Trends in pediatric CNS tumors in Armenia: a multicenter retrospective study.

PURPOSE: Central nervous system (CNS) tumors are the most common solid malignancies in children worldwide, including in Armenia. The current study aims to analyze epidemiological data, treatment, and outcomes of children and young adults (≤25 years) with CNS tumors in Armenia during the last 26 years. METHODS: We collected data from pediatric and young adult patients treated in selected sites in Armenia from 1st January 1995 to 31st December 2020. Incidence by sex, age at diagnosis, time from first complaints to diagnosis, histopathology results, treatment strategies, complications, and overall survival (OS) rates were calculated. RESULTS: The multicenter data analysis revealed 149 patients with diagnosed primary CNS tumors over 26 years. Among them, 84 (56.4%) were male. The median age at diagnosis was 7 years (range, 3 months to 25 years), and the median time from the first complaints to diagnosis was 2 months (range, 1 week to 70 months). Medulloblastomas and other embryonal tumors (47), low-grade gliomas (32), and high-grade gliomas (22) were the most commonly diagnosed malignancies. Ependymomas, craniopharyngiomas, germ cell tumors, and other malignancies were observed in 22 patients. For 26 patients, no histopathological or radiological diagnosis was available. Follow-up information was available for 98 (65.8%) patients. The 5-year OS rate for the whole study group was 67.7%. CONCLUSION: Consistent with international data, embryonal tumors, and gliomas were the most commonly diagnosed CNS malignancies in Armenia. Multimodal treatment was often not available in Armenia during the study period, especially for early cases.

An Update to Hallmarks of Cancer.

In the last decade, there has been remarkable progress in research toward understanding and refining the hallmarks of cancer. In this review, we propose a new hallmark - "pro-survival autophagy." The importance of pro-survival autophagy is well established in tumorigenesis, as it is related to multiple steps in cancer progression and vital for some cancers. Autophagy is a potential anti-cancer therapeutic target. For this reason, autophagy is a good candidate as a new hallmark of cancer. We describe two enabling characteristics that play a major role in enabling cells to acquire the hallmarks of cancer - "tumor-promoting microenvironment and macroenvironment" and "cancer epigenetics, genome instability and mutation." We also discuss the recent updates, therapeutic and prognostic implications of the eight hallmarks of cancer described by Hanahan et al. in 2011. Understanding these hallmarks and enabling characteristics is key not only to developing new ways to treat cancer efficiently but also to exploring options to overcome cancer resistance to treatment.

Opsoclonus-Myoclonus-Associated Neuroblastoma With Bone Marrow Metastases: What Would Be the Best Treatment Option?

A 1.9-year-old girl was presented to the hospital with dancing eye movements, ataxia, and behavioral disorders. The MRI showed a retroperitoneal tumor (transversal size: 3.9 x 2.5 cm, craniocaudal size: 4.6 cm) extending from T12 to L3 vertebral bodies (Figure), which was suspicious for neuroblastoma. Afterwards, biopsy of the lesion and bone marrow was performed. The initial pathological evaluation (CD56+, PHOX2B+, NKX2-, Ki67 50%-55%, NSE+, CD99-) of the tumor and bone marrow confirmed the diagnosis of poorly differentiated, high-risk neuroblastoma.

Pediatric Locally Advanced Synovial Sarcoma: What Would Be the Best Treatment Option?

KEY POINTS • Synovial sarcomas are often mistreated with unplanned tumor resection. • Attention from specialists early in the course of SS can minimize the risk of recurrence, metastases, and the necessity for resurgery, all of which are increased with unplanned tumor resection. • Chemotherapy alone does not provide sufficient local control of the tumor. • Resurgery, in conjunction with radiotherapy and chemotherapy, is the best choice of management for this patient.

Incidence patterns and review of Hodgkin lymphoma in the Republic of Armenia.

Hodgkin lymphoma (HL) accounts for roughly 10% of all lymphomas and 0.6% of all malignant tumours analysed worldwide yearly. Data regarding HL in developing world are exceptionally constrained. The main objective of this research is to investigate the incidence patterns of HL within the Republic of Armenia and to portray disease distribution according to age and sex. There is a very strict evidence on the frequency of HL in Armenia. The results of our research find out that the frequency of HL in Armenia has not changed altogether over the past 15 years and is comparable to that detailed from the USA and Europe.

