A Comprehensive Review on the Role of Lurbinectedin in Soft Tissue Sarcomas.

OPINION STATEMENT: Soft tissue sarcoma (STS), a substantial group of aggressive and rare tumors with tissue heterogeneity, is infrequently represented in clinical trials with an urgent necessity for newer treatment options. Lurbinectedin, an analog of trabectedin, is currently approved, in various countries, as a single agent, for the treatment of patients with relapsed small cell lung cancer (SCLC). However, preclinical and phase I and phase II trials have demonstrated the efficacy of lurbinectedin in different tumor types, including STS. The better understanding of the pathophysiology and evolution of STS as well as the mechanism of action of lurbinectedin in addition to the available data regarding the activity of this drug in this subset of patients will pave the way to newer therapeutic options and strategies.

Systemic Therapy in Advanced Pleomorphic Liposarcoma: a Comprehensive Review.

OPINION STATEMENT: The therapeutic approach of pleomorphic liposarcoma (PLPS), a rare high-grade subgroup of soft tissue sarcoma, is commonly extrapolated from the management of other LPS subtypes. Only published retrospective data on PLPS currently serve as a guide for oncologists without clear recommendations or specific guidelines. In the advanced setting, specific systemic therapy such as eribulin and trabectedin showed promising activity in comparison to conventional therapy (doxorubicin- and gemcitabine-based protocols), which currently remains the current standard of care at initial stages of the disease. The better understanding of soft tissue sarcoma (STS) pathophysiology and disease course has led to the development of adapted clinical trial designs for rare STS histotypes with specific treatment approach.

How to improve issuing, transfusion and follow-up of blood components in Southern and Eastern Mediterranean countries? A benchmark assessment.

To determine the existence of guidelines regarding the appropriate clinical use of blood and blood components, transfusion requests, and blood issuing/reception documents and procedures. The different bedside transfusion organizations/processes and hemovigilance are also analyzed. The ultimate objective is to identify safe potential options in order to improve blood safety at the lowest cost. Data emanating from eight Arabic eastern/southern Mediterranean countries who responded to five surveys were collected and tabulated. National recommendations for the clinical use of blood components especially for hemoglobinopathies are lacking in some countries. In matter of good practices in the prescription, issuing and reception of BCs, efforts were made either on national or local basis. Procedures regarding patient information and ethical issues are still lacking. Almost all Mediterranean countries apply two blood testing procedures on each patient sample. Only Morocco, Tunisia and Algeria perform bed side blood group testing; Egypt and Lebanon perform antibody screen and antiglobulin cross matching universally. Automation for blood testing is insufficiently implemented in almost all countries and electronic release is almost absent. National hemovigilance policy is implemented in Tunisia, Morocco, and Lebanon but the reporting system remains inoperative. Insufficient resources severely hinders the implementation of expensive procedures and programs; however, the present work identifies safe procedures that might save resources to improve other parts in the transfusion process (e.g. electronic release to improve safety in issuing). Moreover, setting up regulations regarding ethics in transfusing recipients along with local transfusion committees are crucially needed to implement hemovigilance in transfusion practice.

Long-term extracranial metastatic relapse of an intraventricular solitary fibrous tumor: a case report.

Solitary fibrous tumors (SFTs), an uncommon subtype of soft tissue sarcomas mesenchymal, are frequently diagnosed in the intra-thoracic region. Distant metastasis is detected in 10-40% of SFT patients with a predilection site to the lungs; nevertheless, these can occur rarely in the liver, brain, and bones. This entity was also reported in the abdomen, trunk, head, and neck, extremities but also, in the central nervous system (CNS). In the latter form of SFTs, the meninges were mostly affected while only a few cases were reported in the intraventricular and intraparenchymal region with distinct clinical and behavioral characteristics. In this article, we report the rare case of a relapsing intraventricular SFT with secondary extra-cranial metastases to the bones and soft tissues after 11 years of initial diagnosis, with focus on the available data in the literature on CNS SFTs.

Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network.

BACKGROUND: Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline-based regimens, gemcitabine-based regimens, and pazopanib in patients with InS. METHODS: Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2-positive InS who were treated with anthracycline-based regimens, gemcitabine-based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence-free survival (RFS), progression-free survival (PFS) and overall survival were computed by Kaplan-Meier method. RESULTS: Seventy-two patients were included (66 anthracycline-based regimens; 26 gemcitabine-based regimens; 12 pazopanib). In the anthracycline-based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real-world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline-related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively. CONCLUSION: This retrospective series shows the activity of anthracycline-based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.

