definite increases for cancers of the female breast and corpus uteri. A dramatic increase in survival from acute lymphocytic leukemia was found for children under 15 years of age, with the 4-year relative survival rate increasing from 51% among those diagnosed in 1973-75 to 65% for those diagnosed in 1976-78.
Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma
Authors: Arun Narayanaswamy, Mani Baskaran, Shamira A. Perera, Monisha E. Nongpiur, Hla M. Htoon, Tin A. Tun, Tina T. Wong, David Goh, Daniel H. Su, Paul T.K. Chew, Ching-Lin Ho, Tin Aung
Journal: Ophthalmology (2015)
Pharmacological and immunological characteristics of the therapeutic anti-EGFR antibodies cetuximab, panitumumab, and nimotuzumab.
Authors: C. Stroh, C. Reusch, J. Schmidt, J. Splittgerber, J. S. Wesolowski, A. Blaukat
Journal: Journal of Clinical Oncology (2010)

e13025 Background: Therapeutic antibodies can affect tumor cells by functionally interfering with the target and/or by employing immune effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). The scope of this study was to analyze the clinically used anti-EGFR therapeutic antibodies cetuximab, panitumumab, and nimotuzumab with regard to both modes of action: interference with EGFR function and ADCC activity. Methods: EGFR binding and inhibition of EGFR signal transduction were characterized in A431, A549, and HCT116 tumor cell lines. The ability to kill these tumor cells via ADCC was analyzed in ex vivo assays using human immune effector cells isolated from blood. Results: In cellular assays using A431, A549, and HCT116 cells cetuximab and panitumumab showed similar EGFR binding affinities (Kd values for binding to A431 cells of cetuximab and panitumumab: 5 nM and 4 nM, respectively) while nimotuzumab bound to EGFR with lower affinity (Kd for binding to A431 cells: ∼ 90 nM). The EGFR binding behavior correlated with the ability to inhibit EGFR signal transduction (phospho-EGFR, phospho-ERK1/2, phospho-Akt, phospho- STAT3) as well as inhibition of VEGF and IL-8 production. Using peripheral blood mononuclear cells (PBMCs) as effector cells, cetuximab mediated a marked, dose-dependent ADCC response in all three cell lines. Nimotuzumab displayed weak ADCC activity, while no or only marginal ADCC was observed with panitumumab. NK cells were the main effector cells of the PBMC fraction. With all three antibodies no ADCC activity was seen when polymymorphonuclear leukocytes were used as effector cells. Conclusions: Although cetuximab, panitumumab, and nimotuzumab are all clinically applied therapeutic antibodies directed against the EGFR, the results of this investigation suggest that different modes of action may contribute to the clinical efficacy of the antibodies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration EMD Serono, Merck KGaA, Merck Serono
Childhood ALL masquerading as Ewing's sarcoma
Authors: P. M. Kent, D. Felten
Journal: Journal of Clinical Oncology (2008)

21516 Background: Lymphoma of the pelvic bone can be confused radiologically and morphologically with Ewings sarcoma (EWS). Immunohistochemistry: FLI-1, CD99, CD20, and CD45 can discriminate these entities. Precursor B cell acute lymphoblastic leukemia (ALL) presenting as a destructive bony mass mimicking EWS has not been previously reported and cannot be discriminated from EWS by these stains. The objective of this report is to describe a case of ALL that mimicked EWS clinically and pathologically. Methods: A 7 yr old boy presented with limping and a large iliac mass. MRI showed a 10× 4cm mass with cortical destruction. Biopsy showed small round blue cells, positive for CD99 and FLI-1 and negative for CD45, CD20 and synaptophysin. The pathologist stated the ‘diagnosis of Ewing's sarcoma is secure.’ Labs showed: WBC = 8,300, Hg = 10.0, platelets = 48,000, and LDH = 680. CT showed mild splenomegaly. A bone marrow biopsy distant from the mass was ‘packed’ with blue cells. Results: Flow cytometry was positive for: CD34, HLA-DR, CD22, CD10 and CD19, and negative for: CD 45 and CD20; while immunohistochemistry was positive for: CD10, CD22, TdT, CD99 and FLI-1 and negative for CD20 and CD45 in all biopsies. F.I.S.H. was negative for: t(11:22), t(9;22), t(12;21), (11q23) and t(8;14). These findings are diagnostic of acute precursor B-cell ALL. Seven days after starting chemotherapy for ALL, the mass vanished and the patient has remained in remission since. CT normalized in 5 months. Conclusion: All biopsies initially stained in a characteristic pattern for EWS and against lymphoma. However this pattern is also seen in pre-B cell ALL (Table 1). Pre-B cell ALL can present as an isolated destructive bony mass, clinically and pathologically consistent with EWS. Attention to the CBC and addition of CD10 and CD22 immunohistochemical stains can uncover the diagnosis of ALL masquerading as EWS. Classic Immunohistochemistry for Bone Tumors, B Cell Lymphoma, and Pre-B Cell Leukemia Marker EWS Lymphoma Pre B Cell Leukemia FLI-1 Positive Negative Positive CD 99 Positive Negative Positive CD 45 Negative Positive Negative CD 20 Negative Positive Negative CD 10 Negative Negative Positive CD 22 Negative Negative Positive No significant financial relationships to disclose.
A randomized double-blind cross-over patient preference study of pazopanib versus sunitinib in treatment-naive locally advanced or metastatic renal cell carcinoma (mRCC).
Authors: B. J. Escudier, D. Cella, J. E. Gschwend, T. Powles, C. N. Sternberg, R. Hodge, M. Lau, M. Neary, F. Mehmud, T. Eisen
Journal: Journal of Clinical Oncology (2010)

