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.

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.

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.

Conflict of Interest Disclosure in Oncology: Preliminary Insights From the Global ONCOTRUST-1 Cross-Sectional Study.

PURPOSE: Conflicts of interest (COIs) between oncologists and industry might considerably influence how the presentation of the research results is delivered, ultimately affecting clinical decisions and policy-making. Although there are many regulations on reporting COI in high-income countries (HICs), little is known about their reporting in low- and middle-income countries (LMICs). Oncology Transparency Under Scrutiny and Tracking (ONCOTRUST-1) is a pilot global survey to explore the knowledge and perceptions of oncologists regarding COI. MATERIALS AND METHODS: We designed an online 27-question-based survey in the English language to explore the perceptions and knowledge of oncologists regarding COI, with an emphasis on LMICs. Descriptive statistics and the Consensus-Based Checklist for Reporting of Survey Studies guidelines were used to report the findings. RESULTS: ONCOTRUST-1 surveyed 200 oncologists, 70.9% of them practicing in LMICs. Median age of the respondents was 36 (range, 26-84) years; 47.5% of them were women. Of the respondents, 40.5% reported weekly visits by pharmaceutical representatives to their institutions. Regarding oncologists' perceptions of COI that require disclosure, direct financial benefits, such as honoraria, ranked highest (58.5%), followed by gifts from pharmaceutical representatives (50%) and travel grants for attending conferences (44.5%). By contrast, personal or institutional research funding, sample drugs, consulting or advisory board, expert testimony, and food and beverage funded by pharmaceutical industry were less frequently considered as COI. Moreover, only 24% of surveyed oncologists could correctly categorize all situations representing a COI. CONCLUSION: These findings underscore the importance of clear guidelines, education, and transparency in reporting COI in oncology. This hypothesis-generating pilot survey provided the rationale for ONCOTRUST-2 study, which will compare perceptions of COI among oncologists in LMICs and HICs.

Global Landscape of the Attack of Predatory Journals in Oncology.

PURPOSE: Open-access publishing expanded opportunities to give visibility to research results but was accompanied by the proliferation of predatory journals (PJos) that offer expedited publishing but potentially compromise the integrity of research and peer review. To our knowledge, to date, there is no comprehensive global study on the impact of PJos in the field of oncology. MATERIALS AND METHODS: A 29 question-based cross-sectional survey was developed to explore knowledge and practices of predatory publishing and analyzed using descriptive statistics and binary logistic regression. RESULTS: Four hundred and twenty-six complete responses to the survey were reported. Almost half of the responders reported feeling pressure to publish from supervisors, institutions, and funding and regulatory agencies. The majority of authors were contacted by PJos through email solicitations (67.8%), with fewer using social networks (31%). In total, 13.4% of the responders confirmed past publications on PJo, convinced by fast editorial decision time, low article-processing charges, limited peer review, and for the promise of academic boost in short time. Over half of the participants were not aware of PJo detection tools. We developed a multivariable model to understand the determinants to publish in PJos, showing a significant correlation of practicing oncology in low- and middle-income countries (LMICs) and predatory publishing (odds ratio [OR], 2.02 [95% CI, 1.01 to 4.03]; P = .04). Having previous experience in academic publishing was not protective (OR, 3.81 [95% CI, 1.06 to 13.62]; P = .03). Suggestions for interventions included educational workshops, increasing awareness through social networks, enhanced research funding in LMICs, surveillance by supervisors, and implementation of institutional actions against responsible parties. CONCLUSION: The prevalence of predatory publishing poses an alarming problem in the field of oncology, globally. Our survey identified actionable risk factors that may contribute to vulnerability to PJos and inform guidance to enhance research capacity broadly.

Exploring scientific misconduct in Morocco based on an analysis of plagiarism perception in a cohort of 1,220 researchers and students.

Plagiarism is widely regarded as an issue of low- and middle-income countries because of several factors such as the lack of ethics policy and poor research training. In Morocco, plagiarism and its perception by academics has not been investigated on a large scale. In this study, we evaluated different aspects of plagiarism among scholars based on a 23-question cross-sectional survey. Factors associated with plagiarism were explored using contingency tables and logistic regression. The survey results covered all public universities (n=12) and included 1,220 recorded responses. The academic level was significantly associated with plagiarism (p<0.001). Having publication records was statistically associated with a reduced plagiarism (p=0.002). Notably, the ability of participants to correctly define plagiarism was also significantly associated with a reduced plagiarism misconduct (p<0.001). Unintentional plagiarism (p<0.001), time constraint to write an original text (p<0.001), and inability of participants to paraphrase (p<0.001) were associated factors with plagiarism. Moreover, participants that considered plagiarism as a serious issue in academic research had significantly committed less plagiarism (p<0.001). The current study showed that various actionable factors associated with plagiarism can be targeted by educational interventions, and therefore, it provided the rationale to build training programs on research integrity in Morocco.

FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?

