tbuckley/cabot-search huggingface dataset:
Molecular tumor profiling (MTP) of poorly differentiated neoplasms (PDN) of unknown primary site.
Authors: F Anthony Greco, David R. Spigel, John D. Hainsworth
Journal: Journal of Clinical Oncology (2013)

11080 Background: The inability to definitively determine the lineage of neoplasms is less common with modern immunohistochemistry (IHC) and genetic profiling. Nonetheless some PDN defy lineage classification by extensive standard pathologic evaluation. The advent of MTP may provide a new method of improving the diagnosis of these challenging cancers. Methods: A total of 30 of 751 (4%) patients (pts) seen from 2000 – 2012 with cancer of unknown primary (CUP) had PDN without a definitive lineage determined by IHC (median 18 IHC stains, range 9 – 51). From 2008 – 2012 the 30 biopsies had MTP (RT-PCR mRNA CancerTYPE ID, bioTheranostics, Inc.). Additional IHC, genetic sequencing, fluorescent in situ hybridization for specific chromosomal changes and repeat biopsies were performed when feasible to support the MTP diagnosis, and clinical features correlated. Results: MTP lineage diagnoses were made in 25 of 30 (83%), including 10 carcinomas (3 germ cell, 2 neuroendocrine, 5 others), 5 melanomas, 8 sarcomas (3 peritoneal mesothelioma, 1 PNET) and 2 hematopoietic neoplasms (1 lymphoma, 1 chloroma). Additional IHC, genetic testing [BRAF, i(12)p] or repeat biopsies confirmed the MTP diagnoses in 11 of 15 tumors, and the clinical features were consistent with the MTP diagnoses in the majority of patients. Conclusions: This MTP assay can frequently provide a diagnosis for CUP pts and PDN without a definitive lineage defined by extensive IHC. The earlier application of MTP will likely provide an expedited diagnosis, and for some neoplasms is the only test capable of defining lineage and a more specific diagnosis. Appropriate therapy, particularly for pts with germ cell tumors, melanoma, and lymphoma depends on a specific tissue of origin diagnosis.
Association of gene expressions of TOP2A, GGH, and PECAM1 with hematogenous, lymph-node, and peritoneal recurrence in patients with stage II/III gastric cancer enrolled in the ACTS-GC study.
Authors: Masanori Terashima, Wataru Ichikawa, Atsushi Ochiai, Koji Kitada, Issei Kurahashi, Sinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura, Mitsuru Sasako
Journal: Journal of Clinical Oncology (2013)

4019 Background: Exploratory biomarker analysis was conducted to identify factors related to relapse sites in the ACTS-GC study, a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients (pts) with stage II/III gastric cancer. Methods: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 pts (78.3%), and 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were analyzed by quantitative RT-PCR after TaqMan assay-based pre-amplification. Gene expression levels were normalized to the geometric mean expressions of GAPDH, ACTB, and RPLP0, used as reference genes. The expression of each gene was categorized as lower or higher than the median value. The impact of gene expression on relapse site was analyzed using the 5-year relapse-free survival (RFS) data of the ACTS-GC. Results: Among the 829 pts, hematogenous, lymph-node, and peritoneal recurrence developed in 72, 105, and 138 pts, respectively. The hazard ratios (HR) (S-1 vs. surgery alone) were 0.79 (95%CI, 0.54-1.16) for hematogenous, 0.51 (95%CI, 0.31-0.82) for lymph-node, and 0.60 (95%CI, 0.42-0.84) for peritoneal recurrence. Among 63 screened genes, topoisomerase II alpha (TOP2A), gamma-glutamyl hydrolase (GGH), and platelet/endothelial cell adhesion molecule 1 (PECAM1) most strongly correlated with hematogenous, lymph-node, and peritoneal recurrence, respectively. Hematogenous RFS was significantly worse in TOP2A high pts than in low pts (HR, 2.35; 95% CI, 1.55-3.57). Lymph-node RFS was significantly worse in GGH high pts than in low pts (HR, 1.87; 95% CI, 1.13-3.08). Likewise, peritoneal RFS was significantly worse in PECAM1high pts than in low pts (HR, 2.37: 95% CI, 1.65-3.41). These factors were independent and stronger risk factors than tumor histological type on multivariate analysis. Conclusions: Expression levels of the TOP2A, GGH, and PECAM1 genes in primary tumors are respectively linked to high risks of hematogenous, lymph-node, and peritoneal recurrence in pts with stage II/III gastric cancer.
