bluuebunny/crossref_metadata_2025 huggingface dataset:
P14.39 How far should it be removal beyond the Gd-enhanced edge in Glioblastoma cases? -Preoperative removal range identification using Methionine-PET and Thallium-SPECT fusion image
Authors: Nakayama N , Yano H , Takei H , Miwa K , Shinoda J , Iwama T
Published: September 2019

BACKGROUND

Mostly, the removal rate of glioblastoma has been discussed in the Gd enhanced area, but tumor cells are surely infiltrated beyond the Gd enhanced edge. Although Methionine-PET (MET) and Thallium-SPECT (Tl) are useful for preoperative tumor invasion range identification, they are off-label use in most countries, and their respective accumulation ranges do not match completely. In this study, Gd-MRI, MET, and Tl were performed, and the accumulation range was compared from the fusion images, and the prediction method of the tumor cell infiltration range was examined.

MATERIAL AND METHODS

The mean interval period between MET and Tl administration was 16.3 days in 21 cases of glioblastoma (12 male and 9 female, average age 59.1 ± 17.8 years). Fusion images were generated using iPlan Cranial 3.0.The MET-area, Tl-area, Overlap-area where MET and Tl overlap, and Accumulation-area where MET and Tl are maximally accumulated were measured in the same cross section as the Gd-enhanced maximum area (Gd-area, X cm2) in axial view. Each volume was also measured similarly.

RESULTS

Gd-area was correlated with all of MET-area, Tl-area, Overlap-area, and Accumulation-area (p ≦0.0001).Gd-volume (X’cm3) showed correlation with all of MET-volume, Tl-volume, Overlap-volume, and Accumulation-volume (p ≦0.0001). The linear approximation was calculated as follows. Overlap-area = 1.942X + 1.0208 (R = 0.937), Accumulation-area = 1.3299X + 6.098 (R = 0.889), Overlap-volume = 1.1539X ‘+ 7.0573 (R = 0.927), Accumulation-volume = 1.8668X ‘+30.06 (R = 0.893).

CONCLUSION

These linear approximations can be used to predict the tumor invasion range from the Gd-enhanced maximum area or Gd-enhanced volume without using off-label use drugs.
P14.42 Diagnostic challenges of infratentorial hemangioblastomas: improvement of current radiological classification scheme
Authors: Jung I , Kim E , Moon J , Kang S , Chang J
Published: September 2019

BACKGROUND

Hemangioblastomas (HBMs) are known to exhibit very typical radiological features and thus classified by well-established radiological classification scheme. However, after we have experienced unusual cases in which current radiological classification system was not enough to categorize them, we reviewed our series of infratentorial HBMs in order not only to evaluate the relevance of current classification scheme, but also to possibly improve it. Also, we added descriptions on several cases with unusual radiological magnetic resonance imaging (MRI) findings in which differential diagnosis was challenging.

MATERIAL AND METHODS

We retrospectively reviewed preoperative MRI of 118 patients with pathologically diagnosed infratentorial HBMs at our institution between 2002 and 2015. Total 128 tumors were included to this study and classified into four categories based on the presence and nature of cystic components: extratumoral cystic (Type Ce, classical cystic with a mural nodule), intratumoral cystic (Type Ci), mixed cystic (Type Cm), and solid (Type S). The association with von Hippel-Lindau (VHL) disease was also investigated.

RESULTS

In 118 patients (65 male and 53 female), 79 (66.9%) had solitary HBMs and 39 (33.1%) were diagnosed with VHL disease. Type Ce with typical radiological findings was the most prevalent type of HBM (63.3%), followed by Type S (21.1%). HBMs with intratumoral cysts were uncommon (Type Ci, 11.7%) and mixed extratumoral and intratumoral cysts (Type Cm) accounted for only 3.9%. No intergroup differences were observed in the proportions of each subtype between the solitary and VHL disease-associated HBMs.

CONCLUSION

Radiological features of HBMs are usually typical thus preoperative presumption is not difficult in majority of cases. Improved radiological classification scheme is more practical because it does not only help surgeons determine whether the cystic wall should be removed or not, but also covers cases with atypical radiological presentations. For solid and extraparenchymal HBMs, differential diagnosis is more difficult as well as very critical as surgical removal is often very challenging.
P14.48 Identification of subsets of IDH-mutant glioblastomas with distinct epigenetic and copynumber alterations and stratified clinical risks
Authors: CHAN A K , Li K K , Shi Z F , Ng H K
Published: September 2019

BACKGROUND

IDH-mutant glioblastoma is classified by the 2016 CNS WHO as a group with good prognosis. However, the actual number of cases examined in the literature is relatively small. We hypothesize that IDH-mutant glioblastoma is not a uniform group and should be further stratified.

MATERIAL AND METHODS

We conducted methylation profiles and estimated copy number variations in 64 IDH-mutant glioblastomas.

