Current
Neuro-Oncology


Volume 22 Number 10
October 2020


Home > Publications > Current Neuro-Oncology > Volume 22, Year 2020 > Number 10, October



Contents


Central nervous system tumors


Gliomas


High-grade gliomas


Low-grade gliomas


Diffuse astrocytic and oligodendroglial tumors


Glioblastoma


Diffuse Midline Glioma


Anaplastic Oligodendroglioma


Other gliomas


Chordoid glioma of the third ventricle


Embryonal tumors


Medulloblastoma


Tumors of the sellar region


Craniopharingioma



Central nervous system tumors


Dudley HJ, Ren ZJ, Bortz DM.
Brain tumor classification in MRI image using convolutional neural network.
Math Biosci Eng. 2020 Sep 15. 2020;17(5):6217-6239. doi: 10.3934/mbe.2020329. Artificial intelligence study. _
In our paper, we introduce the convolutional neural network (CNN) approach along with Data Augmentation and Image Processing to categorize brain MRI scan images into cancerous and non-cancerous.




Fangusaro J, Mitchell DA, Kocak M, Robinson GW, Baxter PA, Hwang EI, Huang J, Onar-Thomas A, Dunkel IJ, Fouladi M, Warren KE.
Phase 1 study of pomalidomide in children with recurrent, refractory, and progressive central nervous system tumors: A Pediatric Brain Tumor Consortium trial.
Pediatr Blood Cancer. 2020 Oct 7. 2020;e28756. doi: 10.1002/pbc.28756. Phase 1 trial. _
The maximum tolerated dose (MTD) of pomalidomide is 2.6 mg/m2. It was well tolerated, and immune correlates showed a serum immune response. These data led to an industry sponsored phase 2 trial of pomalidomide monotherapy in children with recurrent brain tumors (NCT03257631).




Ginalis EE, Danish SF.
Magnetic resonance-guided laser interstitial thermal therapy for brain tumors in geriatric patients.
Neurosurg Focus. 2020 Oct;49(4):E12. doi: 10.3171/2020.7.FOCUS20462. Retrospective analysis. _
Laser interstitial thermal therapy (LITT) can be considered a minimally invasive and safe neurosurgical procedure for the treatment of intracranial tumors in geriatric patients. Careful preoperative preparation and postoperative care is essential as LITT is not without risk. Appropriate patient selection for cranial surgery is essential, because neurosurgeons are treating an increasing number of elderly patients, but advanced age alone should not exclude patients from LITT without considering frailty and comorbidities.




Journy NMY, Zrafi WS, Bolle S, Fresneau B, Alapetite C, Allodji RS, Berchery D, Haddy N, Kobayashi I, Labbé M, Pacquement H, Pluchart C, Schwartz B, Souchard V, Thomas-Teinturier C, Veres C, Vu-Bezin G, Diallo I, de Vathaire F.
Risk Factors of Subsequent Central Nervous System Tumors after Childhood and Adolescent Cancers: Findings from the French Childhood Cancer Survivor Study.
Cancer Epidemiol Biomarkers Prev. 2020 Oct 8. doi: 10.1158/1055-9965.EPI-20-0735. Epidemiology study. _
Childhood or adolescent cancer survivors are at increased risks of subsequent primary neoplasms (SPN) of the central nervous system (CNS) after cranial irradiation. In a large multicentric cohort, we investigated clinical and therapeutic factors associated with the long-term risk of CNS SPN, and quantified the dose–response relationships.




Ostrom QT, Patil N, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2013-2017.
Neuro Oncol. 2020 Oct 30. 2020;22(12 Suppl 2):iv1-iv96. doi: 10.1093/neuonc/noaa200. Epidemiology study. _
All rates (incidence and mortality) are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non malignant tumor was meningioma (38.3% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.14. An estimated 83,830 new cases of malignant and non malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 36.0% and for a non-malignant brain and other CNS tumor was 91.7%.




Stauffer PR, Rodrigues DB, Goldstein R, Nguyen T, Yu Y, Wan S, Woodward R, Gibbs M, Vasilchenko IL, Osintsev AM, Bar-Ad V, Leeper DB, Shi W, Judy KD, Hurwitz MD.
Feasibility of removable balloon implant for simultaneous magnetic nanoparticle heating and HDR brachytherapy of brain tumor resection cavities.
Int J Hyperthermia. 2020 Oct 13. 2020;37(1):1189-1201. doi: 10.1080/02656736.2020.1829103. Preclinical study. _
These preclinical results demonstrate the feasibility of using a temporary thermobrachytherapy (TBT) balloon to deliver heat simultaneously with High Dose Rate (HDR) brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme.



