bluuebunny/crossref_metadata_2025_split huggingface dataset:
P03.02 Risk of leptomeningeal dissemination in patients treated with postoperative stereotactic radiotherapy of brain metastases
Authors: Mousli A , Bihin B , Gustin T , Koerts G , Mouchamps M , Daisne J F 
Published: September 2019

Abstract

Background
There is a body of evidence that the risk of leptomeningeal dissemination (LMD) is increased in the postoperative stereotactic radiotherapy (SRT) of brain metastases (BM) compared to adjuvant whole brain radiotherapy (WBRT). The proposed mechanism is an iatrogenic tumor dissemination into the cerebrospinal fluid at time of surgery. Including a wider volume of meningeal wall and the entire surgical track in the definition of the postoperative SRT clinical target volume (CTV) to decrease LMD is still controversial. The aim of this study was to retrospectively analyze the outcome of adjuvant SRT targeted at resection cavities of BM without previous WBRT.

MATERIAL / METHODS
We reviewed 70 patients treated with postoperative SRT for BM. Stereotactic planning computed tomography and planning MRI were imported into iPlan RT image software for image registration and TV delineation. The CTV consisted of any residual enhancement and all resected cavity including a safety margin of 1 to 2 mm. Only in cases of superficial initial tumor with meningeal contact was the CTV enlarged to the adjacent meningeal wall, but never included edema or the entire surgical track. Patients underwent regular follow-up MRI. The cumulative incidence rates of LMD was retrospectively calculated as well as patterns of failure.

RESULTS
The most common histological type was non small cell lung cancer in 61.4%. There were 38.6% infratentorial locations and 37.2 % superficial lesions. En bloc resection was achieved in 60% and compete resection in 75.7%. After a median imaging follow up time of 16.7 months, 54.3% of patients experienced distant brain failure. LMD occurred in 9 of 70 patients (12.9 %) at a median time of 10.7 months. Survival without LMD was 88% at 1 year (IC 95% 79%-97%) and 82% at 2years (IC 95% 72%-94%). In three quarter of cases, LMD interested superficial lesions. In univariate analysis, survival rates without LMD at 1 year for superficial and deep lesions were 88 % and 94 %, respectively (p=0.49). We report only one recurrence in the surgical track (1.42%).

CONCLUSION
The risk of LMD was comparable to the literature (11–17%). Superficial lesions were slightly more likely to relapse in the meninges, but it was non-significant. The risk of recurrence in the surgical track is negligible. Our results do not support the current guidelines recommending the systematic inclusion of the surgical track and the related meninges in the CTV.
P03.07 Radiosurgical managementof trigeminal schwannomas: A single center experience
Authors: Emad Eldin R M , El-Shehaby A M , Abdel Karim K , Reda W A , Nabeel A , Tawadros S 
Published: September 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.
P03.08 Large cerebral arteriovenous malformations management with Volume-staged gamma knife radiosurgery
Authors: Emad Eldin R M , Reda W A , El-Shehaby A M , Abdel Karim K , Nabeel A , Tawadros S 
Published: September 2019

Abstract

BACKGROUND
Large cerebral arteriovenous malformations (AVM) pose a management dilemma because of the limited success of any single treatment modality by itself. Surgery alone is associated with significant morbidity and mortality. Similarly, embolization alone has limited efficacy. Volume-staged gamma knife radiosurgery (VSGR) has been developed for the treatment of large AVMs, to increase the efficacy and improve safety of treatment of these lesions. The aim of the study was to assess the efficacy and safety of VSGR technique for the treatment of large cerebral AVMs.

METHODS
The study included patients treated by VSGR between May 2009 and July 2015. All cases had large AVMs (>10 cc). These were 29 patients.

RESULTS
Twenty-four patients completed radiographic follow up with 15 obliteration cases (62.5%). There was a total of 56 sessions performed. The mean AVM volume was 16 cc (10.1–29.3 cc). The mean prescription dose was 18 Gy (14–22 Gy). The mean follow up duration was 43 months (21–73 months). One patient died during follow up from unrelated cause. Two cases suffered haemorrhage during follow up. Symptomatic edema developed in 5 (17%) patients. The factors affecting obliteration were smaller total volume, higher dose/stage, non-deep location, compact AVM, AVM score less than 3, >18 Gy dose and <15 cc total volume. The factors affecting symptomatic edema were smaller total volume and shorter time between first and last sessions (p 0.012). T2 image changes were affected by SM grade 3 or more (p 0.013) and AVM score 3 or more (p 0.014).

