Three years follow-up of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer.

Neoadjuvant chemoimmunotherapy plays a crucial role in resectable non-small cell lung cancer (NSCLC). Neoadjuvant chemotherapy before sleeve lobectomy was safe and feasible, but the impact of neoadjuvant chemoimmunotherapy before sleeve lobectomy was unclear. In our retrospective study, patients diagnosed as stage IIB to IIIB resectable NSCLC between December 1, 2018 and December 1, 2020 in the Department of Thoracic Surgery, Zhejiang Cancer Hospital were collected. We analyzed the efficacy and safety of neoadjuvant chemoimmunotherapy for resectable NSCLC patients and analyzed the impact of different types of surgery on postoperative complications, surgical difficulty, and long-term survival. In total, 56 patients were included in this retrospective study. With a median follow-up of 35 months, 1-year EFS, 2-year EFS, and 3-year EFS were 87.5%, 80.4%, and 76.7%, respectively. 1-year OS, 2-year OS, and 3-year OS were 96.4%, 91.1%, and 85.6%. respectively. Both median EFS and OS were not reached. The percentage of patients with pCR was 51.8%. 48 (85.7%) patients had nodal downstaging and primary tumor downstaging. In 40 (61.4%) patients occurred neoadjuvant chemoimmunotherapy-related adverse events (AEs), most of them of Grade 1 and 2. Postoperative complications occurred in 19 (33.9%) patients. Subgroup analysis showed that sleeve lobectomy was related to better survival and had no impact on operation duration, hospital stay, intraoperative blood loss, and postoperative complications. Neoadjuvant chemoimmunotherapy led to a high pCR rate, favorable 3-year survival rate, and acceptable AEs. Sleeve lobectomy was safe and related to better survival.

Soft wetting: an analytical model for pillar topography- and softness-dependent droplet depinning force.

The extent to which a droplet pins on a textured substrate is determined by the dynamics of the contact line and the liquid-vapor interface. However, the synergistic contribution of contact line sliding and interface distortion to the droplet depinning force remains unknown. More strikingly, current models fail to predict the depinning force per unit length of droplets on soft pillar arrays. Therefore, we fabricate soft pillar arrays with varying geometrical dimensions and mechanical properties and measure the depinning forces per unit length by allowing droplets to evaporate on such substrates. We then analyze the decrease in excess Gibbs free energy of the apparent droplet caused by the detachment of the droplet boundary from the previously pinned pillars. In contrast to prior notions, based on the measured decreases in excess Gibbs free energy, we find that the coefficient, that governs the ratio of interface distortion's contribution to the depinning force to that of the sliding contact line, increases with a decrease in pillar packing density. By considering the combined contribution from contact line sliding, liquid-vapor interface distortion, and pillar deflection, we introduce an analytical model to predict the droplet depinning force per unit length and corroborate the model using experimental data reported in this and prior studies.

Soft wetting: Substrate softness- and time-dependent droplet/bubble adhesion.

HYPOTHESIS: The droplet/bubble adhesion characteristics depend on the length of the droplet/bubble three-phase contact line. Since the deformation caused by the liquid-gas interfacial tension on the soft substrate, referred as to the wetting ridge, retards contact line spreading and retraction, we conjecture that the droplet/bubble adhesion characteristics depend also on the substrate softness. EXPERIMENTS: Soft substrates with various shear moduli are prepared and characterized by the spreading and receding dynamics of water droplets and underwater bubbles. Snap-in and normal adhesion forces of droplets/bubbles on such soft substrates are directly measured along with the visualized droplet/bubble shape profiles. FINDINGS: The droplet/bubble snap-in force, which corresponds to the short-time spreading dynamics, decreases with a decrease in the substrate shear modulus because of the retarded contact line spreading. The droplet maximal adhesion force on a soft substrate can be counterintuitively either smaller or larger than its counterpart on the rigid substrate depending on different dwelling times, i.e., the droplet/bubble-substrate contact time before droplet/bubble-substrate separation. The former is attributed to the retarded contact line spreading, whereas the latter is attributed to the retarded contact line retraction. The substrate softness- and dwelling time-dependent droplet/bubble adhesion reported in this study will benefit various applications related to soft substrates.

