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.

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.

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.

Prognostic factors of male breast cancer: A monocentric experience.

BACKGROUND: Male breast cancer (MBC) is a rare malignancy presenting only 1% of all breast cancer. The purpose of this study was to analyze clinical and pathological prognostic factors of MBC. METHODS: This is a retrospective study including 32 men diagnosed and treated for a primary breast cancer at the department of medical oncology in Sfax between 2005 and 2020. RESULTS: The incidence of MBC was 1.3%. The median age of our patients was 55 years (range: 29-85 years). The average tumor size of 3.9 cm. Lymph nodes involvement was present in 18 cases (56.2%) with capsular rupture in 52% cases. Tumor was grade II in 71.8 % of cases. The expression of hormonal receptors was founded in 100% of cases. Two patients had an overexpression of HER2 (6.2%). There was no case of triple negative MBC. The OS at 5 and 10 years was 67.8% and 30.8% respectively. Prognostic factors were T4 (p = 0.015), involved nodes (p = 0.035), M+ (p = 0.01), SBR III (p = 0.0001) and HER2+++ (p = 0.001). CONCLUSION: Contrary to breast cancer in women, our study showed that Tunisian MBC have positive hormone receptors in all cases. Although the overexpression of HER2 was low (8.33%) and there was no case of triple negative MBC, the prognosis was poor because of T4 stage, involved nodes, SBR III and distant metastases.

Complete remission in metastatic hepatocellular carcinoma.

Bone metastases from hepatocellular carcinoma (HCC) are unusual. Optimal treatment strategies are not well defined. The prognosis of this entity is very poor with a survival that does not exceed 1 year. We report here a new case of metastatic HCC with longer overall survival of more than 5 years in a 67-year-old man.

The management of retroperitoneal sarcoma: The experience of a single institution and a review of the literature.

Objectives: Retroperitoneal sarcomas (RPSs) are rare mesenchymal tumors. The objective of this study was to discuss the different clinical, therapeutic and prognostic aspects of RPS in our institution. Methods: This was a retrospective study conducted at the Department of Medical Oncology in the Habib Bourguiba University Hospital in Sfax, including 19 patients who were treated for RPSs between 1999 and 2016. Results: The median age was 49 years (range: 18-83 years); 68.4% of the patients were female. The commonest symptom was abdominal pain (88%) and the median tumor size was 15 cm (range: 4-30 cm). Complete resection was achieved in only five cases (26.3%). The most common histological subtypes were liposarcoma (47.4%) and leiomyosarcoma (26.3%). Eight patients had a high-grade tumor (G2 = 2 or G3 = 6). Adjuvant radiotherapy was administered in 5 patients (26%). Seventeen patients were treated with chemotherapy; six received chemotherapy in an adjuvant treatment, three as a neoadjuvant treatment, and eight were treated during the palliative phase. Relapse was observed in 58% of cases. For all patients, the overall survival (OS) was 89.5% at 1 year and 40.3% at 5 years. Prognostic factors influencing OS were sex (p = 0.037), resection margins (p = 0.02), recurrence (p = 0.042), and radiotherapy (p = 0.023). In multivariate analysis, radiotherapy (p = 0.031) and histological subtype (p = 0.028) were independent factors influencing OS and disease-free survival (DFS) respectively. Conclusion: We showed that the treatment of RPSs relies on surgery with complete resection. Other factors, such as radiotherapy and the occurrence of relapse, also have an impact on OS. To facilitate surgery and to obtain negative resection margins, preoperative radiotherapy is indicated in selected patients with a high risk of relapse. Further prospective trials are warranted to select optimal therapies with less toxicity and better efficacy in reducing recurrences, mainly at a local level.

Mixed Hepatocellular-Neuroendocrine Carcinoma: A Case Report and Literature Review.

Mixed hepatocellular-neuroendocrine carcinoma (HCC-NEC) is a rare entity with a poor prognosis. We report a case of a 44-yearold Tunisian man who was admitted for diffuse abdominal pain. Body computed tomography showed multinodular hepatomegaly. Pathologic findings concluded to HCC-NEC. Clinicians should be aware about this entity. Further collection of case reports is needed to standardize the optimal treatment.

Germ Cell Tumors Revealing a Familial Persistent Müllerian Duct Syndrome.

