Acquired resistance mechanisms to osimertinib: The constant battle.

Lung cancer is the leading cause of cancer-related mortality worldwide. Detectable driver mutations have now changed the course of lung cancer treatment with the emergence of targeted therapy as a novel strategy that widely improved lung cancer prognosis, especially in metastatic patients. Osimertinib (AZD9291) is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used to treat stage IV EGFR-mutated non-small-cell lung cancer. It was initially designed to target both EGFR-activating mutations and the EGFR T790M mutation as well, which is the most common resistance mechanism to first- and second-generation EGFR-TKIs. Following the FLAURA trial, osimertinib is now widely used in the first-line setting. However, resistance to osimertinib inevitably develops, with numerous mechanisms leading to its resistance, classified into two main categories: EGFR-dependent and EGFR-independent mechanisms. While EGFR-dependent mechanisms consist mainly of the C797S EGFR mutation, EGFR-independent mechanisms include bypass pathways, oncogenic fusions, and phenotypic transformation, among others. This review summarizes the molecular resistance mechanisms to osimertinib, with the aim of identifying novel therapeutic approaches to overcome osimertinib resistance and improve patient outcome.

Telehealth in breast cancer following the coronavirus disease 2019 pandemic.

Breast cancer (BC) is the second most diagnosed cancer in 2018 with around 2.3 million cases globally in 2020. In March 2020 and after its worldwide spread, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak, a respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, a pandemic. During this time, cancer patients were heavily impacted and their treatment plans were changed due to measures to fight the disease and solutions had to be found to maintain their follow-up and management from a distance. Some cancer groups worldwide have recommended then the use of telemedicine for oncology patients to ensure the continuity of medical care during the pandemic. This method was considered effective and clinicians worldwide continued using telehealth even after the cessation of worldwide restrictions. To this end, current up-to-date data on the use of telemedicine in BC patient after the COVID-19 outbreak are summarized in this narrative review.

The combination of immune checkpoint inhibitors and chemotherapy in advanced non-small-cell lung cancer: the rational choice.

Lung cancer is the second most common cancer worldwide and the leading cause of death among cancers. The progressive approvals of immunotherapy as first-line treatment options have helped improve cancer prognosis. However, longer follow-up has confirmed the possibility of acquired resistance to immune checkpoint inhibitors (ICIs) which can lead to late relapses. Chemotherapy can act as a priming therapy to increase a tumor's response to immunotherapy. We aim through this review to explain the mechanism behind ICI resistance and the value of chemotherapy in escaping this resistance. Finally, all US FDA approvals regarding the management of metastatic non-small-cell lung cancer using a combination of ICIs and chemotherapy are summarized.

Awareness about the human papillomavirus (HPV) and HPV vaccine among medical students in Lebanon.

As a developing country, Lebanon lacks adequate awareness about Human papillomavirus (HPV) among its population, whether working in the medical field or not. Lebanon is traditionally considered conservative with a low incidence of sexually transmitted infections in general, but recently the incidence of HPV infections has significantly increased. The present cross-sectional study aims to evaluate the level of awareness on HPV and the attitude toward HPV vaccine among Lebanese medical students in a self-administered questionnaire-based survey. A total of 1009 answers were collected and analyzed from a population of about 3000 Lebanese medical students. Our study revealed a significant lack of knowledge and awareness on HPV among medical students in Lebanon, with a strikingly low vaccination rate (16.4%) due to many barriers. Education initiatives in medical schools remain crucial to raise awareness on HPV and promote HPV vaccination, especially among medical students, who represent the country's future healthcare providers and policymakers.

HER2 in metastatic colorectal cancer: a new to target to remember.

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.

Cancer Patients in the Era of Coronavirus: What to Fear Most?

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.

The Opinion of Oncologists on the Practice of Hypnosis among Cancer Patients in Lebanon.

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.

Epidemiologic and histologic characteristics of CNS lesions: a 20-year experience of a tertiary center in Lebanon.

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.

PARP inhibitors: a tsunami of indications in different malignancies.

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.

The emerging use of immune checkpoint blockade in the adjuvant setting for solid tumors: a review.

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.

OSSMAR: An Observational Study to Describe the Use of Sunitinib in Real-Life Practice for the Treatment of Metastatic Renal Cell Carcinoma.

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.

Triple-negative breast cancer: current perspective on the evolving therapeutic landscape.

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.

Lung cancer and immunotherapy: a real-life experience from second line and beyond.

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 <1% in 38.6, 27.3 and 34.1% of patients, respectively. Checkpoint inhibitors were used as second, third and fourth line in 74.7, 21.8 and 3.5%, respectively. Partial response was observed in 25.6% of patients. Median progression-free survival was 4 months and median overall survival was 8.1 months. Conclusion: Immunotherapies are emerging as important tools in the oncologic field with good responses in real-life practice.