A Superhydrophobicity-Slipperiness Switchable Surface with Magneto- and Thermo-responsive Wires for Repelling Complex Droplets.

The inefficacy of repelling water droplets laden with macromolecules (complex droplets or diluted polymer solution) is a long-standing shortcoming of superhydrophobic surfaces, which severely limits their reliability in practical applications. Here, we design a surface termed the superhydrophobicity-slipperiness switchable surface (3S surface), which demonstrates superhydrophobicity at room temperature and slipperiness when heated. The 3S surface is composed of magneto-responsive wires coated with superhydrophobic nanoparticles and impregnated with thermoresponsive paraffin, exhibiting lotus leaf-inspired passive water repellency and respiratory cilia-inspired active water repellency at room temperature. When heated, the impregnated paraffin melts and forms a lubricant layer atop the surface structures, exhibiting the pitcher-plant-inspired removal of complex droplets that remain pinned on conventional superhydrophobic surfaces. The counterintuitive integration of superhydrophobicity (a liquid-solid-gas composite system) and slipperiness (a liquid-lubricant-gas system) into a surface and the on-demand switch between them are not only important to the applicability of self-cleaning surfaces to real-world environments, where complex liquids are inevitable, but also provide insights into various interface-related applications.

Soft Wetting: Droplet Receding Contact Angles on Soft Superhydrophobic Surfaces.

Despite intensive investigations on the droplet receding contact angle on superhydrophobic surfaces, i.e., a key parameter characterizing surface wettability and adhesion, the quantitative correlation between the surface structure mechanical properties (softness) and the droplet receding contact angles remains vague. By systematically varying the geometric dimensions and mechanical properties of soft pillar arrays, we find that the droplet receding contact angles decrease with the decrease in the pillar spring constant. Most surprisingly, the densely packed pillar arrays may result in larger receding contact angles than those on sparsely packed pillars, opposing the understanding of rigid pillar arrays, where the receding contact angles increase with a decrease in the packing density of pillars. This is attributed to the collective effects of capillarity and elasticity, where the energy consumed by the sliding contact line, the energy stored in the distorted liquid-vapor interface, and the energy stored in the deflected pillar contribute to the droplet depinning characteristics. We develop an analytical model to predict the droplet receding contact angles on soft superhydrophobic pillar arrays with knowledge of the material intrinsic receding contact angle, the pillar geometry, and the pillar mechanical properties. The predictions are corroborated by the experimental data measured in this and prior studies.

Dynamic and Quasi-static Droplet Penetration through Meshes.

We investigate experimentally the effects of pore size, surface wettability, and penetration mode on the characteristics of liquid penetration through meshes. Utilizing the impact of droplets and the hydrostatic pressure, we study water penetration through superhydrophobic, hydrophobic, superhydrophilic, and hydrophilic meshes with different uniform radii and pitch values of the pores. In the case of dynamic penetration enabled by the droplet impact, our results show that surface wettability has a negligible effect on either the threshold speed of the droplet penetration or the penetrating liquid mass. The threshold droplet speed is found to be mainly determined by the synergistic effects of global and local dynamic pressures of the impacting droplet, and a modified expression for the threshold droplet speed is proposed. For the quasi-static penetration based on the applied hydrostatic pressure, we find that surface wettability and pore pitch do not affect the penetration threshold pressure but do affect the pressure at which the liquid penetration ceases. This is due to the fact that under quasi-static conditions, the droplet liquid spreads out and merges with that at the adjacent pores on the mesh underside, affecting the wetted area and, hence, the capillary pressure resisting penetration.

Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma.

PURPOSE: The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown. METHODS AND MATERIALS: In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed. RESULTS: Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P = .06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P = .067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P = .028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P = .037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P = .076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P = .038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P = .041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ = -0.45; P = .02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ = -0.56; P = .003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ = 0.40; P = .05) in posttreatment samples. CONCLUSIONS: nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity.

Bioinspired Wire-on-Pillar Magneto-Responsive Superhydrophobic Arrays.