Persistent Mullerian duct syndrome (PMDS) is a congenital disorder related to male sexual development. PMDS is usually diagnosed during an inguinal hernia cure. The diagnosis of PMDS following a testicular germ cell tumor is less common. We report the cases of three infertile male patients who were diagnosed with PMDS after surgery for germ cell tumors. They were 39, 27, and 37 years old men with a medical history of neglected cryptorchidism. All patients had a male karyotype and the ELISA test for the anti-Mullerian hormone was undetectable. Patients underwent chemotherapy followed by resection of residual mass in one patient. One patient is currently alive and disease-free. The two other patients died of systemic relapse. These cases highlight how early recognition and treatment of PMDS can prevent malignant germ cell tumors. The diagnosis of PMDS relies on a systemic assessment and analysis of mutations in the gene coding for AMH and AMHR-II. Key words: Persistent Müllerian duct syndrome (PMDS), anti mullerian hormone, germ cell neoplasm.

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.

An uncommon case of synchronous gastric and colonic metastases from breast cancer.

Invasive lobular carcinoma is the second-most-common subtype of breast cancer. It is characterized by a different metastatic pattern with a propensity to metastasize to pleura, peritoneum, gastrointestinal tract, and ovary. We report a woman with known metastatic disease outside the gastrointestinal tract who had endoscopy and colonoscopy for gastrointestinal symptoms. Extensive metastases were found in the stomach and colon with a diffuse infiltration of signet ring-like cells at histology and immunohistochemical findings consistent with breast carcinoma. To the best of our knowledge, this is the first report of such a case from Africa.

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma.

Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the "classic" EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

Sunitinib-Induced Congestive Heart Failure in a Patient with Gastrointestinal Stromal Tumor.

Common cardiovascular toxicities of sunitinib mainly include hypertension, QT prolongation, left ventricular dysfunction (LVD) and less frequently, congestive heart failure (CHF). Here, we report the case of a 67-year-old woman who developed heart failure after 24 months of sunitinib. Our case highlights the importance of strict and regular cardiovascular monitoring during sunitinib. It also shows that the reintroduction of sunitinib with maintaining heart failure treatment can be safe. The exact mechanisms of this cardiotoxicity have not been understood. There is no protective therapy available. Therefore, further investigations are needed in these areas. Medical specialists who prescribe and treat patients with sunitinib should be aware of the possible occurrence of these conditions and perform regular checkup of sunitinib-treated patients.

The Identification by Exome Sequencing of Candidate Genes in BRCA-Negative Tunisian Patients at a High Risk of Hereditary Breast/Ovarian Cancer.

(1) Background: Germline variants in BRCA1/BRCA2 genes explain about 20% of hereditary breast/ovarian cancer (HBOC) cases. In the present paper, we aim to identify genetic determinants in BRCA-negative families from the South of Tunisia. (2) Methods: Exome Sequencing (ES) was performed on the lymphocyte DNA of patients negative for BRCA mutations from each Tunisian family with a high risk of HBOC. (3) Results: We focus on the canonical genes associated with HBOC and identified missense variants in DNA damage response genes, such as ATM, RAD52, and RAD54; however, no variants in PALB2, Chek2, and TP53 genes were found. To identify novel candidate genes, we selected variants harboring a loss of function and identified 17 stop-gain and 11 frameshift variants in genes not commonly known to be predisposed to HBOC. Then, we focus on rare and high-impact genes shared by at least 3 unrelated patients from each family and selected 16 gene variants. Through combined data analysis from MCODE with gene ontology and KEGG pathways, a short list of eight candidate genes (ATM, EP300, LAMA1, LAMC2, TNNI3, MYLK, COL11A2, and LAMB3) was created. The impact of the 24 selected genes on survival was analyzed using the TCGA data resulting in a selection of five candidate genes (EP300, KMT2C, RHPN2, HSPG2, and CCR3) that showed a significant association with survival. (4) Conclusions: We identify novel candidate genes predisposed to HBOC that need to be validated in larger cohorts and investigated by analyzing the co-segregation of selected variants in affected families and the locus-specific loss of heterozygosity to highlight their relevance for HBOC risk.

An uncommon case of pancreatic adenocarcinoma revealed by dermatitis.

