tbuckley/cabot-search huggingface dataset:
P14.83 Adjuvant chemotherapy after severe myelotoxicity during temozolomide chemoradiation in gliomas. It is feasibile? The talian Multicentric Study (AINO)
Authors: V Villani, A Fabi, P Gaviani, R Rudà, G Lombardi, G Simonetti, A Silvani, E Pronello, G Minniti, A Pace
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Malignant gliomas are aggressive primitive brain tumor in adults. Today, the standard of care is Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ. TMZ treatment has been considered to have a low toxicity profile. However, during concomitant treatment some patient may develop a severe myelosuppression. This toxicity may be in some cases prolonged and lead to treatment discontinuation. MATERIAL AND METHODS We have retrospectively collected data from 5 italian neuro-oncological centers, about glioma patients who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy with TMZ. The purpouse of this study is to evaluate: percentage of patients receiving adjuvant chemotherapy after severe myelotoxicity; rate of toxicity observed during adjuvant chemotherapy. RESULTS 54 glioma patients who developed myelosuppression of grade 3 or 4 were considered. Hystology was Glioblastoma in 45 patients (83%); 63% of patients were female. Myelotoxicity during concomitant phase occurred at a median of 4 weeks (range 1–8) from the start of treatment.After recovery of myelotoxicity 19 patients did not received any treatment while 35 (65%) were treated with chemotherapy (28 received standard TMZ, one TMZ with metronomic schedule, 2 lomustine and 4 other agents). Among patients treated with TMZ, 13 patients presented hematological toxicity grade 3–4 which required treatment discontinuation in 7 cases (20%). CONCLUSION we observed that 80 % of glioma patients presenting severe myelotoxicity during concomitant radiochemotherapy may be treated with maintenance TMZ after blood value recovery.
JS1.1 Specific genetic alterations of breast tumors lead to Yo paraneoplastic cerebellar syndromes
Authors: V Desestret, D Pissaloux, I Treilleux, M Small, M Robert, V Rogemond, G Picard, D Psimaras, A Alentorn, J Honnorat
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) are rare syndromes associated with ovarian or breast cancers and caused by an auto-immune response against neuronal antigens expressed by tumor cells. We previously demonstrated in Yo-PCD ovarian cancers an association between massive infiltration of ovarian tumors by activated immune effector cells and recurrent gains and/or mutations of onconeural Yo genes (CDR2L and CDR2), suggesting that such genetic alterations in ovarian tumor cells may trigger immune tolerance breakdown and initiation of the auto-immune reaction against Purkinje cells. MATERIAL AND METHODS We pursued the characterization of Yo-PCD tumors and specifically studied breast cancer by IHC, FISH, CGH array and RNA sequencing analysis of 17 breast Yo-PCD tumors and by comparing their genetic characteristics with 10 sporadic breast tumors and public databases. RESULTS We confirmed that specific genetic alterations were also present in breast cancers associated with Yo-PCD. Moreover, this study provides additional evidence for a role of tumor cell specificities in PCD immunopathology by revealing peculiarities in Yo-PCD breast tumors compared to Yo-PCD ovarian cancer. Indeed, not only the CDR2L Yo gene was amplified in 8/9 breast Yo-PCD cancers but also the Erb2/Her2 gene in 15/16 (both genes are on chromosome 17q). In addition to this original Her2 and Yo antigen amplification confirmed by FISH, we observed an overexpression of these proteins by IHC analysis. These Yo-PCD breast cancers are also all negative for hormone receptors (HR). Thus, Yo-PCD breast tumors seem to belong to the molecularly and clinically distinct class of HR-negative and Her2-enriched breast cancers, which represents less than 10 % of breast cancers in the general population. Transcriptomic analysis confirmed that breast Yo-PCD tumors differ by their expression programs from classical breast cancers molecular subtypes. CONCLUSION Understanding the tumor genetic features leading to the immune breakdown and anti-tumor immune response as well as nervous tissue attack remains challenging and seems to be specific according to the tumor subtypes. Herein, our results suggest that, despite sharing common genetic alterations (copy number variations and mutations affecting Yo genes), the Yo-PCD immunopathogenesis of breast and ovarian cancers differ by involving different tumor-specific molecular pathways.
