New horizons for platinum-resistant ovarian cancer: insights from the 2023 American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) Annual Meetings.

Platinum-resistant ovarian cancer is difficult to treat and has a poor prognosis. Patients with platinum-resistant ovarian cancer have limited treatment options and often have a limited benefit from existing chemotherapeutic agents. There is a lack of contemporary effective anticancer drugs and reliable predictive biomarkers for this aggressive cancer. Recent cutting-edge research presented at the 2023 American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) Annual Meetings has provided insights into several potential therapeutic targets, such as DNA damage repair proteins, cell-cycle regulators, and immune-modulating agents. In addition, antibody-drug conjugates have provided new practice-changing results in platinum-resistant ovarian cancer. Here, we review the results of research presented at this annual event, with a focus on clinical trials investigating novel treatment approaches for platinum-resistant ovarian cancer, in addition to predictive and prognostic biomarkers for optimal patient selection, and other topics, such as real-world evidence.

Immune-Checkpoint Inhibitors: A New Line of Attack in Triple-Negative Breast Cancer.

Poor prognosis is a distinctive feature of triple-negative breast cancer (TNBC). Chemotherapy has long represented the main and unique treatment for patients with TNBC. Recently, immune checkpoint inhibitors (ICIs) were investigated in several clinical trials and were approved for clinical use in TNBC patients that express programmed cell death protein-1 (PD-1) in combination with chemotherapy in the first-line setting. ICIs are also being investigated in the neoadjuvant and adjuvant settings for TNBC. This chapter aims to discuss different ICIs used to treat all TNBC stages to date.

Antibody-Drug Conjugates: A New Therapeutic Approach for Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subset associated with a worse prognosis and poor response to conventional chemotherapy. Despite recent advances in drug discovery, its management is still a challenge for clinicians, illuminating the unmet need to develop novel treatment approaches. Antibody-drug conjugates (ADC) are innovative oncology drugs that combine the specificity of monoclonal antibodies and the high efficacy of anticancer payloads, to deliver cytotoxic drugs selectively to cancer cells. Various ADCs were investigated for TNBC and have provided a promise for this aggressive women's cancer including the FDA-approved sacituzumab govitecan. In this chapter, we reviewed different ADCs studied for TNBC including their mechanisms of action, efficacy, and tolerability. Moreover, we have also discussed their therapeutic potential based on combinatorial approaches with other targeted therapies in early and metastatic TNBC.

Revisiting antibody-drug conjugates and their predictive biomarkers in platinum-resistant ovarian cancer.

Until to date, platinum derived drugs are still the backbone of treating ovarian cancer (OC). Most patients treated with platinum-based chemotherapy develop resistance during the course of their management. The treatment of platinum-resistant ovarian cancer (PROC) is challenging. Few therapeutic options are available for patients with this aggressive disease. Besides, there are liminal advances regarding new anticancer drugs as well as validated predictive biomarkers of clinical outcomes in this setting. The enrollment of PROC patients in interventional studies is limited as compared to newly launched clinical trials for platinum-sensitive OC. Enthusiastically, the emergence of antibody-drug conjugates (ADCs) has provided promising findings for further clinical development in PROC. ADCs have the advantage to selectively deliver cytotoxic drugs to cancer cells expressing several of antigens using specific monoclonal antibodies based on the concept of immune bioconjugation. This innovative class of therapeutics showed encouraging early signs of clinical efficacy in PROC particularly mirvetuximab soravtansine that has been successfully introduced into three randomized and controlled phase III studies. In this review, the evidence from clinical trials supporting the development of ADCs targeting folate receptor alpha, sodium-dependent phosphate transporter 2B, dipeptidase 3, mesothelin, mucin 16, and tissue factor using various cytotoxic payloads in PROC is reviewed.

Does the "Devil" originate from the fallopian tubes?

Epithelial ovarian cancer (OC) is a heterogeneous disease and continues to be mostly diagnosed in advanced stages. The high lethality, the high rate of platinum-resistance, and the poor survival outcomes are the principal factors for categorizing OC among the most aggressive gynecological cancers. Only recently, a substantial progress has been made in our latest understanding of the origins of OC, particularly of high-grade serous histology. For a long time, the accumulation of genetic alterations in epithelial single layer cells of ovarian cysts caused by cyclic ovulations was considered as the most important driver and the long-standing dogma of ovarian tumorigenesis. Besides, the unique biological features and high histological heterogeneity of OC did not support this hypothesis. Indeed, various extra-ovarian cells of origin and multiple sites to each histotype were proposed, supported by cogent evidence from clinical cohorts and animal studies. In light of this enigma, this review was conducted to discuss the recent evidence supporting the revised origins of ovarian carcinoma histotypes with a particular focus on high-grade serous OC which may impact diagnostic and preventive approaches.

