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.

Cancer in Moroccan elderly: the first multicenter transverse study exploring the sociodemographic characteristics, clinical profile and quality of life of elderly Moroccan cancer patients.

BACKGROUND: Moroccan incidence of cancer is increasing with the lengthening of life expectancy. Data regarding elderly Moroccan cancer patients are lacking. In the context of our project aiming to develop an adapted version of the Comprehensive Geriatric Assessment CGA to the Moroccan population, we launched the first Moroccan multicenter transverse study to explore the characteristics of elderly Moroccan cancer patients. METHODS: The study was conducted in nine Moroccan medical oncology departments. Patients were enrolled over 4 months. Inclusion criteria were patients aged 65 years or over with verified solid cancer. The questionnaire included four sections: socio-demographic and economic data, clinical data, vulnerability and EORTC-QLQ C30. We explored the entire included population. Then, we compared the results according to age (65-70 years old and ≥ 71 years old) and sex. We also explored the correlation between G8 scores and the ability to practice religion as an indicator of fitness level. RESULTS: In total, 164 patients were enrolled. The mean age was 73.18 ± 6.01 years. The majority of patients were married, lived with their children and received their financial income from them. Fifteen percent of families asked to hide the diagnosis from the patient. Breast (23%), colorectal (15.9%) and lung (14%) cancers were the most frequent, and 83.5% had an abnormal G8. The majority of the patients were independent for basic daily activities. Female patients had poorer social and economic conditions. Abnormal G8 was correlated with religious practice and quality of life scores. CONCLUSION: This is the first multicenter prospective study designed to collect data on the lifestyle and clinical profiles of elderly Moroccan cancer patients as an Arab and Muslim population. Our study shows that it is a well-cared-for population with strong social ties. However, there is deep economic vulnerability, especially among women, requiring urgent care. Religious practice is an important daily activity for our elderly patients and should be included in the Moroccan CGA.

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.

The expression of MDM2 in gastrointestinal stromal tumors: immunohistochemical analysis of 35 cases.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal tumors of the digestive system. The assessment of their biological behavior still remains a scientific challenge. To date, there are no well-established biological prognostic markers of GIST. Our aim is to study the expression of the MDM2 oncoprotein in GIST through an immunohistochemical analysis. METHODS: It was a retrospective study of 35 cases of GIST diagnosed from 2009 to 2012 in the department of pathology of Hassan II university hospital, Fès, Morocco. MDM2 immunohistochemical staining was performed on archival paraffin-embedded and formalin-fixed specimens (with a threshold of nuclear positivity > 10%). Analysis of correlations between MDM2 immunoexpression and clinicopathological features of GIST has been performed. RESULTS: The mean age was 55.23 years (range 25-84 years) with a male predominance (sex ratio = 1.5). The stomach was the main site of GIST, with 17 cases (48.57%) followed by the small bowel (9 cases, 25.71%). The spindle cell type GIST was the most frequent morphological variant (29 cases, 82.85%). Tumor necrosis was present in 8 cases (22.85%). Two patients (5.71%) had very low risk GIST, 5 (14.28%) had low risk GIST, 7 patients (20%) had intermediate risk tumors. The remaining 21 cases (60%) had high risk GIST. At the time of diagnosis, 9 patients (25.71%) had metastatic tumors. At immunohistochemical analysis, 40% of cases (14 patients) stained positive for MDM2. Of these MDMD2-positive tumors, 11/14 (78.57%) had high risk tumors and 8/14 cases (57.14%) presented with metastatic GIST. MDM2 positivity was significantly associated with the metastatic status (p = 0.001). CONCLUSION: The current study suggests that MDM2 immunohistochemical expression is a negative histoprognostic factor in GIST with a statistically significant correlation with metastasis.

Askin's tumor: a case report and literature review.

Askin's tumor is a primitive neuroectodermal tumor developing from the soft tissues of the chest wall. Its diagnosis approach is complex and requires a multidisciplinary team. Given the rarity of this entity, no regimen has been validated in the literature. We report two cases of Askin's tumor with a major response to polychemotherapy and surgical resection in one case. These cases show that treatment of Askin's tumor should be multimodal, requiring discussion in multidisciplinary tumor working groups.

Clear Cell Carcinoma of Minor Salivary Glands: The Nasopharynx, an Uncommon Site of Origin.