Exploring the biological hallmarks of cancer of unknown primary: where do we stand today?

Cancer of unknown primary (CUP) affects a small percentage of the general population. Nonetheless, a substantial number of these patients have a poor prognosis and consequently succumb to their illness within a year of diagnosis. The natural history of CUP is characterised by early metastasis from the unknown primary site, aggressive course and resistance to conventional chemotherapy. Unfortunately, the processes by which this orphan disease originates and progresses have not been fully elucidated and its biology remain unclear. Despite the conceptual progress in genetic and molecular profiling made over the past decade, recognition of the genetic and molecular abnormalities involved in CUP, as well as the identification of the tissue of origin remain unresolved issues. This review will outline the biology of CUP by exploring the hallmarks of cancer in order to rationalise the complexities of this enigmatic syndrome. This approach will help the reader to understand where research efforts currently stand and the pitfalls of this quest.

Should we screen patients with hematologic malignancies for COVID-19?

The coronavirus disease (COVID-19) pandemic has posed several challenges to the hematology community to re-organize the medical care of patients with hematologic malignancies. Whereas the oncology societies favored a more or less conservative approach which considered the possibility of delaying treatment administration on a case-by-case basis, the hematology community guidelines were less stringent and recommended adequate individualized regimens. As countries are de-escalating the lockdown and the medical community is unable to foresee the end of the current outbreak will and whether the pandemic would eventually come back as a seasonal infection, there is interest in screening of patients with hematology malignancies with COVID-19 instead of limiting access to curative treatments. The rapidly accumulating knowledge about COVID-19 allows a better understanding of the diagnostic tools that may be potentially used in screening. Herein, we briefly review the pathophysiology of COVID-19, the rationale of screening of patients with hematologic malignancies, tools for screening, and available guidelines.

Palbociclib safety and efficacy beyond Ribociclib-induced liver toxicity in metastatic hormone-receptors positive breast cancer patient.

CDK4/6 inhibitors in association with aromatase inhibitors have led to a paradigm shift in the management of metastatic positive hormone-receptors breast cancer. Liver toxicity is common with these agents, but no data are reported on the sequential use of these CDK4/6 inhibitors in case of confirmed efficacy and intolerable toxicity. In this article, we report the successful use of Palbociclib in a metastatic positive hormone-receptors breast cancer patient after initial response to Ribociclib, which was interrupted for grade 4 liver toxicity.

Quality and safety measures in transfusion practice: The experience of eight southern/eastern Mediterranean countries.

BACKGROUND AND OBJECTIVES: Blood transfusion is inherently associated with risks, and little is known regarding the available quality and safety measures in developing countries. No studies or census has been carried out, and therefore, no data on this compelling issue are available. MATERIALS AND METHODS: Data emanating from eight Arabic eastern/southern Mediterranean countries who responded to five surveys were collected and tabulated. RESULTS: Asepsis during phlebotomy, screening for serological and immuno-haematological parameters and appropriate storage conditions are maintained across all countries. Variations in blood component processing exist. Universal leucoreduction is systematically applied in Lebanon. Nucleic acid testing is only performed in Egypt. Aphaeresis procedure, leucoreduction and quality control for blood components are virtually inexistent in Mauritania. Written donor questionnaire is absent in Algeria and Tunisia. Most donor deferral periods for infectious agents are inconsistent with international standards. CONCLUSION: Gaps in the processing and in the quality/safety measures applied to the manufacture of blood components are quite evident in most eastern/southern Mediterranean countries. The decision of establishing an effective collaboration network and an independent body - aside from WHO - composed of specialists that oversees all transfusion activities in these countries is certainly a crucial step towards ensuring an optimum level of blood safety.

The management of patients with metastatic prostate cancer during the COVID-19 pandemic.

During the ongoing global pandemic of coronavirus disease 2019 (COVID-19), the benefit of treating patients with cancer must be weighed against the COVID-19 infection risks to patients, staff and society. Prostate cancer is one of the most common cancers among men and raises particular interest during the pandemic as recent reports show that the TMPRSS2 (and other serine proteases), which facilitate the entry, replication and budding of the virion from a cell, can be inhibited using androgen deprivation therapy. Nevertheless, patients with metastatic prostate cancer commonly receive chemotherapy which may compromise their immune system. This paper aims to address the current status of the COVID-19 in patients with cancer overall and suggests an optimal approach to patients with metastatic prostate cancer.

