Background: This study aimed to establish a novel nomogram prognostic model to predict death probability for non-small cell lung cancer (NSCLC) patients who received surgery.. Methods: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict mortality of NSCL C patients who received surgery. Results: A total of 44,880 NSCLC patients who received surgery from 2004 to 2014 were included in this study. Gender, ethnicity, tumor anatomic sites, histologic subtype, tumor differentiation, clinical stage, tumor size, tumor extent, lymph node stage, examined lymph node, positive lymph node, type of surgery showed significant associations with lung cancer related death rate (P < 0.001). Patients who received chemotherapy and radiotherapy had significant higher lung cancer related death rate but were associated with significant lower non-cancer related mortality (P<0.001). A nomogram model was established based on multivariate models of training data set. In the validation cohort, the unadjusted C-index was 0.73 (95% CI, 0.72-0.74), 0.71 (95% CI, 0.66-0.75) and 0.69 (95% CI, 0.68-0.70) for lung cancer related death, other cancer related death and non-cancer related death. Conclusions: A prognostic nomogram model was constructed to give information about the risk of death for NSCL C patients who received surgery.
Purpose: We aimed to assess the survival benefit of surgery for patients with stage IA-IIB small cell lung cancer (SCLC) and construct a nomogram for predicting overall survival (OS). Methods: Patients who had been diagnosed with stage IA-IIB SCLC between 2004 and 2014 and who had received active treatment were selected from the Surveillance, Epidemiology, and End Results database. The primary endpoint was OS. Cox proportional hazards models and propensity score (PS) analyses were used to compare the associations between surgery and OS. The probability of 1-and 3-year OS was predicted using a nomogram. Results: We reviewed 2,246 patients. The median OS of the surgery and non-surgery groups was 35 months and 19 months, respectively. Multivariable Cox proportional hazards models showed a survival benefit in the surgery group (hazards ratio [HR], 0.642; 95% confidence interval [CI], 0.557-0.740; P < 0.001). To balance the between-group measurable confounders, the impact of surgery on OS was assessed using PS matching. After PS matching, OS analysis still favored surgical resection. The PS-stratification, PS-weighting, and PS-adjustment models showed similar results to demonstrate a statistically significant benefit for surgery. Further, the nomogram was well calibrated and had good discriminative ability (Harrell's C-index = 0.645). Conclusion: Our analysis suggests that surgery is a viable option for patients with early-stage SCLC. Our nomogram is a viable tool for quantifying treatment trade-off assumptions and may assist clinicians in decision-making. Future work is needed to validate our results and improve our tools.
This study aimed to investigate the pntential of metformin to inhibits the growth and metastasis with enhancement of radiation response in hepatocellular carcinoma (HCC) xenograft mice model. Materials/Methods: Huh-7 HCC cells were injected to the right thigh in Balb/c nude mice. Huh-7 bearing mice were treated with local tumor irradiation with a single 15 Gy of X-ray (RT), intraperitoneal administration of metformin with 150 mg/kg/day until the day of sacrifice (MET), or combination of both (administration of metformin 6 hours prior irradiation) (RT-MET). Tumor response to treatment was determined by a tumor growth delay assay. Metastatic potential was evaluated by gross qualitative observation of spontaneous pulmonary metastasis in a lung metastasis model on day 45 and 60. Results: RT or MET resulted in a significant reduction of tumor growth and RT-MET enhanced it further than each treatment alone (55% reduction compared with RT and 67% reduction compared with MET). More importantly, RT or MET inhibited in the growth of metastatic nodules in lung and RT-MET enhanced it further than each treatment alone (93% reduction compared with RT and 76% reduction compared with MET). RT-MET decreased the expression of vascular endothelial growth factor and matrix metallopeptidase 9 by immunohistochemistry. Conclusion: Metformin inhibits the growth and metastasis of HCC with enhancement of radiation response in vivo. Our data suggest that metformin can be a clinically useful adjunct to radiotherapy in HCC.
Background: Although programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have shown prominent efficacy for treatment of advanced lung cancer, the outcomes of metastatic lung cancer remain poor throughout the world. Although progression-free survival (PFS) and overall survival (OS) have improved in the first-and second-line therapy settings for advanced lung cancer, the response rates to PD-1/PD-L1 inhibition range from 20% to 40%. Furthermore, patients may be at risk for immune-related adverse events (irAEs); hence, appropriate patient selection is crucial. This study aimed to identify a panel of plasma cytokines representing prognostic and predictive biomarkers of the response to anti-PD-1/PD-L1 treatment.Methods: We prospectively studied 32 lung cancer patients who received anti-PD-1/PD-L1 antibody immunotherapy. Plasma cytokines in peripheral blood samples were evaluated and analyzed using flow cytometry at the time of diagnosis and at 2 months after the initiation of PD-1/PD-L1 inhibition. Results:The baseline plasma concentrations of interleukin-18 (IL-18) and C-X-C motif chemokine ligand 10 (CXCL10) were correlated with the degree of tumor response. Moreover, the magnitude of plasma IL-18 and CXCL10 level fluctuations were correlated significantly with the objective tumor response to anti-PD-1/PD-L1 immunotherapy, and patients with high CXCL10 expression had significantly shorter PFS than those with low CXCL10 expression. A strong positive correlation between the fluctuation of IL-18 and interleukin-8 (IL-8) levels was detected, as was a negative correlation between the fluctuation of IL-18 and CXCL10 levels. The level of plasma C-C motif chemokine ligand 5 (CCL5) was significantly higher in patients with irAEs than in those without irAEs.Conclusions: Plasma cytokines are related to the clinical efficacy of PD-1/PD-L1 inhibitors. IL-18 and CXCL10 are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.
Background Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non‐small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long‐term survival in NSCLC patients. Methods Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis. Results There was no significant distinction in overall survival (OS) between right ( n = 53 496) and left ( n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756–1.011; P = 0.432). Left side was associated with superior five‐year cancer‐specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574–0.9969; P = 0.024). No significant difference was observed in OS ( P = 0.689) or CSS ( P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side ( n = 21 245) was associated with poor OS compared to right side ( n = 30 074) NSCLC (HR 1.039, 95% CI 1.011–1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997–1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS ( P = 0.986) or CSS ( P = 0.979) after PSM analysis. Conclusion The prognosis between right and left side NSCLC in stage I–IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment.
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