tbuckley/cabot-search huggingface dataset:
IMMU-18. PDL-1 EXPRESSION ON CIRCULATING CD68 (-) MONOCYTE-LIKE CELLS IN NF2 MENINGIOMA AS A BIOMARKER FOR TUMOR PROGRESSION
Authors: Shiyang Wang, Benjamin Liechty, An Hanna, Seema Patel, Matija Snuderl, Matthias Karajannis, Allen Jeffrey, Sharon Gardner
Journal: Neuro-Oncology (2018)

Program cell death ligand-1 (PD-L1) membranous expression on >5% tumor cells (PD-L1 positive tumors) is an unfavorable prognostic marker in many solid tumors. We previously showed that approximately 40% of neurofibromatosis type 2 (NF2) meningiomas are PD-L1 positive tumors. However, due to the invasive nature of biopsies, collection of tumor tissue is not always feasible. Thus, a non-invasive alternative is needed to evaluate the status of tumor growth and confirm PD-L1 positive tumors before the consideration of immunotherapy. It has recently been revealed that expression of PD-L1 on tumor associated macrophages is also a strong prognostic indicator. We retrieved formalin-fixed paraffin-embedded (FFPE) tissue from 10 NF2 meningioma cases to identify PD-L1 expression on macrophages and/or monocytes. We found that 3 out of 4 PD-L1 positive tumors were associated with expression of PDL-1 on CD68 (-) monocyte-like cells located in the peri- and intravascular lumens. These cells were only observed in 1 out of 6 PD-L1 negative tumors. Compared to others, tumors with PD-L1 expression on monocyte-like cells presented a higher Ki-67 proliferative index that was above 10%. Our results suggest that PD-L1 positive circulating CD68 (-) monocyte-like cells are correlated with tumor cell PD-L1 expression and progression in NF2 meningiomas.
Factors influencing late presentation for health care among men with cancer esophagus attending Hospice Africa Uganda (HAU)
Authors: N. Bandese
Journal: Annals of Oncology (2018)

Introduction: Late presentation for health care among patients with Cancer Esophagus is a major problem in Uganda. Cancer of Esophagus is one of the curable cancers if caught in its early stages. World Health Organization (2010) reports that esophageal cancer is the second most common cancer among men and was responsible for over 25000 deaths in 2010, approximately 80% occurred in developing countries. It was projected that it will increase by 25% over the next 10 years if nothing is done like putting prevention measures of adequate screening and treatment into place. Methods: A recording tape was used to store all the discussions for flexibility. The recorded material was first transcribed from local language then translated into English. Different themes were identified and then coding was done to come up with clear relations to the topic. Results: The results were also presented to Hospice Africa Uganda and Mbarara regional referral hospital management for proper planning. The 60% of the patient had no transport neither finicial support to access or report at the health facilities. The 40% of these patient had financial support but did not have time to visit the health workers. Conclusion: In conclusion, the themes realized which contributed to the late presentation for health care, could be grouped under three main factors: Socio-economic factors, Health system factors and Patient and community factors. These factors are interdependent. These need to be addressed by the responsible personnel in order to realize a change for the better in the health seeking mannerisms of patients.
A SEER analysis of increasing disparities in age-related cause specific survival (CSS) among patients with colorectal cancer
Authors: T. Mehmood
Journal: Annals of Oncology (2018)

Introduction: Survival for patients with colorectal cancer (CRC) has improved over the past decades. However, it is unclear whether older patients have benefited to the same extent as younger patients. Methods: The Surveillance, Epidemiology, and End Results (SEER) 9 registries database was queried for patients diagnosed with colorectal cancer from 1975 to 2009. Patients were categorized by age as being ≤54, 55-64, 65-74, 75-84, and ≥85 years. We presented yearly data for survival with overlying loess smoothing lines across all age groups. Another cohort was created using the SEER 18 registries database for patients diagnosed with CRC from 1973 to 2014. Survival analyses for the periods of 1973-1979, 1980-1989, 1990-1999, and 2000-2012 were conducted. Yearly data for surgery-performed rate and stage proportion were performed with overlying loess smoothing lines across all age groups. Results: In the analysis of the SEER 9 registries database, 5-year CSS of patients aged ≤54, 55-64 and 65-74 years showed robust increase since 1975; however, survival of patients aged 75-84 years remained low despite of modest improvement, and patients aged 85 or older even showed no survival gains since 1990. Same trend exists after stratifying the disease as localized, regional and distant. In the analysis of the SEER 18 registries database, there has been a steady increase in the survival of patients aged ≤54, 55-64, 65-74 and 75-84 years as time period advanced; however, of CRC patients aged 85 years and older, the survival curves of period 1990-1999 and 2000-2012 couldn't be distinguished from each other and presented with a negligibly small gap from the survival curve of 1980-1989. Conclusion: The strong interaction between age and year of diagnosis implies that older patients have benefited less over time than younger patients, especially for patients aged ≥85 years. Further studies are needed to determine the cause for these trends and identify potential strategies.
Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment
Authors: E. Castela, M.K. Tulic, A. Rozières, E. Bourrat, J.‐F. Nicolas, J. Kanitakis, P. Vabres, D. Bessis, J. Mazereeuw, F. Morice‐Picard, D. Baty, F. Berard, J.‐P. Lacour, T. Passeron, C. Chiaverini
Journal: British Journal of Dermatology (2018)

