Efficacy and Safety of Regorafenib Monotherapy among Patients with Previously Treated Metastatic Colorectal Cancer in a Chinese Population: A Real-World Exploratory Study.

BACKGROUND: Present study was condeucted to investigate the efficacy and safety of regorafenib for patients with previously treated metastatic colorectal cancer (mCRC) in a Chinese population and the prognostic implications of adverse reactions. METHODS: This retrospective study a total of 96 consecutive patients with mCRC who had failed standard chemotherapy regimens from June 2017 to December 2020. Patients received regorafenib at an initial dosage of 160 mg or 120 mg. The primary end point was progression-free survival (PFS), and secondary end points objective response rate (ORR), disease-control rate (DCR), overall survival (OS), safety, and associations between prognosis and adverse-reaction status. RESULTS: There were three patients with partial response, 49 with stable disease, and 44 with progressive disease. Consequently, the ORR and DCR of the 96 patients were 3.1% (95% CI 0.6%-8.9%) and 54.2% (95% CI 43.7-64.4%), respectively. Prognosis results showed that median PFS of the 96 patients was 2.5 (95% CI 1.98-3.02) months and median OS 9.8 (95% CI 7.02-12.59) months. Additionally, the most frequent adverse reactions during regorafenib treatment were hand-foot syndrome (HFS; 52.1%), hypertension (38.5%), and fatigue (33.3%). Interestingly, the relevance of prognosis to adverse-reaction status exhibited that median PFS of patients with HFS and patients without HFS was 3.3 months and 2.0 months, respectively (P=0.013). Similarly, median PFS of patients with hypertension and without hypertension was 3.6 months and 2.2 months, respectively (P=0.023). CONCLUSION: Potential clinical benefit of regorafenib monotherapy was observed for patients with mCRC who had failed standard chemotherapy regimens. Hypertension and HFS induced by regorafenib therapy could be used as valuable biomarkers to predict the prognosis of regorafenib.

Interstitial tumor-associated macrophages combined with tumor-derived colony-stimulating factor-1 and interleukin-6, a novel prognostic biomarker in non-small cell lung cancer.

OBJECTIVES: Recent experimental evidence has indicated that interstitial tumor-associated macrophages (TAMs), tumor-derived macrophage colony-stimulating factor (also known as CSF-1), and interleukin-6 (IL-6) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. The present study aimed to explore their relationship and prognostic significance in surgically resected non-small cell lung cancer (NSCLC). METHODS: Tissue microarray and immunohistochemistry were used to detect the expression of CSF-1, IL-6, and CD68-positive TAMs in 417 patients with NSCLC undergoing complete pulmonary resection from 2003 to 2008. Their correlations and clinicopathologic data were analyzed using chi-square testing. Their prognostic values were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. RESULTS: The expression of CSF-1 and IL-6 in NSCLC correlated positively with the infiltration degree of TAMs in the tumor stroma (r=0.184 and r=0.196, respectively; P<.001). The expression of both CSF-1 and IL-6 was statistically significant for survival (P<.001). Nevertheless, no such relationship was observed for CD68 in the tumor stroma (P>.05). When CSF-1 and/or IL-6 and CD68 were taken into consideration together, the result became statistically significant. Multivariate analysis showed that co-expression of CD68, CSF-1, and IL-6 remained the most significant and independent prognostic factor for survival (P<.05) but not the combinations of CSF-1 and IL-6, CD68 and CSF-1, or CD68 and IL-6 (P>.05). The 5-year survival rate in the CD68-negative and CSF-1- and IL-6-positive group was better than the rate in the CD68, CSF-1-, and IL-6-positive group (P<.05). CONCLUSIONS: The combination of CD68 plus TAMs, CSF-1, and IL-6 is very likely to be a valuable independent predictor of survival in patients with NSCLC. Perhaps co-expression of CSF-1 and IL-6 induces interstitial TAMs to shift toward the tumor-promoting phenotype.

Expressions of CLDN1 and insulin-like growth factor 2 are associated with poor prognosis in stage N2 non-small cell lung cancer.

BACKGROUND: Patients with single station mediastinal lymph node (N2) non-small cell lung cancer (NSCLC) have a better prognosis than those with multilevel N2. The molecular factors which are involved in disease progression remain largely unknown. The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC. METHODS: Gene expression analysis was performed using Agilent 4×44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients. Real-time reverse transcription (RT)-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed. Immunohistochemical staining for these validated genes was performed on formalin-fixed, paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray. RESULTS: We identified a 14 gene expression signature by comparative analysis of gene expression. Expression of these genes strongly differed between single station and multilevel N2 NSCLC. Four genes (ADAM28, MUC4, CLDN1, and IGF2) correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients. Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC. CONCLUSIONS: Our results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC. Further, CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.