Current Status and Challenges in Rare Genitourinary Cancer Research and Future Directions.

PURPOSE OF REVIEW: In contemporary urological practice, managing rare genitourinary (GU) malignancies presents significant challenges, necessitating a comprehensive understanding of their unique characteristics and tailored treatment approaches. RECENT FINDINGS: Rare GU malignancies, whether per se, variants of common histologies, or common tumors in uncommon locations, often lack widely available clinical guidelines. Consequently, treatment decisions are frequently based on empirical evidence, risking suboptimal outcomes. However, recent advances in molecular profiling, targeted therapies, and immunotherapy offer promising avenues for improving management strategies and patient outcomes. This review provides a comprehensive overview of some rare GU malignancies encountered in clinical practice, including their distinct pathological features, current management approaches, and ongoing research directions. Understanding the complexities of these rare tumors and implementing multidisciplinary treatment strategies are essential for optimizing patient care and improving survival outcomes.

Afebrile chemotherapy-induced neutropenia: an international survey spots oncologists' routine clinical practice versus the standard of care and the impact of COVID-19.

INTRODUCTION: Afebrile chemotherapy-induced neutropenia represents a frequent clinical situation where chemotherapy protocol, patient's comorbidities, and disease status determine the risk of infection hence the management plan. Internationally distributed, this questionnaire aims to evaluate the routine practice and the impact of the COVID-19 pandemic on afebrile chemotherapy-induced neutropenia management. MATERIAL AND METHODS: Coordinators from Egypt, Morocco, Azerbaijan, and Russia developed a 12-item questionnaire using Google forms to explore how oncologists deal with afebrile chemotherapy-induced neutropenia. The link to the survey was available internationally through social media and to their local societies over the period from July to September 2021. RESULTS: We received 151 responses from 4 world regions: 58.9, 9.9, 11.3, and 15.2% from the Mena area, Russia, Europe, and Asia. The responses deviated from the guideline-driven practice as G-CSF was the most chosen option for intermediate risk that was statistically different based on the academic background of the treating physician. Half of the responders ignored patients and disease risk factors in the intermediate-risk cases that trend was statistically different based on the geographical distribution. The steroid was a valid option for intermediate and low-risk as per oncologists practicing in Russia. COVID-19 pandemic positively affected the rate of prescription of G-CSF as expected. CONCLUSION: The disparities in the routine practice of oncologists based on their geographical and academic backgrounds highlight the need to analyze the underlying obstacles that hinder guideline-based practice like workload or lack of the proper knowledge.

Therapeutic Approaches With Immune Checkpoint Inhibitors in Head and Neck Cancers and the Role of PD-L1 as a Biomarker.

Head and neck squamous cell carcinoma (HNSCC) is a potential curative disease at its localized stage, by the use of multimodal treatment including surgery, radiation, and chemotherapy. While the metastatic stage is considered incurable and is characterized by poor prognosis. Conventional cytotoxic chemotherapy in addition to cetuximab were the only available systemic treatment with limited efficacy and modest median overall survival barely crossing the 1 year limit. Immunotherapy with PD-1 and PD-L1 inhibitors has revolutionized the treatment of multiple cancers. Recently, Immunotherapy is being extensively explored in head and neck cancer and clinical trials have shown impressive results that allowed to immune check point inhibitors to be the new standard of care. In this article we tried to explain the rationale and mechanisms of targeting the immune system in head and neck carcinoma and to report the results from the phase III clinical trials that put the immunotherapy as a new standard of care for head and neck cancer.

How Is Morocco Reacting to COVID-19 Crisis in Anticancer Centers?

The world is facing the pandemic linked to COVID-19 virus infection that has rapidly spread worldwide, and severe complications have been reported to occur in around a third of patients. To date, there is no approved vaccine or specific therapy against COVID-19, but many trials are ongoing with some of them showing promising results. It has been shown recently that patients with cancer are at high risk of infection and they are more susceptible to develop severe events such as the necessity of invasive ventilation and death. Therefore, this crisis presents a real challenge for health systems especially in low- and middle-income countries where the health systems are already fragile such as African countries. In this article, we describe the epidemiological situation of the infection in Morocco and the different challenges in cancer centers in the era of COVID-19, in addition to various strategies that have been implemented to prevent and control the infection spread in oncological units in order to ensure the continuation of adequate cancer care.

Personalized treatment in metastatic triple-negative breast cancer: The outlook in 2020.