Epidermolysis bullosa simplex generalized severe (EBS‐gen sev) is a genetic disorder caused by mutation in the KRT5 or KRT14 genes. Although it is usually considered a mechanical disease, recent data argue for additional inflammatory mechanisms. To assess the inflammation in the skin of patients with EBS‐gen sev. A first immunohistochemical retrospective study was performed on frozen skin samples from 17 patients with EBS‐gen sev. A second multicentre prospective study was conducted on 10 patients with severe EBS‐gen sev. Blister fluid and epidermis were processed for immunochemical analysis and quantitative real‐time polymerase chain reaction. Cytokine expression was analysed in blister fluid and compared with that in controls. Histological analysis showed a constant dermal perivascular CD4+ lymphocyte infiltrate in skin biopsies of both blister (n = 17) and rubbed skin (n = 5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases, and increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of T helper 17 cytokines were detected in lesional skin. Three adult patients with EBS‐gen sev were treated with apremilast, with a dramatic improvement of skin blistering and good tolerance. Our study demonstrates the importance of inflammation in patients with EBS‐gen sev and underlines the key role for T helper 17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder.
HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling
Authors: Yu-Syuan Chen, Ching-Wen Chang, Yeou-Guang Tsay, Liu-Ying Huang, Yi-Chen Wu, Li-Hao Cheng, Cheng-Chieh Yang, Cheng-Hsien Wu, Wan-Huai Teo, Kai-Feng Hung, Chih-Yang Huang, Te-Chang Lee, Jeng-Fan Lo
Journal: Theranostics (2018)

Human tumorous imaginal disc (Tid1), a DnaJ co-chaperone protein, is classified as a tumor suppressor.Previously, we demonstrated that Tid1 reduces head and neck squamous cell carcinoma (HNSCC) malignancy.However, the molecular details of Tid1-mediated anti-metastasis remain elusive.Methods: We used affinity chromatography and systemic mass spectrometry to identify Tid1-interacting client proteins.Immunohistochemical staining of Tid1 in HNSCC patient tissues was examined to evaluate the association between the expression profile of Tid1-interacting client proteins with pathologic features and prognosis.The roles of Tid1-interacting client proteins in metastasis were validated both in vitro and in vivo.The interacting partner and downstream target of Tid1-interacting client protein were determined.Results: Herein, we first revealed that Galectin-7 was one of the Tid1-interacting client proteins.An inverse association of protein expression profile between Tid1 and Galectin-7 was determined in HNSCC patients.Low Tid1 and high Galectin-7 expression predicted poor overall survival in HNSCC.Furthermore, Tid1 abolished the nuclear translocation of Galectin-7 and suppressed Galectin-7-induced tumorigenesis and metastasis.Keratinocyte-specific Tid1-deficient mice with 4-nitroquinoline-1-oxide (4NQO) treatment exhibited increased protein levels of Galectin-7 and had a poor survival rate.Tid1 interacted with Galectin-7 through its N-linked glycosylation to promote Tid1-mediated ubiquitination and proteasomal degradation of Galectin-7.Additionally, Galectin-7 played a critical role in promoting tumorigenesis and metastatic progression by enhancing the transcriptional activity of TCF3 transcription factor through elevating MMP-9 expression.Conclusions: Overall, future treatments through activating Tid1 expression or inversely repressing the oncogenic function of Galectin-7 may exhibit great potential in targeting HNSCC progression.
RONC-20. VERTEBRAL BODY GROWTH RETARDATION FOLLOWING PROTON CRANIOSPINAL RADIATION
Authors: Myrsini Ioakeim-Ioannidou, Drosoula Giantsoudi, Andrzej Niemierko, Roshan V Sethi, Torunn I Yock, Nancy J Tarbell, F Joseph Simeone, Shannon M MacDonald
Journal: Neuro-Oncology (2018)

