bluuebunny/crossref_metadata_2025_split huggingface dataset:
P13.08 1H-MRS metabolomics as a predictor of overall survival in glioma patients
Authors: Solivera J , Fuentes Fayos A , Luque R M , Barrios L , Roda J M , Cerdán S , Gandía-González M L 
Published: September 2019

Abstract

BACKGROUND
We assess the efficacy of the metabolomic profile from glioma biopsies, in providing estimates of postsurgical Overall Survival in glioma patients.

MATERIAL AND METHODS
Tumor biopsies from 46 patients bearing gliomas, obtained neurosurgically in the period 1992–1998, were analyzed by high resolution 1H magnetic resonance spectroscopy (HR- 1H MRS), following retrospectively individual postsurgical Overall Survival up to 720 weeks.

RESULTS
The Overall Survival profile could be resolved in three groups; Short (shorter than 52 weeks, n=19), Intermediate (between 53 and 364 weeks, n=19) or Long (longer than 365 weeks, n=8), respectively. Classical histopathological analysis assigned WHO grades II-IV to every biopsy but notably, some patients with low grade glioma depicted unexpectedly Short Overall Survival, while some patients with high grade glioma, presented unpredictably Long Overall Survival. To explore reasons underlying this behavior, we analyzed HR- 1H MRS spectra from acid extracts of these biopsies, to identify the metabolite patterns underlying OS predictions. Poor prognosis was found in biopsies with higher contents of alanine, acetate, glutamate, total choline, phosphorylcholine and glycine, while more favorable prognosis was achieved in biopsies with larger contents of total creatine, glycerol-phosphorylcholine and myo-inositol. We implemented then a multivariate analysis approach to identify hierarchically the influence of these metabolomic biomarkers on OS predictions, using Classification Regression Trees (CRTs). Metabolomic CRTs grew up to 3 branches and split into 8 nodes, predicting correctly the outcome of 94.7% of the patients in the Short Overall Survival group, 78.9 % of the patients in the Intermediate Overall Survival group, and 75% of the patients in the Long Overall Survival group, respectively.

CONCLUSION
Present results suggest that metabolic profiling by HR-1H MRS provides more accurate Overall Survival estimates of glioma patients than classical histopathological grading, thus allowing to implement more accurate therapeutic decisions.
P13.11 Metabolomics and molecular profiling in glioma patients: an interactomic approach
Authors: Fuentes-Fayos A C , Gandía-González M L , Cano-Rojas A , Blanco C J , Negro-Moral E M , Toledano Á , Ramos M J , Cano-Sánchez A , Luque R M , Ortega-Salas R M , Roda J M , Cerdán S , García-Martín M L , Solivera J 
Published: September 2019

Abstract

BACKGROUND
A wider view of the interaction between different omic-domains is needed to identify potential biomarkers of low- and high-grade gliomas. Using an interactomic approach, we analyzed the correlation between radiological data, IDH mutation, gene expression profiling and metabolic signature in glioma samples.

MATERIAL AND METHODS
Tumor biopsies from 25 patients with clinical diagnosis of glioma were surgically collected during 2017–2019 at the senior author’s institution. Metabolomic data was obtained by high resolution 31P and 1H magnetic resonance spectroscopy (MRS, 19 metabolites quantified with LCModel). Gene expression profiling was performed using real-time qPCR of 19 genes related to energy metabolism. IDH1/2 common mutation (IDH1R132H/IDH2R172H) was verified by immunohistochemistry and amplicon sanger sequencing. All data was integrated using the R package mixOmics, and we built correlation network plot graphs and correlation maps to identify the most significant interactions, that were analyzed thereafter.

