The determination of the mutation load, a total number of nonsynonymous point mutations, by whole-exome sequencing was shown to be useful in predicting the treatment responses to cancer immunotherapy. However, this technique is expensive and time-consuming, which hampers its application in clinical practice. Therefore, the objective of this study was to construct a mutation load estimation model for lung adenocarcinoma, using a small set of genes, as a predictor of the immunotherapy treatment response. Using the somatic mutation data downloaded from The Cancer Genome Atlas (TCGA) database, a computational framework was developed. The estimation model consisted of only 24 genes, used to estimate the mutation load in the independent validation cohort precisely (R² = 0.7626). Additionally, the estimated mutation load can be used to identify the patients with durable clinical benefits, with 85% sensitivity, 93% specificity, and 89% accuracy, indicating that the model can serve as a predictive biomarker for cancer immunotherapy treatment response. Furthermore, our analyses demonstrated the necessity of the cancer-specific models by the constructed melanoma and colorectal models. Since most genes in the lung adenocarcinoma model are not currently included in the sequencing panels, a customized targeted sequencing panel can be designed with the selected model genes to assess the mutation load, instead of whole-exome sequencing or the currently used panel-based methods. Consequently, the cost and time required for the assessment of mutation load may be considerably decreased, which indicates that the presented model is a more cost-effective approach to cancer immunotherapy response prediction in clinical practice.

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.

Ciliated muconodular papillary tumor is a rare tumor of the lung with 38 cases reported to date in the English literature. It is typically found incidentally in older adults (average age, 67 years) as a small, peripheral, ground glass opacity or nodule on computed tomography. Microscopically, the tumor is composed of a mixture of ciliated columnar, mucous, and basal cells in a variety of architectural patterns including glandular, papillary, lepidic, and micropapillary growth patterns. Recently, studies have shown the tumor has several associated gene alterations, supporting that the lesion is indeed neoplastic. The tumor seemingly follows an indolent clinical course, as there have been no reported recurrences or metastases. In this article, we review the clinical, radiographic, pathologic, and molecular findings of ciliated muconodular papillary tumors. Diagnostic pitfalls and the diagnostic considerations are discussed.