Efficacy of axitinib in renal cell carcinoma: Real-world experience at Gustave Roussy (IGR).
Authors: Margarida Matias, Laurence Albiges, Nathalie Lassau, Baya Benatsou, Charlotte Ablard, Francesco Massari, Bernard Escudier
Journal: Journal of Clinical Oncology (2014)

e15593 Background: Axitinib has shown activity in metastatic renal cell carcinoma (mRCC) in a large phase III, and has been recently approved in patients (pts) who failed sunitinib. It is available in France since November 2012, with recommended dose titration up to 10 mg bid in pts without hypertension (HTN) or grade >2 toxicity. Methods: We report the updated IGR real world experience with axitinib in mRCC. CT scans were performed at baseline, at 2 months (M) and every 2-3M thereafter. Each time possible, Dynamic Contrast Enhanced Ultrasonography (DCE-US) was performed at baseline, D15 and D30. Radiological Response and DCE-US results were assessed for determination of tumor response, progression-free survival (PFS), and DCE-US parameters. Results: From 11/2012 to 11/2013, 45 mRCC pts received axitinib for second orfurther line. Pts received axitinib in 2nd line (n=18) or further line (n=27). IMDC group was good, intermediate or poor in respectively 10, 15 and 20 pts. Dose titration was performed in 42% pts at 2 weeks (7 mg bid) and in 18% pts at 4 weeks (10 mg bid). HTN was the most common adverse event, with 40% and 7% grades 3 and 4 respectively. Other toxicities were as previously reported. Partial response was observed in 16% of pts with 5.9 months median PFS. PFS was similar in 2nd (5.03 M) or further lines (5.87 M) without impact of dose titration. HTN(grade ≥2 and ≥3) during treatment with axitinib was predictive of absence of progression (p=0.001 and 0.002) as well as better OS (p=0.002 and 0.012). DCE-US was performed in 15 pts, with a strong correlation between decrease in AUC and PFS (p=0.002) and OS (p=0.009). Median OS was not reached. Conclusions: Efficacy of axitinib in real life is similar to previously reported one. Efficacy appears comparable in 2nd or further line in our series. DC-US significantly predicts PFS and OS.
Homozygosity mapping of the gene for Hallervoden-Spatz syndrome to chromosome 20p12.3-p13 (Nature Genetics (1996) 14 (479-481))
Authors: T. Taylor, M. Litt, Patricia Kramer, M. Pandolfo, L. Angelini, N. Nardocci, M. Pineda, S. Davies, H. Hattori, P. J. Flett, M. R. Cilio, E. Bertini, S. J. Hayflick
Journal: Nature Genetics (1997)
Plasma levels of IL-8 and g-CSF in high-grade gliomas treated with bevacizumab.
