Tumor regression rate, PD-L1 expression, pembrolizumab/nab-paclitaxel–based regimens, squamous cell carcinoma, and comorbidities were independently associated with efficacy of neoadjuvant chemoimmunotherapy in non-small cell lung cancer

BackgroundNeoadjuvant chemoimmunotherapy (NCIO) is more effective than neoadjuvant immunotherapy alone for pathological response in non-small cell lung cancer (NSCLC) patients, but the processes for determining patient suitability for its implementation are not clear. We aimed to identify the most relevant factors and build a convenient model to select NSCLC patients who would benefit most from NCIO.Methods We retrospectively collected the clinical data of patients with locally advanced NSCLC who received NCIO followed by surgery at our institution between January 2019 and July 2022.ResultsA total of 101 eligible stage IIB-IIIC NSCLC patients were included. After NCIO, all patients successfully underwent surgical resection. A total of 46.53% (47/101) of patients achieved pathological complete response (pCR), and 70.30% (71/101) achieved major pathologic response (MPR). Tumor regression rate (adjusted odds ratio OR = 12.33), PD-L1 expression (adjusted odds ratio (OR) = 9.66), pembrolizumab/nab-paclitaxel–based regimens (adjusted OR = 4.92), and comorbidities (adjusted OR = 0.16) were independently associated with pCR rate (all P < 0.05). Tumor regression rate (adjusted OR = 8.45), PD-L1 expression (adjusted OR = 5.35), and presence of squamous cell carcinoma (adjusted OR = 7.02) were independently associated with MPR rate (all P < 0.05). We established and validated an easy-to-use clinical model to predict pCR (with an area under the curve [AUC] of 0.848) and MPR (with an AUC of 0.847). Of note, the present study showed that CD4+ T-cell count/rate and total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels in the peripheral blood of pre-NCIO patients were also significantly correlated with pathological response in univariate analyses.ConclusionsThe tumor regression rate, PD-L1 expression, pembrolizumab/nab-paclitaxel–based regimens, presence of squamous cell carcinoma, and comorbidities were the main influential factors for incidence of pCR/MPR in patients with stage IIB-IIIC NSCLC in the present study. Through predictive models, we can predict who will benefit most from NCIO prior to the emergence of clinical outcomes in locally advanced NSCLC

Efficacy and safety of immunotherapy combined with single-agent chemotherapy as second- or later-line therapy for metastatic non-small cell lung cancer

ObjectiveThis study sought to assess the efficacy and safety of immunotherapy combined with single-agent chemotherapy as a second- or later-line setting for metastatic non-small cell lung cancer (NSCLC) and to provide clinical evidence for this treatment regimen. The predictive value of extracellular vesicle (EV) membrane proteins was explored in patients who underwent this treatment.MethodsClinical data from patients diagnosed with metastatic NSCLC who received immunotherapy plus single-agent chemotherapy as a second- or later-line setting were retrospectively collected between March 2019 and January 2022. A total of 30 patients met the inclusion criteria, and all were pathologically confirmed to have NSCLC. Short-term efficacy, progression-free survival (PFS), EV markers for response prediction, and adverse events were assessed.ResultsEfficacy data were available for all 30 patients and included a partial response in 5 patients, stable disease in 18 patients, and disease progression in 7 patients. The objective response rate was 16.7%, the disease control rate was 76.7%, and the median PFS was 3.2 months. Univariate analysis showed that PFS was not associated with sex, age, smoking status, treatment lines, prior use of immunotherapy, or prior use of antiangiogenic drugs. The EV membrane proteins MET proto-oncogene, receptor tyrosine kinase (c-MET), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor 2 (VEGFR2) at baseline were associated with poor prognosis and correlated with the efficacy of immunotherapy plus chemotherapy. According to the receiver operating characteristics and Kaplan–Meier curve analyses, patients with high c-MET, EGFR, and VEGFR2 expression at baseline had significantly shorter PFS than those with low expression. In addition, VEGFR2 expression was increased after combined immunotherapy in responders, which was decreased in non-responders. The most common grade 2 or higher adverse events were neutropenia, gastrointestinal reactions, and thyroid dysfunction, all of which were tolerated.ConclusionsImmunotherapy plus single-agent chemotherapy as a second- or later-line treatment is safe, effective, and tolerable for metastatic NSCLC. EV markers can be used as predictive markers of efficacy in patients with metastatic NSCLC treated with immunotherapy plus chemotherapy to help monitor treatment efficacy and guide treatment decisions

Known actionable driver oncogene mutations were excluded from neoadjuvant chemoimmunotherapy of non-small cell lung cancer.