Gliomas


Forster MT, Behrens M, Lortz I, Conradi N, Senft C, Voss M, Rauch M, Seifert V.
Benefits of glioma resection in the corpus callosum.
Sci Rep. 2020 Oct 6. 2020;10(1):16630. doi: 10.1038/s41598-020-73928-x. Prospective study. _
After surgery, the proportion of impaired patients increased in all neurocognitive domains. Most interestingly, after 6 months, significantly fewer patients showed impairments in attention, executive functioning, memory and depression, which are domains considered crucial for everyday functionality. Thus, the results of our study strongly support our hypothesis that in patients with gliomas infiltrating the corpus callosum the benefit of tumor resection might outweigh morbidity.




Gao M, Huang S, Pan X, Liao X, Yang R, Liu J.
Machine Learning-Based Radiomics Predicting Tumor Grades and Expression of Multiple Pathologic Biomarkers in Gliomas.
Front Oncol. 2020 Sep 11. 2020;10:1676. doi: 10.3389/fonc.2020.01676. Radiomics study. _
The machine-learning based radiomics approach can provide a noninvasive method for the prediction of glioma grades and expression levels of multiple pathologic biomarkers, preoperatively, with favorable predictive accuracy and stability.




Kondo N, Hikida M, Nakada M, Sakurai Y, Hirata E, Takeno S, Suzuki M.
Glioma Stem-Like Cells Can Be Targeted in Boron Neutron Capture Therapy with Boronophenylalanine.
Cancers (Basel). 2020 Oct 19. 2020;12(10):3040. doi: 10.3390/cancers12103040. In vitro and in vivo study. _
Boron Neutron Capture Therapy (BNCT) is a unique radiation therapy that uses boron compounds and thermal neutrons. This study is aimed to investigate whether glioma stem cells, which is resistant to chemo-radiation therapy, take up a boron compound, p-oronophenylalanine (BPA) or not. Both in vitro and in vivo studies, more glioma stem like cells took up BPA compared with the di fferentiated glioma cells and indicated that BNCT can target to kill GSCs and be an eff ective therapy for malignant glioma.




Ma L, Li G, Wei M.
Neutrophil-to-Lymphocyte Ratio and Its Changes are Related to Grade II-IV Glioma Recurrence.
Cancer Manag Res. 2020 Sep 30. 2020;12:9429-9434. doi: 10.2147/CMAR.S267523. Retrospective analysis. _
The progression-free survival (PFS) of patients with high basic (before the first surgery) neutrophil-to-lymphocyte ratio (NLR) (≥4) (median 9 months) was shorter than that of patients with low basic NLR (<4) (median 23 months). The PFS is also varied with NLR changes before two surgeries. The PFS of patients with two low NLR (<4) at both initial surgical resection and section for tumor recurrence had the longest PSF. The patients with two high NLR (≥4) at both initial surgical resection and section for tumor recurrence had the shortest PSF. The patients with one high NLR (≥4) at initial surgical resection or section for tumor recurrence had an average PSF. Multivariate analysis showed that the change of NLR was of prognostic significance independent of glioma grade.




Makarevic A, Rapp C, Dettling S, Reuss D, Jungk C, Abdollahi A, von Deimling A, Unterberg A, Herold-Mende C, Warta R.
Increased Radiation-Associated T-Cell Infiltration in Recurrent IDH-Mutant Glioma.
Int J Mol Sci. 2020 Oct 21. 2020;21(20):7801. doi: 10.3390/ijms21207801. In vitro study. _
Here, we analyzed T-cell infiltration and, therefore, a major prerequisite for successful immunotherapy in a series of primary and recurrent isocitrate dehydrogenase (IDH)-mutant glioma and their changes following treatment with radio- and/or chemotherapy. Newly diagnosed diffuse IDH-mutant gliomas displayed a median T-cell infiltration of 0.99 T cells/mm2, which was about two-fold increased for CD3+, helper, and cytotoxic T cells in recurrent glioma. Furthermore, T-cell infiltration of recurrent tumors was associated with the type of adjuvant treatment of the primary tumor. Interestingly, only glioma patients solely receiving radiotherapy presented consistently with increased T-cell infiltration in their recurrent tumors. In conclusion, differences in the T-cell infiltration of primary and recurrent gliomas were demonstrated, and evidence was provided for a beneficial long-term effect on T-cell infiltration upon treatment with radiotherapy.




