tbuckley/cabot-search huggingface dataset:
CMET-49. RECURRENTLY MUTATED GENES DIFFERENTIATE LEPTOMENINGEAL FROM SOLID LUNG CANCER BRAIN METASTASES
Authors: Ian Connolly, Yingmei Li, Boxiang Liu, Melanie Hayden Gephart
Journal: Neuro-Oncology (2017)

Brain metastases have unique genetic mechanisms which enable them to engraft and grow either within the brain (solid) or on the surface of the brain and nerves (leptomeningeal disease; LMD) A solid brain metastasis occurs in up to 45% of all cancer patients compared to an approximate 5% incidence of LMD. Unlike solid brain metastases, LMD cannot be resected and has a worse survival, often times weeks to months after diagnosis. Why metastatic cells favor one brain site over the other has yet to be determined. To date, there has been no systematic study of the genetic differences between LMD and solid brain metastases. Through whole exome sequencing we compared the mutational landscape of lung-to-brain metastases in eight cytology-positive LMD samples and 38 solid brain tumor metastases. Cerebral spinal fluid and normal control samples (blood or saliva) of patients with LMD were collected at Stanford Hospital. Samples underwent DNA extraction, indexed library preparation, exome enrichment, and sequencing with pair end-reads on an Illumina NextSeq system. LMD mutations were compared to exome sequencing data of solid brain metastases in the Cancer Genome Atlas. We identified a subset of recurrently mutated genes (e.g. EGFR, TAS2R31, CACNA1I) that occured more frequently in our LMD samples. Another subset of genes (e.g. KRAS, LRP1B, CSMD3) were more frequently mutated in the solid brain metastasis samples. TP53, MUC16, MUC17 were among the genes shared across LMD and solid lung-to-brain metastases. No recurrent mutations were shared between all LMD samples, highlighting LMD heterogeneity. Solid brain metastases and LMD appear to harbor distinct genetic mutations, suggesting unique mechanisms for growth in these unique brain niches. A better understanding of the genomic events facilitating lung-to-brain metastases will improve targeted treatment options, and eventually patient outcomes.
MA 13.06 New Risk Factors for Overall Survival After SBRT in Early Stage NSCLC: A Role of RT Plan Optimization
Authors: F. Kong, Y. Liu, H. Zhang, H. Yao, A. Cerra-Franco, K. Shiue, D. Vile, W. Wang, M. Langer, G. Watson, G. Bartlett, K. Diab, T. Birdas, T. Lautenschlaeger, J. Jin
Journal: Journal of Thoracic Oncology (2017)
P2.03-045 Updated Results of Phase II, Liquid Biopsy Study in EGFR Mutated NSCLC Patients Treated with Afatinib (WJOG 8114LTR)
Authors: H. Hayashi, H. Akamatsu, Y. Koh, S. Morita, D. Fujimoto, I. Okamoto, A. Bessho, K. Azuma, K. Nakagawa, N. Yamamoto
Journal: Journal of Thoracic Oncology (2017)
ATIM-06. A PILOT STUDY OF STEREOTACTIC RADIOSURGERY (SRS) COMBINED WITH IPILIMUMAB PROLONGED SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED MELANOMA BRAIN METASTASES
Authors: Michael Lim, Lawrence Kleinberg, Xiaobu Ye, Sarah Nicholas, Doris Lin, Kristin Redmond, Chetan Bettegowda, William Sharfman, Evan Lipson
Journal: Neuro-Oncology (2017)

Pre-clinical and clinical data have shown that administering a high dose of radiation (SRS) directly to a tumor up-regulates MHC expression and pro-inflammatory cytokines in the tumor microenvironment. Studies have suggested that SRS works synergistically with checkpoint inhibitors to improve an antitumor immune response. We examined the combination of ipilimumab with SRS in patients with melanoma brain metastases. Johns Hopkins IRB approved a pilot study for safety and efficacy of SRS concurrent with ipilimumab to treat adults with newly diagnosed melanoma brain metastases. Key inclusion criteria are adult, prior stage IV melanoma, immunotherapy naïve, brain metastases > 3 mm, KPS ≥70%, and informed consent. Patients were treated with ipilimumab at 3mg/kg every 21 days and one SRS per SOC. Safety is the primary objective with a target DLT rate ≤33%. The clinical outcomes are the secondary objectives. Four patients were enrolled into the study with a median age at 67, KPS 95%, and an average 2.5 lesions in the brain. The number of ipilimumab treatment cycle were 2–3. There were two grade 3 diarrhea and two grade 3 fatigue attributed to ipilimumab. One grade 3 headache was due to SRS. The grade 1–2 hypothyroidism were observed attributed to ipilimumab. Two patients were off treatment due to diarrhea, one for a new lesion, and one death due to progressive disease of melanoma. To date, two patients are still alive: The median OS was 33.9 months. The median PFS was 3 months due to new brain lesions. Pembrolizumab (anti-PD-1) also was provided to patients after it had FDA approval. Combining ipilimumab with SRS is feasible to treat brain metastases and possibly prolongs overall survival. Since anti-PD-1 is available for melanoma patients, the study has been amended to use anti-PD-1 instead of ipilimumab and is ongoing.
