Clinical-Pathological Features and Treatment Modalities of Primary Brain Tumors in Tanzania—4 Years of Institutional Experience

Background: The profile of primary brain tumors and treatment modalities employed in Tanzania remains largely unknown. The study aimed to describe the baseline clinical-pathological profile and treatment modalities for primary brain tumors in adults treated at the Ocean Road Cancer Institute (ORCI) from 2017 to 2020. Materials and Methods: This was a retrospective study conducted at ORCI by reviewing 61 medical records of patients with primary brain tumors over the age of 15 from January 2017 to December 2020. A structured questionnaire was used to retrieve information on sociodemographic, clinical-pathological characteristics, and treatment modalities. The 2007 WHO classification system and the International Classification of Cancer Diseases (ICD-0-3) were used for classification and diagnosis. The X2 test and Fisher’s exact test were used to compare the proportions and an independent t-test was used to compare the means. A P-value less than 0.05 was deemed statistically significant. The Results: The mean age of the females was 41.8 years and the mean age of males was 42.9 years. Overall M: F ratio was 1:1.2. Meningioma was the only tumor that was more commonly found in women with M:F of 1:2.1. The most prevalent symptom was headache (57.4%). Glioblastoma (GBM) was the most common tumor among adults (38%), followed by astrocytomas (23%) and meningioma (18%). Approximately 91.8% of all tumors occurred in the supratentorial region. The Frontal lobe was the most common site (29.5%). Approximately 81.9% of patients received surgery. The gross tumor resection (GTR) rate was 26.2%, and the subtotal tumor resection (STR) rate was 55.7%. Roughly 18% of the tumors were inoperable. An estimated 80.3% of respondents received radiation therapy. The radiotherapy technique was 3DCRT in two-thirds of the patients and the rest received conventional 2D radiotherapy. The mean equivalent dose in the 2 Gy fractions (EQD2) was 43.9 Gy. Respondents with low-grade intracranial tumors were treated with a mean EQD2 of 47.3 Gy, while those with high-grade intracranial tumors were treated with a mean EQD2 of 44.3 Gy and the difference was statistically significant. Only half of the patients who received adjuvant radiotherapy received it concurrently with chemotherapy. Temozolomide was the most widely used cytotoxic medication. Conclusion: Mean age of the patients was 41 years old. Most tumors were in the supratentorial area and GBM was the most common tumor. Only meningioma was a bit more common amongst females. Overall, radiotherapy doses and the gross tumor resection rates were low. Concurrent chemotherapy with radiotherapy was given to a few patients.

Prevalence estimates for primary brain tumors in China： a multi-center cross-sectional study

Background Although the first leading cause of death in China was malignant neoplasms （mortality, 374.1 per 100 000 person-years）, the full impact of primary brain tumors （PBT） on the healthcare system is not completely described because there are a few well documented reports about the epidemiologic features of brain tumors. This study aimed to report a comprehensive assessment on the prevalence of PBT. Methods A multicenter cross-sectional study on brain tumor （MCSBT） in China was initiated in five regional centers： Daqing （northeast）, Puyang （north of China）, Shiyan （center of China）, Ma＇anshan （center of China） and Shanghai （southeast）. Prevalence rate was calculated by counting the number of people living with a PBT between October 1,2005 and September 30, 2006 and dividing by the total population of the five communities at January 1, 2006. Estimates of prevalence were expressed as percentages and grouped according to gender and to age in fifteen-year categories. Within these strata, the rates were estimated with 95% confidence intervals （C/） using the accurate calculation of CI for Poisson distribution. A chi-square test was used to compare the various frequencies with a 〈0.05. Age-standardized prevalence with the direct method was calculated with the ten-year age-specific prevalence and the age distribution of population prospects： the 2008 revision. Results We estimated that the overall prevalence of PBT was 24.56 per 100 000 （95% CI, 14.85 to 34.27）, and the overall prevalence of PBT in female population （30.57 per 100 000 and its 95% Cl ranged from 19.73 to 41.41） was higher than that in male population （18.84 per 100 000 and its 95% Cl ranged from 10.33 to 27.35）. However, the discrepancy between genders was not statistically significant because the 95% Cl overlapped. Of 272 cases of newly diagnosed PBT, the proportion of histological subtypes by age groups, gender was statistically different （X2=52.6510, P 〈0.0001）. More than half of all reported tumors （52.57%） were either gliomas or meningiomas. For the youngest （aged from 0-19） strata of the population, glioma appeared to occur more than other subtypes, accounting for 55.56% of all of cases. The majority of brain tumors presented in those aged from 20 to 59 years was pituitary adenomas （45.12%） and gliomas （31.10%）. Opposed to brain tumors in adults and teenage, gliomas only accounted for 22.22%. Meanwhile, the median ages at diagnosis of the patients with PBT were similar between males and females except for pituitary adenomas （male： 59 years old; female： 45 years old）. Conclusions Age standardized prevalence of PBT is 22.52 per 100 000 （95% CI, 13.22 to 31.82） for all populations, 17.64 per 100 000 （95% CI, 9.41 to 25.87） for men, and 27.94 per 100 000 （95% Cl, 17.58 to 38.30） for women. Age standardization to China＇s 2010 population yielded an estimated population of 304 954 cases with PBT. Our prevalence estimates provide a conservative basis on which to plan health care services and to develop programmatic strategies for surviving. Inthe future, it would be helpful to have long-term observed survival rates that would make the assumptions and the resulting imprecision in the current estimates unnecessary.

