Neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma: Data from literature review and a real-world analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real-world study and a meta-analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. METHODS: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1-, 2-, and 3-year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1-year recurrence rate, R0 resection rate and adverse events. Moreover, a meta-analysis of 27 published literatures was also conducted for comparison. RESULTS: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1-, 2-, and 3-year OS rates were 91.41% (95% CI: 85.15%-95.63%), 75.00% (95% CI: 66.58%-82.23%) and 64.84% (95% CI: 55.91%-73.07%).ORR and DCR were 31.2% (95% CI: 23.31-39.99) and 64.1% (95% CI: 55.15%-72.38%), and the 1-year recurrence rate was 26.7% (95% CI: 22.5%-38.1%). Treatment-related events occurred in 96.1% but were acceptable. In a meta-analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1-year recurrence rate of 12%. CONCLUSION: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.

PD-L1 mRNA derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer.

Background: To date, the role of programmed death ligand-1 (PD-L1) messenger RNA (mRNA) derived from tumor-educated platelets (TEPs) has not been well investigated in patients with advanced non-small cell lung cancer (NSCLC). A few reports have examined whether mRNA in TEPs can predict the clinical responses of patients with advanced NSCLC following immunotherapy. This study aimed to identify novel biomarkers to improve the clinical benefits and outcomes of NSCLC patients. Methods: Advanced NSCLC patients receiving a combination of immunotherapy and chemotherapy, or immunotherapy alone as a first- or second-line treatment at the Fudan University Shanghai Cancer Center were enrolled in this study. All the patients had wild-type epidermal growth factor receptor/anaplastic lymphoma kinase. The patients were enrolled in clinical trials for immune checkpoint inhibitors (ICIs), including nivolumab, pembrolizumab, atezolizumab, durvalumab, tremelimumab, and camrelizumab. Tumoral PD-L1 expression was tested by immunohistochemistry (PD-L1 22C3 pharmDx kit, Agilent, Santa Clara, CA, USA) in archived tissue samples, when available, to calculate the tumor proportion scores (TPSs). RNA and exosomal RNA of blood were isolated before immunotherapy using the Yunying RNA extraction kit (Yunying Medicine, Shanghai, China). The concentration and quality of the RNA was determined using a Qubit fluorometer (Life Technologies, Carlsbad, CA, USA). Finally, we analyzed the predictive value of TEP-derived PD-L1 mRNA expression and association with the level of the tumoral PD-L1 expression. Results: In total, 72 patients were enrolled in this study. Most of the patients were male (n=54, 75.0%), had adenocarcinoma (n=49, 68.1%). We found there was no significant correlation between the TEP-derived mRNA of PD-L1 and tumoral PD-L1 expression based on the results of the Pearson Correlation test (r=-0.19, P=0.233). Based on the median of PD-L1 mRNA, 72 patients were divided into a high PD-L1 group and a low PD-L1 group. We found that 19 patients (44.4%) responded to immunotherapy [partial response or progression-free survival (PFS) >6 months] in the high PD-L1 group, but only five patients (13.9%) responded to immunotherapy in the low PD-L1 group (P<0.01). The median PFS of the low PD-L1 group was lower than that of the high PD-L1 group (2.8 vs. 8.3 months, P<0.001). For the patients who were treated with immunotherapy alone (n=64), a similar PFS advantage was observed in the high PD-L1 group (2.8 vs. 8.0 months, P=0.002). Conclusions: This article presented the first data on TEP-derived PD-L1 mRNA in advanced NSCLC patients following immunotherapy and showed the potential advantage of using it as the surrogate biomarker for predicting the PFS and overall survival of patients following immunotherapy.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

A novel neoadjuvant therapy for early-stage non-small cell lung cancer in a mouse model.

