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In this issue

Volume 3, Issue 2, Oct. 2014www.behestandarou.com

NOSCs perspectives.44 Neuro-Oncology Events Updates.45 Report from the latest NOSC meet-up,Tehran,

Aug 2014.......46 Mashhad NOSCs abstract to be communicated

during EANO 2014 Meeting, Turin,Italy.49 Hotspots in Neuro-oncology50 A case study in Neuro-Oncology.52

In this issue:

Nuro-Oncology ScientificClub (NOSC);

the beckoning future for a

more integrated care to braintumor patients

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NOSC; the beckoning future for amore integrated care to braintumor patients

The Neuro-Oncology Scientific Club, NOSC, is a non-governmental community to foster interdisciplinaryapproaches in brain tumor care in Iran.

Since 2011, the proven advantages of interdisciplinarycare in brain tumor has prompted NOSC members to

advocate the working team concept in neuro-oncologycare across the country. Multiple health careprofessionals contribute to the care of the brain tumor patients, and this connect approach becomesparticularly crucial in case of high grade andcomplicated tumors. The benefits of interdisciplinaryapproach in such clinical conditions has been well-established both for the clinicians and the patients. Weat NOSC believe that education, frequent field updatesand shared initiatives are the mainstay to reach our goals. NOSC has attempted the above through holdingscientific meetings, neuro-oncology update sessionsand round table discussions in different provinces. Along these lines, NOSC has published severalscientific reports, original research findings andconsensus statements since establishments. Withover 250 members from all allied disciplines, NOSCsoverall strategies and plans are governed by itssteering board and provincial founding panels. NOSCcontinues to receive endorsement and support fromthe related national scientific societies, and believesthat such collaboration will allow serving the braintumor patients better.

NOSC has received continued organizational andscientific support from the medical division at BehestanDarou PJS-MSD since 2011.

44

OSC : Neuro-Oncologyentific Clube newsletter Editorial desk.it 22, Sorayya Bldg. Pardis St.llasadra Ave. Tehran, Iran. 00982188774200

itorial Committee:abi Nami M.dras A.khomorova L.

farieh L.

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Neuro-Oncology Events Update

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The 11th EANO 2014 meeting is going to beheld in Turin, Italy. EANO gives the opportunityto share the most up-to-date advances inbasic science, translational and clinicalresearch. All fields of neuro-oncology are tobe covered, such as biology and pathology,imaging, surgery, radiotherapy, chemotherapy,targeted therapies, supportive/palliative care

and quality of life.Mashhad NOSC is communicating an abstractin EANO meeting 2014.This poster communication by Anvari et al,entitled Intracranial meningioma: prognostic factors and treatment outcome in patientsundergoing radiation thera py will beabstracted in the Neuro-Oncology Journal.See page 49.During EANO meeting 2014, an integrated

satellite symposium (MSD) on 10 th October,would aim to: 1)Educate participants onrecent data of the new treatments for GrII/IIIGliomas, 2)Discuss the role of novel treatmentfor recurrent gliomas and 3) provide insight onnovel immunology (check point inhibitors)treatments and development in treatment of gliomas.

Options In The Treatment Of Recurrent Gliomas, and Active Immunotherapy and Check PointInhibitors: where is it going in glioma.

The faculty Wolfgang Wick, Heidelberg(DE), Martin van den Bent, Rotterdam (NL)and Roger Stupp, Zurich (CH), would inturn touch on:Update On The TreatmentOf Newly Diagnosed Grade II/III Gliomas;

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t s p o

t s i n N e u r o -

O n c o

l o yAssociation between DNArepair gene polymorphisms

and risk of glioma. Asystematic review and meta-analysis Association studies of germline DNA repair single nucleotide polymorphisms (SNPs)and glioma risk have yielded inconclusiveresults. Fahsmideh et al have performed asystematic review and metanalysis of studies investigating this association: 27eligible studies investigating 105 SNPs in42 DNA repair genes were identified. The

authors found that SNPs rs3212986,rs13181, andrs25487 in DNA repair genesERCC1, ERCC2 and XRCC1 may increasethe risk of glioma, while SNPs rs1136410and rs12917 in PARP1 (ADPRT) andMGMT are associated with decreasedsusceptibility to glioma. These data mustbe further confirmed in robust statisticalanalyses.http://www.ncbi.nlm.nih.gov/pubmed/24500421

Deferred use of bevacizumab for recurrent glioblastoma is notassociated with diminished efficacyThe optimal timing to initiate bevacizumab (BV) for recurrent glioblastoma (GBM) is still unclear. Inthe June issue Piccioni et al investigated progression-free survival (PFS) and survival time (ST) ina retrospective cohort of 468 patients with GBM patients treated with BV at different recurrences.They found that PFS and ST did not differ between 1st, 2ndand 3rd recurrences; therefore theyconcluded that deferred use of BV is not associated with diminished efficacy. However, patientswith age more than 60 years and low extent of resection were unable to tolerate BV delay. Overall,

these data are in line with the well-known antiedema mechanism of action of BV.http://www.ncbi.nlm.nih.gov/pubmed/24627236

Evaluation of amifostine forprotection against cisplatin-induced serious hearing loss inchildren treated for average-risk orhigh-risk medulloblastoma

Currently, no established treatments orprocedures exist to prevent platinum-inducedhearing loss in children or adults. Gurney et alinvestigated amifostine for protection fromcisplatin-induced serious hearing loss in patientswith both average-risk and high-riskmedulloblastoma who received cisplatin in 2sequential clinical trials at St. Jude Hospital.