Regnery S, Behl NGR, Platt T, Weinfurtner N, Windisch P, Deike-Hofmann K, Sahm F, Bendszus M, Debus J, Ladd ME, Schlemmer HP, Rieken S, Adeberg S, Paech D.
Ultra-high-field sodium MRI as biomarker for tumor extent, grade and IDH mutation status in glioma patients.
Neuroimage Clin. 2020 Sep 12. 2020;28:102427. doi: 10.1016/j.nicl.2020.102427. Prospective study. _
23Na MRI correlates with the IDH mutation status and could therefore enhance image guidance towards biopsy sites as wells as image-guided surgery and radiotherapy. Furthermore, the successive decrease of 23Na concentration from central necrosis to normal-appearing white matter suggests a correlation with tumor infiltration.




Sakai Y, Yang C, Kihira S, Tsankova N, Khan F, Hormigo A, Lai A, Cloughesy T, Nael K.
MRI Radiomic Features to Predict IDH1 Mutation Status in Gliomas: A Machine Learning Approach using Gradient Tree Boosting.
Int J Mol Sci. 2020 Oct 27. 2020;21(21):E8004. doi: 10.3390/ijms21218004. PMID: 33121211. Radiomics study. _
In patients with gliomas, isocitrate dehydrogenase 1 (IDH1) mutation status has been studied as a prognostic indicator. Recent advances in machine learning (ML) have demonstrated promise in utilizing radiomic features to study disease processes in the brain.We investigate whether ML analysis of multiparametric radiomic features from preoperative Magnetic Resonance Imaging (MRI) can predict IDH1 mutation status in patients with glioma. … The results show that a XGBoost classifier using multiparametric radiomic features derived from preoperative MRI can predict IDH1 mutation status with > 90% accuracy.



High-grade gliomas



Cloughesy TF, Petrecca K, Walbert T, Butowski N, Salacz M, Perry J, Damek D, Bota D, Bettegowda C, Zhu JJ, Iwamoto F, Placantonakis D, Kim L, Elder B, Kaptain G, Cachia D, Moshel Y, Brem S, Piccioni D, Landolfi J, Chen CC, Gruber H, Rao AR, Hogan D, Accomando W, Ostertag D, Montellano TT, Kheoh T, Kabbinavar F, Vogelbaum MA.
Effect of Vocimagene Amiretrorepvec in Combination With Flucytosine vs Standard of Care on Survival Following Tumor Resection in Patients With Recurrent High-Grade Glioma: A Randomized Clinical Trial.
JAMA Oncol. 2020 Oct 29:e203161. doi: 10.1001/jamaoncol.2020.3161. Randomized trial. _
Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of vocimagene amiretrorepvec (Toca 511) and flucytosine (Toca FC), compared with standard of care, did not improve overall survival or other efficacy end points.



*

Hu C, Lin Q, Liu C, Liu J, Chen X, Li X, Zhao G, Zhang L.
Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China.
Cancer Chemother Pharmacol. 2020 Oct 21. 2020;86(6):793-801. doi: 10.1007/s00280-020-04175-0. Randomized trial. _
It can be concluded that 20-mg and 100-mg capsules of TOZ309 are bioequivalent to Temodal® capsules of the same strength under fasting conditions.



Low-grade gliomas



Li G, Wu F, Zeng F, Zhai Y, Feng Y, Chang Y, Wang D, Jiang T, Zhang W.
A novel DNA repair-related nomogram predicts survival in low-grade gliomas.
CNS Neurosci Ther. 2020 Oct 16. doi: 10.1111/cns.13464. Nomogram development. _
An individualized prediction model was created to predict 1-, 2-, 3-, 5-, and 10-year survival and recurrent rate of patients with low-grade glioma, which may serve as a potential tool to guide postoperative individualized care.




Selt F, van Tilburg CM, Bison B, Sievers P, Harting I, Ecker J, Pajtler KW, Sahm F, Bahr A, Simon M, Jones DTW, Well L, Mautner VF, Capper D, Hernáiz Driever P, Gnekow A, Pfister SM, Witt O, Milde T.
Response to trametinib treatment in progressive pediatric low-grade glioma patients.
J Neurooncol. 2020 Oct 7. 2020;149(3):499-510. doi: 10.1007/s11060-020-03640-3. Retrospective analysis. _
Trametinib was an active and feasible treatment for progressive pediatric low-grade glioma (pLGG) leading to disease control in all patients. However, treatment related toxicity interfered with treatment in individual patients, and disease control after Trametinib withdrawal was not sustained in a fraction of patients. Our data support in-class efficacy and necessity for upfront randomized testing of trametinib against current standard chemotherapy regimens.




