Local and systemic side effects of COVID-19 vaccine in Tunisian cancer patients: A prospective single center study.

OBJECTIVE: We aimed to evaluate the local and systemic side effects of the COVID-19 vaccine in cancer patients. METHODS: we conducted a cross-sectional study including cancer patients treated at Habib Bourguiba Hospital in Sfax, Tunisia between January and March 2022. Patients should have received at least 1 dose of a COVID-19 vaccine. RESULTS: We interviewed a total of 106 patients, of which 80.2% were actively treated. Mean age was 52.52. Patients were vaccinated by the Pfizer/BioNTech in 59.8% and the Oxford/AstraZeneca in 22.5%. The most frequent grade 1 or 2 adverse events occurring within 7 days were: pain at injection site (71.7%) and fatigue (38.7%). Only 2 patients developed grade 3 toxicity following vaccination. The most systemic side effects were fatigue (35.8%), fever (25.4%), headache (16.9%) and arthralgia (15.1%). They were more common after the first dose of Oxford/AstraZeneca vaccine compared to the Pfizer/BioNTech vaccine (69.6% vs 42.6%; p = 0.03). Risk of any grade toxicity (local or systemic) following the first dose was correlated with female sex (p = 0.033). CONCLUSION: Our study showed that systemic side effects were more common after the first dose of Oxford/AstraZeneca vaccine compared to the Pfizer/BioNTech vaccine in cancer patient, with the predominance of any grade of local or systemic toxicity in women.

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.

International recommendations for plasma Epstein-Barr virus DNA measurement in nasopharyngeal carcinoma in resource-constrained settings: lessons from the COVID-19 pandemic.

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment.

Immune checkpoint CD155 promoter methylation profiling reveals cancer-associated behaviors within breast neoplasia.

BACKGROUND: CD155 immune checkpoint has recently emerged as a compelling immunotherapeutic target. Epigenetic DNA methylation changes are recognized as key molecular mechanisms in cancer development. Hence, the identification of methylation markers that are sensitive and specific for breast cancer may improve early detection and predict prognosis. We speculate that CD155 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its immunoregulatory functions. METHODS: Methylation analyses were conducted on 14 CpGs sites in the CD155 promoter region by bisulfite pyrosequencing. To elucidate the related gene expression changes, a transcriptional study using RT-qPCR was performed. Statistical analyses were performed to evaluate correlations of CD155 methylation profiles with mRNA expression together with clinical-pathological features, prognosis and immune infiltrate. RESULTS: CD155 promoter methylation profile was significantly associated with SBR grade, tumor size, molecular subgroups, HER2 and hormonal receptors expression status. Low CD155 methylation rates correlated with better prognosis in univariate cox proportional hazard analysis and appeared as an independent survival predictor in cox-regression multivariate analysis. Further, methylation changes at CD155 specific CpG sites were consistent with CD155 membranous mRNA isoform expression status. Statistical analyses also showed a significant association with immune Natural Killer cell infiltrate when looking at the CpG7, CpG8, CpG9 and CpG11 sites. CONCLUSION: Altogether, our results contribute to a better understanding of the impact of CD155 immune checkpoint modality expression in breast tumors, revealing for the first time that specific CpG sites from CD155 promoter may be a potential biomarker in breast cancer monitoring.

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.

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.

Chemotherapy induced alopecia in breast cancer patients: A monocentric prospective study.

INTRODUCTION: Alopecia is one of the main adverse events of chemotherapy in breast cancer. However, its impact is often ignored and underestimated by clinicians. Our aim was to evaluate the quality of life of breast cancer patients with chemotherapy induced alopecia. METHODS: We conducted a prospective study including 72 breast cancer patients who developed alopecia on or after stopping chemotherapy in the last 6 months. Clinical information and characteristics of alopecia were assessed using a self-prepared questionnaire. DLQI score was used to evaluate patients' quality of life. RESULTS: We interviewed a total of 72 women with a mean age of 53.5 ± 6 years. Alopecia appeared soon after the first course in 62.5%. All patients actively tried to hide induced hair fall (either by a hat in 6.9% or by a headscarf in 93.1%). Quality of life was impacted in 97.2% of patients with a median DLQI score of 6.5. Women who did not underwent mastectomy were significantly more bothered by hair loss than those who had radical surgery (78.1% vs 55%, p = 0.04). Working status was a significant predictor factor of a bad quality of life due to alopecia (100% in working women vs 58.3% in homemaker or retired patients, p = 0.006). CONCLUSION: Chemotherapy induced alopecia had a negative impact on quality of life of patients with breast cancer, especially in working women and those who did not have radical surgery. Prior wearing of headscarves did not impact significantly the DLQI score.

Synchronous primary breast angiosarcoma with invasive ductal carcinoma.

Primary angiosarcoma (PAS) of the breast is an extremely uncommon variant of breast malignancies. Highly aggressiveness and dismal prognosis characterize this endothelial neoplasm. We report here an unusual case of PAS of the breast occurring in a 46-year-old woman associated with concurrent bilateral invasive ductal carcinoma and ovarian metastases.

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.

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.

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.

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.

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.

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.