These known actionable driver oncogene mutations were excluded from neoadjuvant chemoimmunotherapy of non-small cell lung cancer in a retrospective cohort study, as they had corresponding target treatments.</p

Domains of Dirichlet forms and effective resistance estimates on p.c.f. fractals

We consider post-critically finite self-similar fractals with regular harmonic structures. We first obtain effective resistance estimates in terms of the Euclidean metric, which in particular imply the embedding theorem for the domains of the Dirichlet forms associated with the harmonic structures. We then characterize the domains of the Dirichlet forms

Known actionable driver oncogene mutations were excluded from neoadjuvant chemoimmunotherapy of non-small cell lung cancer.

Cases Genes Mutation sitesCase 1 EGFR Exon 19 DeletionsCase 2 EGFR Exon 19 DeletionsCase 3 EGFR Exon 19 DeletionsCase 4 EGFR Exon 21 (L868R) MutationsCase 5 EGFR Exon 19 DeletionsCase 6 EGFR Exon 21 (L868R) MutationsCase 7 EGFR Exon 19 Deletions</p

A re-irradiation dose of 55–60 Gy improves the survival rate of patients with local recurrent esophageal squamous cell carcinoma after radiotherapy

Abstract Introduction Local recurrence (LR) is clinical challenge in the treatment of esophageal squamous cell carcinoma (ESCC). The current study aimed to determine the optimal re-irradiation dose for local recurrent esophageal squamous cell carcinoma (LRESCC) following radical (chemo) radiotherapy. Methods We retrospectively analyzed 125 patients with LRESCC after receiving initial radiotherapy. For radiotherapy treatment, 58 patients were assigned to low-dose (LD) group (50–54 Gy) and 67 were assigned to the high-dose (HD) group (55–60 Gy). The response rate (complete + partial response), 1-, 2- and 3-year survival rate, and toxicity were recorded. We then analyzed the impact of different radiotherapy doses and combination chemotherapy on the survival of patients with LRESCC. Results After re-irradiation, the 1-, 2- and 3-year survival rates in the LD and HD groups were 48.3%, 24.1% and 10.3% and 61.2%, 34.3% and 19.4% in the HD group, respectively, and the difference in overall survival rate between the two groups were significant (P < 0.05). The median survival time of patients receiving radiotherapy alone was 9 months in the LD group and 15 months in the HD group (P < 0.05). The survival rate of patients treated with chemoradiotherapy was higher than that of patients treated with radiotherapy alone in the LD group. However, chemoradiotherapy showed no advantage over radiotherapy alone in the HD group. In addition, the incidence of radiation esophagitis, the most common toxicity, was higher in the HD group compared to the LD group (68.7% vs 58.6%). Multivariate analysis demonstrated that re-irradiation dose was an independent favorable prognostic factor in patients with LRESCC. Conclusion Higher re-irradiation dose (55–60 Gy) can improve the long-term survival of patients with LRESCC after radiotherapy, with tolerable toxicity

Recombinant Human Endostatin in the Treatment of Advanced Lung Squamous Cell Carcinoma

Background and objective Squamous cell carcinoma (SCC) is a common pathological type of non-small cell lung cancer, and advanced lung SCC is incurable. Chemotherapy combined with anti-angiogenesis agents can prolong the patients’ survival time. The aim of the study was to analyze the efficacy and safety of recombinant human endostatin (Endostar) in treating advanced lung SCC. Methods We retrospectively analyzed the short-term efficacy and toxicity of recombinant human endostatin combined with traditional chemotherapy regimens in treating 15 advanced lung squamous cell carcinoma patients in Department of Medical Oncology retrospectively, Cancer Hospital, Chinese Academy of Medical Sciences from November 2011 to May 2015. Treatment-related survival was also analyzed. Results Among the evaluble 14 patients, the best overall response was partial response in 5 patients (35.7%), stable disease in 7 patients (50.0%), and progressive disease in 2 patients (14.3%). The objective response rate (ORR) was 35.7%, and disease control rate (DCR) was 85.7%. The median progression-free survival (PFS) was 9.3 months. The main grade 3 toxicity was neutropenia (2/15, 13.3%) and vomitting (1/15, 6.7%). Conclusion Chemotherapy combined with recombinant human endostatin enabled good objective response in advanced SCC patients and had well security

