Immunotherapy for bilateral multiple ground glass opacities: An exploratory study for synchronous multiple primary lung cancer.

Background: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. Methods: A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. Results: Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy (> 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19- and PCDHB5- mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. Conclusion: Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=36878, identifier ChiCTR1900022159.

Circulating tumor DNA integrating tissue clonality detects minimal residual disease in resectable non-small-cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the standard of care. METHODS: We prospectively recruited 128 patients with stage I-III NSCLCs who received curative surgical resections in our Lung Cancer Tempo-spatial Heterogeneity prospective cohort. Plasma samples were collected before the surgery, 7 days after the surgery, and every 3 months thereafter. Targeted sequencing was performed on a total of 628 plasma samples and 645 matched tumor samples using a panel covering 425 cancer-associated genes. Tissue clonal phylogeny of each patient was reconstructed and used to guide ctDNA detection. RESULTS: The results demonstrated that ctDNA was more frequently detected in patients with higher stage diseases pre- and postsurgery. Positive ctDNA detection at as early as 7 days postsurgery identified high-risk patients with recurrence (HR = 3.90, P < 0.001). Our results also show that longitudinal ctDNA monitoring of at least two postsurgical time points indicated a significantly higher risk (HR = 7.59, P < 0.001), preceding radiographic relapse in 73.5% of patients by a median of 145 days. Further, clonal ctDNA mutations indicated a high-level specificity, and subclonal mutations informed the origin of tumor recurrence. CONCLUSIONS: Longitudinal ctDNA surveillance integrating clonality information may stratify high-risk patients with disease recurrence and infer the evolutionary origin of ctDNA mutations.

[Experience of carinal resection and reconstruction in the treatment of carinal tumor and bronchogenic carcinoma].

BACKGROUND: Carinal resection and reconstruction is an emphasis in surgical treatment of carinal tumor and bronchogenic carcinoma involving carina. The aim of this study is to discuss the clinical value of carinoplasty in lung cancer surgery. METHODS: From 1982 to 2004, 41 cases of central bronchogenic carcinoma that invaded the carina accepted carinal resection and reconstruction in this hospital. Of the 41 patients, 25 patients underwent simutaneously additional cardiovascular plasty operation besides carinoplasty. There were 12 different types of carinal resection and reconstruction in this series. RESULTS: There was 1 perioperative death (because of anastomotic leakage) in this group. Arrhythmia occured in 12 patients, atelectasis in 6 patient and pneumonia in 5 patients. Five patients were assisted ventilation through breathing machine because of pulmonary function failure. The 1-, 3-, and 5-year survival rates were 76.21%, 47.23% and 26.83% respectively. CONCLUSIONS: The carinoplasty is a good method to treat central bronchogenic carcinoma which invaded the carina. With this method lung cancer tissue can be resected maximally, meanwhile, it can save pulmonary function of patient maximally. Postoperative multi-modality therapy is helpful to increase postoperative survival rate and improve quality of life.

[Surgical treatment for locally advanced lung cancer invading heart and great vessels].

BACKGROUND: To summarize the surgical treatment for locally advanced lung cancer invading heart and great vessels. METHODS: One hundred and eighteen cases of lung cancer accepting cardiovascular plasty operation from 1980 to 2001 were reviewed. RESULTS: The operations included partial resection of left atrium in 38 cases, pulmonary artery resection and restruction in 48 cases, replacement or partial resection of superior vena cava in 25 cases, partial resection of pulmonary conus in 3 cases, and lober replantation in 4 cases respectively. There was no perioperative death, and the 1-, 3-, 5- and 10 year survival rate was 72.68%, 55.20%, 28.62% and 20.36% respectively. CONCLUSIONS: Cardiovascular plasty in the surgical treatment of locally advanced lung cancer invading heart or great vessels can remarkably increase the long-term survival and improve the life quality of the patients.