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The evolution of precision medicine in the field of oncology has led to a radical change in the course of malignancies. PARP inhibitors are drugs that block the activity of the PARP enzyme responsible for base excision repair and have shown significant positive response when used for tumors lacking homologous recombination, namely high efficacy among BRCA-mutated tumors. Since 2014, when olaparib received an accelerated US FDA approval in ovarian cancer, we witnessed many other FDA approvals for olaparib, rucaparib, niraparib and talazoparib. Additionally, many Phase I, II and III trials were published presenting revolutionizing results. Other ongoing trials combined PARP inhibitors with checkpoint inhibitors. We aimed in this review to state the FDA approvals for PARP inhibitors in breast, ovarian, fallopian tube and primary peritoneal cancers, report the major published trials in high impact medical journals, and mention the ongoing trials combining these drugs with checkpoint inhibitors.

PURPOSE Sunitinib offers improved efficacy for patients with metastatic renal cell carcinoma (mRCC). To provide better disease management in the Middle East, we studied its use in mRCC in real-life practice in this region. MATERIAL AND METHODS Patients diagnosed with mRCC and started on sunitinib between 2006 and 2016 from 10 centers in Africa and the Middle East region were studied in this regional, multicenter, observational, retrospective trial to obtain routine clinical practice data on the usage patterns and outcomes of sunitinib in mRCC in real-life practice. RESULTS A total of 289 patients were enrolled. Median age at diagnosis was 58.7 years. The patient characteristics were as follows: 73.6% of patients were males; 85.8% had clear-cell renal cell carcinoma (RCC); 97.5% had unilateral RCC; 66.3% had metastatic disease at initial diagnosis; 56.3% received previous treatment for RCC, among which 98.7% had undergone surgery; and 15.2% and 31.4% were classified in the favorable and poor-risk groups (expanded Memorial Sloan Kettering Cancer Center criteria), respectively. On treatment initiation, the mean total sunitinib dose was 48.1 mg, and 87.6% of patients were started on a sunitinib dose of 50 mg. The mean duration of sunitinib treatment was 9.6 months. Overall response rate was 20.8%, with a median duration of 8.2 months. Median time to progression was 5.7 months. Median follow-up time was 7.8 months. By months 12 and 24, 34.3% and 11.4% of patients, respectively, were still alive. Seventy-six patients (60.9%) experienced 314 adverse events. Twenty-three patients (8.0%) experienced 28 serious adverse events. Overall, 83 patients (28.7%) discontinued their sunitinib treatment. CONCLUSION The results are indicative of the general treatment outcomes of patients with mRCC in the Middle East using sunitinib in routine clinical practice. Reported adverse events are similar to those described in the literature but at lower frequencies.

The use of immune checkpoint inhibitors has been approved in the advanced and metastatic setting for many types of solid tumors. Nonetheless, their role in the adjuvant setting is limited to the treatment of surgically resected melanoma. Ipilimumab was the first immune checkpoint inhibitor approved for this indication, followed by nivolumab and pembrolizumab. Many ongoing trials are evaluating these molecules in the postoperative setting, alone or in combination with other therapies. Preliminary results are promising regarding the treatment of other cutaneous tumors, lung cancers, head and neck squamous cell carcinomas, bladder cancer and renal cell carcinomas. Some data assessing their use for the adjuvant treatment of esophageal, colorectal, ovarian cancer and other solid tumors are similarly emerging.

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy.

Stage III non-small cell lung cancer is a border line stage between localized and metastatic disease. PDL-1 is gaining an important role in the therapeutic arsenal of lung cancer, the most frequent cancer worldwide. We report for the first time a negativation of PDL-1 status in 2 cases of stage IIIA NSCLC with conversion to operable disease after using immunotherapy. The first patient was a 59-year old female diagnosed incidentally to have stage IIIA inoperable NSCLC that was treated with combination chemo-immunotherapy, and converted to operable disease with a negative PD-L1 in the postoperative setting. The second case is that of a 56-year old male that also had an inoperable stage IIIA NSCLC treated with chemotherapy first line followed by pembrolizumab at progression, then operated after surgical conversion, with negative PD-L1 postoperatively. In front of these findings, further work should be done to elucidate if the reverse of the PDL-1 status and the conversion to operability were due to the use of immunotherapy or to an incidental finding. If confirmed, it may have a therapeutic impact.

