tbuckley/cabot-search huggingface dataset:
NCOG-12. NEUROCOGNITIVE OUTCOME IN CHILDREN WITH SENSORINEURAL HEARING LOSS FOLLOWING TREATMENT FOR MALIGNANT EMBRYONAL BRAIN TUMORS
Authors: Iska Moxon-Emre, Christine Dahl, Vijay Ramaswamy, Ute Bartels, Uri Tabori, Annie Huang, Sharon L Cushing, Vicky Papaioannou, Normand Laperriere, Eric Bouffet, Donald J Mabbott
Journal: Neuro-Oncology (2017)

Children treated for embryonal tumors are at risk for sensorineural hearing loss (SNHL). We report the prevalence of SNHL in children treated for malignant posterior fossa (PF) tumors and evaluate its impact on intellectual outcome, as a function of treatment. Data from 104 survivors of malignant PF embryonal tumors, treated between 1996 and 2016 at The Hospital for Sick Children (Toronto, Canada) were included. Patients were treated with chemotherapy alone, or in combination with less radiation (reduced-dose radiation with a focal boost) or more radiation (treatments with higher radiation doses and/or larger boost volumes). All patients had audiological evaluations prior, during and following treatment, and 91 patients had 1 or more neuropsychological assessment. Growth curve analysis was used to determine stability or change in IQ scores over time. Severe SNHL was identified in 43 patients. Patients who developed SNHL had lower means than patients without SNHL on all IQ indices except processing speed (all P < 0.05). Patients with SNHL had lower intercepts for full scale IQ and verbal comprehension (all P < 0.05); however, all IQ indices declined by 0.9 points per year, regardless of SNHL (all P < 0.05). In patients treated with chemotherapy alone, those who developed SNHL had lower mean full scale IQ, perceptual reasoning and working memory than those who did not develop SNHL (all P < 0.05). In contrast, patients treated with radiation with and without SNHL did not differ in any IQ indices (all P > 0.05). Hearing loss is a much more significant complication than previously estimated in children treated for embryonal brain tumors. We demonstrate a profound impact of SNHL on intellectual functioning, in particular for patients treated with chemotherapy alone. Our results have implications for future trial design and follow-up for children with embryonal brain tumors.
P2.03-046 Lymhocyte-To-Monocyte Ratio and Mean Platelet Volume as Prognostic Factor in EGFR Mutant NSCLC Treated with EGFR TKI
Authors: K. Watanabe, Y. Amano, H. Kage, Y. Goto, D. Takai, T. Nagase
Journal: Journal of Thoracic Oncology (2017)
MA 05.11 Endothelial Adhesion Molecule Overexpression Correlates to Decreased CD8 T Cells and Increased B/Treg Cells in Lung Cancer
Authors: Y.K. Chae, W. Choi, W. Bae, J. Anker, A. Davis, W. Iams, M. Cruz, M. Matsangou, F. Giles
Journal: Journal of Thoracic Oncology (2017)
RARE-01. CHALLENGES IN GERM CELL TUMOR DIAGNOSIS PERSIST: AN 18-YEAR RETROSPECTIVE
Authors: Bette DeMasters, Ryan Ormond
Journal: Neuro-Oncology (2017)

Germ cell tumors of the central nervous system (GCTs CNS) are usually strongly suspected and easily diagnosed when they occur in the usual demographic, ie. young males with a pineal mass. However, when tumors occur in adults, in unusual anatomic sites, demonstrate dissemination at clinical presentation, or require small biopsy, the same diagnostic challenges may remain today in 2017 as were evident 15 years ago. We reviewed our 18-year experience from our adult and pediatric hospitals to address this question. Text-word database searches of in-house and consult cases at our adult and pediatric hospitals (01/01/1999 - 06/01/2017). Focus was placed on whether tumors were located in unusual anatomic site, patient age, generated confusing clinical features, or required multiple biopsies for diagnosis. Of the 48 patients with primary GCTs, 32 had germinoma, 11 had teratoma, and 5 were mixed GCTs. Metastatic GCTs included 7 choriocarcinoma and 3 mixed GCTs. The majority of patients were Caucasian. Two biopsies for GCT documentation were needed in 5 patients. Challenging primary cases included those at the extremes of the age spectrum (suprasellar masses in a neonate diagnosed on ultrasound at 20 weeks’ gestation and a 40 year male) or in unusual anatomical locations (midbrain, septum, frontal lobe, bilateral thalamic, massive basilar “meningitis”/ventriculitis). The latter, seen in a young man from Mexico was thought to be neurocysticercosis or tuberculous meningitis prior to biopsy. Other leading differential diagnoses were high-grade glioma (for lobar cases) or pilocytic astrocytoma/craniopharyngioma/pituitary adenoma (for suprasellar/sellar examples). One was discovered at forensic autopsy. In contrast, our text-word search generated 4 cases where the leading preoperative differential diagnosis had been germinoma, but were biopsy-proven to be pilocytic astrocytoma (n=2), congenital glioma (n=1), or sellar xanthogranuloma (n=1). Unusual anatomic site/demographics and/or small biopsies continue to challenge some GCT diagnoses.
CBIO-31. SEX DIFFERENCES IN THE ACTIVITY OF CYCLIN DEPENDENT KINASE INHIBITORS UNDERLIE GREATER THRESHOLD FOR GLIOMIC TRANSFORMATION IN FEMALE ASTROCYTES
Authors: Nathan Rockwell, Najla Kfoury, Tao Sun, Kwanha Yu, Kelsey Tinkum, Peter McDonald, Anu Roy, Scott Weir, Carrie Mohila, Benjamin Deneen, Joshua Rubin
Journal: Neuro-Oncology (2017)

