Preoperative and Postoperative Systemic Therapy for Operable Non–Small-Cell Lung Cancer

Cisplatin-based adjuvant chemotherapy remains the standard of care for patients with resected stage II or III non–small-cell lung cancer. However, biomarker-informed clinical trials are starting to push the management of early-stage lung cancer beyond cytotoxic chemotherapy. This review explores recent and ongoing studies focused on improving cytotoxic chemotherapy and incorporating targeted and immunotherapies in the management of early-stage, resectable lung cancer. Adjuvant osimertinib for patients with EGFR-mutant tumors, preoperative chemoimmunotherapy, and adjuvant immunotherapy could improve outcomes for selected patients with resectable lung cancer, and ongoing or planned studies leveraging biomarkers, immunotherapy, and targeted therapy may further improve survival. We also discuss the unique barriers associated with clinical trials of early-stage lung cancer and the need for innovative trial designs to overcome these challenges.

Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer

With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed.

Deciphering the Immune–Tumor Interplay During Early-Stage Lung Cancer Development via Single-Cell Technology

Lung cancer is the leading cause of cancer-related death worldwide. Cancer immunotherapy has shown great success in treating advanced-stage lung cancer but has yet been used to treat early-stage lung cancer, mostly due to lack of understanding of the tumor immune microenvironment in early-stage lung cancer. The immune system could both constrain and promote tumorigenesis in a process termed immune editing that can be divided into three phases, namely, elimination, equilibrium, and escape. Current understanding of the immune response toward tumor is mainly on the “escape” phase when the tumor is clinically detectable. The detailed mechanism by which tumor progenitor lesions was modulated by the immune system during early stage of lung cancer development remains elusive. The advent of single-cell sequencing technology enables tumor immunologists to address those fundamental questions. In this perspective, we will summarize our current understanding and big gaps about the immune response during early lung tumorigenesis. We will then present the state of the art of single-cell technology and then envision how single-cell technology could be used to address those questions. Advances in the understanding of the immune response and its dynamics during malignant transformation of pre-malignant lesion will shed light on how malignant cells interact with the immune system and evolve under immune selection. Such knowledge could then contribute to the development of precision and early intervention strategies toward lung malignancy.

Proportions of Beneficial Factors in MLR, NLR, PLR and D-dimer in Preoperative Peripheral Blood of Patients With Early Stage Lung Cancer as Predictors of Patient Survival After Surgery

ObjectiveThe purpose of this paper is to predict the following items. preoperative baseline monocyte-to-lymphocyte ratio (MLR)、neutrophil-to-lymphocyte ratio (NLR) Platura-to-lymphocyte ratio (PLR) and dimeric fibrin fragment D (D-dimer) associated with clinical outcome in patients with Early Lung Cancer (LC).MethodsWe performed a retrospective analysis of 376 patients with LC. Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier, and univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Finally, multivariate Cox regression analysis was used to evaluate the influence of favorable factors on patients’ OS and PFS combined with the basic clinical characteristics of the patient ResultsAmong the variables screened by univariate Cox regression, MLR < 0.22, NLR < 1.99, PLR < 130.55 and D-Dimer < 70.5 (ng/ml) were significantly associated with both better OS and PFS. In multivariate Cox regression analysis, it was determined that MLR and D-Dimer had a better independent correlation with OS (p = 0.009, p = 0.05, respectively), while MLR was only better independently associated with PFS (P = 0.005). Furthermore, according to the number of favorable factors, patients with none of these factors had a significantly worse prognosis than patients with at least one of these factors.ConclusionBaseline characteristics of low MLR, low NLR, low PLR and low D-dimer were associated with better outcomes.

Bibliometric Analysis of the Top-Cited Publications and Research Trends for Stereotactic Body Radiotherapy

ObjectiveThis study aims to analyze the 100 most cited papers and research trends on stereotactic body radiotherapy (SBRT).MethodsWe used Web of Science to identify the 100 most frequently cited papers on SBRT on September 29, 2021 and extracted the following data: publication year, source title, country/region, organization, total citations, and average number of citations per year. The research type and research domain were classified independently by the authors. Then we carried out a bibliometric analysis to determine the trends in research on SBRT.ResultsThese 100 papers were cited a total of 26,540 times, and the median number of citations was 190 (range, 138-1688). “Stereotactic body radiation therapy for inoperable early stage lung cancer” by Timmerman et al. had the highest number of total citations (1688 times). International Journal of Radiation Oncology, Biology, Physics published the largest number of papers (37 papers), followed by Journal of Clinical Oncology (13 papers). The USA contributed the most papers (67 papers), followed by Canada (18 papers). Primary lung cancer (33 papers, 10,683 citations) and oligometastases (30 papers, 7,147 citations) were the most cited research areas.ConclusionsTo the best of our knowledge, this is the first bibliometric analysis of the most frequently cited papers on SBRT. Our results provide insight into the historical development of SBRT and important advances in its application to cancer treatment. Early-stage non–small-cell lung cancer and oligometastases were the most cited research areas in the top 100 publications on SBRT, and SBRT combined with immunotherapy was a hot topic in the past few years. This study is helpful for researchers to identify the most influential papers and current research hotspots on SBRT.

Genetic and immunologic features of recurrent stage I lung adenocarcinoma

Although surgery for early-stage lung cancer offers the best chance of cure, recurrence still occurs between 30 and 50% of the time. Why patients frequently recur after complete resection of early-stage lung cancer remains unclear. Using a large cohort of stage I lung adenocarcinoma patients, distinct genetic, genomic, epigenetic, and immunologic profiles of recurrent tumors were analyzed using a novel recurrence classifier. To characterize the tumor immune microenvironment of recurrent stage I tumors, unique tumor-infiltrating immune population markers were identified using single cell RNA-seq on a separate cohort of patients undergoing stage I lung adenocarcinoma resection and applied to a large study cohort using digital cytometry. Recurrent stage I lung adenocarcinomas demonstrated higher mutation and lower methylation burden than non-recurrent tumors, as well as widespread activation of known cancer and cell cycle pathways. Simultaneously, recurrent tumors displayed downregulation of immune response pathways including antigen presentation and Th1/Th2 activation. Recurrent tumors were depleted in adaptive immune populations, and depletion of adaptive immune populations and low cytolytic activity were prognostic of stage I recurrence. Genomic instability and impaired adaptive immune responses are key features of stage I lung adenocarcinoma immunosurveillance escape and recurrence after surgery.