We report a 63-year-old-woman who presented with a pruritic rash on both thighs. Radiologic investigations revealed a pancreatic mass. Pancreatic cancer was confirmed by biopsy and the rash resolved after chemotherapy followed by pancreatoduodenectomy. Urticarial dermatitis is a rare paraneoplastic manifestation of pancreatic cancer in Africa.

Localized stomach cancer: Perioperative or postoperative approach? A meta-analysis of phase III studies.

Background and Aim: Despite the development and standardization of surgical techniques in the treatment of localized gastric adenocarcinoma, the loco-regional and metastatic recurrence rate remains high. A combined radiochemotherapeutic regimen (the MacDonald regimen) as well as perioperative chemotherapy allows a significant improvement in the survival of patients with localized gastric adenocarcinoma with a reduction in the recurrence rate compared to surgery alone. The purpose of this review is to specify the best therapeutic approach in the treatment of localized gastric cancer. Methods: We performed a systemic search of Medline, Embase, and the Cochrane Central Register of Controlled Trials using PubMed, Google Scholar, and Ovid without language restriction. Hazard ratio (HR) with 95% confidence interval (CI) was reported. Results: We pooled 727 patients from two phase III randomized controlled trials. There was a benefit of perioperative chemotherapy versus surgery alone on the overall survival (OS) (HR = 0.72, 95% CI: 0.55-0.95) and on disease free survival (DFS) (HR = 0.65, CI: 0.50-0.85). Adjuvant chemotherapy was superior to surgery alone based on OS and disease free survival (CLASSIC study HR = 0.72, CI: 0.52-1 and HR = 0.56, CI: 0.44-0.72, respectively). Adjuvant radiochemotherapy was superior to surgery alone (HR = 1.35, 95% CI: 1.09-1.66; P = 0.005). Conclusion: A face-to-face comparison of perioperative chemotherapy versus adjuvant chemotherapy versus chemoradiotherapy is necessary.

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.

Prognostic factors in metastatic nasopharyngeal carcinoma / Fatores prognósticos no carcinoma nasofaríngeo metastático

Abstract Introduction: Nasopharyngeal carcinoma has the highest metastatic potential of all head and neck cancers. The survival time of patients with nasopharyngeal carcinoma has improved significantly in the last decades due to the use of combination of chemotherapy and radiotherapy, as well as advances in radiotherapy techniques. However, appropriately 30% of patients with nasopharyngeal carcinoma suffer a poor prognosis, mainly due to distant metastasis. Objective: The study aimed to identify the survival and prognostic factors in metastatic nasopharyngeal carcinoma. Methods: A retrospective analysis was conducted in patients treated for synchronous metastatic nasopharyngeal carcinoma or metachronous metastatic nasopharyngeal carcinoma for 14years (2003-2016). Overall survival was analyzed using the Kaplan-Meier method and compared using the log-rank test for the whole population and both groups of patients. Multivariate analysis was performed using the Cox model; p-values < 0.05 were considered to indicate statistical significance. Results: One hundred and twelve patients with metastatic nasopharyngeal carcinoma were included (51 patients with metastatic nasopharyngeal carcinoma, and 61 patients with metachronous metastatic nasopharyngeal carcinoma). In the whole population, the median overall survival was 10 months (1-156 months). In the multivariate analysis, female gender, poor performance status (WHO > 1) and metachronous metastasis were independent prognostic factors. In the metastatic nasopharyngeal carcinoma patients, the median overall survival was 13 months (1-156 months). In multivariate analysis, independent prognostic factors were non-oligometastatic disease, severe (G3-G4) chemotherapy toxicity and the lack of nasopharyngeal and metastatic site irradiation. In the metachronous metastatic nasopharyngeal carcinoma patients, the median overall survival was 7 months (1-41 months). In multivariate analysis, the poor performance status (WHO > 1) was an independent metastatic nasopharyngeal carcinoma prognostic factor. Conclusion: Oligometastatic patients with synchronous metastatic nasopharyngeal carcinoma had better survival. The locoregional treatment of primitive nasopharyngeal carcinoma improved survival in patients with metastatic nasopharyngeal carcinoma who responded to induction chemotherapy. Local irradiation of metastatic sites improved survival of metastatic nasopharyngeal carcinoma patients. Grade 3 or 4 chemotherapy toxicity altered survival among patients with synchronous metastatic nasopharyngeal carcinoma.