Wang Y, Wang Z, Zhao B, Chen W, Wang Y, Ma W.
Development of a nomogram for prognostic prediction of lower-grade glioma based on alternative splicing signatures.
Cancer Med. 2020 Oct 13. doi: 10.1002/cam4.3530. Nomogram development. _
The alternative splicing events and clinical factors that can predict the prognosis of lower-grade glioma patients were screened, and a prognostic prediction model was established. The results of this study can play an important role in clinical work to better evaluate the prognosis of patients and impact treatment options.



Diffuse astrocytic and oligodendroglial tumors


Butenschoen VM, Hubertus V, Janssen IK, Onken J, Wipplinger C, Mende KC, Eicker SO, Kehl V, Thomé C, Vajkoczy P, Schaller K, Gempt J, Meyer B, Wostrack M.
Surgical treatment and neurological outcome of infiltrating intramedullary astrocytoma WHO II-IV: a multicenter retrospective case series.
J Neurooncol. 2020 Oct 22. doi: 10.1007/s11060-020-03647-w. Retrospective analysis. _
Infiltrating intramedullary astrocytomas WHO IIIV present rare entities with dismal prognosis. Due to the high incidence of surgery-related neurological impairment, the aim of the surgical approach should be limited to obtaining the histological tissue via a biopsy or, tumor debulking in cases with rapidly progressive severe preoperative deficits.



Glioblastoma



Awada G, Ben Salama L, De Cremer J, Schwarze JK, Fischbuch L, Seynaeve L, Du Four S, Vanbinst AM, Michotte A, Everaert H, Rogiers A, Theuns P, Duerinck J, Neyns B.
Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx).
J Immunother Cancer. 2020 Oct 16. 2020;8(2):e001146. doi: 10.1136/jitc-2020-001146. Phase 2 trial. _
The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with recurrent glioblastoma.




Awada G, Serruys D, Schwarze JK, Van De Voorde L, Duerinck J, Neyns B.
Durable Complete Response of a Recurrent Mesencephalic Glioblastoma Treated with Trametinib and Low-Dose Dabrafenib in a Patient with Neurofibromatosis Type 1.
Case Rep Oncol. 2020 Sep 1. 2020;13(2):1031-1036. doi: 10.1159/000509773. Case report. _
We report the case of a young NF1 patient with a recurrent, heavily pretreated mesencephalic glioblastoma who was treated with the MEK-inhibitor trametinib (2 mg once daily). A partial response was documented, but unfortunately, he developed dose-limiting cutaneous toxicity (rash, paronychia). Based on interim results of a phase 2 trial in advanced BRAFV600 wild-type melanoma indicating that a low dose of the BRAF-inhibitor dabrafenib is able to counter trametinib-related cutaneous toxicity, dabrafenib 50 mg twice daily was added. The cutaneous adverse events gradually recovered after addition of dabrafenib to trametinib. The patient eventually achieved a durable complete response, has excellent tolerance of his treatment and remains fully active.




Certo F, Altieri R, Maione M, Schonauer C, Sortino G, Fiumanò G, Tirrò E, Massimino M, Broggi G, Vigneri P, Magro G, Visocchi M, Barbagallo GMV.
FLAIRectomy in Supramarginal Resection of Glioblastoma Correlates With Clinical Outcome and Survival Analysis: A Prospective, Single Institution, Case Series.
Oper Neurosurg (Hagerstown). 2020 Oct 9. 2020;opaa293. doi: 10.1093/ons/opaa293. Prospective case series. _
Extent of tumor resection (EOTR) based on fluid-attenuated inversion recovery (FLAIR) and 5-aminolevulinic acid (5-ALA) fluorescence is feasible. Safety of resection relies on the use of neuromonitoring and intraoperative multimodal imaging tools. FLAIR-based EOTR appears to be a stronger survival predictor compared to gadolinium enhancing, T1-based resection.




Chen C, Zheng A, Ou X, Wang J, Ma X.
Comparison of Radiomics-Based Machine-Learning Classifiers in Diagnosis of Glioblastoma From Primary Central Nervous System Lymphoma.
Front Oncol. 2020 Sep 15. 2020;10:1151. doi: 10.3389/fonc.2020.01151. Radiomics study. _
Radiomics-based machine-learning algorithms potentially have promising performances in differentiating GBM from PCNSL.




