Neuro-Oncology Scientific Club (NOSC) July 2013; 2(2): 31-42

In this issue

Volume 2, Issue 2, July 2013

N E W S L E T T E R

NOSC on its Way to Grow.31 NOSCs Steering Board Meeting

Report.32 NOSCs Recently Published

Articles. 34 NOSC Case Study Periodical,

Call for Papers.. 35 Neuro-Oncology Events Updates.

36 Featured NOSC Contributors3 7 The International Brain Tumor

Awareness Week.. 38 Highlights from ASCO 2013. 39 Neuro-Oncology News Blast41

In this issue

www.behestandarou.com

The Neuro-Oncology Scientific

Club (NOSC), on its way to

grow

NOSC was established almost two years ago and continued to grow and consolidate. This scientific-professional community aims to help improving the management of brain tumors through a collaborative approach and the ongoing patient support. NOSC with its neuro-oncology field experts and brain tumor care providers (over 200 members now), pursues its defined goals towards improving brain tumor patients care, survival and quality of life.NOSC comprises neuro-oncology professionals from various disciplines not limited to neurosurgery, radiation oncology, pathology, neuroradiology, hematology and oncology and neurology across Iran.

This scientific club owns provincial founding panels as well as a country-wide steering board. Given the endorsement and support received from the related national scientific societies, and the road map drawn by the steering committee , NOSC continues to strongly peruse its aim with the central belief that: together we can serve the brain tumor patients better.

31

On the Cover

The most detailed 3D image of the human brain ever taken revealing structures as tiny as 20 microns (50 times smaller than the best MRI technology).The image, made as part of a project called the BigBrain, would serve as a reference point for future studies including the neuro-oncology research. Discovery News 2013-06-21

First, Dr. Fazlalizadeh addressed the meeting with his welcome note. He emphasized that the allied societies taking role in the management of brain tumors should put together patient-centered interests to define shared strategies within NOSC. He further mentioned, when these ideas emerge, we should let them develop as opportunities for the exchange of expertise and optimized practice.These would not only serve the scholars and participants scientific needs but also be expected to improve our patients outcome.

NOSCs Steering Board Meeting Report

NOSC steering board held its first meeting to strategize future scientific/professional activities within the club.Following the initial endorsements NOSC received from the related national scientific societies, the steering board of this scientific club was formed.NOSCs steering boards central mission is to define its mid to long-term goals, strategies and tactics towards brain tumor patients better and extended lives.

The first NOSCs steering board meeting which was held on 7th March 2013, Tehran, was hosted by the Cancer Society of Iran. Present at the meeting were (alphabetically) : Dr.Amouheidari- Isfahan NOSC lead-faculty; Dr.Fazlalizadeh- Iranian Cancer Society; Dr. Ghadyani- Iranian Cancer Society; Dr.Hashemi-Iranian Radiology Society; Dr. Nayyeri- Iranian Radiology Society; Dr. Nilipour-Iranian Pathology Society; Dr.Samiei- Iranian Society of Radiation Oncology; Dr.Seyednejad- Tabriz NOSC lead-faculty and Dr.Tabatabaeefar-Iranian Society of Radiation Oncology. For informed reasons some invitees including Dr. Ansari- Shiraz NOSC lead-faculty; Dr.Anvari-Mashhad NOSC lead-faculty; Dr. Haddad-Iranian Society of Radiation Oncology; Dr.Vosough- Iranian Society of Pediatric Hematology-Oncology; Dr. Zali- National Society of Surgeons (Neurosurgery Branch) and Dr.Zendehdel- National Cancer Research Network, could not attend the meeting.