RESULTS
Mean age was 48±10 years and 72% were men. The most frequent clinical presentation was intracranial hypertension and focal deficit. Imaging revealed 88% of single lobar tumors, 96% of contrast enhancement, 52% located near eloquent areas, 48% with augmented perfusion (mean values of 300±130%) and 60% showed restricted diffusion. WHO 2016 diagnosis were glioblastoma IDH mutated (IDHmut, 16%), IDH wildtype (IDHw, 56%); anaplastic astrocytoma IDHmut (4%), IDHw (16%); diffuse astrocytoma IDHmut (4%), SEGA (4%). The genetic and metabolic profiles were normalized per sample using the total sum of all the studied variables per case. This step made the interactomic approach possible. We found no differences between the metabolic or genetic profiles of glioma grade III and IV samples. However, there was a statistical significance or near-threshold correlation between some metabolic patterns and IDH-mutation, where Alanine (4.7±1.3% IDHw vs 2.5±0.7 IDHmut, p=0.046), Glycine (2.7±0.5% vs. 1.6±0.4%, p=0.095), Glycerophosphorylcholine (3.9±0.4% vs. 6.4±0.9%, p=0.013) and Myo-inositol (4.9±1.0% vs 11.9±2.1%, p=0.004) were the most important biomarkers. Overexpression of Lactate Dehydrogenase subunit B (LDHB, 19±3% vs. 31±6%, p=0.039) and Aconitase 1 (ACO1, 0.5±0.1% vs 1.2±0.3%, p=0.08) had also a significant or near-threshold relationship with IDH-mutation. These correlations were shown as hot spots in the correlation graphs and maps.

CONCLUSION
These preliminary results indicate that metabolic patterns by high resolution 31P and 1H MRS could be a useful tool to improve our knowledge about glioma gene expression profiles and to identify potential biomarkers to tackle this pathology.
P13.12 Development and validation of a radiomic model for the preoperative prediction of transsphenoidal surgical response in patients with acromegaly
Authors: Fan Y , Feng M , Wang R 
Published: September 2019

Abstract

BACKGROUND
The preoperative prediction of transsphenoidal surgical (TSS) response is important for determining individual treatment strategies for acromegaly. Therefore, this study aimed to predict TSS response in a non-invasive way based on radiomic analysis.

MATERIAL AND METHODS
273 patients with acromegaly were enrolled and divided into primary (n=180) and validation cohorts (n=93) according to time point. Radiomic features were extracted from the MR images and determined using the ‘Elastic Net’ feature selection algorithm. A radiomic signature was built using a support vector machine. Subsequently, multivariable logistic regression analysis was used to select the most informative clinical features, and a radiomic model, incorporating the radiomic signature and selected clinical features, was constructed and used as the final predictive model. The performance of this radiomic model was validated using receiver operating characteristics analysis, and its calibration, discriminating ability, and clinical usefulness were assessed.

RESULTS
The radiomic signature, which was constructed with six radiomic features selected using the primary cohort, showed a favorable discriminatory ability in the validation cohort. The radiomic model incorporating the radiomic signature and three selected clinical features showed good discrimination abilities and calibration, with an area under the curve (AUC) of 0.93 for the primary cohort and 0.89 for the validation cohort. The radiomic model better estimated the treatment responses of patients with acromegaly than did the clinical features. Decision curve analysis showed the radiomic model was clinically useful.

CONCLUSION
This radiomic model could aid neurosurgeons in the preoperative prediction of TSS response in patients with acromegaly, and could contribute to determining individual treatment strategies.
P13.13 Clinical factors involved in brain metastasis edema: results of a retrospective cohort and evaluation of the best edema descriptor
Authors: Pin Y , Loo M , Waissi W , Paix A , Todeschi J , Antoni D , Proust F , Ahle G , Noël G 
Published: September 2019

Abstract

BACKGROUND
Brain metastasis (BM) are frequently surrounded by brain edema with a variable extension. This pathological increase in the water mass from the interstitial or intracellular space is the source of neurological symptoms but some studies also showed a prognosis impact of this edema. Nevertheless, the current edema evaluation methods are poorly reproducible and were not extensively evaluated. From a series of patients with brain metastasis, we analyzed factors influencing perilesional edema extension in function of three edema descriptors which were qualitatively evaluated: the absolute cumulative intracranial edema volume (CIEV, in mL), the edema on tumor volume ratio (ER), and the Edema Theoretical Thickness (ETT, in mm), new factor designed to be more independent from geometrical considerations.