Leukemic Transformation of Post-Essential Thrombocythemia Myelofibrosis: A Unique Case Presenting with Double MPL and CALR Mutations
Authors: Cédric Cleyrat, Devon S Chabot-Richards, David T Lynch, Jason Gotlib, Tracy I. George, Bridget S. Wilson, Mohammad A Vasef, Cecilia Arana-Yi
Journal: Blood (2017)
Potential impact on prevalence of obesity in the UK of a 20% price increase in high sugar snacks: modelling study
Authors: Pauline F D Scheelbeek, Laura Cornelsen, Theresa M Marteau, Susan A Jebb, Richard D Smith
Journal: BMJ (2019)

To estimate the potential impact on body mass index (BMI) and prevalence of obesity of a 20% price increase in high sugar snacks.Modelling study.General adult population of the United Kingdom.36 324 households with data on product level household expenditure from UK Kantar FMCG (fast moving consumer goods) panel for January 2012 to December 2013. Data were used to estimate changes in energy (kcal, 1 kcal=4.18 kJ=0.00418 MJ) purchase associated with a 20% price increase in high sugar snacks. Data for 2544 adults from waves 5 to 8 of the National Diet and Nutrition Survey (2012-16) were used to estimate resulting changes in BMI and prevalence of obesity.The effect on per person take home energy purchases of a 20% price increase for three categories of high sugar snacks: confectionery (including chocolate), biscuits, and cakes. Health outcomes resulting from the price increase were measured as changes in weight, BMI (not overweight (BMI <25), overweight (BMI ≥25 and <30), and obese (BMI ≥30)), and prevalence of obesity. Results were stratified by household income and BMI.For income groups combined, the average reduction in energy consumption for a 20% price increase in high sugar snacks was estimated to be 8.9×103 kcal (95% confidence interval -13.1×103 to -4.2×103 kcal). Using a static weight loss model, BMI was estimated to decrease by 0.53 (95% confidence interval -1.01 to -0.06) on average across all categories and income groups. This change could reduce the UK prevalence of obesity by 2.7 percentage points (95% confidence interval -3.7 to -1.7 percentage points) after one year. The impact of a 20% price increase in high sugar snacks on energy purchase was largest in low income households classified as obese and smallest in high income households classified as not overweight.Increasing the price of high sugar snacks by 20% could reduce energy intake, BMI, and prevalence of obesity. This finding was in a UK context and was double that modelled for a similar price increase in sugar sweetened beverages.
NCMP-05. THE INCIDENCE AND IMPACT OF POST-OPERATIVE STROKE IN SURGERY FOR LGG
Authors: Asaf Berger, Garry Tzarfati, Mathias Costa, Marga Serafimova, Akiva Korn, Tali Alfassi, Daniel Aviram, Alon Kashinian, Zvi Ram, Rachel Grossman
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Postoperative neurological deficits may outweigh the benefit conferred by maximal resection of gliomas. We evaluated the incidence of ischemic events in patients undergoing surgery for low-grade gliomas (LGG) and the long-term neurological and cognitive sequelae. METHODS Between 2013–2017, 168 patients underwent surgical resection or biopsy for LGG at our center. A full dataset, including pre- and postoperative magnetic resonance imaging (MRI) and long-term clinical evaluation findings, was available for 82 patients (study group). Ischemic complications, overall and progression-free survival, and functional and neurocognitive outcomes were evaluated. RESULTS The immediate postoperative MRI revealed an acute ischemic stroke adjacent to the tumor resection cavity in 19 patients (23%), 13 of whom developed new neurological deficits due to the ischemic event. Infarcts were more common in patients with recurrent tumors, especially those involving the Sylvian fissure (p&lt; 0.05). Surgery for insular gliomas had the strongest association with postoperative infarcts. Survival of patients w/wo a postoperative infarct was the same. The median Karnofsky-Performance Status was lower for the infarct group vs. the non-infarct group at 3 months post-surgery (p=0.016), with a gradual significant improvement for the former over one year (p=0.04). Immediately after surgery, 27% of the patients without infarcts and 58% of those with infarcts experienced a new motor deficit (p=0.037), decreasing to 16% (p=0.028) and 37% (p=0.001), respectively, at one year. Neurocognitive analysis findings before and 3 months after surgery were unchanged, but patients with an infarct had a significant decrease in naming (p=0.04). Confusion during awake craniotomy was a strong predictor of an ischemic stroke. CONCLUSIONS Intraoperative strokes are more prevalent among patients who undergo recurrent surgeries, especially in the insula. Although they do not affect survival, these strokes negatively impact the patients’ activity and performance status, especially during the first 3 postoperative months, with gradual functional improvement over one year.