NOSC NL 2013;2(2) 32

Such forums as NOSC can be utilized as a common place for case presentations through which the cross-talk between disciplines can solve many hard-to-tackle issues.Then, Dr.Samiee continued by sharing the positive feeling he had to see experts with brain tumor interest coming from different societies, around a table. He encouraged all societies to support not only NOSC but all similar interdisciplinary communities similarly aiming at oncology patients better life. While recognizing the distinctive role of NOSCs organizing committee under Behestan Darous (BD) support, he recommended that NOSC should be strategically steered by the societies (through their official delegates) in order to continue receiving support and endorsement from the health authorities and policy makers. This will allow NOSC become more authorized and visible in a national scope; he indicated. Later, Dr.Tabatabaeefar refocused on the issue that this club is not intended to belong to a specific group or society. NOSC would remain under the umbrella of all contributing societies as all agreed. Since start, NOSC tried to brand itself as a scientific community disclosing no competing or distinct commercial interest, even though the whole concept was initiated and supported by BD. BD is the main organizer putting together collaborators and members to run NOSC. Moreover, the present steering board is behind all decisions made to let this scientific club pursue its aims. We are here to help this collaborative functional group continue its journey towards optimizing neuro-oncology practice and helping our patients the best we can, he said.

Other contributors such as Dr.Amouheidari and Dr. Hashemi discussed the significance of such activities when related societies equally interact. This will be a major step forward in neuro-oncology practice across Iran, they agreed. Dr.Ghadyani commented on the pivotal role of the steering board and that NOSC can seek registration with the ministry of health as a focus-group and functions independently. Later on, when NOSC becomes a well-established and organized community, societies may take over to further officialize the club. Dr.Samiee, however, was not in agreement and shared his self-experience with the process of officializing such activities. As he indicated, there is no upfront limitations and obstacles to engage societies from the beginning. Most of the participants agreed with the latter ( i.e. top-down) approach. Other delegates including Dr. Nilipour, Dr.Nayeri, Dr.Hashemi and Dr.Seyednejad, commented on the importance of the connect-approach with regard to neuro-oncology applied science and patient care. Documentation of shared updates together with the evidence-based experiences can effectively provide a common pool for all scholars and clinicians in the field to communicate and transfer their expertise in order to find solutions to optimally manage patients. This has been something NOSC tried to render so far. Since NOSCs scientific contributions to the field have strongly been perceived effectual, all participants agreed that parallel to the official process under the societies umbrella, NOSC should continue its scientific activities even stronger than before.

Continued on page.42

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NOSCs Recently Published Articles

Following the two PubMed indexed citations and three international widely indexed peer reviewed publications which NOSC came up with over the past two years (below links);

http://neuro-oncology.oxfordjournals.org/content/14/suppl_3/iii1

http://neuro-oncology.oxfordjournals.org/content/14/suppl_1/i106.abstract

http://www.webmedcentral.com/wmcpdf/Article_WMC002381.pdf

http://www.sciencepub.net/report/report0402/007_8292report0402_42_53.pdf

http://www.bioinfo.in/uploadfiles/13470961443_5_2_IJMCR.pdf

we are pleased to announce that the scientific report from the Isfahan NOSC, which was derived from an interdisciplinary meeting few months ago in Isfahan, is now published and widely accessible online. This work underwent an strict peer-review process since January and got published recently.

Article HTML link: http://article.sapub.org/10.5923.j.rct.20130201.01.html

PDF link: http://www.sapub.org/global/showpaperpdf.aspx?doi=10.5923/j.rct.20130201.01.v

This paper is published in the international journal of Research In Cancer and Tumor 2013; 2(1): 1-9 (doi: 10.5923/j.rct.20130201.01).

This American journal is released by the Scientific and Academic Publishing house (sapub.org) Rosemead, CA, 91731, USA. SAP journals are indexed with EBSCO, Embase, Gale, WorldCat, Index Copernicus, Journal TOCs, and CrossRef.

More recently, we had the other submitted manuscript entitled:

Classifying pediatric CNS tumors through near optimal feature

selection and mutual information; A single center cohort

accepted for publication in the Middle East Journal of Cancer

(MEJC). This valuable report which has been contributed by

MAHAKs Pediatric Cancer Treatment and Research Center

(MPCTRC), is now in press and soon will be published.

MEJC is indexed with EMBASE/Excerpta Medica, EBSCO, ISC,

CINAHL, DOAJ and Index Copernicus.

