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Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next‐generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7–27.0 months). ctDNA‐positive or ‐negative patients with tumors of any stage had similar disease‐free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non‐tissue derived. Patients with detectable postoperative ctDNA with tissue‐derived mutations had comparable DFS with those with non‐tissue‐derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.

Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next‐generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7–27.0 months). ctDNA‐positive or ‐negative patients with tumors of any stage had similar disease‐free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non‐tissue derived. Patients with detectable postoperative ctDNA with tissue‐derived mutations had comparable DFS with those with non‐tissue‐derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test. [ABSTRACT FROM AUTHOR]

The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/− radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and effective therapeutic strategy for the treatment of advanced NSCLC. Therefore, it is possible that ICIs for early-stage NSCLC may follow the pattern established in metastatic disease. Currently, there are several ongoing trials to determine the efficacy in the neoadjuvant setting for patients with local or regional disease. To date, only nivolumab in combination with chemotherapy has been approved by the U.S. FDA in the preoperative setting, but data continue to evolve rapidly, and treatment guidelines need to be determined. In this article, we review the current preclinical and clinical evidence on neoadjuvant ICIs alone and combination in the treatment of early-stage NSCLC. [ABSTRACT FROM AUTHOR]

For resectable cancer patients, a method that could precisely predict the risk of postoperative recurrence would be crucial for guiding adjuvant treatment. Since T cell receptor (TCR) repertoires had been shown to be closely related to the dynamics of cancers, here we enrolled a cohort of patients to evaluate the potential of TCR repertoires in predicting the prognosis of resectable non-small cell lung cancers. Specifically, TCRβ repertoires were analyzed in surgical tumor tissues and matched adjacent non-tumor tissues from 39 patients enrolled with resectable non-small cell lung cancer, through target enrichment and high-throughput sequencing. As a result, there are significant differences between the TCR repertories of tumor samples and those of matched adjacent non-tumor samples as evaluated by criteria like the number of clonotypes. In addition, TCR repertoires were significantly associated with a few clinical features, as well as somatic mutations. Finally, certain TCRβ variable-joining (V-J) pairings were featured to build a logistic regression model in predicting postoperative recurrence of resectable non-small cell lung cancers with a testing area under the receiver operating characteristic curve (AUC) of around 0.9. Thus, we hypothesize that TCR repertoires could be potentially used to predict prognosis after curative surgery for non-small cell lung cancer patients.

The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/− radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and effective therapeutic strategy for the treatment of advanced NSCLC. Therefore, it is possible that ICIs for early-stage NSCLC may follow the pattern established in metastatic disease. Currently, there are several ongoing trials to determine the efficacy in the neoadjuvant setting for patients with local or regional disease. To date, only nivolumab in combination with chemotherapy has been approved by the U.S. FDA in the preoperative setting, but data continue to evolve rapidly, and treatment guidelines need to be determined. In this article, we review the current preclinical and clinical evidence on neoadjuvant ICIs alone and combination in the treatment of early-stage NSCLC.

Competing Interests: Disclosure Janakiraman Subramanian is in the Speaker Bureau of Astra-Zeneca, G1 therapeutics, Jazz, Janssen; and Advisory board of Astra-Zeneca, Cardinal, DSI, GLG, Guidepoint, OncoHost, Regeneron, and Sanofi.

Objectives Surgical resection and adjuvant chemotherapy have become standard of care for treating resectable early stage non-small cell lung cancer (NSCLC). The purpose was to describe and compare the overall and regional resource utilization and costs of resected NSCLC treated with and without adjuvant chemotherapy. Materials & Methods A population-based retrospective cohort study of resected NSCLC patients, diagnosed between 2004 and 2006 (representing the cohort immediately affected by the change in clinical practice) was performed using administrative data. Patients were followed for four years from the date of surgery. The healthcare system perspective was used, and cost estimates (2012 US$) were derived from administrative data and the literature. Results 3354 patients were included. The average cost per patient treated with surgery and adjuvant chemotherapy was $37,860.88 and was significantly higher than the average cost per patient treated with surgery alone $32,221.45 ( p < 0.0001). Among regions, the costs of patients treated with surgery and chemotherapy ($32,672–$45,453) and the costs of those treated with surgery alone ($28,679–$36,845) varied significantly ( p < 0.0001). Rates of chemotherapy, the proportion of patients who received any imaging scans, hospitalizations, specialist visits, emergency room visits, mean number of imaging scans, general physician visits, and blood transfusions all varied significantly among geographic regions. Conclusions This population-based study demonstrates an average cost per patient similar to that shown in randomized controlled trials; however, costs for either treatment approach varied by geographic region. Understanding the regional variation in costs and resource utilization is important with respect to delivering optimal treatment in a cost-effective strategy. [ABSTRACT FROM AUTHOR]

While lung cancer remains the leading cause of cancer death worldwide, lung cancer mortality has notably decreased in the past decade. Immunotherapy with immune checkpoint inhibitors have played a noteworthy role in contributing to this improved survival, particularly for patients with non-small cell lung cancer (NSCLC). However, until now the benefits have primarily been seen in patients with advanced or metastatic disease. Several recent early phase and ongoing phase III trials have been assessing whether the treatment benefit of immunotherapy in NSCLC can extend to the neoadjuvant setting for resectable diseases. In this comprehensive narrative review, we evaluate the most recent efficacy and safety data from these studies. We also outline questions that will need to be further examined to legitimate neoadjuvant immunotherapy's role in NSCLC treatment, including the best surrogate marker of response, the incorporation of liquid biopsy for disease monitoring, the ability to be combined with other treatment modalities, the need for further adjuvant therapy, and potential future treatment combinations.

For resectable cancer patients, a method that could precisely predict the risk of postoperative recurrence would be crucial for guiding adjuvant treatment. Since T cell receptor (TCR) repertoires had been shown to be closely related to the dynamics of cancers, here we enrolled a cohort of patients to evaluate the potential of TCR repertoires in predicting the prognosis of resectable non-small cell lung cancers. Specifically, TCRβ repertoires were analyzed in surgical tumor tissues and matched adjacent non-tumor tissues from 39 patients enrolled with resectable non-small cell lung cancer, through target enrichment and high-throughput sequencing. As a result, there are significant differences between the TCR repertories of tumor samples and those of matched adjacent non-tumor samples as evaluated by criteria like the number of clonotypes. In addition, TCR repertoires were significantly associated with a few clinical features, as well as somatic mutations. Finally, certain TCRβ variable-joining (V-J) pairings were featured to build a logistic regression model in predicting postoperative recurrence of resectable non-small cell lung cancers with a testing area under the receiver operating characteristic curve (AUC) of around 0.9. Thus, we hypothesize that TCR repertoires could be potentially used to predict prognosis after curative surgery for non-small cell lung cancer patients., (© 2020 The Author(s).)

This Review Article provides a multi-stakeholder view on the current status of neoadjuvant therapy in lung cancer. Given the success of oncogene-targeted therapy and immunotherapy for patients with advanced lung cancer, there is a renewed interest in studying these agents in earlier disease settings with the opportunity to have an even greater impact on patient outcomes. There are unique opportunities and challenges with the neoadjuvant approach to drug development. To achieve more rapid knowledge turns, study designs, endpoints, and definitions of pathologic response should be standardized and harmonized. Continued dialogue with all stakeholders will be critical to design and test novel induction strategies, which could expedite drug development for patients with early lung cancer who are at high risk for metastatic recurrence., (Published by Elsevier Inc.)