Compared with other breast cancer subtypes, patients with triple-negative breast cancer (TNBC), and irrespective to their disease stage, were always recognized to have the worst overall survival data. Although this does not seem different at the present time, yet the last few years have witnessed many breakthrough genomic and molecular findings, that could dramatically improve our understanding of the biological complexity of TNBC. Based on genomic analyses, it was consistently evident that TNBC comprises a heterogeneous group of cancers, which have numerous diverse molecular aberrations. This-in return-has provided a platform for a new generation of clinical trials using many innovative therapies, directed against such novel targets. At the present time, two PARP inhibitors and one anti-PD-L1 monoclonal antibody (in combination with chemotherapy) have been approved in certain subpopulations of metastatic TNBC (mTNBC) patients, which have finally brought this disease into the era of personalized medicine. In the current review, we will explore the genomic landscape of TNBC, through which many actionable targets were graduated. We will also discuss the results of the key-practice changing-clinical studies, and some upcoming personalized treatment options for patients with mTNBC, that may be clinically adopted in the near future.

Awareness and practices of Arab oncologists towards oncofertility in young women with cancer.

Background: Cancer in young women is a major health problem in the Middle Eastern and North African population. We explored the awareness, barriers and practice of Arab oncologists towards oncofertility. Methods: Oncologists from Arab countries treating female cancer patients were invited to complete a 30-item web-based questionnaire that explores oncologists' demographics, available techniques and barriers to oncofertility. Results: 170 oncologists working in 9 different Arab countries responded to the questionnaire. Among the responders, 89 (52.4%) were from Egypt and the central region, 60 (35.3%) were from North Africa and 21 (12.4%) were from the Gulf region.While most participants considered a dedicated training 'necessary', only 43 oncologists (25.3%) received a formal training. Only 17 participants (10%) had a fertility clinic in their centre, 44 (25.9%) and 13 (7.6%) had to refer patients to other centres or other cities, respectively. A total of 96 oncologists (56.5%) did not have access to a fertility preservation service.Out of 147 responders, 79 (53.7%) offered fertility preservation only in patients presenting with early disease and 38 (25.9%) did not offer fertility preservation. In terms of proposed strategies, 50 responders (29.4%) offered embryo cryopreservation, 79 (46.5%) oocyte cryopreservation and 48 (28.2%) ovarian tissue cryopreservation. Conclusion: A large gap exists between international clinical practice guidelines and current practices of fertility preservation in Arab countries. Barriers to optimum service delivery include the lack of physician awareness/training, unavailability of some advanced techniques and a lack of dedicated fertility clinics within the cancer centres.

Worse Outcome with Imatinib Mesylate as Neoadjuvant Therapy in Locally Advanced Rectal Gastrointestinal Stromal Tumors: Case Series of Four Patients.

BACKGROUND: Rectal gastrointestinal stromal tumors are rare and optimal treatment is yet to be defined. The aim of this report is to highlight the possible aggressive behavior of four cases of rectal GISTs treated with neoadjuvant imatinib in a tertiary care medical hospital. METHODS: Four cases of rectal GISTs were retrospectively reviewed for patients demographics, clinical presentation, histology, and imatinib therapy. RESULTS: GISTs were common in men. Age ranged to symptoms were nonspecific. All cases were initially considered to have locally unresectable. Patients received preoperative imatinib. Course was unfavorable. 3 patients died of progressive disease, and one from infectious complications. CONCLUSION: Rectal GISTs may be aggressive and resistant to medical treatment. Thus only early diagnosis may offer the best chance of recovery. KEY WORDS: Rectal - gastrointestinal stromal tumor - neoadjuvant imatinib - resistance.

Small bowel carcinoid tumor causing intestinal ischemia: A case report with review of the literature.

Background: Intestinal carcinoid tumors are well-differentiated neuroendocrine tumors that are capable of secreting bioactive hormones and/or amines; These tumors are uncommon but are the most common primary tumors of the small intestine. Case presentation: We report the case of an 80-year-old woman who presented with a long history (about 14 years ago) of atypical digestive symptoms such as vague abdominal pain, alternating diarrhea, and constipation, treated as functional colopathy without improvement, until the day when she presented with worsening pain that prompted her consultation. CT scan revealed typical manifestations of a carcinoid tumor associated with signs of subacute small bowel ischemia. Despite the surgery being considered a gold standard treatment, it was rejected due to the extent of tumor mesenteric involvement, therefore, the patient received only somatostatin treatment. Conclusion: Small bowel carcinoid tumors are rare, with typical imaging features based on cross-sectional imaging (CE CT/MRI). Intestinal ischemia is a well-known complication that can be a factor in mortality.

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020.

PURPOSE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. METHODS: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. RESULTS: The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. CONCLUSION: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

A primary mediastinal germ cell tumor of yolk sac type: case report.