NOSC NL 2013;2(2) 34

NOSC Case Study Periodical, Call for Papers

Following the 3 published case studies contributedby some of the Iranian field experts in neuro-oncology, NOSC editorial office is in the process ofpublishing two other interesting brain tumor case-studies communicated by its members. This twoshort case study papers will be available to NOSCmembers quite soon.NOSC case study periodical continues topublish interesting brain tumor case-studiesreported from joint neuro-oncology clinics in Iran.The main focus would be newly diagnosed high-grade glial brain tumors.

You might have encountered with brain tumor casesfor whom the effective management really needs aninterdisciplinary approach. To get them publishedwithin NOSC CSP please contact the editorial desk.Our contact info can be found at the end of thisnewsletter.

The publishing source for your communicatedinteresting clinical case scenarios will be the NOSC,which is now becoming a well-recognized self-operated neuro-oncology experts forum in anational scope.

You are then cordially invited to submit interesting cases NOSC editorial desk . For those who are interested to contribute; following items of the reportable cases should be taken into account:

Initial oncology workup Neurosurgical discussion Antiepileptic prophylaxis Treatment response to concomitant

chemoradiation and adjuvant therapy.

Radiation oncology commentary Hematology oncology commentary Further interesting details.

We plan to publish cases with clinically valuable lessons. Therefore brain tumor cases with diagnostic, ethical and therapeutic challenges or pharmacology and histopathology highlights are deemed of particular educational value for NOSC Case Study Periodicalpapers.

35

2013 World Federation of Neuro-Oncology Meeting

The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology to be held in Conjunction with the 2013 Scientific Meeting and Education Day of the Society for Neuro-Oncology (SNO). You may want to mark your calendars for the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology to be held November 21-24, 2013, in San Francisco, CA.

Neuro-Oncology Events Update

Leksell Gamma Knife Perfexion Course19-23 Aug 2013Cleveland Clinic Gamma Knife CenterCleveland OH

Event description Five Day Course Description for new Gamma Knife users:This educational experience provides an opportunity to expand the practitioner's range of treatment options to include this precise form of stereotactic radiosurgery. The course will provide hands-on sessions with Leksell Gamma Plan PFX with experienced experts in Gamma Knife radiosurgery. Upon completion of the course, participants will have completed training approval for Gamma Knife usage. Target audience will be Neurosurgeons, Medical Physicists, Radiation Oncologists, Neuro-otolaryngologists.Further info: http://my.clevelandclinic.org/neurological_institute/brain-tumor-neuro-oncology/for-medical-professionals.aspx

NOSC NL 2013;2(2) 36

Featured NOSC Contributors

Dr. Kazem Anvari, Radiation Oncologist NOSC Lead-Faculty, Mashhad

Dr. K. Anvari is a lead faculty member at NOSC. The neuro-Oncology scientific club in Mashhad has so far received spectacular contribution from his side. He is currently a faculty member at the Department of Radiation Oncology, Omid Hospital, Mashhad University of Medical Sciences (MUMS).Below is a brief bio-sketch of this featured NOSC lead faculty.

Dr. Anvari holds a graduate degree in Radiation Oncology, MUMS, since 2000. He began his academic career in Omid Hospital, Mashhad, since then.He has held academic positions such as:- Chief of the Radiation Oncology Department: 2008 to 2012.

- Chairman of the Radiation Oncology Department, Imam Reza Hospital, MUMS-2012 to date- Vice chancellor for educational affairs, Division of Radiation Oncology, MUMS- 2008 to date - Vice Chancellor for education and research affairs at Omid Hospital, MUMS- 2012His academic research interests are CNS, head and neck tumors as well as gastrointestinal and prostate cancers.Dr. Anvari has published over 30 papers mainly on gastrointestinal tract, CNS, head and neck and breast cancers.Together with his colleagues, he has succeeded to register the clinical data of nearly one thousand patients with CNS tumors who have been treated in Ghaem and Omid hospitals in Mashhad over the past 10 years.Some of his current topics in CNS tumor research are : 1) MGMT gene promoter methylation study of GBM patients and its relation to treatment regimens, using the MSQP method.2) Evaluating cancer markers expression ( e.g. GAGE, MAGE-E1, SOX-6, GAGE) in GBM using the IHC method and 3) Specific expression of testicular cancer markers ( e.g. ADAM29 FTHL17 HORMAD1) in GBM, using PCR.He is also involved in some registered cohorts to address the following issues: re-irradiation outcome in recurrent glial brain tumors as well as the evaluation of treatment results and prognostic factors in pediatric brain tumors, adult gliomas, meningiomas, pituitary adenoma.

