Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study.

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.

[Efficacy of Osimertinib Combined with Bevacizumab in Advanced Non-small Cell 
Lung Cancer Patients with Acquired EGFR T790M Mutation].

BACKGROUND: Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) capable of overcoming non-small cell lung cancer (NSCLC) with EGFR T790M mutation. Although the addition of bevacizumab to 1st generation EGFR-TKIs confers a significant improvement in progression-free survival (PFS) in treatment-naive EGFR mutant NSCLC patients, osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L. Data of such combination in Chinese patients are still lacking. This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data, and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation. METHODS: A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021, with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib. The treatment effect of patients were analyzed. RESULTS: The objective response rate (ORR) in combination group and osimertinib group were 43.8% and 50.0% respectively (P=0.694). No statistically significant difference in median PFS (14.0 mon vs 13.0 mon, P=0.797) and overall survival (OS) (29.0 mon vs 26.0 mon, P=0.544) between the combination group and osimertinib group were observed. Prior history of bevacizumab was identified as an independent predictor of PFS (P=0.045) and OS (P=0.023). CONCLUSIONS: Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.

Lung Adenocarcinoma with Metachronous Ovarian Metastasis: a long survival case report.

BACKGROUND: Lung adenocarcinoma which invades ovaries is very rare. However, with the increase of long-survival female lung cancer, more patients will suffer ovarian metastasis. On grounds of the paucity of reported cases, the clinicopathological features and treatment strategies remain unknown. CASE PRESENTATION: This patient was stage IV lung adenocarcinoma at first diagnosis. Following multiple-line systemic treatments, she experienced extensive pelvic metastasis. After debulking surgery and reevaluation about the drive genes, she was administered by targeted therapy. Up to now, the patient has shown no evidence of progression for 8 years after the initial diagnosis of primary lung cancer and 46 months after her ovarian metastasis. CONCLUSION: The comprehensive treatment modality for the bilateral ovarian metastasis is effective in clinical course.

[Research Progress of Raman Spectroscopy in the Diagnosis of Early Lung Cancer].

Lung cancer (LC) is the most common cancer and the leading cause of cancer-related death worldwide. The 5-year survival rate for LC remains low at 18% and is 5% for patients with metastatic disease, while the 5-year overall survival rate of patients with stage I NSCLC can reach 77.9%, hence early diagnosis and treatment of LC is the key to improve the prognosis. As a non-invasive detection technique, Raman spectroscopy can realize the non-destructive detection of the differences in molecular level structure between cancerous tissues and normal tissues, which can be used for the early diagnosis of lung cancer. The aim of this review is to summarize the progress of Raman spectroscopycombined with different tissue or body fluid samplesin the diagnosis of early LC.
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