Hazem I. Assi

Immune checkpoint inhibitors in advanced non-small cell lung cancer: Immunotherapy in NSCLC

The emergence of immune checkpoint inhibitors for the treatment of cancer has led to major changes to the therapeutic landscape of lung cancer. Improvements in overall survival relative to standard chemotherapy have been observed in the first‐line and second‐line therapy settings for patients with advanced non–small cell lung cancer (NSCLC) who are treated with immune checkpoint inhibitors. Consequently, every patient with advanced‐stage NSCLC is now a candidate for immune checkpoint inhibitor therapy. However, it is clear that the benefit from therapy is not universal, and identification of biomarkers to select therapy has assumed importance. In addition to programmed cell death receptor ligand 1 expression, both tissue‐based and blood‐based markers are under evaluation to select patients. In an era of increasing costs of care and potential for toxicities related to immune checkpoint inhibition, proper patient selection is critical to the optimal use of this new class of agents. In addition, development of novel combination approaches has also emerged as an important way to improve the efficacy of immune checkpoint inhibition. Studies in earlier stages of NSCLC are already underway with the hope of improving the cure rate. In this article, the authors review the current landscape of immune checkpoint inhibitors in the treatment of advanced NSCLC. Cancer 2018;124:248‐61.

Controversial indications for sentinel lymph node biopsy in breast cancer patients.

Sentinel lymph node biopsy (SLNB) emerged in the 1990s as a new technique in the surgical management of the axilla for patients with early breast cancer, resulting in lower complication rates and better quality of life than axillary lymph node dissection (ALND). Today SLNB is firmly established in the armamentarium of clinicians treating breast cancer, but several questions remain. The goal of this paper is to review recent work addressing 4 questions that have been the subject of debate in the use of SLNB in the past few years: (a) What is the implication of finding micrometastases in the sentinel nodes? (b) Is ALND necessary in all patients who have a positive SLNB? (c) How accurate is SLNB after neoadjuvant therapy? (d) Can SLNB be used to stage the axilla in locally recurrent breast cancer following breast surgery with or without prior axillary surgery?

Recent Progress in Mutation-driven Therapy, Immunotherapy and Combination Therapy for the Treatment of Melanoma.

With increases in our understanding of the human genome and immune system, the treatment armamentarium for melanoma has benefitted from the development and approval of BRAF inhibitors, MEK inhibitors, immune checkpoint modulators via cytotoxic T-lymphocyte antigen-4 blockade, and PD-1 and PD-L1 inhibitors. These advances, however, have raised questions about combination therapy, the optimal sequential use of these agents, the limited assessment of response using traditional metrics, and the optimal selection of the population to be treated. In this review we summarize recent breakthroughs and then itemize the development of newer agents, potential prognostic and predictive biomarkers, resistance mechanisms, and strategies of combination therapy. We also emphasize the multifaceted attributes of immunotherapy in terms of durable responses and longterm survival that paradoxically necessitate further research into the underlying mechanisms and longer patient follow-up.

Anxiety, Depression and Quality of Life in Breast Cancer Patients in the Levant

Background: Limited data are currently available regarding the psychological well-being and quality of life of breast cancer patients after active treatment in Lebanon and the Arab region in general. The objective of this study was to determine the prevalence of anxiety and depression among Arab breast cancer patients and assess the quality of life with reference to socio-demographic and clinical characteristics. Methods: This cross-sectional study was conducted among female breast cancer patients diagnosed between January 2009 and March 2014, who were recruited from the outpatient clinics of Naef K. Basile Cancer Institute at the American University of Beirut Medical Center (AUBMC) from November 2015 till December 2016. An interview was conducted utilizing two validated questionnaires: the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Socio-demographic and clinical characteristics that might predict patient quality of life were collected and summarized. Results: A total of 150 patients were interviewed (median age 53.5±10.4 years). Most were assessed 3 to 5 years (68.7%) after initial diagnosis and had undergone surgery, chemotherapy, radiation, or hormonal therapy (97.3%, 79.3%, 80.7% and 86.0%, respectively). The median total HADS score was 10.0 ± 8.0, with approximately 41.3% of study participants having abnormal scores on the anxiety subscale and 24.7% on the depression subscale. Significant predictors of total HADS score were nationality and level of education (p=0.001, p=0.001 respectively; R2=0.181). Participants who were Iraqi, had stage IV disease, had a household monthly income below 1000 USD, or had received chemotherapy exhibited significantly lower total FACT-B scores, these being highly negatively correlated with total HADS scores (rs= -0.73, p=0.001). Conclusion: There is a vital need for the development of individualized interventions and psychosocial support programs tailored to the physical and psychological well-being of breast cancer patients in the Levant region.

Anaplastic Meningioma Presenting as a Left Parietal Mass: A Case Report

Patient: Female, 67 Final Diagnosis: Meningioma Symptoms: Headache Medication: — Clinical Procedure:— Specialty: Oncology Objective: Unusual clinical course Background: Meningiomas are slow-growing tumors attached to the dura mater and are composed of neoplastic meningothelial cells. The tumors are most commonly located in convexities, and it is relatively rare to find such a growth in the parietal region such as the one presented in this case report. Case Report: Because of its uncommon presentation, we hereby report the case of a 67-year-old, previously healthy, white Lebanese female patient who presented with forgetfulness, unsteady gait, right-sided motor weakness, and dysphagia. She was found to have an anaplastic meningioma located in the left parietal lobe that was treated by surgical resection. The patient had an uneventful postoperative course, and was stable at later follow-ups. Conclusions: This case report describes the clinical presentation, pathological findings, and the prognosis of this mass, which is atypical in this location, and has been rarely reported in the literature. We also review the literature on anaplastic meningiomas.