Versatile surfaces demonstrating multiple interfacial functionalities are highly demanded as a surface typically serves various duties and faces multiple challenges in real practice. However, such versatile surfaces are rarely reported mainly due to the challenges in integrating multiple structural characteristics. Here, by mimicking lotus leaves, butterfly wing, and respiratory cilia, we develop a surface termed wire-on-pillar magneto-responsive superhydrophobic arrays (WP-MRSA), which possess interfacial properties of structural superhydrophobicity, anisotropicity, stimuli responsiveness, and flexibility. By combining soft lithography and self-alignment of iron-laden aerosols under a magnetic field, iron-laden wires are planted atop prefabricated pillar arrays, resulting in well-ordered, sparse, high-aspect-ratio, flexible, and superhydrophobic wires, which largely deflect in response to a magnetic field. This unique integration of structural properties and configurations enables various functionalities, such as on-demand control of droplet impact dynamics, real-time regulation of surface lateral adhesion force, fast removal and sorting of objects, and precise manipulation of droplets for selective reactions. Those functionalities benefit various applications especially droplet-based microfluidics and active self-cleaning surfaces.

The control of dry-out patterns using bubble-containing droplets.

HYPOTHESIS: For an evaporating nanofluid droplet that contains a bubble inside, we suspect the bubble boundary remains pinned during evaporation whereas the droplet perimeter recedes. Thus, the dry-out patterns are mainly determined by the presence of the bubble and their morphology can be tuned by the size and location of the added bubble. EXPERIMENTS: Bubbles with varying base diameters and lifetimes are added into evaporating droplets that contain nanoparticles with different types, sizes, concentrations, shapes, and wettability. The geometric dimensions of the dry-out patterns are measured. FINDINGS: For a droplet containing a long-lifetime bubble, a complete ring-like deposit forms, and its diameter and thickness increases and decreases with the bubble base diameter, respectively. The ring completeness, i.e., the ratio of actual ring length to its imaginary perimeter, decreases with the decrease in bubble lifetime. The pinning of droplet receding contact line by particles near the bubble perimeter has been found to be the key factor leading to ring-like deposits. This study introduces a strategy of producing ring-like deposit and allows a control of the ring morphology in a simple, cheap, and impurity-free fashion, which is applicable to various applications associated with evaporative self-assembly.

Surgical selection and regional lymph node dissection for stage I second primary lung cancer patients following surgery for stage I first primary lung cancer.

Introduction: Studies investigating surgery for second primary non-small cell lung cancer (SP) patients are rare. The aim of this study was to explore the effects of surgical methods and regional lymph node (LN) dissection on lung cancer-specific mortality (LCSM) in stage I SP patients following surgery for stage I first primary non-small cell lung cancer (FP). Methods: Data on patients diagnosed with stage I SP after surgery for stage I FP were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative incidence function (CIF) curves, a competing risk model and propensity score matching (PSM) were adopted to compare the LCSM among different subgroups (including surgery and regional LN dissection). Results: A total of 238 stage I SP patients were extracted from the SEER database. Overall, the 5-year LCSM rate was 29.8% (CI: 23.1%-36.5%) for the whole cohort. Both before and after PSM, lobectomy had a similar LCSM incidence as sublobectomy, and ≥4 regional LN dissections had a significantly lower LCSM incidence than 1~3 regional LN dissections.In addition, patients who underwent 1~3 regional LN dissections had a comparable incidence of LCSM to those without LN dissections. Discussion: Stage I SP patients tended to gain more survival benefits when surgeons dissect ≥4 regional LNs. Allowing for the comparable LCSM incidence of sublobectomy to lobectomy, sublobectomy may be a reasonable choice for thoracic surgeons when performing surgery for these patients.