Craniospinal irradiation (CSI) is standard treatment for several pediatric brain tumors, known to cause growth impairment for growing children. However limited publications exist quantifying the effect and none for proton therapy (PT). This work qualitatively and quantitatively analyzes the effect of proton CSI on growth impairment. Retrospective analysis of 87 pediatric patients with CNS tumors treated with PT at the Massachusetts General Hospital between years 2002 and 2010. 55 patients received CSI while 32 patients, our control group, received cranial irradiation only. Vertebral body (VB) height was measured in midline at multiple levels of the spine (C3, C3-C4, T4, T4-T5, C3-T6, T4-T7, L3, L1-L5) on follow-up sagittal T1-weighted MRI scans. Our data was fitted using a mixed effects regression multivariable model, including follow-up time, CSI dose, age at CSI, hypothalamic dose and gender as parameters. With a median follow up of 69.6 months for patients treated with CSI and 52.9 months for our control group, a strong dependence of VB growth retardation on CSI dose, age at treatment and hypothalamic dose was found. Accounting for the difference in growth between genders, growth retardation was shown to be independent of gender. Although current practice of proton CSI allows for sparing of the anterior organs, the entire VB gets irradiated resulting in growth impairment of pediatric patients. Our work suggests a model quantitatively predicting the growth retardation of treated patients based on age at treatment, CSI dose and hypothalamic dose.
GERM-09. WHOLE VENTRICULAR IRRADIATION FOR INTRACRANIAL GERM CELL TUMORS: DOSIMETRIC COMPARISON OF PENCIL BEAM SCANNED PROTONS VS. IMRT
Authors: Dora Correia, Alessia Pica, Dario Terribilini, Stefan Zepter, Nicola Bizzocchi, Sonja Stieb, Frank Ahlhelm, Evelyn Herrmann, Michael K Fix, Peter Manser, Daniel M Aebersold, Damien C Weber
Journal: Neuro-Oncology (2018)

Whole ventricular irradiation (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for localized intracranial germ cell tumors (GCT). As the eloquent brain areas are mainly in direct vicinity of the target volume, it is unknown if proton therapy indeed substantially spares these organs at risk (OAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether protons or modern photon radiotherapy achieve better critical organ sparing. Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Respective intensity-modulated radiation therapy (IMRT) plans were generated for these patients. Additional critical structures for neurocognition (NCS) have been delineated and plans compared for target volume coverage (TVC) (homogeneity index (HI) and inhomogeneity coefficient (IC)), NCS and OAR sparing. TVC was similar for both modalities. Compared to IMRT, PBS-PT showed statistically significant dose reduction (p<0.05) in: maximum (Dmax), mean (Dmean) and integral dose (ID) of the normal brain (2.6%, 35.4%, 35.7%); Dmean of the Willis’ circle (6.7%), and brainstem (7.4%). Likewise, the volume receiving ≥20 Gy (V20Gy) of the right (24.2%) and left (20.9%) temporal lobes was significantly decreased. No significant difference was observed for the dose-metrics/hippocampus. Dosimetric comparison of WV-RT/TB in GCT demonstrates PBS-PT’s advantage over IMRT in critical organ sparing, while keeping TVC the same. PBS-PT may decrease the likelihood of vascular/neurological sequelae, as well as the risk of radio-induced secondary malignancies.
NURS-09. INTRODUCTION OF SKIN CARE GUIDELINES FOR CHILDREN AND TEENS TAKING MOLECULARLY TARGETED AGENTS
Authors: Kaaren Waters, Kasey Rangan, Ashley Margol, Nathan Robison, Girish Dhall, Anna Evans
Journal: Neuro-Oncology (2018)