MATERIAL AND METHODS
Clinical, biological and imaging factors were retrospectively recorded from patients referred for upfront stereotactic radiotherapy of one to three BMs. CIEV, ER and ETT were calculated for each patient. Non-colinear factors were selected using the Farrar-Glauber test. Impact of these factors on edema was tested with an univariate then a multivariate linear regression for each edema descriptor. Each resulting regression model was qualitatively evaluated using the F-test, R square value and residuals calculation.

RESULTS
Between January 2012 to December 2017, 182 patients were included. Upon 20 potentially prognostic factors recorded, 10 were kept, including clinical, biological and imaging factors. In the multivariate analysis, the CIEV was influenced by the cumulative intracranial tumor volume (CITV) (coefficient of 1.95, p<.001). The CIEV F-statistic p-value and R square were <10–15 and 0.30, respectively. The ETT was significantly influenced by the CITV (0.31, p<.001) and the extracerebral disease control (-1.58, p=.049). The F-test p-value and R square were <10-10 and 0.25, respectively. No significant linear regression was found for the ER. Residuals were more clinically relevant for the ETT compared to the CIEV.

CONCLUSION
Being significantly influenced by the cumulative brain tumor volume and the extracerebral disease control, the ETT might be a factor to include in future BM works because its strong relationships with confounding factors and its ability to provide robust intra and inter subjects comparisons.
P14.07 Complete response under treatment with proton therapy followed by chemotherapy together with Tumor Treating Fields in a biopsied IDH wildtype glioblastoma patient
Authors: Stein M , Dohmen H , Woelk B , Uhl E , Kolodziej M , Jensen A 
Published: September 2019

Abstract

BACKGROUND
Proton therapy is able to apply high radiation doses to the tumor while sparing healthy tissues by reducing integral dose. Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) and intermediate frequency (100–300 kHz) alternating electric fields that demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma (ndGBM). Especially in ndGBM IDH wildtype with unmethylated MGMT promotor therapeutic options are restricted. Here, we report on a patient with biopsied ndGBM IDH wildtype with complete radiological response.

MATERIAL AND METHODS
Brain MRI demonstrated an occlusive hydrocephalus and a ring enhancing lesion in the right posterior thalamus in a 42 year old male. Endoscopic third ventriculostomy and stereotactic biopsy of the lesion were performed. Histopathological examination resulted in the diagnosis of a glioblastoma (WHO grade IV), IDH 1 wildtype (R132), IDH 2 wildtype (R172), HIST1H3B/C wildtype, TERT wildtype (C228 and C250), BRAF wildtype, and unmethylated MGMT promotor. In view of the tumor site, resection was not feasible. Consequently, the patient received definitive chemoradiation with TMZ to a total dose of 60Gy incl. proton boost of 5x2 GyRBE. TTFields therapy in combination with TMZ was initiated 4 weeks after completion of chemoradiation, TMZ maintenance was completed per protocol after 6 cycles. TTFields therapy was continued for more than 13 month and to-date the patient is still on therapy.

RESULTS
Current follow up time is 20 months after initial diagnosis with the patient showing a radiological complete response. The first MRI following chemoradiation with TMZ and protons (showed pseudoprogression. After 3 months, the MRI again showed slightly increasing contrast enhancement. However, no clinical symptoms of tumor progression were present. The TTFields usage (compliance) rate, i.e. the rate per time the patient is applying the therapy, of the patient was 86 %. This was well above the independent prognostic threshold of 75 % and supports the feasibility of this approach. A further MRI after 8 weeks showed a stable disease. In a MRI 4 months later, partial response with decreased contrast enhancement plus perfusion restriction in the tumor area was observed. Another MRI after 3 months showed a complete response without perfusion signal in the tumor area. In the clinical examination the patient had no neurological deficits and to-date the patient is still stable

