tbuckley/cabot-search huggingface dataset:
Amethyst NSCLC trial: Phase 2, parallel-arm study of receptor tyrosine kinase (RTK) inhibitor, MGCD265 in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with activating genetic alterations in mesenchymal-epithelial transition factor (MET)
Authors: L. Bazhenova, R. Mehra, T. Nagy, L. Cavanna, J.-S. Lee, J.-Y. Han, H.K. Kim, B. Halmos, M. Shum, M. Schreeder, I. Rybkin, F. Badin, R. Mena, P.A. Jänne, J. Christensen, V. Tassell, R. Chao, D. Faltaos, D.-W. Kim
Journal: Annals of Oncology (2016)
BMET-25. SECTOR IRRADIATION VS. WHOLE-BRAIN IRRADIATION AFTER RESECTION OF SINGULAR BRAIN METASTASIS – INTERIM ANALYSIS OF A PROSPECTIVE RANDOMIZED MONOCENTRIC TRIAL
Authors: Johannes Kerschbaumer, Daniel Pinggera, Marcel Seiz-Rosenhagen, Meinhard Nevinny-Stickel, Claudius Thomé, Christian Freyschlag
Journal: Neuro-Oncology (2016)

Microsurgical resection of cerebral metastases leads to prolonged survival and rapid relief of symptoms in selected patients. To minimize the risk of local recurrence whole-brain irradiation (WBRT) has been established as standard adjuvant treatment in these patients. With prolonged overall survival (OS), deleterious effects of WBRT become more relevant. Sector-irradiation (SI) aims to spare brain tissue by focusing the irradiation in the area of the tumor bed and a surrounding 6 mm security margin. The study is a monocentric, randomized trial in patients with a singular brain metastasis. Efficacy was evaluated by visits every 3 months to control for local recurrence, distant recurrence and general condition. At the time of interim analysis 28 patients were enrolled in this trial. There were 3 drop-outs (1 protocol violation, 2 due to deterioration not related to the surgical treatment). 12 patients were assigned to WBRT and 13 patients were randomized to SI therapy. Treatment started within 30 days after resection in both groups. There was no local recurrence in the sector group, whereas one patient recurred within 3 months after WBRT locally. A distant progression was noted in 3 patients after WBRT within 9 (3-20) months and 4 patients after SI developed distant metastases after a mean of 5 (1-9) months (n.s.). The OS was higher in the SI-group with 12,2 months (10 of 13 patients still alive) compared to 11,2 months (7 of 12 patients still alive, n.s.). Sector irradiation as a method sparing brain tissue achieves local control comparable to WBRT after resection of a singular brain metastasis. Our preliminary results thus indicate equivalent efficacy. With the unexpectedly long average survival of the patient cohort (17 of 25 patients still alive after an average of 11,68 months), further follow-up is mandatory to determine any impact of OS.
P08.57 Involvement of both the extrinsic and intrinsic apoptotic pathways with clomipramine treatment of human glioblastoma cells under normoxic and hypoxic conditions
Authors: S. C. Higgins, A. Alagbaoso, T. Javid, S. Polyzoidis, K. Ashkan, H. L. Fillmore, G. J. Pilkington
Journal: Neuro-Oncology (2016)