Emerging Biomarkers of the Future: Changing Clinical Practice for 2020

Progress in biomarker development has greatly enhanced our ability to categorize breast cancer into several clinical subtypes and to deliver better personalized therapies. Technological advances in gene expression profiling, signaling pathways, proliferation markers and tumor monitoring through detection of circulating tumor cells and free DNA, and measurements of genomic instability and germline mutations are being vigorously pursued in breast cancer research. Their application in routine clinical practice is increasing and helping further development of precision medicine. Ongoing challenges include assessing the utility and feasibility of these tests, interpreting the large amounts of genomic data that are being generated, translating the information to clinical practice, and constructing clinical trials on molecularly driven approaches. In this article, we will review current and emerging promising biomarkers and their roles in the management of patients with breast cancer.

Phyllodes tumors of the breast treated in a tertiary health care center: case series and literature review:

Objective This study was performed to determine the subtypes of phyllodes tumor (PT) in patients at a single tertiary healthcare center in Lebanon and to describe their characteristics along with a review of the literature. Methods This single-institution retrospective cohort study included all cases of PT of the breast treated at the American University of Beirut Medical Center from 1 January 2010 to 31 December 2014. The patients’ demographic data, tumor characteristics, treatment data, and pathology reports were analyzed. Results Thirty patients were enrolled. Their median age was 42 years. In total, 66.7% had benign disease and 22.3% had malignant disease. Twenty-seven patients underwent surgery, four received radiotherapy, and one received systemic chemotherapy after PT progression. Twenty-seven patients had no recurrence at the last follow-up, two had local recurrence, and one had metastatic disease. All three patients with recurrence had an adequate negative surgical margin at the first excision. Conclusion This is the first cohort of patients with PT described in Lebanon and one of few in the Middle East. Our findings provide insight into the epidemiology, treatment modalities, and prognosis of PT in this geographical region.

EGFR as a clinical marker in glioblastomas and other gliomas

Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and a member of the tyrosine kinase superfamily receptor. Gliomas are tumors originating from glial cells, which show a range of aggressiveness depending on grade and stage. Many EGFR gene alterations have been identified in gliomas, especially glioblastomas, including amplifications, deletions and single nucleotide polymorphisms (SNPs). Glioblastomas are discussed as a separate entity due to their high correlation with EGFR mutants and the reported association of the latter with survival and response to treatment in this glioma subgroup. This review is a comprehensive report of EGFR gene alterations and their relations with several clinical factors in glioblastomas and other gliomas. It covers all EGFR gene alterations including point mutations, SNPs, methylations, copy number variations and amplifications, assessed with regard to different clinical variables, including response to therapy and survival. This review also discusses the current prognostic status of EGFR in glioblastomas and other gliomas, and highlights gaps in previous studies. This serves as an update for the medical community about the role of EGFR gene alterations in gliomas and specifically glioblastomas, as a means for targeted treatment and prognosis.

Management of leptomeningeal metastasis in breast cancer

Leptomeningeal metastasis (LM), which occurs when malignant cells spread to the central nervous system, is becoming an increasingly common complication in patients with breast cancer. Diagnosis and treatment of LM is challenging. Moreover, prognosis of patients with LM is poor, with a median survival of 6 months after diagnosis. This review highlights the strengths and limitations of currently available diagnostic tools and therapies for LM. The current treatments for LM, including radiotherapy, systemic therapy, and intrathecal treatment, aim to maintain the quality of life of patients by correcting neurological deficits and arresting neurological degeneration. However, there is no standardized therapy for LM because of a lack of randomized trials on this condition.

Thiotepa 10 mg/kg Treatment Regimen Is Superior to Thiotepa 5 mg/kg in TBF Conditioning in Patients Undergoing Allogeneic Stem-Cell Transplantation

Micro‐Abstract A study evaluating the optimal dose of myeloablation in thiotepa, busulfan, and fludarabine (TBF) conditioning included 29 patients who received TBF conditioning before allogeneic stem‐cell transplantation. Thirteen patients received 5 mg/kg thiotepa; the remaining 16 patients received 10 mg/kg. Patients deemed fit to receive 10 mg/kg conditioning had better overall and progression‐free survival than those who received 5 mg/kg, with no additional toxicities. Introduction The optimal intensity of myeloablation with a reduced‐toxicity conditioning regimen to decrease relapse rate after allogeneic stem‐cell transplantation without increasing transplant‐related mortality (TRM) has not been well established. Materials and Methods We compared outcomes between 5 mg/kg (T5) and 10 mg/kg (T10) thiotepa‐based conditioning regimens in 29 adults who underwent allogeneic stem‐cell transplantation for hematologic malignancies. Results After a median follow‐up of 11 months, TRM was 0% and 14% at 100 days and 1 year, respectively, with TRM observed only in the T5 group (P = .016). The relapse incidence at 1 year was 20%. No patient had disease in first complete remission at the time of transplantation. At 1 year, progression‐free and overall survival were 30% versus 87% (P = .012) and 46% versus 87% (P = .008) in the T5 and T10 groups, respectively. In univariate and multivariate analysis, only age at transplantation and total dose of thiotepa had a significant impact on TRM, overall, and progression‐free survival. Conclusion Patients deemed fit to receive T10‐based conditioning for allogeneic stem‐cell transplantation to treat high‐risk hematologic malignancies had better overall and progression‐free survival than those who received T5 with no additional toxicities. Patients should be stratified before conditioning, and those judged fit should receive T10, while the others should consider alternative reduced‐intensity conditioning regimens.