Molecularly targeted therapies, such as MEK, BRAF, and EGFR inhibitors, are prescribed in pediatric neuro-oncology practice with increasing frequency. Although these targeted medications have demonstrated inhibition of tumor growth without traditional chemotherapy side effects, they are not without associated toxicities. Dermatologic findings are among the most commonly reported toxicities. Collaboration between providers, patients and families through prevention, early recognition, and promptly initiated treatment of associated skin toxicities can decrease strain and avoid interruption and/or early termination of these therapeutic agents resulting in overall increased treatment compliance. After an extensive review of the available published literature, a skin care teaching tool was created, in collaboration with nurse practitioners and physicians. The handout was implemented into practice to educate patients and families on preventative and early interventional measures to identify and treat skin toxicities related to treatment with targeted therapies. The fact sheet outlined the most common skin side effects including dry, itchy, scaly scalp and skin, cracked lips, dermatitis, acneiform rash, hair thinning, photosensitivity, ingrown and infected nails, and development of new moles. This introduction of skin care guidelines into a clinical neuro-oncology program represents a feasible and effective strategy for providing educational and supportive care to patients and families and preventing and treating skin toxicities associated with innovative targeted treatments. These guidelines can easily be initiated at other pediatric neuro-oncology practices, demonstrate adaptation in provider practice to newer oncology therapies, and exemplifies an evidence based collaborative team approach together with patients and families.
LGG-47. CARBOPLATIN AND VINBLASTINE THERAPY FOR PEDIARIC LOW-GRADE GLIOMA
Authors: Anandani Nellan, Erin Wright, Molly Hemenway, Jennifer Raybin, Nicholas Foreman, Sarah Rush, Kathleen Dorris
Journal: Neuro-Oncology (2018)

Low grade gliomas (LGG) represent the most common pediatric central nervous system tumor. LGG therapy usually involves surgical resection; when total resection is not feasible, management strategies may include chemotherapy. Multiple pediatric LGG chemotherapy regimens have been investigated with variable 2-year progression free survival (PFS) rates of 39-68%. To date, treatment of pediatric LGG with a carboplatin and vinblastine chemotherapy regimen has not been fully evaluated. A retrospective review of pediatric patients with LGG treated with carboplatin and vinblastine (C/VBL) at Children’s Hospital Colorado and Akron Children’s Hospital from 2011-2017 was conducted. Data collected included patient demographics, tumor location/response, neurofibromatosis status, C/VBL duration and toxicities. Thirty-five patients (24:11; males:females) were identified for analysis; 29 patients were treated with C/VBL as upfront therapy; six at disease progression. The majority of the patients had tumors in the optic pathway/hypothalamic region (46%). Four patients had multifocal disease at diagnosis. Five patients had neurofibromatosis type 1 (NF1). BRAF alterations were identified in 12/20 tested patients. The median age at start of therapy was 6.32 years (range, 0.55-17.66 years). Best therapy response was partial response in 4 patients and stable disease in 22 patients. Nine patients progressed during therapy. Two-year PFS rates were 51% (all patients), 60% (NF1 patients) and 49% (non-NF1 patients). Only four patients experienced delays in C/VBL therapy due to cytopenias, and 10 febrile neutropenia admissions were noted. This experience suggests that C/VBL achieves similar PFS rates to other investigated chemotherapy regimens for pediatric LGG with minimal toxicities.
Reducing demand for antibiotic prescriptions: evidence from an online survey of the general public on the interaction between preferences, beliefs and information, United Kingdom, 2015
Authors: Laurence S J Roope, Sarah Tonkin-Crine, Christopher C Butler, Derrick Crook, Tim Peto, Michele Peters, A Sarah Walker, Sarah Wordsworth
Journal: Eurosurveillance (2018)

Background: Antimicrobial resistance (AMR), a major public health threat, is strongly associated with human antibiotic consumption. Influenza-like illnesses (ILI) account for substantial inappropriate antibiotic use; patient understanding and expectations probably play an important role. Aim: This study aimed to investigate what drives patient expectations of antibiotics for ILI and particularly whether AMR awareness, risk preferences (attitudes to taking risks with health) or time preferences (the extent to which people prioritise good health today over good health in the future) play a role. Methods: In 2015, a representative online panel survey of 2,064 adults in the United Kingdom was asked about antibiotic use and effectiveness for ILI. Explanatory variables in multivariable regression included AMR awareness, risk and time preferences and covariates. Results: The tendency not to prioritise immediate gain over later reward was independently strongly associated with greater awareness that antibiotics are inappropriate for ILI. Independently, believing antibiotics were effective for ILI and low AMR awareness significantly predicted reported antibiotic use. However, 272 (39%) of those with low AMR awareness said that the AMR information we provided would lead them to ask a doctor for antibiotics more often, significantly more than would do so less often, and in contrast to those with high AMR awareness (p &lt; 0.0001). Conclusion: Information campaigns to reduce AMR may risk a paradoxical consequence of actually increasing public demand for antibiotics. Public antibiotic stewardship campaigns should be tested on a small scale before wider adoption.
HGG-06. USE OF TUMOR TREATING FIELDS DELIVERED WITH CONCURRENT TEMOZOLOMIDE AND LOMUSTINE AS ADJUVANT THERAPY IN A PATIENT WITH PEDIATRIC GLIOBLASTOMA
Authors: Sarah Supples, Daniel Couture, Christopher Whitlow, Katharine Pearsall, Michael Chan, David Kram
Journal: Neuro-Oncology (2018)