How to manage transfusion systems in developing countries: The Experience of Eastern and Southern Mediterranean countries.

OBJECTIVES: To outline and analyse the national organisation, infrastructure and management of transfusion systems in countries sharing common historical, cultural and economic features and to decipher management trends, in order to potentially benchmark. BACKGROUND: Little is known regarding transfusion systems in Eastern/southern Mediterranean at a time international organisations are calling for the establishment of a safe and sustainable blood system. MATERIALS AND METHODS: Data emanating from eight Arabic-speaking Eastern/Southern Mediterranean countries who responded to five surveys were collected and tabulated. RESULTS: While similarities in terms of supervision by national authorities, authorization of blood centres, quality control and management information system are evident, some significant divergence between these countries do exists. Only Lebanon does not possess a national blood establishment or organisation for blood supply. Blood components are fully government-subsidised in Algeria and Mauritania. Algeria, Morocco and Tunisia have a blood supply that relies mainly on Voluntary non-remunerated donors. Plateletpheresis is performed in all countries except Mauritania while plasmapheresis exists only in Algeria and Egypt. Morocco is the sole country outsourcing its plasma for Plasma derived products. CONCLUSION: Despite the various challenges facing these countries, lot of progresses have been made so far in the field of transfusion medicine. Yet, nationally coordinated blood programs overviewed by national regulatory authorities and actively supported by local governments are still needed to ensure the optimum level of blood safety.

Overcoming the resistance to BRAF inhibitor by the double BRAF and MEK inhibitions in advanced melanoma: a case report.

The advent of BRAF and MEK inhibitors changed the landscape of the management of BRAF mutated melanoma patients. In this article, we report the case of a 51-year-old man with BRAF mutated locally advanced cutaneous melanoma of the head who demonstrated a limited response to initial anti-BRAF monotherapy followed by extensive surgery. Anti-PD1 therapy failed to reverse the disease progression. However, subsequent double inhibition of the BRAF and MEK pathways induced a fast and remarkable tumour response.

Second-line Treatments of Advanced Hepatocellular Carcinoma: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) constitutes the second leading cause of cancer-related deaths. First-line therapy is either sorafenib or lenvatinib. Several treatment options have been recently added to the second-line treatment of advanced HCC. The aim of this network meta-analysis of randomized controlled trials was to compare the second-line treatments of advanced HCC. METHODS: Network meta-analyses were computed for overall survival (OS), progression-free survival, rates of grade 3 to 5 adverse events, and for treatment discontinuation due to adverse events. OS was considered to be the primary outcome of this study, and everolimus was chosen to be the common comparator for efficacy analyses and placebo for safety analyses. Subgroup analyses were computed for OS in patients with hepatitis B, patients with hepatitis C, Asian patients, patients with macrovascular invasion, and patients with extrahepatic metastases. RESULTS: Thirteen randomized controlled trials including 5076 patients and evaluating 11 agents were found to be eligible. Regorafenib [hazard ratio (HR)=0.60, 95% confidence interval (CI)=0.44-0.81] and cabozantinib (HR=0.72, 95% CI=0.55-0.95) were found to significantly prolong OS compared with everolimus. The effect of regorafenib on OS tended to be conserved across patient subgroups. Regorafenib was also found to significantly prolong progression-free survival (HR=0.46, 95% CI=0.35-0.62) and significantly increase the rates of grade 3 to 5 adverse events (odds ratios=3.18, 95% CI=2.22-4.54) and treatment discontinuation due to adverse events (odds ratios=2.67, 95% CI=1.21-5.87). CONCLUSIONS: This network meta-analysis concludes that, based on current evidence, regorafenib could be the agent of choice in the second-line treatment of HCC, with cabozantinib as a possible alternative for sorafenib-intolerant patients.

Comparison of second-line treatments of recurrent and/or metastatic squamous cell carcinoma of the head and neck.