AbstractIntroduction:The tricyclic antidepressant clomipramine, used clinically since the 1960’s, has been shown to have selective cytotoxicity against glioma cells in vitro and has also been shown to cross the blood brain barrier. While reports suggest clomipramine acts via the mitochondria, the mechanism of action is not fully understood.Materials and Methods:In this study, 8 human biopsy-derived glioblastoma early passage cell lines were treated with 0–200µM clomipramine over 72hrs. Cell viability was measured using the MTS assay, cellular ATP levels using the Cell Titer Glo assay and capsase activation by Caspase-Glo 3/7, 8 and 9 assays. Immunocytochemistry using Mitotracker Red and cytochrome C antibodies was performed. The JC-1 dye was used to evaluate mitochondrial transmembrane potential and DAPI was used to characterise the cell cycle.Results:Clomipramine reduced cell viability in a dose and time dependent manner with IC50 values in the range of 22–60µM at 24hrs. Compared to controls, following 24 hr treatment with 75µM clomipramine, there was a significant reduction of cellular ATP levels (by approximately 100%, p<0.0001), depolarisation of the mitochondrial transmembrane potential and release of cytochrome C from the mitochondria. The extrinsic apoptotic pathway was activated at 12 hours whereas the intrinsic (mitochondrial-mediated) pathway was activated at 24 hours as shown by elevation of caspase 8, 9 and 3/7 levels. The reduction in cell viability in response to clomipramine was attenuated by the pan-caspase inhibitor Z-VAD-FMK, indicating involvement of caspases in the mechanism of action. With the most significant effects observed with SEBTA-023; 24 hours at 75µM clomipramine cell viability increased by 50% and 67% under hypoxic and normoxic conditions respectively (p<0.0001). The effects on the cell cycle were evaluated and clomipramine treatment led to cell cycle arrest in G2/M phase. Two other tricyclic antidepressants, imipramine and amitriptyline were also examined and clomipramine was deemed to be the most effective inducer of apoptosis.Conclusions:This work provides further insights to the mechanism of action of this class of repurposed drug as a potential adjuvant treatment for GBM.
Cisplatin-raltitrexed vs cisplatin-pemetrexed in the treatment of advanced pleural mesothelioma. final results of a network meta-analysis
Authors: S.L.V. Nicoletti, C. Cherubini, M. Papi, E. Tamburini, M. Fantini, M. Nicolini, C. Ridolfi, C. Santelmo, L. Gianni, L.A. Lazzari Agli, D. Tassinari
Journal: Annals of Oncology (2016)
Cetuximab in combination with platinum-based chemotherapy or radiotherapy in recurent and/or metastatic SCCHN in a non-selected patient cohort (interim analysis of the phase IV SOCCER trial)
Authors: M. Hecht, D. Hahn, D. Beutner, D. Reichert, T. Göhler, R. Wurm, M. Welslau, L. Renziehausen, P. Balermpas, T. Bergmann, M. Aßmann, C. Belka, K. Orlowski, M. Finzsch, G. Illerhaus, R. Fietkau
Journal: Annals of Oncology (2016)
EPID-08. TREATMENT OUTCOME FOR EPENDYMAL TUMORS IN THE UNITED STATES
Authors: Kailin Yang, Leo Kim, John Suh, Erin Murphy, Samuel Chao
Journal: Neuro-Oncology (2016)

Ependymal tumors are rare CNS neuroectodermal neoplasm with a significant impact on patient mortality and quality of life. This study is to compare the effect of surgery and adjuvant radiation therapy (RT) on survival outcomes for ependymal tumors in the United States. 2091 patients aged >=18 with ependymal tumors were identified from the Surveillance, Epidemiology, and End Results registry (2000-2009). Surgical treatment was categorized into gross total resection (GTR) and no GTR. Log-rank test and multivariate Cox proportional hazard modeling were used to examine treatment effect on overall survival (OS). On univariate analysis, GTR was associated with improved OS for ependymoma (89% vs. 81%, p<0.01) and similar trend was observed for myxopapillary ependymoma (97% vs. 94%, p=0.13), subependymoma (93% vs. 89%, p=0.37), anaplastic ependymoma (50% vs. 26%, p=0.10). In multivariate analysis adjusting for age, sex, race, marital status, and year of diagnosis, GTR was associated with significantly improved OS for ependymoma (HR 0.711, 95% CI 0.527-0.953, p=0.02) but only a trend toward OS for anaplastic ependymoma (HR 0.703, 95% CI 0.426-1.145, p=0.16). Using multivariate analysis, adjuvant RT was found to associate with worse OS for ependymoma (HR 2.049, 95% CI 1.207-3.387, p=0.01), and no association was observed for the other histological groups. Among all prognostic factors, advanced age was determined to most significantly affect OS for all 4 histological groups: for age group 60-74 (compared to age group 18-44), myxopapillary ependymoma (HR 17.661, 95% CI 4.326-82.000, p<0.01), subependymoma (HR 4.932, 95% CI 1.522-19.044, p=0.01), ependymoma (HR 5.943, 95% CI 3.967-8.996, p<0.01), anaplastic ependymoma (HR 3.076, 95% CI 1.389-6.520, p=0.01). Ependymoma was the most common histological subtype among all ependymal tumors in the United States. Age at diagnosis was found to significantly contribute to patient long term survival. Surgery in the format of GTR provided survival benefit particularly in ependymoma.
Long-term outcome of almost 3,000 patients with carcinoma of the esophagus: Evaluation of the new UICC/AJCC staging system.
Authors: R. Gertler, T. Schuster, M. Feith
Journal: Journal of Clinical Oncology (2011)