RESULTS

Our results showed that 10.9%, 53.1%, and 35.9% of tumors belonged to Codel, G-CIMPhigh, and G-CIMP-low methylation subgroups, respectively. G-CIMP-low subgroup was associated with significantly worse OS as compared to G-CIMP-high (P=0.005) and Codel groups (P=0.009). CDKN2A deletion (37.5%) was the most common gene copy number variation, and was associated with G-CIMP-low subgroup (P=0.001). Other frequent copy number changes included MET (4.7%), CCND2 (17.2%), PDGFRA (14.1%), CDK4 (12.5%), and EGFR (12.5%) amplification. Both CDKN2A deletion (P=0.008) and MET amplification (P<0.001) were associated with poor OS in IDH-mutant glioblastomas. Combined epigenetic signatures and gene copy number variations separated IDH-mutant glioblastomas into Group 1 (Codel), Group 2 (GCIMP- high), Group 3 (G-CIMP-low without CDKN2A and MET alterations), and Group 4 (G-CIMP-low with CDKN2A/MET alteration). Survival analysis revealed Group 1 had a favorable OS (median survival: 41.3 months), while Groups 2 and 3 exhibited an intermediate OS (median survival: 20.6 and 21.8 months, respectively). Group 4 exhibited the worst OS (median survival: 8.4 months). Multivariable analysis confirmed the independent prognostic significance of our Groups.

CONCLUSION

IDH-mutant glioblastomas should be stratified for risk with combined epigenetic signature and CDKN2A/MET status and some cases have poor outcome.
P14.64 Primary Central Nervous System Lymphoma (PCNSL) with HD- MTX based chemotherapy: tolerability and results
Authors: Silvani A , Anghileri E , Simonetti G , Eoli M , Finocchiaro G , Pollo B , Farinotti M , Fariselli L , Gaviani P
Published: September 2019

BACKGROUND

Primary Central nervous system (CNS) lymphomas (PCNSL) are extranodal, malignant non- Hodgkin lymphomas of the diff use large B-cell type, confined to CNS. It accounts for up to 1% of all lymphomas and about 3% of all CNS tumours. The incidence continues to rise in immuno- competent elderly patients.Although the prognosis of PCNSL remains poor, it has improved in the past two decades as a result of better treatment strategies. However, treatment recommendations still result mainly from retrospective series or single-arm phase 2 studies and a few three completed randomised trials. We described a series of patients with newly diagnosis of PCNSL treated with modified-schedula published by Omuro

MATERIAL AND METHODS

Patients was treated with HD-MTX, procarbazine, vincristine, received four 28-day cycles of chemotherapy, on schedule: HD-MTX (3·5 g/m²) days 1 and 15; Procarbazine (100 mg/m²) on days 1–7. Vincristine (1·4 mg/m²) on days 1 and 15. Toxicity was assessed with Common Terminology Criteria for Adverse Events version 4. The International PCNSL Collaborative Group Response Criteria were used for response assessment. Endpoints include overall survival (OS) and adverse events (AE).

RESULTS

21 immunocompetent patients (12 females and 9 males) were retrospectively studied, among 2014 to 2019. Median age at diagnosis 61 years (range 41–76). Median KPS at diagnosis was 70 (range 40–100). Clinical and radiological data and treatment related toxicity were described

CONCLUSION

Present combination regimen is effective; however, AE incidence is high, and often induces schedule modification
P14.65 Anaplastic pleomorphic xanthoastrocytoma: literature review& case report
Authors: Agabekyan G , Kobyakov G , Lodygina K , Kobyakov N , Absalyamova O , Ryzhova M , Inozemcevа M , Poddubsky A
Published: September 2019

Pleomorphic xanthoastrocytoma (PXA) is a rare glial brain tumor. 9% to 30% cases have anaplastic features which determine poor prognosis. Anaplastic features may be found either in primary tumor or in recurrent PXA in any time frame. According to WHO 2016 Brain Tumor Classification, anaplastic pleomorphic xanthoastrocytoma (aPXA) was reclassified as grade III tumor (previously grade II). Characteristic features for aPXA are mitotic index of 5% or higher and worse 5-year survival rates in comparison with PXA: 57.1% and 90.4%, respectively. About 6% cases have TP53 gene mutation. About 60–78% tumors are BRAF-mutated, which is a potential target for therapy. Currently there are ongoing clinical trials to determine efficacy of BRAF and MEK inhibitors in pediatric patients with high-grade glioma with BRAF mutation. There is a number of publications showing positive outcome of targeted therapy both in children and adults. Treatment protocol for aPXA has not been defined. Case report Patient N. 14-y.o. female. MRI showed tumor of left occipital lobe. 02.03.2016 stereotactic biopsy was performed. Histological examination revealed diffuse astrocytic glioma WHO grade III-IV. Radiation therapy was performed, after which patient’s condition abruptly deteriorated with back pain, patient became almost unable to walk, however control MRI showed no signs of spinal dissemination. 01.12.2016 surgery to remove left occipital lobe tumor was performed. 07.12.2016 MRI showed contrast enhancing lesions throughout entire length of the spinal cord. Histological examination revealed aPXA gr. III, Ki-67 up to 8%. From December to June 2017 patient received 6 cycles of chemotherapy with temozolomide. Molecular testing discovered BRAF V600 mutation in exon 15. Chemotherapy regimen was thereby changed to vemurafenib 1920 mg/day from July 2017. After a month of treatment patient developed cutaneous toxicity and the dose was lowered to 960 mg/day. Patient’s condition improved: back pain syndrome regressed, lower extremity muscle strength increased, patient became able to walk. MRI 03.12.2017 revealed an increase of contrast enhancing lesion and T2-FLAIR hyperintense signal area in left occipital lobe, no progression in spinal cord. Methionine PET/CT was performed, the findings were evaluated as a combination of radiation necrosis and glioma growth. In view of MRI and PET/CT findings, amount of time passed after radiation therapy, we decided to include bevacizumab 400 mg every 2 weeks in the regimen. Since January 2018 patient is receiving vemurafenib 960 mg/day and bevacizumab 400 mg every 2 weeks. There is a marked positive dynamic in clinical findings and imaging data (MRI and PET/CT). We report the patient with aPXA and prolonged response to targeted therapy. The presence of the BRAF V600E mutation was possibility of treatment which led to successful results.
P14.66 TTFields dose distribution and tumor growth patterns confirm clinical activity of TTFields: MRI analysis of the randomized phase 3 EF-14 trial
Authors: Kebir S , Ballo M T , Jeyapalan S , Toms S A , Hottinger A , Pollom E , Glas M
Published: September 2019