Background: Lung cancer is the common malignancy with high mortality rate in the world. Even with curative resection for early-stage lung cancer patients, the rate of postoperative recurrence and metastasis is still high. Neoadjuvant nivolumab combined with chemotherapy leads to improved pathological complete response rate and event-free survival in resectable non-small cell lung cancer (NSCLC) patients. However, the neoadjuvant therapy is not only accompanied by grade 3 or above adverse events which resulting in the potential missing out on the window for curative surgery for the patients, but also has low efficacy especially in patients with low programmed death ligand 1 (PD-L1) expression. Hence, it is particularly important to explore innovative ways to inhibit tumour recurrence and metastasis. Methods: In the present study, we investigated whether neoadjuvant therapy with intralesional Rose Bengal (RB) elicited specific immune responses compared with control group, and then the lung cancer mouse model was used to evaluated the immunological mechanism. Results: The secondary Lewis lung cancer cells (LLCs) tumour growth was significantly suppressed by RB intralesional injection into subcutaneous tumour; the formation rate of secondary tumours induced by the B16 melanoma cell injection was 100%. Intralesional RB neoadjuvant therapy before surgical resection exhibited effectively enhanced T central memory cells (Tcm) and T memory stem cells (Tscm) + naïve T cells (Tn) infiltration, elicited stronger cytotoxic T lymphocyte (CTL) responses against LLCs, and displayed markedly higher proportions of splenic lymphocytes that produce tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) upon restimulation in a lung cancer mouse model. Conclusions: Based on our preclinical data, neoadjuvant therapy with intralesional RB injection generated immune memory and prevented the recurrence and metastasis of tumour in a lung cancer mouse model, which provides a new strategy for neoadjuvant treatment of early-stage NSCLC.

Mechanisms of Resistance to Tyrosine Kinase Inhibitors in ROS1 Fusion-Positive Nonsmall Cell Lung Cancer.

BACKGROUND: ROS1 fusion-positive (ROS1+) nonsmall cell lung cancer (NSCLC) patients are highly sensitive to tyrosine kinase inhibitor (TKI) treatments. However, acquired TKI resistance remains the major hurdle preventing patients from experiencing prolonged benefits. METHODS: 107 advanced or metastatic ROS1+ NSCLC patients who progressed on crizotinib and lorlatinib were recruited. Tissue and plasma samples were collected at baseline (N = 50), postcrizotinib (N = 91), and postlorlatinib (N = 21), which were all subject to the 139-gene targeted next-generation DNA sequencing. Molecular dynamics modeling was performed to investigate the effects of ROS1 mutations on binding to different TKIs. RESULTS: In patients with postcrizotinib and postlorlatinib samples, an accumulation of on- and off-target resistance alterations after multiple TKI treatments was observed. ROS1 G2032R and MET amplification were the most common on-target and off-target alterations, respectively. Patients with CD74-ROS1 and SLC34A2-ROS1 had longer progression-free survival (PFS) (P < 0.001) and higher rates of resistance mutations (on-target, P = 0.001; off-target, P = 0.077) than other ROS1 fusion variants following crizotinib treatment. Ten distinct on-target resistance mutations were detected after TKI therapies, of which 4 were previously unreported (ROS1 L2010M, G1957A, D1988N, L1982V). Molecular dynamics simulations showed that all 4 mutations were refractory to crizotinib, while G1957A, D1988N, and L1982V were potentially sensitive to lorlatinib and entrectinib. CONCLUSIONS: This study provided a comprehensive portrait of TKI-resistance mechanisms in ROS1+ NSCLC patients. Using in silico simulations of TKI activity, novel secondary mutations that may confer TKI resistance were identified and may support clinical therapeutic decision-making.

Application of the quality of recovery-40 questionnaire to evaluate the effectiveness of enhanced recovery after surgery protocols in gastric cancer.

Patient reported outcomes is currently considered to be an important supplement to evaluate the effectiveness of enhanced recovery after surgery (ERAS) clinical practice. The Quality of Recovery-40 Questionnaire (QoR-40) is one of the most frequently used and validation tool to assess the subjective feelings of quality of life after surgery. The present study aimed to use the QoR-40 to evaluate the effectiveness of ERAS protocols in gastric cancer from the perspective of patient-reported quality of recovery. The study was designed as a prospective, non-randomized clinical trial, conducted in a single center. Patients in our hospital who were scheduled to undergo radical surgery for gastric cancer were divided into ERAS group and control group (Contr group). The QoR-40 were administered one day before surgery (Baseline) and on postoperative day 1, 3, 6, and 30. The difference in QoR-40 scores between the ERAS and Contr groups was compared by repeated-measures ANOVA. A total of 200 patients completed the study, including 100 patients in the ERAS group and 100 patients in the Contr group. The Baseline time point QoR-40 scores of the ERAS and Contr groups were 179.68 ± 14.46 and 180.12 ± 17.12, respectively, and no significant difference was noted between the two groups (p = 0.845). The postoperative QoR-40 score of the ERAS group was significantly higher than that of the Contr group, and the difference was statistically significant (p = 0.006). This study demonstrated that, in terms of patient-reported quality of recovery, the postoperative recovery effect of ERAS protocols in gastric cancer is significantly better than that of the traditional treatment model.