Bevacizumab in metastatic colorectal cancer in a real-life setting - toxicity profile, survival outcomes, and impact of tumor sidedness.

Introduction: Targeting angiogenesis in metastatic colorectal cancer (mCRC) using bevacizumab is a standard of care. The addition of this targeted biological agent to first-line infusional fluoropyrimidine-based chemotherapy was associated with superior overall survival (OS) in several randomized and controlled studies for CRC patients in the metastatic setting. However, access to this therapy in countries with limited resources is challenging. In Morocco, bevacizumab was introduced for this indication after considerable efforts of the Ministry of Health and Lalla Salma Foundation to support cancer patients with a limited income. In this report, the real-world efficacy and safety of the combination of bevacizumab with chemotherapy in mCRC are reported based on a retrospective cohort in Eastern Morocco. Material and methods: The archives of the medical records of 98 mCRC patients treated with first-line bevacizumab at the Hassan II Regional Cancer Center (Oujda, Morocco) were sampled from 1st January 2014 to 31st December 2019 and analyzed using descriptive statistics, Kaplan-Meier estimation, and a multivariable Cox regression model for a time-to-event study. Results: The toxicity profile was dominated by grade I-II proteinuria (10%), bleeding events (10%), thromboembolic events (9%), grade I-III hypertension (3%), and other rare events such as delayed healing of the stoma, scar dehiscence, intestinal perforation, and heart failure deterioration. In terms of survival, median OS and progression-free survival in the whole cohort were 22 and 13 months respectively. Patients who benefited from a metastasectomy after bevacizumab treatment had 31 months of median OS as compared to 14 months in the matched cohort with non-resectable liver metastasis. Notably, we demonstrated that tumor sidedness is a predictive factor of OS [hazard ratio (HR) = 2.452; 95% CI: 1.434-4.191, p = 0.001]. Moreover, the median OS for patients who received between 10 and 20 or more than 20 bevacizumab administrations was 24 and 33 months respectively as compared to those who received less than 10 cures (17 months) (log rank p < 0.0001). These markedly improved outcomes were also confirmed in multivariate Cox regression. A highly significant association of bevacizumab use and OS was found after adjusting for covariates (HR = 0.518, 95% CI: 0.374-0.717; p < 0.0001). Conclusions: The current study confirmed the important place of this therapeutic strategy in mCRC. Additional studies with prospective enrollment are awaited to validate these findings.

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.

Consumption of modern and traditional Moroccan dairy products and colorectal cancer risk: a large case control study.

PURPOSE: The main objective of this study is to describe the association between the consumption of either traditional or modern dairy products or calcium intakes and the risk of colorectal cancer (CRC) in the adult Moroccan population. METHODS: A case-control study was conducted in five Moroccan hospital centers. The study was matched on sex, age (± 5 years) and center. Data were collected using validated food frequency questionnaire (FFQ) taking into account different types of Moroccan dairy products. Conditional logistic regression models were used to assess the association between dairy products consumption, calcium intakes and CRC risk subtypes. In all statistical tests, the significance level was set at 0.05. RESULTS: Among 1453 cases and 1453 matched controls, 50.7% were women and 49.3% were men. Milk ORb 0.84, 95% CI 0.74-0.96 and yogurt ORb 0.74, 95% CI 0.64-0.86 were inversely associated with CRC risk. Similar inverse associations were observed for traditional dairy products namely Lben ORb 0.77, 95% CI 0.67-0.88, Raib ORb 0.86, 95% CI 0.76-0.96 and Jben ORb 0.77, 95% CI 0.67-0.88. The dairy calcium intake was inversely associated to CRC overall ORb 0.83, 95% CI 0.74-0.93. CONCLUSIONS: Our study supports previous international evidence and suggests that individuals who have a high intake of either modern or traditional dairy products are at lower risk for CRC. These findings should be further confirmed by longitudinal data and studies investigating potential pathways involved.

Prediction of therapy response in ovarian cancer: Where are we now?

Therapy resistance is a major challenge in the management of ovarian cancer (OC). Advances in detection and new technology validation have led to the emergence of biomarkers that can predict responses to available therapies. It is important to identify predictive biomarkers to select resistant and sensitive patients in order to reduce important toxicities, to reduce costs and to increase survival. The discovery of predictive and prognostic biomarkers for monitoring therapy is a developing field and provides promising perspectives in the era of personalized medicine. This review article will discuss the biology of OC with a focus on targetable pathways; current therapies; mechanisms of resistance; predictive biomarkers for chemotherapy, antiangiogenic and DNA-targeted therapies, and optimal cytoreductive surgery; and the emergence of liquid biopsy using recent studies from the Medline database and ClinicalTrials.gov.

First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases.