BACKGROUND

The randomized phase 3 EF-14 trial showed that the addition of tumor treating fields (TTFields) to temozolomide (TMZ) treatment improved survival in newly diagnosed glioblastoma patients over TMZ alone. As TTFields delivery is designed to optimize dose at the tumor bed, we hypothesized that tumor recurrence is likely to occur in distant sites and we investigated the pattern of tumor growth at relapse in due consideration of TTFields dose intensity distribution.

METHODS

Patients on therapy for more than 2 months who exhibited radiological progression were included in the study (treatment: N=280/466, control: N=122/229) Contrast-enhanced T1-weighted scans at baseline and at relapse served for segmentation of enhancing tumor and necrosis. Lesions outside a proximal boundary zone of 20mm surrounding lesions identified at baseline were defined as distal. In addition, infratentorial progression was assessed. Moreover, we identified patients treated with TTFields with sufficient MRI data for dose calculations and radiographically confirmed tumor relapse (N=225/466). TTFields intensity distributions were computed in a finite element method applied in a realistic head model with virtual transducer arrays. TTFields dose density (mW/cm3) was defined as TTFields power loss density multiplied by average patient compliance during the first 6 months of therapy. At baseline, regions of residual tumor and regions of normal brain were identified to calculate TTFields dose within each of these regions and noted its relationship with subsequent recurrence.

RESULTS

Distal progressions were more common in the TTFields arm (18% vs. 8%). Infratentorial progression was seen in 4% of the treatment arm vs. 0 patients in the control. Lesions at progression were more distant from the original lesion in the TTFields arm (57.0 + 26.2 mm vs. 46.6 + 14.8 mm). Local tumors grew at a significantly lower pace in the TTFields arm as compared to the control arm (3.6 + 14.5 ml vs. 8.3 + 17.9 ml). The average dose density in areas of enhancing tumor that regressed to normal was higher than in the areas of normal brain that progressed to enhancing tumor (0.84 mW/cm3 vs. 0.75 mW/cm3). Regardless of the expansion margin used for analysis, TTFields dose density in areas of normal brain that remained normal at the time of progression was higher than in the areas that progressed to enhancing tumor.

CONCLUSIONS

TTFields appear to induce distant tumor growth pattern and are associated with a lower tumor growth rate. In addition, the importance of dose density at the tumor bed is stressed as higher dose densities were seen in areas of normal brain that remain normal at the time of progression providing further rationale for carefully planning array placement to maximize delivery to areas at higher risk of recurrence. Taken together, these findings confirm the clinical activity of TTFields.
P14.71 Tumor Treating Fields combined with radiotherapy and temozolomide for newly diagnosed glioblastoma: final safety and efficacy results from a pilot study
Authors: Grossman R , Bokstein F , Blumenthal D , Ben Harush C , Limon D , Ram Z
Published: September 2019

BACKGROUND

Tumor Treating Fields (TTFields) are a non-invasive, loco-regional, anti-mitotic treatment consisting of low intensity alternating electric fields. The combination of TTFields with maintenance temozolomide significantly improved survival versus temozolomide alone in the phase 3 EF-14 study in newly diagnosed glioblastoma (ndGBM). In preclinical studies, TTFields increased the number of glioma cells undergoing cellular death following radiotherapy (RT) by inhibiting DNA damage repair, suggesting a radio-sensitizing effect of TTFields. This pilot study is the first to evaluate the safety and feasibility of administering TTFields concomitant to RT and TMZ in ndGBM patients.

MATERIAL AND METHODS

Patients diagnosed with ndGBM were treated with TTFields/RT/TMZ followed by maintenance TMZ and TTFields for up to 24 months. TTFields (200kHz) were delivered for >18 hours/day while the transducer arrays were removed during delivery of RT. TMZ was administered at a dose of 75 mg/m2/daily for 6 weeks and RT at a total dose of 60 Gy. The primary endpoint was safety of the combined TTFields/RT/TMZ; secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity. Adverse events (AEs) were graded according to CTCAE V4.0.

RESULTS

10 ndGBM patients that recovered from maximal debulking surgery or biopsy were enrolled at a single center in Israel between April and December 2017. Five patients (50%) had undergone gross total resection while the rest had biopsy only. Eight of the patients were male, median age was 59, median KPS was 80 and median dose of RT was 60 Gy. Six patients (60%) reported at least one AE. The most common AE was TTFields-related skin toxicity, reported in four patients (40%), all of which were grade 1–2 in severity. Two patients reported serious AEs (seizures and general deterioration) that were considered unrelated to TTFields. Median PFS with RT/TMZ/TTFields was 10.5 months. Median OS has not yet been reached.