Variation of anti-CCP antibodies and IGM rheumatoid factor during follow-up of patients with recent-onset polyarthritis correlations with clinical outcomes
Authors: Gilles Boire, Pierre Cossette, Claude Daniel, Artur J. de Brum-Fernandes, D Hercelin, P Liang, H A Menard, Theo Niyonsenga, S Roux
Journal: Annals of the Rheumatic Diseases (2005)
P14.72 Multicentric glioblastoma - A retrospective study of imaging characteristics, treatment approach, pattern of relapse and survival
Authors: A Benouaich Amiel, V Khasminsky, O Gal, S Fichman, T Weiss, T Siegal, S Yust-Katz
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Multicentric glioblastoma (m-GBM), defined as well separated tumoral foci, is a rare GBM variant comprising 6–13% of all GBM cases. Published data regarding m-GBM is scarce and is largely reporting on multicentric enhancing foci. We performed a retrospective study to determine the incidence, imaging characteristics, treatment approach, pattern of relapse and prognosis of m-GBM. MATERIAL AND METHODS The neuropathological database of our institution was surveyed for histological diagnosis of adult GBM diagnosed between 01/01/2015 and 31/05/2018. All pre-operative MRI were reviewed to identify patients with m-GBM. We included in the definition of m-GBM well separated enhancing as well as non-enhancing tumor foci. The medical records and follow-up MRI studies were reviewed in order to retrieve the data. RESULTS Of the 170 patients with newly diagnosed GBM 14 (8%) presented with m-GBM. All of them had at least one enhancing lesion and 11 (78.5%) patients had additional well separated non-enhancing tumor foci. The total number of lesions was 37 (19 enhancing and 18 non-enhancing) with a median number of lesions per patient of 2 (range 2 to 4). Median age at diagnosis was 66 (range: 49–79) years. Nine of the patients (64%) underwent surgical resection of the enhancing component whereas 5 patients had only a biopsy. Median follow up was 14.3 (range: 2–30) months. All but one patients were treated by standard concurrent radiotherapy with temozolomide. Median progression free survival is 6.2 (range: 0–13.3) months. Five of the 18 non-enhancing tumor foci eventually displayed contrast enhancement during the course of the disease. At last follow up, 12 patients died, with an overall survival of 12.3 months. Information regarding radiation fields, pattern of disease progression and molecular profile will be presented at the meeting. CONCLUSION m-GBM presents therapeutic dilemas regarding the optimal surgical approach and radiation field planning. Better understanding of the disease course and pattern of progression may help to optimize the therapeutic approach implying particularly to non-enhancing tumor foci.