Chen X, Zeng M, Tong Y, Zhang T, Fu Y, Li H, Zhang Z, Cheng Z, Xu X, Yang R, Liu Z, Wei X, Jiang X.
Automatic Prediction of MGMT Status in Glioblastoma via Deep Learning-Based MR Image Analysis.
Biomed Res Int. 2020 Sep 23. 2020;2020:9258649. doi: 10.1155/2020/9258649. Artificial intelligence study. _
Methylation of the O6-methylguanine methyltransferase (MGMT) gene promoter is correlated with the effectiveness of the current standard of care in glioblastoma patients. In this study, a deep learning pipeline is designed for automatic prediction of MGMT status in 87 glioblastoma patients with contrast-enhanced T1W images and 66 with fluid-attenuated inversion recovery (FLAIR) images. The end-to-end pipeline completes both tumor segmentation and status classification. The better tumor segmentation performance comes from FLAIR images compared to contrast-enhanced T1WI, and the better status prediction is also from the FLAIR images. This proposed pipeline not only saves the time in tumor annotation and avoids interrater variability in glioma segmentation but also achieves good prediction of MGMT methylation status. It would help find molecular biomarkers from routine medical images and further facilitate treatment planning.




Dastghaib S, Shojaei S, Mostafavi-Pour Z, Sharma P, Patterson JB, Samali A, Mokarram P, Ghavami S.
Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells.
Cells. 2020 Oct 22. 2020;9(11):E2339. doi: 10.3390/cells9112339. In vitro study. _
Simvastatin sensitizes GBM cells to TMZ-induced cell death via a mechanism that involves autophagy and unfolded protein response (UPR) pathways.




Franco P, Delev D, Cipriani D, Neidert N, Kellner E, Masalha W, Mercas B, Mader I, Reinacher P, Weyerbrock A, Fung C, Beck J, Heiland DH, Schnell O.
Surgery for IDH1/2 wild-type glioma invading the corpus callosum.
Acta Neurochir (Wien). 2020 Oct 23. doi: 10.1007/s00701-020-04623-z. Retrospective analysis. _
Our study suggests that in patients with corpus callosum glioblastoma, gross-total resection prolongs survival without negatively impacting neurological outcome as compared to biopsy.




Ho KG, Uhlmann EN, Wong ET, Uhlmann EJ.
Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma.
Mol Clin Oncol. 2020 Oct 1. 2020;13(6):80. doi: 10.3892/mco.2020.2150. Retrospective analysis. _
Leukopenia was associated with longer survival independent of age or extent of surgery. A possible interpretation is that grade 2 leukopenia is a biomarker of adequate temozolomide dosing in a population with diverse DNA repair function, which may be the consequence of variable O6methylguanine‑DNA methyltransferase activity. A prospective dose escalation trial is necessary to determine if treatment‑induced leukopenia is beneficial for all patients receiving temozolomide.




Hsu PYH, Folkman F, Ghosh S, de Robles P, Leckie C, Dersch-Mills D, Coppens R, Chambers C.
Actual body weight dosing of temozolomide and overall survival in patients with glioblastoma.
J Oncol Pharm Pract. 2020 Oct 29. doi: 10.1177/1078155220968613. Retrospective analysis. _
Temozolomide doses at full actual body weight calculated body surface area dosing during the concurrent phase is required to achieve a similar median OS as seen in the pivotal trial by Stupp et al.




Huang R, Li G, Li Y, Wang Y, Yang P, Zhang C, Wang Z, Zhou D, Zhang W, Zhang Z, Jiang T.
Long-term efficacy of surgical resection with or without adjuvant therapy for treatment of secondary glioblastoma in adults.
Neurooncol Adv. 2020 Aug 21. 2020;2(1):vdaa098. doi: 10.1093/noajnl/vdaa098. Retrospective analysis. _
For patients with secondary glioblastoma, aggressive postoperative adjuvant therapy after gross total resection was recommended. However, we did not detect a benefit in IDH1-wildtype patients in our cohort.




Peereboom DM, Ye X, Mikkelsen T, Lesser GJ, Lieberman FS, Robins HI, Ahluwalia MS, Sloan AE, Grossman SA.
A Phase II and Pharmacodynamic Trial of RO4929097 for Patients With Recurrent/Progressive Glioblastoma.
Neurosurgery. 2020 Oct 7:nyaa412. doi: 10.1093/neuros/nyaa412. Phase 2 trial: _ _
RO4929097 was inactive in recurrent GBM patients and demonstrated minimal inhibition of neurosphere formation in fresh tissue samples.