CONCLUSION

The proportion of patients with TTFields-related skin toxicity was similar to that reported in ndGBM patients in the randomized Phase III study (52%), where patients started TTFields at least 4 weeks after RT. No other TTFields-related toxicities were reported and there were no increase in RT- or TMZ-related toxicities as a result of combining TTFields with RT in addition to TMZ. Based on the safety and preliminary efficacy results of this pilot study, a phase II randomized study has been initiated to investigate the efficacy of concomitant RT/TMZ/TTFields in 60 ndGBM patients.
P14.72 Multicentric glioblastoma - A retrospective study of imaging characteristics, treatment approach, pattern of relapse and survival
Authors: Benouaich Amiel A , Khasminsky V , Gal O , Fichman S , Weiss T , Siegal T , Yust-Katz S
Published: September 2019

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.
P14.74 Remarkable response to Combined BRAF and MEK Inhibitors in two Adults with leptomeningeal carcinomatosis secondary to Pleomorphic Xantoastrocytoma grade II with BRAFv600E mutation
Authors: Eoli M , Pollo B , Silvani A , Paterra R , Erbetta A , Anghileri E , Gaviani P , Finocchiaro G
Published: September 2019

BACKGROUND

Several cancers with the BRAF V600E mutations have been successfully treated with targeted therapy. Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor, with an incidence of 0.07cases per 100,000. The BRAFV600 mutation is present in 38–60% of PXA. Typical treatment is gross total resection, followed by radiotherapy and cytotoxic chemotherapy at recurrence

MATERIAL AND METHODS

Two cases are described.

RESULTS

The first case is a 37 old man with a left temporal lobe lesion who underwent a craniotomy with total tumor resection. Histological diagnosis was PXA WHO grade 2with BRAF V600E mutation.Five months after, MR imaging of his brain and spine showed tumor progression with extensive leptomeningeal disease. The patient received adjuvant brain and spinal radiotherapy Two weeks after, due to rapid clinical worsening he had a new brain and spinal MRI showing hydrocephalus and progression of the pachymeningeal-based masses and received an emergency ventricular -peritoneal shunt. Given the genetic analysis, the extent of disease and rapidity of the progression, BRAF and MEK inhibitors, dabrafenib (150 mg, twice daily) and trametinib (2 mg, daily) were started. Remarkably, within 2 week of initiating dual-targeted therapy, the patient experienced a dramatic improvement in consciousness and overall strength; brainand spinal MRI revealed initial reduction of the leptomenigeal enhacement and no evidence of progression of the intraparenchymal disease. The therapy was well-tolerated. Currently, after sixteen months,the patient remains on treatment with a consistent functional status improvement and no radiological evidence of disease progression. The second case is a 51 old women who developed leptomeningeal carcinomatosis seven year after resection of a frontal left PXA WHO grade 2 with BRAFv600E mutation. The patient had received brain radiotherapy five years after diagnosis and Cyber Knife for tumor progression. Ten months later MR imaging of his brain and spine showed tumor progression with extensive leptomeningeal disease, she was treated with temozolomide for 8 after clinical and radiological worsening she had a second surgery with resection of recurrent frontale left lesion Histopathology PXA WHO grade 2 with BRAF V600E mutation. She developed hydrocephalus, received an emergency ventricular -peritoneal shunt. BRAF and MEK inhibitors, dabrafenib (150 mg, twice daily) and trametinib (2 mg, daily) were started three months ago with initial clinical benefit

CONCLUSION

All patients with PXA should be tested for the BRAFV600 mutation, since, in these cases, targeted therapy with BRAF and MEK inhibitors seems to be a useful option for salvage treatment.
P14.77 Reduced dose craniospinal irradiation (CSI) is feasible for standard risk adult medulloblastoma (MBL) patients similarly to pediatric population
Authors: Massimino M , Sunyach M , Gandola L , Pecori E , Spreafico F , Bonneville Levard A , Biassoni V , Schiavello E , Diletto B , Stefini R , Frappaz D
Published: September 2019

BACKGROUND

MBL is the most common malignant pediatric brain tumor but represents 1% of adult brain tumors. Recent molecular classification suggests that MBL is not the same disease in children and adults. For standard risk pediatric medulloblastomas current therapy includes CSI at reduced doses (23.4Gy) associated with chemotherapy. Most adult patients with similar risk factors still receive CSI at 36 Gy±chemotherapy (CT): in the adult series treated according to the HIT protocol (CSI 35.2 Gy + boost to 55.2 Gy to posterior fossa followed in most patients by maintenance CT with lomustine, vincristine and cisplatin) a 73% 5-year PFS was reported {Friedrich, Eur J Cancer 2013}, so far the best published data. Hence retrospective experience of 23.4 Gy together with CT for adult patients in some institutions is worthwhile reporting.

MATERIAL AND METHODS

We gathered M0 patients, aged over 18 years with medulloblastomas and no/minimal post-surgical residues/no biological negative factor, between 1996–2018 in Centre Léon Bérard of-Lyon and Fondazione IRCCS Istituto Nazionale dei Tumori-Milan.