CONCLUSION
Complete response was observed following combination treatment of chemoradiation with TMZ including proton boost, TMZ maintenance and TTFields in a patient with pathologically confirmed GBM IDH wildtype. To our knowledge, this is the first report on a ndGBM patient receiving proton therapy followed by TTFields therapy.
P14.12 The cost-effectiveness of tumor-treating fields in patients with newly diagnosed glioblastoma
Authors: Armoiry X , Auguste P , Dussart C , Guyotat J , Connock M 
Published: September 2019

Abstract

BACKGROUND
The addition of novel therapy “Tumor-Treating fields” (TTF) to standard radio-chemotherapy with Temozolomide (TMZ) has recently shown superiority over conventional TMZ regimen in patients with glioblastoma. Despite the clinical benefit of TTF, there is a strong concern regarding the cost of this new treatment. A first cost-effectiveness analysis, which was published in 2016, was based on effectiveness outcomes from an interim analysis of the pivotal trial and used a “standard” Markov model. Here, we aimed to update the cost-effectiveness evaluation using a partitioned survival model design and using the latest effectiveness data.

MATERIAL AND METHODS
A partitioned survival model was developed with three mutually exclusive health states: stable disease, progressive disease, and dead. Parametric models were fitted to the Kaplan-Meier data for overall and progression-free survival. These generated clinically plausible extrapolations beyond the observed data. The perspective of the French national health insurance was adopted and the time horizon was 20 years. Base case results were expressed as cost/life-years (LY) gained (LYG). Secondary analyses were undertaken, with the results presented as cost/per quality adjusted life years (QALY) gained. Last, we undertook deterministic and probabilistic sensitivity analyses.

RESULTS
After applying 4% annual discounting of benefits and costs, the base case model generated incremental benefit of 0.507 LY at a incremental cost of €258,695 yielding an incremental cost effectiveness ratio (ICER) of €510,273 / LYG. Secondary analyses yielded an ICER of €667,173/QALY. Sensitivity analyses and bootstrapping methods showed the model was relatively robust. The model was sensitive to TTF device costs and the parametric model fitted to the Kaplan-Meier data for overall survival. The cost-effectiveness acceptability curve showed TTF has 0% of being cost-effective under conventional thresholds.

CONCLUSION
Using a partitioned survival model, uprated costs and more mature survival outcomes, TTF when compared to standard radio-chemotherapy with TMZ is not likely to be cost-effective. This has major implications in terms of access of newly eligible patients
P14.14 Scalp invasion of diffuse large b-cell lymphoma without systemic involvement
Authors: Hasturk A E , Eyupoglu E E , Gel G , Gokce C 
Published: September 2019