The mediastinal malignant germ cells tumor represents less than 0.5% of thoracic tumors, although the mediastinum is one of the main extragonadic locations of these tumors. In the majority of cases, young people are those most affected. The prognosis of mediastinal malignant germ cells tumors is poor, especially non-seminomatous germ tumors. In this article, we report a rare case of a young 19-years-old patient treated for a mediastinal germ cell tumor of yolk sac. The patient presented a chest pain; the chest computed tomography (CT) showed a right paramedian mediastinal mass with a pleural effusion associated with supraclavicular and cervical lymph nodes. Biopsy revealed a non-seminomatousgerm cell tumor of yolk sac. The exams showed elevated alpha-fetoprotein (AFP), without any meaningful elevation of other serictumor markers. The patient received 4 cycles of chemotherapy based on etoposide, ifosfamide and platinum salts then a complete excision of the mass.

[Malignant mesothelioma of the ovary: a case report]. / Mésothéliome malin de l´ovaire: à propos d´un cas.

Primary malignant mesothelioma of the ovary (PMMO) is an extremely rare tumor which can develop from mesothelial cells. This neoplasia is caused predominantly by exposure to asbestos or other cancer-causing agents. Preoperative assessment, based on computed tomography (CT) scan, magnetic resonance imaging and positron emission tomography, is essential for cancer staging. Anatomopathological diagnosis is based on immunohistochemical findings. PMMO is an exceptional disease involving a multidisciplinary therapeutic strategy including the use of chemotherapy which improves the management and prognosis of patients. This study reports the case of a female patient undergoing suboptimal surgery complemented by adjuvant chemotherapy with complete radiological response and 1-year disease-free survival.

Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives.

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%-20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.

[Chemotherapy induced ovarian failure in breast cancer: Retrospective study of 100 cases]. / L'insuffisance ovarienne chimio-induite dans le cancer du sein : étude rétrospective de 100 cas.

INTRODUCTION: Breast cancers affect about a quarter of women of reproductive age worldwide. Chemotherapy is frequently indicated due to the aggressive biomolecular cancer subtypes usually observed in the localized forms, which may compromise the fertility of these young patients. The aim of our study is to report the incidence of chemotherapy induced ovarian failure in premenopausal breast cancer patients after chemotherapy, and to identify related risk factors. METHODS: It is a retrospective cross-sectional cohort study which included all premenopausal patients with early breast cancer treated at the department of medical oncology, Hassan II University Hospital of Fez, during a period of one year. Chemotherapy induced amenorrhea (CIA) and associated risk factors were studied. RESULTS: The study included 100 patients. The mean age of the subjects was 36 years. The incidence of CIA was 82 %, 66.7 % regained menstruations. Risk factors associated with CIA were analyzed, only the patient age at diagnosis was found to be statistically significantly associated with CIA. CONCLUSION: Our study found a high incidence of CIOF (Chemotherapy-induced ovarian failure) with a relatively low incidence of reversible amenorrhea. Only the patient age has been shown to be an independent factor, statistically significantly associated with ovarian failure after chemotherapy. Methods of fertility preservation should be considered in those patients to reduce the impact of chemotherapy on ovarian reserves.

Primary neuroendocrine tumors of the breast: two case reports and review of the literature.

BACKGROUND: Neuroendocrine carcinomas mainly affect the bronchopulmonary and the gastrointestinal systems. Breast localizations are very rare. They represent less than 0.1% of all breast cancers. A definitive diagnosis relies on histological and immunohistochemical examinations. CASE PRESENTATION: Case 1 We report a case of primary neuroendocrine carcinoma of the breast in a 71-year-old Arabic woman who presented with a 3 cm palpable and mobile tumor of the right breast. Clinical and radiological assessment excluded any other primary tumor. Radical mastectomy and axillary lymph node resection were performed. A histopathological examination disclosed the diagnosis of primary breast neuroendocrine tumors, with negative surgical margins and lymph nodes (18 N-/18 N). The tumor cells were positive for neuroendocrine markers, a weak Ki-67 proliferation index and negative Her2/neu. Our patient received adjuvant hormonal treatment with anti-aromatase for 21 months. She is on regular follow-up, and she remains free of disease to date. Case 2 A 48-year-old Arabic woman consulted for a right breast nodule. She underwent lumpectomy with right axillary lymphadenectomy. The diagnosis was breast neuroendocrine tumor. Systemic treatment was proposed, but she was lost to follow-up. She consulted 1 year later for a mass in the same breast. A histological and immunohistochemical examination of a mammary biopsy was consistent with a recurrence of the previous neuroendocrine tumor. A radiological assessment showed a large mass in her right breast, ipsilateral axillary lymphadenopathies, and hepatic and pulmonary metastases. She received first-line metastatic chemotherapy, with good clinical and radiological improvement. She refused the mastectomy and was given hormone therapy. One year later, the tumor expanded clinically and radiologically, and she underwent second-line metastatic chemotherapy, with good clinical progress and radiological stability, and she then underwent maintenance hormonal therapy. CONCLUSION: Due to the rarity of primary breast neuroendocrine tumors, no standard therapy exists and the prognosis remains difficult to determine. Studies, including larger series, are needed in order to understand the biological behavior of these tumors.

