Acute renal failure during cisplatin-based chemotherapy: A prospective monocentric study.

INTRODUCTION: Cisplatin is a widely used antineoplastic in the treatment of various types of solid cancers. The objectives of our study were to evaluate the prevalence of acute renal failure (ARF) during cisplatin-based chemotherapy and to determine the factors correlated with renal toxicity. METHODS: This is a prospective study that was conducted over a period of 6 months. We included patients followed for histologically confirmed solid cancer and treated with cisplatin-based chemotherapy. Assessment of renal function was made by calculating renal creatinine clearance before starting cisplatin, before every cycle, at 3 months and at 6 months. RESULTS: Forty patients were included. The median age was 54 years (31-71 years). The mean cumulative dose received was 286 mg/m² (100-560 mg/m²). Twelve patients (30%) developed ARF which was grade 1 in 83% of cases. Cisplatin ARF was observed after a mean cumulative dose of 208 mg/m². Digestive toxicity (67%) and obstruction of the excretory tracts of tumoral origin (8%) were aggravating factors. Cisplatin cycle number >3 (p = 0.04) and dose ≥330 mg/m2 (p = 0.04) were the factors associated with cisplatin renal toxicity. CONCLUSION: This study concluded that ARF is dose-dependent with the predominance of grade 1 toxicity. A cumulative dose exceeding 330 mg/m2 was correlated with an increased risk of occurrence of ARF.

Milano Policlinico ONCOVID modified Score for risk evaluation in oncology during the COVID-19 pandemic: a prospective monocentric study.

PURPOSE: Due to their immunosuppressed status, patients with cancer have been reported to be at increased risk of COVID-19 infection. We aimed to assess the prevalence of COVID-19 in patients with cancer and to identify its risk factors. METHODS: A prospective study was conducted at the Department of Medical oncology of Sfax from November 2020 to February 2021. We analyzed data of 226 patients treated for solid cancer. We used the Milano Policlinico ONCOVID modified Score to quantify the risk of infection in patients with cancer. RESULTS: Patients aged less than 70 years represented 85%. The most common primary tumors were breast cancer (37%) and colorectal cancer (22%). Comorbidities were observed in 39% of cases. Among 226 patients with cancer, 19 patients (8.4%) had COVID-19 disease. In 42% of cases, patients were under chemotherapy and 63% of them have a metastatic disease. Fifteen patients (79%) were symptomatic. A severe form of COVID-19 requiring hospitalization was seen in 4 patients (21%). Of 19 patients who tested positive for COVID-19, 47% had an intermediate and high risk of infection. COVID-19 infection was correlated with intermediate or high risk (p = 0.018), age < 70 years (p = 0.035), and chemotherapy treatment (p = 0.032). In multivariable analysis, only the intermediate or high risk were correlated with COVID-19 infection in cancer patient (p = 0.025). CONCLUSION: This study concluded that using the Milano Policlinico ONCOVID modified Score is very helpful for clinicians to identify vulnerable patients and to make the appropriate decision in the management of cancer patients.

Discordance in receptor status between primary and metastatic breast cancer and overall survival: A single-center analysis.

BACKGROUND: The tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival. MATERIALS AND METHODS: It was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis. RESULTS: Our study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors. CONCLUSION: This study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.

Novel and recurrent BRCA1/BRCA2 germline mutations in patients with breast/ovarian cancer: a series from the south of Tunisia.

BACKGROUND: The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. METHODS: We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC. RESULTS: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41-50 years, BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively). CONCLUSIONS: The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.

An uncommon breast metastasis of mediastinal neuroblastoma within a child: A case report.

A 13-year-old girl presented with dull lumbar pain and recent paraplegia. Clinical examination found a breast mass associated with an axillary adenopathy. Imaging revealed a large mass in the posterior mediastinum with spinal cord compression. Histological analysis confirmed the diagnosis of neuroblastoma with mammary metastases. To the best of our knowledge, breast metastasis is being reported for the first time in a mediastinal neuroblastoma.

Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients.

Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1 and BRCA2 account for 10% of all MBC cases suggesting that other genetic factors are involved. The aim of the present study is to screen whole BRCA1 and BRCA2 exons using the Ampliseq BRCA panel in Tunisian MBC patients with family history. Furthermore, we performed exome sequencing using the TruSight One sequencing panel on an early onset BRCA negative patient. We showed that among the 6 MBC patients, only one (MBC-F1) harbored a novel frameshift mutation in exon 2 of the BRCA2 gene (c.17-20delAAGA, p.Lys6Xfs) resulting in a short BRCA2 protein of only 6 amino-acids. We selected 9 rare variants after applying several filter steps on the exome sequencing data. Among these variants, and based on their role in breast carcinogenesis, we retained 6 candidate genes (MSH5, DCC, ERBB3, NOTCH3, DIAPH1, and DNAH11). Further studies are needed to confirm the association of the selected genes with family MBC.