Sex differences in cancer incidence are pervasive regardless of age or race. However, the molecular mechanisms underlying these differences remain undefined. Previously, we showed that sex differences in the regulation of retinoblastoma protein (Rb) function has been shown to correlate with differential vulnerability to malignant transformation to mesenchymal glioblastoma (mes-GBM) in male and female cortical astrocytes lacking functional neurofibromin and p53. We hypothesized that these sex differences in susceptibility to transformation may be driven by the differential activities of cyclin dependent kinase inhibitors. We found that p16 and p21, but not p27 exhibited sexually dimorphic activity corresponding to sex differences cell cycle arrest and transformation. In response to serum deprivation and DNA damage, female mes-GBM astrocytes increase p16 and p21 expression respectively, leading to cell cycle arrest. In contrast, male mes-GBM astrocytes continue to proliferate, acquire chromosomal aberrations, and display greater clonogenic cell frequency and in vivo tumorigenesis. Abrogation of p16 and p21 activity in female mes-GBM astrocytes mitigates these phenotypic differences. An analysis of pharmacological CDK inhibition revealed that the sex differences in p16 and p21 activity are correlated with sex differences in response to CDK4/6 and CDK5-CDK2 pathway inhibitors. These data provide new evidence for sex differences in growth regulation and transformation and suggest that these differences can render male and female cells differentially sensitive to targeted therapeutics. Finally, they indicate that sex differences should be considered in the investigation of novel cancer therapeutics in both the lab and clinical setting.
MNGI-14. LONG-TERM OUTCOMES FOLLOWING SURGERY AND/OR RADIATION THERAPY IN PATIENTS WITH HIGH-GRADE MENINGIOMA
Authors: Olayode Babatunde, Collin Kent, Yvonne Mowery, Frances McSherry, James E Herndon, Ato Wright, Robert Clough, William Sperduto, John P Kirkpatrick
Journal: Neuro-Oncology (2017)

Meningiomas are common intracranial neoplasms with a typically indolent natural history. However, WHO Grade II-III tumors account for ~20% of meningiomas and exhibit high rates of recurrence. Limited data are available regarding long-term outcomes for these patients. Patients treated for WHO Grade II or III intracranial meningioma between 1993 and 2017 at our institution were analyzed retrospectively on an IRB-approved protocol. Overall (OS) and Progression-Free Survival (PFS) were calculated from date of high-grade diagnosis, estimated by Kaplan-Meier method, and compared by log-rank test. Group distributions were compared by Fisher’s exact test. 60 patients (30/30 male/female; median age 56, IQR 45 – 70) were identified. Most patients had grade II disease (46 grade II; 14 grade III). Nine patients had transformed from grade I to high-grade disease. Median follow-up was 11.5 years. Median OS was 8.6 years (95% CI: 6.7, 15.5). OS at 5, 10, 15, and 20 years from high-grade diagnosis was 68.1% (54.7%, 78.4%), 43.5% (28.7%, 57.4%), 35.3% (20.1%, 50.9%), and 29.4% (14.1%, 46.6%), respectively. PFS and OS did not differ significantly by grade. Patients received surgery (n=32), surgery + XRT (n=26), or definitive XRT (n=2). Eight patients also underwent systemic therapy. Surgical resections were Simpson grade IV in 34% of surgery only vs. 62% of surgery + XRT patients (p = 0.04). Median PFS was 1.5 years for surgery vs. 4.2 years for surgery + XRT (p = 0.009). Median OS was 8.5 years for surgery alone vs. 9.7 years for surgery + XRT (p = 0.51). After first salvage treatment, median PFS and OS were 1.6 and 6.3 years, respectively. Patients with grade II-III meningiomas often have prolonged OS despite short PFS after initial treatment. Given the frequent recurrences and apparent efficacy of salvage therapy, these patients should be systematically monitored after diagnosis.
Editorial: Bench to Bedside—and Back Again: Finding the Goldilocks Zone Within the Scleroderma Universe
Authors: Janet E. Pope, Jason J. Lee, Christopher P. Denton
Journal: Arthritis & Rheumatology (2017)