Incidence of and risk factors for suspected and definitive glaucoma after bilateral congenital cataract surgery: a 5-year follow-up.

AIMS: To report the incidence and associated risk factors for developing suspected and definitive glaucoma after bilateral congenital cataract (CC) removal with a 5-year follow-up. METHODS: Secondary analysis of a prospective longitudinal cohort study. Bilateral CC patients who had undergone cataract surgery between January 2011 and December 2014 at Zhongshan Ophthalmic Centre were recruited. Suspected glaucoma was defined as persistent ocular hypertension requiring medical treatment. Definitive glaucoma was defined as accompanied by the progression of glaucomatous clinical features. According to postoperative lens status in 5 years follow-up: 130 eyes in the aphakia group; 219 in the primary intraocular lens (IOL) implantation group and 337 in the secondary IOL implantation group. The Kaplan-Meier survival and Cox regression analyses were used to explore the cumulative incidence and risk factors for suspected and definitive glaucoma. RESULTS: Three hundred fifty-one children (686 eyes) with bilateral CCs were enrolled in the study. The mean age at surgery was 1.82±2.08 years, and the mean follow-up duration was 6.26±0.97 years. Suspected and definitive glaucoma developed at a mean time of 2.84±1.75 years (range 0.02-7.33 years) postoperatively. The cumulative incidence of suspected and definitive glaucoma was 9.97% (35 of 351 patients), including 6.12% (42 eyes) for definitive glaucoma and 2.48% (17 eyes) for suspected glaucoma. Microcornea (HR 4.103, p<0.0001), CC family history (HR 3.285, p=0.001) and initial anterior vitrectomy (HR 2.365 p=0.036) were risk factors for suspected and definitive glaucoma. Gender, age at surgery, intraocular surgery frequency, length of follow-up and frequency of neodymium-doped yttrium aluminumaluminium garnet laser were non-statistically significant. Primary IOL implantation was a protective factor (HR 0.378, p=0.007). CONCLUSIONS: Identifying suspected and definitive glaucoma after bilateral CC surgery can lower the risk of secondary blindness in children. Patients with related risk factors need to pay more attention and thus reach early intervention and treatment during clinical practice. Primary IOL implantation may be a potential protective factor, need more clinical trials to be verified. TRIAL REGISTRATION NUMBER: NCT04342052.

Correction to: Targeted therapy for cisplatin-resistant lung cancer via aptamer-guided nano-zinc carriers containing USP14 siRNA.

[This corrects the article DOI: 10.1002/mco2.237.].

Edible gum addition improves the quality of freeze-dried restructured strawberry blocks.

Freeze-dried restructured strawberry blocks (FRSB) have become an increasingly popular product. In this study, the effects of six edible gums (guar gum, gelatin, xanthan gum, pectin, konjac gum, and carrageenan) on the FRSB quality were investigated. For FRSBs, compared with those in untreated samples, the 0.6 % guar gum addition increased texture profile analysis (TPA) hardness, chewiness, and puncture hardness by 29.59%, 174.86%, and 25.34%, respectively; after the 0.6% gelatin addition, the sensory evaluation sourness was reduced by 8.58%, whereas yield, TPA chewiness, and puncture hardness were increased by 3.40%, 28.62%, and 92.12%, respectively; with the 0.9% gelatin addition, the sensory evaluation sourness was reduced by 8.58%; with the 0.9% pectin addition, the yield, TPA hardness, chewiness, and puncture hardness were increased by 4.55%, 5.94%, 77.49%, and 103.62%, respectively. In summary, 0.6-0.9% pectin, gelatin, and guar gum addition are recommended to improve the main qualities of FRSBs.

