tbuckley/cabot-search huggingface dataset:
Detection of serum proteomic profile predictive for epidermal growth factor receptor tyrosine kinase inihibitors (EGFR-TKIs) in 1st line chemotherapy responders
Authors: C. Belli, A. Spreafico, M. G. Viganò, C. Lazzari, E. Roca, E. Villa, H. Roder, J. Grigorieva, M. Tsypin, V. Gregorc
Journal: Journal of Clinical Oncology (2008)

8091 Background: Positive and negative predictive profiles detected by Matrix Assisted Laser-Desorption Ionization Time of Flight Mass Spectrometry (MALDI ToF MS) corresponding to the spectra of pts who benefit from EGFR-TKIs as 2nd/3rd line of therapy in terms of overall survival (OS) were already reported in the previous study (JNCI, 2007). Moreover, it was also evidenced that proteomic profiles do not predict outcome in 2nd line chemotherapy in EGFR-TKIs naïve pts. Aim of this study was to test the association of proteomic profiles evaluated by MALDI ToF MS and detected before 2nd/3rd line EGFR-TKIs with response to 1st line chemotherapy. Methods: Eigthy-one pts with advanced NSCLC were included in analysis: 80% males, median age 64 years (range 37–87); ECOG performance status (PS) 0–1 (75%), 2 (25%), 90% of pts received cisplatinum-based therapy 10% 3rd generation of mochemotherapy due to PS and age. The proteomic stratification was performed using the already optimized classification algorithm (JNCI, 2007), in which each replicate spectrum was assigned a label as VeriStrat+ (good) or VeriStrat- (bad profile). Results: The correlation between the response to 1st line chemotherapy and the spectra classification obtained with MALDI MS before EGFR-TKIs was analysed. Fifty four (66.6%) pts were classified as VeriStrat+: 18 (33%) of these had stable disease, 9 (16%) progression and 27 (50%) were responded to chemotherapy before gefitinib treatment. Twenty four (29.6%) pts were VeriStrat-: 8 (33.3%) had stable disease, 8 (33.3%) progression and 8 (33.3%) were responders. Moreover, 3 pts (3.7%) had a undefined profile: 2 with stable disease and 1 with progressive disease. Conclusions: This study suggests a correlation between response to 1st line chemotherapy and proteomic profiles obtained before 2nd line therapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Biodesix Company
Reduction in radiographic progression in the hands and feet of patients with early rheumatoid arthritis after receiving infliximab in combination with methotrexate
Authors: D Van der Heijde, Patrick Durez, P. Emery, JM Bathon, RN Maini, Rene Westhovens, J. Han, E St Clair, J. Smolen
Journal: Annals of the Rheumatic Diseases (2005)
Controlling the quality of RAS mutation testing by a dichotomous approach: Ring trials and benchmarking mutation frequencies by a RAS monitor.
Authors: Andreas Jung, Manfred Dietel, Helmut E Gabbert, Matthias Kloor, Roland Penzel, Karl-Ludwig Schafer, Peter Schirmacher, Christine Sers, Thomas Kirchner
Journal: Journal of Clinical Oncology (2015)

536 Background: The PRIME study (Douillard et al. New Engl. J. Med. 2014) demonstrated that testing all coding exons of both KRAS and NRAS proto-oncogenes (all-RAS) predicted response for anti-EGFR targeting antibody panitumumab better than testing only KRAS exon 2 (PFS: 8.9 vs 9.6 mo, OS: 20.2 vs. 26 mo). Thus, the EMA changed the label of this drug for Europe. Now all RAS testing has to be done on a high quality level. Therefore, an improved quality assurance (QA) system was developed. Methods: The German RAS Advisory Board as part of QuIP (Quality initiative Pathology) launched ring-trials to assure quality of RAS mutation detection. 12 test cases of metastatic colorectal cancers (mCRC) containing WT or mutated sequences in one of the three coding exons 2 – 4 of either the KRAS or the NRAS oncogenes. Additionally many QA passed participants supplied the results of all-RAS testing of mCRC for one year resulting in a RAS monitor. Results: In less than half a year an area-wide coverage of quality certified all-RAS testing laboratories was reached. In three ring-trials 89 of 93 (96%) institutions for pathology passed the QA using Sanger-Sequencing (60%), pyrosequencing (25%) or the COBAS system (15%). None of the methods was superior to another as comparable amounts of methods passed or failed the ring trials. As only 12 cases were tested the result is reliable with a lower limit of confidence of only 0.7. Thus, a RAS monitor was introduced as an additional instrument of QA. Here, the results of almost 4000 cases of mCRC tested for all-RAS were collected indicating RAS mutations in 45.7% of investigated cases (KRAS: 41.5%, NRAS: 4.2%). Conclusions: Ring-trials are a versatile tool to establish a network of quality tested diagnostic laboratories in a short time. In parallel data sets for benchmarking the frequencies of RAS mutations were generated region specifically. Thereby quality was brought to a higher level than without the RAS monitor.
Aneuploidies of chromosome 17 in breast cancer: Relative prevalence in a series of 170 patients from Córdoba, Argentina, studied with fluorescent <i>in-situ</i> hybridization (FISH)
Authors: A. Sturich, P. Calafat, M. Botterón, A. Borello, A. Diller, B. Ricchi, E. Palazzo, N. Rossi, J. J. García
Journal: Journal of Clinical Oncology (2009)