A combined predictive model based on radiomics features and clinical factors for disease progression in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

Purpose: To accurately assess disease progression after Stereotactic Ablative Radiotherapy (SABR) of early-stage Non-Small Cell Lung Cancer (NSCLC), a combined predictive model based on pre-treatment CT radiomics features and clinical factors was established. Methods: This study retrospectively analyzed the data of 96 patients with early-stage NSCLC treated with SABR. Clinical factors included general information (e.g. gender, age, KPS, Charlson score, lung function, smoking status), pre-treatment lesion status (e.g. diameter, location, pathological type, T stage), radiation parameters (biological effective dose, BED), the type of peritumoral radiation-induced lung injury (RILI). Independent risk factors were screened by logistic regression analysis. Radiomics features were extracted from pre-treatment CT. The minimum Redundancy Maximum Relevance (mRMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for the dimensionality reduction and feature selection. According to the weight coefficient of the features, the Radscore was calculated, and the radiomics model was constructed. Multiple logistic regression analysis was applied to establish the combined model based on radiomics features and clinical factors. Receiver Operating Characteristic (ROC) curve, DeLong test, Hosmer-Lemeshow test, and Decision Curve Analysis (DCA) were used to evaluate the model's diagnostic efficiency and clinical practicability. Results: With the median follow-up of 59.1 months, 29 patients developed progression and 67 remained good controlled within two years. Among the clinical factors, the type of peritumoral RILI was the only independent risk factor for progression (P< 0.05). Eleven features were selected from 1781 features to construct a radiomics model. For predicting disease progression after SABR, the Area Under the Curve (AUC) of training and validation cohorts in the radiomics model was 0.88 (95%CI 0.80-0.96) and 0.80 (95%CI 0.62-0.98), and AUC of training and validation cohorts in the combined model were 0.88 (95%CI 0.81-0.96) and 0.81 (95%CI 0.62-0.99). Both the radiomics and the combined models have good prediction efficiency in the training and validation cohorts. Still, DeLong test shows that there is no difference between them. Conclusions: Compared with the clinical model, the radiomics model and the combined model can better predict the disease progression of early-stage NSCLC after SABR, which might contribute to individualized follow-up plans and treatment strategies.

Droplet Spreading and Adhesion on Spherical Surfaces.

Adhesion of a liquid droplet to a solid surface is a result of solid surface interactions with surrounding fluids, affected by its wettability and morphology. Unfortunately, the direct measurements of adhesion forces are rarely reported in the scientific literature, especially for solids with curvatures. In this study, by using a high-sensitivity microelectronic mechanical balance which vertically deposits and then pulls liquid droplets, the spreading and adhesion forces for water and ethylene glycol droplets on spherical surfaces of polyethylene terephthalate (PET) with radii of curvature from 2 to 8 mm were recorded. Results show that the surface curvature does not affect the advancing and most-stable contact angles but affects the extent of spreading and maximum adhesion forces. The solid surface curvature affects both surface tension and Laplace pressure forces at the spreading point, whereas it mainly affects the Laplace pressure force at the maximum adhesion point.

Crosstalk between the gut microbiome and clinical response in locally advanced thoracic esophageal squamous cell carcinoma during neoadjuvant camrelizumab and chemotherapy.

Background: The gut microbiome is associated with the response to immunotherapy in a variety of advanced cancers. However, the influence of the gut microbiome on locally advanced esophageal squamous cell carcinoma (ESCC) during programmed cell death protein 1 (PD-1) antibody immunotherapy plus chemotherapy is not clearly demonstrated. To explore the crosstalk between the gut microbiome and clinical response in locally advanced thoracic ESCC during neoadjuvant camrelizumab and chemotherapy. Methods: Patients who were diagnosed with locally advanced thoracic ESCC and had not received treatment were enrolled. The treatment regimen was two cycles of camrelizumab combined with carboplatin and albumin paclitaxel before surgery. The research endpoints were pathological complete response (pCR) and major pathological response (MPR). Fecal samples were collected at three time points: before neoadjuvant therapy, after two cycles of neoadjuvant therapy, and after surgery. We performed 16S ribosomal ribonucleic acid (rRNA) V3-V4 sequencing of the gene amplicons of fecal samples, as well as bacterial diversity and differential abundance analyses. Results: A total of 46 patients were recruited, and 44, 42, and 35 fecal samples were collected at the three time points, respectively. Statistically significant differences were observed in the amplicon sequence variant (ASV)-level alpha diversity indices, including Chao1, Shannon, and Good's coverage, between the three time points. The non-pCR-enriched gut microbiota included Proteobacteria, Dialister, Aeromonadales, Pseudomonadales, Thermi, Deinococci, Moraxellaceae, Rhodocyclales, Rhodocyclaceae, and Acinetobacter. The non-MPR-enriched gut microbiota included Pseudomonadales and the mitochondria family. The MPR-enriched gut microbiota included the Barnesiellaceae, Pyramidobacter, Dethiosulfovibrionaceae, Odoribacteraceae, Butyricimonas, Prevotella, Barnesiella, and Odoribacter. Patients with ≥3 grade adverse events (AEs) exhibited enrichment in the Succiniclasticum, Nakamurella, Rhizobium, Granulicella, Phyllobacteriaceae, Pelagibacteraceae, Actinosynnemataceae, Aquirestis, Flavisolibacter, Chelativorans, Coxiellaceae Acidicapsa, Acidobacteriaceae, Lentzea, Staphylococcus, Plesiomonas, Dysgonomonas, Pseudonocardia, and Ellin6075. Conclusions: We found that the diversity of the gut microbiome declined after neoadjuvant PD-1 antibody immunotherapy plus chemotherapy and surgery. Patients with pCR had different types and proportions of gut microbiota before treatment compared to those without pCR. We also observed the difference between patients with or without ≥ grade 3 AEs. The taxonomic features of the gut microbiome are potential biomarkers that could predict the pathological response and AEs.