Rubin MC, Sagberg LM, Jakola AS, Solheim O.
Primary versus recurrent surgery for glioblastoma-a prospective cohort study.
Acta Neurochir (Wien). 2020 Oct 14. doi: 10.1007/s00701-020-04605-1. Prospective study. _
Outcomes after primary and recurrent surgeries were quite similar in our practice. As surgery may prolong life in patients where gross total resection is obtainable with reasonable risk, the indication for surgery in glioblastoma should perhaps not differ that much in primary and recurrent resections.




Saeed AM, Khairnar R, Sharma AM, Larson GL, Tsai HK, Wang CJ, Halasz LM, Chinnaiyan P, Vargas CE, Mishra MV.
Clinical Outcomes in Patients with Recurrent Glioblastoma Treated with Proton Beam Therapy Reirradiation: Analysis of the Multi-Institutional Proton Collaborative Group Registry.
Adv Radiat Oncol. 2020 Apr 22. 2020;5(5):978-983. doi: 10.1016/j.adro.2020.03.022. Prospective study. _
This is the largest series to date reporting outcomes for Proton Beam Therapy (PBT) reirradiation of patients with recurrent Glioblastoma. Our analysis indicates that PBT is well tolerated and offers efficacy rates comparable with previously reported photon reirradiation.




Stewart J, Sahgal A, Lee Y, Soliman H, Tseng CL, Detsky J, Husain Z, Ho L, Das S, Maralani PJ, Lipsman N, Stanisz G, Perry J, Chen H, Atenafu EG, Campbell M, Lau AZ, Ruschin M, Myrehaug S.
Quantitating Interfraction Target Dynamics During Concurrent Chemoradiation for Glioblastoma: A Prospective Serial Imaging Study.
Int J Radiat Oncol Biol Phys. 2020 Oct 14. Doi: 10.1016/j.ijrobp.2020.10.002. Prospective study. _
Clinically meaningful tumor dynamics were observed during chemoradiation for Glioblastoma, supporting evaluation of daily Magnetic Resonance Image-guided Radiotherapy and treatment plan adaptation.




Tzaridis T, Schäfer N, Weller J, Steinbach JP, Schlegel U, Seidel S, Sabel M, Hau P, Seidel C, Krex D, Goldbrunner R, Tonn JC, Grauer O, Kebir S, Schneider M, Schaub C, Vatter H, Coch C, Glas M, Fimmers R, Pietsch T, Reifenberger G, Herrlinger U, Felsberg J.
MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA-09 trial.
Int J Cancer. 2020 Oct 28. doi: 10.1002/ijc.33363. Randomized Phase 3 trial.
_
In patients with IDH-wildtype glioblastoma, methylation of the MGMT promoter allows for improved survival after chemotherapy, due to reduced ability to repair DNA damage. Here, the authors set out to evaluate the use of different tests for promoter methylation, with an eye toward their usefulness at allocation of chemotherapy, and on their prognostic applicability. They show that three different methods of testing methylation—quantitative methylation-specific PCR, pyrosequencing, and DNA methylation arrays—agree more than 90% of the time. Patients with lower MGMT promoter methylation had shorter survival times, but still benefited from CCNU/TMZ therapy.



*

Wang LM, Song C, Li YX, Zhang XD, Ji YH, Wen WJ.
A novel isocitrate dehydrogenase 1 G131D mutation in glioblastoma.
Chin Med J (Engl). 2020 Oct 15. doi: 10.1097/CM9.0000000000001172. Letter. _
Here, we present a case of IDH1 G131D mutant glioblastoma diagnosed based on histopathological and molecular genetic findings. To the best of our knowledge, the IDH1 G131D mutation has not been reported in gliomas to date. Although there were some oligodendroglioma-like cells in the present case, chromosome 19q was intact and there was no mutation of the TERT promoter. Moreover,the tumor had an EGFR amplification, CDKN2A/B deletion, and loss of chromosome 10. Therefore, these results support the integrated diagnosis of glioblastoma or “Astrocytoma, IDH-mutant, grade 4.” Our findings suggest that the IDH1 G131D mutation may also be a pathogenic event in the gliomas mutagenesis cascade leading to glioma, which expands the spectrum of known pathogenic IDH mutations. Given that IDH1 mutations are often associated with less aggressive behavior and favorable outcomes in brain tumors in adults, the effect of this novel IDH1 G131D mutation on prognosis in the present case requires longer follow-up.



