Effect of different treatment modalities on ovarian cancer patients with liver metastases: A retrospective cohort study based on SEER.

BACKGROUND: To examine the trends in morbidity and mortality among ovarian cancer patients with liver metastases, and investigate the impact of different treatments on both overall survival (OS) and cancer-specific survival (CSS). METHODS: 2,925 ovarian cancer patients with liver metastases from Surveillance, Epidemiology, and End Results 2010-2019 were included. The primary endpoint was considered as OS and CSS. We conducted trend analysis of the incidence, OS and CSS rates of liver metastases in ovarian cancer. Univariate and multivariate COX proportional risk models were used to investigate the association between different treatment methods and OS, and univariate and multivariate competing risk models were employed to evaluate the impact of treatment methods on CSS. RESULTS: At the end of follow-up, 689 patients remained alive. The OS and CSS rates were 76.44% and 72.99% for all patients, respectively. There was a significant decreasing trend in the incidence [average annual percent change (AAPC) = -2.3, 95% confidence interval (CI): -3.9, -0.7], all-cause mortality (AAPC = -12.8, 95% CI: -15.6, -9.9) and specific mortality (AAPC = -13.0, 95% CI: -16.1, -9.8) rate of liver metastases in ovarian cancer. After adjusting all confounding factor, only receiving surgery was associated with OS [hazard ratio (HR) = 0.39, 95%CI: 0.31-0.48]/CSS (HR = 0.37, 95%CI: 0.30-0.47). Chemotherapy was found to be protective factor for OS (HR = 0.33, 95%CI: 0.30-0.37)/CSS (HR = 0.44, 95%CI: 0.39-0.50) of ovarian cancer patients, while not receiving surgery remained a risk factor. Additionally, the result of subgroup analyses also showed that only receiving surgery and chemotherapy still were significant protective factor of OS and CSS for patients without other distant metastases, with distant metastases to the bone, lung, brain or other organs, with bone metastasis, and with lung metastasis. CONCLUSION: Our research has elucidated a downward trend in morbidity and mortality rates among patients with liver metastases originating from ovarian cancer. Only receiving surgery and chemotherapy as therapies methods confer survival benefits to patients.

Creatinine-to-cystatin C ratio and body composition predict response to PD-1 inhibitors-based combination treatment in metastatic gastric cancer.

Background: Creatinine-to-cystatin C ratio (CCR) and body composition (BC) parameters have emerged as significant prognostic factors in cancer patients. However, the potential effects of CCR in gastric cancer (GC) remains to be elucidated. This multi-center retrospective study explored the predictive and prognostic value of CCR and BC-parameters in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy. Methods: One hundred and thirteen GC patients undergoing PD-1 inhibitors-based combination therapy were enrolled at three academic medical centers from January 2021 to July 2023. A deep-learning platform based on U-Net was developed to automatically segment skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI). Patients were divided into two groups based on the median of CCR or the upper tertile of BC-parameters. Logistic and Cox regression analysis were used to determine the effect of CCR and BC-parameters in predicting response rates and survival rates. Results: The CCR was positively correlated with SMI (r=0.43; P<0.001), but not with SATI or VATI (P>0.05). Multivariable logistic analysis identified that both low CCR (OR=0.423, P=0.066 for ORR; OR=0.026, P=0.005 for DCR) and low SATI (OR=0.270, P=0.020 for ORR; OR=0.149, P=0.056 for DCR) were independently associated with worse objective response rate (ORR) and disease control rate (DCR). Patients with low CCR or low SATI had significantly lower 8-month progression-free survival (PFS) rate and 16-month overall survival (OS) rate than those with high CCR (PFS rate, 37.6% vs. 55.1%, P=0.011; OS rate, 19.4% vs. 44.9%, P=0.002) or those with high SATI (PFS rate, 37.2% vs. 53.8%, P=0.035; OS rate, 8.0% vs. 36.0%, P<0.001). Multivariate Cox analysis showed that low CCR (HR=2.395, 95% CI: 1.234-4.648, P=0.010 for PFS rate; HR=2.528, 95% CI: 1.317-4.854, P=0.005 for OS rate) and low SATI (HR=2.188, 95% CI: 1.050-4.560, P=0.037 for PFS rate; HR=2.818, 95% CI: 1.381-5.752, P=0.004 for OS rate) were both independent prognostic factors of poor 8-month PFS rate and 16-month OS rate. A nomogram based on CCR and BC-parameters showed a good performance in predicting the 12- and 16-month OS, with a concordance index of 0.756 (95% CI, 0.722-0.789). Conclusions: Low pre-treatment CCR and SATI were independently associated with lower response rates and worse survival in patients with metastatic GC receiving PD-1 inhibitors-based combination therapy.

NPLOC4 is a potential target and a poor prognostic signature in lung squamous cell carcinoma.

Few prognostic biomarkers exist for lung squamous cell carcinoma (LUSC), which has a poor five-year survival rate. Using bioinformatics, this study evaluated NPLOC4 as a prognostic marker for patients with lung squamous cell carcinoma. Shorter survival periods and tumor growth were linked to high NPLOC4 expression.Disulfiram (DSF) combined with copper (Cu) targets NPLOC4 to achieve antitumor effects in lung squamous cell carcinoma. Thus, we investigated the effects of DSF with Cu in LUSC. Gene-set enrichment analysis identified ubiquitin-mediated proteolysis as the NPLOC4-associated mechanism influencing LUSC prognosis. In SK-MES-1 cell lines, DSF + Cu increased K48-linked ubiquitinated protein expression and apoptosis. This study identified NPLOC4 as a prognostic biomarker and a potential therapeutic target for LUSC.