e18035 Background: Neoadjuvant chemotherapy (NCT) combination with PD-1 inhibitor has a significant efficacy and approved indications in the first-line treatment of R/M head and neck squamous cell carcinoma (HNSCC), but the efficacy of the combination therapy in locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) remains unexplored. This study aimed to explore the efficacy and safety of NCT with PD-1 inhibitor for laryngeal preservation in patients with HPSCC. Methods: Patients with cT1N1-3M0 or cT2-3N0-3M0 (AJCC 8th) were eligible after multidisciplinary team (MDT) discussion. All patients received 2 cycles of intravenous docetaxel (60mg/m2 on d1), cisplatin (60mg/m2 on d1), fluorouracil (600mg/m2 per day as a continuous 120h infusion on d1-5) and toripalimab (240mg on d1) every 21 days. And the MDT underwent efficacy evaluation according to RECIST 1.1. Patients with complete response (CR)/partial response (PR) of the primary lesion(P) and no progressive disease (PD) in neck lymph nodes (LN) received definitive radiotherapy (RT) combined with toripalimab. Patients with stable disease (SD)/PD of P and no PD in LN or with PD in LN underwent surgery. Patients completed the third cycle of neoadjuvant therapy(NAT) before RT or surgery. The primary endpoint was the CR rate at 3 months (3m-CR) after NAT and definitive RT, and the secondary endpoints were the objective response rate (ORR) of NAT, laryngeal preservation rate, and adverse effects(AE). The sample size was calculated by the Simon-II-stage method: 27 patients in first stage (if ≥9 patients got 3m-CR, second stage started) , and a cumulative total of 81 patients in second stage. Results: From October 2020 to August 2023, 23 patients (median age:59, range:51-69, male:100%, stage II/III/IVA/IVB:4.3%/4.3%/26.1%/65.2%) were enrolled. After NAT, the ORR of primary tumor was 78.3% (18/23, including 2 CR), the ORR of lymph node was 65.2%% (15/23, including 9 CR), and the overall ORR was 70.0% (16/23). Fifteen patients received non-surgical treatment after NAT, and 8 patients underwent surgery (6 underwent laryngeal preservation surgery). At 3 months after RT or surgery, 18 patients completed evaluation. The CR rate was 77.8%, and the laryngeal preservation rate was 88.9%. In 13 evaluable patients who received NAT followed by definitive RT, 10 patients (76.9%) had an overall response of 3m-CR. During the NAT, 43.5% (10/23) of patients experienced grade 3-4 AEs, with grade 3-4 leukopenia or neutropenia in 30.4% (7/23) and grade 3 immune enteritis in 13.0% (3/23). Conclusions: NCT combination with PD-1 inhibitor may improve the ORR of HPSCC, potentially further increasing the laryngeal preservation rate, with manageable treatment-related AEs. The study results are pending publication after completion of the enrollment. Clinical trial information: NCT04624308 .

Neoadjuvant PD-1 inhibitor is promising in cutaneous melanoma but remains unknown in acral melanoma (AM). This phase Ib trial study (Clinicaltrials.gov NCT04197882) assessed the efficacy and safety of the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable AM. Thirty patients of stage III/IV received neoadjuvant therapy of ori and tori for 12 weeks before surgery, followed by adjuvant treatment with tori for 1 year. Primary endpoints were radiographic and pathological response rates, with secondary endpoints of 1- and 2-year recurrence-free survival (RFS) rates, event-free survival (EFS) rates, and safety. Twenty-seven completed surgery and tori adjuvant treatment and median follow-up was 35.7 months. Radiographic and pathological response rates were 36.7% and 77.8%, with complete response rates of 3.3% and 14.8%, 1- and 2-year RFS rates of 85.2% and 81.5%, and 1- and 2-year EFS rates of 83% and 73%, respectively. Adverse events occurred in all patients, mainly grade 1-2. There was no correlation between PET/CT evaluation and pathological response or progression-free survival/overall survival. Patients with pathological response showed tumor beds with high tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs). Cytokines and chemokines analysis showed the combination therapy significantly increases the secretion of proinflammatory cytokines and chemokines in both responders and non-responders. Therefore, neoadjuvant ori and tori demonstrated promising antitumor activity with high response rates and high 2-year RFS/EFS for AM with acceptable tolerability.