Tuberculosis and non-pulmonary malignancies : study of ten cases.

INTRODUCTION: Tuberculosis (TBC) is a major public health problem with high mortality especially in developing countries. It is associated with a higher risk of developing pulmonary and non-pulmonary malignancies including solid and hematologic cancers. Association between TBC and nonpulmonary malignancies is rarely described in the literature. AIM: To describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients treated for cancer and TBC. METHODS: This is a retrospective study conducted over a period of 19 years (between 1993 and 2012), including 10 patients followed up for cancer and tuberculosis at the department of oncology and the department of infectious disease, CHU Habib Bourguiba Hospital and CHU HediChaker, Sfax, Tunisia. RESULTS: The average age of patients was 55 years old. The sex ratio was 1. The different locations of cancer were represented by the breast (4 cases), the nasopharynx (1 case), the colon (1 case), the kidney (1 case) the gum (1 case), the endometrium (1 case) and the blood (1 case).TBC and cancer were synchronous in 5 cases. Concerning the metachronous presentation that interested 5 patients, the average time betweenthe onset of TBC after cancer diagnosis was 3.5 years. Three of these patients were treated by chemotherapy with radiation therapy. TBClocalization was nodal in 6 cases, spinal one case, nasopharyngeal in one case, peritoneal in one case and urogenital in one case. The diagnosisof TBC was made incidentally in two cases during axillary lymph node dissection. The therapeutic management of cancer was based on surgery,chemotherapy and / or radiotherapy. All patients received anti TBC treatment for at least six months. Surgery was indicated in one case(laminectomy). A complete remission of cancer was observed in 9 patients. Concerning TBC, recovery was observed in 8 patients, 1 patient hada spinal recurrence and 1 patient is being treated. CONCLUSION: Chronic inflammation during TBC can lead to cancer development. The etiopathogenesis of this association is still imperfectly known. Association between TBC and non-pulmonary cancer, although rare, should be always kept in mind in order to handle in time these two diseases in order provide the best chances of recovery for patients.

Cardiac metastases: 4 cases report.

Cardiac metastases are rare. They are found in one to 10% of autopsies of patients withmalignant neoplasm. Adenocarcinoma represents the most common histologicaltype. The most common neoplasms that metastasize to the heart are lung andbreast cancers, melanoma, mesothelioma and lymphoma. However, Cardiacinvolvement is unusual in Hepatic, cutaneous and gastric cancer. We reportedthese three primary localizations in our cases.

[Adjuvant chemotherapy in colon cancer. About 119 cases]. / Chimiothérapie adjuvante dans les cancers coliques. A propos de 119 cas.

BACKGROUND: colon cancer is a public health problem worldwide and in Tunisia. The prognosis of patients with unresectable colorectal cancer varies according to the stage. The indication for adjuvant chemotherapy is well established in the colon cancer stage III, while it remains a matter of controversy for stage II. The aim of this work is to identify the epidemiological and anatomoclinical assess therapeutic outcomes in terms of overall survival of patients with high-risk stage II and stage III colon cancer treated with surgery and adjuvant chemotherapy. METHODS: DS: It's a retrospective study based on 119 patients with colon adenocarcinoma from 1996 to 2010. This patients suffering from colon cancer classified stage II and III having them all radical surgery and adjuvant chemotherapy. RESULTS: The average age of our patients was 53 years. The surgery was performed in an emergency situation in 53 patients (44%). Stages II and III, respectively, were observed in 47% and 53% of cases. Three regimens of chemotherapy were used: protocol FUFOL (50%), followed by FOLFOX (34%) and the protocol LV5FU2 (16%). Overall survival of patients all stages combined was 73.4% at 5 years. Stage III of the TNM classification (p = 0.03) and the number of cycles of chemotherapy <6 (p=0.02) were a negative prognostic factors influencing overall survival. Patients stage III treated with FOLFOX chemotherapy type had a better survival than those treated with chemotherapy type LV5FU2 or FUFOL with a significant difference (p= 0.05). CONCLUSION: Our results are consistent with those in the literature. The prognosis of colon cancer is improving thanks to recent advances that have enabled the integration of new cytogenetic factors in the therapeutic decision.

[Chemotherapy-induced febrile neutropenia: About 186 episodes. Clinical, microbiological and therapeutic characteristics]. / Les neutropénies fébriles chimio-induites: A propos de 186 épisodes Aspects épidémiologiques, diagnostiques et thérapeutiques.

