Real-world effectiveness and safety of recombinant human endostatin plus PD-1 inhibitors and chemotherapy as first-line treatment for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. CONCLUSIONS: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

Which Definition of Upper Rectal Cancer Is Optimal in Selecting Stage II or III Rectal Cancer Patients to Avoid Postoperative Adjuvant Radiation?

BACKGROUND: In most guidelines, upper rectal cancers (URC) are not recommended to take neoadjuvant or adjuvant radiation. However, the definitions of URC vary greatly. Five definitions had been commonly used to define URC: 1) >10 cm from the anal verge by MRI; 2) >12 cm from the anal verge by MRI; 3) >10 cm from the anal verge by colonoscopy; 4) >12 cm from the anal verge by colonoscopy; 5) above the anterior peritoneal reflection (APR). We hypothesized that the fifth definition is optimal to identify patients with rectal cancer to avoid adjuvant radiation. METHODS: The data of stage II/III rectal cancer patients who underwent radical surgery without preoperative chemoradiotherapy were retrospectively reviewed. The height of the APR was measured, and compared with the tumor height measured by digital rectal examination (DRE), MRI and colonoscopy. The five definitions were compared in terms of prediction of local recurrence, survival, and percentages of patients requiring radiation. RESULTS: A total of 576 patients were included, with the intraoperative location of 222 and 354 tumors being above and straddle/below the APR, respectively. The median distance of the APR from anal verge (height of APR) as measured by MRI was 8.7 (range: 4.5-14.3) cm. The height of APR positively correlated with body height (r=0.862, P<0.001). The accuracy of the MRI in determining the tumor location with respect to the APR was 92.1%. Rectal cancer above the APR had a significantly lower incidence of local recurrence than those straddle/below the APR (P=0.042). For those above the APR, there was no significant difference in local recurrence between the radiation and no-radiation group. Multivariate analyses showed that tumor location regarding APR was an independent risk factor for LRFS. Tumor height as measured by DRE, MRI and colonoscopy were not related with survival outcomes. Fewer rectal cancer patients required adjuvant radiation using the definition by the APR, compared with other four definitions based on a numerical tumor height measured by MRI and colonoscopy. CONCLUSIONS: The definition of URC as rectal tumor above the APR, might be the optimal definition to select patients with stage II/III rectal cancer to avoid postoperative adjuvant radiation.

Risk factors of acute kidney injury induced by hemorrhagic shock / 解放军医学杂志

Objective To explore the risk factors of acute kidney injury (AKI) complicating hemorrhagic shock (HS). Methods Clinical data of 1589 patients admitted to Intensive Care Unit (ICU) of the Second People's Hospital of Shenzhen from January 1st, 2010 to December 31th, 2015 were analyzed retrospectively. Univariable and multivariable logistic regressions were used to analyze the independent risk factors of AKI induced by HS. The area under receiver operating characteristic (AU-ROC) and Youde's index were used to determine the optimal cut-off value of nadir platelet count in AKI induced by HS. The Kaplan-Meier method was used to draw the 28-day survival curve and log-rank test was done to evaluate it in AKI and non-AKI groups. Results Of 1589 patients screened, 84 (mean age 37.1 years) were included in the primary analysis in whom 30 suffered AKI. Univariate and multivariate logistic regression analyses showed platelet count, lactic acid, carbon dioxide partial pressure, alanine aminotransferase, APACHE Ⅱ score, sequential organ failure assessment (SOFA) score, and mechanical ventilation were the independent factors for HS complicated by AKI, the differences were statistically significant (P<0.05). The nadir platelet count in the first 48h was an independent risk factor for AKI induced by HS (OR=0.71, P=0.0128). The optimal cut-off value was 75×109/L, and the AU-ROC was 0.838 (P<0.01, 95% CI: 0.731-0.929; P0.01), and the sensitivity and specificity were 0.815 and 0.767, respectively. The Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in HS patients with AKI than non-AKI (P<0.001). Conclusions Nadir platelet count in the first 48 hour is a dependent risk factor for occurence of AKI after HS and more than 75×109/L for platelet count may reduce its occurrence.

[Clinical value of the comprehensive treatment in intermediate and advanced cervical cancer with uterine arterial interventional chemoembolization and radiotherapy].

OBJECTIVE: To investigate the long-term curative effect of the radiotherapy combined uterine arterial interventional chemoembolization for cervical cancer. METHODS: Records of 632 patients with cervical cancer stage II - IVa proved by pathology in Lanzhou Command General Hospital from January 1st, 1999 to August 31st, 2009 were retrospective analysed. One hundred and twenty-six cases of them were treated with radical radiotherapy combined uterine arterial interventional chemoembolization (arterial chemoembolization + radiotherapy group), 506 cases of them were treated with radical radiotherapy only (radiotherapy group); the evaluation of the late radiation injury was done, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) advanced radiation injury criteria. Prognosis and complications were compared between two groups, relative risk factors of radiotherapy complications were identified by method of logistic regression. RESULTS: (1) Survival: the total survival rates of 1-year, 2-year, 5-year and 8-year were 94.4%, 82.3%, 48.8%, 29.1%, respectively. The survival rates of arterial chemoembolization + radiotherapy group were 96.0%, 82.1%, 37.2%, 25.7%, while the survival rates of radiotherapy group were 94.1%, 80.8%, 51.1%, 31.5%, in which there were significant differences between two groups (χ(2) = 0.009, P = 0.993; χ(2) = 0.158, P = 0.691; χ(2) = 11.197, P = 0.001;χ(2) = 9.649, P = 0.002). During the follow-up period, the rate of recurrence and metastasis in arterial chemoembolization + radiotherapy group were 77.0% (97/126), while 73.3% (371/506) in radiotherapy group (χ(2) = 0.705, P = 0.401). (2) Radiotherapy complications and relative risk factors: the total incidence of tardive bladder injury higher than RTOG/EORTC stage II was 5.5% (35/632), while it was 11.1% (14/126) in arterial chemoembolization + radiotherapy group, 4.2% (21/506) in the radiotherapy group (χ(2) = 9.344, P = 0.002). The results of logistic regression showed that the uterine arterial interventional chemoembolization was relative risk factors of the tardive bladder injury (χ(2) = 6.440, OR = 2.869, P = 0.011). CONCLUSIONS: Compared with the simple radiotherapy, there are a similar short-term survival rate and significant poor 5-year, 8-year survival rate in the patients treated with the uterine arterial interventional chemoembolization combined with radiotherapy, which also may be strong dangerous factor for the occurrence of tardive bladder injury. The results shown that the uterine arterial interventional chemoembolization do not recommend to be routine adjuvant therapy for the radical radiotherapy of cervical cancer.