Amifostine was not randomly administered at adose of 600 mg/m2 immediately before and 3hours into each cisplatin infusion. They found aprotective effect of amifostine in average-riskpatients but not in those that were high-risk.These data need to be confirmed in arandomized trial.http://www.ncbi.nlm.nih.gov/pubmed/24414535

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o t s p o t s i n N e u r o - O n c o l o y

Integrating diffusion kurtosis,dynamic susceptibility-weightedcontrast-enhanced MRI and shortecho time chemical shift imagingfor grading gliomasSeveral studies of advanced MRI techniques tograde gliomas have been published withdifferent set-ups and mixed results. Van Cauter and collegues have evaluated the diagnosticaccuracy of diffusion kurtosis imaging (DKI),dynamic susceptibility-weighted contrast-enhanced (DSC) MRI and short echo timechemical shift imaging (CSI) for grading gliomStatistically significant differences among tumogrades were shown for MK, MD, mean rrCBV,mean rrCBF, rDR, lipids over total choline, lipidover creatine, sum of myo-inositol, and sum ofcreatine. DSC-MRI proved to be the modalitywith the best performance when comparingmodalities individually, while the multimodaldecision tree proved to be most accurate inpredicting tumor grade, with a performance of86%. All these results must be validated inlarger prospective cohort of patients.

http://www.ncbi.nlm.nih.gov/pubmed/24470551

Anti-PD-1 Antibody MK-3475Advances Into Multiple TumorTypesThe PD-1 targeting antibody pembrolizumab(MK3475) has high and long-lasting activity againstmetastatic melanoma, according to the results of alarge Phase I trial that found high survival rates,

including in patients with advanced melanoma whowere previously treated with ipilimumab. PD-1blocking antibodies unleash an immune responseagainst cancer by releasing a break on antitumor Tcells. At last year's ASCO Annual Meeting, earlyresults from this trial on the first 135 patients withmetastatic melanoma treated with pembrolizumab,showed that the drug, led to a 41 percent response.The report for this year's meeting was an updatebased on 411 patients. This drug is now approved forthe treatment of non resectable advanced metastaticmelanoma; and being studied in a multiple tumortypes. MK3475 (keytruda) has been brought to theclinical practice by Merck (MSD).

Glioblastoma prognosis is found to be linked toneuronal programmed death ligand 1 (PD-L1)expression in tumor-adjacent tissue. Expression ofPD-L1 by neurons surrounding glioblastoma tissueincreases neuronal killing of tumor cells and isassociated with prolonged survival, a new study hasshown. The results shed light on the dynamicinfluence of the microenvironment on tumor growth.

1) http://www.nature.com/nrneurol/journal/v9/n11/full/nrneurol.2013.197.html

2) http://journals.lww.com/oncologytimes/Fulltext/2014/07100/Metastatic_Melanoma__Immunotherapy_with.10.aspx

3) http://www.keytruda.com/hcp/

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MK-3475

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52NOSC NL 2013;3(2)

A 27 year-old man presented to the emergencydepartment of a country hospital with diplopia, ticklingparesthesia and a right sided hemiparesis. He underwentcontrast enhanced brain MRI which documented a lesionwith inhomogeneous enhancement in the rightparamedian pontine region. Other examinations (CSFanalysis with isoelectric focussing, EMG, SSEPs) werenegative and steroids (dexamethasone 8 mg pd) werethen administered with clinical improvement.The MRI examinations at 1 month and 6 months aftersteroid therapy were stable and the patient remainedasymptomatic.

Sixteen years after the first episode the man wasadmitted to the hospital with dizziness and diplopia. A contrast-enhanced MRI showed multipleenhancing areas in the left cerebellar hemisphere,the floor of the fourth ventricle, and themesencephalic-diencephalic region. The originalpontine lesion on brain MRI was unchanged and

spine MRI was normal. The patient was extensivelyinvestigated (systemic workup and CSF analysis),and the spectrum of steroid responsive nonneoplastic lesions in the CNS (multiple sclerosis,neurosarcoidosis, Behcet disease and atypicaltuberculosis) was ruled out. A PCNSL was thensuspected. HIV serum test was negative. Thepatient refused a biopsy, then was treated withsteroids and a complete clinical and radiologicalremission was achieved.

Two years later, at the age of 45, the patient presented again to the emergency department with headache, vomiting anddizziness. He performed contrast-enhanced brain MRI which showed a new large enhancing lesion in the left cerebellum withdistortion of the fourth ventricle but no evidence of hydrocephalus. Primary CNS lymphoma (PCNSL), when affects youngimmunocompetent subjects and is located in critical areas for biopsy, can present diagnostic problems at onset. Treatment wsteroids can lead to a regression of lesions in up to 40% of patients, thus deferring the definite histological diagnosis.

This case shows some peculiar features: a long disease history (overall, 21 years) with multiple recurrences involving excluthe brain stem, cerebellum and thalamus; an unusual and protracted response to steroids alone and a complete response tostandard chemotherapy and radiotherapy even if performed very late (18 years after the onset of symptoms).[Case file, courtesy of C. Bosa, et al. Department of Neuro-Oncology, University and Citt della Salute e della Scienza, Italy, Aug

A CASE STUDY inNEURO-ONCOLOGY

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NOS s Newsletter Editorial DeskNo.22, Sorayya Bldg, Pardis St. Mollasadra Ave. Tehran, Iran +982188774200 Ext. 1634

Neuro-Oncology Scientific ClubNewsletter

Volume 3 Issue 2 October 2014

NOSC Receives Unrestricted Scientific, Medicaland Organizational Support from the Medical

Division of Behestan Darou PJS.

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