TPS237 Background: Angiogenesis inhibitors have demonstrated significant clinical efficacy in mRCC. Pazopanib and sunitinib are both oral tyrosine kinase inhibitors primarily of VEGFR (−1, −2, and −3), PDGFR (-a and -b) and c-Kit. Pazopanib has a more selective kinase specificity profile compared to sunitinib and has demonstrated low rates of fatigue, hand foot syndrome and mucositis/stomatitis. There is an ongoing phase III head to head study of pazopanib vs. sunitinib in treatment naïve mRCC patients (pts). The outcomes of cancer therapy are traditionally evaluated using RECIST response and survival criteria. There is increasing emphasis on assessment of health related quality of life (HRQoL) particularly relevant to tolerability of agents. However, HRQoL questionnaires might not reflect the pt preference. Studies have shown an association between toxicity/intolerability and a response on HRQoL, suggesting that pt preference is a legitimate and useful endpoint. This study evaluates whether tolerability differences between these two agents translate into an actual pt preference for one drug over the other. Methods: This is a randomised, double blind, cross-over study of pazopanib versus sunitinib in pts with mRCC who have received no prior systemic therapy for mRCC. Approximately 160 pts are stratified based on the ECOG performance status (0 vs. 1) and number of metastases (0 and 1 vs. 2+). Pts are randomized 1:1 to receive blinded study drug starting either with 800mg pazopanib for 10 weeks followed by 50 mg sunitinib for 10 weeks or vice versa. A 2-week washout period is included prior to cross over. Plasma and blood samples are collected during the study for PK and biomarker analyses. The primary endpoint collected by pt preference questionnaire after being treated with each drug is the pts' stated preferences for continuing treatment on either the first or the second drug, assuming equal efficacy. Secondary endpoints are reason for pt preference, fatigue, QoL, dose modifications and time to dose modification, and safety. Data on cross-toxicity and cross-resistance will also be evaluated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, Novartis, Pfizer, Roche GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline, Pfizer
PTH-095 Oral carbon therapy is associated with a selective modulation of the microbiome in cirrhotic rats which is associated with a significant reduction in inflammatory activation
Authors: J Macnaughtan, I Ranchal, J Soeda, R Sawhney, J Oben, N Davies, R Mookerjee, J Marchesi, J Cox, R Jalan
Journal: Gut (2015)