e22195 Background: The amplification of HER-2 oncogen, located in 17q11.2–12, occurs in 20–30% of invasive breast cancer. Numerical anomalies of chromosome 17 are frequent findings in these patients, during the study of the amplification of HER-2 oncogen with FISH technique, though clinical implications are yet not defined. Objectives: To determine the presence of chromosome 17 aneuploidies in a series of patients with histological diagnosis of breast cancer and to correlate these data with amplification and overexpression of HER-2 oncogen. Methods: Samples of 170 patients included in paraffin were analyzed with FISH technique, using the PathVysion system. We analyzed the number of HER-2 oncogen specific signals and chromosome 17 centromere (CEP 17) signals. We followed the ASCO 2007 guidelines to evaluate FISH and immunohistochemical analysis (IHC). Criteria for aneuploidy: diploid at 1.5–2.25 average CEP 17 signals /cell; hyperdiploidy: values over 2.25 and hypodiploidy: lower than 1.5. Results: We found 73 cases of chromosome 17 aneuploidies (42.9%), 68/73 polysomies (93%) and 5/73 monosomies (7%). The monosomies were observed in 4/5 patients with HER-2 amplification. Polysomies occurred simultaneously with HER-2 amplification in 48% (35/73), 45% (33/73) were not amplified and 7% (5/73) were equivocal. FISH and IHC could be correlated in 136 patients: the higher percentage of polysomies observed corresponded to groups IHC+3/HER-2+ (46%) and IHC+2/HER- (29%). Polysomy 17 was detected in 3 cases IHC+3/HER-2-. Conclusions: The relative prevalence of chromosome 17 aneuploidy in our series was 43%. According to the literature, this finding in 3 patients IHC+3/HER-2- could be responsible for the overexpression of protein cerbB2. The clinical effect of chromosome 17 aneuploidy continues under study. No significant financial relationships to disclose.
Modified (m)Folfox7/bevacizumab (B) or modified (m)Xelox/bevacizumab with or without erlotinib (E) in first-line metastatic colorectal cancer (MCRC): Results of the feasibility phase of the DREAM-OPTIMOX3 study (GERCOR)
Authors: C. Tournigand, G. Lledo, J. Delord, T. André, F. Maindrault-Goebel, C. Louvet, W. Scheithauer, A. de Gramont
Journal: Journal of Clinical Oncology (2007)