Systemic sclerosis (SSc) is a complex inflammatory connective tissue disease characterized by skin thickening, organ fibrosis and vasculopathy [1, 2]. The underlying disease mechanisms and pathophysiology are not fully understood. However, it appears to be, at least in part, driven by autoimmunity and inflammation associated with microvascular dysfunction ultimately resulting in excess extracellular matrix deposition in target organs [2-4]. Clinical heterogeneity coupled with our lack of understanding of the disease pathogenesis means that current treatment strategies are mostly organ based therapies using anti-rheumatic drugs that were originally approved for other indications [5]. Of course, this clinical diversity not only provides challenges to discovery of disease mechanisms, it also complicates often underpowered clinical trials that aim to find the right drugs for the right patient at the right time.

This article is protected by copyright. All rights reserved.
Microenvironmental Stiffness of 3D Polymeric Structures to Study Invasive Rates of Cancer Cells
Authors: Enrico Domenico Lemma, Barbara Spagnolo, Francesco Rizzi, Stefania Corvaglia, Marco Pisanello, Massimo De Vittorio, Ferruccio Pisanello
Journal: Advanced Healthcare Materials (2017)

Cells are highly dynamic elements, continuously interacting with the extracellular environment. Mechanical forces sensed and applied by cells are responsible for cellular adhesion, motility, and deformation, and are heavily involved in determining cancer spreading and metastasis formation. Cell/extracellular matrix interactions are commonly analyzed with the use of hydrogels and 3D microfabricated scaffolds. However, currently available techniques have a limited control over the stiffness of microscaffolds and do not allow for separating environmental properties from biological processes in driving cell mechanical behavior, including nuclear deformability and cell invasiveness. Herein, a new approach is presented to study tumor cell invasiveness by exploiting an innovative class of polymeric scaffolds based on two-photon lithography to control the stiffness of deterministic microenvironments in 3D. This is obtained by fine-tuning of the laser power during the lithography, thus locally modifying both structural and mechanical properties in the same fabrication process. Cage-like structures and cylindric stent-like microscaffolds are fabricated with different Young's modulus and stiffness gradients, allowing obtaining new insights on the mechanical interplay between tumor cells and the surrounding environments. In particular, cell invasion is mostly driven by softer architectures, and the introduction of 3D stiffness "weak spots" is shown to boost the rate at which cancer cells invade the scaffolds. The possibility to modulate structural compliance also allowed estimating the force distribution exerted by a single cell on the scaffold, revealing that both pushing and pulling forces are involved in the cell-structure interaction. Overall, exploiting this method to obtain a wide range of 3D architectures with locally engineered stiffness can pave the way for unique applications to study tumor cell dynamics.
TMIC-03. ONCOLYTIC VIRAL THERAPY WITH DELTA24-RGD INDUCES A TUMOR-DETRIMENTAL ENVIRONMENT VIA PHENOTYPIC SHIFT OF MACROPHAGES
Authors: Wouter van den Bossche, Anne Kleijn, Charlotte Teunissen, Jane Voerman, David Noske, Jacques van Dongen, Clemens Dirven, Martine Lamfers
Journal: Neuro-Oncology (2017)

