Predictive value of primary tumor volume change during concurrent chemoradiotherapy in patients with unresectable stage III non-small cell lung cancer.

BACKGROUND AND PURPOSE: No established early biomarkers currently exist to predict responses during concurrent chemoradiotherapy (CCRT) in patients with unresectable non-small cell lung cancer (NSCLC). This study investigated the potential of gross tumor volume (GTV) and its changes during CCRT as predictors of survival outcomes. MATERIALS AND METHODS: We identified 227 patients with unresectable stage III NSCLC who underwent definitive CCRT followed by durvalumab between November 2018 and December 2022. GTV was defined as the volume of the primary tumor, assessed at two time points: before starting CCRT for initial planning (GTV1), and at the fourth week of CCRT for adaptive planning (GTV2). Both relative and absolute regressions between GTV1 and GTV2 were calculated. RESULTS: The median GTV1 volume was 90 mL (range, 5-840 mL), and the median GTV2 volume was 64 mL (range, 1-520 mL), resulting in median absolute and relative regressions of 18.6 mL and 25.0 %, respectively. Among the GTV parameters, relative GTV regression exhibited the strongest predictive value, with an area under the curve (AUC) of 0.804 for in-field progression and 0.711 for overall progression. The 1-year progression-free survival rates for the high (>30 %), intermediate (0-30 %), and low (≤0%) relative regression groups were 88.0 %, 62.6 %, and 14.3 %, respectively (p = 0.006 for high vs. intermediate; p < 0.001 for intermediate vs. low). Additionally, GTV2 volume demonstrated stronger associations with survival outcomes than GTV1 volume. CONCLUSION: Relative GTV regression was identified as a promising early predictor for patients with unresectable stage III NSCLC. Further development of a multi-parametric predictive model is warranted to guide patient-tailored therapeutic approaches.

Sarcopenia increases the risk for mortality in patients who undergo amputation for diabetic foot.

BACKGROUND: Although there have been reports that diabetes affects the prevalence of sarcopenia, no studies have examined the relationship between sarcopenia and mortality in patients undergoing leg amputation. The purpose of this study is to determine whether sarcopenia affects the mortality rate of patients undergoing diabetic foot amputation. METHODS: From among patients who underwent limb amputation for diabetes complications, this study included 167 patients who underwent abdominal CT within 1 year of amputation. We defined sarcopenia using sex-specific cut-off points for the L3 skeletal muscle index. The 5-year survival rate was analyzed. All patients were divided into two groups and compared according to the presence of sarcopenia. The mortality rate according to sarcopenia was assessed via the Kaplan-Meier method and log-rank test. Uni- and multivariate Cox regression analyses evaluated factors associated with survival rate. RESULTS: Among the total of 167 patients, the overall 5-year mortality rate was 52.7%. Of the 112 patients with sarcopenia, the 5-year mortality rate was 60.7%. Of the 55 patients without sarcopenia, the 5-year mortality rate was 36.4%. Kaplan-Meier analysis showed a high mortality of the sarcopenia group in the univariate (p = 0.016) and multivariate (p = 0.047) analysis. CONCLUSIONS: Our study is the first to analyze the relationship between diabetic amputation and sarcopenia. Sarcopenia increases the risk of mortality in patients who undergo amputation for diabetic foot. Therefore, patients with diabetes should be careful to prevent sarcopenia with enough regular exercise as well as prevent diabetic foot disease.

Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast.

Excessive bone resorption caused by increased osteoclast number or activity leads to a variety of bone diseases including osteoporosis, rheumatoid arthritis and periodontitis. Thus, the therapeutic strategy for these diseases has been focused primarily on the inhibition of osteoclast formation and function. This study shows that euphorbia factor L1 (EFL1), a diterpenoid isolated from Euphorbia lathyris, inhibited osteoclastogenesis and induced osteoclast apoptosis. EFL1 suppressed osteoclast formation and bone resorption at both initial and terminal differentiation stages. EFL1 inhibited receptor activator of NF-κB ligand (RANKL)-induced NFATc1 induction with attenuated NF-κB activation and c-Fos expression. EFL1 decreased the level of reactive oxygen species by scavenging them or activating Nrf2, and inhibited PGC-1ß that regulates mitochondria biogenesis. In addition, EFL1 induced apoptosis in differentiated osteoclasts by increasing Fas ligand expression followed by caspase activation. Moreover, EFL1 inhibited inflammation-induced bone erosion and ovariectomy-induced bone loss in mice. These findings suggest that EFL1 inhibits osteoclast differentiation by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast, and may provide therapeutic potential for preventing or treating bone-related diseases caused by excessive osteoclast.