Abstract
Diffuse large B-cell lymphoma of the scalp with extra and intracranial extension without systemic invasion in a non-immune compromised patient is extremely rare. It should be considered in the differential diagnosis of scalp masses and meningeal lesions. Early diagnosis and surgical treatment is associated with a good outcome. 74 years old male patient with no known history of malignancy came to our clinic for left frontal swelling. He had no systemic cancer involvement. Contrast-enhanced cranial MRI showed a mass lesion invading left frontal skin, subcutaneous tissue, temporal muscle, bone and the underlying dural layer (Figure 1). Surgical excision was decided and after planning with the plastic surgery consultation, the patient was taken into surgery. Skin was lifted with a left frontal flap and the invasion was observed. Skin flap was placed down and the tumoral tissue was totally excised with a margin of normal bone tissue. The pathology assessment of the frozen specimen was found concordant with lymphoma. No injury or invasion of the dura was seen macroscopically. After dural closure, metacrilate cranioplasty was performed in order to replace the removed bone flap. Afterwards patient was handed over to the plastic surgeon. To ensure tumor resection with a safe margin, a transposition scalp flap was designed in the parieto-occipital region. The flap was raised in the supraperiosteal plane with preservation of the pericranium and it was transferred to the defect site. In addition, the flap donor area was reconstructed with a split-thickness skin graft taken from the right thigh region. Then, a wound dressing was applied to the surgical area and opened on postoperative 4th day. No complications such as necrosis, hematoma, infection or wound dehiscence occurred postoperatively. Both the graft and the flap completely healed (Figure 2). The patient showed no new neurological deficits or wound problems postoperatively and did not experience any problems both in plastic surgical and neurosurgical follow-up period (Figure 3). The final pathology result reported as diffuse large B cell lymphoma with invasion of the skin, subcutaneous tissue, temporal muscle and bone. Afterwards, medical treatment was planned with consultation to the hematology and radiotherapy clinics. Primary Non-Hodgkin’s lymphoma (NHL) extending extra cranially and intra cranially without any systemic or skeletal findings is extremely rare. These lesions usually get misdiagnosed as they mimic other conditions such as meningiomas. Both radiological and histopathological diagnoses are very important. Radical surgical resection and reconstruction must be contemplated in treatment and also chemotherapy and radiotherapy alternatives should be considered. Malignant NHL should be taken into account for differential diagnosis in the mass lesions of the scalp.
P14.15 Benefit of Bevacizumab for recurrent glioblastoma. Results of 81 patients from a single institution
Authors: Absalyamova O , Kobiakov G , Agabekyan G , Poddubsky A , Belyashova A , Lodygina K , Absalyamov A , Kobiakov N 
Published: September 2019

Abstract

BACKGROUND
No standard of care has been established for patients with progressive glioblastoma (rGBM). Previous studies suggested that bevacizumab (BEV) is safe and produces responses that result in a decreased use of glucocorticoids and increased progression-free survival (PFS) with an unclear effect on overall survival (OS). Crossover to BEV in the control arm is the possible reason why the advantage of BEV has not been proven in Phase III trials. We retrospectively analyzed own results of BEV treatment in rGBM.

MATERIAL AND METHODS
81 patients progressed after radiotherapy plus concomitant and maintenance temozolomide (TMZ) and undergo BEV as monotherapy (BevMo, 11 patients) or in combinations (Irinotecan (BevI) - 53, lomustine (BevL)- 11, TMZ (BevT) - 6. Median age 54 years. Among them 33 patients were re-irradiated: 11 - radiosurgery (RS), 20 fractionated irradiation (RT), 2 - RS+RT. 33 patients continued BEV after progression with changing or adding cytostatic. PFS was calculated from the date of verification, PFS1 - from the date of 1-st progression, PFS2 - from the date of 2-nd progression.

RESULTS
Median PFS was 9.0 ([CI] 7.0–10.9) months. Median PFS1 was 10.5 ([CI] 8.1–12.9) months. In the BevMo, BevI, BevL, BevT group PFS1 was 15.7, 10.1, 10.5, 13.2 months, respectively, p=0.7. Objective response (OR) was reached in 34%, stable disease (SD) in 28%, progression (PD) in 37% patients. 16 patients stopped BEV without progression (4-patient`s decision, 7- doctor`s decision, 2 - adverse event, 3 - concomitant disease). Median time of BEV treatment was 11.6 months. Median BEV-free interval till progression was 3.7 months. 33 patients continued or restarted BEV after progression. Median PFS2 was 8.0 ([CI] 4.9–11.1) months. The median OS from the date of 1-st progression was 23.5 months ([CI] 18.7–27.4). In groups with RT, RS, RS+RT and no re-irradiarion OS was 24.6 ([CI] 17.6–31.5), 35.4 ([CI] 35.0–35.8), 17.8, 20.6 ([CI] 15.2–26.0), respectively, p=0.2.

CONCLUSION
OS in our group is outrageously high. Maintaining BEV after progression was effective. In our group BEV discontinuation led to rapid progression. The resumption of Bev with progression was effective, which indicates the advisability of its continuous application.