Ki-67: role in diagnosis, prognosis and follow-up after treatment of breast cancers.

AIM: To evaluate the literature data about diagnostic value, prognosis value and interest in follow-up of Ki-67 antibody after treatment for breast cancer. METHODS: We performed a literature search in pubmed using the keywords : Ki-67, anti-Ki-67, breast cancer, prognosis, proliferation, chemotherapy, hormone therapy. RESULTS: Ki-67 is routinely used as a static marker of proliferative activity and in follow-up-monitoring before and after treatment by chemotherapy and more recently hormonotherapy. Ki-67 was also used at a cut-off of 14% to differentiate between luminal A and B breast cancers. A high Ki-67 expression is probably related to a poorer prognosis but also a better response to neoadjuvant chemo and/or targeted therapy. More recently, genomic analysis is more reliable to classify the molecular breast cancer subtypes avoiding the possible cases of discordant Ki-67 rate. Ki-67 is also interesting in predicting histological response to neoadjuvant chemo and hormone therapy. CONCLUSION: Ki-67 evaluated by immunohistochemistry is important in routine in countries without bimolecular plateforms despite technical insufficiencies. When available, genomic grading is better to classify molecular subtypes and determine breast cancer prognosis in adjuvant and neoadjuvant setting.

Managing the Adverse Events Associated with Pembrolizumab and Lenvatinib Therapy in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months.

An Unusual Presentation of Choriocarcinoma in a Postmenopausal Woman: A case report.

Choriocarcinoma (CC) is a malignant neoplasm of the trophoblastic tissue, with a potential to metastasise to distant organs. Limited case of gestational CC develops after a long latent period. We report a 52-year-old postmenopausal woman who developed metastatic choriocarcinoma presumably of gestational origin, 8 years after the last pregnancy and 2 years after the last menstrual period. The patient was brought to the emergency room of a tertiary care centre in Muscat, Oman, in 2022 and was diagnosed with CC metastatic to the brain, spleen, lung and the kidney. The ß-human chorionic gonadotrophin level was found to be raised (1,292,867 mIU/mL). The International Federation of Gynecologic Oncology risk score was calculated to be 14 (very high risk). The patient was initially treated with whole-brain radiotherapy and splenic artery embolisation because of a hemoperitoneum. Afterwards the patient received systemic treatment using the standard EMA/CO regimen till complete serological remission.

Successful Treatment of a Case of Crescentic Glomerulonephritis in a Patient with Primary Peritoneal Carcinoma: A case report.

Crescentic glomerulonephritis has been associated with several solid tumour malignancies. Only a few cases of nephropathy have been reported in association with tubo-ovarian/peritoneal malignancies. We report a 55-year-old female patient who presented to a tertiary care centre, Muscat, Oman, in 2022. She developed combined immune complex-mediated glomerulonephritis and pauci-immune necrotising crescentic vasculitis simultaneously with the diagnosis of tubo-ovarian/peritoneal cancer. The baseline estimated glomerular filtration rate (eGFR) was 13 mL/min. The patient received two doses of rituximab and three doses of pulse corticosteroids, leading to significant improvement in renal function and the disappearance of her proteinuria. The eGFR improved to >60mL/min; her proteinuria gradually resolved after 10 weeks of treatment. She was then given a combination chemotherapy treatment for tubo-ovarian/peritoneal cancer leading to a normalisation of her CA-125 after three months of therapy.

Mucinous Carcinoma of Ovary in a 15-Year-Old Girl, A Rare Case Report and Literature Review.

Ovarian epithelial tumors are common in adults, and the median patient age at presentation is 55 years. In children, epithelial tumors are rare and mostly benign. Mucinous cystadenocarcinoma is reported in only 11 cases less than 15 years old. This report describes the case of a 15-year-old postmenarchal Omani girl with ovarian mucinous carcinoma. She was admitted with severe epigastric pain and abdomen distension. CT scan showed a huge cystic lesion arising from the left adnexa filling the entire abdominal and pelvic cavity. The patient underwent laparotomy with left ovarian cystectomy and omental biopsy which revealed a 35 x 30 cm left ovarian cyst filled with turbid straw color fluid. Histopathology was reported as mucinous carcinoma. The patient later underwent cytoreductive surgery with left salpingo-oophorectomy, omentectomy, appendicectomy, and lymph node dissection that were negative for malignancy or metastatic disease. During follow-up, she developed a lymphocele in the pelvic cavity that was drained. There were no other significant issues during follow-up, as well as no evidence of recurrence or metastasis. Epithelial tumors of the ovary are rare in young girls, with malignant tumors being exceedingly rare. Fertility-sparing surgery is adopted over radical surgery in these patients, even though the recurrence rates with this treatment protocol are high. All cases should be under follow-up to look for recurrence and timely management.

Predominance of Candida glabrata in candidemia among patients with solid tumor cancer in Oman: A retrospective study.