Authors: Marica Eoli, Cristina Rabascio, Lucia Cuppini, Elena Anghileri, Serena Pellegatta, Angelica Calleri, Patrizia Mancuso, Paola Porrati, Francesco Bertolini, Gaetano Finocchiaro
Journal: Journal of Clinical Oncology (2012)

2083 Background: Bevacizumab, an anti-VEGF antibody, has shown significant activity in high grade gliomas (HGG). However, tumor recurrence inevitably occurs. Methods: We treated 63 recurrent HGG patients with poor prognostic factors with bevacizumab (10 mg/kg) and irinotecan (125 or 340 mg/m 2 ) every 2 weeks, and investigated IL-12, IL-13, IL-17, FGF basic, G-CSF, MIP-1b, PDGF-beta, plasma levels before starting treatment and every 8 weeks by Bioplex. Ten age- and sex-matched healthy controls were used for comparison. Results: After a median follow-up of 27 weeks, median OS and PFS were 33 and 18 weeks, respectively. PFS at 6 and 12 months were 32% and 12%, respectively. OS at 6 months was 60%. Toxicity was mild. Baseline higher amounts of IL-13 (48±174 pg/ml vs 3.44±0.9 pg/ml, p=0.0001) and lower amounts of MIP-1b (35.3±20.9 pg/ml vs 67.2±18.8 pg/ml, p=0.0002), PDGF-beta (1585.5±1585 pg/ml vs 7098±1585 pg/ml, p=0.0001) and VEGF (27±39.8 pg/ml vs 54.5±32 pg/ml, p=0.001) were detected in patients than in healthy controls. In a cohort of 15 non-responders (patients who progressed 8 weeks after treatment onset), baseline IL-8 (15.7±10.8 pg/ml vs 10.9±9.4 pg/ml, p=0.03) and G-CSF (113.3±54 pg/ml vs 84.9±59.2 pg/ml, p=0.03) were significantly higher than in patients responding to treatment. In the same cohort no significant reduction of VEGF and other cytokines was observed after 8 weeks of treatment, while a decrease of plasma VEGF was observed in the remaining patients (26±32 pg/ml vs 13.3±28.5 pg/ml, p=0.001). Furthermore, in a cohort of 22 long-term responders (patients who progressed after more than 18 weeks of treatment), levels of VEGF decreased after 8 weeks of treatment when compared to baseline, whereas no difference was observed in baseline levels (23.9±22.6 pg/ml vs 9.8±9.4 pg/ml, p=0.001). Conclusions: Data suggest that high levels of IL-8 and G-CSF at baseline associated with a lack of VEGF decrease after 8 weeks of treatment identify patients who are resistant to bevacizumab. This hypothesis should be tested in a large number of patients.
Contents Vol. 85, 2016
Authors: Gregor Hasler, Chiara Rafanelli, Matteo Bonomo, Sara Gostoli, Elena Tomba, Lucia Tecuta, Richard Balon, Per Bech, Falk Leichsenring, Christiane Steinert, Antonio Piolanti, Emanuela Offidani, Maria Fara De Caro, Domenico Laera, Francesca De Robertis, Alessandro Taurino, Jing Wei, Lan Zhang, Xudong Zhao, Kurt Fritzsche, Michael Schaefer, Rebecca Harke, Claudia Denke, Małgorzata Anna Basińska, Agnieszka Woźniewicz, Carlo Dallocchio, Michele Tinazzi, Natale Arnó, Roberto Erro, Jenny Guidi, Sara Gostoli, Giovanni A. Fava, Nicoletta Sonino, Martin Sack, Peter Henningsen, Johannes Kruse, Stefanie Zehl, Alexander Otti, Claas Lahmann, Markus Stingl, Frederica Bombieri, Christian Schmahl, Mathias Berger, Lisa Lyssenko, Gerhard Müller, Nikolaus Kleindienst, Georg Eifert, Alexander Kölle, Siegmar Nesch, Jutta Ommer-Hohl, Michael Wenner, Martin Bohus, Hans M. Nordahl, Patrick A. Vogel, Gunnar Morken, Tore C. Stiles, Pål Sandvik, Adrian Wells, Elisabeth Schramm, Johannes Michalak, Thomas Probst, Thomas Heidenreich, Nicolai Bissantz, Satz Mengensatzproduktion, Druckerei Stückle, Druckerei Stückle
Journal: Psychotherapy and Psychosomatics (2016)

and/or infrequently employed drug.
Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small cell lung cancer: An analysis of the Spanish Lung Cancer Group pharmacogenomic study of cisplatin and docetaxel combination (PLATAX)
Authors: C. Camps, R. De Las Peñas, G. López-Vivanco, J. Garde, J. Sanchez, N. Viñolas, R. García-Gómez, S. Barón, J. Terrasa, E. Pujol
Journal: Journal of Clinical Oncology (2006)

7124 Background: Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. Methods: We analysed data of 493 patients who received chemotherapy (cisplatin and docetaxel) within the pharmacogenomic, open-label, single-arm, multicentric PLATAX trial. Three subgroups of patients were considered: global population, patients who received at least three cycles of chemotherapy, and those who received at least six cycles. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). Relative dose intensity was analysed for both drugs. The primary endpoint was overall survival. Results: Median overall survival was 9 months (8.2–9.7). Median relative dose intensity was 0.97 for cisplatin and docetaxel. 403 patients received at least three cycles of chemotherapy, and 255 received six or more. Neutropenia appeared in 172 patients (30.8%), 72 of them G3–4 (18.6%). Dose intensity was lower in patients who presented any grade of neutropenia versus those without neutropenia in the three analyzed subgroups, for both drugs (p &lt; 0.05). Factors associated with higher risk of death were ECOG 1–2 (HR 1.8, p = 0.00) and female (HR 1.5, p = 0.02). There were no differences in overall survival between patients with G0 vs G1–2 vs G3–4 neutropenia (8.7 vs 11.6 vs 9.6 m, p = 0.41), however the risk of death was lower in patients with ECOG 0, that presented neutropenia (HR: 0.545, IC 95%: 0.31, 0.96; p = 0.034). Conclusions: Neutropenia during chemotherapy may be associated with increased survival of patients with advanced non-small cell lung cancer and ECOG 0. Its absence is not a result of underdosing. Prospective trials are needed to assess whether neutropenia could be a biological measure of drug activity and a marker of efficacy. No significant financial relationships to disclose.
Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1
Authors: A Cosson, E Chapiro, N Bougacha, J Lambert, L Herbi, H-A Cung, C Algrin, B Keren, F Damm, C Gabillaud, M-N Brunelle-Navas, F Davi, H Merle-Béral, M Le Garff-Tavernier, D Roos-Weil, S Choquet, M Uzunov, V Morel, V Leblond, K Maloum, S Lepretre, P Feugier, C Lesty, J Lejeune, L Sutton, Y Landesman, S A Susin, F Nguyen-Khac
Journal: Leukemia (2017)
Development of brain metastases in patients with metastatic melanoma treated with ipilimumab plus temozolomide.
Authors: Jennifer Wang, Sapna Pradyuman Patel, Wen-Jen Hwu, Kevin B. Kim, Nicholas E. Papadopoulos, Patrick Hwu, Laszlo George Radvanyi, Sandy Mahoney, Tawania L Deburr, Roland Bassett, Agop Y. Bedikian
Journal: Journal of Clinical Oncology (2012)

e19014 Background: Melanoma has a high predilection for brain metastasis (BM), and despite treatment, survival is often 3 to 6 months. There have been a number of reports of disease regression in BM with each Ipilimumab (Ipi), an anti-CTLA 4 antibody, and temozolomide (Tem), an alkylating drug capable of crossing the blood-brain barrier, in patients with metastatic melanoma (MM). Previous Ipi trials excluded patients with BM. Previous Tem trials have BM incidence ranging from 20 to 36%. Here we describe our experience with the combination of Ipi+Tem and BM. Methods: Patients (pts) are from a 64-patient cohort with unresectable Stage III or Stage IV metastatic melanoma enrolled in a single-center Phase II trial of Ipi+Tem. Induction phase consisted of Ipi 10mg/kg intravenous (IV) on Day 1 and oral Tem 200mg/m2 Days 1-4 every 3 weeks for 4 courses. Maintenance phase was Ipi 10mg/kg IV every 12 weeks and oral Tem 200mg/m2 on Days 1-5 every 4 weeks. Brain MRI was obtained every 2 cycles as part of the protocol. We evaluated development of BM in these pts. Results: At a median follow-up of 41 weeks, 11 pts (17%) developed new BM. Two pts with a history of prior BM were enrolled; one developed new BM while the other achieved a complete response of disease in the lungs and remains on study. All pts who developed BM had Stage IV disease at baseline, five (45%) had elevated baseline LDH, and nodular melanoma was the most common histology (55%). The median time to development of BM with Ipi+Tem was 12 weeks. Mutation status, stage, and primary tumor location and depth were not significantly associated with the development of BM. Elevated baseline LDH was a significant predictor for development of BM (p=0.001, log-rank test). The median overall survival for both the BM and non-BM groups has not been reached. Conclusions: There is little known about the development of BM with various treatments for MM. To our knowledge, this is the first study to evaluate the development of BM in pts receiving Ipi-based treatment. Our data suggest that Ipi+Tem and Ipi monotherapy warrant further research in the prevention and treatment of BM in MM.
