Background & Aims: The application of circulating tumor DNA (ctDNA) has been studied for predicting recurrent disease after surgery and treatment response during systemic treatment. Metastasectomy can be curative for well-selected patients with metastatic colorectal cancer (mCRC). This prospective study investigated the ctDNA level before and after metastasectomy in patients with mCRC to explore its potential as a predictive biomarker. Methods: We collected data on 98 metastasectomies for mCRC performed from March 2017 to February 2020. Somatic mutations in the primary and metastatic tumors were identified and tumor-informed ctDNAs were selected by ultra-deep targeted sequencing. Plasma samples were mandatorily collected before and 3–4 weeks after metastasectomy and serially, if patients agreed. Results: Data on 67 of 98 metastasectomies (58 patients) meeting the criteria were collected. ctDNA was detected in 9 (29%) of 31 cases treated with upfront metastasectomy and in 7 (19.4%) of 36 cases treated with metastasectomy after upfront chemotherapy. The detection rate of ctDNA was higher in liver metastasis (p = 0.0045) and tumors measuring ≥1 cm (p = 0.0183). ctDNA was less likely to be detected if the response to chemotherapy was good. After metastasectomy, ctDNA was found in 4 (6%) cases with rapid progressive disease. Conclusion: The biological factors affecting the ctDNA shedding from the tumor should be considered when applying ctDNA assays in a clinical setting. After metastasectomy for oligometastatic lesions in good responders of chemotherapy, most ctDNA was cleared or existed below the detection level. To assist clinical decision making after metastasectomy for mCRC using ctDNA, further studies for improving specific outcomes are needed.

This study aimed to identify novel biomarkers for metastatic colorectal cancer progression using exosomal RNA expression profiling. The exosomal RNA expression profiles of 54 patients with mCRC were investigated. Exosomal RNA profiling was performed at the time of relapse immediately before metastasectomy and cancer recurrence or progression after metastasectomy. The up- and down-regulated RNA expression profiles were screened and analyzed using H-cluster, principle component analysis and gene ontology. The tissue expression profile of the liver metastases was compared with the GSE 41258 set using GSEA tools. We identified two distinctive biological process gene sets (IFNA and PCDB families) related to metastatic progression. The interferon-α response gene set was enriched, especially when the tumor volume was ≥1 cm³. CXCL10, CXCL11 and SAMD 9 mRNA were highly expressed in the plasma exosome samples of patients with mCRC to the liver. Furthermore, high expression of CXCL10 but not CXCL11 or SAMD9 was associated with a poor prognosis and shorter progression-free survival. Conclusions: Cancer-derived exosomal CXCL10 may be a novel biomarker for liver metastasis of mCRC and a potential target for the prevention and treatment of mCRC with liver metastasis.

Oligometastasis is defined as the presence of several limited metastatic lesions and is generally limited to three or fewer than five metastatic lesions. Previously, the treatment of metastatic cancer aimed to alleviate symptoms rather than cure them; however, the use of immunotherapy or targeted therapy has greatly improved patient life expectancy. Additionally, the effectiveness and safety of local treatment have recently been proven for oligometastatic cancers and have significantly improved patient survival and decreased recurrence rates. A few metastatic studies on lung cancer have demonstrated the usefulness of combining radiation therapy and immunotherapy. Recently, local and targeted therapy combinations have shown promising results in treating non-small cell lung cancer, predominantly caused by the epidermal growth factor receptor and anaplastic lymphoma kinase gene mutations, suggesting the potential of these new treatment strategies. It is well known that oligometastasis has better clinical results than polymetastasis; however, research on the biological profile of oligometastasis is still lacking. Studies using circulating tumor DNA and circulating tumor cells are at the initial stages of providing a better understanding of oligometastatic cancers, and the biological characteristics of these cancers may be revealed based on more diverse studies. With the development of these treatments, the prognosis for patients with oligometastatic cancers is steadily improving, and if the biological profile is revealed, customized treatment may be provided.

Background: The prognosis for patients with lung cancer bone metastases has improved with the use of novel systemic agents. These patients might need surgery or radiotherapy to alleviate symptoms or maintain function. However, there is currently no disease specific algorithm to guide multidisciplinary decisions. Methods: The inclusion criteria encompassed studies with ≥10 patients offering multivariate analysis data on survival that were published after 2000 until September 2023. Clinical factors were categorized based on their characteristics and the pooled hazard ratios (HRs) for each category were calculated. A treatment algorithm was proposed based on clinical importance and the pooled HRs. Results: Fifteen studies involving 3759 patients with lung cancer bone metastases were included. The median survival ranged between 1.8–28.3 months (median: 12.4). Among the studies involving patients with EGFR+ or treated with TKIs, the median survival ranged between 19.5–28.3 months. The most reported significant factor was ECOG performance (nine studies) followed by chemotherapy use (six studies). In the pooled analyses, the pooled HR [95% confidence interval (CI)] of the EGFR status category was 2.109 (1.345–3.305); the ECOG performance category was 2.007 (1.536–2.622); the visceral metastases category was 2.060 (1.370–3.098); the bone metastases characteristics category (e.g., multiplicity, weight-bearing bone metastases) was 1.910 (1.443–2.527); the body weight category was 1.805 (1.334–2.442); the anti-absorbants category was 1.784 (1.448–2.196); the systemic treatment category was 1.695 (1.407–2.041); the skeletal-related event category was 1.616 (1.063–2.458); the smoking status category was 1.530 (1.306–1.793); the gender category was 1.482 (1.270–1.729); and the histology category was 1.450 (1.186–1.772). Conclusions: Oncological prognoses are influenced by various interrelated factors. Our treatment algorithm supports multidisciplinary strategies for managing NSCLC bone metastases, considering the complex factors influencing prognosis.