Objectives: Candida species frequently cause bloodstream infections; however, there is a lack of epidemiological studies on candidemia in Oman. Methods: To address this, we conducted a retrospective study at Sultan Qaboos Comprehensive Cancer and Research Center from October 2021 to October 2023. Results: Our study identified 27 episodes of candidemia among 26 patients with cancer, with an incidence of 4.9 per 1000 admissions. Non-albicans Candida (NAC) prevailed over C. albicans (70.37% vs 29.62%), with C. glabrata as the predominant NAC species (n = 10; 37%). The 30-day mortality rate was 40.7%, showing no significant difference between NAC and C. albicans but was notably higher in critically ill patients (P = 0.03). Conclusion: In Oman, NAC surpasses C. albicans as a causative pathogen for candidemia with a high mortality rate.

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.

Gemcitabine-Related Atrial Fibrillation: A Case Report and Review of the Literature.

INTRODUCTION: Gemcitabine is a commonly used antimetabolite that has been effective in a broad spec- trum of tumors so far. The main grade three and four known toxicity of this drug is myelosuppres- sion. Cardiac adverse events have been rarely reported and gemcitabine-induced Atrial-Fibrillation (AF) has been described in only five previous cases so far. Here we report the 6th case of gemc- itabine-related AF. CASE PRESENTATION: A 68-year-old man diagnosed with metastatic nasopharyngeal cancer was referred to our oncology department. He started first-line chemotherapy with gemcitabine and cisplatin. He presented poorly tolerated atrial fibrillation related to gemcitabine infusion that lasted for six days. The treatment was then withdrawn, and the patient received the best supportive care. CONCLUSION: We conclude that medical oncologists and cardiologists should be aware of such toxicities of gemc- itabine, especially in the elderly who seem to be at a higher risk of such adverse events and which may dictate discontinuation of the drug.

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.

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.

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.

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.

Urothelial bladder carcinoma in childhood: a case report.

We report an exceptional case of transitional cell carcinoma of the bladder in a 14-years old boy without personal nor family history who consulted for a total hematuria. Work-up showed a bladder lesion sized 5cm with histology of urothelial cancer. Treatment consisted of a transurethral surgery with carcinologic complete resection. Patient is alive, free of disease with a follow-up of 36 months.

Oxaliplatin-induced peripheral neuropathy risk factors and management in Tunisian population.

The most important limits of oxaliplatin treatment is its peripheral neurotoxicity. The aim of our study was to evaluate the oxaliplatin-induced peripheral neuropathy, its impact on treatment and its management. One hundred chemo-naive patients treated with oxaliplatin-based regimen in the medical oncology department of the military hospital of Tunis between 2012 and 2017 were recruited retrospectively. Evaluation of neuropathy was done according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE V4). Fifty-six patients were aged more than 60 years. The sex-ratio was 1.56. Twenty-seven patients were overweight, 17 were obese and 56 had a BMI inferior to 25 kg/m2. Two patients were consuming alcohol. Twenty-three patients had diabetes. Sixty-four patients developed chronic peripheral neuropathy because of oxaliplatin (grade 1-2 in 58 cases and grade 3 in 6 cases). Sex, BMI, diabetes and alcohol consumption were not associated with the development of peripheral neuropathy. No association was found between grades of neuropathy and sex, alcohol consumption and diabetes. The median cumulative dose of oxaliplatin that induced neuropathy was 432.4 mg/m2. The most prescribed treatment was gabapentin (81%) and carbamazepine (16.8%). The treatment was not sufficient to stop neuropathy in 82.6% of cases. Dose reduction was done in 64.2% of cases, treatment delay in 10.7% of cases and treatment interruption in 10.7% of cases. We didn't find any association between known risk factors and peripheral neuropathy. The cumulative dose is interesting to define or to predict the timing of neurotoxicity.

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.

Clival chordoma in a young male patient: a case report.

Chordoma is a rare malignant tumor of the spine. We report the case of a 26-year-old man who presented with facial paralysis and upper limbs paresthesia. Cerebral CT-scan and cerebro-spinal MRI revealed a 58mm locally advanced middle clival mass with deviation of median cerebral structures. Endoscopic biopsy concluded to a chondroid chordoma. Skeletal survey and thoraco-abdomino-pelvic CT-scan were normal. Treatment consisted in complete surgical removal of the tumor followed by adjuvant radiotherapy. The patient is alive free of disease with a follow up of 12 months.

Transformation of a prostatic adenocarcinoma into squamous cell carcinoma after luteinizing hormone-releasing hormone (LHRH) agonist and radiotherapy treatment.

Squamous cell carcinoma of the prostate is rare and represents 0.5% to 1% of prostatic carcinomas. Transformation of prostatic adenocarcinoma into squamous cell carcinoma after LH-RH agonist intake has been reported in only 8 cases in the literature. To our knowledge, our case is the second pure squamous cell carcinoma observed after hormonotherapy and radiotherapy. We reported a case of a patient with prostatic adenocarcinoma treated by radical prostatectomy followed by radiotherapy. Eleven years later, he had a vesical recurrence of prostatic adenocarcinoma. Our patient had an endoscopic resection followed by injections of Triptorelin. Six months later, he developed a local recurrence of a squamous cell carcinoma.