Background: The tricarboxylic acid cycle (TCA cycle) is an important metabolic pathway and closely related to tumor development. However, its role in the development of esophageal squamous cell carcinoma (ESCC) has not been fully investigated.Methods: The RNA expression profiles of ESCC samples were retrieved from the TCGA database, and the GSE53624 dataset was additionally downloaded from the GEO database as the validation cohort. Furthermore, the single cell sequencing dataset GSE160269 was downloaded. TCA cycle-related genes were obtained from the MSigDB database. A risk score model for ESCC based on the key genes of the TCA cycle was built, and its predictive performance was evaluated. The association of the model with immune infiltration and chemoresistance were analyzed using the TIMER database, the R package “oncoPredict” score, TIDE score and so on. Finally, the role of the key gene CTTN was validated through gene knockdown and functional assays.Results: A total of 38 clusters of 8 cell types were identified using the single-cell sequencing data. The cells were divided into two groups according to the TCA cycle score, and 617 genes were identified that were most likely to influence the TCA cycle. By intersecting 976 key genes of the TCA cycle with the results of WGCNA, 57 genes significantly associated with the TCA cycle were further identified, of which 8 were screened through Cox regression and Lasso regression to construct the risk score model. The risk score was a good predictor of prognosis across subgroups of age, N, M classification and TNM stage. Furthermore, BI-2536, camptothecin and NU7441 were identified as possible drug candidates in the high-risk group. The high-risk score was associated with decreased immune infiltration in ESCC, and the low-risk group had better immunogenicity. In addition, we also evaluated the relationship between risk scores and immunotherapy response rates. Functional assays showed that CTTN may affect the proliferation and invasion of ESCC cells through the EMT pathway.Conclusion: We constructed a predictive model for ESCC based on TCA cycle-associated genes, which achieved good prognostic stratification. The model are likely associated with the regulation of tumor immunity in ESCC.

Background To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). Methods Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan–Meier method. Results 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14–103.66), 6.83 (95%CI, 1.08–43.08) and 42.67 (95%CI, 3.66–496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825–0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). Conclusions Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.

Objective:To retrospectively analyze the failure patterns and outcomes of patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) after undergoing induction chemotherapy (IC) followed by definitive radiotherapy.Methods:For patients with locally advanced HPSCC who were treated with IC and definitive radiotherapy from August 2008 to December 2019, their data were collected from the medical records system, and their clinical characteristics, failure patterns, and survival were retrospectively analyzed.Results:A total of 116 eligible patient with squamous cell carcinoma were included in this study. with a median age of 59 (39-79), and 3, 3, 60, and 50 of them had stage Ⅱ, Ⅲ, Ⅳ A, and Ⅳ B HPSCC, respectively. Among these patients, 81 received 1~2 cycles of IC, and 35 received 3-4 cycles of IC. After treatment with IC, 54, 13, and 49 patients received concurrent chemoradiotherapy, radiotherapy combined with targeted therapy, and radiotherapy alone, respectively. The median follow-up was 34.6 months (95% CI: 28.7-40.5 months). The 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), metastasis-free survival (MFS), progression-free survival (PFS), and overall survival (OS) of all the patients were 63.5%, 82.8%, 75.2%, 47.3%, and 43.1%, respectively. Median PFS and OS were 26.1 and 28.0 months, respectively. Treatment failure was reported in 59 patients, of whom 22, 5, 12, 10, 3, 6 and 1 experienced local, regional, distant only, local-regional, regional-distant, local-distant, and local-regional-distant failure, respectively. The objective response rate (CR+ PR) of patients after IC was 55.2% (64/116). The LRFS, RRFS, PFS, and OS of IC responders (CR+ PR) were better than those of IC non-responders (SD+ PD) ( χ2 = 12.52, 5.16, 13.19, 11.72, all P< 0.05). Conclusions:IC combined with radical radiotherapy has efficacy to a certain extent in the treatment of locally advanced HPSCC, and locoregional recurrence predominates the failure patterns. The prognosis of IC responders is significantly better than that of IC non-responders.