64 Background: In the new 7th edition of the TNM classification for cancers of the esophagus, the UICC stage groups are still based on the anatomic extent of the tumor alone. In contrast, the AJCC prognostic groupings is the first staging system for esophageal cancer to add histologic tumor type, tumor site and grade. Methods: Data of a single center cohort of 2,920 patients operated for cancers of the esophagus were analyzed. Statistical methods to evaluate survival of the patients and the prognostic performance of the new staging systems included Kaplan-Meier analyzes and time dependent ROC-analysis. Results: UICC stage, R-status, histologic tumor type and age were identified as independent prognostic factors for cancers of the esophagus. Grade and tumor site, additional parameters in the new AJCC prognostic groupings, were not significantly correlated with survival. Patients with esophageal adenocarcinoma had a significantly better long-term prognosis after resection than patients with squamous cell carcinoma (p &lt; 0.0001). The new number-dependent N- classification proved superior to the former site-dependent classification with significantly decreasing prognosis with increasing number of lymph node metastases (p &lt; 0.001). The new subclassification of T1 tumors also revealed significant differences in prognosis between pT1a and pT1b patients (p &lt; 0.001). However, the multiple new UICC and AJCC subgroupings did not prove distinctive for survival between stages IIA and IIB, IIIA and IIIB, and between IIIC and IV. Conclusions: The new 7th edition of the TNM classification improved the predictive ability for cancers of the esophagus, however, stage groups could be condensed to a clinically relevant number. Differences in patient characteristics, pathogenesis and especially survival clearly identify adenocarcinomas and squamous cell carcinoma of the esophagus as two separate tumor entities requiring differentiated therapeutic concepts. No significant financial relationships to disclose.
Phosphoinositide-3-kinase single-nucleotide polymorphisms frequencies between malignant melanoma patients and healthy volunteers shared by sex
Authors: F. Morgese, S. Pagliaretta, S. Rinaldi, M. Torniai, A. Savini, A. Onofri, D. Soldato, A. Fabbri, R. Berardi
Journal: Annals of Oncology (2016)
Exploiting Cytokine Secretion to Rapidly Produce Multivirus-Specific T Cells for Adoptive Immunotherapy
Authors: Yuriko Fujita, Ann M. Leen, Jiali Sun, Yozo Nakazawa, Eric Yvon, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney
Journal: Blood (2008)
FGFR4 exerts differential roles in tumorigenesis through a mechanism of cooperation
Authors: A. Quintanal-Villalonga, I. Ferrer, Á Marrugal, L. Ojeda-Márquez, L. García-Redondo, R. Suarez, J. Zugazagoitia, A. Carnero, L. Paz-Ares, S. Molina-Pinelo
Journal: Annals of Oncology (2016)
A randomized phase II study to investigate the addition of PD-L1 antibody MEDI4673 (durvalumab) to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (GeparNuevo)
Authors: S. Loibl, A. Schneeweiss, N. Burchardi, J.-U. Blohmer, C. Hanusch, S.D. Costa, J. Huober, C. Jackisch, G. von Minckwitz, S. Kümmel, S. Paepke, C. Denkart, M. Untch
Journal: Annals of Oncology (2016)
Poly (ADP-ribose) polymerase 1 mRNA levels strongly correlate with the prognosis of myelodysplastic syndromes
Authors: P Diamantopoulos, K Zervakis, P Zervakis, M Sofotasiou, T Vassilakopoulos, I Kotsianidis, A Symeonidis, V Pappa, A Galanopoulos, E Solomou, E Kodandreopoulou, V Papadopoulou, P Korkolopoulou, M Mantzourani, G Kyriakakis, N-A Viniou
Journal: Blood Cancer Journal (2017)

Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0.011) and the cytogenetic risk (P=0.008). In all cases, higher PARP1 levels were correlated with a higher risk category. Moreover, we found a significant survival disadvantage for patients with high PARP1 levels (median survival of 37.4 months versus 'not reached' for low PARP1 levels, P=0.0001, and a 5-year survival rate of 29.8 versus 88.9%, respectively). PARP1 mRNA levels were found to be the stronger predictor of survival in multivariate analysis. These correlations have never been reported in the past and may render PARP1 a prognostic factor to be incorporated in the current prognostic systems for MDS, also laying the basis for clinical trials evaluating PARP1 inhibitors in higher-risk MDS.
STUDIES ON THE TOTAL BILE
Authors: Peyton Rous, G. O. Broun, Philip D. McMaster
Journal: The Journal of Experimental Medicine (1923)

Carbohydrate feeding or injection produces often a temporary increase in the rate at which bilirubin is put forth in the bile, but none in the amount of the pigment secreted from day to day. There would appear to be no ground for the supposition that bilirubin is normally derived in part from the carbohydrates of the food.
MIBG Localization of a Subclinical Paraganglioma of the Bladder
Authors: Ayman Mithqal, Pasha Darvishi, Patrice Rehm
Journal: Clinical Nuclear Medicine (2017)

Urinary bladder paragangliomas are very rare, and the majority are hormonally active. Nonfunctioning paragangliomas are even rarer and more difficult to diagnose because of absence of catecholamine secretion. We present a 27-year-old woman with an asymptomatic paraganglioma of the urinary bladder discovered incidentally in a patient with prior resection of a functional pararenal paraganglioma. Metabolic profiles and cystoscopy were nondiagnostic. We demonstrate the increased sensitivity of I-MIBG SPECT/CT compared with planar scintigraphy for detection of a nonfunctional paraganglioma of the urinary bladder, which makes it valuable in evaluation of functional and nonfunctional paragangliomas.
Retro-orbital, Breast, Cardiac, Skin, and Subcutaneous Metastases of Neuroendocrine Tumor From a Tail Gut Cyst on 68Ga-DOTATATE PET/CT Imaging
Authors: Emine Acar, Hatice Durak, Sare Kabukcuoğlu, Serap Işiksoy, Gamze Çapa Kaya
Journal: Clinical Nuclear Medicine (2017)

Tail gut cysts are rare congenital lesions developing from postanal primitive gut remnants. They are mostly benign but carry a potential of malignant transformation, such as adenocarcinoma, neuroendocrine tumor, adenosquamous carcinoma, and pseudomyxoma peritonei. We present a 39-year-old woman with a neuroendocrine tumor arising within a tail gut cyst. She underwent complete resection in 2011. After 4 years, she was admitted with breast nodules, left proptosis, and gaze difficulties. Ga-DOTATATE PET/CT demonstrated extensive metastases including pelvic, lymph node, adrenal gland, bone, retro-orbital, cardiac, breast, skin, and subcutaneous metastases.
MNGO-17. MENINGIOMA VOLUME RESPONSE TO RADIATION
Authors: William Broaddus, Jacob Hall, Timothy Harris, Sherry Zhao, Aravind Somasundaram, Charles Opalak, Kathryn Workman, Sharon Wolber, Emmy Miller
Journal: Neuro-Oncology (2016)

