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Volume 2, Issue 2, July 2013

In this issue

NEWSLETTER

In this issue
• • • • • • • • • NOSC on its Way to Grow…….31 NOSC’s Steering Board Meeting Report………….32 NOSC’s Recently Published Articles……. 34 NOSC Case Study Periodical, Call for Papers….. 35 Neuro-Oncology Events Updates……. 36 Featured NOSC Contributors…3 7 The International Brain Tumor Awareness Week…….. 38 Highlights from ASCO 2013…. 39 Neuro-Oncology News Blast…41

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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 scientificprofessional 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”.

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

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NOSC’s 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. NOSC’s steering board’s central mission is to define its mid to long-term goals, strategies and tactics towards brain tumor patients’ better and extended lives.

The first NOSC’s 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.HashemiIranian 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.TabatabaeefarIranian Society of Radiation Oncology. For informed reasons some invitees including Dr. Ansari- Shiraz NOSC lead-faculty; Dr.AnvariMashhad NOSC lead-faculty; Dr. HaddadIranian 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.

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 patientcentered 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.

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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 NOSC’s organizing committee under Behestan Darou’s (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 NOSC’s 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.

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NOSC’s 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 MAHAK’s 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.

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NOSC Case Study Periodical, Call for Papers
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. Following the 3 published case studies contributed by some of the Iranian field experts in neurooncology, NOSC editorial office is in the process of publishing two other interesting brain tumor casestudies communicated by its members. This two short case study papers will be available to NOSC members quite soon. “NOSC case study periodical” continues to publish interesting brain tumor case-studies reported from joint neuro-oncology clinics in Iran. The main focus would be newly diagnosed highgrade glial brain tumors. You might have encountered with brain tumor cases for whom the effective management really needs an interdisciplinary approach. To get them published within NOSC CSP please contact the editorial desk. Our contact info can be found at the end of this newsletter. The publishing source for your communicated interesting clinical case scenarios will be the NOSC, which is now becoming a well-recognized selfoperated neuro-oncology experts’ forum in a national scope. 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 Periodical” papers.

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…………… Neuro-Oncology Events Update
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.

Leksell Gamma Knife Perfexion Course
19-23 Aug 2013 Cleveland Clinic Gamma Knife Center Cleveland 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, Neurootolaryngologists. Further info: http://my.clevelandclinic.org/neurological_institute/brain-tumor-neuro-oncology/for-medicalprofessionals.aspx

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Featured NOSC Contributors
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 Anvari’s 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. - Chairman of the Radiation Oncology Department, Imam Reza Hospital, MUMS2012 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- 2012 His 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.

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.

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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 - Fact Sheet # 2 - Fact Sheet # 3 -Fact Sheet #4 -Fact Sheet #5 - Fact Sheet #6 - Fact Sheet # 7 ” Brain Tumors“ “Why Me? –the Diagnosis“ “Questions to ask your Doctor“ “Telling Family and Friends about your brain tumor“ “Helpful Suggestions“ “What is a Seizure and How Does it Occur“ “Factors Contributing to Behavior and Personality Changes with the Brain Tumor “

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Highlights from

ASCO ’13
4 June 2013
The 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 (progressionfree 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 placebocontrolled 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 Administration’s (FDA) “sort of conditional” approval for bevacizumab and brain tumours in 2009. The “worry” revolves around the survival advantage as expressed by progressionfree 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 littlereported media release on 17 June it was stated that bevacizumab had been approved in Japan for newlydiagnosed 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/

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Here’s the link to all ASCO’s abstracts on CNS tumors
http://meetinglibrary.asco.org/abstractbysubcategory/2013%20ASCO%2 0Annual%20Meeting/153

The Stupp regimen preceded by early post-surgery temozolomide versus the Stupp regimen alone in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM).
J Clin Oncol 31, 2013 (suppl; abstr 2022)

ASCO
‘13

Background: In treatment of newly diagnosed GBM with the Stupp chemo-radiotherapy regimen, following by adjuvant chemotherapy, patients were treated with temozolomide (TMZ) & combined radiotherapy 4-5 weeks after surgery. In the interval between surgery and chemo-radiotherapy, it is not known whether additional TMZ treatment will improve efficacy or safety. This trial evaluated the safety and efficacy of the Stupp regimen + early post-surgery TMZ chemotherapy in the treatment of patients with newly diagnosed GBM. Methods: The trial was a multi-center, randomized open-label study. 99 newly diagnosed GBM patients were enrolled and randomly assigned to the Stupp regimen + early postsurgery 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 at 75mg/m2/day for 14 days. The primary endpoint of the study was the overall survival (OS). The secondary endpoints included the progression-free survival (PFS), objective tumor assessment and adverse 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 (logrank test, p = 0.021). There is no significantly difference in the median PFS between experiment group and control group (8.74 months, 95% CI: 6.41-14.85 months vs 10.38 months, 95% CI: 8.18-15.44 months, p = 0.695). No statistically significant difference was detected as regards to the objective tumor assessments. There is no significance in OS or PFS between MGMT positive and MGMT negative groups. TMZ treatment was well tolerated in the study. AE types and rates were generally similar between the two groups. There were 22 SAEs in this study, with only 1 SAE (lung infection) in Stupp regimen group was possibly drug-related. Conclusions: The addition of early post-surgery TMZ chemotherapy to the Stupp regimen for newly diagnosed GBM resulted in a statistically significant survival benefit with minimal additional toxicity. Clinical trial information: NCT00686725.

…………………………………….. and… Some other noteworthy abstracts from ASCO 2013!
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

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Neuro-Oncology News Blast
June 2013: Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role. Venous thromboembolism (VTE) may complicate the clinical course of glioblastoma multiforme (GBM). Circulating microparticles (MPs) have been associated with cancer-related VTE. Sixty-one consecutive patients with GBM undergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy were prospectively evaluated. MPs numbers according to cellular origin and the procoagulant activity of annexin V positive (AV+) MPs (MP-activity) were measured before surgery and then 1 week and 1, 4, and 7 months after surgery. Glial (GFAP+) and endothelial (CD62E+) derived MPs, AV+ and tissue factor-bearing (TF+) MPs were measured using flow cytometry. Baseline levels of GFAP+/TF-, TF+/GFAP-, and GFAP+/TF+ MPs were significantly higher in GBM patients than in healthy controls, and significantly increased at each time point after surgery; at 7 months, a further significant increase over the level found a week after surgery was only seen in the subtotally resected patients. The number AV+/CD62E- MPs increased in GBM patients and correlated with MP activity. TF+/GFAP- MPs numbers were significantly higher in 11 GBM patients who developed VTE than in those who did not (p 0.04). TF+/GFAP- MPs levels above the 90th percentile (calculated in GBM patients without VTE) were associated with a higher risk of VTE (RR 4.17, 95% CI 1.57-11.03). In conclusion, the numbers of glial-derived and/or TFbearing MPs were high in GBM patients both before and even more after the neoplasm was treated, especially in patients with subtotal resection likely according to disease progression. 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

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The rationale for the continuation of NOSC’s 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 NOSC’s 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 board’s planned activities. NOSC is to receive support from national scientific societies contributing to such a viable field; the Neuro-Oncology.

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

In collaboration with the NOSC lead-faculty members in Mashhad, Dr. Anvari has 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.

Neuro-Oncology Scientific Club Newsletter Volume 2, Issue 2, July 2013

NOSC’s Newsletter Editorial Desk
No.22, Sorayya Bldg, Pardis St. Mollasadra Ave. Tehran, Iran +982188774200 Ext. 1634

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

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