Uncovering the clinical relevance of unclassified variants in DNA repair genes: a focus on BRCA negative Tunisian cancer families.

Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families. Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed. Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity. Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries.

Genetic testing for hereditary cancer syndromes in Tunisian patients: Impact on health system.

INTRODUCTION: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings.

CDH1 Germline Variants in a Tunisian Cohort with Hereditary Diffuse Gastric Carcinoma.

Mutational screening of the CDH1 gene is a standard treatment for patients who fulfill Hereditary Diffuse Gastric Cancer (HDGC) testing criteria. In this framework, the classification of variants found in this gene is a crucial step for the clinical management of patients at high risk for HDGC. The aim of our study was to identify CDH1 as well as CTNNA1 mutational profiles predisposing to HDGC in Tunisia. Thirty-four cases were included for this purpose. We performed Sanger sequencing for the entire coding region of both genes and MLPA (Multiplex Ligation Probe Amplification) assays to investigate large rearrangements of the CDH1 gene. As a result, three cases, all with the HDGC inclusion criteria (8.82% of the entire cohort), carried pathogenic and likely pathogenic variants of the CDH1 gene. These variants involve a novel splicing alteration, a missense c.2281G > A detected by Sanger sequencing, and a large rearrangement detected by MLPA. No pathogenic CTNNA1 variants were found. The large rearrangement is clearly pathogenic, implicating a large deletion of two exons. The novel splicing variant creates a cryptic site. The missense variant is a VUS (Variant with Uncertain Significance). With ACMG (American College of Medical Genetics and Genomics) classification and the evidence available, we thus suggest a revision of its status to likely pathogenic. Further functional studies or cosegregation analysis should be performed to confirm its pathogenicity. In addition, molecular exploration will be needed to understand the etiology of the other CDH1- and CTNNA1-negative cases fulfilling the HDGC inclusion criteria.

Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers.

BACKGROUND: Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1/2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations. METHODS: A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated. RESULTS: In the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2, of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1_c.915T>A; BRCA2_c.-227-?_7805+? and BRCA2_c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations. CONCLUSION: Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases.

Identification of BRCA2 Cis Double Heterozygous Breast Cancer Cases Using Whole Exome Sequencing: Phenotypic Expression and Impact on Personalized Oncology.

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity (Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors.

Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia.

Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.

Toxicity profile of taxanes in Tunisian cancer patients: A retrospective study of 90 cases.

INTRODUCTION: Taxanes are widely used in medical oncology. The aim of our study was to report and analyze the toxicity features of these drugs in Tunisian patients and to determine their impact on treatment response. METHODS: Our retrospective study concerned 90 patients treated by taxanes in a medical oncology unit, from January 2014 to January 2017. We collected their epidemiologic and anatomo-clinical data and we detailed toxicity features including types grades and impact on tumor response. RESULTS: Median age was 46 years. 80% of patients had breast cancer. Tumors were metastatic in 23.3% of cases. Nail toxicity was observed in 100% of patients. Grade I-II digestive toxicity was observed in 54.4% of cases. Hematological toxicity was noted in 42.2% of patients and it reached grade III-IV in five patients. Neurological toxicity occurred in 31% of patients and was grade III-IV in 6 cases. Alopecia was observed in 60% of patients. Fatigue was noted in 57.8% of patients. Myalgia was observed in 42.2% of patients. Toxicity did not affect the response to treatment. CONCLUSION: The taxanes' toxicity profile in Tunisian patients is characterized by more frequent digestive and nail toxicities and less frequent hematological toxicities, dose reduction and treatment delays than other populations.

An unusual and severe case of paclitaxel-induced hand-foot syndrome.

Although paclitaxel is known to cause mild skin toxicity, it may induce severe HFS requiring drug withdrawal. Patients with high disease burden might receive prolonged paclitaxel chemotherapy. Hence, a grade 2 toxicity would better indicate withdrawal of paclitaxel instead of suspension and rechallenge, to prevent such severe HFS requiring long-time recovery.

The Predictive Value of 2D Myocardial Strain for Epirubicin-Induced Cardiotoxicity.