Comparison of the performance of the GLIM criteria, PG-SGA and mPG-SGA in diagnosing malnutrition and predicting survival among lung cancer patients: A multicenter study.

BACKGROUND & AIMS: The present study aimed to compare the ability of the GLIM criteria, PG-SGA and mPG-SGA to diagnose malnutrition and predict survival among Chinese lung cancer (LC) patients. METHODS: This was a secondary analysis of a multicenter, prospective, nationwide cohort study, 6697 LC inpatients were enrolled between July 2013 and June 2020. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and quadratic weighted Kappa coefficients were calculated to compare the ability to diagnose malnutrition. There were 754 patients who underwent follow-up for a median duration of 4.5 years. The associations between the nutritional status and survival were analyzed by the Kaplan-Meier method and multivariable Cox proportional hazard regression models. RESULTS: The median age of LC patients was 60 (53, 66), and 4456 (66.5%) were male. There were 617 (9.2%), 752 (11.2%), 1866 (27.9%), and 3462 (51.7%) patients with clinical stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ LC, respectively. Malnutrition was present in 36.1%-54.2% (as evaluated using different tools). Compared with the PG-SGA (used as the diagnostic reference), the sensitivity of the mPG-SGA and GLIM was 93.7% and 48.3%; the specificity was 99.8% and 78.4%; and the AUC was 0.989 and 0.633 (P < 0.001). The weighted Kappa coefficients were 0.41 for the PG-SGA vs. GLIM, 0.44 for the mPG-SGA vs. GLIM, and 0.94 for the mPG-SGA vs PG-SGA in patients with stage Ⅰ-Ⅱ LC. These values were respectively 0.38, 0.39, and 0.93 in patients with stage Ⅲ-Ⅳ of LC. In a multivariable Cox analysis, the mPG-SGA (HR = 1.661, 95%CI = 1.348-2.046, P < 0.001), PG-SGA (HR = 1.701, 95%CI = 1.379-2.097, P < 0.001) and GLIM (HR = 1.657, 95%CI = 1.347-2.038, P < 0.001) showed similar death hazard ratios. CONCLUSIONS: The mPG-SGA provides nearly equivalent power to predict the survival of LC patients as the PG-SGA and the GLIM, indicating that all three tools are applicable for LC patients. The mPG-SGA has the potential to be an alternative replacement for quick nutritional assessment among LC patients.

Targeted therapy for cisplatin-resistant lung cancer via aptamer-guided nano-zinc carriers containing USP14 siRNA.

Cisplatin (DDP) is a common therapeutic option for non-small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin-specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP-resistant lung cancer cells and couple them with nano-zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP-resistant lung cancer compared to DDP-sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin-resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer-targeted nano-zinc carriers were loaded with USP14 siRNA to target DDP-resistant lung cancer cells. Aptamer-targeted nano-zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer-guided nano-zinc carriers may be a potent carrier for the precise treatment of drug-resistant tumors.

Plasma extracellular vesicle transcriptomics identifies CD160 for predicting immunochemotherapy efficacy in lung cancer.

Better biomarkers are needed to improve the efficacy of immune checkpoint inhibitors in lung adenocarcinoma (LUAD) treatment. We investigated the plasma extracellular vesicle (EV)-derived long RNAs (exLRs) in unresectable/advanced LUAD to explore biomarkers for immunochemotherapy. Seventy-four LUAD patients without targetable mutations receiving first-line anti-programmed cell death 1 (PD-1) immunochemotherapy were enrolled. Their exLRs were profiled through plasma EV transcriptome sequencing. Biomarkers were analyzed against response rate and survival using pre- and post-treatment samples in the retrospective cohort (n = 36) and prospective cohort (n = 38). The results showed that LUAD patients demonstrated a distinct exLR profile from the healthy individuals (n = 56), and T-cell activation-related pathways were enriched in responders. Among T-cell activation exLRs, CD160 exhibited a strong correlation with survival. In the retrospective cohort, the high baseline EV-derived CD160 level correlated with prolonged progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.005), with an area under the curve (AUC) of 0.784 for differentiating responders from non-responders. In the prospective cohort, the CD160-high patients also showed prolonged PFS (P = 0.003) and OS (P = 0.014) and a promising AUC of 0.648. The predictive value of CD160 expression was validated by real-time quantitative PCR. We also identified the dynamics of EV-derived CD160 for monitoring therapeutic response. The elevated baseline CD160 reflected a higher abundance of circulating NK cells and CD8+ -naïve T cells, suggesting more active host immunity. In addition, increased CD160 levels of tumors also correlated with a favorable prognosis in LUAD patients. Together, plasma EV transcriptome analysis revealed the role of the baseline CD160 level and early post-treatment CD160 dynamics for predicting the response to anti-PD-1 immunochemotherapy in LUAD patients.