AIM: The literature lacks direct evidence comparing the different regimens evaluated in the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: We conducted a network meta-analysis (NMA) of the randomized controlled Phase III trials reporting on the second-line drug treatment options in R/M SCCHN. RESULTS: The eligible trials included 11 regimens among which six targeted therapies, two immune checkpoint inhibitors and three chemotherapy regimens. Only nivolumab has shown statistically significant superiority over methotrexate in terms of overall survival (HR: 0.64; 95% CI: 0.43-0.96) and objective response rate (OR: 2.51; 95% CI: 1.07-5.86). CONCLUSION: Based on the efficacy and safety outcomes of this network meta-analysis, nivolumab seems the most favorable regimen inthe management of R/M SCCHN.

Factors associated with the time to first palliative care consultation in Lebanese cancer patients.

INTRODUCTION: Early palliative care is recommended for cancer patients. However, palliative care consults (PCC) are often delayed in Lebanon. The aim of this study was to identify the factors associated with timing of PCC and their impact on the place of death. METHODS: This is a retrospective, single institution, study conducted at Hotel Dieu de France University Hospital in Lebanon. The clinical and demographic characteristics of oncology patients who received PCC were obtained. Cox and logistic regression models were used to evaluate the factors determining the time to first PCC and location of death, respectively. RESULTS: Two hundred and ten patients were included in our analyses with a median age of 69 years (range 22-92 years). The median survival times were: overall survival 18.7 months, time to first PCC 17.9 months, and survival post-PCC 0.6 months. Among patients who were followed-up at home, the median time spent at home was 0.6 months. Late PCC were associated with a childless status (HR = 0.57, 95%CI = 0.37-0.86, p = 0.007), awareness of the diagnosis (HR = 0.64, 95%CI = 0.45-0.91, p = 0.013), and lack of palliative home care (HR = 0.42, 95%CI = 0.25-0.65, p < 0.001). Older patients (OR = 1.03, 95%CI = 1.01-1.05, p = 0.026) and those who had been followed up at home during the PCC (OR = 160.56, 95%CI = 21.39-1205.50, p < 0.001) were significantly more likely to have died at home as opposed to the hospital. DISCUSSION: Cancer patients often receive PCC only shortly before their death. PCC for Lebanese cancer patients were found to be significantly delayed in patients that are childless, knowledgeable of their diagnosis, and lack home palliative care.

Different inhibitors for the same target in metastatic luminal breast cancer: is there any difference?

AIM: To determine which of the CDK4/6 inhibitors is the optimal treatment in metastatic luminal breast cancer. MATERIALS & METHODS: A network meta-analysis using the frequentist approach and generalized pairwise modeling was computed. RESULTS: The associations of aromatase inhibitor with ribociclib, palbociclib and abemaciclib were similar in efficacy. Palbociclib-based regimen was associated with significantly lower treatment discontinuation rates compared with the other approved drugs in this indication. CONCLUSION: In the absence of direct comparative evidence, the results of this network meta-analysis represent the best available evidence for decision making in the first-line treatment of metastatic luminal breast cancer.

Allergic diseases, smoking, and environmental exposure among university students in Lebanon.

INTRODUCTION: Smoking habits among university students in Lebanon are not clearly identified, and studies correlating these habits to asthma and allergic diseases are lacking. The primary objective of this study is to assess asthma and allergic diseases' predictors, particularly cigarette and/or waterpipe smoking and other environmental exposures, among university students. A second objective is to evaluate the potential role of these predictors as correlates of health-related self-assessment. METHODS: A cross-sectional study, using a proportionate cluster sample of 3000 Lebanese students in both public and private universities, was conducted between January 2015 and December 2015. RESULTS: The number of smokers at home, living close to an electricity generator and exposure to sand and dust significantly increased the odds of having asthma or allergic diseases (p = 0.015; OR = 1.183; p = 0.01; OR = 2.062; p = 0.001; OR = 3.558 respectively). Having tried cigarette smoking and having an air conditioner inside the means of transportation would decrease the odds of having asthma or allergic diseases by around 68% and 56.1% respectively (p = 0.009; ORa = 0.320; p = 0.01; ORa = 0.439 respectively). CONCLUSION: Although students with asthma or allergic diseases tended to avoid all identifiable atopic risk factors, lesser known environmental factors such as living close to an electricity generator, exposure to sand and dust, and exposure to car exhaust fumes were associated with a higher risk of asthma and a decrease in health related self-assessment. Students with asthma and allergic diseases smoked cigarettes and waterpipe at similar percentages, but cigarette smokers had a lower health related self-assessment.