MA 02.10 Phase I Study of ABBV-399 (Telisotuzumab Vedotin) as Monotherapy and in Combination with Erlotinib in NSCLC
Authors: J. Goldman, E. Angevin, J. Strickler, D.R. Camidge, R. Heist, D. Morgensztern, M. Barve, H. Yue, J. Beaulieu, M. Motwani, D. Afar, L. Naumovski, K. Kelly
Journal: Journal of Thoracic Oncology (2017)
Salivary proteins and microbiota as biomarkers for early childhood caries risk assessment
Authors: Abdullah S Hemadi, Ruijie Huang, Yuan Zhou, Jing Zou
Journal: International Journal of Oral Science (2017)

Early childhood caries (ECC) is a term used to describe dental caries in children aged 6 years or younger. Oral streptococci, such as Streptococcus mutans and Streptococcus sorbrinus, are considered to be the main etiological agents of tooth decay in children. Other bacteria, such as Prevotella spp. and Lactobacillus spp., and fungus, that is, Candida albicans, are related to the development and progression of ECC. Biomolecules in saliva, mainly proteins, affect the survival of oral microorganisms by multiple innate defensive mechanisms, thus modulating the oral microflora. Therefore, the protein composition of saliva can be a sensitive indicator for dental health. Resistance or susceptibility to caries may be significantly correlated with alterations in salivary protein components. Some oral microorganisms and saliva proteins may serve as useful biomarkers in predicting the risk and prognosis of caries. Current research has generated abundant information that contributes to a better understanding of the roles of microorganisms and salivary proteins in ECC occurrence and prevention. This review summarizes the microorganisms that cause caries and tooth-protective salivary proteins with their potential as functional biomarkers for ECC risk assessment. The identification of biomarkers for children at high risk of ECC is not only critical for early diagnosis but also important for preventing and treating the disease. Tests for proteins in saliva that control cavity-causing microbes could help predict a young child's risk of dental caries. In a review article, Jing Zou and colleagues from Sichuan University in Chengdu, China, outline the roles of oral microorganisms and salivary proteins in the development and prevention of tooth decay in preschool-aged children. Streptococcus bacteria are the main cause of caries in young children, although other bacteria and fungi also contribute. Various proteins and other biomolecules found in saliva affect the survival of these microbes. The authors suggest that the concentrations of these proteins could serve as early indicators of tooth decay risk. However, studies have not found a correlation between total salivary proteins and decay risk, suggesting that more work is needed to identify the best biomarker in saliva.