INTRODUCTION: Although epirubicin has significantly improved outcome in breast cancer (BC) patients, it is responsible for myocardial dysfunction that affects patients' quality of life. The use of 2D global longitudinal strain (GLS) has been reported to detect early myocardial dysfunction. The aim of this study was to evaluate how GLS changes can predict cardiotoxicity. METHODS: We conducted a prospective study from March 2018 to March 2020 on 66 patients with no cardiovascular risk factors, who presented with BC and received epirubicin. We measured left ventricular ejection fraction (LVEF) and GLS before chemotherapy, at three months (T3), and at 12 months (T12) from the last epirubicin infusion. Chemotherapy-Related-Cardiac-Dysfunction (CTRCD) was defined as a decrease of 10% in LVEF to a value below 53% according to ASE and EACI 2014 expert consensus. RESULTS: The mean age at diagnosis was 47 ± 9 years old. At baseline, median LVEF was 70% and median GLS was -21%. Shortly after chemotherapy completion, two patients presented with symptomatic heart failure while asymptomatic CTRCD was revealed in three other patients at T12. Three months after the last epirubicin infusion, median LVEF was 65%, median GLS was -19%, and median GLS variation was 5%. However, in patients who presented with subsequent CTRCD, median GLS at T3 was -16% and median GLS variation was 19% (p=0.002 and p < 0.001, respectively, when compared to patients who did not develop cardiotoxicity). Persistent GLS decrease at T3 was an independent predictor of CTRCD at T12. Age and left-sided thoracic irradiation did not increase the risk of cardiotoxicity in our study while the cumulative dose of epirubicin significantly affected cardiologic findings (p=0.001). CONCLUSION: This was the first North African study that assesses the value of measuring GLS to early detect cardiotoxicity. Patients whose GLS remained decreased after 3 months from anthracyclines-base chemotherapy had an increased risk for developing subsequent CTRCD. Further studies with larger sample size are warranted to identify the best cardioprotective molecules to be initiated in these patients before LVEF declines.

Identification of Novel BRCA1 and RAD50 Mutations Associated With Breast Cancer Predisposition in Tunisian Patients.

BACKGROUND: Deleterious mutations on BRCA1/2 genes are known to confer high risk of developing breast and ovarian cancers. The identification of these mutations not only helped in selecting high risk individuals that need appropriate prevention approaches but also led to the development of the PARP-inhibitors targeted therapy. This study aims to assess the prevalence of the most frequent BRCA1 mutation in Tunisia, c.211dupA, and provide evidence of its common origin as well as its clinicopathological characteristics. We also aimed to identify additional actionable variants using classical and next generation sequencing technologies (NGS) which would allow to implement cost-effective genetic testing in limited resource countries. PATIENTS AND METHODS: Using sanger sequencing, 112 breast cancer families were screened for c.211dupA. A set of patients that do not carry this mutation were investigated using NGS. Haplotype analysis was performed to assess the founder effect and to estimate the age of this mutation. Correlations between genetic and clinical data were also performed. RESULTS: The c.211dupA mutation was identified in 8 carriers and a novel private BRCA1 mutation, c.2418dupA, was identified in one carrier. Both mutations are likely specific to North-Eastern Tunisia. Haplotype analysis supported the founder effect of c.211dupA and showed its recent origin. Phenotype-genotype correlation showed that both BRCA1 mutations seem to be associated with a severe phenotype. Whole Exome Sequencing (WES) analysis of a BRCA negative family revealed a Variant of Unknown Significance, c.3647C > G on RAD50. Molecular modeling showed that this variant could be classified as deleterious as it is responsible for destabilizing the RAD50 protein structure. Variant prioritization and pathway analysis of the WES data showed additional interesting candidate genes including MITF and ANKS6. CONCLUSION: We recommend the prioritization of BRCA1-c.211dupA screening in high risk breast cancer families originating from the North-East of Tunisia. We also highlighted the importance of NGS in detecting novel mutations, such as RAD50-c.3647C > G. In addition, we strongly recommend using data from different ethnic groups to review the pathogenicity of this variant and reconsider its classification in ClinVar.

[Impact of early lymphopenia on the risk of febrile neutropenia and hematological toxicity]. / Impact de la lymphopénie précoce sur la survenue de neutropenia fébrile et de toxicité hématologique.