BACKGROUND: One of the major side effects of anti-proliferative treatment is their medullar toxicity. This toxicity is particularly important in neutrophils and leads to a neutropenia. Fever during these episodes of neutropenia is a frequent complication but remains of indeterminate origin in 60% of cases. It's a medical emergency because of rapid evolution and a significant increase in mortality up to 10%. Thus, these episodes should be prevented and treated in priority with un empiric and large spectrum antibiotherapy, taking into account the bacterial ecology of each hospital. AIM: The aim of this study was to determinate the clinical, therapeutic and evolutive characteristics of febrile neutropenia (FN). METHODS: This retrospective study concerned 186 episodes of FN in 136 patients treated for solid tumors and lymphoma in the department of medical oncology of Sfax from january 2006 to December 2010. RESULTS: Mean age was 40 years (1 to 81) and sex ratio at 0.97. They were trated mainly solid tumors in 86.02%. Median time to onset of FN was 11 days and the mean duration of neutropenia was 5 days. 24.2% had a neutrophil count (ANC) <100 / mm3. Fever was clinically documented in 33.87%. Patients have mainly ORL clinical manifestations (38.46%) and specially mucositis (50%). Only 17.2% of cases were microbiologically documented and a bacteria was isolated in 76.46% of them in blood cultures, Gram-negative bacilli (GNB) accounted for the majority of organisms isolated in different samples in 66.66% of cases. Enterobacteriaceae were the most frequent dominated by Klebsiella spp, followed by Escherichia coli. Pseudomonas aeruginosa ranked second after the Enterobacteriaceae (21.21%). The Gram-positive cocci (GPC) were found in 24.24% mainly Staphylococcus aureus. The first line of empirical antibiotic therapy was associated in 88.7% of ceftazidime and amikacin or a fluoroquinolone that has to have an efficiency of 72.12%. The rate of death due to infection in our series was 9.14%. CONCLUSION: Our results are consistent with data in the literature concerning the short duration of neutropenia, causing fever and mortality, but our bacterial epidemiology is different from the current literature, where there is a predominance of CGP unlike our predominantly the BGN. And prescribing empiric antibiotic therapy must take into account the epidemiological and ecological particularities of each country, each hospital or each department.

[Prognostic factors in metastatic colorectal cancer in Tunisia: A retrospective study of 130 patients]. / Facteurs pronostiques des cancers colorectaux métastatiues (CCRM) en Tunisie. Etude retrospective à propos de 130 patients.

BACKGROUND: The survival of patients with a metastatic colon cancer has improved with palliative chemotherapy, targeted therapies and surgery. Several prognostic factors influencing the survival of these patients were identified in the literature represented mainly by clinical factors: general condition, number and site of metastases, rate of white blood cells, initial carcinoembryonic antigen (CEA) rate, hemoglobin level, and therapeutic factors mainly represented by resection of metastases. AIM: To evaluate within a Tunisian retrospective study the significant prognostic factors on survival of metastatic colorectal cancer (MCRC). METHODS: We collected retrospectively 130 patients with MCRC treated in Sfax from january 2000 to December 2007. Uni and multivariate analysis were performed according to cox model for the following factors : Age or > 40 years, gender, synchronous vs metachronous metastases, disease-free survival (DFI) 1 > 1year, tumor site(colon vs rectum), performance status or PS ( 0-1or 2-3), white blood cells count (< or > 103/ml3 , haemoglobin rate (Hb) or > 11g/dl, seric carcinoembryonic antigen rate (CEA) < vs > 10 ng/ml, number of metastatic sites (single vs multiple), site of metastatic site (liver vs extrahepatic) and resection or not of the metastatic localizations. RESULTS: Statistical analysis showed for univariate analysis the positive impact of : PS 1, (Hb) rate > 11 g/dl, CEA) < 10 ng/ml and resection of metastases, while in in multivariate analysis, they were : a good PS and Hb > 11 g/dl. CONCLUSION: Our retrospective study confirmed the known prognostic impact of simple clinical tools like a good performance Status and Hb > 11 g/dl, a (CEA) rate lower than 10 ng/ml and resection of metastases which were identified by several other series such as predictive factors of a better survival in patients with metastatic colorectal cancer.

Chemotherapy-induced peripheral neurotoxicity: single-centre prospective study.