RESULTS

Forty-four patients were included, median age 26 (18–48) years,20 females. Median follow-up 90 months(10–227). Thirty-six and 8 received 23.4Gy and 30Gy CSI, respectively, + posterior fossa/tumor bed boost and CT in all: pre-RT (carbo/VPx2 courses or 8 drugs-in-one day x 2 courses (13 patients)) and/or post-RT (carbo/VPx2 courses in 11 and 8 drugs-in-one day x 2 courses in 10; CDDP/VCR/CCNU x 8courses in other 22).

The 5/10 year PFS and OS were respectively 80.9±6.5%/76.8±7.4% and 88.4±5.5%/73.1±8.5%. Median progression time was 44 months.

Relapses (8) were local (4), local+CSF or spine or bone in one instance each and bone only in one.

Among variable considered, higher CSI dose than 23.4 Gy, pre-RT CT did not influence PFS, while females had a trend to better PFES and OS (P=0.07).

CONCLUSION

These combined series present results comparable to - or even better than- those obtained after high CSI doses highlighting the need for treatment redefinition in adults.
P14.91 Study glycolytic metabolism in 1H-MRS monovoxel in the most aggressive part of 62 glioblastomas before and after 18 months of treatment
Authors: Heintz A , Boussida S , Saida Z , Chombar J , Lefranc M , Desenclos C , Galmiche A , Chauffert B , Boone M , Constans J
Published: September 2019

BACKGROUND

To study the relationship between glycolytic metabolism, tumor proliferation, survival and treatment response in patients with glioblastoma (GBM).

MATERIAL AND METHODS

Patients: 62 patients with glioblastoma, all having a STUPP Protocol (radiotherapy and concomitant chemotherapy), were selected and separated into 2 groups: Biopsies (30) and resections (32). In total, 269 NMR spectra (PRESS at GE 1.5T and 3T; multi-TEs TE=35ms and TE=144ms) were acquired. Processing: MRS data were processed with jMRUI software and quantitated using HLSVD and QUEST algorithms. Statistical analysis of longitudinal MRS data (every 3 months)

RESULTS

1H-MRS glucose (Glc/tCr) and lactate (Lac/tCr) measurements are highly correlated before the beginning of treatment. This correlation is less obvious after 3, 6, 9 and 12 months of treatment. Proliferation is also strongly correlated with Lactate and Glucose before the beginning of treatment in both groups, whereas these correlations decrease in resected patients.The variability of ratios follow-up is higher in biopsied patients. Tumoral proliferation (tCho/tCr) and Glucose ratio (Glc/tCr) levels decreased along the follow-up. Although, the Lac/tCr ratio progressively decreased, its level remains high until 6 months. After 15 months of treatment, glucose increased although the lactate decreased.

CONCLUSION

The study of glycolytic metabolism in GBM could be used to evaluate the response to treatment. Being able to have a treatment response biomarker at 3 months, especially for patients who could not be resected could help to monitor and adapt treatment. The increase of Glucose at the end of the follow-up shows the interest of spectral and metabolic follow-up of glioblastoma after 18 months of treatment.
P14.96 Gliomatosis cerebri imaging pattern: a treatment-independent marker for worse overall survival in WHO grade II and III gliomas
Authors: Divé I , Steidl E , Wagner M , Burger M C , Franz K , Harter P N , Bähr O , Fokas E , Herrlinger U , Steinbach J P
Published: September 2019

BACKGROUND

The term gliomatosis cerebri (GC) refers to glial brain tumors with widespread tumor expansion affecting three or more cerebral lobes. Formerly considered a distinct tumor entity, recent studies found no difference in the mutational profile of glial tumors with GC growth pattern compared to non-GC gliomas. Thus, in the new WHO classification of brain tumors, GC is no longer included as a separate diagnosis. While the presence of gliomas with GC growth pattern is associated with worse overall survival (OS), the underlying factors remain to be identified. Here, we asked whether differing therapeutic strategies in first line treatment could account for the worse outcome of patients with GC growth pattern and grade II and III histology.

MATERIAL AND METHODS

From the patient data bank of the University Cancer Center (UCT) Frankfurt, 47 patients with histological diagnosis of WHO grade II or III glioma, and with record of GC imaging pattern were identified. GC tumor expansion was confirmed by review of MRI scans prior to treatment initiation. Patients with WHO grade II or III glioma without GC growth pattern served as control cohort (n=379). IDH mutational status was available for 75% of GC tumors (IDH R132H mutated 32%; non-mutated 43%) and 69% of non-GC tumors (IDH R132H mutated 57%; non-mutated 12%).

RESULTS

Within the GC patient cohort, patients with tumors without contrast enhancement, lower WHO grade and mutated IDH status showed better OS. Compared to the control cohort, patients with GC had significantly shorter OS. This was independent of histological diagnosis or IDH mutation status. Patients with GC more frequently underwent radiochemotherapy (17% vs. 9% in the non-GC cohort), and drastically more often received chemotherapy alone (51% vs. 5%). We then analyzed OS in GC and non-GC patients that had received the same first line treatments. For radiochemotherapy in GC versus non-GC patients, OS was 1.1 years vs. 12.7 years (p =0.0075, log-rank test). For upfront chemotherapy alone, OS was significantly shorter in the GC cohort than in the non-GC cohort (3,6 years vs. undefined, p =0.0016, log-rank test).