4097 Background: Targeted therapy against VEGF and EGFR both demonstrated clinical activity in combination with chemo in MCRC. In 1st line, B with Folfox or Xelox increase progression-free survival (Cassidy ESMO 2006). In 2 nd L, B with Folfox increases overall survival (Giantonio 2005). In this preliminary study, a double inhibition is tested combining mFolfox+B or mXelox+B with or without E, an oral EGFR tyrosine kinase inhibitor. Methods: 38 pts with untreated MCRC were randomly assigned to: mFolfox+B (1A), mFolfox+B+E (1B), mXelox+B (2A) or mXelox+B+E (2B). mFolfox-B=LV 400 mg/m 2 , Oxaliplatin (ox) 100 mg/m 2 , B 5 mg/kg day 1, 5FUc 2.4- 3g/m 2 46h q2w, mXelox-B=Ox 100 mg/m 2 d1 q2w, capecitabine 3–3.5 g/m 2 d1 to 7 q2w, B 5mg/kg q2w. Erlotinib=100 mg/day. 6 cy planned. The primary end-points were toxicity and RR. Results : 9pts/41cy in 1A, 10/60 (1B), 9/39 (2A), 10/44 (2B). Median age 62yrs (43–78). 24/38 pts had poor prognosis factors (&gt;1 met. site and/or PS2, LDH&gt;3N, elevated alk Ph): 5, 6, 7, 6 in each arm respectively. 17 pts had a gr3- 4 toxicity: 4/9 arm 1A, 4/10 arm 1B, 2/9 arm 2A, 7/10 arm 2B. Diarrhea (dia) was the main gr3–4 tox: 2/10pts in 1B, 1/9 in 2A &amp; 6/10 in 2B. 3 pts had gr4 dia in arm 2B. Other gr3 tox were nausea-vomiting 4pts (2/0/0/2), cutaneous rash 2 pts (0/1/0/1), hypertension 1 pt (1B), mucositis 1pt (1A), neutropenia 1 pt (1A), thrombocytopenia 1 pt (1A). 1pt had a gr4 venous thrombosis (2A) and 1pt had pulmonary embolism. 1pt died with perforation in arm 1A, and 1pt died with gr4 dia in arm 2B. Amongst the 17pts with gr3–4 toxicity, 11 pts had poor prognosis criteria and 6 had good prognosis. PR, SD, PD and NE are respectively: arm 1A: 5/2/0/2, 1B: 4/6/0/0, 2A:5/3/1/0, 2B:4/3/0/3. Conclusion: The results of this feasibility phase indicate that adding E with mXelox and bevacizumab increases toxicity (70% gr3–4) and is not feasible. Based on these results, the DREAM study was redesigned to evaluate erlotinib in maintenance with B after 6 cycles of mXelox-B or mFolfox-B. No significant financial relationships to disclose.
Early prediction of response in patients with advanced/metastatic non-small cell lung cancer during chemotherapy with FDG-PET-CT
Authors: D. Lee, S. Kim, H. Kim, J. Choo, J. Song, J. Han, H. Kim, J. Lee
Journal: Journal of Clinical Oncology (2006)

13154 Background: To evaluate the use of 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for prediction of response and survival early during the course of treatment in patients with advanced/metastatic NSCLC. Methods: Between May 2004 and November 2005, 31 patients (gender, 23M, 8F; stage, 2IIIB/29IV, histology, 6 squamous cell ca, 22 adenoca, 3 NOS; age median 57 (30–73 y)) with histopathologically proven NSCLC stage IIIB/IV were enrolled into this study. PET-CT was performed prior to and after one cycle of treatment. Early changes of primary tumor FDG-uptake measured by standardized uptake values (SUV) were correlated with best response to therapy as assessed by CT scan according to WHO response criteria. Results: Patients underwent standard treatment with gemcitabine/vinorelbine (15), gemcitabine/cisplatin (1) gemcitabine/vinorelbine/cisplatin (1), irinotecan/cisplatin (9) or gefitinib (5). In the 25 patients evaluable for response, other 6 patients ongoing, 9 patients achieved a partial response (36%), 5 showed stable diseases and 11 were progressive. Using a cut-off value of 20% reduction of FDG-uptake as a criterion for a response in PET-CT, subsequent best response was predicted with a sensitivity of 88.9% and a specificity of 87.5%. The positive predictive value of a metabolic response was 80.0% and the negative predictive value 93.3%, respectively. There was a significant correlation between the decrease of tumor metabolic activity and subsequent best response (p&lt; 0.001). The median time to progression for PET-CT responder was 10.1 months when compared with that of non-responders with 2.6 months (log-rank p=0.009). Conclusions: Using FDG-PET best response to standard treatment and patient outcome can be predicted very early and therefore, the use of PET-CT may allow to reduce side effects and costs of ineffective therapy in non-responding patients No significant financial relationships to disclose.
Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy
Authors: Minbiao Ji, Spencer Lewis, Sandra Camelo-Piragua, Shakti H. Ramkissoon, Matija Snuderl, Sriram Venneti, Amanda Fisher-Hubbard, Mia Garrard, Dan Fu, Anthony C. Wang, Jason A. Heth, Cormac O. Maher, Nader Sanai, Timothy D. Johnson, Christian W. Freudiger, Oren Sagher, Xiaoliang Sunney Xie, Daniel A. Orringer
Journal: Science Translational Medicine (2015)