CONCLUSION
VSGR provides an effective and safe treatment option for large cerebral AVMs. Smaller AVM volume is associated with higher obliteration rate.
P04.01 Return to work i patients with low grade glioma
Authors: Rydén I 
Published: September 2019

Abstract

BACKGROUND
We now treat patients with low-grade gliomas (LGG) more aggressively as this prolong survival. Patients are typically in working age, but their ability to return to work (RTW) following treatment has not been studied. We aimed to study patterns of sick leave and return to work among LGG patients in Sweden. In addition, we explored predictors for RTW following LGG diagnosis.

MATERIAL AND METHODS
We performed a nationwide register-based study of patients with grade II diffuse LGG. Data on adult patients aged 18–60 years with a histopathological diagnosis of LGG between 2005–2015 were obtained from the Swedish Brain Tumor Registry (n=381). A matched control sample (n=1900) was acquired from Statistics Sweden. Patients and controls were linked to the social insurance agency data for individual information on sick leave and disability compensation. Multivariable logistic regression was used in order to find predictors for RTW.

RESULTS
One year prior to surgery there was no apparent difference between cases and controls with 90 % working. Among LGG patients there was a rapid increase in sick leave starting approximately six months prior to surgery, while the proportion of controls on sick leave remained constant. One year after surgery, 53 % had returned to work with 29 % working full time. Independent predictors for patients working one year after surgery were higher age (OR 0.96, 95 % CI 0.93–0.99, p <0.01) and more days absent from work prior to procedure (OR 0.91, 95 % CI 0.97-0.95, p <0.001), both negatively associated with RTW.

CONCLUSIONS
In this cohort, more than half of the patients being diagnosed with LGG RTW within one year. Higher prior absence from work and higher age are risk factors for no-RTW. This study provides new information on rates of and factors influencing RTW in patients with LGG.

FUNDING
This project was funded by research grant from the Swedish Research Council (2017-00944).
P04.04 Different stages of astrocytoma in young adult patient
Authors: Susanti E , Kamarlis R , Suci Rahayu N 
Published: September 2019

Abstract

BACKGROUND
astrocytoma is a type of cancer that involve brain parenchym or spinal cord. It arises from glial cells, called astrocytes-star shaped cells which function as supportive tissue of the brain. About 50% of primary brain tumors are astrocytomas. It’s more common in men than women and most often occur at the age of after 45. There are several types of astrocytoma and some of them grow faster than other. We found a rare case where different stages of astrocytoma occur in different areas of the brain and where the latter seemed to show up just within 8 months after the first.

MATERIAL AND METHODS
a 43 year old male patient admitted to neurology ward after a convulsion and hemiparesis on the left extremities. Patient was known to have suffered from astrocytoma in the frontal lobe in October 2017, and had undergone craniectomy evacuation and subsequent radiotherapy which was completed in March 2018. A few months while during recovery at home, patient complained about headache which increased in intensity over a period of 3 months before admission. The first and only convulsion occurred just 12 hours before admission, while left side weakness occurred 7 days prior. Patient underwent a series of radiologic examination after the radiotherapy and also while admitted into hospital. We found a new and large mass in the right temporoparietal lobe from the latest head ct scan. This large mass was not found from the last MRI and head ct scan which was done 8 months prior. pathology anatomy examination was done to the first and second mass found.

RESULTS
Pathology anatomy examination depicted different stages from the two masses, the first one was pleomorphic xanthoastrocytoma (WHO grade II) and the second one was pilocytic astrocytoma (WHO grade I)

CONCLUSION
pleomorphic xanthoastrocytoma (WHO grade II) and pilocytic astrocytoma (WHO grade I) both are considered low grade glioma. neverthless treatment for this devastating disease still far from favorable result or outcome
P09.04 Natural history of meningiomas: review with meta-analyses
Authors: Nakasu S , Nakasu Y 
Published: September 2019

Abstract

BACKGROUND
A recent investigation using MRI showed 2.5% frequency of meningioma as an incidental finding in the population-based neuroimaging study. Although observation has been a mainstay in asymptomatic meningiomas, it may increase the risk of surgery due to enlargement of the tumors and aging of patients. It is important to characterize tumors that will grow to be symptomatic in order to select appropriate treatments and radiological follow-up.

MATERIAL AND METHODS
We reviewed 26 studies (3 from the same institute) that analyzed natural courses in asymptomatic or untreated meningiomas. Radiological progression of tumor was redefined as tumor growth by 15% of initial volume or more whenever possible. To adjust the difference of follow-up interval in each study, the percentages of growing tumors in each study were compared with each mean follow-up period. Individual data were extracted from seven studies for univariate or multivariate analyses. Weighted meta-analyses were performed using the 25 studies.