BACKGROUND Acral melanoma (AM) is less responsive to immunotherapy than nonacral cutaneous melanoma. Variable responses are seen during immunotherapy, including pseudoprogression, hyperprogressive disease (HPD) and heterogeneous responses. There are currently no studies on the response patterns of patients with AM treated with immunotherapy and the impact on the outcome. OBJECTIVES To evaluate the response patterns and prognosis of patients with AM treated with anti-programmed death (PD)-1 antibodies. METHODS Patients with advanced AM treated prospectively in five clinical trials of anti-PD-1 monotherapy at Peking University Cancer Hospital were included. Responses of individual metastases and heterogeneous responses were evaluated during immunotherapy. Cox proportional hazards regression analysis was conducted to identify the possible predictive factors and generate a nomogram to predict the risk of 1-year and 2-year mortality. RESULTS The overall response rate was 18·0%, the disease control rate was 36·1%, median progression-free survival was 3·5 months [95% confidence interval (CI) 1·7-5·3] and median overall survival was 17·5 months (95% CI 15·1-19·9) for anti-PD-1 monotherapy. Overall, 9·8% of patients met the criteria of HPD, and displayed a dramatically worse outcome than patients without HPD. In total, 369 metastatic lesions were assessed, with the highest response rate in lymph nodes (20·4%) and the lowest in the liver (5·6%). Homogeneous response, heterogeneous response and heterogeneous or homogeneous progression had different prognoses from the best to the worst. A predictive model was constructed and achieved good accuracy with a C-index of 0·73 (95% CI 0·63-0·84) in the training set and 0·74 (95% CI 0·61-0·86) in the validation set. CONCLUSIONS HPD during immunotherapy serves as an essential biomarker of poor prognosis in advanced AM. Metastases in different sites respond distinctively to immunotherapy. Clinically heterogeneous responses to immunotherapy affect the outcome of patients. A predictive model was built to distinguish the prognosis of acral melanoma under immunotherapy.

AIM:To assess the diagnostic efficacy in response evaluation of hypopharyngeal carcinoma (HPC) using different CT measurement methods.METHODS AND MATERIALS:One hundred and three patients with locally advanced HPC receiving neoadjuvant chemotherapy (NACT) and radical radiotherapy (RT) were retrospectively enrolled. The long diameter, short diameter and largest axial area of the tumors and the largest metastatic cervical lymph node (LN) were measured before and after NACT, at the end of RT and 1 month after RT. Tumor regression ratios of the sum of the tumor's long diameter and LN's short diameter (LDTSDL), the sum of tumor and LN's short diameter (TTSDL), the sum of tumor and LN's largest axial area (AATML) were calculated. Analysis was conducted for overall survival (OS), metastasis-free survival, regional recurrence-free survival (RRFS), and local recurrence-free survival (LRFS).RESULTS:Note that 35, 28, 23, and 16 patients suffered death, local recurrence, regional recurrence and distant metastasis, respectively. TTSDL-defined effective group demonstrated better LRFS (p = .039) and RRFS (p = .047) after NACT and better OS since the end of RT (p = .037); AATML-defined effective groups demonstrated better OS, LRFS, and RRFS since the end of RT (p = .015, .008, and .005). While LDTSDL-defined groups showed differences in OS and LRFS until 1 month after RT (p = .013 and .014).CONCLUSIONS:The regression rate of TTSDL and AATML can distinguish prognosis at an earlier time and demonstrated better reliability compared with LDTSDL. They were recommended for response evaluation in HPC.