Promising efficacy of immune checkpoint inhibitor plus chemotherapy for thoracic SMARCA4-deficient undifferentiated tumor.

PURPOSE: Thoracic SMARCA4-deficient undifferentiated tumor (SD-UT) is a highly aggressive disease that is nosologically related to but distinct from SMARCA4-deficient non-small cell lung cancer (SD-NSCLC). No standard treatment guidelines were established for SD-UT. This research explored the efficacy of different treatments in SD-UT, and the prognostic, clinicopathologic and genomic difference between SD-UT and SD-NSCLC. MATERIALS AND METHODS: Information of 25 SD-UT and 22 SD-NSCLC patients diagnosed and treated in Fudan University Shanghai Cancer Center from January, 2017 to September, 2022 was analyzed. RESULTS: SD-UT was similar to SD-NSCLC in characteristics of onset age, male prevalence, heavy smoking history and metastatic pattern. SD-UT showed a rapid relapse pattern after radical therapy. For Stage IV SD-UT patients, immune checkpoint inhibitor (ICI) plus chemotherapy significantly improved median progression-free survival (PFS) compared to traditional chemotherapy as first-line treatment (26.8 vs. 2.73 months, p = 0.0437), while objective response rates of two arms were comparable (71.4% vs. 66.7%). No significant survival differences were observed between SD-UT and SD-NSCLC under similar treatment settings. SD-UT or SD-NSCLC patients receiving ICI in the first line had significantly prolonged OS than those with ICI in the latter lines or without ICI treatment throughout clinical courses. Genetic study found frequent SMARCA4, TP53 and LRP1B mutations in SD-UT. CONCLUSION: To the best of our knowledge, this is the largest series to date to compare the efficacy of ICI-based treatment to chemotherapy and document frequent mutations of LRP1B in SD-UT. ICI plus chemotherapy is an effective strategy for Stage IV SD-UT.

Efficacy and safety of immune checkpoint inhibitors in post-TKI NSCLC patients harboring EGFR mutations.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) have been validated in epidermal growth factor receptor (EGFR) wild-type advanced non-small cell lung cancer (NSCLC) patients. However, there exists no evidence regarding NSCLC patients harboring EGFR mutations, experiencing EGFR-TKI (tyrosine kinase inhibitor) treatment failure. We collected clinical information from real world and conducted a time series-based meta-analysis to determine the efficacy and safety of ICIs in patients harboring EGFR mutations and experienced EGFR-TKIs resistance. METHODS: Twenty-two NSCLC patients with EGFR mutations after TKI resistance were included from two hospitals. PubMed, Embase and Cochrane Library were searched for relevant literature published until December 31, 2021. Endpoint outcomes included mortality and progression-free survival (PFS) at different times of follow-up. RESULTS: In total, 22 patients showed that the median PFS was 5.6 months (range 2.0-9.0 months). According to treatment strategies, the median PFS was 2.4 months (range 2.0-5.3 months) in the ICI monotherapy group and 5.9 months (range 2.8-9.0 months) in the ICI combined Chemotherapy group. Additionally, sixteen studies, including 5 trials, 10 controlled cohorts and 1 real-world study, were assessed, involving a total of ICI-treated NSCLC patients with EGFR mutation after TKI failure. The 6-month survival and PFS rate were 0.82 (95% CI 0.36-0.97) and 0.55 (95% CI 0.34-0.74), respectively. ICI combined chemotherapy showed the best survival outcome among these groups, as demonstrated by the 12-month survival rate and PFS. No new safety signals were identified with the combination therapy. The frequency of treatment-related adverse events was similar to that in previously reported studies of chemotherapy combined with checkpoint inhibitors. CONCLUSIONS: The addition of ICIs plus chemotherapy may significantly improve progression-free survival among patients with locally advanced or metastatic non-squamous NSCLC who EGFR-TKIs resistance.