CONCLUSION

Differences in first-line treatment cannot account for the worse prognosis of patients with GC imaging pattern. Further studies are needed to pinpoint biological or clinical factors that might influence responsiveness to therapy and prognosis of GC tumors.
P14.105 High incidence of brain metastases in lung cancer patients at the time of primary diagnosis
Authors: Kobyakova E , Nechipay E , Sashin D , Kobiakov N , Kobyakov G L
Published: September 2019

BACKGROUND

Brain metastases (BM) affect 8%-10% of all cancer patients and 40% of patients with metastatic cancer. The majority of BM originate from lung cancer (40%-50%), breast cancer (15%-25%), and melanoma (5%-20%). Total incidence proportions percentage (IP %) of brain metastases was reported as 9.6% for all primary sites combined, and was highest for lung cancer (19.9%). The incidence of BM is believed to be increasing, likely resulting from longer patient survival due to more effective systemic therapies for the primary cancer and the increased use of neuroimaging in neurologically asymptomatic patients.

MATERIAL AND METHODS

Our aim was to determine incidence of brain metastases in lung cancer patients at the time of primary diagnosis on cohort of our regular clinical practice. Since September 2014 till December 2017 189 primarily diagnosed patients with suspected lung cancer were evaluated with brain MRI as obligatory part of diagnostic protocol at N.N. Blokhin Russian Cancer Research Center. MR imaging protocol included T1, T2-weighted images, FLAIR, DWI, VIBE (with contrast enhancement, slice thickness <1.2 mm). According to diagnostic guidelines for lung cancer in Russia, all patients underwent chest CT scan with contrast enhancement, bronchoscopy, abdominal ultrasonography, ultrasonography of cervical lymph nodes (+ CT to evaluate detected abnormalities), bone scintigraphy with X-ray control of detected abnormalities, surgical removal (in case of T1-T2 tumor) or tumor biopsy to determine morphology. Additionally, all patients underwent Whole Body MR DWI, some patients received FDG-PET/CT scan.

RESULTS

Brain metastases were detected in 89 (48%) of 189 patients, while only 9 patients (10.1% of patients with brain metastases) had neurological deficits. Lesion sizes were as follows: 0.1–0.5 cm in 46 (51.7%) patients, 0.5–1.0 cm in 21 (23.6%) patients, 1.0–2.0 cm in 7 (7.9%) patients, 2.0–3.0 cm in 8 (9.0%) patients and >3.0 in 7 (7.9% patients). The majority of patients (45 - 50.56%) had solitary metastases, 10 patients (11.24%) had two lesions and 34 (38.20 %) patients had three and more lesions. Metastatic disease most commonly affected frontal lobes - 45 (50.56%) patients, temporal lobes - 36 (40.45%) patients, parietal lobes - 22 (24.72%) patients, occipital lobes - 22 (24.72%), basal ganglia and brainstem - 18 (20.22%), - 3 (3.37%), cerebellum - 30 (33.71%) patients. Concerning morphology, in 80 of 89 brain metastases NSCLC was identified and in 9 patients SCLC was observed.

CONCLUSION

Very high incidence of brain metastases in lung cancer patients at the time of primary diagnosis in our study cohort may be explained by the use of precision brain MRI as an obligatory part of diagnostic protocol at the time of primary admission. We suggest including precision brain MRI in guidelines for primary diagnosis of lung cancer patients as an obligatory examination
P14.114 Tumor treating fields in glioblastoma clinical practice guidelines: a European and North American landscape analysis
Authors: Lawson McLean A , Kalff R , Walter J
Published: September 2019

BACKGROUND

Tumor treating fields (TTFields) are low-intensity alternating electric fields delivered at intermediate frequencies to disrupt cancer cell division and inhibit tumor growth, with significantly longer mean lifetime survival of 1.8 additional years in glioblastoma (GBM). International, national and local clinical practice guidelines have implications for clinical, personal and policy decision-making. Furthermore, they may impact on patients’ decisions to choose treatment at a given institution or even lead to commencement of legal proceedings for withholding therapies recommended by international guidelines. We performed an in-depth landscape analysis of clinical practice guidelines for GBM in Europe and North America to explore variation in treatment recommendations with a specific focus on TTFields.

MATERIAL AND METHODS

A systematic search was conducted of web sites of international guideline developers, relevant cancer agencies and the MEDLINE and Web of Science literature databases. The following information was extracted from each document meeting the inclusion criteria: whether TTFields is discussed and/or recommended in the guideline, the indications for and role of TTFields in the care protocol, the strength of the recommendation and any constraints placed on the situations where this therapy can or may be offered, including on cost grounds, where applicable. Dates of production and validity periods of the guidelines were also noted. In addition, standard operating procedures (SOPs) from several accredited comprehensive cancer centres in Germany, covering GBM care are compared, with a series of clinical vignettes presented.

RESULTS

The guidelines produced by the National Comprehensive Cancer Network (USA), National Institute for Health and Care Excellence (UK), German Society for Neurology, German Society for Haematology and Medical Oncology, European Association for Neuro-Oncology and European Society for Medical Oncology were critically compared. Wide variation in recommendations relating to the TTFields therapy was observed. Many guidelines had not been updated to reflect the results of the EF-14 study.