Visual field is the main sensory modality for birds to gather information on food and threats; however, this has been largely unexplored for the passeriform birds having a varying foraging behaviour. Visual field and eye movements of the red-billed starling Spodiopsar sericeus, a passeriform bird with multiple foraging behaviours in different habitats, were determined using ophthalmoscope reflection technology. We found that projection of the bill was below the centre of the binocular field and part of the retinal visual field was impeded by the bill when eyes converged. The vertical extent of the binocular field above the bill was significantly longer than that below the bill. The amplitude of eye movement, mainly occurring in the regions of ventral-nasal and dorsal-temporal, had a very significant effect on the visual field. The widest extent of binocular field was at the elevation below bill when eyes converged forward, but was at the elevation above bill when eyes diverged backward. Our findings suggested that visual field configuration and eye movement in the red-billed starling may be the integrated adaptability to visual demand dependant on their varying foraging behaviour at different habitats.

目的 探讨基于胸部增强CT影像组学特征预测免疫治疗用于难治性恶性黑色素瘤肺转移疗效的价值.方法 回顾性分析49例难治性恶性黑色素瘤肺内转移患者,均接受程序性死亡受体(PD-1)单抗免疫治疗,采用实体瘤疗效评价标准(RECIST)1.1评价疗效,并将患者分为进展组(n=17)和未进展组[n= 32,包括稳定组(n=16)及部分缓解组(n=16)].提取免疫治疗前增强CT图像中肺转移病灶信息,以3D-Slicer软件手动逐层勾画整个病灶并进行分割;采用Pyradiomics程序提取病灶形状特征、灰度一阶特征、纹理特征和小波特征,以Pearson相关性分析和递归式特征消除策略进行降维.以支持向量机(SVM)方法建立分类模型,预测病变进展的可能性.绘制受试者工作特征(ROC)曲线,评价模型预测进展组、非进展组的效能.结果 对每个靶病灶提取841个增强CT影像组学特征,最终筛选出3个影像组学纹理特征,分别为wavelet-HHH_glszm_Low Gray Level Zone Emphasis、wavelet-HHL_first order Skewness 和 wavelet-LLL_gldm_Small Dependence High Gray Level Emphasis,用于构建影像组学模型.模型预测训练组病变进展的曲线下面积(AUC)为0.913[(95％CI(0.777,1.000)],测试组为0.860[95％CI(0.643,1.000)];预测训练组病变进展的敏感度、特异度、准确率、阳性预测值和阴性预测值分别为83.3％、95.5％、91.2％、90.9％和91.3％,测试组分别为80.0％、80.0％、80.0％、66.7％和88.9％.结论 基于治疗前胸部增强CT影像组学特征建立的模型对恶性黑色素瘤肺转移免疫治疗疗效具有较好预测价值.

8522 Background: Early stage non-small-cell lung cancer (NSCLC) could benefit from anti-programmed cell death-1 (PD-1) monotherapy; however, the survival profiles remain to be disclosed. Here, we presented the two-year follow-up outcomes from a phase 1b study of sintilimab, an anti-PD-1 inhibitor in the neoadjuvant setting of NSCLC. Methods: Treatment-naive pts with resectable NSCLC (stage IA–IIIB) received two cycles of sintilimab followed by surgical resection. Postoperative treatment of sintilimab was at the discretion of investigator. The primary endpoint was AE, and key secondary endpoints included major pathological response (MPR), disease free survival (DFS) rate of 1 year and 2 years, and overall survival (OS) rate of 2 years. Results: Among 40 enrolled pts, 36 (90%) underwent R0 resection and were included in the R0 resection population. By data cutoff (January 20, 2021), the median follow-up for DFS and OS for all the enrolled pts was 23.9 (IQR 20.5–24.4) months and 26.4 (IQR 24.2–29.0) months. A total of 12 (33.3%) pts experienced relapse, and 6 pts died. The 1-yr and 2-yr DFS rate was 91.7%/73.3%. The 2-yr OS rate for overall population and R0 population was 87.5%/91.7%, respectively. In the R0 resection population, the median DFS and OS were both not reached. Superior 2-year DFS rates were observed in pts who achieved MPR (MPR vs. Non-MPR: 86.7% vs. 63.8%). DFS of pts with non-squamous cell carcinoma tended to be shorter than that of pts with squamous cell carcinoma (HR 2.71 [95%CI 0.67–11.0], p=0.1479). Pts with tumor mutation burden (TMB) ≥10 mutations/Mb and PD-L1 tumor proportion score (TPS)≥50% tended to have a better 2-yr DFS rate compared to those with TMB<10 and TPS<50. [table] For the post-hoc event free survival (EFS) analysis, the same trend was observed with DFS among different subgroups, and patients with TMB ≥10 mutations/Mb had a significant improved EFS (HR 0.125[95% CI 0.02,1.03], P=0.0222). Conclusions: Anti-PD-1 monotherapy emerged to be a promising neoadjuvant therapeutic strategy for resectable NSCLC with improved clinical outcomes. MPR could serve as a surrogate efficacy biomarker in this setting. Clinical trial information: ChiCTR-OIC-17013726. [Table: see text]