Prognostic value of hematologic parameters in advanced non-small cell lung cancer patients receiving anti-PD-1 inhibitors.

Background: The association between hematologic parameters and anti-programmed death-1 (PD-1) inhibitors was generally examined without considering therapy lines and medicine types. The study was aimed to identify potential hematologic biomarkers associated with clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab and subsequent-line nivolumab. Materials and methods: 161 NSCLC patients were categorized into first-line pembrolizumab group (pembrolizumab group) and subsequent-line nivolumab group (nivolumab group). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of hematologic parameters for clinical outcomes. Results: The median progression-free survival (mPFS) was 9.6 months in the pembrolizumab group and 4.1 months in the nivolumab group (HR =1.61; P = 0.012); the median overall survival (mOS) was not reached in the pembrolizumab group and 17.7 months in the nivolumab group (HR =1.37; P = 0.23). Of the 79 patients in the pembrolizumab group, baseline PD-L1 tumor proportion score (TPS)≥1% was an independent factor of longer PFS and OS. Age≥60 years, absolute platelet count (APC)≥220×109/L and platelet-to-lymphocyte ratio (PLR)≥120 were associated with inferior PFS. Of the 82 patients in the nivolumab group, absolute neutrophil count (ANC)≥3×109/L was associated with longer PFS, while LDH (lactate dehydrogenase)≥160 U/L was associated with inferior PFS and derived neutrophil-to-lymphocyte ratio (dNLR)≥1.2 was associated with longer OS. Conclusion: Our study identified multiple clinically accessible prognostic biomarkers in the peripheral blood in both the pembrolizumab and nivolumab subgroups.

Pegylated Liposomal Doxorubicin Combined with Ifosfamide for Treating Advanced or Metastatic Soft-tissue Sarcoma: A Prospective, Single-arm Phase II Study.

PURPOSE: This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS). PATIENTS AND METHODS: Patients received PLD (30 mg/m2; day 1) in combination with IFO (1.8 g/m2; days 1-5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772). RESULTS: Overall, 69 patients with chemotherapy-naïve advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 [95% confidence interval (CI): 5.7-8.9] and 20.6 (95% CI: 16.3-25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3-4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (P < 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056). CONCLUSIONS: Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.

Design and Synthesis of Cobalt-Based Hollow Nanoparticles through the Liquid Metal Template.

Co-based compounds have attracted much attention due to their competitive catalytic activities. To enhance their intrinsic electrocatalytic activity, morphology engineering is one of the effective strategies. Hollow structures have fascinating properties due to their low density and high loading capacity. In this work, we introduce a Ga-based liquid alloy as a reactive template for the synthesis of varying Co-based hollow nanoparticles. The fluidity character of the Ga-based liquid alloy facilitates the large-scale production of nanoparticles via a top-down shearing process. The pre-installed active species (here is Zn) in the liquid alloy serve as a sacrificial source to quantitatively reduce Co2+ ions and form Co-based compounds. Well-structured Ga/CoOOH core-shell nanospheres are thus successfully prepared, and more varied Co-based hollow nanoparticles can be obtained by post-treatment and reaction. Hollow structures can offer enhanced interfacial area and increased active sites, benefiting the catalytic performance. Among the prepared Co-based catalysts, CoSe2 hollow nanoparticles exhibited the best oxygen evolution reaction (OER) activity with an overpotential of 340 mV at the current density of 10 mA/cm2. This work provides a novel strategy for the rational design and simple preparation of hollow nanoparticles.

Corrigendum: Research on Improving Online Purchase Intention of Poverty-Alleviation Agricultural Products in China: From the Perspective of Institution-Based Trust.

[This corrects the article DOI: 10.3389/fpsyg.2022.900328.].