Clinical signs of dying in cancer patients: A prospective longitudinal observational study.
Authors: David Hui, Renata dos Santos, Kelly L. Kilgore, Thiago Buosi Silva, Gary B. Chisholm, Pedro Emilio Perez-Cruz, Camila Souza Crovador, Raphael de Almeida Leite, Egidio Del Fabbro, Maria Salete de Angelis Nascimento, Donna S. Zhukovsky, Fabiola de Lourdes GonÃƒÂµaves de Freitas Seriaco, Suresh K. Reddy, Luciana Machado Frascari, Sriram Yennurajalingam, Carlos Eduardo Paiva, Rony Dev, Stacy Hall, Julieta Fajardo, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

e19528 Background: The fundamental process of dying has not been well characterized. We determined the frequency, onset, accuracy and likelihood ratio (LR) for various clinical signs in dying cancer patients. Methods: We systematically documented 100 signs/symptoms on consecutive advanced cancer patients admitted to palliative care units at MD Anderson Cancer Center (MDA) in the United States and Barretos Cancer Hospital (BCH) in Brazil every 12 hours from admission to death/discharge in 2010/2011. We analyzed the serial data from death backwards using generalized estimating equations for decedents, and calculated the accuracy and LRs for all patients. Results: 203/357 (MDA 52, BCH 151) patients died, and had the following characteristics: average age 58 (range 18-88), female 49%, Caucasian 76%, median admission length 6(Q1-Q3 4-9) days. The average palliative performance scale decreased from 50% to 20% (P&lt;0.001). The frequency of pulselessness of radial artery (PRA), decreased urine output, respiration with mandibular movement (RMM), inability to close eye lids (EL), death rattle, vocal cord grunting, Cheyne Stokes and nasolabial drooping increased as death approached (P&lt;0.001 for all), with high LR+ for impending death (Table 1). Presence of PRA, RMM and EL had a high specificity (100%), positive predictive value (99.4%) and LR+ (13) for death in 3 days. Conclusions: We identified highly specific cardiovascular, respiratory and neuromuscular signs associated with imminent death. [Table: see text]
The association of toxicities and outcomes with circulating endothelial cells (CEC) in non-small cell lung cancer (NSCLC) patients (pts) treated with bevacizumab (Bev).