BACKGROUND: Breast cancer is the most frequent malignancy among women in Eastern Morocco. In this paper, we provide the first report on molecular breast cancer subtypes in this region. This is the largest population-based study on breast cancer among Moroccan women. METHODS: We analyzed 2260 breast cancer cases diagnosed at the Hassan II Regional Oncology Center between October 2005 and December 2012. Clinico-pathological and therapeutic features were studied. Molecular subtypes were determined and their associations with the clinico-pathological characteristics of the tumors were examined. RESULTS: The mean age at diagnosis was 48.7 years ±11.4. Invasive ductal carcinoma was the predominant histological type (77.1%), followed by lobular invasive carcinoma (15.3%). The mean size of breast tumors was 3.5 cm ± 1.96, and 84% of our patients are diagnosed with tumors of more than 2 cm. Histological grade II tumors were the most frequent (70.4%), followed by advanced histological grade (18%). Lymph node positive tumors were observed in 64.8% of cases and 29.3% of patients had distant metastasis. Most tumors were hormone receptor-positive (73%) and 28.6% were HER2 positive. 86.1% of patients with hormone receptor-positive breast cancer were given hormone therapy, while 68.9% of patients with HER2+ breast cancer received targeted therapy with Herceptin. Luminal A was the commonest molecular subtype, followed by Luminal B, Triple Negative and HER2. The highest prevalence of premenopausal patients was observed in Triple Negative subtype (72.2%), followed by HER2 (64.1%), Luminal B (62.2%), and Luminal A (55.1%). Luminal B subtype had a poorer prognosis than Luminal A. Compared with Triple Negative, HER2 subtype tend to spread more aggressively and is associated with poorer prognosis. CONCLUSIONS: Unlike Western countries, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage in Eastern Morocco. In this region, hormone receptor-positive tumors are predominant and so the majority of breast cancer patients should benefit from hormone therapy. HER2 subtype presents an aggressive tendency, suggesting the importance of anti-HER2 therapy. This study will contribute in developing appropriate screening and cancer management strategies in Eastern Morocco.

A Case Report of Uterine Müllerian Adenosarcoma With Sarcomatous Overgrowth.

Uterine adenosarcoma remains a highly aggressive tumor and is less described in the literature, with an unfavorable prognosis and an increased risk of local and distant recurrence. However, surgery, chemotherapy, and radiotherapy offer local control of the disease, and overall survival remains reduced. We report the case of a 79-year-old patient with stage IIIB uterine adenosarcoma, confirmed by immunohistochemistry and initially diagnosed with postmenopausal metrorrhagia. The patient was managed through a multimodal treatment by conducting a multidisciplinary consultation.

Primary Mediastinal Dysgerminoma: A Case Report and Literature Review.

Germ cell tumors are malignant tumors that mostly develop in the gonads. Extragonadal localization is rare and may affect the mediastinal and sacrococcygeal regions. Mediastinal seminoma is a malignant germ cell tumor of the mediastinum. The tumor typically occurs in the anterosuperior mediastinum in males and often has a very slow growth pattern and limited potential for metastasis. And symptoms are not very characteristic, with many patients being asymptomatic and the tumor being discovered incidentally. In this paper, we report the case of a 26-year-old patient admitted for the management of a large anterosuperior mediastinal tumor encasing the vital structures of the mediastinum.

Neck Epithelioid Sarcoma at an Unusual Location Mimicking Lymph Node Metastases of Nasopharyngeal Carcinoma: A Case Report.

Epithelioid sarcoma (ES) is an uncommon soft tissue sarcoma. It is usually located in the extremities and exceptionally in the neck. Its diagnosis constitutes a real challenge which is based on histology and immunohistochemistry staining that must be interpreted with caution given the anatomopathological similarities to other tumors. In this article, we report a case of a 37-year-old man admitted for a locally advanced ES of the neck. There were suspicions of lymph node metastases of nasopharyngeal carcinoma at the first pathological examination. The patient received palliative chemotherapy and was referred to the supportive care department. Through this case, we will discuss the clinical and anatomopathological characteristics and therapeutic options of this extremely rare tumor which poses a diagnostic challenge.

Synchronous occurrence of primary breast cancer and renal cell carcinoma: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Multiple Primary Malignant Neoplasms (MPMNs) are rare and refer to the occurrence of two or more distinct primary cancers with unrelated histopathological features in one patient. MPMNs can be classified as synchronous when tumors appear simultaneously or within six months of each other, and as metachronous when identified six months or more after the initial cancer diagnosis. While breast cancer often co-occurs with other primary cancers such as colorectal, endometrial, and ovarian cancers, the simultaneous presence of invasive lobular breast carcinoma and clear cell renal cancer is rare. CASE PRESENTATION: Here, we present the case of a 59-year-old postmenopausal woman who initially presented with breast carcinoma. Further investigation revealed a mass in the left kidney. The patient underwent a radical mastectomy and axillary dissection, followed by a left nephrectomy. After 8 months follow up, the patient is doing well and disease-free. CLINICAL DISCUSSION: Based on our case and literature review, the co-occurrence of breast carcinoma with renal cell carcinoma (RCC) is uncommon. Most reported cases involve metastatic tumors or metachronous breast malignancy with RCC. The etiology of synchronous malignancy is complex, and treatment options usually include a combination of surgery and/or adjuvant therapy. CONCLUSION: This case report contributes valuable insights to the limited literature on synchronous breast cancer with renal cell carcinoma. The rarity of this simultaneous occurrence underscores the importance of considering such cases. Documenting these cases is crucial for increasing awareness and reducing the resulting morbidity and mortality.