Gastric cancer (GC) is the third leading cause of cancer-associated death worldwide. The majority of patients are diagnosed at an advanced/metastatic stage of disease due to a lack of specific symptoms and lack of screening programs, especially in Western countries. Thus, despite the improvement in GC therapeutic opportunities, the survival is disappointing, and the definition of the optimal treatment is still an unmet need. Novel diagnostic techniques were developed in clinical trials in order to characterize the genetic profile of GCs and new potential molecular pathways, such as the Fibroblast Growth Factor Receptor (FGFR) pathway, were identified in order to improve patient's survival by using target therapies. The aim of this review is to summarize the role and the impact of FGFR signaling in GC and to provide an overview regarding the potential effectiveness of anti-FGFR agents in GC treatment in the context of precision medicine.

Inexpensive Systemic Inflammatory Biomarkers in Ovarian Cancer: An Umbrella Systematic Review of 17 Prognostic Meta-Analyses.

The association of several inflammation-based biomarkers [lymphocyte-to-monocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios (LMR, NLR, and PLR, respectively)] with the survival of epithelial ovarian cancer (EOC) patients has been extensively investigated in several systematic reviews and meta-analyses (MAs) of observational studies. The aim of this umbrella systematic review is to appraise all available results in published MAs that explored the association between these biomarkers and EOC outcomes. An umbrella systematic review of the current evidence for systemic inflammatory biomarkers in the peripheral blood of EOC patients was performed by searching several databases including PubMed/Medline and Web of Science. The quality of the MAs was appraised using the AMSTAR-2 tool as well as other qualitative criteria. The evidence was graded from convincing (Class I) to weak (Class IV). Our umbrella review appraised 17 MAs of retrospective studies (range: 7-16) with a number of enrolled patients ranging from 1,636 to 4,910 patients in each MA. All these MAs demonstrated that pretreatment high NLR and PLR, as well as low LMR, were independent predictors of poor overall survival and progression-free survival in EOC. Nearly all published MAs were conducted by Chinese researchers (16/17) and were redundant in their character. Another issue in these MAs is the absence of prior PROSPERO database registration as well as the earlier exclusion of the gray literature. On the other hand, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE)-based reporting guidelines were used in nine out of the 17 MAs. A good number of MAs have transparently provided funding acknowledgment. The AMSTAR-2-based assessment showed low quality in 11 out of the 17 reviewed MAs. This negative rating was largely due to the absence of critical domains. Finally, all evaluated MAs were rated as Class III or IV (suggestive and weak, respectively). Despite the power of MAs in increasing sampling and precision, the quality of the current non-randomized evidence on this topic is still weak. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020201493.

Ovarian cancer in Morocco: Time to act is now.

•Ovarian cancer seems is a neglected cancer in Morocco.•No publications that impact clinical practice were published in the last decade.•In this editorial, we provide our vision to develop this ignored area of gynecologic oncology.

Tracing ovarian cancer research in Morocco: A bibliometric analysis.

BACKGROUND: The burden of ovarian cancer (OC) in low-income countries continues to increase annually. This gynecological cancer, known for its poor survival outcomes, has not attracted much interest in medical research as compared to other women's malignancies such as breast cancer. This bibliometric study was conducted to better depict the global map and the future directions of scientific productivity in the area of OC research in Morocco. METHODS: Publication trends on OC were retrospectively analyzed using a number of bibliometric parameters based on the Pubmed database and other resources. RESULTS: During the time period (1900-2018), a total number of 74 publications responding to the inclusion criteria were found and incorporated in the bibliometric analysis. This was dominated by case reports and case series on rare ovarian tumors (n = 60). In the core cluster, only 10 original studies and 3 reviews on OC were published by Moroccan researchers. After full-text appraisal for study population, only two clinical original articles included OC patients. The other clinical studies included breast cancer patients only or were suggestive of inherited OC. In addition, 3 preclinical in vitro studies were found during the literature search. The majority of these publications were covered by Pubmed and Web of Science core collection and all published in English language. The H-index of top 10 Moroccan scientists in this area didn't exceed 10. Importantly, research and review articles were frequently published in influential journals. However, the number of publications as compared to other African countries was very low. Moreover, a similar trend in terms of article per each newly diagnosed OC case, GDP per capita and per million was also noticed. For gender distribution, female scientists were first authors in the majority of these papers but less represented as leading last authors. In the complementary cluster of other article types on rare ovarian tumors, 70% of the items were published in French and approximately 60% were indexed on Pubmed. During the last five years, a marked acceleration of publishing this research category with little impact in the evidence-based practice was noticed. CONCLUSIONS: This research area in gynecologic oncology seems to be neglected and needs to be prioritized in future research projects in Morocco particularly given the aggressive behavior of this women's cancer and the few available therapeutic options. There is an unmet need for studies on OC in all fields particularly epidemiology, clinic-pathological characteristics, and survival outcomes.

Practical Tools and Guidelines for Young Oncologists From Resource-Limited Settings to Publish Excellence and Advance Their Career.