Clear cell carcinoma is a rare minor salivary gland neoplasm. Its occurrence in the nasopharynx is uncommon. A limited number of cases are reported in the literature. Here, we report an additional case of clear cell carcinoma of the nasopharynx managed by induction chemotherapy followed by chemoradiotherapy, and we describe the clinical presentation, pathological features, and outcome. A 63-year-old man presented with an exophytic, ulcerative, and easily hemorrhagic tumor on the left side of the nasopharynx. A diagnosis of primary, cT4N0M0, clear cell carcinoma of the minor salivary gland was confirmed by a core needle biopsy through nasopharyngoscopy and staging procedures. The patient was treated by induction chemotherapy followed by concomitant chemoradiotherapy with clinical benefit and disease stabilization. Primary salivary gland clear cell carcinoma of the nasopharynx is uncommon. A definitive diagnosis requires an appropriate workup. The optimal treatment is unclear. Chemoradiotherapy might be a good option to manage such cases.

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.

Exploring the landscape of immunotherapy approaches in sarcomas.

Sarcomas comprise a heterogenous group of malignancies, of more than 100 different entities, arising from mesenchymal tissue, and accounting for 1% of adult malignancies. Surgery, radiotherapy and systemic therapy constitute the therapeutic armamentarium against sarcomas, with surgical excision and conventional chemotherapy, remaining the mainstay of treatment for local and advanced disease, respectively. The prognosis for patients with metastatic disease is dismal and novel therapeutic approaches are urgently required to improve survival outcomes. Immunotherapy, is a rapidly evolving field in oncology, which has been successfully applied in multiple cancers to date. Immunomodulating antibodies, adoptive cellular therapy, cancer vaccines, and cytokines have been tested in patients with different types of sarcomas through clinical trials, pilot studies, retrospective and prospective studies. The results of these studies regarding the efficacy of different types of immunotherapies in sarcomas are conflicting, and the application of immunotherapy in daily clinical practice remains limited. Additional clinical studies are ongoing in an effort to delineate the role of immunotherapy in patients with specific sarcoma subtypes.

A rare case of sphenoid giant cell tumor: Case report & review of imaging features post short-term denosumab treatment.

Background: Giant cell tumors (GCTs) are locally aggressive but rarely malignant bone neoplasms that uncommonly involve the skull. In this report, we describe a tumor of the sphenoid sinus. Case presentation: A 51-year-old female was presented with headache, and bilateral decreased visual acuity, CT scan, and brain MRI revealed an infra-sellar enhancing tumor expanding to the sellar and supra-sellar region which proved to be a GCT. the patient had received 03 months of preoperative denosumab-based treatment and imaging follow-up showed regression in size and morphology modifications of tumor tissue. Conclusion: This is one of few reports to describe the appearance of sphenoid bone GCT, and the first report to highlight the effects of short-term denosumab treatment in GCTb in such a location.

Molecular classification of soft tissue sarcomas for adequate diagnosis: A study on the northeast population of Morocco.

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors. For adequate therapeutic management, an accurate diagnosis is necessary. In Morocco, the diagnosis is essentially based on the morphological and immunohistochemical study. Compared to other techniques, fluorescence in situ hybridization (FISH) is easier to develop and less expensive. This study aims to assess the feasibility and utility of implementing FISH technique to improve diagnostic accuracy and establish a good classification. Material and methods: This is a retrospective cohort study. 211 cases of mesenchymal tumors were included. Hematoxylin Eosin Safran (HES) staining was performed in all cases followed by immunohistochemistry (IHC). FISH was performed in all cases with suspected STS. The probes used were EWSR1, MDM2 and SS18. The performance of FISH and histopathological test were evaluated by the ROC curve method (receiver operating characteristic). We evaluated the concordance between FISH and real time PCR by Cohen test. Results: The real-time PCR technique showed good agreement with the FISH test by a Kappa coefficient of 60% (p = 0.035). FISH was able to confirm that it is more accurate (Youden's Index = 91%) than histological/immunohistochemical analysis (Youden's Index = 51%), as well as the positive predictive value was higher (100%) with an ROC curve finding a larger area under the curve of 0.953 (95% CI: 0.918-0.988), p = 0.000 which supports that FISH shows high performance to present an accurate final diagnosis. Conclusion: This is the first and the largest Moroccan series for the molecular diagnosis of STS by FISH. Our study shows that paraffin FISH is a sensitive and specific ancillary tool in the diagnosis of STS when used in the appropriate clinicopathological context.

Managing the risk of toxicity in the treatment of elderly patients with soft tissue sarcomas.