Pediatric glioblastoma (GBM; WHO grade IV astrocytoma) continues to carry a poor prognosis. While the use of concurrent and adjuvant temozolomide (TMZ) has been adopted as a standard treatment in adults, there is no standard systemic therapy for pediatric GBM. Recent studies in adults suggest benefit to the addition of tumor treating fields (TTF) to standard TMZ-based chemoradiotherapy, while a recent study in children showed improvement with the addition of lomustine (CCNU) to standard TMZ-based chemoradiotherapy. No studies to this point have been published using the combination of TMZ, TTF, and CCNU in either adult or pediatric GBM. A single patient was treated with aggressive local surgery achieving gross total resection. This was followed by 60 Gy in 30 fractions with concurrent temozolomide (75 mg/m2) given daily during radiotherapy. Post-radiation adjuvant therapy consisted of dose escalated temozolomide (160 mg/m2) given on days 1-5 of a 42-day cycle, CCNU (90 mg/m2) on day 1, and continuous tumor treating fields (started with cycle 1 of adjuvant chemotherapy). Chemoradiotherapy was tolerated well without grade III or IV toxicity. Thus far, the patient has received 2 cycles of adjuvant temozolomide/CCNU without grade III or IV toxicity. At 3 months post-radiotherapy, there is no evidence of tumor recurrence. We report the first case of a pediatric patient with GBM receiving a maintenance combination of TTF, TMZ, and CCNU after tumor resection and standard TMZ-based chemoradiotherapy. Prospective trials are necessary to validate the tolerability, safety, and efficacy of this aggressive combination therapy.
A phase II study of dose-escalation of regorafenib for patients with previously treated metastatic colorectal cancer – DEREGULATE study - Trial in progress
Authors: K. Kawaguchi, R. Nishitai, D. Manaka, T. Ota, Y. Nishikawa, R. Kudo, H. An, S. Hamasu, S. Konishi
Journal: Annals of Oncology (2018)

Introduction: Regorafenib (REG) is a standard salvage line therapy for metastatic colorectal cancer (mCRC) after a pivotal phase III study (CORRECT). However, administration of full dose of REG often leads to severe adverse effects, which makes the clinical use of this drug restricted to the patients(pts) relatively in good conditions. In a phase II ReDOS study (regorafenib dose optimization study NCT02368886), the median overall survival (OS) was improved more favorably in dose escalating regimen, which began at 80mg per day and increased weekly up to 160mg per day, than in standard regimen of 160mg per day. The Japanese subpopulation of CORRECT is reported to have received only 69.3% (110.9 mg/day) of the planned dose of REG, although non-Japanese subpopulation has received 80.4%, which suggests that dose escalating regimen may be more suitable for Japanese pts. The aim of this DEREGULATE study is to test the hypothesis that this dose-escalation regimen might have better sustainability and comparative disease-control compared with the standard dose regimen in Japanese pts. Methods: DEREGULATE is a multi-center phase II study. Pts are eligible when they have heavily treated mCRC and sufficient organ functions regardless of performance status grades. Patients are initially administered 80 mg/day of REG, and dose-escalation is considered every two weeks during the course of treatment. Primary endpoint is time to treatment failure (TTF). Secondary endpoints are disease control rate, survival and safety. The median TTF of CORRECT was 1.7 months, and that of Japanese post-marketing surveillance was 2 months. Thirty participants will be recruited to prove the hypothesis that the dose-escalation regimen should prolong the TTF by 40% (2.8 months) with the alpha and beta errors of 0.1. Clinical trial identification: UMIN000014661.