BACKGROUND: Hematologic toxicity is a severe complication of chemotherapy. The objective of our study is to evaluate the impact of early lymphopenia on the risk of occurrence of febrile neutropenia and hematological toxicity after aggressive chemotherapy for Hodgkin lymphoma or high grade non-Hodgkin lymphoma. METHODS: This prospective study involved 42 patients who received 193 cycles of chemotherapy in 2009. We assessed the impact of lymphopenia on day 1 and 8 on the risk of occurrence of febrile neutropenia. We also investigated the relation between the occurrence of hematologic toxicity after the first cycle and the subsequent cycles. RESULTS: Febrile neutropenia was observed in 25% of cycles. Grade 3/4 hematologic toxicity occurred in 63% of cycles. Growth factors were used in 79% of cycles. Lymphopenia ≤ 700/mm3 on day1 and 8 was noted in 21% and 65% of cycles. If the lymphocyte count was ≤700/mm3 on day1, the risk of febrile neutropenia was significantly higher (p=0.042) and the mean duration of antibiotic therapy longer (p = 0.013). Lymphopenia ≤700/mm3 on day 8 was associated with a greater risk of febrile neutropenia in univariate analysis (OR=2.4; p=0.02). Moreover analyzes showed that this factor was significantly associated with increase in hematologic toxicity (p=0.02), duration of neutropenia (p=0.001) and duration of antibiotics (p=0.05). Hematologic toxicity during the first cycle was predictive of its occurrence in subsequent cycles of chemotherapy (p=0.028). CONCLUSION: Our results confirmed the impact of early lymphopenia on the occurrence of febrile neutropenia and hematologic toxicity after aggressive chemotherapy for Hodgkin lymphoma or high grade non Hodgkin lymphoma.

[Metastatic non-small cell lung cancer: a Tunisian retrospective study about 100 cases]. / Cancers Broncho-pulmonaires non à petites cellules métastatiques : Etude tunisienne retrospective à propos de 100 cas.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common histologic form, leading causes of cancer death among masculine population. Half of CNPC was metastatic at diagnosis. AIM: To report the epidemiologic, anatomoclinic profile, therapeutic protocols and results of a retrospective study of non-small cell lung cancer (NSCLC) initially metastatic. METHODS: our retrospective study include patients with NSCLC histologically confirmed with inaugural metastasis collected from January 1999 to december 2012. We had analysed epidemiologic, anatomopathologic data (TNM 2009), therapeutic protocols and results in term of overall survival, median survival and event free survival. RESULTS: 100 case of NSCLC have been collected, mea nage was 57 years (22 to 81) and sex -ratio was 4,6. The majority of cases (74%) had a good performance statut (PS ≤ 2). Pathologic analysis leads to 81 cases of adenocarcinoma (ADK), 16 epidermoid carcinoma. 34% was stager T4 and 31% N2. Metastasis was located to bone in 36 cases, pleural in 26 cases, controlateral lung 26 cases, adrenal gland 17 cases and brain in 13 cases. 82% of patients underwent polychemotherapy as first line of treatment based on regimens conteined platine with mean number of 4 cycles. We have observed 4% of complete response, 61 of partial response, 20% of stabilisation, and 15% of progression. A palliatif radiotherapy of bone or brain metastasis was performed in 38 % of cases. With a median follow-up of 71 months (12 to 130 months), mean survival was 11 months; overall survival (Kaplan-Meier) at 1, 3 and 5 years was respectively 44, 13 and 0 %. CONCLUSION: Despite therapeutic progress in management of NSCLC, the prognosis of metastatic forms still reserved with a poor mean survival reported in litterature (12 years) valideted in our study. This push us to improve research mainly since advent of targeted therapy wich still a promising way in the management of these tumors.

Exocrine Pancreatic carcinoma in Tunisia: A retrospective study about 158 cases.