CONCLUSION

Discrepancy in the adoption of TTFields across clinical practice guidelines and SOPs has potential implications for care practices. This ultimately affects patient outcomes, safety and quality of care. Ideally, guidelines should be updated dynamically when new evidence indicates a need for a substantive change in the guideline based on a priori criteria. An ongoing revision process for guidelines, perhaps with shorter validity periods or a more flexible approach, may facilitate more expedient adoption of novel therapies in clinical practice guidelines and in practice. Meanwhile, therapies significantly improving OS and PFS should be recommended to patients and this should be documented.
P14.121 Use of corticosteroids in glioblastoma patients A single institution experience
Authors: Smrdel U , Skoblar Vidmar M
Published: September 2019

INTRODUCTION

Corticosteroids are group of drugs widely used in patients with glioblastoma. As they control peritoumoral oedema, virtually all patients are at some time receiving one. Though, they are effective drugs, their use comes with many side effects affecting the QoL, and might even have a detrimental effect on survival.

PATIENTS AND METHODS

We collected the data of patients treated for glioblastoma in Slovenia between 1997 and 2016. In our database of 1051patients, we calculated the survival and progression free survival. Then we checked the corticosteroid use for every individual patient at the time of referral, beginning of radiotherapy (RT), completion of RT, at 3 and 6 months. We stratified patients according to the resection extent, performance status, age groups, and treatment intent. We also looked for any adverse effect which could be connected to corticosteroid usage. Due to historical circumstances, we did not have a peroral dexamethasone in Slovenia until 2012, so patients regularly received methyl prednisolone instead, though they received parenteral dexamethasone. We are reporting all corticosteroid doses calculated and expressed in milligrams of dexamethasone.

RESULTS

At the time of referral, 90 % of patients received corticosteroids. Median dose was 4 mg of dexamethasone 2 times daily (0 to 8 mg 3 times daily). In around half of patients, dexamethasone could be lowered prior to radiotherapy. Factors preventing early tapering were: biopsy only, higher age and performance status. Tapering of dexamethasone than continued after completion of RT. Beside corticosteroid diabetes, proximal myopathy was the most frequent adverse effect, followed by osteoporosis. The group of patients, surviving more than 3 years, had significantly lower dose of corticosteroids at the end of RT than other patients, while there was no difference in dose at the time of referral and afterwards. Tapering of the dose was quicker with the younger patients and also when patients received methyl prednisolone. The patients receiving methyl prednisolone also had more problems with osteoporosis.

DISCUSSION

Our data confirms the benefits and dangers of corticosteroid usage. While all are aware of the corticosteroid diabetes and osteoporosis, the myopathy was most commonly expressed complaint in our patients and might be underreported, especially, when weakness might also be attributed to underlying disease. Not only, is the higher dose of dexamethasone associated with more common and more severe adverse affects, but one could question if there is more direct connection of corticosteroids and survival.

CONCLUSION

While the corticosteroids remain essential medications in glioblastoma patients, they should be used with care. Tapering of the corticosteroids should start as early as possible. Balance between the beneficial effects of corticosteroids and their detrimental effects should be reached.
P14.128 Lack of development of Pneumocystis Jirovecii Pneumonia in a cohort of 103 Italian glioblastoma patients not receiving prophylaxis during post-surgical chemoradiotherapy
Authors: Rifino N , Rigamonti A , Guida F , Bonato C , De Nobili G , Spena G , Salmaggi A
Published: September 2019

BACKGROUND

Patients diagnosed with high grade gliomas (HGG) usually receive surgery, radiation, temozolomide (TMZ) and corticosteroids. A major concern in patients who receive chemoradiotherapy (CRT) is the risk of developing secondary myelosuppression and a related infection during treatment. CRT may also lead to a long-lasting reduction of WBC, associated with early death from tumor progression. Among treatment-related infections, Pneumocystis Jirovecii Pneumonia (PJP) has been reported, since then, PJP prophylaxis has been required by the FDA. However, evidence for PJP during CRT is very limited limited and the rate of PJP still low.

MATERIAL AND METHODS

We did a retrospective, Institutional Review Board-approved cohort study in 103 patients (60 men and 43 women), who were consecutively diagnosed with GBM in “A. Manzoni” Hospital in Lecco during the period May 2007 to December 2013. All of these patients were treated with CRT according to the Stupp protocol without PJP prophylaxis. Haematological toxicities of CRT were assessed according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0; November 27, 2017). The objective of our study was to investigate the association between CRT and myelosuppression and we evaluated the types of infection contracted on CRT and in particular if the absence of a proper PJP prophylaxis led to an increased rate of PJP.

RESULTS

In our cohort, among 103 patients receiving CRT, 18% developed severe lymphopenia. Among all the subjects enrolled, a total of 9 patients (8.7%) had documented infectious complications during the CRT. Three patients developed community acquired pneumonia. Moreover, we documented three cases of fever without source, two urinary tract infections, one herpes zoster, one herpes simplex 1, one phlegmon and one purulent otitis. However, no one of these patients was diagnosed as PJP despite PJP prophylaxis was not given.