Background Real-world data have suggested a detrimental effect of steroid use in patients with advanced non–small-cell lung cancer (NSCLC) receiving immunotherapy. However, previous studies included heterogeneous cohorts of patients receiving different lines of treatment with several immuno-oncology agents and various combinations of chemotherapy and immuno-oncology agents. Patients and Methods A comprehensive clinicopathologic database of patients with NSCLC and programmed cell death ligand 1 >50% treated with frontline pembrolizumab monotherapy was constructed in 14 centers in Italy, Spain, Greece, and Switzerland. A multivariate analysis adjusting for the established prognostic factors was performed using a Cox regression model. Results For the 265 eligible patients, the median age at diagnosis was 67 years, 66% were male, 90% were current or former smokers, 18% had had an Eastern Cooperative Oncology Group performance status of 2 or 3. Of the NSCLC subtypes, 64% were adenocarcinoma and 25% were squamous cell. Of the patients, 18% had had brain metastases at diagnosis and 24% had received steroids before or during pembrolizumab treatment. The median time to progression was 4.4 months with and 13.7 months without steroid use (hazard ratio [HR], 2.55; 95% confidence interval [CI], 1.69-3.85; log-rank P < .001). The median survival was 22.5 months for the whole cohort, 7.7 months for the steroid group, and not reached for the non-steroid group (HR, 3.64; 95% CI, 2.34-5.68; log-rank P < .001). On multivariate analysis accounting for all established prognostic variables, steroid use was still independently associated with a high risk of progression (HR, 1.864; 95% CI, 1.179-2.949; P = .008) and death (HR, 2.292; 95% CI, 1.441-3.644; P < .001) Conclusions In patients with advanced NSCLC and programmed cell death ligand 1 expression > 50% receiving frontline pembrolizumab monotherapy, any use of steroids before or during treatment was associated with an 86% increase in the risk of progression and a 2.3-fold increase in the risk of death, even accounting for palliative indication-related bias, including the presence of central nervous system metastasis. The use of steroids for palliative indications should be restricted to absolutely necessary for patients receiving immuno-oncology monotherapy.

INTRODUCTION:Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting. METHODS:Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomography-computed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726). RESULTS:A total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p = 0.0471). CONCLUSIONS:Neoadjuvant sintilimab was tolerable for patients with NSCLC, and 40.5% MPR rate is encouraging. The decrease of maximum standardized uptake values after sintilimab might predict pathologic response.

[This corrects the article DOI: 10.2147/OTT.S245710.].

OBJECTIVE:Spread through air spaces (STAS) has been reported to be an invasive histological pattern with poor prognosis in lung cancer; however, little is known about its intrinsic risk factors. This work analyzed the correlation between pathological and radiological features and STAS in resected lung adenocarcinomas.PATIENTS AND METHODS:We retrospectively reviewed 1821 consecutive surgically treated patients with histologically diagnosed lung adenocarcinoma (174 positive for STAS and 1647 negative for STAS) from December 2017 to November 2018 at our institution. Propensity score matching identified 170 well-balanced pairs of patients. The correlations between pathological and radiological features and the presence of STAS were analyzed.RESULTS:Before propensity matching, the incidence rate of STAS was 9.6% in all patients. In matched cohorts, multivariate analysis showed that the presence of STAS was significantly correlated with pure solid nodules (SNs) (p = 0.001) and solid/micropapillary patterns (SMPs) (p = 0.002). The odds ratio for STAS in SN-positive and SMP-positive adenocarcinoma against that in SN-negative and SMP-negative adenocarcinoma was 10.922 (95% confidence interval, 5.826-20.475; p < 0.001). Tumor differentiation, visceral pleural invasion (VPI), lymphovascular invasion (LVI), invasive adenocarcinoma, and non-lepidic subtype were significantly associated with STAS in the univariate analysis (p < 0.05); however, the differences failed to reach a significant level in the multivariate analysis.CONCLUSION:We found that STAS was significantly correlated with several invasive clinicopathological patterns. The presence of SNs and SMPs were revealed as independent predictors for STAS, which could offer clinicians clues to identify STAS-positive adenocarcinoma.