Detection of internal humidity in a transformer via optical interferometry.

To detect the internal humidity of the transformer accurately and sensitively and eliminate the interference caused by electromagnetic fields, an interferometric measurement is proposed in this paper for the first time, to the best of our knowledge. The phase value distribution of the interferogram affected by humidity can be extracted quantitatively. The peak-to-peak value (P-P) of the phase image can reflect the humidity, according to theoretical analysis, and the main factors affecting the P-P are current and humidity. It has been tested by currents of 800 A, 1000 A, and 1200 A and different humidities. The paper reveals the relationship between humidity and P-P, proving that it is a reasonable application of real-time measurement of internal humidity in the transformer.

Maximum Spreading of Impacting Ferrofluid Droplets under the Effect of Nonuniform Magnetic Field.

This article investigates the maximum spreading of ferrofluid droplets impacting on a hydrophobic surface under nonuniform magnetic fields. A generalized model for scaling the maximum spreading is developed. It is observed that, if the magnetic field strength is zero, a ferrofluid droplet not only demonstrates similar spreading dynamics as the water droplet but also obeys the same scaling law for the maximum spreading factor. Therefore, this article emphasizes the effects of magnetic field strength. In this regard, a dimensionless parameter (Nm) is introduced as the ratio between inertial force and Kelvin force, with an assumption that the kinetic energy mainly transforms to thermal energy. This parameter allows us to rescale all experimental data on a single curve with the Padé approximant, which is applicable to a wide range of impact velocities and magnetic field strengths.

Long non-coding RNA MCM3AP antisense RNA 1 promotes non-small cell lung cancer progression through targeting microRNA-195-5p.

Lung cancer (LC) ranks first among all causes of cancer-related death, with non-small cell lung cancer (NSCLC) taking up 85% of lung cancer cases. Although lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) has been reported to be an oncogenic factor in NSCLC, its detailed mechanism in NSCLC is unknown. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine MCM3AP-AS1, microRNA (miR)-195-5p and E2F transcription factor 3 (E2F3) mRNA expressions in NSCLC tissues and cells. Western blot was utilized to determine the expression levels of E2F3, BCL2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), E-cadherin and N-cadherin. CCK-8 and Transwell assays were conducted to examine cell proliferation, migration and invasion, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation experiments were used to determine the regulatory relationships between MCM3AP-AS1 and miR-195-5p, and miR-195-5p and E2F3. We demonstrated that MCM3AP-AS1 was overexpressed in NSCLC tissues and cells, and MCM3AP-AS1 overexpression accelerated the proliferation, migration and invasion of NSCLC cells. In addition, MCM3AP-AS1 overexpression markedly up-modulated Bcl-2 expression and repressed Bax expression; MCM3AP-AS1 overexpression also significantly up-regulated N-cadherin expression and suppressed E-cadherin expression in NSCLC cells. What is more, in NSCLC cells, miR-195-5p was a target of MCM3AP-AS1, and the latter worked as a molecular sponge for miR-195-5p to regulate E2F3 expression. Collectively, MCM3AP-AS1, serving as a competitive endogenous RNA (ceRNA) to regulate miR-195-5p/E2F3 axis, promotes NSCLC progression, which is a promising therapeutic target for NSCLC.