Authors: Nooshin Hashemi Sadraei, Lingling Du, Ruchi Yadav, Ronald Grane, Barbara Jacobs, John Hamulak, Patrick C. Ma, Nathan A. Pennell, Paul Elson, Ernest C. Borden
Journal: Journal of Clinical Oncology (2013)

e19012 Background: Bev in combination with chemotherapy (CT) is a standard treatment for pts with stage IV NSCLC. However, there are no established biomarkers to improve benefit-to-risk profile of therapy. CEC are a marker of vascular turnover. We hypothesized CEC may be associated with treatment outcome/toxicity. Methods: Stage IV NSCLC pts were treated with Bev along with CT of choice per clinician. CEC were measured at baseline and after 2 cycles of Bev-containing therapy. CellSearch (Veridex, New Jersey) was used to capture and quantify CEC via immunomagnetic and immunofluorescence techniques. CEC were enumerated as nucleated, CD146+/CD105+/CD45- cells in 4 mL of blood. For comparison, baseline CEC were also collected in 3 other groups; healthy subjects, stage I-III NSCLC, and advanced solid tumor pts. Chi-square tests and non-parametric methods were used to assess associations between CEC and pt/disease characteristics, toxicity, and proportional hazards models were used for comparisons of progression free and overall survival (PFS and OS). Results: Evaluated were 62 individuals: 29 stage IV NSCLC, 10 stage I-III NSCLC, 13 advanced solid tumors (melanoma, sarcoma, renal and adrenal cancers), and 10 healthy subjects. The median of CEC/ml blood in healthy subjects was 6. Based on its distribution, CEC &gt;13/ml was deemed elevated. Elevated CEC was seen in 48% of stage IV NSCLC (median 12/ml), in comparison to 20% of stage I-III NSCLC (8/ml) and 23% of advanced solid tumors (6/ml) Baseline CEC in stage IV NSCLC was independent of patient/ disease characteristics including site of disease and tumor size. CEC increased during treatment in most patients (61%). CEC doubling between baseline and cycle2 was associated with more cytopenia and hemorrhage. (75% vs 20%, p=0.05 and p=0.03 for absolute and relative CEC changes). Baseline CEC and changes during treatment did not correlate with response (p≥ 0.32) and pts with elevated baseline CEC had a trend towards worse PFS (p=0.09) and OS (p=0.10). Conclusions: CEC are commonly elevated in advanced NSCLC. CEC increases may be predictive of adverse events from Bev-CT and when elevated at baseline may suggest worse PFS.
MIMEB: A phase II trial to evaluate FDG-PET/FLT-PET and DCE-MRI for early prediction of efficacy in patients with advanced non-small cell lung cancer treated with erlotinib and bevacizumab.
Authors: Matthias Scheffler, Marc Christiaan Allardt Bos, Martin Sos, Lucia Nogova, Christian Mattonet, Irini Papachristou, Deniz Kahraman, Carsten Kobe, Ronald Boellaard, Adriaan A. Lammertsma, Lukas Carl Heukamp, Reinhard Büttner, Thomas Elter, Karin Toepelt, Walburga Engel-Riedel, Erich Stoelben, Bernd Neumaier, Markus Dietlein, Thomas Zander, Juergen Wolf
Journal: Journal of Clinical Oncology (2012)

7603 Background: Since the introduction of targeted therapy into the treatment of NSCLC, molecular imaging tools gain in importance for assessment of pharmacodynamics, pharmacokinetics and prediction of therapeutic outcome. Tumor metabolism (by FDG-PET), proliferation (by FLT-PET), and vascularization (by DCE-MRI) can be noninvasively assessed to quantify the effects of targeted therapy on tumor biology. We set up a trial to evaluate the effects of combined erlotinib (E) and bevacizumab (B) treatment in patients with advanced non-squamous cell NSCLC and to identify prospectively patients who benefit from this combination. Methods: Patients with non-squamous NSCLC stage IV without prior systemic therapy received at least six weeks of combined E and B. FLT and FDG-PET scans as well as DCE-MRI-scans were performed at baseline, after 1 week of therapy and after 6 weeks of therapy. Standard uptake values of the PET scans and vascularization parameters of the DCE-MRI scans were analyzed and coregistrated. Tumor specimens were analysed within a network screening panel. The primary objective of this trial was to evaluate the accuracy of the imaging tools for early prediction of nonprogression and PFS and its association with molecular markers. Results: Of the 40 patients, all received FDG-PET analyses, whereas FLT-PET was performed in 38 patients and DCE-MRI in 36 patients. Median OS was 13.4 months, median PFS was 5.9 months. Until January 2012, tissue specimens from 25 patients have been genetically analysed. First results show that even patients with KRAS, PI3K and BRAF mutations profiting from the combination either by response or prolonged PFS could be identified by early imaging assessment. Conclusions: The efficacy of E +B in unselected patients with NSCLC was comparable with platinum-based chemotherapy. In order to identify imaging-based predictive biomarkers to identify the subpopulation of patients with pronounced benefit of this combination FDG-, FLT- PET and DCE–MRI were successfully implemented in the treatment plan. Results of the imaging analysis and the correlation with tissue-based biomarkers will be presented.