Quantitative SRS microscopy can detect human brain tumor infiltration with high sensitivity and specificity, even in tissues appearing grossly normal.
High prevalence of asbestos exposure in bile duct cancer patients.
Authors: S. Di Girolamo, F. de Rosa, E. Nobili, V. Agostini, J. Corbelli, G. Biasco, G. Brandi
Journal: Journal of Clinical Oncology (2010)

e14658 Background: Asbestos exposure is a well recognized risk factor in mesothelioma and lung cancer development but the association with other tumors, such as gastrointestinal and bile ducts cancers (BTC), is uncertain and has not been univocally demonstrated. Asbestos fibers can cross the alveolar barrier after inhalation and penetrate the gastrointestinal mucosa by ingestion. Than they can reach the interstitial environment, the circulatory system and are finally delivered to all tissues, including liver and bile ducts. This work aims at evaluating the potential correlation between previous asbestos exposure and BTC occurrence. Methods: Over the previous year, we carefully interviewed 70 consecutive BTC patients using a standardized questionnaire asking about their exposure to asbestos and other known risk factors linked to bile duct carcinogenesis. Results: In addition to the association with known risk factors for the onset of BTC, we observed occupational or household exposure to asbes-tos in 25 patients (36%), 11 of whom were intrahepatic (ICC), 8 extrahepatic (ECC) and 6 patients had gallbladder cancer (GBC). 11 patients did not have other certain risk factors. The remaining 14 patients presented HCV chronic infection, exposure to proven or suspected carcinogenic compounds, or primary sclerosing cholangitis. Occupational exposure occurred in 5/11 ICC and 4/8 ECC; household exposure was noticed in 7/11 ICC, 4/8 ECC and 6/6 GBC. Only one ICC patient had both exposure type. Conclusions: A substantial proportion of BTC patients had an history of asbestos exposure. Further studies could clarify this putative relation and perhaps explain the increasing incidence of ICC in Western countries observed during the last decades. No significant financial relationships to disclose.
N02C1: A phase III randomized, placebo-controlled, double-blind trial of risedronate for prevention of bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer (BC)
Authors: S. L. Hines, B. A. Mincey, J. A. Sloan, S. P. Thomas, E. G. Chottiner, C. L. Loprinzi, P. J. Atherton, M. D. Carlson, M. Salim, E. A. Perez
Journal: Journal of Clinical Oncology (2008)

525 Background: Risedronate is used for preventing postmenopausal osteoporosis. Its effect in preventing bone loss in premenopausal women undergoing chemotherapy for BC is unknown. Methods: A randomized, placebo controlled, double blind phase III trial assessed the effect of risedronate in premenopausal women undergoing adjuvant chemotherapy for BC (Stage I-IIIB). Women ≥ 18 years were randomized to risedronate 35 mg weekly or placebo for 1 year; all pts received daily calcium 600 mg/vitamin D 400 units. Chemotherapy regimens included anthracyclines, taxanes, cyclophosphamide, methotrexate, or fluorouracil, with a mean duration of 146 days. Patients were stratified by tamoxifen, taxane use, time from last menses, and age. The primary endpoint was the change in lumbar spine bone mineral density (BMD) from baseline to 1 year. A two-sided two-sample t-test with 200 patients had 80% power to detect a 5% difference in the change over 12 months between treatment groups with a 5% Type I error rate. Linear regression modeling of the BMD at 1 year was used to adjust for covariates. Results: 216 women enrolled. 154 completed treatment. There was no difference in mean BMD change at 1 year vs. placebo (Table) and no difference in success rates (increase in BMD) between arms (p =0.43). Regression modeling confirmed no treatment effect (p=0.13) when controlled for baseline BMD and tamoxifen. No significant differences in adverse events were noted, except that arthralgias and chest pain were worse with placebo p=0.04). Conclusions: Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for BC. We gratefully acknowledge support from Aventis, Proctor & Gamble, and NCCTG (NIH CA25224) for this study. Changes in BMD from Baseline Measurement (g/cm) Risedronate Placebo P Value L Total - change at 1 year −0.06 −0.07 0.324 Femoral neck - change at 1 year −0.03 −0.03 0.364 Total hip - change at 1 year −0.03 −0.04 0.453 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aventis
Survival and prognostic factors in patients with malignant pleural mesothelioma (MPM) treated with neoadjuvant cisplatin- based chemotherapy and extrapleural pneumonectomy (EPP) (SITMP Study)
Authors: V. Mutri, C. Pinto, A. Marino, M. Di Bisceglie, D. Dell’Amore, R. Sacco, M. Boaron, G. Colucci, A. A. Martoni
Journal: Journal of Clinical Oncology (2007)

