Overview of Ca2+ signaling in lung cancer progression and metastatic lung cancer with bone metastasis

Intracellular Ca2+ ions that are thought to be one of the most important second messengers for cellular signaling, have a substantial diversity of roles in regulating a plethora of fundamental cellular physiology such as gene expression, cell division, cell motility and apoptosis. It has been suggestive of the Ca2+ signaling-dependent cellular processes to be tightly regulated by the numerous types of Ca2+ channels, pumps, exchangers and sensing receptors. Consequently, dysregulated Ca2+ homeostasis leads to a series of events connected to elevated malignant phenotypes including uncontrolled proliferation, migration, invasion and metastasis, all of which are frequently observed in advanced stage lung cancer cells. The incidence of bone metastasis in patients with advanced stage lung cancer is estimated in a range of 30% to 40%, bringing about a significant negative impact on both morbidity and survival. This review dissects and summarizes the important roles of Ca2+ signaling transduction in contributing to lung cancer progression, and address the question: if and how Ca2+ signaling might have been engaged in metastatic lung cancer with bone metastasis, thereby potentially providing the multifaceted and promising solutions for therapeutic intervention.

Durable Response to Immunotherapy Plus Chemotherapy in a Patient With Untreated, Brain-metastatic, EGFR Exon 20 Insertion Mutation Lung Adenocarcinoma

Epidermal growth factor receptor (EGFR) 20 exon insertion is the second most common EGFR aberrations in non-small cell lung cancer (NSCLC). Despite some novel EGFR inhibitors showing encouraging antitumor activity, clinically obtainable management for this subset of patients remains an unmet need. Although immune checkpoint inhibitors (ICIs) have led to unprecedented clinical benefit in metastatic NSCLC, clinical evidence suggests that EGFR mutant lung cancers rarely derive benefit from treatment with ICIs. We report that a lung adenocarcinoma patient harboring an actionable gene mutation of EGFR exon 20 insertion, high PD-L1 expression, high tumor mutational burden, as well as alterations in immune-related genes including CTNNB1 (Catenin β1) S37F and ARID2 (AT-rich interactive domain-containing protein 2) E1056X responded to upfront PD-1 inhibitor plus chemotherapy. As an advanced-stage lung cancer with brain metastases indicating poor prognosis, the patient achieved an unusual and durable response over 15 months. Upfront ICIs plus chemotherapy might be an option for some NSCLC patients harboring EGFR exon 20 insertion mutation. Further study is needed to validate the predictor involved in responders to ICIs-based therapy with EGFR mutations.

“Randomized trial of physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study”

Background Lung cancer survivors need more options to improve quality of life (QoL). It is unclear to what extent patients with advanced stage disease are willing to participate in home-based physical activity (PA) and if these interventions improve QoL. The goal of our study was to determine interest in participating in our 3-month home-based walking regimen in patients with advanced stage lung cancer. We used a randomized design to evaluate for potential benefit in PA and patient-reported outcomes. Methods We performed an open-label, 1:1 randomized trial in 40 patients with stage III/IV non-small cell lung cancer (NSCLC) evaluating enrollment rate, PA, QoL, dyspnea, depression, and biomarkers. Compared to usual care (UC), the intervention group (IG) received an accelerometer, in-person teaching session, and gain-framed text messages for 12 weeks. Results We enrolled 56% (40/71) of eligible patients. Participants were on average 65 years and enrolled 1.9 years from diagnosis. Most patients were women (75%), and receiving treatment (85%) for stage IV (73%) adenocarcinoma (83%). A minority of patients were employed part-time or full time (38%). Both groups reported low baseline PA (IG mean 37 (Standard deviation (SD) 46) vs UC 59 (SD 56) minutes/week; p = 0.25). The IG increased PA more than UC (mean change IG + 123 (SD 212) vs UC + 35 (SD 103) minutes/week; p = 0.051)). Step count in the IG was not statistically different between baseline (4707 step/day), week 6 (5605; p = 0.16), and week 12 (4606 steps/day; p = 0.87). The intervention improved EORTC role functioning domain (17 points; p = 0.022) with borderline improvement in dyspnea (− 13 points; p = 0.051) compared to UC. In patients with two blood samples (25%), we observed a significant increase in soluble PD-1 (219.8 (SD 54.5) pg/mL; p < 0.001). Conclusions Our pilot trial using a 3-month, home-based, mobile health intervention enrolled over half of eligible patients with stage III and IV NSCLC. The intervention increased PA, and may improve several aspects of QoL. We also identified potential biomarker changes relevant to lung cancer biology. Future research should use a larger sample to examine the effect of exercise on cancer biomarkers, which may mediate the association between PA and QoL. Clinical trial registration Clinicaltrials.gov (NCT03352245).