Availability of Essential Medicines for Pediatric Oncology in Armenia

Background: One of the main contributors in low survival rate in LMIC is the lack of availability of cancer medications for curative, supportive and palliative care. In many developing countries access to cytotoxic medicine is a major challenge. The information about the availability of essential medicines for pediatric cancer in the country is not known. The main objective of this study was to determine whether the medications used during the treatment of pediatric cancer are available in Armenia. Methods: In summer 2016 we conducted a survey in the 3 main pharmacies in Yerevan, which import pediatric cancer medications to Armenia to evaluate whether medications used during cancer treatment are officially registered and available in the country. In addition, the information on official registration was cross-checked with the Ministry of Health of the Republic of Armenia (MOH). Simultaneously, detailed information about the drugs, on type of produced drug company, doses and price intervals was confined from the price lists of the national drug importer companies. Results: The survey included 64 agents in three classes of medication: anti-neoplastics, anti-microbials, and drugs used in supportive care. All of these medications were included in the recent version of the WHO model list of essential medicines. From 30 anti-neoplastic medications on the essential medicines list 22 (73%) were officially registered in Armenia; from 19 anti-microbial drugs all were registered except caspofungin and from 15 supportive care agents 13 (87%) were registered. From registered anti-neoplastic drugs 18% and from antimicrobial drugs 33% were not available in the drug stores. Conclusion: This study showed that not all the drugs from the SIOP PODC Essential Medication list for pediatric oncology are officially registered and available in Armenia, and effective drug regulation focusing on the childhood cancer care medicine is needed for improving the situation in the country.

Younger age and previous exposure to radiation therapy are correlated with the severity of chemotherapy-induced thrombocytopenia.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a significant complication of cancer therapy. Data on the optimal management approaches of this morbidity in children and young adults are still limited. AIM: The aim of the study is to estimate the frequency and severity of CIT and associated clinically significant bleeding in children and young adults with solid tumours and haematologic malignancies. METHODS: For this retrospective, hospital-based study, children (0-18 y) and young adults (19-40 y) with different types of solid tumours and haematologic malignancies who received chemotherapy at the Muratsan Hospital Complex of Yerevan State Medical University were identified from the patients' database and included in the study (overall 122 patients). Thrombocytopenia was defined as a decrease of platelet count below <100 × 109/L. For assessing bleeding, WHO scale had been used. RESULTS: Overall, the whole group of patients received 430 chemotherapy cycles. During 131 (31.6%) chemotherapy cycles, patients developed CIT. The study revealed a statistically significant inversely proportional correlation between the age and the severity of CIT. Another important finding of the study was that the patients, who previously were exposed to radiation therapy, were more likely to develop CIT, than those who have not received radiation therapy (68% and 28.7%, p = 0.001). From 430 cycles of chemotherapy, 31 (7.2%) cycles reported to have bleeding events. CONCLUSION: Our study showed that clinically significant thrombocytopenia and bleeding are quite rare among children and young adults. Younger age and previous exposure to radiation therapy are positively correlated with the severity of thrombocytopenia. Larger studies are needed to investigate these findings.

Identifying barriers to treatment of childhood rhabdomyosarcoma in resource-limited settings: A literature review.

We performed a literature review to examine barriers for rhabdomyosarcoma treatment in low-resource settings, and identified 29 articles from 14 middle-income countries, with none from low-income countries. Notable findings included inconsistent use of local control modalities, lack of diagnostics in some settings, and high rate of abandonment specifically in low middle-income countries. Reported limitations included lack of surgical expertise and/or radiation therapy, advanced stage of disease, and absence of health insurance. Although very poor outcomes were prevalent in several settings, good outcomes were achievable in others when multidisciplinary therapy and financial coverage of medical care were made available.

Denosumab treatment for progressive skull base giant cell tumor of bone in a 14 year old female - a case report and literature review.

BACKGROUND: Giant cell tumor of bone (GCT) is a rare primary bone tumor, which can metastasize and undergo malignant transformation. The standard treatment of GCT is surgery. In patients with unresectable or metastatic disease, additional therapeutic options are available. These include blocking of the receptor activator of NF-kappa B ligand (RANKL) signaling pathway, which plays a role in the pathogenesis of GCT of bone, via the anti-RANKL monoclonal antibody denosumab. CASE PRESENTATION: Herein we report on a female teenager who presented in a very poor clinical condition (cachexia, diplopia, strabismus, dysphonia with palsy of cranial nerves V, VI, VIII, IX, X, XI and XII) due to progressive disease, after incomplete resection and adjuvant radiotherapy, of a GCT which affected the cervical spine (C1 and C2) as well as the skull base; and who had an impressive clinical response to denosumab therapy. To the best of our knowledge, this is the youngest patient ever reported with a skull base tumor treated with denosumab. CONCLUSION: In situations when surgery can be postponed and local aggressiveness of the tumor does not urge for acute surgical intervention, upfront use of denosumab in order to reduce the tumor size might be considered. Principally, the goal of denosumab therapy is to reduce tumor size as much as possible, with the ultimate goal to make local surgery (or as in our case re-surgery) amenable. However, improvement in quality of life, as demonstrated in our patient, is also an important aspect of such targeted therapies.