P1.02-007 TP53 and DNA-Repair Gene Polymorphisms as Risk Factors for the Development of Advanced Lung Adenocarcinoma in Serbia
Authors: J. Spasic, A. Krivokuca, B. Zaric, D. Radosavljevic, B. Perin, S. Radulovic, R. Jankovic, M. Cavic
Journal: Journal of Thoracic Oncology (2017)
PDCT-06. RADIO-IMMUNOTHERAPY USING THE IDO-INHIBITOR INDOXIMOD IN COMBINATION WITH RE-IRRADIATION FOR CHILDREN WITH PROGRESSIVE BRAIN TUMORS IN THE PHASE 1 SETTING: AN UPDATED REPORT OF SAFETY AND TOLERABILITY (NCT02502708)
Authors: Theodore S Johnson, Dolly Aguilera, Ahmad Al-Basheer, Raven M Cooksey, Bree R Eaton, Natia Esiashvili, Selim Firat, John B Fiveash, Nicholas Foreman, Diana Fridlyand, Gregory K Friedman, Cole A Giller, David R Grosshans, Ian M Heger, Michael Kelly, Eugene P Kennedy, Jeffrey Knipstein, Ravindra B Kolhe, Arthur K Liu, William Martin, Waleed F Mourad, Rafal Pacholczyk, Rebecca Parker, Amyn M Rojiani, Ramses F Sadek, Allan Thornton, Nicholas N Vahanian, Tobey MacDonald, David Munn
Journal: Neuro-Oncology (2017)

The indoleamine 2,3-dioxygenase (IDO) pathway is a natural immune-checkpoint mechanism often exploited by tumors to escape anti-tumor immunity. Small-molecule IDO pathway inhibitor drugs, such as indoximod, are in multiple trials for adults. Combining indoximod immunotherapy with re-irradiation is a highly innovative approach for treating children with progressive brain cancer. The goal of this first-in-children trial is to assess the feasibility, safety, and preliminary evidence of efficacy of combining indoximod either with temozolomide, or with radiation followed by maintenance therapy with indoximod/temozolomide, for children age 3 to 21 with progressive malignant brain tumors. The study includes two dose-escalation cohorts using a standard 3 + 3 design to determine a recommended phase-2 dose (RP2D) for indoximod in combination with either temozolomide (planned n=12) or radiation (planned n=12). Indoximod dose-levels are 80%, 100%, and 120% of the adult RP2D. We present up-to-date toxicity/side-effect data and follow-up results for all patients treated with indoximod plus radiation. Currently, 26 children have enrolled, and 15 of these have been treated with indoximod plus radiation, including children with ependymoma (n=9), medulloblastoma (n=3), glioblastoma (n=1), bithalamic glioma (n=1), PNET (n=1). Some children received more than one radiation plan over time. All patients were heavily pre-treated, and many patients required target volume and dose adaptation to reduce toxicity risks. Among patients treated to date, median total radiation dose was 30 Gy (range 14-54 Gy), median number of radiation fraction was 20 (range 1-30), and median follow-up duration was 8 months (range 2-15 months). Overall, indoximod combined with re-irradiation has been well tolerated with manageable adverse events. To date, all patients have been able to complete their planned radiation and start maintenance therapy with indoximod/temozolomide without delay. The combination of indoximod and radiation has been well tolerated in this patient population with good overall quality-of-life.
