Ongoing progress in BRAF-mutated non-small cell lung cancer.

Activating BRAF mutations are detected in 1.5% to 4.5% of patients with non-small cell lung cancer (NSCLC). These mutations involve the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway, and affect proliferation, differentiation, transcriptional regulation, and survival of cancer cells. Today, the combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib is the preferred first-line treatment option in patients with advanced BRAF V600-mutated NSCLC, with an objective response rate of 64%, a median progression-free survival of 10.2 months, a median overall survival of 24.6 months, and a median duration of response of 10.4 months, according to a pivotal phase 2 study. These outcomes remain inferior to those achieved with other targeted therapies in advanced NSCLC with other driver alterations. First-generation BRAF inhibitors are not active in the class II and III BRAF mutations that form the other half of BRAF mutations in NSCLC. New RAF inhibitors are being investigated in early trials. Novel treatment combinations, particularly with immune checkpoint inhibitors, are also underway. Patient referral to expert centers and enrollment in basket trials as well as serial tissue and liquid biopsies are needed to improve the understanding and the treatment outcomes of this relatively rare disease subset.

Complete Remission After Immunotherapy-Induced Abdominal Tuberculosis in a Patient With Advanced NSCLC Treated With Pembrolizumab: A Case Report.

The use of immune checkpoint inhibitors (ICIs) has drastically transformed the therapeutic landscape in lung cancer. Special focus has been put on immune-related toxicity; however, infections can also seem during ICI treatment. Although rare, tuberculosis (TB) has been increasingly identified after ICIs, and it seems that the programmed cell death protein 1 and programmed death-ligand 1 pathway is directly involved in its pathophysiology. Here, we describe the case of a patient with advanced NSCLC who developed abdominal TB after 32 months of pembrolizumab and who remains in tumor remission 10 months after discontinuation of this drug. Routine screening for latent TB before ICI treatment is advised, with closer collaboration between infectious disease specialists and oncologists.

Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer.

Antibody-drug conjugates (ADCs) are rapidly establishing their place and have shown promising preliminary data in lung cancer with impressive response rates and survival outcomes in previously treated patients.There are several ADCs currently in clinical trials for NSCLC and small cell lung cancer (SCLC). These ADCs often have different targets which include HER2, HER3, TROP2, CEACAM5, and MET in NSCLC and DLL3 in SCLC.Here we review the safety, and efficacy of newer ADCs in lung cancer including ado-trastuzumab emtansine, trastuzumab deruxetecan, patritomab deruxetecan, datopotamab deruxetecan, sacituzumab govitecan, SAR408701, Telisotuzumab vedotin, rovalpituzumab tesirine, lorvotuzumab mertansine, and sacituzumab govitecan.  Several novel methods are underway to improve the safety and efficacy of ADCs which include increasing the drug to antibody ratio (DAR), the potency of the payload, using more innovative payloads and replacing the antibody.

Update on molecular pathology and role of liquid biopsy in nonsmall cell lung cancer.

Personalised medicine, an essential component of modern thoracic oncology, has been evolving continuously ever since the discovery of the epidermal growth factor receptor and its tyrosine kinase inhibitors. Today, screening for driver alterations in patients with advanced lung adenocarcinoma as well as those with squamous cell carcinoma and no/little history of smoking is mandatory. Multiplex molecular platforms are preferred to sequential molecular testing since they are less time- and tissue-consuming. In this review, we present the latest updates on the nine most common actionable driver alterations in nonsmall cell lung cancer. Liquid biopsy, a simple noninvasive technique that uses different analytes, mostly circulating tumour DNA, is an appealing tool that is used in thoracic oncology to identify driver alterations including resistance mutations. Additional roles are being evaluated in clinical trials and include monitoring the response to treatment, screening for lung cancer in high-risk patients and early detection of relapse in the adjuvant setting. In addition, liquid biopsy is being tested in immune-oncology as a prognostic, predictive and pharmacodynamic tool. The major limitation of plasma-based assays remains their low sensitivity when compared to tissue-based assays. Ensuring the clinical validity and utility of liquid biopsy will definitely optimise cancer care.

Safety of current immune checkpoint inhibitors in non-small cell lung cancer.

Introduction: Immune checkpoint inhibitors (ICIs) achieved response rates around 20% in advanced non-small cell lung cancer (NSCLC) with 8% of patients becoming long-term survivors. Outcomes have improved with the addition of chemotherapy to immunotherapy or the combination of anti-PD(L)1 with anti-CTLA-4 agents.Areas covered: The incidence of immune-related adverse events (irAEs) in patients with NSCLC treated with ICIs varied across clinical trials and real-life studies. The onset of irAEs was 10 weeks. Toxic deaths from irAEs following anti-PD(L)1 administration resulted mainly from pneumonitis. Some irAEs such as rash and thyroiditis were probably associated with better clinical outcomes, though confounding biases exist. Investigations are on-going to determine ideal biomarkers to predict the occurrence, to screen for and to diagnose irAEs.Expert opinion: Prevention, anticipation, detection, treatment and careful monitoring are the five principles that characterize our management of irAEs. Distinguishing immune-induced pneumonitis from progression, pseudo progression, hyper progression, or other etiologies (COVID-19) can be particularly challenging in lung cancer due to the baseline vulnerable pulmonary function and thus requires caution and teamwork. We treat patients according to institutional and international guidelines and we only rechallenge them with ICIs after resolution of the AE and corticosteroid tapering.

Attenuated cytarabine, etoposide, dexamethasone plus rituximab (R-Mini-CYVE) regimen for patients with relapsed or refractory B-cell non-Hodgkin's lymphoma not eligible for intensive chemotherapy.