P13.09 Genomic analysis of paired IDHwt glioblastoma (GB) reveals recurrent alterations of MPDZ at relapse after radiotherapy and temozolomide (RTCT)
Authors: B Chanez, R Appay, A Guille, A Lagarde, C Bequet, C Jiguet-Jiglaire, T Graillon, H Dufour, D Figarella-Branger, O Chinot, E Tabouret
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND GB are highly aggressive tumors which systematically relapse. Our objective was to identify disease progression mechanisms and genomic drivers of GB treatment resistance. MATERIAL AND METHODS Ten paired frozen tumors from initial and recurrent surgery after RTCT were screened by CGH Array. Next, NGS of the selected genes was performed on 19 paired tumors (38 samples). Molecular alterations were correlated with patient data. TCGA was used to characterize the molecular profile of MPDZ. RESULTS Nineteen IDHwt GB patients with a median age of 54.5 years (37.2–72.8) were included. Using CGH array, unsupervised analysis clustered the whole samples by paired of initial and recurrent tumors. However only 44% of CGH Array alterations were shared between initial and recurrent tumors (amplifications: 55%; deletions: 30%). The new alterations detected at relapse were amplifications in 25% and deletions in 23% of tumors. Two regions corresponding to 171 genes were lost at relapse (p=0.03): 19q13.33 and 19q13.41. Using DAVID genome, 3/171 genes (related to neutrophil chemotactic factors) were identified: FPR1, FPR2, FPR3. Moreover, 24 genes were lost (including MPDZ) and 2 genes were gained in 20% of recurrent tumors. Totally, 29 genes were analyzed by NGS and 4 genes showed pathogenic mutations shared by initial and recurrent tumors: FPR2, REL, TYRP1 and MPDZ. Only MPDZ showed, at relapse, an increasing rate of mutated variants and a new mutation affecting the splicing site. These alterations were independent from classical prognostic factors (age, sexe, karnofsky performans status, MMS and MGMT status) and from patient survivals. To explore MPDZ expression, we used TCGA initial dataset and observed that a lower RNA expression of MPDZ was associated with IDHwt (p&lt;0.001) and grade IV (p&lt;0.001) gliomas, reinforcing the potential pejorative impact of MPDZ loss. CONCLUSION Our results suggest that MPDZ is frequently altered at initial diagnosis with increased alterations in recurrent IDHwt GB after RTCT, suggesting that MPDZ impairment could contribute to the resistance/relapse mechanisms. Further investigations are needed to validate these results. Our results suggest that MPDZ is frequently altered at initial diagnosis with increased alterations in recurrent IDHwt GB after RTCT, suggesting that MPDZ impairment could contribute to the resistance/relapse mechanisms. Further investigations are needed to validate these results.
P03.07 Radiosurgical managementof trigeminal schwannomas: A single center experience
Authors: R M Emad Eldin, A M El-Shehaby, K Abdel Karim, W A Reda, A Nabeel, S Tawadros
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Trigeminal schwannomas are a rare form of intracranial schwannomas. They can occur anywhere along the track of the trigeminal nerve, including the middle, posterior fossa or both. It can even extend extracranially. The variability of its location and extent, in addition to its close proximity to critical neurovascular structures makes surgical intervention challenging. Taking from the success of treating vestibular schwannomas with stereotactic radiosurgery, it has been used as an alternative to surgery for the treatment of trigeminal schwannomas. Because these tumors are rare more clinical evidence is required to assess the response of these tumors to stereotactic radiosurgery.The aim of this study was to evaluate the efficacy and complications associated with treatment of the trigeminal schwannomas by gamma knife radiosurgery. MATERIAL AND METHODS The study included 51 patients with trigeminal schwannomas not associated with NF2, treated by Leksell gamma knife. There were 25 males and 26 females. The mean age at presentation was 43 years. The patients underwent a total of 58 gamma knife sessions (44 single and 7 volume-staged sessions). Eight patients had previous surgery. The tumor nature was solid in 46, cystic in 3 and mixed in 2 patients. The mean target volume was 8.5 cc (0.6–30.7 cc) with the mean overall tumor volume being 9.6 cc (0.6–31.1 cc). The mean prescription dose was 12 Gy. RESULTS The mean follow up was 57 months (12–152 months). The tumor shrank in 23 (45%) patients and remained stable in 25 (49%). Tumor progressions occurred in 3 (6%) patients. The tumor control rate was 92%. The progression-free survival at 5,7 and 10 years was 95%, 88% and 79%, respectively. Clinical improvement occurred in 27 (53%) patients and was significantly associated with tumor shrinkage (p 0.03). Twenty patients (39%) remained clinically unchanged. Adverse radiation events occurred in 7 patients and were significantly associated with target and overall tumor volume (p 0.028 and 0.004). CONCLUSION Gamma knife radiosurgery appears to be an effective and safe adjuvant and primary treatment modality for trigeminal schwannomas. Large tumors should be debulked first before radiosurgery, when feasible.
Combination treatment for giant cell tumors of the bone.