A testicular mass found to be a rare testicular adult-type granulosa cell tumor: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Granulosa cell tumors (GCTs) are rare tumors, which mostly affect the ovaries. GCTs are classified into two types: juvenile and adult. Adult testicular GCTs are potentially malignant sex cord-stromal tumors. CASE PRESENTATION: Here, we report a case of a 63-year-old man who presented with a right testicular nodule. Testicular ultrasound showed a hypoechoic tissue mass, measuring 3 cm and hyper vascularized in the color Doppler. A radical orchidectomy was performed. Histology showed a typical adult-type Granulosa cell tumor. After 12 months follow up, the patient is doing well and disease-free. CLINICAL DISCUSSION: According to our case and a review of the literature, this type of tumor is an uncommon and slow-growing neoplasm. The diagnosis is confirmed by histology, treatment is based on surgery, radical orchidectomy. Long-term follow-up of patients is essential because distant metastases may emerge late in the clinical course. CONCLUSION: This case report adds valuable insights to the limited literature on adult testicular Granulosa cell tumors. Radical orchidectomy remains the optimal treatment, and early diagnosis, coupled with surgery, significantly enhances prognosis.

Unusual Metastasis of Gastric Signet Ring Cell Carcinoma to the Breast: A Case Report of a Young Moroccan Patient.

Although gastric cancer is known to be an aggressive tumor that can spread throughout the body, breast metastases are uncommon. This entity is rarely reported in the literature, with an estimated incidence of 0.5 to 1.3%. We report a case of a rare association between a gastric subtype of signet ring cell carcinoma and metastasis to the breast. This uncommon situation is only documented through case reports. Most breast metastases have been detected after diagnosis of primary gastric cancer, during the first year. Several risk factors have been suggested to explain the aggressive behavior of these tumors, which correlates with very poor prognosis and short survival. We report the case of a 22-year-old female patient presenting with widespread metastatic gastric signet ring cell carcinoma with an unusual secondary site in the breast. The diagnosis was confirmed by immunohistochemistry (IHC) and radiology, and the patient was treated with palliative chemotherapy in accordance with the decision of the multidisciplinary tumor board.

A Pigmented Lesion of the Vulva Revealing Aggressive Melanoma: A Case Report.

Vulvar melanoma (VM) is a rare and aggressive malignancy presenting unique challenges in diagnosis and management. This report presents the case of a 61-year-old female patient and explores the clinical characteristics, diagnostic modalities, treatment strategies, and prognosis associated with VM. The patient presented with a painless mass on the labia majora, which turned out to be an undifferentiated malignant tumor process consistent with melanoma on examination. Immunohistochemical analysis confirmed the diagnosis and subsequent imaging revealed metastatic disease necessitating palliative chemotherapy following radiotherapy. VM is a rare and aggressive form of melanoma. While surgery is the standard of care for early stages, advanced stages require a combination of immunotherapy and targeted treatments. Clinical trials are vital to improve our understanding of this condition and the various aspects of its care. Collaboration among experts is essential to achieve progress in managing these patients.

Metastatic Epithelioid Hemangioendothelioma of the Bone: A Case Report and Literature Review.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular tumor, which can pose a diagnostic dilemma. It affects women more than men and is mainly found in the liver, lung, and bone. To date, there are no known predisposing factors. Limited data are available on the management of EHE at metastatic stages. The only optimal treatments to prevent metastatic dissemination are surgical resection and amputation in addition to radiotherapy at early stages. The oncologist in this rare entity plays an important role in the guided and standardized management of this disease, especially for advanced stages. In this article, we report the case of a 74-year-old patient admitted with swelling on the outer aspect of the right calf associated with pain and total functional impairment of the limb. The diagnosis favored a high-risk vascular tumor resembling EHE, confirmed by bone (tibia) and soft tissue biopsy. The patient underwent staging investigations, revealing diffuse metastases to the liver, bones, and lungs. The objective of this article is to advocate for oncological intervention in this entity, particularly in the advanced stages of the disease. Despite its rarity, the advancement of clinical trials and therapeutic recommendations remains crucial for optimal treatment.