BACKGROUND: Exocrine pancreatic carcinoma (EPC) occurs in the majority of cases with early locoregional spread and distant metastasis at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provide only modest benefit to patients with EPC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies with a crucial therapeutic role in this cancer setting. OBJECTIVE: Our aim is to study the epidemiological, clinicopathological characteristics, treatment modality and clinical outcome of pancreatic adenocarcinoma in Tunisian patients treated in the department of medical oncology Abderrahmane Mami Ariana. METHODS: This retrospective study concerned patients with exocrine pancreatic carcinoma treated between 2009 and 2012. We analysed the following data: Anamnesis, age, sex, delay to diagnosis(DD), symptoms, clinical exam, performance status, stage, therapeutic protocol and results. RESULTS: We collected 158 patients (113 males/45 females, SR 2.5) with a median age of 64 years (20-93). The median DD was 2 months (1-12). Abdominal pain, jaundice and weight loss were the most frequent symptoms, 88.6%, 43% and 55.1% of cases respectively. Performance status was < 2 in 56.9% (90 pts). Seric CA19-9 was increased in 86.6% of cases. Tumor was at stage III in 24.7% and stage IV in 58.2%. Surgery was done in 24.7% of cases (39pts), curative in 21 patients. Neoadjuvant chemotherapy(NACT) was administrated to 10.8% of patients, adjuvant to 13.9% (22 pts) and palliative chemotherapy(PCT) concerned 58.8% of patients. We used weekly Gemcitabine, Gemcitabine-CDDP, Gemcitabine-Oxaliplatine and LV5-FU2-CDDP in palliative setting respectively in 20%, 31.1%, 2.2 and 36.7% of cases. Median survival was 6 months (2-60) and the 1year overall survival at 38.8%. CONCLUSION: EPC remains a rare cancer in Tunisia. The prognosis is still grim worldwide and so does in our country. In this retrospective serie, we noted the predominance of locally advanced and metastatic cases with a long delay to diagnosis. Awareness campaigns have to be programmed to improve early diagnosis in EPC and improve outcomes.

Perioperative chemotherapy in locally advanced gastric cancer. A retrospective study about 25 cases.

BACKGROUND: Perioperative chemotherapy containing 5FU, Cisplatin ± Docetaxel is one of the most active regimens in advanced gastric cancer. OBJECTIVE: To report epidemiological and clinical profile and therapeutic results of perioperative chemotherapy in locally advanced gastric cancer in Tunisia. METHODS: Our retrospective study concerned patients with histologically confirmed advanced gastric cancer treated at the institute Salah Azaiez of Tunis. They received 2-3 cycles / 3 weeks of neoadjuvant chemotherapy based on FP (5FU and Cisplatin) or TPF (Docetaxel-Cisplatin-5FU). RESULTS: From 2010 to 2012, 25 patients with a median age of 60 years and 7.3 sex-ratio received neoadjuvant chemotherapy. Protocols used were TFP in 20 and FP in 5 patients, 17 patients receiving more than 2 cycles. Side effects were represented by mucositis grade 3 in 2 patients, neutropenia grade ¾ in 3 patients and renal failure in 5 patients. After neoadjuvant chemotherapy, we observed 40% of partial response and 20% of stable disease. Six patients (24%) underwent surgery, curative in 4 (R0 in 3 cases) by total gastrectomy and D2 lymphadenectomy and palliative in 2 cases due to peritoneal carcinomatosis. With a median follow up of 16 months, median overall survival was 16 months (2-21 months). CONCLUSION: Probably due to the very bulky and advanced stages of our gastric cancer cases, neoadjuvant chemotherapy using FP±T showed no benefit in the treatment of locally advanced gastric cancer in Tunisian patients.

Glioblastoma in Tunisia: A retrospective study about 41 cases.

BACKGROUND: Glioblastoma (GB) is the most common and lethal primary brain tumor in adults representing 25% of primary brain tumors in adults. The objective of our study was to report the epidemiologic, clinical and therapeutic features of GB in Tunisia. METHODS: Our retrospective study included 41 patients with histologically confirmed GB treated between 2006 and 2012 at the medical oncology departments of Abderrahmane Mami hospital in Ariana and the military hospital in Tunis. RESULTS: Median age was 54 years (13 to 72 years) and sex-ratio was 2.3. Karnofsky performance status (KPS) was <70% in 31.7% of cases, while Recursive partitioning analysis radiation therapy oncology group (RTOG-RPA) classification was III in 11 (26.8%), IV in 19 (46.3%), V in 10 (24.3%) and VI in 1 (2.4%) cases. Complete resection (CR) was achieved in 29 patients (70.7%), partial resection (PR) or tumor debulking in 5 patients (12.2%) and biopsy alone (BA) in 7 patients (17.1%). All patients received brain radiotherapy (RT) at a dose of 60 Gy combined with concurrent temozolomide (TMZ). Nineteen patients (46.3%) received adjuvant TMZ, 8 of them completed 6 cycles. Median overall survival (OS) was 12 months (2 to 56 months). Six, 12, 18 and 24-months OS rates were 84.6%, 57.6%, 35.4% and 20.7%, OS being correlated to age, KPS, RPA and quality of resection. CONCLUSION: Our retrospective study is the first African GB series. Despite it included predominantly poor prognosis patients with impaired neurocognitive function and adjuvant treatment discontinuation, our median OS was comparable to Stupp.