Diffuse midline glioma



DeWire M, Fuller C, Hummel TR, Chow LML, Salloum R, de Blank P, Pater L, Lawson S, Zhu X, Dexheimer P, Carle AC, Kumar SS, Drissi R, Stevenson CB, Lane A, Breneman J, Witte D, Jones BV, Leach JL, Fouladi M.
A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).
J Neurooncol. 2020 Oct 9. 2020;149(3):511-522. Doi: 10.1007/s11060-020-03641-2. Phase 1-2 trial. _
Ribociclib administered following radiotherapy is feasible in diffuse intrinsic pontine glioma and diffuse midline glioma. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies.




Dorfer C, Czech T, Gojo J, Hosmann A, Peyrl A, Azizi AA, Kasprian G, Dieckmann K, Filbin MG, Haberler C, Roessler K, Slavc I.
Infiltrative gliomas of the thalamus in children: the role of surgery in the era of H3 K27M mutant midline gliomas.
Acta Neurochir (Wien). 2020 Oct 22. doi: 10.1007/s00701-020-04589-y. Retrospective analysis. _
We advocate to still consider an attempt at maximal safe resection in the multidisciplinary treatment of unilateral thalamic non-pilocytic gliomas irrespective of their H3 K27-mutational status.




Hipp SJ, Goldman S, Kaushal A, Krauze A, Citrin D, Glod J, Walker K, Shih JH, Sethumadhavan H, O'Neill K, Garvin JH, Glade-Bender J, Karajannis MA, Atlas MP, Odabas A, Rodgers LT, Peer CJ, Savage J, Camphausen KA, Packer RJ, Figg WD, Warren KE.
A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas.
J Neurooncol. 2020 Oct 11. 2020;149(3):437-445. doi: 10.1007/s11060-020-03627-0. Phase 1 trial. _
The recommended phase 2 dose of lenalidomide administered daily during radiation therapy is 116 mg/m2/day. Children with malignant gliomas tolerate much higher doses of lenalidomide during radiation therapy compared to adults. This finding is critical as activity was observed primarily at higher dose levels suggesting a dose response.



Anaplastic oligodendroglioma



Geben LC, Mobley BC, Brockman AA, Pastakia D, Naftel R, Ihrie RA, Esbenshade AJ.
Sustained response to erlotinib and rapamycin in a patient with pediatric anaplastic oligodendroglioma.
Pediatr Blood Cancer. 2020 Oct 1. 2020;e28750. doi: 10.1002/pbc.28750. Case report. _
One goal of precision medicine is to identify mutations within individual tumors to design targeted treatment approaches. This report details the use of genomic testing to select a targeted therapy regimen of erlotinib and rapamycin for a pediatric anaplastic oligodendroglioma refractory to standard treatment, achieving a 33-month sustained response. Immunohistochemical analysis of total and phosphorylated protein isoforms showed abnormal signaling consistent with detected mutations, while revealing heterogeneity in per-cell activation of signaling pathways in multiple subpopulations of tumor cells throughout the course of disease. This case highlights molecular features that may be relevant to designing future targeted treatments.



Other gliomas



Chordoid glioma of the third ventricle



Zhang GB, Huang HW, Li HY, Zhang XK, Wang YG, Lin S.
Intracranial chordoid glioma: A clinical, radiological and pathological study of 14 cases.
J Clin Neurosci. 2020 Sep 18. 2020;80:267-273. doi: 10.1016/j.jocn.2020.09.019. Case series. _
According to our experience, we recommend gross total resection as the primary goal, which is associated with improved rates of tumor control and without increasing rates of postoperative complications.



Embryonal tumors



Medulloblastoma



Climans SA, Macdonald DR, Sutherland DE, Mason WP.
Prolonged response to vismodegib in a patient with systemic medulloblastoma metastases.
BMJ Case Rep. 2020 Oct 29;13(10):e236406. doi: 10.1136/bcr-2020-236406. Case report. _
Some patients with metastatic medulloblastoma can be successfully treated with targeted therapy. We report the case of a 42-year-old woman who was diagnosed with sonic hedgehog (SHH)-subgroup medulloblastoma. She was treated with surgery, radiation and chemotherapy. She then developed bone pain. A positron emission tomography (PET) scan confirmed widespread bone metastases from her medulloblastoma. She was started on vismodegib, an oral smoothened inhibitor that targets her tumour type. Her bone pain resolved. A repeat PET scan showed resolution of almost all metastases. Fourteen months after starting vismodegib, her disease recurred and she was transitioned to temozolomide chemotherapy. We document an important case of prolonged response to vismodegib in a patient with systemic SHH-subgroup medulloblastoma metastases.