Utility of NSE, ProGRP and LDH in Diagnosis and Treatment in Patients with Small Cell Lung Cancer

Background and objective Small cell lung cancer (SCLC) is a rapidly growing tumor with characteristic of neuroendocrine cellular function. Neuron specific enolase (NSE), pro-gastrin-releasing peptide (ProGRP) and lactic dehydrogenase (LDH) are valuable in diagnosis and treatment of SCLC. By analyzing the variation of NSE, ProGRP and LDH before and after treatment, the aim of this study is to investigate the efficacy of tumor markers in diagnostic staging, therapeutic evaluation and prediction of disease relapsing. Methods Patients with SCLC who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic (includes NSE, ProGRP and LDH level before and after 2 cycles chemotherapy), efficacy evaluation, progression-free survival (PFS) were analyzed. Results Before treatment, Serum NSE, ProGRP and LDH in patients with extensive disease (ED) were significantly higher than those with limited disease (LD)(all P4 cycles chemotherapy and with obvious decrease of ProGRP than those who accepted ≤4 cycles chemotherapy and with less obvious decrease of ProGRP in LD group; ED patients with no more than 2 distant metastasis, normal LDH level before treatment and obvious decrease of ProGRP after chemotherapy had lower short term relapse risk. In addition, the types of relapse (sensitive relapse, drug resistance relapse and refractory relapse) were negatively correlated with decrease of ProGRP (P=0.044). By multivariate analysis, numbers of chemotherapy cycle was independent prognostic factor for PFS in LD SCLC; numbers of distant metastasis and decrease of ProGRP were independent prognostic factors for PFS in ED SCLC. Conclusion Increase level of serum tumor markers is related to tumor burden. Decrease level of ProGRP after treatment may prognose efficacy and relapse risk

Research on Subsidence Induced by the Dewatering–Curtain Interaction in the Deep Foundation Pit of the Shield Launching Shaft in Shenzhen, China

The waterproof curtain plays an important role in the dewatering of a deep foundation pit. Recognition of the depth of the waterproof curtain inserted into the confined aquifer at different depths may help control ground subsidence due to dewatering, but subsidence analysis of the interaction between dewatering and the waterproof curtain requires further study. In this study, we mainly analyze the relationship between ground subsidence and dewatering based on the shield shaft pit of the Qianhai-Nanshan deep tunnel project in Shenzhen. Our numerical simulation results show that the ground subsidence around the foundation pit decreases with an increase in the depth of the waterproof curtain inserted into the confined aquifer, and when the waterproof curtain completely penetrates the confined aquifer, the ground subsidence caused by pit dewatering is minimal. Our numerical simulation results are consistent with the actual on-site dewatering monitoring data. Our results suggest that the diaphragm wall is an effective measure to control the ground subsidence in deep foundations, helping to reduce excessive dewatering

Impact of selected non-steroidal anti-inflammatory pharmaceuticals on microbial community assembly and activity in sequencing batch reactors.

This study covers three widely detected non-steroidal anti-inflammatory pharmaceuticals (NSAIDs), diclofenac (DCF), ibuprofen (IBP) and naproxen (NPX), as NSAIDs pollutants. The objective is to evaluate the impact of NSAIDs at their environmental concentrations on microbial community assembly and activity. The exposure experiments were conducted under three conditions (5 μg L-1 DCF, 5 μg L-1 DCF+5 μg L-1 IBP and 5 μg L-1 DCF+5 μg L-1 IBP+ 5 μg L-1 NPX) in sequencing batch reactors (SBRs) for 130 days. Removals of COD and NH4+-N were not affected but total nitrogen (TN) removal decreased. IBP and NPX had the high removal efficiencies (79.96% to 85.64%), whereas DCF was more persistent (57.24% to 64.12%). In addition, the decreased removals of TN remained the same under the three conditions (p > 0.05). The results of oxidizing enzyme activities, live cell percentages and extracellular polymeric substances (EPS) indicated that NSAIDs damaged the cell walls or microorganisms and the mixtures of the three NSAIDs increased the toxicity. The increased Shannon-Wiener diversity index suggested that bacterial diversity was increased with the addition of selected NSAIDs. Bacterial ribosomal RNA small subunit (16S) gene sequencing results indicated that Actinobacteria and Bacteroidetes were enriched, while Micropruina and Nakamurella decreased with the addition of NSAIDs. The enrichment of Actinobacteria and Bacteroidetes indicated that both of them might have the ability to degrade NSAIDs and thereby could adapt well with the presence of NSAIDs