Recurrent meningiomas and those for which surgery is not a good option have a high rate of response to radiation treatment. It is well known that meningiomas treated with radiation may shrink in volume, but they seldom demonstrate complete responses. However, the pattern of volume change following radiation is poorly understood and not well characterized. We performed a retrospective analysis of tumor volumes in sequential imaging studies in patients with meningiomas who received radiation treatment. We identified 27 patients, 5 who received stereotactic radiosurgery (SRS: 5 or fewer fractions) and 22 who received radiotherapy (RT) in 28-30 fractions. They had the following demographics: 19 females and 8 males; age range of 31-87 years, with a median age of 59; follow up range of 0.4-7 years, median of 2.4 years. There were 6 WHO grade II and 21 WHO grade I meningiomas, and treated tumor volumes ranged from 0.3 – 50 cc, with a mean and median of 7.9 cc and 4.7 cc, respectively. At last follow up, 2 patients showed volume increases of 5% and 16%, respectively, and 25 patients showed a volume decrease of as much as 71%. The average change for all patients was a decrease of 24% +/- 20% (SD). There were no significant differences in tumor volume change based on age, type of therapy (SRS vs. RT) or grade of tumor. There was a trend toward greater decrease in tumor volume with follow up time, but wide variability was noted. Quantitative analysis and mathematical modeling of individual tumor responses over time are underway and should provide important information on the individual responses of meningiomas following radiation. This will help guide clinical decision making on the use of radiation for management and follow up of patients with meningiomas.
P11.08 Even the good can be bad: malignant evolution of a “benign” WHO grade I meningioma
Authors: A. Innocenti, G. Simonetti, P. Gaviani, A. Botturi, E. Lamperti, M. Terreni, A. Silvani
Journal: Neuro-Oncology (2016)

Introduction:
Generally considered the model of benign tumors of Central Nervous System (CNS) and associated with a good outcome, meningioma may rarely have an aggressive behavior such as metastatic disease. Unusually, even grade I meningiomas can assume that malignant behavior. We report a case of non-CNS metastases of WHO grade I meningioma, focusing on predisposing factors and predictors of malignant behaviour.
Successful Early Outcome with Low-Dose (400 cGY) Total Body Irradiation in Combination with Busulfan and Fludarabine Myeloablative Conditioning Followed By Matched Unrelated Donor Allogeneic Peripheral Blood Stem Cell Transplantation in a Patient with Non-Remission Acute Myelogeneous Leukemia with Diffuse Extramedullary Disease in Multiple Sites
Authors: Gorgun Akpek, Sunita Nathan, John J. Maciejewski, Deborah A. Katz, Ashley Echeverria, Lindsay Hodges, Aidnag Z. Diaz, Ross Allen Abrams
Journal: Blood (2016)
RARE-01. INTRAVASCULAR LYMPHOMA (IVL). A SINGLE INSTITUTION STUDY FROM THE MODERN NEURO-IMAGING ERA
Authors: Brian Patrick O’Neill, Claudia Chou, Nabila Bennani, Patrick Johnston, Ellen McPhail, David Schiff
Journal: Neuro-Oncology (2016)