The safety and efficacy of neoadjuvant programmed death 1 inhibitor therapy with surgical resection in stage IIIA non-small cell lung cancer.

BACKGROUND: Lung cancer ranks as the most prevalent solid cancer in the world. The non-small-cell lung cancer (NSCLC) histological subtype accounts for the largest proportion of lung cancers. Even though neoadjuvant therapy has shown encouraging efficacy for resectable NSCLC, there is a lack of clinical data on the treatment of stage IIIA NSCLC patients. Therefore, we carried out an evaluation of the safety and efficacy of programmed cell death 1 (PD-1) inhibitor as an addition to neoadjuvant chemotherapy. METHODS: This prospective study involved 72 treatment-naive adult subjects with stage IIIA NSCLC between September 2019 and July 2020. Two circles PD-1 inhibitor with chemotherapy (Albumin paclitaxel 100 mg/m2 d1,8 + Carboplatin AUC 5 d1) were administered intravenously every 3 weeks. The patients were operated on between 3 and 5 weeks following the second cycle. Feasibility and safety served as the primary endpoints for this study. The rates of pathologic complete response, complete resection, response rate, and operative and postoperative complications among the patients were also analyzed. RESULTS: Seventy-two patients with untreated stage IIIA NSCLC were enrolled. The postoperative pathological specimens of 21 (29.1%) and 47 (65.2%) patients suggested pathologic complete response and partial remission, respectively. Neoadjuvant PD-1 inhibitor with chemotherapy had an acceptable side effect profile, and none of the subjects withdrew from the study preoperatively due to disease progression or toxicity. According to Response Evaluation Criteria in Solid Tumors (RESIST), responses evaluated by CT scan before surgery, 21 and 47 patients achieved complete response (CR) and partial response (PR), respectively, and a single patient was evaluated as stable disease (SD). There were no postoperative deaths. CONCLUSIONS: The outcomes of PD-1 inhibitor with chemotherapy as a novel treatment for stage IIIA NSCLC in the neoadjuvant setting are satisfactory with respect to the high R0 resection rate and low toxicity profile. Prospective comparative and longer follow-up trials are needed to confirm the long-term outcomes of this novel treatment and to reach definitive conclusions.

Neoadjuvant pembrolizumab with chemotherapy for the treatment of stage IIB-IIIB resectable lung squamous cell carcinoma.

BACKGROUND: Researches on programmed cell death (PD-1) as neoadjuvant immunotherapy for resectable non-small cell lung cancer is underway, which brings hope for individuals with the disease. However, a study dedicated to lung squamous cell carcinoma (LUSC) specifically has yet to be conducted. Now, data from our pilot prospective research neoadjuvant study provide new insights in the field of neoadjuvant regimen for LUSC. METHODS: Between June 2019 and July 2020, 37 adults with untreated, surgically resectable stage IIB-IIIB LUSC were enrolled into this prospective study. Patients received 2 cycles of pembrolizumab (2 mg/kg) with chemotherapy (albumin-bound paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin AUC 5) via intravenous administration every 3 weeks, and underwent surgical treatment 3-4 weeks after the second cycle. The primary endpoint of the study was the tumor pathologic complete response (pCR) rate. The toxicity profile, tumor major pathological remission, complete resection rate, response rate, and operative and postoperative complications were also evaluated. RESULTS: The postoperative pathological specimens of 17 (45.9%) patients suggested pCR. Neoadjuvant pembrolizumab with chemotherapy had an acceptable side-effect profile, and no patients withdrew from the study preoperatively due to disease progression or toxicity. A major pathological response occurred in 24 (64.9%) resected tumors. All tumors were completely resected (R0, 100%). According to the Response Evaluation Criteria in Solid Tumors (RESIST), a response was evaluated before surgery in 32 (86.5%) patients by computed tomography. Twenty-five (67.6%) patients underwent thoracoscopic surgery. No deaths or postoperative major complications requiring reoperation occurred. Recurrence or metastasis was found in 2 patients during follow-up of 2-14 months. CONCLUSIONS: The early outcomes of pembrolizumab with chemotherapy in the neoadjuvant setting as a novel treatment for resectable stage IIB-IIIB LUSC showed a high pCR rate that has not been seen previously, as well as a high R0 resection rate and a low toxicity profile. The long-term efficacy of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.