Metastatic colorectal cancer is the second most common cause of cancer death. Standard chemotherapy in combination with targeted therapies represent the backbone for the treatment of advanced disease. However, options are limited for patients progressing on these regimens. Genetic testing can offer patients the opportunity to benefit from novel therapies, namely immune checkpoint inhibitors in microsatellite instability-positive tumors. HER2 overexpression has recently emerged as a potentially targetable tumor marker in colorectal cancer (CRC). Despite the absence of approvals for anti-HER2 therapies in CRC, many agents such as trastuzumab and pertuzumab were tested and demonstrated significant antitumor activity, even in heavily pretreated patients. Early trials are also evaluating lapatinib, T-DM1, tucatinib and other anti-HER2 agents in patients with metastatic CRC, with promising results.

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to a worldwide medical crisis, affecting mostly immunocompromised patients, such as cancer patients. Various cancer societies have issued recommendations regarding patients care, but few studies addressed the perception of cancer patients regarding this pandemic. Objective The aim of the study was to assess the perception of cancer patients regarding their health risks during this pandemic and the preventive measures taken. Materials and methods An anonymous survey was conducted among cancer patients presenting for their treatment, during 10 consecutive working days, at the one-day clinic of Hotel-Dieu de France University hospital in Beirut. We evaluated their state of disease, comorbidities, precautions taken, and their concerns regarding the virus spread. Results A total of 216 patients responded with a mean age of 60 years. The majority had a good performance status (performance status = 0-1 in 79.6%), 51.4% had metastatic disease, and chemotherapy was the main therapy used (65.7%). A total of 52.3% of patients considered themselves to be at increased risk of contracting the virus. A total of 55.1% were more worried about the coronavirus rather than their disease. The priority was for the treatment of their cancer in 47.7% of the total patients studied. Of note, only 2.8% of planned one-day clinic reservations were canceled or postponed to avoid COVID-19 exposure. Conclusions Although cancer is a disease with a high mortality rate, many patients are more concerned about the actual pandemic rather than their disease. Nevertheless, the absenteeism from their treatment sessions during the COVID-19 atmosphere was minimal.

Aim: Report the epidemiologic and histologic characteristics of CNS lesions in the Lebanese population. Methods: We conducted a retrospective study evaluating 2025 CNS lesions diagnosed between 1998 and 2017 in the pathology laboratory of a Lebanese tertiary center. Results: 52.2% of patients were men with a median age of 50 years. The most frequent symptoms were epilepsy (22.5%), headache (20.6%) and motor impairment (19.9%). 90.7% of tumors were primary. Lung (35.6%) and breast (16.5%) were the most frequent primaries of metastases. 46.2% of primary CNS tumors were glial, predominantly astrocytic (56.4%), and (42.5%) were nonglial, predominantly meningeal tumors (58%). Conclusion: Compared with Western literature, the Lebanese population is characterized by a younger age of onset of brain tumors, a lower rate of meningiomas and a higher rate of gliomas.

Aim: As no meta-analyses have evaluated tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma (RCC), the aim was to evaluate the benefit of sunitinib and pazopanib in the adjuvant setting. Methods: This meta-analysis included all Phase III randomized controlled trials evaluating adjuvant sunitinib and pazopanib in high-risk RCC. Primary outcome was the comparison of disease-free survival (DFS) between tyrosine kinase inhibitors and placebo. Results: There was a tendency for significant overall effect of both sunitinib and pazopanib on DFS (hazard ratio: 0.85; 95% confidence interval: 0.72–1.01; p = 0.06). There was no significant difference between the effect of sunitinib and pazopanib on DFS (p = 0.51; I2 = 0%). Conclusion: Pazopanib and sunitinib could prolong DFS in the adjuvant treatment of high-risk RCC and seem equally effective in this setting.

Driving molecular mutations such as rearrangement of ALK and EGFR mutation is present in 5–10% of non-small-cell lung cancer. Tyrosine kinase inhibitors have shown good efficacy and thus become the standard of care. However, tumors have developed several resistance mechanisms against tyrosine kinase inhibitors, including transformation to small-cell lung carcinoma (SCLC). Transformation to SCLC after administration of anti-EGFR in EGFR-mutated adenocarcinoma has been well documented. Similarly, it appears that the same transformation happens in ALK-rearranged adenocarcinoma after the use of anti-ALK. In fact, to date eight cases have been reported in the literature. We aimed in this paper to focus on the characteristics, prognosis and treatment of these transformed SCLC.

Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months. The EXTREME protocol is commonly used in first-line setting. Recently, pembrolizumab, an anti-programmed death-1 agent, has been approved by the US Food and Drug Administration for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy. It demonstrated a durable objective response rate with a good safety profile and quality of life. Many ongoing trials are evaluating the use of pembrolizumab for the treatment of HNSCC in various indications such as adjuvant and neoadjuvant setting, maintenance and recurrent disease, alone or in combination with chemotherapy, radiation and targeted therapy. Finding those biomarkers predictive of response to immune checkpoints inhibitors has been a major concern. However, markers have been identified, such as PD-L1 expression, human papilloma virus infection, interferon-γ signature score, microsatellite instability and neoantigen production.

Aim: This study assessed the efficacy of anti-PD-1/PD-L1 agents in real life when used in second line or beyond. Materials & methods: Patients with advanced non-small-cell lung cancer progressing after standard chemotherapy and receiving immunotherapy in the second line or beyond were included. Results: One hundred and ten patients were included with PD-L1 expression above 50%, between 1–49 and

Testicular germ cell tumors are chemosensitive with very high cure-rates even in the metastatic setting. However, patients with platinum-refractory and relapsing tumors after autologous stem cell transplant have very poor outcomes despite salvage treatments, and with no effective alternative therapies. Immunotherapy, notably with PD-1 inhibitors, has proven to be very effective in treating various solid tumors. This review summarizes the experience with anti-PD-1 agents (pembrolizumab, nivolumab) in the treatment of testicular germ cell tumor relapsing after multiple lines of treatment, and exposes future trials evaluating newer checkpoint inhibitors in this setting.

Introduction Medical hypnosis has received an increasing attention during the past decades. Various applications of hypnosis can be incorporated into the oncology field. This study aims to assess the knowledge of Lebanese medical oncologists on the use of hypnosis in the management of cancer patients. Material and methods An anonymous questionnaire was sent to all Lebanese medical oncologists to assess their knowledge, opinion and understanding of hypnosis and its use in oncology, as well as the obstacles facing its application in Lebanon. Results Hundred and three Lebanese medical oncologists responded to the survey, with a response rate of 65%. The findings revealed that most oncologists had little or no knowledge about hypnosis, but recommended it due to the benefits they believed it provided for the patients in improving chronic pain, invasive procedures, chemotherapy-induced nausea and anxiety. Around 40% of participants were interested in receiving a training in hypnosis. Lebanese oncologists also described many obstacles to the practice of hypnosis, mainly the lack of training for this technique and the lack of financial resources. Conclusion Despite all obstacles, the majority of Lebanese oncologists would recommend hypnosis to their patients in order to improve their quality of life.

Aim: This study aims to recognize the distribution of different seizures etiologies in cancer patients, the most common primary tumors responsible for brain metastases, the most epileptogenic primary tumors and the therapeutic modalities. Methods: A retrospective study was conducted at Hotel-Dieu de France Hospital targeting patients admitted to hematology–oncology department between 2005 and 2016 who presented a seizure. Results: Of the 153 included patients, mean age was 57 years (standard deviation = 16 years) and a male predominance (66%). The majority of seizures were due to a primary tumor (49%) or brain metastases (32%). Other reversible (metabolic and drug) or nonreversible causes (carcinomatous meningitis, radiation and cardiovascular complications) formed the remaining causes. Regarding antiepileptic treatments, sodium valproate was mostly used, followed by levetiracetam and phenytoin. Conclusion: Numerous reversible causes are involved in the onset of epileptic seizures, including metabolic disorders, antibiotics and chemotherapies.

According to the latest data of the World Cancer Research Fund International (2012), Lebanon has the second highest age-standardized incidence rate of bladder cancer worldwide, both for "men" and "both-sexes" categories. This study was designed to assess bladder cancer knowledge among the Lebanese population. Between November 2017 and January 2018, a cross-sectional study was directed, including patients and visitors of one of the largest university hospitals in the capital Beirut. A face-to-face questionnaire evaluated knowledge regarding, among others, the most important risk factor for bladder cancer and the most frequent revealing symptom. This survey also obtained information regarding smoking habits. A total of 701 participants completed the survey. A total of 49.1% were younger than 50 years, 56.3% were male, 56.6% had a college degree and 54.4% were ever smokers. Two-hundred and thirty-two (33.1%) of the 701 surveyed individuals have never heard about bladder cancer. 157 (33.5%) of the 469 individuals who have heard about bladder cancer were unaware that bladder cancer is different from prostate cancer. Overall, 312 (44.5%) individuals have heard about bladder cancer and knew that it is different from prostate cancer. Of these 312 subjects, 94 (30.1%) knew that tobacco smoking was the most important risk factor for bladder cancer, 166 (53.2%) associated blood in the urine with the most frequent revealing symptom of this disease and 66 (21.2%) considered that bladder cancer is frequent in Lebanon compared to other cancers. This study suggests the lack of knowledge of the Lebanese population towards bladder cancer, including its association with tobacco.