A Case of Fahr’s Disease with Epilepsy as the First Symptom in Infancy

Background: Fahr’s disease, also recognized as Idiopathic Basal Ganglia Calcification (IBGC) or Primary Familial Brain Calcification (PFBC), was first identified by the German neurologist Karl Theodor Fahr in 1930. This rare condition, which involves the calcification of the basal ganglia and presents significant treatment challenges, is most commonly diagnosed in middle-aged adults and is notably uncommon in children. Purpose: We report a case of a younger patient and review this disease as an aid to early detection and diagnosis of the disease. Case Introduction: In this report, we present a unique case of Fahr’s disease in a child, where epilepsy manifested as the initial symptom during infancy. In this report, we present a case of Fahr’s disease in a child who presented with epilepsy as the first symptom in infancy. The child had no imaging abnormalities at the onset of the seizure, and subsequent antiepileptic drugs were reduced and discontinued, and when the seizure recurred 3 years later, a perfect cranial CT revealed symmetrical calcifications in the brain, which gradually worsened, and subsequently the child was unable to take care of himself and had regression of his psychomotor development, and the family requested discharge from the hospital, and then the child died during the follow-up visit. Conclusion: The disease is currently associated with a number of disorders for which there is no specific treatment, and half of all patients currently have a well-defined gene, emphasizing more importantly the importance of genetic counseling for parents known to be at risk prior to conception.

The Pathology of Primary Familial Brain Calcification:Implications for Treatment

Primary familial brain calcification(PFBC)is an inherited neurodegenerative disorder mainly characterized by progressive calcium deposition bilaterally in the brain,accompanied by various symptoms,such as dystonia,ataxia,parkinsonism,dementia,depression,headaches,and epilepsy.Currently,the etiology of PFBC is largely unknown,and no specific prevention or treatment is available.During the past 10 years,six causative genes(SLC20A2,PDGFRB,PDGFB,XPR1,MYORG,and JAM2)have been identified in PFBC.In this review,considering mechanistic studies of these genes at the cellular level and in animals,we summarize the pathogenesis and potential preventive and therapeutic strategies for PFBC patients.Our systematic analysis suggests a classification for PFBC genetic etiology based on several characteristics,provides a summary of the known composition of brain calcification,and identifies some potential therapeutic targets for PFBC.

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Local infiltration and distal dissemination of tumor cells hamper efficacy of current treatments against central nervous system(CNS)tumors and greatly influence mortality and therapy-induced long-term morbidity in survivors.A number of in vitro and ex vivo assay systems have been established to better understand the infiltration and metastatic processes,to search for molecules that specifically block tumor cell infiltration and metastatic dissemination and to pre-clinically evaluate their efficaciousness.These systems allow analytical testing of tumor cell viability and motile and invasive capabilities in simplified and well-controlled environments.However,the urgent need for novel anti-metastatic therapies has provided an incentive for the further development of not only classical in vitro methods but also of novel,physiologically more relevant assay systems including organotypic brain slice culture.In this review,using publicly available peer-reviewed primary research and review articles,we provide an overview of a selection of in vitro and ex vivo techniques widely used to study growth and dissemination of primary metastatic brain tumors.Furthermore,we discuss how our steadily increasing knowledge of tumor biology and the tumor microenvironment could be integrated to improve current research methods for metastatic brain tumors.We believe that such rationally improved methods will ultimately increase our understanding of the biology of brain tumors and facilitate the development of more efficacious anti-metastatic treatments.

Mechanisms of PiT2-loop7 Missense Mutations Induced Pi Dyshomeostasis

PiT2 is an inorganic phosphate(Pi)transporter whose mutations are linked to primary familial brain calcification(PFBC).PiT2 mainly consists of two ProDom(PD)domains and a large intracellular loop region(loop7).The PD domains are crucial for the Pi transport,but the role of PiT2-loop7 remains unclear.In PFBC patients,mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion.To date,six missense mutations have been identified in PiT2-loop7;however,the mechanisms by which these mutations cause PFBC are poorly understood.Here,we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2.Furthermore,we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase(AMPK)-or protein kinase B(AKT)-mediated PiT2 phosphorylation.In contrast,the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities.These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2.This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.