OBJECTIVE: Chemotherapy-induced peripheral neurotoxicity (CIPN) ranges from simple paresthesia to paralysis, which may be transient or irreversible. The aim of our study was to detect CINP in our patients undergoing chemotherapy and to study the cumulative neurotoxic doses for the different drugs. METHODS: This is a cross-sectional prospective study carried out in the medical oncology department of the Habib Bourguiba University Hospital in Sfax. A survey was conducted to detect and explore possible chemo-induced peripheral neuropathy in patients undergoing known potentially neurotoxic anti-cancer treatments. RESULTS: Seventy-three patients were included in the study. The average age was 51.8 years (13-80 years). The prevalence of CIPN was 52.1%. CIPN was classified as grade I in 24 (63.2%) cases and grade II in 14 (36.8%) cases. No grade III or IV peripheral neuropathy was detected in our patients. Paclitaxel was the drug with the highest incidence of CIPN (76.9%). The chemotherapy (CT) protocols most prone to chemotherapy-induced peripheral neurotoxicity (CIPN) were based on taxanes (47.3%) and oxaliplatin (59%). Paclitaxel was the drug most likely to cause CIPN (76.9%) (p=0.031). Paclitaxel single dose per cycle of 175 mg/m2 (66.67%) was more associated with the occurrence of CIPN than 80 mg/m2 (40%), but without significant difference (p=0.437). The average cumulative dose was estimated at 315 mg/m2 for docetaxel, 474 mg/m2 for oxaliplatin and 579 mg/m2 for paclitaxel (p=0.16). CONCLUSION: The prevalence of NPCI was 51.1% in our series. Oxaliplatin and taxanes were the main contributors to this complication with cumulative dose over than 300 mg/m2.

Intramedullary spinal cord metastasis from breast cancer: an ambiguous entity.

Intramedullary spinal cord metastasis (IMSC) from solid tumors is rare. In this report, we describe the case of a patient treated at our center for breast cancer with intramedullary spinal cord metastases without bone and brain metastases or meningitis. Management of the disease remains challenging even with recent advances in the treatment of metastatic breast cancer. Treatment options include surgery, radiotherapy and chemotherapy. The prognosis of these patients still very poor.

A novel PIK3CA hot-spot mutation in breast cancer patients detected by HRM-COLD-PCR analysis.

BACKGROUND: The PI3K protein is involved in the PI3K/AKT/mTOR pathway. Deregulation of this pathway through PIK3CA mutation is common in various tumors. The aim of this work is to identify hotspot mutation at exons 9 and 20 in Tunisian patients with sporadic or hereditary breast cancer. METHODS: Hotspot mutations in exon 9 and exon 20 of the PIK3CA gene were identified by QPCR-High Resolution Melting followed by COLD-PCR and sequencing in 63 (42 sporadic cases and 21 hereditary cases) tumor tissues collected from Tunisian patient with breast cancer. MCF7, and BT20 breast cancer cell lines harboring the PIK3CA hotspot mutations E545K and H1047R in exon 9 and exon 20 respectively, were used as controls in HRM experiments. RESULTS: PIK3CA hotspot mutations were detected in 66.7% (28 out of 42) of sporadic BC cases, and in 14.3% (3 out of 21) of hereditary BC. The E545K and the H1048Y were the most prevalent mutations identified in patients with sporadic and hereditary BC, whereas the H1047R hotspot mutation was not found in our patients. Statistical analysis showed that PIK3CA mutation associated with an aggressive behavior in patients with sporadic BC, while it's correlated with age, tumor stage and tumor size in the group patients with hereditary breast cancer. CONCLUSIONS: Our results showed a novel PIK3CA hotspot mutation in Tunisian breast cancer patients detected by HRM-COLD-PCR. Moreover, the absence of PIK3CA hotspot mutation associated with good prognosis.

Prognostic factors and survival in metastatic breast cancer: A single institution experience.

BACKGROUND: The current retrospective study aims to identify some determinants of survival in metastatic breast cancer. METHODS: The study concerned 332 patients with synchronous (SM) or metachronous (MM) metastatic breast cancer treated between January 2000 and December 2007. Statistical comparison between subgroups of patients concerning survival was carried out employing log-rank test for the invariable analysis and Cox model for the multivariable analysis. Factors included: age group (≤50 years vs. >50; ≤70 years vs. >70; ≤35 years vs. >35), menopausal status, presentation of metastatic disease (SM vs. MM), disease free interval (DFI) (≤24 months vs. >24 months; ≤60 months vs. >60 months), performance status at diagnosis of metastatic disease (PS) (0-1 vs. >1), hormone receptors (HR), number of metastatic sites (1 site vs. >1), nature of the metastatic site (visceral vs. non visceral), first line therapy, surgery of the primary tumor (SPT), locoregional radiotherapy (LRRT) and use or not of bisphosphonates. RESULTS: Overall survival at 5 years was 12%. Positive prognostic factors in univariate analysis were: age ≤ 70 years, hormono-dependence of the tumor, good PS (PS 0-1), less than two metastatic sites, no visceral metastases, DFI ≥ 24 months, SPT or LRRT. In multivariate analysis, favorable independent prognostic factors included: good PS (PS 0-1), absence of visceral metastases (liver, lung, brain) and age ≤ 70 years. CONCLUSION: Many of the prognostic factors in metastatic breast cancer found in our study are known in the literature but some of them, like the application of locoregional treatment (radiotherapy or surgery) and the use of bisphosphonates, need to be further investigated in randomized clinical trials.