Cancer research is evolving worldwide. However, publishing high-quality academic literature in oncology remains challenging for authors in the developing world. Young oncologists in low- and middle-income countries experience several barriers including lack of funding and research facilities, as well as inadequate training. Publication best practices, science integrity, and ethics are required to improve oncology research quality and therefore, improve patients' care in these countries. To achieve this goal, we propose some basic principles and tools that may help young oncologists especially in developing countries overcome these issues and boost their academic careers.

The Emerging Role of Liquid Biopsy in Gastric Cancer.

(1) Background: Liquid biopsy (LB) is a novel diagnostic method with the potential of revolutionizing the prevention, diagnosis, and treatment of several solid tumors. The present paper aims to summarize the current knowledge and explore future possibilities of LB in the management of metastatic gastric cancer. (2) Methods: This narrative review examined the most recent literature on the use of LB-based techniques in metastatic gastric cancer and the current LB-related clinical trial landscape. (3) Results: In gastric cancer, the detection of circulating cancer cells (CTCs) has been recognized to have a prognostic role in all the disease stages. In the setting of localized disease, cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) qualitative and quantitative detection have the potential to inform on the risk of cancer recurrence and metastatic dissemination. In addition, gastric cancer-released exosomes may play an essential part in metastasis formation. In the metastatic setting, the levels of cfDNA show a positive correlation with tumor burden. There is evidence that circulating tumor microemboli (CTM) in the blood of metastatic patients is an independent prognostic factor for shorter overall survival. Gastric cancer-derived exosomal microRNAs or clonal mutations and copy number variations detectable in ctDNA may contribute resistance to chemotherapy or targeted therapies, respectively. There is conflicting and limited data on CTC-based PD-L1 verification and cfDNA-based Epstein-Barr virus detection to predict or monitor immunotherapy responses. (4) Conclusions: Although preliminary studies analyzing LBs in patients with advanced gastric cancer appear promising, more research is required to obtain better insights into the molecular mechanisms underlying resistance to systemic therapies. Moreover, validation and standardization of LB methods are crucial before introducing them in clinical practice. The feasibility of repeatable, minimally invasive sampling opens up the possibility of selecting or dynamically changing therapies based on prognostic risk or predictive biomarkers, such as resistance markers. Research is warranted to exploit a possible transforming area of cancer care.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of outcomes in inflammatory breast cancer.

Background: Inflammatory breast cancer (IBC) is uncommon, aggressive and associated with poor survival outcomes. The lack of prognostic biomarkers and therapeutic targets specific to IBC is an added challenge for clinical practice and research. Inflammatory biomarkers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios (NLR and PLR) demonstrated independent prognostic impact for survival in breast cancer. In our study, these biomarkers were investigated in a cohort of patients with nonmetastatic IBC. Methods: A retrospective cohort of 102 IBC patients with nonmetastatic disease was conducted at the Mohammed VI University Hospital (Oujda, Morocco) between January 2010 and December 2014. NLR and PLR were obtained from blood cell count at baseline before neoadjuvant chemotherapy (NACT) from patients' medical records. The receiver operating characteristic was used to find the optimal cut-off. Correlation between these blood-based biomarkers and response to NACT was analyzed by Chi-squared and Fisher's exact test. Their prognostic value for predicting disease-free survival (DFS) and overall survival (OS) was performed based on Cox regression models. Results: Totally, 102 patients with IBC were included in the analysis. Pathologic complete response (pCR) after NACT, defined by the absence of an invasive tumor in the breast tissues and nodes after surgery (ypT0 ypN0), was observed in eight patients (7.8%). NACT response was found to be associated with menopausal status (p = 0.039) and nodal status (p < 0.001). Patients with a low NLR had a higher pCR rate as compared with the high-NLR group (p = 0.043). However, the pCR rate was not significantly associated with age (p = 0.122), tumor side (p = 0.403), BMI (p = 0.615), histological grade (p = 0.059), hormone receptors status (p = 0.206), HER2 (p = 0.491) and PLR (p = 0.096). Pre-treatment blood-based NLR of 2.28 was used as the cut-off value to discriminate between high and low NLR according to the receiver operating characteristic curves. Similarly, a value of 178 was used as the cut off for PLR. Patients with low-NLR had a significantly better 5-year DFS (p < 0.001) and OS (p < 0.001) than the high-NLR group. Moreover, low-PLR was significantly associated with higher DFS (p = 0.001) and OS (p = 0.003). The NLR showed a significant prognostic impact for DFS (HR: 2.57; 95% CI: 1.43-4.61; p = 0.01) and for OS (HR: 2.92; 95% CI: 1.70-5.02; p < 0.001). Similarly, a meaningful association between PLR and 5-year DFS (HR: 1.95; 95% CI: 1.10-3.46; p = 0.021) and OS (HR: 1.82; 95% CI: 1.06-3.14; p = 0.03) was noticed. Conclusions: High NLR and PLR were found associated with reduced DFS and OS in nonmetastatic IBC. Further studies are awaited to confirm these findings.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.