RESULTS
In time-growth rate analysis, nearly 70% of meningiomas showed radiological progression defined by a volume criteria and the rate approached plateau at 5–6 years. Meta-analyses showed that each radiological progression, growth speed (annual volume change (AVC) or relative growth rate (RGR)) and symptomatic progression had different factors related to their progression. Age, calcification and high intensity on T2 weighted image related to radiological progression and growth speed but not to clinical progression. In individual data analyses, tumor size (diameter 2.6cm (AUC 0.773; specificity 0.759, sensitivity 0.800), volume 5.6cm3 (AUC 0.775, specificity 0.717, sensitivity 0.800)) was a possible marker for symptomatic growth.AVC (>= 2.1cm3/year) was the strongest indicator for clinical progression. In the group of >=2.1cm3/year, Kaplan-Meier analysis showed that progression free rate was 69.3% at 3 years, and reached to 55.4% at 6 years whereas 100% in slower growth group.

CONCLUSION
Radiological features may not be very much useful for prediction of clinical progression except for perifocal edema. This may be due to dynamic changes of these radiological markers in a long term. Initial quantitative tumor size and growth speed especially AVC were reliable factors for decision of treatment for asymptomatic meningiomas.
P09.06 Risk factors associated with Meningioma in a Cohort of 2 Million Israeli Adolescents
Authors: Yust-Katz S , Derzane E , Keinan L , Amiel A , Honig A , Laviv Y , Kanner A , Twig G , Siegal T 
Published: September 2019

Abstract
Background: Meningiomas are the most common primary central nervous system tumors. Risk factors including- obesity, height, history of allergy/atopy or autoimmune diseases, have been assessed with conflicting results. In this study, we reviewed the database of a large cohort of Israeli adolescents in order to assess potential risk factors for the development of meningiomas.
Methods: This study analyzed a cohort of 2,035,915 Jewish men and women who underwent compulsory physical examination as part of screening for army drafting between the age of 16 to 19 from 1948 to 1991. Meningioma incidence was identified by linkage to the national cancer registry. Cox proportional hazard models were used to estimate the hazard ratios for meningioma according the several risk factors including sex, BMI, height, history of allergic and autoimmune disease.
Results: Linkage of the adolescent military database with the Israeli cancer registry revealed 480 cases of meningioma. The median age at diagnosis of meningioma was 42.1 ± 9.4 (range 17.4–62.6). On univariate analysis, only gender (female) and height were significantly associated with the risk of meningioma for the whole study population (p<0.01 for both variables). When analyzed separately for gender- height was significant only for men. Spline analysis in the men group showed the minimum risk at a height of 1.62 meters and a statistically significant increase in the risk for meningioma at heights taller than 1.85 meters. BMI was not associated with an elevated risk of meningioma even when analyzed separately for gender. Past medical history including asthma, diabetes, and other atopic and autoimmune diseases were not found to be associated with the risk of meningioma.
Conclusion: In this large population study, we found that sex and taller height in adolescent males was associated with an increased risk of meningioma.
P11.03 Next generation sequencing-identified IDH-1, ATRX, TP53 mutation and MYCN amplification in glioblastoma with primitive neuroectodermal tumor-like feature and extensive subarachnoid spread: a case report
Authors: Lee K , Gheeyoung C 
Published: September 2019

Abstract

BACKGROUND
In recent years, there have been numerous molecular studies in the glioblastoma. With regard to glioblastoma showing primarily extensive subarachnoid spreading, however, the pathogenesis remains to be determined due to its low incidence. Present report is a rare case of glioblastoma with primitive neuroectodermal tumor (PNET)-like feature, showing extensive subarachnoid spread, as well as the distinguishing result of its molecular analysis using next generation sequencing (NGS).

DESCRIPTION
A 37-year-old male presented with a new onset, severe headache. Magnetic resonance imaging (MRI) test revealed a diffuse infiltrative mass in the right frontal lobe. The tumor was also spread broadly in subarachnoid space. The patient underwent craniotomy and tumorectomy. Microscopically, glioblastoma showed PNET-like feature. Tumor cells had high nuclear/cytoplasmic ratios, oval, slightly elongated or angulated hyperchromatic nuclei, markedly increased mitotic activity, and obvious apoptotic bodies. Immunohistochemical analysis showed partly positivity of GFAP. Also this tumor demonstrated CD56 and synaptophysin immunoreactivity. IDH-1 immunohistochemistry was negative, which initially led to the diagnosis of glioblastoma, IDH wild-type. However, IDH-1 (p.Arg132His) mutation was found in subsequent NGS test. Additionally, two frame shift genetic alteration was found including ATRX (p.Tyr2208fs) and TP53 (p.Pro301fs). Interestingly, also MYCN (2p24.3) amplification was identified by both NGS and fluorescence in situ hybridization (FISH) test. Estimated MYCN copy number was 18. Despite the post-operative therapy including temozolomide and radiotherapy was performed, the tumor aggressively progressed and the patient expired nine months after the first symptom onset.