RTHP-15. INCIDENCE OF MASTOID EFFUSION IN PATIENTS RECEIVING PHOTON RADIATION THERAPY FOR GLIOBLASTOMA
Authors: Lindsay Rowe, Megan Mackey, Mary Hawes, Holly Ning, Theresa Cooley Zgela, Mark R Gilbert, Andra Krauze, Kevin Camphausen
Journal: Neuro-Oncology (2017)

Radiation therapy (RT) induced mastoid effusion has been documented after-RT to the cranium, or head and neck. Grade 2/3 mastoid effusions (G2/3M) have been documented in nasopharyngeal cancers at rates of 20 – 30% and are correlated with the mean dose and volume of mastoid irradiated. However, mastoid effusions in patients with gliomas have not been well characterized. We hypothesized that different radiation volumes, tumor location, and the addition of radiosensitizing chemotherapy may impact the incidence and severity of mastoid effusions in patients irradiated for glioblastoma. A retrospective analysis of patients treated for glioblastoma from 2010 to 2015 was conducted. Patients received a median dose of 60Gy to the primary lesion with concurrent temozolomide. Mastoid opacification on T2-weighted MR images was a surrogate for effusion and scored as Grade 0 (not seen), Grade 1 (mild), Grade 2 (moderate), or Grade 3 (severe). Charts were reviewed for clinical signs or symptoms of ear disorders. Unpaired t-test was used to compare groups. A total of 51 patients were included. Prior to RT, 19.6% (10/51) had baseline mastoid effusions. An additional 9.8% (4/41) developed G2/3M, with an average time to onset of 1mo (range 0.5 – 3mo) and resolution at 3.7mo (range 3 – 7mo) after completion of RT. Mastoid D50 (dose to 50%) was 12.8Gy vs. 30.5Gy(p=0.027), with a mean mastoid dose of 16.9Gy vs. 30.5Gy(p=0.454) for Grade 0/1 vs. G2/3M, respectively. Three patients with G2/3M experienced clinical sequela, including otalgia, sensation of fullness, serous otitis media, and mastoid tenderness. The incidence of mastoid effusion in patients with glioblastoma was lower than in patients treated for head and neck cancers. Though less common in gliomas, radiation induced mastoid effusion is an important consideration in patients who present with middle ear signs and symptoms after RT.
EXTH-77. LIGAND CONJUGATED QUANTUM DOTS FOR THE DETECTION OF CANCER STEM CELLS AND EXOSOMES
Authors: A B Madhankumar, Oliver Mrowczynski, Becky Slagle-Webb, Brad Zacharia, Michael Glantz, Akiva Mintz, James Connor
Journal: Neuro-Oncology (2017)

High grade astrocytomas and other metastatic brain cancers possess high tumor invasive and infiltrating properties making them difficult to detect and treat. In our study we demonstrate the unique and selective uptake of a variant of interleukin 13 (TQM13) conjugated quantum dots in glioma in an in vitro and in vivo model. As IL13Rα2 and EGFRVIII are known to be expressed in invasive and therapeutically resistant forms of glioma tumors, the cell lines expressing these receptors were targeted using ligand conjugated quantum dots. Monolayer and spheroidal cell culture models of glioma stem cells were utilized for demonstrating the receptor specific uptake of the targeted quantum dots. To demonstrate the in vivo specificity of the IL13Rα2 receptor targeted quantum dots, the quantum dots were injected intraperitoneally in an intracranial glioma tumor mouse model. After sacrificing the mice, the tumor sections were analyzed for the accumulation of quantum dots using 2-photon fluorescence microscopy. The interaction of exosomes with ligand conjugated quantum dots to alter the tumor cell binding was also verified in a cell culture model. For this purpose, we utilized exosomes derived from a glioma patient derived cell line and Jurkat T cell line. Our in vitro binding study indicated an effective binding of the tumor targeted quantum dots to the cancer stem cells expressing IL13Rα2 and EGFRVIII. The 2-photon fluorescence microscopy confirms a perinuclear accumulation of quantum dots in the tumor region in the in vivo model. The exosome bound quantum dots showed either increased or decreased uptake by the glioma cells depending on the source of the exosomes and the cell lines under investigation.
P1.01-020 Translocation ALK/EML4+ in Non-Squamous NSCLC Population and Crizotinib: What Can We Tell?
Authors: N. Pereira, M. Dias, D. Coutinho, J. Pimenta, S. Campaínha, S. Conde, A. Barroso
Journal: Journal of Thoracic Oncology (2017)
Malaria nella Regione Europea dell'OMS (1971-1999)
Authors: G Sabatinelli, M Ejov, P Joergensen
Journal: Eurosurveillance (2001)

Nella Regione Europea dell'OMS, tra il 1996 e il 1999, e diminuito il numero di casi autoctoni di malaria, da 90.506 a 37.170. Fin dagli anni '70 c'e stato, tuttavia, un aumento di otto volte di casi importati: nel 1972 sono stati notificati 1500 casi, 13.000 nel 1999. La Francia, la Germania, l'Italia e il Regno Unito sono i paesi dell'Europa occidentale con il maggior numero di casi.