Continued on page.42

In this part, and in each issue, we would feature one of the spectacular contributors to NOSC activities across the country. This time Dr. Kazem Anvaris bio-sketch is shared with other NOSC members. Other key contributors to NOSC will be individually featured in turn in forthcoming issues of the NOSC newsletter.

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The International Brain Tumor Awareness Week

The 7th International Brain Tumour Awareness Week

will be held between

(27 October - 2 November, 2013).

We as NOSC members plan to organize activities to increased awareness about brain tumors. Public awareness will be addressed using posters and leaflets during this

week. By this, NOSC expects to further draw attention to the particular challenges of a brain tumor and the need for a special response and an increased research effort.

To better aware the brain tumor patients of their condition and to provide patient

education, NOSC editorial has prepared some fact-sheets in Farsi addressing some of

the main questions brain tumor patients have.

These fact-sheets are supposed to be widely distributed to brain tumor patients before

and during the international brain tumor awareness week .

- Fact Sheet # 1 Brain Tumors

- Fact Sheet # 2 Why Me? the Diagnosis

- Fact Sheet # 3 Questions to ask your Doctor

-Fact Sheet #4 Telling Family and Friends about your brain tumor

-Fact Sheet #5 Helpful Suggestions

- Fact Sheet #6 What is a Seizure and How Does it Occur

- Fact Sheet # 7 Factors Contributing to Behavior and Personality Changes with the Brain Tumor

NOSC NL 2013;2(2) 38

Highlights from

ASCO 13

4 June 2013The results of two important clinical trials on

glioblastoma were presented at the annual meeting

of the American Society of Clinical Oncology

(ASCO) held in Chicago during 31 May 4 June

2013. The two trials were AVAglio (progression-

free survival and health-related quality of life

involving temozolomide and radiotherapy plus

bevacizumab in newly-diagnosed GBM, abst#

2023) and RTOG 0825 (a double-blind placebo-

controlled trial of bevacizumab in patients with

newly-diagnosed GBM). The results created

discussion and controversy.

Dr. Mark Gilbert, from the MD Anderson Cancer

Center, who presented the RTOG 0825 results

was reported as stating that in relation to using

bevacizumab in newly-diagnosed GBM: Our study

would strongly suggest that it is not beneficial to do

it as front-line treatment but to reserve it as

second-line or salvage therapy.

Some commentators worried that the overall

results might have an adverse effect on the US

Food and Drug Administrations (FDA) sort of

conditional approval for bevacizumab and brain

tumours in 2009. The worry revolves around the

survival advantage as expressed by progression-

free survival (PFS) and overall survival (OS) but

Dr. Richard Pazdur from the FDA was reported in

the New York Times as stating We have approved

a lot of drugs without a survival advantage.

Brain tumour patient advocates

need to be alert to this ongoing

debate about the measurement of

the survival advantage of new

therapies for brain tumours and

express their views when

necessary.

Meanwhile, in a relatively little-

reported media release on 17 June

it was stated that bevacizumab had

been approved in Japan for newly-

diagnosed GBM in combination

with TEMOZOLOMIDE plus

RADIOTHERAPY and as

monotherpy for recurrent GBM.

The approval was based on the

Phase II BRAIN study, a Japanese

Phase II study (JO22506) and the

Phase III AVAglio study.

Furthermore, it was stated that

applications for first-line treatment

have been filed in the European

Union and Switzerland. However ,

the FDA has not yet approved this

combination and according to the

so far established protocols, the

standard-of -care for GBM remains

six weeks concomitant

temozolomide and radiotherapy

followed by adjuvant

temozolomide.