[Dermatomyositis and rectal cancer: case study and literature review]. / Dermatomyosite et cancer rectal: à propos d'un cas avec revue de la littérature.

Dermatomyositis is a systemic idiopathic disease characterized by a combination of both muscle and skin symptoms. It is a paraneoplastic dermatosis. Its association with rectal cancer has been rarely described in the literature. We here report the case of a female patient with paraneoplastic dermatomyositis associated with metastatic rectal adenocarcinoma presenting with clinical symptoms commonly found in subjects with paraneoplastic dermatomyositis. Other complementary examinations (CPK test + EMG + skin biopsy) were performed which confirmed this diagnosis. The patient underwent chemotherapy, but after the second cycle, she experienced a rapid worsening of her general condition and died after some days in a state of multisystem organ failure. This study aims to highlight paraneoplastic dermatomyositis' aggressive nature and to update current knowledge on the importance of chemotherapy in the management of neoplastic dermatomyositis.

Novel therapeutic strategies in the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that is defined by negative estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Treating patients with TNBC remains clinically challenging, as patients are not candidates for endocrine or HER2-directed therapy. As a result, chemotherapy with traditional agents such as anthracyclines and taxanes remains the only available option with moderate success. Recent discoveries have revealed that TNBC is a heterogeneous disease at the clinical, histological and molecular levels. The use of biomarkers to identify distinct subsets of TNBC that derive the greatest benefit from presently approved as well as novel therapeutics has become the main focus of current research. The aim of this review is to explore the clinical and biological complexity of TNBC as well as identify novel therapeutic options that target the various molecular subsets of TNBC.

Effect of Bleomycin Administration on the Development of Pulmonary Toxicity in Patients With Metastatic Germ Cell Tumors Receiving First-Line Chemotherapy: A Meta-Analysis of Randomized Studies.

BACKGROUND: Limited information is available about the effect of bleomycin administration on the development of pulmonary toxicity in metastatic germ cell tumors (GCT). PATIENTS AND METHODS: A literature search was conducted to identify randomized trials of first-line chemotherapy for GCT. We conducted univariate and multivariate analyses using random effects models to evaluate the predictive role of bleomycin administration in the development of all Grade and Grade 3 to 4 (G3-4) pulmonary toxicity. The results were adjusted for length of follow-up, prognostic risk group, year of treatment, presence of lung metastases, and primary mediastinal GCT. RESULTS: Fifty-three study arms of 25 phase II and III trials encompassing 6498 patients were selected: 40 that used bleomycin (n = 5093) and 13 that did not (n = 1405). The pooled probability of all-Grade pulmonary toxicity in the bleomycin and nonbleomycin arms was 11.7% (95% confidence interval [CI], 8.4%-16.0%) and 1.7% (95% CI, 0.7%-4.2%), respectively. Univariate analysis indicated that bleomycin administration was associated with the incidence of all-Grade (odds ratio [OR], 7.57; 95% CI, 2.84-20.18; Wald test P < .001) and G3-4 pulmonary toxicity (OR, 5.19; 95% CI, 1.57-17.16; P = .007). Multivariate analysis showed a significant association of bleomycin administration with the incidence of all-Grade pulmonary toxicity (OR, 4.14; 95% CI, 1.36-12.59; P = .012) and a trend toward significance for G3-4 toxicity (OR, 2.24; 95% CI, 0.91-5.51; P = .080). CONCLUSION: We quantified the bleomycin-associated effect on the development of pulmonary toxicity in patients with GCT who received first-line chemotherapy. This information might be useful for planning clinical trials aimed at reducing chemotherapy as well as to inform patients in the clinic.

[Pleural epithelioid sarcoma: about a case and review of the literature]. / Sarcome épithélioide pleural, à propos d'un cas avec revue de la littérature.

Proximal epithelioid sarcoma (PES) originating from the pleura is a clinical entity rarely reported in the literature. We report the case of a young patient with immediately metastatic proximal epithelioid sarcoma (PES) treated at the Department of Medical Oncology, Fes. Treatment consisted of chemotherapy based on doxorubicin and ifosfamide. After the first cycle of chemotherapy, the disease led to a fatal outcome. Our case study highlights the potentially aggressive behaviour of PES which represents a clinical trap and can be life-threatening.