18061 Background: The aim of this study is to evaluate the impact on survival of preoperative chemotherapy in potentially resectable MPM and correlations with prognostic factors. Methods: The eligibility criteria were: histologically MPM, stage T1–3N0–2M0, age =75 years, KPS = 80, adequate organ function. A first group of pts (group A) received cisplatin 75 mg/m 2 d1 and gemcitabine 1,200 mg/m 2 d1,8, every 3 weeks for 4 courses, followed by EPP and by 6 courses of adjuvant chemotherapy with mitoxantrone 10 mg/m 2 d1, methotrexate 35 mg/m 2 d1 and mitomycin 7 mg/m 2 d1, every 3 weeks with mitomycin in alternate cycles. A second group of pts (group B) received cisplatin 75 mg/m 2 d1 plus pemetrexed 500 mg/m 2 d1 for 4 cycles. In each group, only those pts with metastatic lymph nodes and/or positive resection margins received radiotherapy after EPP. The prognostic factors evaluated were: sex, histotype, stage at diagnosis, clinical objective response. Results: Between February 2000 and December 2006, 32 pts were enrolled (8 group A, 24 group B). Pt characteristics were: 27M (84.4%), 5F (15.6%), median age 64 years (51–72), median KPS 100 (80–100), histological subtype: 27 (84.4%) epithelial, 2 (6.3%) sarcomatous, 3 (9.4%) mixed; IMIG stage: 6 (18.8%) I, 16 (50%) II, 10 (31.2%) III. The clinical response to neoadjuvant chemotherapy was: 10 (31.3%) CR + PR, 16 (50%) SD and 6 (18.7%) PD. Eighteen (56.3%) pts underwent EPP. In the 14 pts who did not undergo EPP: 5 (15.6%) were treated with pleurectomy and 9 (28.1%) were not treated with surgery. Two postoperative deaths (1 contralateral pneumonia and 1 ARDS) occurred after EPP. No pts were treated with radiotherapy after EPP. The estimated median overall survival, 1-year and 2-year survival rates in the pts treated with EPP and not treated with EPP were 20 and 12 months (p=0.468), 60 and 41%, 42 and 20%, respectively. In the multivariate analysis (Cox regression analysis), none of evaluated prognostic factors was significantly associated with an improved OS. Conclusions: These data show that preoperative chemotherapy followed by EPP is a feasible approach, while initial analysis suggests favourable survival. No significant prognostic factors were identified. No significant financial relationships to disclose.
Pulmonary viral infection in hematologic patients with and without stemcell transplantation
Authors: Lilian Junker, Jörg Halter, Alexis Dumoulin, Daiana Stolz, Dominik Heim, Martin Stern, Christoph Bucher, Jakob Passweg, Hans Hirsch, Michael Tamm
Journal: European Respiratory Journal (2011)

Pulmonary complications are frequent in hematologic patients. Regular investigation of BAL fluid includes bacterial/fungal culture, staining and PCR for mycobacteria, immunohistochemistry/Grocott staining for pneumocystis and cell differentiation. The increasing use of PCR allows to search for different viruses. In this study we analysed the diagnostic yield of a recently established multi PCR for detection of 13 viruses. 219 hematologic patients underwent diagnostic bronchoscopy with BAL from september 2009 to january 2011. 28 of patients received high dose chemotherapy, 143 underwent allogeneic and 13 autologous stemcell transplantation. Bacteria were cultured from 43 (20%) BALs: staphyloccocus aureus, pseudomonas aeruginosa, streptococcus pneumoniae, enterococcus, moraxella, enterobacteriaceae, klebsiella, corynebacterium, mycoplasma pneumoniae, mycoplasma hominis, chlamydia pneumoniae, bordetella pertussis. There were 7 cases of pneumocystis. In two patients we found mycobacterium gordonae. Aspergillus was cultured in 4 cases. In 81 (37%) patients viruses were documented. Most often we found rhinovirus (n=31; 14%), followed by CMV (n=18; 8%), HSV (n=13; 6%), RSV (n=10; 4.5%), coronavirus (n=8; 3.6%), adenovirus (n= 7; 3.2%), parainfluenza- and metapneumovirus (each n=5; 2.2%), H1N1 (n=4; 1.8%), influenza (n=3; 1.4%), and HHV6 (n=1; 0.4%).

Summary and conclusion: The incidence of viral infections is very high in patients with hematologic diseases and pulmonary symptoms. Multiplex PCR in the BAL should be introduced as a routine diagnostic procedure in this specific patient group allowing to withdraw or avoid antibiotic or antifungal therapy in many cases.
Cutting medical bed occupancy is linked to reduced patient mortality in UK hospital, study shows
Authors: Jacqui Wise
Journal: BMJ (2015)

Lowering medical bed occupancy was associated with reduced patient mortality and improved performance against the four hour emergency department target in one large UK hospital, research published online in the Emergency Medicine Journal shows.1

The researchers acknowledged that the association did not equate to causality and that several factors may have accounted for the findings. But they noted a possible link between overcrowding in the emergency department and poorer patient care, adding that this warranted further research.

Derby Teaching Hospitals NHS Foundation Trust introduced a 90% medical—as opposed to surgical—bed occupancy target in July 2013. …