Source:

http://chicago2013.asco.org/

39

ASCO

40

http://meetinglibrary.asco.org/abstractbysubcategory/2013%20ASCO%20Annual%20Meeting/153

13The Stupp regimen preceded by early post-surgery temozolomideversus the Stupp regimen alone in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM).

J Clin Oncol 31, 2013 (suppl; abstr 2022)

Background: In treatment of newly diagnosed GBM with the Stupp chemo-radiotherapy regimen,following by adjuvant chemotherapy, patients were treated with temozolomide (TMZ) & combinedradiotherapy 4-5 weeks after surgery. In the interval between surgery and chemo-radiotherapy, it is notknown whether additional TMZ treatment will improve efficacy or safety. This trial evaluated the safetyand efficacy of the Stupp regimen + early post-surgery TMZ chemotherapy in the treatment of patientswith newly diagnosed GBM. Methods: The trial was a multi-center, randomized open-label study. 99newly diagnosed GBM patients were enrolled and randomly assigned to the Stupp regimen + early post-surgery TMZ chemotherapy arm (experimental group, n = 52) or to Stupp regimen alone (control group,n = 47). Fourteen days after surgery, the patients in experiment group recieved TMZ orally at75mg/m2/day for 14 days. The primary endpoint of the study was the overall survival (OS). Thesecondary endpoints included the progression-free survival (PFS), objective tumor assessment andadverse events (AEs). Results: The median OS time was 17.58 months (95% CI: 15.18 23.03 months)in the experiment group and 13.17 months (95% CI: 11.14 18.76 months) in the control group (log-rank test, p = 0.021). There is no significantly difference in the median PFS between experiment groupand control group (8.74 months, 95% CI: 6.41-14.85 months vs 10.38 months, 95% CI: 8.18-15.44months, p = 0.695). No statistically significant difference was detected as regards to the objective tumorassessments. There is no significance in OS or PFS between MGMT positive and MGMT negativegroups. TMZ treatment was well tolerated in the study. AE types and rates were generally similarbetween the two groups. There were 22 SAEs in this study, with only 1 SAE (lung infection) in Stuppregimen group was possibly drug-related. Conclusions: The addition of early post-surgery TMZchemotherapy to the Stupp regimen for newly diagnosed GBM resulted in a statistically significantsurvival benefit with minimal additional toxicity. Clinical trial information: NCT00686725.

Efficacy and safety of radiotherapy (RT) plus temozolomide(TMZ) in elderly patients (EP) with glioblastoma (GBM).http://meetinglibrary.asco.org/content/112236-132

Bevacizumab in combination with TMZ in patients with recurrent GBM: Final OS and PFS analysis.http://meetinglibrary.asco.org/content/114390-132

Heres the link to all ASCOs abstracts on CNS tumors

Some other noteworthy abstracts from ASCO 2013!

and..

NOSC NL 2013;2(2)

Neuro-Oncology News Blast

June 2013: Circulating microparticles of glial origin andtissue factor bearing in high-grade glioma: a potentialprothrombotic role.

Venous thromboembolism (VTE) may complicate the clinical course ofglioblastoma multiforme (GBM). Circulating microparticles (MPs) have beenassociated with cancer-related VTE. Sixty-one consecutive patients with GBMundergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy

were prospectively evaluated. MPs numbers according to cellular origin and the procoagulantactivity of annexin V positive (AV+) MPs (MP-activity) were measured before surgery and then1 week and 1, 4, and 7 months after surgery. Glial (GFAP+) and endothelial (CD62E+) derivedMPs, AV+ and tissue factor-bearing (TF+) MPs were measured using flow cytometry. Baselinelevels of GFAP+/TF-, TF+/GFAP-, and GFAP+/TF+ MPs were significantly higher in GBMpatients than in healthy controls, and significantly increased at each time point after surgery; at7 months, a further significant increase over the level found a week after surgery was only seenin the subtotally resected patients. The number AV+/CD62E- MPs increased in GBM patientsand correlated with MP activity. TF+/GFAP- MPs numbers were significantly higher in 11 GBMpatients who developed VTE than in those who did not (p 0.04). TF+/GFAP- MPs levels abovethe 90th percentile (calculated in GBM patients without VTE) were associated with a higher riskof VTE (RR 4.17, 95% CI 1.57-11.03). In conclusion, the numbers of glial-derived and/or TF-bearing MPs were high in GBM patients both before and even more after the neoplasmwas treated, especially in patients with subtotal resection likely according to diseaseprogression. A contribution of TF+/GFAP- MPs to the risk of VTE is suggested.Thromb Haemost. 2013 Jun 27;110(2)http://www.ncbi.nlm.nih.gov/pubmed/23803674

Jan 2013: Mechanisms of evasive resistance to anti-VEGF therapy in glioblastoma.