OBJECTIVES: To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R-mini-CYVE) in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). METHODS: We included pretreated adult patients with B-cell NHL who were ineligible for high-dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty. Up to 8 cycles were administered. RESULTS: Between 2013 and 2019, 56 patients with diffuse large B-cell lymphoma (n = 45, 80%) and indolent B-cell lymphoma (n = 11, 20%) were included. Median age was 75 (range: 36-88). Nineteen patients (35%) had a performance status ≥2. Patients received a median of 4 cycles of R-mini-CYVE. The objective response and the complete response rates were 50% and 33%, respectively. Median progression-free survival and overall survival times were 5.7 (95% CI: 0.5-10.9) and 14.7 (95% CI: 3.5-25.9) months, respectively. Grade ≥3 anaemia, thrombocytopenia and neutropenia occurred in 44%, 55% and 60% of the patients, respectively. The most frequent non-haematological grade ≥3 adverse events were sepsis (21%), fatigue (13%) and cytarabine-related neurotoxicity (5%). CONCLUSION: R-mini-CYVE demonstrated a meaningful antitumour efficacy and an acceptable safety profile in patients with relapsed/refractory B-cell NHL who were ineligible for HDT.

Impact of female gender and perspectives of pregnancy on admission in residency programs.

BACKGROUND: Motherhood is a demanding part of any women's life. Female interns could encounter difficulties during selection for residency program according to their plans of conceiving. Our aim is to explore the influence of female gender on the selection process of residency programs. METHOD: A cross sectional study was conducted in 2016 at a University Hospital in Beirut, Lebanon. Female residents and chief of departments were interviewed about the impact of the timing of motherhood during residency on the interview for admission. The questionnaire reviewed concerns among female Lebanese medical residents as well as the head of departments revolving around the choice of opting for motherhood and the decision of integrating into a residency program while juggling motherhood responsibilities. RESULTS: Eighty nine female residents and 22 head of department agreed to participate in this study. During the interviews for residency acceptance, 29 residents (34.5%) were directly asked about their family and motherhood plans; 9% of them did not reveal their intention. 35% of the residents thought that this subject could affect the program directors' decision. 47% of residents felt that having pregnant colleagues would add to their workload, and almost half of them (46%) believed that pregnant colleagues showed less productivity. 45% of program directors stated that it was an important factor taken into consideration during the interview, and 68% believed that residents tended to choose their specialty according to their life priorities. CONCLUSION: Pregnancy during residency training represents major challenges for female residents and their program directors. Rules and laws designed to set a balance between career and personal life are required to improve women's ability to participate equally in the workforce.

Feminine hygiene practices among female patients and nurses in Lebanon.

BACKGROUND: Inappropriate feminine hygiene practices are related to vulvovaginitis. We investigated the prevalence of personal hygiene habits among Lebanese women as well as their awareness of adequate practices. METHODS: Consists of a cross-sectional observational study. Female patients and nurses at Hotel-Dieu de France University Hospital in Beirut- Lebanon filled a questionnaire about their intimate hygiene habits and knowledge of proper practices. RESULTS: The study included 249 women. 21.3 % of the 136 nurses and 38.9 % of the 113 patients reported a history of vulvovaginitis. The majority of women took an intimate bath at least twice daily. 14 % of nurses and 17 % of patients douched.20. Seven percent of the nurses and 43.4 % of the patients used wet wipes. 1.5 % of nurses and 4.4 % of patients used feminine deodorant sprays. There was a significant lack of awareness mainly among patients about suitable hygiene practices as well for their adverse effects. CONCLUSION: Education provided by nurses, and other healthcare providers is essential to promote reproductive health among Lebanese women.

Anal cancer treatment: current status and future perspectives.

Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human papilloma virus. The majority of anal cancers are squamous cell carcinomas, and they are treated according to stage. In local and locally advanced AC, concomitant chemoradiation therapy based on mitomycin C and 5-Fluorouracil (5-FU) is the current best treatment, while metastatic AC, chemotherapy with 5-FU and cisplatin remains the gold standard. There are no indications for induction or maintenance therapies in locally advanced tumors. Many novel strategies, such as targeted therapies, vaccination, immunotherapy and photodynamic therapy are in clinical trials for the treatment of AC, with promising results in some indications.

Phase I and II Study of Gemcitabine and Vinorelbine in Heavily Pretreated Patients with Metastatic Breast Cancer and Review of the Literature.

BACKGROUND: Many phase II trials investigated the combination of Gemcitabine (G) and Vinorelbine (V) in the treatment of metastatic breast cancer (MBC) with variable outcomes. This study was conducted to explore whether this combination was effective and tolerable in MBC patients who were heavily pretreated with anthracyclines and taxanes. METHODS: A phase I study was conducted first to establish the maximum tolerated dose (MTD) of the G and V combination in MBC patients. Then, a phase II study evaluated the response rates, the median time to progression (TTP), the overall survival (OS) as well as the toxicities resulting from this combination at the MTD. RESULTS: Nine patients were enrolled in the phase I study. The MTD was identified as 700mg/m(2) of G on days 1 and 8 in combination with 15 mg/m(2) of V on days 2 and 9, every 21 days. Twenty-one of 25 patients involved in the phase II study were evaluable for response. No complete or partial responses were achieved; 6 patients (24.0%) had stable disease and 15 (60.0%) progressed. The median TTP was 2 months and the median OS 10 months. Grade 3/4 Neutropenia was the major hematologic toxicity, occurring in 52% of the cycles. The most common non-hematologic grade 3/4 toxicities were fatigue (18%), myalgias (17%) and arthralgias (13%). CONCLUSION: In heavily pretreated patients with MBC, the combination of G and V at the doses stated above was ineffective as it did not induce partial or complete responses. Other chemotherapy agents or combinations should be evaluated in future studies.