P1.16-002 Management of Local Recurrence after Segmentectomy for Stage IA Lung Cancer
Authors: T. Mori, F. Kosuke, T. Yamada, H. Osumi, Y. Motooka, E. Matsubara, K. Shiraishi, K. Ikeda, M. Suzuki
Journal: Journal of Thoracic Oncology (2017)
SURG-35. ENDOSCOPIC TRANSNASAL SURGERY FOR NON-ADENOMA LESIONS OF THE PITUITARY AND ANTERIOR SKULL BASE
Authors: David Penn, William Burke, Mina Safain, Edward Laws
Journal: Neuro-Oncology (2017)

Endoscopic transnasal surgery (ETS), commonly used for treatment of pituitary adenomas, is effective for other neoplastic and unusual lesions in the parasellar region and anterior skull base. We evaluated our experience treating oncologic and inflammatory lesions with this approach. We retrospectively analyzed 808 ETS performed between 2008 and 2017 at our institution by one surgeon (ERL). Patients with final pathological diagnoses other than adenoma or cyst were selected. Presentation and operative outcomes were reviewed. Seventy-three of 808 (9.0%) cases met inclusion criteria. Pathological diagnoses included metastastic cancers (n=7, 9.6%), craniopharyngioma (n=30, 41.1%), meningioma (n=7, 9.6%), chordoma/chondrosarcoma (n=5, 6.8%), germ cell tumors (n=1, 1.4%), dermoid/epidermoid tumors (n=2, 2.7%), lymphoma (n=1, 1.4%), other tumors of the sellar region (n=8, 11.0%), lymphocytic hypophysitis (n=7, 9.6%), granulomatous lesions (n=2, 2.7%), sarcoidosis (n=1, 1.4%), Wegner’s Granulomatosis (n=1, 1.4%) and fibrous dysplasia (n=1, 1.4%). Common presenting symptoms were visual loss (67.1%), headaches (52.1%), and hypopituitarism (34.2%). Complications included postoperative CSF leak (11.0%), infection/meningitis (8.2%), visual loss (4.1%), carotid injury (4.1%), and postoperative hydrocephalus (1.4%). There were no peri-operative mortalities. Of the 61 patients with documented clinical follow up for visual symptoms, 68.9% (n=42) had improvement. Likewise 58 patients had documented follow up for headache with improvement in 62.1% (n=36). With regards to endocrinologic function, 12.3% and 17.8% experienced new transient and permanent diabetes insipidus, respectively. Postoperatively, patients required hormone replacement for thyroid (60.3%), testosterone/estradiol (16.4%), cortisol (60.3%), and vasopressin (41.1%). Finally, 12.3% (n=9) of patients received radiation therapy post-operatively. ETS offers a potentially less invasive approach to neoplastic and inflammatory diseases of the parasellar region and the anterior skull base compared to conventional craniotomy, with acceptable morbidity and mortality. This technique can be effective for resection of lesions, to halt progression of neurological deficits, or to obtain tissue diagnosis for adjunctive therapy.
Clinical trials and risk-based approach: reality or Utopia?