Breast cancer is the most common malignancy among women worldwide and the leading cause of cancer death in many countries (1). In around 20% to 25% of breast cancer cases, there is an overexpression of HER2 or an amplification of its gene (HER2-positive subtype); HER2 is a transmembrane receptor implicated in tumor replication, invasion and dissemination (2). HER2-positive breast cancer is characterized by a worse prognosis, aggressive disease, higher mitotic index, worse nuclear grade and lymph nodes positivity (3).

BACKGROUND Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (WandW) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W and W strategy in Lebanese CLL patients. MATERIALS AND METHODS A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W and W strategy, different chemotherapeutic regimens and the indications for treatment. RESULTS Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was 39885/mm3 [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was 191255/mm3 [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W and W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W and W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade. CONCLUSIONS This retrospective review of CLL clinical practice showed an important implementation of the W and W strategy with a long duration, especially in early stage cases with low RAI or Binet scores.

e13045 Background: Hereditary breast (BC) and ovarian cancer (OC) genetic alterations are considered the most prevalent among familial cancer. To date, four studies have exposed the mutations related to hereditary BC predisposition in the Lebanese population , with percentage of BRCA-related pathogenic mutations ranging between 5 % and 15 %. Methods: Between 2017 and 2019, 117 patients with high risk hereditary breast and ovarian cancer were referred to undergo the testing at the Unité de Génétique médicale (UGM) of Saint-Joseph University of Beirut, Lebanon. The sequencing was accomplished by using the 21-panel Next-Generation Sequencing (NGS) method for all of our patients, to which we also added the MLPA technique followed by the Sanger sequencing for validation whenever a genetic alteration was found. Results: From 117 Lebanese women with high-risk hereditary breast and ovarian cancer predisposition, 19 pathogenic mutations were identified in this study: 11 BRCA1, 1 BRCA2, 2 PALB2, 1 ATM, 1 CDH1, 1 MSH6, 1 RAD51C, and 1 BRIP1. Among those, 13 patients had BC, one had OC and five were healthy individuals. Five similar mutations were found within the BRCA1 gene, the p.C44F mutation, accounting for 45.4 %, thus suggesting a founder effect. Average age at diagnosis in the BC patients carrying a mutation was 41 years and 38.5% had a triple negative BC. Conclusions: The overall pathogenic mutation rate was equal to 16.2% while the BRCA deleterious mutation rate was 10.3% lower to those reported in the literature. The p.C44F mutation appeared five times suggesting a founder effect. [Table: see text]

e15141 Background: In terms of frequency, colorectal cancer (CRC) is the 3rd cancer in Lebanon with 1093 incidences registered in 2015. To this date not a single screening campaign has been organized in the country. Fecal immunochemical test (FIT) is an advised screening technique. We found it useful to organize a screening campaign using FIT to determine the prevalence of CRC in a population of 3000 healthy Lebanese allowing the extraction of useful data. Methods: 3000 tubes were distributed to Lebanese adults (45-80 years old) at average risk of developing CRC, followed by explanations. FIT analysis was done at the medical genetics unit (UGM) of Saint-Joseph University and patients with positive FIT were asked to undergo further investigations. Results: Out of the 3000 distributed tests, 705 were returned (23.5%) with 459 fully analyzable. The age median was 56 (45-80). Sex ratio F/M 2.3. Out of the 459 patients, 278 (60.5%) showed 0ng/ml, 137 (29.8%) showed 1-79ng/ml, 3 (0.6%) showed 80-99ng/ml (intermediate risk values), 33 (7.1%) showed 100-800ng/ml considered as a positive value and finally 8 (1.7%) showed over range values. Among the 44 positive patients we contacted 41. Out of the 8 (18%) colonoscopies results received: 5 showed hemorrhoids leading to false positive, 1 ulcerative ileitis, 1 tubular adenomas and 1 carcinoma. Conclusions: While it was hard for us to quantify people for whom a free FIT was proposed, the low restitution rate among those who took the test shows the necessity of national screening and sensitization campaigns.