Intravascular lymphoma (IVL) is a rare and aggressive variant of systemic non-Hodgkin’s lymphoma (NHL). IVL typically presents as a multi-infarct state involving the central nervous system (CNS). The diagnosis is confirmed by the demonstration of large tumor cells within the lumina of small to medium-sized vessels. Cases were sourced from the Mayo Lymphoma Registry, and the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE. All cases were confirmed by a pathologist expert in hematologic malignancies. Data points comprised clinical, pathology, laboratory, imaging, initial therapeutics, salvage regimens, and outcomes domains. This study was approved by the Mayo Foundation Institutional Review Board. All study patients were seen and diagnosed at Mayo Clinic, Rochester MN. The cohort comprised 13 women and 13 men, aged 44 to 85 years old at diagnosis (mean 63.9; median 65.5). Neoplastic cells were of B-cell histiotype in all patients. No patient was HIV-positive. All but 6 had symptoms of CNS IVL present at diagnosis. Symptom duration before diagnosis ranged from 4 to 36 weeks (mean 16.45 weeks; median 13 weeks). Nine patients had findings of extra-CNS IVL on physical exam - splenomegaly (5 patients) and skin lesions (4 patients). Ten patients had positron emission tomography (PET) and 7 displayed evidence for systemic IVL or lymphoma at diagnosis. All but one patient received chemotherapy at diagnosis. Thirteen patients were alive at last followup. Overall median survival for the 13 patients who were dead at last followup was 8 weeks (range 0-126 weeks). IVL is a clinical entity with neurologic and systemic manifestations. Although typically presenting with neurologic symptoms most patients will have clinical and imaging features of systemic lymphoma. If diagnosed early before significant and permanent morbidity occurs, IVL may have a good outcome.
Incidence of Cytogenetic Abnormalities in Newly Diagnosed Binet Stage A B-CLL and Relationship with Prognostic Biomarkers: Preliminary Results On 305 Patients Included in the Prospective O-CLL1 GISL Study.
Authors: Sonia Fabris, Giovanna Cutrona, Massimo Gentile, Serena Matis, Emanuela Anna Pesce, Francesco Di Raimondo, Caterina Musolino, Marco Gobbi, Nicola Di Renzo, Francesca Mauro, Renato Cantaffa, Maura Brugiatelli, Francesco Merli, Simonetta Zupo, Caterina Mammi, Luca Baldini, Francesco Angrilli, Gianni Quintana, Ugo Consoli, Giovanni Bertoldero, Emilio Iannitto, Paolo Di Tonno, Antonio Fragasso, Stefano Molica, Pellegrino Musto, Maria Cristina Cox, Gianluca Festini, Vincenzo Callea, Stefano Sacchi, Agostino Cortelezzi, Giorgio Lambertenghi Deliliers, Robert Foà, Massimo Federico, Manlio Ferrarini, Fortunato Morabito, Antonino Neri
Journal: Blood (2009)
RARE-29. HIGH-DOSE METHOTREXATE (HD MTX)-BASED TREATMENTS OF PRIMARY CNS LYMPHOMA: OPTIMAL DOSE REVISITED - A RETROSPECTIVE ANALYSIS OF OUTCOMES IN TERTIARY MEDICAL CENTER
Authors: Or A. Bainhoren, Noam Asna, Liran Mendel, Deborah T. Blumenthal, Felix Bokstein
Journal: Neuro-Oncology (2016)

Standard treatment regimens for PCNSL typically combine HD MTX in various doses with other cytotoxic drugs, with or without WBRT. To evaluate efficacy and tolerability of different MTX doses in PCNSL. We screened records of PCNSL patients treated in TASMC between 2003-2015. A comparison of safety and effectiveness of various MTX doses (ranging from 1.5 to 8 gm/m2) for response rate, OS and PFS was performed using Cox Proportional Hazard Model. Fifty-three cases treated with HD MTX at first line were available for analysis. The median age was 65 (31-84) and median KPS was 80 (40-100). Eight of 53 patients received concurrent cytotoxic therapies with MTX, 22/53 patients received rituximab with MTX, and 5/53 patients received WBRT. Twenty-eight patients (52.8%) were treated with MTX at the dose of 8 gm/m2 (Cohort A); all other patients received lower MTX doses according to their age, KPS, renal function, and protocols used at the time of treatment (Cohort B). The median number of MTX cycles was 4 (1-11). In cohort A, 56% had CR, 22% had PR and 22% had PD. The proportion of CR, PR and PD in cohort B was 17%, 29% and 54%, respectively. OS and PFS in cohort A were 30 and 13.5 months, as compared to 5 and 2 months in cohort B. HRs for OS in cohorts B and A, adjusted for known prognostic factors and confounders, were 5.56 (1.33-23.27), 3.91 (1.6-9.57), and 4.44 (1.87-10.58) after 12, 36 and 60 months, respectively. HRs for PFS in the same cohorts were 2.32 (0.92-5.88), 2.69 (1.15-6.31), and 3.03 (1.3-7.05). Treatment with HD MTX at the dose of 8 g/m2improved response rates, OS and PFS in patients with PCNSL after 12, 36 and 60 months, compared with treatment at lower MTX doses.
Chemosensitive Relapse in Small Cell Lung Cancer Proceeds through an EZH2-SLFN11 Axis
Authors: Eric E. Gardner, Benjamin H. Lok, Valentina E. Schneeberger, Patrice Desmeules, Linde A. Miles, Paige K. Arnold, Andy Ni, Inna Khodos, Elisa de Stanchina, Thuyen Nguyen, Julien Sage, John E. Campbell, Scott Ribich, Natasha Rekhtman, Afshin Dowlati, Pierre P. Massion, Charles M. Rudin, John T. Poirier
Journal: Cancer Cell (2017)