Structural and functional radiomics for lung cancer

Introduction Lung cancer ranks second in new cancer cases and first in cancer-related deaths worldwide. Precision medicine is working on altering treatment approaches and improving outcomes in this patient population. Radiological images are a powerful non-invasive tool in the screening and diagnosis of early-stage lung cancer, treatment strategy support, prognosis assessment, and follow-up for advanced-stage lung cancer. Recently, radiological features have evolved from solely semantic to include (handcrafted and deep) radiomic features. Radiomics entails the extraction and analysis of quantitative features from medical images using mathematical and machine learning methods to explore possible ties with biology and clinical outcomes. Methods Here, we outline the latest applications of both structural and functional radiomics in detection, diagnosis, and prediction of pathology, gene mutation, treatment strategy, follow-up, treatment response evaluation, and prognosis in the field of lung cancer. Conclusion The major drawbacks of radiomics are the lack of large datasets with high-quality data, standardization of methodology, the black-box nature of deep learning, and reproducibility. The prerequisite for the clinical implementation of radiomics is that these limitations are addressed. Future directions include a safer and more efficient model-training mode, merge multi-modality images, and combined multi-discipline or multi-omics to form “Medomics.”

Video-assisted thoracoscopic lobectomy is feasible for selected patients with clinical N2 non-small cell lung cancer

Few studies have evaluated the usefulness of video-assisted thoracoscopic surgery (VATS) for advanced-stage lung cancer. We aimed to evaluate the feasibility of VATS for treating clinical N2 (cN2) lung cancer. A retrospective cohort analysis was performed with data from 268 patients who underwent lobectomy for cN2 disease from 2007 to 2016. Using propensity score-based inverse probability of treatment weighting (IPTW), perioperative and long-term survival outcomes were compared. We performed VATS and open thoracotomy on 121 and 147 patients, respectively. Overall, VATS was preferred for patients with peripherally located tumors (p < 0.001). After IPTW-adjustment, all preoperative information became similar between the groups. Compared to thoracotomy, VATS was associated with shorter hospitalization (7.7 days vs. 9.1 days, p = 0.028), despite equivalent complete resection rates (92.6% vs. 90.5%, p = 0.488) and dissected lymph nodes (mean, 31.9 vs. 29.4, p = 0.100). On IPTW-adjusted analysis, overall survival (50.5% vs. 48.4%, p = 0.127) and recurrence-free survival (60.5% vs 44.6%, p = 0.069) at 5 years were also similar between the groups. Among selected patients with resectable cN2 disease and peripherally located tumors, VATS is feasible, associated with shorter hospitalization and comparable perioperative and long-term survival outcomes, compared with open thoracotomy.

Predictive molecular pathology in the time of coronavirus disease (COVID-19) in Europe

AimsLung cancer predictive biomarker testing is essential to select advanced-stage patients for targeted treatments and should be carried out without delays even during health emergencies, such as the coronavirus (COVID-19) outbreak.MethodsFifteen molecular laboratories from seven different European countries compared 4 weeks of national lockdown to a corresponding period in 2019, in terms of tissue and/or plasma-based molecular test workload, analytical platforms adopted, number of cases undergoing programmed death-ligand1 (PD-L1) expression assessment and DNA-based molecular tests turnaround time.ResultsIn most laboratories (80.0%), tissue-based molecular test workload was reduced. In 40.0% of laboratories (6/15), the decrease was >25%, and in one, reduction was as high as 80.0%. In this instance, a concomitant increase in liquid biopsy was reported (60.0%). Remarkably, in 33.3% of the laboratories, real-time PCR (RT-PCR)-based methodologies increased, whereas highly multiplexing assays approaches decreased. Most laboratories (88.9%) did not report significant variations in PD-L1 volume testing.ConclusionsThe workload of molecular testing for patients with advanced-stage lung cancer during the lockdown showed little variations. Local strategies to overcome health emergency-related issues included the preference for RT-PCR tissue-based testing methodologies and, occasionally, for liquid biopsy.