INTRODUCTION: Nearly half of soft tissue sarcomas (STS) occur after the age of 65 years. Treating these patients is a complex issue in the absence of specific guidelines. AREAS COVERED: This is a narrative review that summarizes current data on the efficacy and the safety of different treatment strategies in this subpopulation. EXPERT OPINION: Age per se should not be a limiting factor to treatment. Surgery remains the treatment of choice offering the only chance of cure. The potential for benefit from adjuvant therapies must be discussed in the context of expected treatment-related toxicities and impairment of quality of life. Efficacy of systemic treatment in advanced disease did not differ from that in younger patients. However, safety must be considered when selecting treatments. Managing the risk of toxicity requires an assessment of vulnerabilities with validated tools. The Comprehensive geriatric assessment has become increasingly accepted but need to be validated in STS patients. Frailty should not exclude patients from potentially life-saving therapy. The correction of reversible conditions and active supportive care may make the treatment safer. Future studies are warranted to define better the patterns, benefits, risks of existing treatments. New options remain to be identified to reduce toxicity.

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.

Perineal and pelvic aggressive angiomyxoma: Imaging finding in an uncommon case report.

Aggressive angiomyxoma is a rare benign and locally invasive mesenchymal tumor that is found most frequently in women at reproductive age. We report typical CT and MRI appearances of a 36-year old young woman with an aggressive angiomyxoma of the pelvis and perineum that was proved by ultrasound guided biopsy.This study describe the imaging features of theses tumors,wich may help to approch the diagnosis by their distinctive imaging with high signal intensity on T2-weighted image related to the myxomatous stroma and their characteristic of swirling or layering internal pattern after intravenous gadolinium contrast administration.We also review the CT and MRI features of this disease in the current literature.

How Can a Multidisciplinary Approach Improve Prognosis of Soft-Tissue Sarcomas of Extremities?

Soft-tissue sarcomas are malignant tumors that require good management within specialized centers. Our study aims to assess the benefit of handling these kinds of tumors using the Multidisciplinary Meeting (MDM) approach. The current paper details this approach through a prospective study that has lasted for 42 months in the HASSAN II University Hospital Center, Fez, Morocco. During this research work, 116 cases were selected with an average age of 53 years. In 95.7% of the cases, it was found that the lower limb was the most frequent tumor type (78.4%). Also, ninety-two (92) patients (79.3%) have had a prior biopsy. Ninety-nine (99) patients (85.3%) have received a magnetic resonance imaging scan (MRI) before surgery. Sixty-three (63) patients were operated on, including R0 resection used for 37 patients, R1 used for 21 patients, and R2 used for five patients. As a result, liposarcomas were the most frequent type (30.1%), followed by synovial sarcomas (14.6%), leiomyosarcomas (9.5%), ewing sarcoma (8.6), and undifferentiated pleomorphic sarcomas (7.7%). In addition, neoadjuvant chemotherapy was used for 36 patients. The other 22 patients received adjuvant chemotherapy and/or radiotherapy. The overall survival rate was 60.56 months, which proves a significant improvement, thanks to the multidisciplinary meeting approach. Conclusion. The conducted investigation has shown that using MDM for managing soft-tissue sarcomas of extremities improves the patients' survival rate. Moreover, results have proven MDM might allow optimal treatment regarding less local recurrence and metastasis.

A rare case of locally advanced fibrosarcoma of diaphysal humerus managed successfully with limb-sparing procedures after neoadjuvant chemotherapy.

Fibrosarcomas (FS) of bone are a rare malignancy accounting for less than 5% of all primary malignant bone neoplasms. Diagnosis and treatment approaches of this entity are complex and require a skilled and experienced multidisciplinary team.Authors report their experience with a case of FS of humerus showing a pathologic complete response to neo-adjuvant chemotherapy based on adriamycin, cisplatin and ifosfamid. This approach allowed limb-sparing surgery with an excellent functional and psychological result.

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.

[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.

[Outcome of locally advanced Darier and Ferrand dermatofibrosarcoma: about a case and literature review]. / Une réponse complète d'un dermatofibrosarcome de Darrier et Ferrand localement avancé: à propos d'un cas et revue de la littérature.

Darier and Ferrand dermatofibrosarcoma (DFS) is a rare skin tumor characterized by its local aggressiveness and a high risk of recurrences. Prognosis depends essentially on the quality of treatment. Complete response in Darier and Ferrand dermatofibrosarcoma with healthy margins, initially judged inoperable after 1 year of neoadjuvant imatinib-based treatment, has been rarely described in literature. We here report the case of a young female patient treated in the Department of Medical Oncology in FES for locally advanced DFS with complete response, in order to assess the role of imatinib and of targeted therapies in the treatment of DFS.