Angiogenesis inhibitors targeting the VEGF signaling pathway have been US FDA approved for various cancers including glioblastoma (GBM), one of the most lethal and angiogenic tumors. This has led to the routine use of the anti-VEGF antibody bevacizumab in recurrent GBM, conveying substantial improvements in radiographic response, progression-free survival and quality of life. Despite these encouraging beneficial effects, patients inevitably develop resistance and frequently fail to demonstrate significantly better overall survival. Unlike chemotherapies, to which tumors exhibit resistance due to genetic mutation of drug targets, emerging evidence suggests that tumors bypass antiangiogenic therapy while VEGF signaling remains inhibited through a variety of mechanisms that are just beginning to be recognized. Because of the indirect nature of resistance to VEGF inhibitors there is promise that strategies combining angiogenesis inhibitors with drugs targeting such evasive resistance pathways will lead to more durable antiangiogenic efficacy and improved patient outcomes. Further identifying and understanding of evasive resistance mechanisms and their clinical importance in GBM relapse is therefore a timely and critical issue.

CNS Oncol. 2013 Jan;2(1):49-65.http://www.ncbi.nlm.nih.gov/pubmed/23750318

NOSC NL 2013;2(2) 41

In collaboration with the NOSC lead-faculty members in Mashhad, Dr. Anvarihas notably contributed to the so far conducted NOSC activities there. He has been a member of the NOSC founding panel and the moderator of the so far conducted scientific activities. He also functions as a member of NOSC steering committee across the country. Since last year, Dr. Anvari has invited distinguished oncologists - pathologist -immunologist and geneticist to form a CNS tumor study group in Mashhad. This study group has been working on defined brain tumor research projects in collaboration with the Oncology Research Center and related authorities in Mashhad University of Medical Sciences.

The rationale for the continuation of NOSCs scientific patient-oriented activities was agreed upon during this meeting. Everybody was in line with the pre-specified mission and vision of this scientific club. Attendees agreed that further steering board meetings should be conducted during which many detailed questions will be addressed. Exploring some central questions such as : Radio-diagnostic advances in CNS tumors; how this can optimize care?; Safe maximal resection of brain tumors and functional surgery set up; where? when? how?; Brain tumor tissue bank, ifs and buts!; Brain tumor collaborative registry (BTCR), how to make it a real success?; Priorities in forth coming provincial NOSC meetings?; Co-chair panel and speakers for the following NOSC sessions?; Newsletter, comments? NOSC case study periodical, how to boost contributions? NOSC membership?; International collaborations (International members/patrons?); International speakers board?; NOSC member, faculty and lead-faculty definition?; Brain tumor joint seminars (problem case discussions)? Where/when to hold such a thing? would line up NOSCs future strategies even clearer, and are expected to be the main constituent of the future steering board meetings.Cancer society has graciously accepted to host this session and even

further gatherings while re-emphasized that NOSC belongs to all contributing societies. Participants were delighted for this invitation and agreed to expect invitation to the following NOSC steering board meeting issued by the cancer society of Iran aiming to catalyze the steering boards planned activities.NOSC is to receive support from national scientific societies contributing to such a viable field; the Neuro-Oncology.

Disclosure: Conduction of the NOSCs steering board meeting was made possible through logistic supports from Behestan Darou PJS.

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NOSC NL 2013;2(2) 42

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

Neuro-Oncology Scientific ClubNewsletterVolume 2, Issue 2, July 2013

NOSC receives scientific support from the Medical Division of Behestan Darou PJS.

www.behestandarou.com