Escudero L, Llort A, Arias A, Diaz-Navarro A, Martínez-Ricarte F, Rubio-Perez C, Mayor R, Caratù G, Martínez-Sáez E, Vázquez-Méndez É, Lesende-Rodríguez I, Hladun R, Gros L, Ramón Y Cajal S, Poca MA, Puente XS, Sahuquillo J, Gallego S, Seoane J.
Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma.
Nat Commun. 2020 Oct 27. 2020;11(1):5376. doi: 10.1038/s41467-020-19175-0. In vitro study. _
The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. Ultimately, CSF ctDNA analysis could facilitate the clinical management of medulloblastoma patients and help the design of tailored therapeutic strategies, increasing treatment efficacy while reducing excessive treatment to prevent long-term secondary effects.




Qin Q, Huang D, Jiang Y.
Survival difference between brainstem and cerebellum medulloblastoma: the surveillance, epidemiology, and end results-based study.
Medicine (Baltimore). 2020 Oct 9. 2020;99(41):e22366. Doi: 10.1097/MD.0000000000022366. Retrospective analysis. _
This study uncovers a survival advantage for cerebellum medulloblastoma patients versus brainstem patients. Additionally, prognostic factors include age, extent of surgical resection, and receipt of radiotherapy or chemotherapy. Radiotherapy after surgery and rational use of chemotherapy drugs are crucial for treatment of medulloblastoma patients. Further studies of these prognostic factors are required to improve the survival time.




Yan J, Liu L, Wang W, Zhao Y, Li KK, Li K, Wang L, Yuan B, Geng H, Zhang S, Liu Z, Duan W, Zhan Y, Pei D, Zhao H, Sun T, Sun C, Wang W, Hong X, Wang X, Guo Y, Li W, Cheng J, Liu X, Ng HK, Li Z, Zhang Z.
Radiomic Features From Multi-Parameter MRI Combined With Clinical Parameters Predict Molecular Subgroups in Patients With Medulloblastoma.
Front Oncol. 2020 Oct 2;10:558162. doi: 10.3389/fonc.2020.558162. Radiomics. _
Prediction performance was excellent for WNT and SHH subgroups, while that for Group 3 and Group 4 needs further improvements. Machine learning algorithms offer potentials to non-invasively predict the molecular subgroups of Medulloblastoma.




Zhu S, Lin F, Chen Z, Jiang X, Zhang J, Yang Q, Chen Y, Wang J.
Identification of a Twelve-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival for Medulloblastoma.
Front Genet. 2020 Sep 3. 2020;11:563882. doi: 10.3389/fgene.2020.563882. Nomogram development. _
Medulloblastoma (MB) is the common pediatric malignant tumor with poor prognosis in cerebellum. However, MB is always with clinical heterogeneity. To provide patients with more clinically beneficial treatment strategies, there is a pressing need to develop a new prognostic prediction model as a supplement to the prediction outcomes of clinical judgment. … Our study identified a twelve-gene signature and established a prognostic nomogram that reliably predicts overall survival in medulloblastoma. The above results will help us to better analyze the pathogenesis and treatment of medulloblastoma in the future.



Tumors of the sellar region



Craniopharingioma



Prince EW, Whelan R, Mirsky DM, Stence N, Staulcup S, Klimo P, Anderson RCE, Niazi TN, Grant G, Souweidane M, Johnston JM, Jackson EM, Limbrick DD Jr, Smith A, Drapeau A, Chern JJ, Kilburn L, Ginn K, Naftel R, Dudley R, Tyler-Kabara E, Jallo G, Handler MH, Jones K, Donson AM, Foreman NK, Hankinson TC.
Robust deep learning classification of adamantinomatous craniopharyngioma from limited preoperative radiographic images.
Sci Rep. 2020 Oct 9. 2020;10(1):16885. doi: 10.1038/s41598-020-73278-8. Radiomics study. _
For patients with brain tumors, non-invasive diagnosis would represent a substantial clinical advance, potentially sparing patients from the risks associated with surgical intervention on the brain. Such an approach will depend upon highly accurate models built using the limited datasets that are available. Herein, we present a novel genetic algorithm (GA) that identifies optimal architecture parameters using feature embeddings from state-of-the-art image classification networks to identify the pediatric brain tumor, adamantinomatous craniopharyngioma (ACP). We optimized classification models for preoperative Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and combined CT and MRI datasets with demonstrated test accuracies of 85.3%, 83.3%, and 87.8%, respectively. Notably, our GA improved baseline model performance by up to 38%. This work advances DL and its applications within healthcare by identifying optimized networks in small-scale data contexts. The proposed system is easily implementable and scalable for non-invasive computer-aided diagnosis, even for uncommon diseases.



bottom