<h3>Introduction</h3> The host-microbiome interaction is pathological in cirrhosis promoting a dysregulated inflammatory response resulting in organ injury and diminished survival. Yaq-001 is an oral non-absorpable carbon shown to result in improvement in hepatic haemodynamics and markers of liver injury but the mechanism of how this is achieved in unknown. The aims of this study were to determine whether the beneficial effects of Yaq-001 was related to the composition and associated functional state of the microbiome in bile-duct ligated cirrhotic animals. <h3>Method</h3> BDL (n = 12) or sham (n = 12) rats were randomised to treatment with Yaq-001 (Yaqrit Ltd. UK) from weeks 2–4. Analysis of urine samples was performed using <sup>1</sup>NMRs. Bacterial DNA from stool was extracted, amplified and sequenced. Arterial plasma was co-incubated with HEK-Blue hTLR4 and IL-1β/IL-18 reporter cell lines. Constitutive ROS and LPS-induced ROS production from circulating monocyte populations was determined using flow cytometry. <h3>Results</h3> BDL was associated with a significant reduction in Peptidostreptococcaceae and Clostridium XI (p &lt; 0.05) in stool compared to sham controls. Carbon therapy was associated with significant increases in firmicutes, in particular clostridia populations in stool with significant reductions in bacteroides populations (p &lt; 0.05). Functionally, BDL rats were found to have significantly higher urinary bile acids, Trimethylamine N-oxide, benzoate, glycine, acetate and lactate than sham controls (p &lt; 0.05). Significantly lower levels of citrate, dimethylamine (DMA) and creatinine were observed in BDL compared to sham animals (p &lt; 0.05). Carbon treatment results in a significant increase in urinary creatinineand bile acids and reduction in urinary glycine (p &lt; 0.05). A significant increase in IL18/IL1B expression was observed in untreated BDL rats compared to sham which was significantly attenuated with carbon treatment (p &lt; 0.05). Monocyte LPS-induced ROS production was significantly higher in BDL rats but attenuated with carbon treatment (p &lt; 0.05). <h3>Conclusion</h3> The results of this study show that Yaq-001, which is a non-specific adsorbent has substantial effects on the composition and function of the microbiome in cirrhotic rats and positively modulates the function of monocytes regarding ROS production and inflammasome activation. These data provide compelling evidence that the gut bacterial products are important in mediating immune dysfunction in cirrhosis and is a target of therapy. <h3>Disclosure of interest</h3> None Declared.
Differential Cytotoxicity of Tumorigenic and Nontumorigenic Strain-2 Guinea Pig Cells as Mediated by Syngeneic Phytohemagglutinin-Stimulated Peritoneal Exudate Cells
Authors: B S Zwilling, M S Meltzer, C H Evans
Journal: JNCI Journal of the National Cancer Institute (1975)

Phytohemagglutinin (PHA)-stimulated peritoneal exudate (PE) cells from strain-2 guinea pigs were more cytotoxic in culture to syngeneic tumorigenic cells than to syngeneic nontumorigenic cells. Cytotoxicity was measured by the release of 3H-thymidine from prelabeled target cells. Tumor-producing guinea pig fetal cells transformed in culture by chemical carcinogen released up to 70% of their label in the presence of PHAstimulated PE cells. Non-tumor-producing cells, regardless of their morphologic characteristics, were less affected by PHA-stimulated PE cells. Nontumorigenic cultures included untreated early passage and long-term cultures previously treated with a carcinogenic or noncarcinogenic chemical. Differential cytotoxicity to tumorigenic versus nontumorigenic cells was dependent upon both PE cell and PHA concentration. Tumorigenic cultures were best distinguished from nontumorigenic cultures when 0.51–1×106 PE cells and 50–100 µug PHA were incubated with 1×1043H-thymidine-labeled target cells for 48 hours.
Medical error prevention: The role of oncological nursing
Authors: N. Kohen, E. Morgenfeld, G. Ernesto, A. Negro, M. Muiño, D. Juarez, S. Aguirre, D. Santillan, E. Rivarola, F. G. Gercovich
Journal: Journal of Clinical Oncology (2009)

6591 Background: The medical care of oncological patients is a multidisciplinary task. The nurse is a key member of the team. The aim of this study is to analyze the incidence rate and the type of intravenous chemotherapy prescription errors detected by the nurses in the the ambulatory setting at the IOHM in a 3 months period. Methods: The intravenous chemotherapy treatments (tx) prescribed by the IOHM's staff (14 oncologists and 4 onco-hematologists) between Aug 1, 2008 and Nov 1, 2008, were analyzed. A database was prospectively built with the following variables: attending physician, diagnosis, treatment cycle, drug, dosage, time of perfusion, type of error detected, and potential harm from it. Frequency tables were established for the type of error. The correlation between the rate of errors by prescribing physician and his expertise, weekly hours of work at the institution, number of patients under his care and number of consults were also studied. Results: A total of 5,015 tx administered to 2,492 pt were evaluated (mean of 2.1 tx per pt, range 1–5). The most common cancer diagnoses were breast (20%), colon (16%), lung (10%), and lymphoma (7%). Forty-five medical prescription errors before administration of treatment were found. There were no errors found in the preparation and administration of treatment. Of the 45 errors detected, 18 were related to drug selection (in 2 cases the error could lead to serious complications). Twenty seven errors were related to a dosage mistake (3 cases with serious potential harm). The frequency of medical errors between the attending physicians did not differ statistically (Fisher Exact Test 0.082) and due to the low error rate, none of the other variables could be properly studied. Conclusions: 1. Specialized nursing is a key element in the safety of the patient and the prevention of malpractice, 2. The rate of errors in this population is 0.9% (45 errors out of 5,015) and the rate of potentially serious harm to the patient is 1/1000 tx.; 3) All errors were corrected before drug administration. No significant financial relationships to disclose.