Authors: Artem A. Barashev, Oleg I. Kit, Larisa N. Vashchenko, Evgeniya M. Nepomnyashchaya, Nikolay S. Karnaukhov, Elena P. Ulianova, I. P. Sidorenko, Tatiana V. Ausheva, Irina Dashkova, Elena A. Andreyko, V. V. Mozulyaka
Journal: Journal of Clinical Oncology (2019)

e22504 Background: Positive effect of the monoclonal antibody denosumab in cancer treatment has been reported in recent years. Since surgical treatment is considered the main method of treatment for giant-cell tumors of the bone (GCTB), the purpose of our study was to improve treatment outcomes using denosumab. Methods: The study included 10 patients with verified GCTB (5 men, 5 women, mean age 36±3.14 years). Tumors were located in the upper third of the tibia (3 patients), the lower third of the tibia (3), iliac bone (1), heel bone - 1, the lower third of the femur - 1, the lower third of the humerus - 1.Patients received 2 cycles of neoadjuvant denosumab treatment (120 mg subcutaneously once every 4 weeks) with further tumor resection. The bone defect was reconstructed with bone grafting in marginal resections and endoprosthetics in segmental resections. The effect of neoadjuvant therapy was assessed morphologically by optical light microscopy; histological and histochemical methods were used. Results: Neoadjuvant treatment reduced pain syndrome and restored the support ability. X-ray and spiral X-ray CT showed sclerotic sites in the lytic foci. Consolidation of pathological fractures in the tumor area was registered, as well as fibrosis of the tumor focus. The tissue on the sections of removed material appeared dryish and whitish, it replaced the medullary canal. Microscopic examination of tumors revealed areas of extensive sclerosis foci, and a slight lymphohistiocytic infiltration in some cases. Osteoclasts and osteoblasts were absent in the histological preparations. Conclusions: Neoadjuvant denosumab in GCTB with the following surgery has a pronounced positive effect. This was confirmed by the morphological picture of the operative material demonstrating the development of extensive foci of loose and dense fibrous connective tissue with a small amount of lymphohistiocytic elements.
High hydrostatic pressure to induce immunogenic cell death in human tumor cells.
Authors: Iva Truxova, Jitka Fucikova, Irena Moserova, Simona Partlova, Jirina Bartunkova, Radek Spisek
Journal: Journal of Clinical Oncology (2013)

3076 Background: Recent studies have identified molecular events characteristic of immunogenic cell death. These include surface exposure of calreticulin, HSP70 and HSP90, release of intranuclear HMGB1 and secretion of ATP from dying cells. Several chemotherapeutic agents, including anthracyclins, oxaliplatin and bortezomib, and hypericin-based photodynamic therapy have been described to induce the immunogenic cell death in human tumor cells. We investigated the potential of high hydrostatic pressure (HHP) to induce immunogenic cell death in human tumor cells. Methods: Prostate and ovarian cancer cell lines and primary tumor cells were treated by HHP and we analyzed the kinetics of the expression of immunogenic cell death markers. HHP killed tumor cells expressing immunogenic cell death markers were tested for their ability to activate dendritic cells (DCs), to induce tumor specific T cells and regulatory T cells. Results: HHP induced rapid expression of HSP70, HSP90 and calreticulin on the cell surface of all tested cell lines and primary tumor cells. HHP also induced release of HMGB1 and ATP from treated cells. The kinetics of expression was similar to doxorubicin, HHP, however, induced 1.5-2 fold higher expression of HSP70, HSP90 and calreticulin. The interaction of DCs with HHP-treated tumor cells led to the faster rate of phagocytosis, significant upregulation of CD83, CD86 and HLA-DR and release of IL-6, IL-12p70 and TNFα. The ability of HHP-killed tumor cells to promote DCs maturation was cell contact dependent. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor-specific CD4 + and CD8 + IFN-g-producing T cells even in the absence of additional maturation stimulus. DCs pulsed with HHP treated tumor cells also induced the lowest number of regulatory T cells among the tested conditions. Cells treated by HHP can by cryopreserved in liquid nitrogen and retain their immunogenic properties upon thawing thus allowing for their convenient use in the manufacturing of cancer immunotherapy products. Conclusions: High hydrostatic pressure is a reliable and very potent inducer of immunogenic cell death in the wide range of human tumor cell lines and primary tumor cells.