CONCLUSION

In conclusion, our data seem to support a lack of undisputable evidence for a favorable risk/benefit profile in the use of PJP prophylaxis for all newly diagnosed GBM patients undergoing the CRT, also considering the rate of adverse reactions (15.2%) and severe adverse reactions (around 3%, mainly leukopenia) in non-HIV adults receiving trimethoprim/sulphametoxazole for prolonged periods.
Sleep in the completely locked-in state (CLIS) in amyotrophic lateral sclerosis
Authors: Malekshahi Azim , Chaudhary Ujwal , Jaramillo-Gonzalez Andres , Lucas Luna Alberto , Rana Aygul , Tonin Alessandro , Birbaumer Niels , Gais Steffen
Published: September 2019

Persons in the completely locked-in state (CLIS) suffering from amyotrophic lateral sclerosis (ALS) are deprived of many zeitgebers of the circadian rhythm: While cognitively intact, they are completely paralyzed, eyes mostly closed, with artificial ventilation and artificial nutrition, and social communication extremely restricted or absent. Polysomnographic recordings in eight patients in CLIS, however, revealed the presence of regular episodes of deep sleep during night time in all patients. It was also possible to distinguish an alpha-like state and a wake-like state. Classification of rapid eye movement (REM) sleep is difficult because of absent eye movements and absent muscular activity. Four out of eight patients did not show any sleep spindles. Those who have spindles also show K-complexes and thus regular phases of sleep stage 2. Thus, despite some irregularities, we found a surprisingly healthy sleep pattern in these patients.
Age Diversity and Age-Based Faultlines in Teams: Understanding a Brezel Phenomenon Requires a Brezel Theory
Authors: Wegge Jürgen , Meyer Bertolt
Published: September 2019

Demographic changes in developed countries increase age diversity within organizations and age-based faultlines in work teams. With the current commentary, we briefly take stock of the literature and review the relationships among age diversity, age-based faultlines, and team outcomes. In particular, we argue that current meta-analyses take a much too narrow focus on main effects of objective diversity. We also argue that studies on age-based faultlines, hypothetical dividing lines splitting a team into relatively homogeneous subgroups, focus too narrowly on faultlines based on objective criteria without taking perceptions into account. The conclusions of such studies are of limited value because subjective perceptions of team members (i.e., salience of age and age differences) are ignored, and central contextual influences and moderating variables such as diversity mindsets and team climate are not taken into account. We thus advocate a more complex approach (a “Brezel theory”) for understanding the complex effects of age diversity and age-based faultlines on team functioning (“Brezel” phenomena). Our approach also incorporates the idea that some team members react differently to diversity than others. Two relevant models and associated findings on when and how age diversity and age-based faultlines affect team processes are illustrated. Using these approaches in future research and related training interventions in practice will promote potential benefits and reduce potential disadvantages of age diversity and age-based faultlines in work teams.
Preoperative Behavioral Health, Opioid, and Antidepressant Utilization and 2-year Costs After Spinal Fusion—Revelations From Cluster Analysis
Authors: Lerner Jason , Ruppenkamp Jill , Etter Katherine , Headd Jeffrey J. , Bhattacharyya Samir , Menzie Ann M. , Pracyk John B. , McGuire Kevin J.
Published: September 2019

Study Design.

Retrospective administrative claims database analysis.

Objective.

Identify distinct presurgery health care resource utilization (HCRU) patterns among posterior lumbar spinal fusion patients and quantify their association with postsurgery costs.

Summary of Background Data.

Presurgical HCRU may be predictive of postsurgical economic outcomes and help health care providers to identify patients who may benefit from innovation in care pathways and/or surgical approach.

Methods.

Privately insured patients who received one- to two-level posterior lumbar spinal fusion between 2007 and 2016 were identified from a claims database. Agglomerative hierarchical clustering (HC), an unsupervised machine learning technique, was used to cluster patients by presurgery HCRU across 90 resource categories. A generalized linear model was used to compare 2-year postoperative costs across clusters controlling for age, levels fused, spinal diagnosis, posterolateral/interbody approach, and Elixhauser Comorbidity Index.

Results.

Among 18,770 patients, 56.1% were female, mean age was 51.3, 79.4% had one-level fusion, and 89.6% had inpatient surgery. Three patient clusters were identified: Clust1 (n = 13,987 [74.5%]), Clust2 (n = 4270 [22.7%]), Clust3 (n = 513 [2.7%]). The largest between-cluster differences were found in mean days supplied for antidepressants (Clust1: 97.1 days, Clust2: 175.2 days, Clust3: 287.1 days), opioids (Clust1: 76.7 days, Clust2: 166.9 days, Clust3: 129.7 days), and anticonvulsants (Clust1: 35.1 days, Clust2: 67.8 days, Clust3: 98.7 days). For mean medical visits, the largest between-cluster differences were for behavioral health (Clust1: 0.14, Clust2: 0.88, Clust3: 16.3) and nonthoracolumbar office visits (Clust1: 7.8, Clust2: 13.4, Clust3: 13.8). Mean (95% confidence interval) adjusted 2-year all-cause postoperative costs were lower for Clust1 ($34,048 [$33,265–$34,84]) versus both Clust2 ($52,505 [$50,306–$54,800]) and Clust3 ($48,452 [$43,007–$54,790]), P < 0.0001.

Conclusion.

Distinct presurgery HCRU clusters were characterized by greater utilization of antidepressants, opioids, and behavioral health services and these clusters were associated with significantly higher 2-year postsurgical costs.

Level of Evidence: 3