CONCLUSION
Although there have been several previous reports of MYCN amplification in glioblastoma with PNET-like feature, this is the first case report which finding in IDH-mutant type. IDH-1 mutation and younger age are usually associated with a better prognosis in glioblastoma. However, this case may suggest that when MYCN amplification coexists in IDH-mutant type, the tumor behavior could be contrarily aggressive.
P11.06 Non epigenetic effect of vorinostat in glioblastoma cells
Authors: Perez T , Berges R , Maccario H , Braguer D , Honoré S 
Published: September 2019

Abstract

BACKGROUND
Glioblastoma multiform (GBM) is the most frequent primitive brain tumor. GBM has a high recurrence and mortality. Histone deacetylase (HDAC) inhibitors have evoked great interest because they are able to change transcriptomic profiles to promote tumor cell death but also show undesirable side effects due to the lack of selectivity.We show new properties of low dose vorinostat, which inhibits cytoplasmic HDAC6 and display interesting non-epigenetics effects, especially on the microtubular cytoskeleton.

MATERIAL AND METHODS
We used murine (GL261) and human (U87 and GBM6 stem cells) cellular models. The cell proliferation was assessed by MTT tests, the migration by the 24 hours Transwell technic and by wound/healing tests. The expression levels of proteins of interest were assessed by Western Blot. Microtubules dynamics were assessed by time-lapse videomicroscopy. The synergy between drugs was tested by Loewe model.

RESULTS
Vorinostat inhibited the proliferation and the migration of the three cell lines mentioned above at level below the EC50.Vorinostat induces tubulin acetylation and alpha-tubulin c-terminal detyrosination that signed microtubular stabilization and these effects are independent of histone acetylation (HADC3). Interestingly, vorinostat decreases EB1 expression (a bad prognostic factor in GBM) and decreases microtubule dynamics. Moreover, vorinostat decreases neural markers such as GFAP, beta3-tubulin and CNPase and increases mural markers expression such as SMA/EGFR and PDGFR. Finally, it showed a synergy combined with erlotinib.

CONCLUSION
Low dose vorinostat, which do not affect histone désacetylase, has antitumor effect on glioblastoma cells by a new mechanism involving microtubule cytoskeleton. Interestingly, combination of low doses vorinostatand erlotinibshowed a strong synergy. Low dose, vorinostat could therefore represent an interesting therapeutic option and fewer side effects and that could be used to increased GBM patient sensitivity to erlotinib.
P11.10 The IFNγ pathway mediates brain metastasis formation of breast cancer
Authors: Pedrosa R , Kros J M , Schrijver B , Marques R , Leenen P , Dik W , van Eijck C , Mustafa D 
Published: September 2019

Abstract

BACKGROUND
In previous work we showed the prominence of the T-cell response in the formation of brain metastases of primary ER negative breast cancers (Mustafa et al, Acta Neuropathol 2018). We also showed that breast cancer cells co-cultured with stimulated T lymphocytes overexpress Guanylate-binding protein 1 (GBP1) accompanying increased trespassing ability through an in vitro blood-brain barrier (BBB) model. In addition, we demonstrated a predilection for metastasizing to brain of breast cancer cells that were co-cultured with activated T cells in a mouse model. We now scrutinize the importance of the IFNγ pathway for tresspassing of the tumor cells through the BBB following T cell contact.

MATERIAL AND METHODS
Anti-hIFN-γ-IgA antibodies were used to neutralize the IFNγ effects on the tumor cells. The effects on the tumor cells is only due to native IFNγ produced by activated T cells, not by recombinant IFNγ. Since the IFNγ expression itself enhances its expression by the T cells, we blocked IFNγ receptors prior to adding CD3+ T cell conditioned media to the breast cancer cells. The receptor blocking was achieved by antibodies to the IFNγα and IFNγβ subunits. Activation of the STAT1 pathway was monitored by GBP1 expression. For functional read-out the in vitro BBB model was used.

RESULTS
The presence of T-lymphocyte-secreted IFNγ in the primary breast cancer microenvironment activates the STAT1-dependent IFNγ pathway in breast cancer cells, endowing them with an increased ability to trespass the in vitro BBB. Moreover, direct inhibition of soluble IFNγ, or blocking of the IFNγ-specific receptor in breast cancer cells significantly decreases their ability to cross the BBB.

CONCLUSION
The results illustrate the specific action of T lymphocytes in the formation of cerebral metastasis involves the IFNγ signaling pathway as one of the crucial entangled pathways Subsequent studies should aim at the interference with the IFNγ pathway to develop preventive strategies against the formation of cerebral metastases of breast cancer.