The effect of liver metastases on clinical efficacy of first-line programmed death-1 inhibitor plus chemotherapy in esophageal squamous cell carcinoma: A post hoc analysis of ASTRUM-007 and meta-analysis.

OBJECTIVE: To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. METHODS: A post hoc exploratory analysis of ASTRUM-007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta-analysis. Study-level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. RESULTS: The post hoc analysis of ASTRUM-007 showed that although patients with liver metastases had a worse prognosis comparing with the non-liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15-2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09-1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01-2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84-2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37-0.97; HR of OS: 0.68; 95% CI, 0.43-1.11) and the non-liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49-0.80; HR of OS: 0.69; 95% CI, 0.55-0.87) with similar magnitude. Three randomized controlled trials were included in the meta-analysis. Pooled HRs demonstrated that the addition of anti-PD-1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. CONCLUSIONS: This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD-1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.

First-line serplulimab or placebo plus chemotherapy in PD-L1-positive esophageal squamous cell carcinoma: a randomized, double-blind phase 3 trial.

First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m2) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m2) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48-0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53-0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov ( NCT03958890 ).

Lamina Variation and Its Relationship with Sedimentary Facies in Alkaline Lacustrine, Permian Fengcheng Formation, Junggar Basin, Northwest China.

The Permian Fengcheng Formation in the Mahu Sag was deposited in a volcanic-alkaline lacustrine evaporative environment and contains a unique variety of fine-grained sediments. This study examines, at a millimeter-scale, the influence of sedimentary microfacies on variability of lamina quality in fine-grained sediments in the second member of the Fengcheng Formation (P1f2). The methods used include thin-section identification, X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy (SEM), nitrogen adsorption, and nuclear magnetic resonance (NMR). Six types of lamina were identified in two different lithofacies: fan-delta front facies (FDFF) and semideep/deep lacustrine facies (SDDLF). The laminae in FDFF are predominantly feldspar-quartz laminae (FQL), reedmergnerite laminae (RL), shortite laminae (SL), alkaline mineral laminae (AML), and chert laminae (CL). The laminae in SDDLF are predominantly FQL, RL, SL, CL, and dolomite laminae (DOL). Variations in reservoir quality, oil-bearing properties, and the fracability of laminae in different sedimentary facies are determined by the combined effects of lamina density, mineral composition, rock structure, organic matter abundance, and microfractures. Analysis of these factors indicates superior reservoir qualities in FDFF. In SDDLF, the pore structure is limited by high lamina density, chert content, and fine grain size with the NMR porosities of FQL, RL, SL, and CL being 1.32, 0.18, 0.84, and 0.39%, respectively. However, in FDFF, the combination of high organic matter content, feldspar, pyrite, and clay minerals has a superior effect on the organic matter and minerals deposited resulting in better pore structure and more storage space for shale oil. The NMR porosities of FQL, RL, SL, and CL are 2.81, 2.53, 1.80, and 1.12%, respectively. Overall, analysis of lamina variations and their relationships with sedimentary facies indicates that the reservoir in FDFF may offer more favorable targets for "sweet spot" evaluation.

Prognostic Value of White Blood Cells Detected for the First Time After Adjuvant Chemotherapy in Primary Operable Non-Small Cell Lung Cancer.

OBJECTIVE: To investigate the prognostic value of white blood cells detected for the first time after adjuvant chemotherapy in primary operable non-small cell lung cancer. METHODS: From January 2010 to May 2016, data from 208 patients who underwent surgery for non-small cell lung cancer were retrospectively analyzed. RESULTS: A white blood cell count detected for the first time after adjuvant chemotherapy greater than 7.00 was an independent predictor of poor disease-free survival (Hazard ratio: 1.736, 95% confidence interval: 1.267-2.378; P = .001) and overall survival (Hazard ratio: 1.802, 95% confidence interval: 1.305-2.471; P = .000). In a further study, after myelosuppression, survival analysis indicated that the patients with white blood cell counts <2.5 had poorer survival than patients with blood cell counts 2.5 to 4.0, P = .031. When the analysis was stratified by the type of histology, patients with a white blood cell count >7.00 and increased white blood cell after chemotherapy compared to pretreatment had a poorer prognosis than patients with white blood cell ≤7.00 and no increase in white blood cell, P = .000 and P = .002, respectively. We further evaluated the prognosis of the 2 groups in different levels of white blood cell. In the group of patients with white blood cell ≤4.0, patients with chemotherapy cycles ≤2, and >2 showed no differences (Hazard ratio: 2.346, 95% confidence interval: 0.288-19.073, P = .425). In the group of patients with white blood cell of 4.0 to 7.0, the prognosis of patients with chemotherapy cycles ≤2 and patients with chemotherapy cycles >2 showed no difference (Hazard ratio: 0.560, 95% confidence interval: 0.248-1.261, P = .161). In the group of patients with white blood cell >7.0, patients with >2 chemotherapy cycles had a better prognosis than patients with chemotherapy cycles ≤2 (Hazard ratio: 0.573, 95% confidence interval: 0.338-0.971, P = .037) Conclusions: The level of white blood cells detected for the first time after adjuvant chemotherapy is an independent risk factor for non-small cell lung cancer, especially for patients with nonadenocarcinoma. In addition, the level of white blood cells after postoperative adjuvant chemotherapy and its change compared with pretreatment might also provide useful information regarding the best choice of cycles of adjuvant chemotherapy.

[Reconstruction of chest wall after resection].

OBJECTIVE: To evaluate the results of chest wall reconstruction (CWR) in patients who underwent chest wall tumor resection accompanying huge chest wall defect. METHODS: From Jan. 1998 to Mar. 2003, 31 patients underwent CWR. Among them, 20 were male and 11 female. The age ranged from 8 to 72 years. The indications for resection were primary chest wall tumor in 21 patients, lung cancer with invasion of chest wall 6, recurrence of breast cancer 2, radiation necrosis 1 and skin cancer 1. The number of rib resected was 2-7 ribs (3.6 in average). The defect was 20-220 cm2 (97.1 cm2 in average). Concomitant resection was done in 13 patients, including lobectomy or wedge resection of lung 10, partial resection of diaphragm 2, and partial sternotomy 1. Seven patients underwent soft tissue reconstruction alone (latissimus dorsi+greater omentum, latissimus dorsi myocutaneous flap, latissimus dorsi muscle flap), 5 patients bony reconstruction alone (Prolene web), and simultaneous BR and STR were performed in 19 patients (latissimus dorsi, pectoralis major, latissimus dorsi+fascia lata, and Prolene web). RESULTS: Three patients (9.7%) developed postoperative complications. Postoperative survival period was 6-57 months with a median of 22 months. CONCLUSION: A favorable clinical outcome can be achieved by CWR for the patients with huge chest wall defects that result from resection of chest wall tumors.