Macrophages are reported to play an important role in pathogenesis and progression of glioblastoma (GBM). Indeed, the immunosuppressive and pro-tumorous M2-macrophage is abundantly present in these tumors. Current therapeutic options for GBM only minimally improve the dismal prognosis of these patients, which has prompted the design of several clinical trials using oncolytic viruses, including the oncolytic adenovirus Delta24-RGD. Since the initiation of an anti-tumor immune response can be hampered by M2-macrophages, we studied the effect of Delta24-RGD treatment on tumor-associated macrophages in GBM. Human peripheral blood monocytes were isolated, cultured and polarized towards the M1- or M2-macrophage phenotype and subsequently cultured with either Delta24-RGD, glioma stem-like cells (GSC’s), or Delta24-RGD-infected GSC’s. The gene expression, immunophenotype and cytokine profiles were assessed at multiple timepoints. Resected tumor material of a Delta24-RGD-treated GBM patient and 5 untreated GBM patients, was analyzed by flow cytometry to assess tumor macrophage phenotype. Cytokines in the cerebrospinal fluid of 18 Delta24-RGD-treated patients were measured by MSD electrochemiluminescence panels. Macrophages co-cultured with Delta24-RGD-infected GSC’s for 72 hours, shifted in gene expression and immunophenotype from M2- to M1-macrophage. This shift required both a virus-induced change in tumor-produced soluble factors as well as the presence of viral particles. Furthermore, tumor-associated macrophages in resected Delta24-RGD-treated patient material showed more M1-immunophenotypic characteristics compared to macrophages in untreated GBM. In addition, CSF of Delta24-RGD-treated GBM patients revealed cytokine levels indicative of a pro-inflammatory microenvironment. Treatment of GBM with the oncolytic virus Delta24-RGD changes the gene expression profile, immunophenotype and cytokine profiles of the tumor-resident macrophages from pro-tumorous M2- to anti-tumorous M1-phenotype, therewith changing the microenvironment to promote the anti-tumor immune response. Our results show that Delta24-RGD, in addition to inducing oncolysis and initiating an anti-tumor immune response, creates a tumor detrimental microenvironment by changing the tumor macrophage phenotype.
P1.07-034 Pretreatment Neutrophil &amp; Platelet Count as a Predictor for Unfavorable Clinical Outcome in Non-Small Cell Lung Cancer (NSCLC)
Authors: S. Agte, Y.K. Chae, A. Davis, A. Pan, N. Mohindra, V. Villaflor
Journal: Journal of Thoracic Oncology (2017)
CMET-14. CLINICAL PRESENTATION, TREATMENT, AND OUTCOME IN PATIENTS WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT OF EXTRANODAL NATURAL KILLER/T-CELL LYMPHOMA
Authors: Kathryn Nevel, Mariza Daras
Journal: Neuro-Oncology (2017)

Extranodal natural killer (NK)/T-cell lymphoma is an uncommon malignancy that rarely metastasizes to the central nervous system (CNS). Due to rarity of CNS involvement, natural history and treatment response is not well known. We sought to identify patient characteristics, treatments, and outcomes in patients with CNS NK/T-cell lymphoma. A single institution retrospective review of patients with extranodal NK/T-cell lymphoma with CNS involvement treated at MSKCC from 1995 to 2016. Ten of 63 patients (15.8%) with extranodal NK/T-cell Lymphoma followed at MSKCC for at least 2 months (or until death) were diagnosed with CNS involvement using a combination of clinical, radiographic, and cerebrospinal fluid findings. Presenting symptoms included confusion (n=5), cranial neuropathies (n=3), seizure (n=1), and none (n=1). Sites of CNS involvement included leptomeningeal metastases (n=8), parenchymal metastases (n=1), or both (n=1). Eight of 10 patients had active systemic disease at time of CNS diagnosis. One patient never developed systemic disease (primary CNS extranodal NK/T-cell lymphoma), and one was in remission of systemic disease at the time of CNS relapse. Median time from diagnosis of systemic disease to CNS disease was 3.9 months (range 0–12 months). Median survival after diagnosis of CNS involvement was 3.8 months (range 0.5–17 months, alive in remission). Treatment of CNS disease varied and included one or more of the following: high-dose methotrexate (n=7), intrathecal methotrexate (n=6), intrathecal cytarabine (n=4), radiation (n=1), complete or modified SMILE regimen (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide; n=3), cytarabine (n=1), ICE regimen (rituximab, ifosfamide, carboplatin, etoposide; n=1), whole brain radiation (n=1), and autologous stem cell transplant (ASCT; n=2). CNS involvement of extranodal NK/T-cell lymphoma portends a grim prognosis, for which there is no standard treatment. One patient with leptomeningeal metastases who successfully underwent an ASCT is still alive and in complete remission 17 months from diagnosis.
P3.02-025 65 Cases of Molecular Profiling Analysis in Surgical Resected Pulmonary Neuroendocrine Carcinoma
Authors: C. Xu, W. Wang, W. Zhuang, Z. Song, J. Lin, Y. Chen, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
ACTR-80. COMBINING A KETOGENIC DIET WITH INITIAL CHEMOTHERAPY &amp; RADIATION THERAPIES FOR AGGRESSIVE GLIOMAS, A PILOT STUDY
Authors: Kenneth Schwartz, Mary Noel, Michele Nikolai, Karl Olson, Michael Zakem, Mohamed Elnabtity, Justin Clark, Brian Figueroa, Howard Chang
Journal: Neuro-Oncology (2017)
P1.01-069 Clinical Experience with IBM Watson for Oncology (WFO) Cognitive System for Lung Cancer Treatment in China
Authors: N. Zhou, H. Lv, C. Zhang, T. Li, J. Zhu, M. Jiang, H. Hou, D. Liu, A. Li, G. Liu, K. Liu, G. Zhang, X. Zhang
Journal: Journal of Thoracic Oncology (2017)
HOUT-11. META-ANALYSIS OF SURVIVAL TRENDS IN GLIOBLASTOMA IN TEMOZOLOMIDE TREATED PATIENTS FROM 2004 TO 2016: NO EVIDENCE FOR INCREASE IN SURVIVAL BENEFIT OVER TIME
Authors: Kristin McIntire, Albert Wong
Journal: Neuro-Oncology (2017)