Authors: C. Cagnazzo, F. Arizio, M. Piccinni Leopardi, A. Di Costanzo, L. Crotto, R. Matocci, A. Lucarelli, E. Grassi, V. Saracino, C. Fugazza, M. Cinefra, F. Marchetti, C. Taverniti, S. Stabile, M. Monti, E. Marchesi
Journal: Annals of Oncology (2017)
NIMG-34. 99MTC-MIBI SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY-COMPUTED TOMOGRAPHY (SPECT-CT) TO DETECT TUMOR PROGRESSION IN GLIOBLASTOMAS (GB)
Authors: Carolina Victor, Rossana Lopez, Rafael Nunes, Gustavo Marta, Helder Picarelli, Carlos Alberto Buchpiguel, Olavo Feher
Journal: Neuro-Oncology (2017)

Post-treatment assessment of primary brain tumors presents a diagnostic challenge to distinguish real tumor progression (PD) from pseudoprogression or radiation necrosis (PsP/RN). Brain MRI, the gold standard imaging modality is often misleading, even when adding functional sequences (perfusion and/or spectroscopy). SPECT-CT (99mTc-MIBI SPECT with CT) might add complimentary data to MRI in this regard, merging the molecular imaging capabilities of SPECT with more accurate morphologic data from CT images in one single exam. This retrospective study included consecutive patients (pts) treated for glioblastomas (GB) in our institution that had at least one MIBI for suspected PD. Main objective was to assess MIBI early uptake performance in differentiating PD from PsP/RN. PD is defined as unequivocal active tumor on surgical resection/biopsy specimens when available, and/or clinical/radiological PD in the ensuing three months following the MIBI. Uptake in the suspected area was calculated relatively to uptake in the contralateral normal brain. The primary outcomes are sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and accuracy (A), based on the ROC curve generated from early uptake data against outcome. We included 27 pts, comprising of 30 independent observations (3 pts underwent repeated MIBIs for suspected PD in two distinct occasions). 19 males and 8 females, median age of 50 years (range 25 to 70). The ROC curve identified 4.2 as the most appropriate cut-off value for early uptake (Youden´s Index 0,62). With this, MIBI reached 91,3% Sn, 71,4% Sp, 91,3% PPV, 71,4% NPV and 86,7% A. MIBI seems to be an accurate and inexpensive imaging modality to assess in glioblastomas. We plan to do a prospective study evaluating MIBI in this setting in GB.
ACTR-51. CLINICAL EVALUATION OF THE IMIPRIDONE ONC201 IN RECURRENT GLIOBLASTOMA: PREDICTIVE AND PHARMACODYNAMIC BIOMARKER ANALYSES
Authors: Isabel Arrillaga-Romany, Joshua E Allen, Varun V Prabhu, Rohinton S Tarapore, Andrew Zloza, Wolfgang Oster, Patrick Y Wen, Tracy Batchelor
Journal: Neuro-Oncology (2017)

The imipridone ONC201 is the first selective antagonist of the G protein-coupled receptor DRD2 for clinical oncology. ONC201 induces p53-independent apoptosis in newly diagnosed and recurrent glioblastoma in vitro, ex vivo, and in vivo. We performed a Phase II clinical trial that enrolled an initial cohort of 17 patients with recurrent, bevacizumab-naïve, IDH1/2 WT glioblastoma who received 625mg ONC201 every three weeks. One patient continues to have a durable objective response that has deepened over time, exhibiting an 92% regression by 92% after 15 months of therapy. Another patient remains disease-free 14 months after enrolling on this trial following a re-resection. Median OS was 41.6 weeks with an OS12 of 35%. No drug-related SAEs or treatment discontinuation due to toxicity occurred. Plasma PK at 2 hours post-dose was 2.6 ug/mL and serum prolactin induction was observed as a surrogate marker of target engagement. In addition to cytotoxic effects in tumor cells, DRD2 antagonism can induce the activation of NK and other immune cells. We found that immune effector levels in the serum correlated with the kinetics of the objective response. Preclinical studies have identified a DRD2+DRD5- tumor biomarker signature that is predictive of innate sensitivity to ONC201. Among the 15 available archival tumor tissue specimens, all had expression of DRD2 and 8/17 patients had low expression of DRD5. Patients with PFS>5 month had no detectable expression of DRD5 unlike those with PFS<5 months. In addition, 4/8 DRD2+DRD5- are still alive after >57 weeks and 0/7 DRD2+DRD5+ patients remain alive. In summary, ONC201 is a well tolerated novel therapy with potential anti-glioblastoma activity that may be associated with a predictive biomarker signature and immune activation. The pharmacodynamic activity and clinical efficacy of ONC201 continues to be explored in additional cohorts of glioblastoma patients at first recurrence (NCT02525692).
Topical 15% resorcinol for hidradenitis suppurativa: An uncontrolled prospective trial with clinical and ultrasonographic follow-up
Authors: José C. Pascual, Belén Encabo, Rosa F. Ruiz de Apodaca, David Romero, Juan Selva, Gregor B. Jemec
Journal: Journal of the American Academy of Dermatology (2017)