Resumo Introdução: O carcinoma nasofaríngeo tem o maior potencial metastático de todos os tipos de câncer de cabeça e pescoço. O tempo de sobrevida dos pacientes com carcinoma nasofaríngeo melhorou significativamente nas últimas décadas devido ao uso combinado de quimioterapia e radioterapia e os avanços nas técnicas de radioterapia. No entanto, aproximadamente 30% dos pacientes com carcinoma nasofaríngeo têm um prognóstico ruim, principalmente devido a metástases a distância. Objetivo: Identificar a sobrevida e os fatores prognósticos no carcinoma nasofaríngeo metastático. Método: Foi feita uma análise retrospectiva de pacientes tratados por carcinoma nasofaríngeo metastático sincrônico ou carcinoma nasofaríngeo metastático metacrônico por 14 anos (2003-2016). A sobrevida global foi analisada pelo método de Kaplan-Meier e comparada pelo teste de log-rank para toda a população e ambos os grupos de pacientes. A análise multivariada foi feita com o modelo de Cox; valores de p < 0,05 foram considerados como significância estatística. Resultados: Foram incluídos 112 pacientes com carcinoma nasofaríngeo metastático (51 com carcinoma nasofaríngeo metastático sincrônico e 61 com carcinoma nasofaríngeo metastático metacrônico). Em toda a população, a mediana da sobrevida global foi de 10 meses (1-156 meses). Na análise multivariada, sexo feminino, baixo status de desempenho (OMS > 1) e metástase metacrônica foram fatores prognósticos independentes. Nos pacientes com carcinoma nasofaríngeo metastático sincrônico, a mediana da sobrevida global foi de 13 meses (1-156 meses). Na análise multivariada, os fatores prognósticos independentes foram doença não oli-gometastática, toxicidade grave à quimioterapia (G3 - G4) e falta de irradiação nasofaríngea e do sítio metastático. Nos pacientes com carcinoma nasofaríngeo metastático metacrônico, a mediana da sobrevida global foi de 7 meses (1-41 meses). Na análise multivariada, o baixo status de desempenho (OMS > 1) foi um fator prognóstico independente. Conclusão: Pacientes oligometastáticos com carcinoma nasofaríngeo metastático sincrônico tiveram melhor sobrevida. O tratamento locorregional do carcinoma nasofaríngeo primário melhorou a sobrevida em pacientes com carcinoma nasofaríngeo metastático sincrônico que responderam à quimioterapia de indução. A irradiação local dos locais metastáticos melhorou a sobrevida dos pacientes com carcinoma nasofaríngeo metastático. A toxicidade de quimioterapia de grau 3 ou 4 alterou a sobrevida entre pacientes com carcinoma nasofaríngeo metastático sincrônico.

Prognostic factors and treatment of relapsed osteosarcoma: A monocentric Tunisian retrospective study.

BACKGROUND: This study aimed to explore the treatment modalities of relapsed osteosarcoma, treatment results, and prognostic factors. METHODS: We conducted a retrospective study of patients treated for relapsed osteosarcoma between 2005 and 2019. Patient survival was compared according to age, performance status, time to relapse, and surgical treatment at the relapse. Values of p<0.05 were considered to indicate statistical significance. RESULTS: We included 49 patients who were treated for osteosarcoma. During the 13-year study period, 16 patients had relapsed osteosarcoma (32.7%). Prognostic factors of relapse were age over 18 years (p = 0.03), axial tumors (p = 0.01), and positive surgical margins (p = 0.018). Nine patients had palliative chemotherapy at the time of relapse. After a median follow-up of 8 months (range: 4-65 months), the overall survival at 1 year, 2 years, and 5 years after diagnosis of the relapse was 46.7%, 31.1%, and 20.7%, respectively. Relapsed osteosarcoma patients who had good performance status, late relapse (after 12 months), as well as surgery of the relapsed disease had better overall survival (OS). CONCLUSION: Surgical treatment of relapsed osteosarcoma should be performed whenever possible since it improves significantly the survival of patients. Good performance status and late relapse were also associated with better survival.