Since establishment of current standard of care using temozolomide with radiation therapy (TMZ/RT), several studies have reported superior median overall survival (mOS). It has been speculated that mOS using TMZ/RT has increased over time partially accounting for these results. This study was conducted to evaluate potential improvement in mOS over time. We performed a meta-analysis of adult primary glioblastoma Phase II/III studies published from 2004-2016. Included studies measured survival, used TMZ/RT alone or with experimental treatment, and had at least 20 patients. Studies restricted to children, elderly patients, or minimal surgery were excluded. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 110 studies published since 2004 were initially considered, with 62 meeting criteria for inclusion. We found no trend towards improved mOS relative to the study closing date (R2 =0.23). Data on progression-free survival (PFS) also showed no trend over time. The difference in mOS with TMZ/RT alone compared to TMZ/RT plus any study drug also did not reach significance (p=0.107), though some promising studies with improved outcomes emerged as outliers. Parameters such as smaller study size, certain drugs in conjunction with TMZ/RT, and improving gross-total resection rates, may explain these pockets of improvement. Interestingly, addition of any study agent to standard TMZ/RT irrespective of year improved average PFS significantly (from 7.49 months to 9.63 months, p=0.012; 95% CI: 6.72 to 8.26 for TMZ alone, 8.63 to 10.63 with additional drug). There is no evidence for increasing mOS since 2004. Some studies achieve survival far superior to standard TMZ/RT but while promising in initial studies fail in larger trials. It is critical to understand how these studies can be improved for larger studies. Perhaps ancillary factors such as treatment aggressiveness and therapy for recurrence can make the difference for success or failure of these trials.
Book: The Hills of Angheri
Authors: Sanjay A Pai
Journal: BMJ (2006)

Kavery Nambisan is among the few Indian doctors who is also a published writer and novelist. Moreover, she is that rarity, a woman surgeon. The Hills of Angheri is based loosely on her own experiences (see also http://careerfocus.bmjjournals.com/cgi/content/full/324/7347/S158).​).




Figure 1



Kavery Nambisan

Penguin Books India, 350 rupees, pp 393 ISBN 0 14 303271 2 www.penguinbooksindia.com Available in the UK through moc.puorgniugnep.ni@selas

Rating: ★★★⋆




The protagonist of this novel, Nalli, is a girl in a male dominated village in southern India and wishes, against all odds and advice, to become a doctor. The book takes us through her travels and travails, through graduate medical college, postgraduate training in surgery in England, and the years thence. Nalli learns—as we all do—that challenges in medicine keep presenting themselves in different forms and responsibilities always increase.

Many—perhaps most—medical students are idealists. Many, but not all, change gradually over the years, usually because of the lure of Mammon, wrong role models, or other reasons. Nalli and other characters in the book experience all of this. Some survive the bad influences, others don't. The incidents ring true, and medical student and doctor readers are likely to identify with them, recalling their own victories, defeats, and romances.

Nalli's experiences in England, written in the first person, are particularly striking. As a resident she is often plagued by self doubt and worries about medical errors—whether over diagnosing rare “bladder tumours” or at retained swabs in the abdomen. (So much so that at a recent book reading session a member of the audience questioned the author about Nalli's obsession with error.)

Later, after returning from England, Nalli works in an ashram or religious retreat in northern India, before moving on to a city practice and then making the final, expected move back to the village. She wonders “why we become surgeons at all when we have to die so many deaths in a single life.”

Although the story begins in the late 1960s, the issues it deals with are relevant today. These include informed consent (although it is hard to believe that a government run hospital in the late 1960s would have given so much importance to informed consent), corruption in government and private hospitals, and the odd ethical physician who refuses drug company gifts.​gifts.




Figure 2



Kavery Nambisan: a medical rarity




The Hills of Angheri will appeal to both the doctor and non-doctor reader alike. It is a simple tale with no twists, but is refreshing and engrossing.