The safety and efficacy of neoadjuvant PD-1 inhibitor with chemotherapy for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant therapy followed by esophagectomy has been recognized as an effective treatment for locally advanced esophageal cancer, though still has a dismal prognosis. Antibodies against programmed death 1 (PD-1) protein improve survival in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with chemotherapy in second-line therapy. However, neoadjuvant PD-1 inhibitor combined with chemotherapy has not been tested in locally advanced ESCC. We conducted this study to evaluate the efficacy and safety of pd-1 inhibitor in neoadjuvant chemotherapy. METHODS: In this study, we administered 28 adults with untreated, surgically resectable locally advanced ESCC. PD-1 inhibitor with chemotherapy [albumin paclitaxel 100 mg/m2 on days 1 and 8 + carboplatin with an area under the curve (AUC) of 5 on day 1] were administered every 3 weeks intravenously, and surgery was performed approximately 3-5 weeks after the second dose. The primary purpose of the study was to evaluate the feasibility and safety of this regimen. RESULTS: In all, 28 locally advanced ESCC patients were enrolled, 27 patients received surgery, 9 (33.3%) patients' postoperative pathological specimens suggested pCR, and 11 (40.7%) patients' primary tumor suggested complete response. Neoadjuvant PD-1 inhibitor with chemotherapy had an acceptable side-effect profile, 26 patients' tumors were completely resected (96.3% were R0). According to the RESIST v.1.1, the response in all 27 patients was evaluated by a computed tomography (CT) scan before surgery, showing 12 patients with complete response (CR), 12 with partial response (PR), and 3 with stable disease (SD). For surgical procedures, 15 (55.6%) patients underwent minimal invasive surgery, 4 (14.8%) underwent right transthoracic open esophagectomy, and 8 (29.6%) underwent hybrid approaches. CONCLUSIONS: The novel treatment of PD-1 inhibitor with chemotherapy in the neoadjuvant setting for locally advanced ESCC produced satisfactory outcomes: an unprecedentedly high pCR rate for neoadjuvant chemotherapy, a high R0 resection rate, and a low-toxicity profile were achieved. The long-term efficiency of this novel treatment and the validity of the present findings should be confirmed with longer follow-up and prospective comparative trials.

Neoadjuvant immunotherapy for elderly patients with non-small-cell lung cancer: a case report and literature review.

Although neoadjuvant immunotherapy has achieved remarkable results in the treatment of lung cancer, it is still infrequently applied in geriatric patients. We report on a 76-year-old male patient with a long-term history of heavy smoking presenting with cough and hemolysis. There was no related underlying disease or positive findings on physical examination. On July 23, 2019, his chest computed tomography (CT) showed small nodules in the upper lobe of the right lung and multiple enlarged lymph nodes in the mediastinum. Fiberoptic bronchoscopy showed a neoplasm in a subsegment of the upper lobe of the right lung. Following biopsy the patient was diagnosed with squamous cell carcinoma of the right upper lung, with lymph node metastasis in the mediastinum (CT1N2M0, IIIA). Between late July and mid-August of 2019, he received chemotherapy (TP regimen) combined immunotherapy for 2 cycles of preoperative neoadjuvant therapy. Three weeks later he underwent chest CT re-examination which revealed his focus was significantly shrunken in size, and multiple lymph nodes in the mediastinum and right hilum were smaller in comparison to the first examination. The patient then underwent thoracoscopic radical resection of the right upper lung cancer under general anesthesia and recovered uneventfully after surgery. The postoperative pathology examination showed complete response and no signs of recurrence were discovered on the 6 months follow up during which time the patient received immunotherapy on a monthly basis. We report on a case of immunotherapy in a geriatric patient with literature review which supports new treatment strategies for the treatment of elderly patients with lung cancer.