喉癌常见于嗜烟酒者,其发生率与开始吸烟时年龄、烟龄、吸烟数量均有关.喉癌症状出现的早晚与病灶发生部位、大小有关.大部分喉癌病变可直接以喉镜活检确诊,其治疗方法 主要取决于病变部位及 TNM 分期.但临床上,喉镜检查不能判定癌组织深部浸润情况,故薄层 CT 扫描对喉癌的术前定位及分期至关重要.本期视频,北京大学肿瘤医院的高顺禹教授对喉癌的 TMN 分期进行了详细的解读,并结合大量临床病例对喉癌的解剖结构、不同类型喉癌的 CT 成像特点及对喉癌进行分型、分期需要注意的事项等进行了详细的阐述.最后高顺禹教授归纳总结了喉癌的 CT 应用要点.

目的 探讨周围型非小细胞肺癌(NSCLC)发生纵隔淋巴结转移的影响因素及其临床意义.方法 回顾性分析45例术前胸部CT显示病灶同侧纵隔最大淋巴结短径≥10 mm(临床N2期)的周围型NSCLC患者的临床及CT检查资料,对周围型NSCLC纵隔淋巴结转移(病理分期为N2期)的影响因素进行单因素及多因素分析,并以病理结果为金标准,评价其诊断效能.结果 术前CT诊断纵隔淋巴结转移的临床N2期NSCLC患者中,假阳性率为42.22％(19/45).病灶同侧纵隔最大淋巴结短径(P=0.022)及术前血清癌胚抗原(CEA)水平(P=0.004)均为临床N2期周围型NSCLC纵隔淋巴结转移的影响因素;术前血清CEA水平为独立影响因素(P=0.007).结合术前CT诊断及血清CEA水平进行筛选后,假阳性率降至7.69％(3/39).结论 术前血清CEA水平是临床N2期周围型NSCLC纵隔淋巴结转移的独立影响因素,有利于降低CT诊断假阳性率.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Here we generated a new anti-CD19 CAR molecule (CD19-BBz(86)) derived from the CD19-BBz prototype bearing co-stimulatory 4-1BB and CD3ζ domains. We found that CD19-BBz(86) CAR T cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity. We performed a phase 1 trial of CD19-BBz(86) CAR T cell therapy in patients with B cell lymphoma (ClinicalTrials.gov identifier NCT02842138 ). Complete remission occurred in 6 of 11 patients (54.5%) who each received a dose of 2 × 108–4 × 108 CD19-BBz(86) CAR T cells. Notably, no neurological toxicity or CRS (greater than grade 1) occurred in any of the 25 patients treated. No significant elevation in serum cytokine levels after CAR T cell infusion was detected in the patients treated, including in those who achieved complete remission. CD19-BBz(86) CAR T cells persistently proliferated and differentiated into memory cells in vivo. Thus, therapy with the new CD19-BBz(86) CAR T cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T cell therapy. A new anti-CD19 CAR T cell therapy induces potent antitumor responses without causing severe cytokine-release syndrome or neurotoxicity in patients with lymphoma.

OBJECTIVE:To determine the capability of dynamic enhanced computed tomography (CT) to differentiate liver metastases (LMs) of well-differentiated from poorly-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).METHODS:Patients with LMs of GEP-NENs who underwent dynamic enhanced CT examination in Peking University Cancer Hospital from January 2009 to October 2015 were included and data were retrospectively analyzed. We assessed the qualitative and quantitative CT features to identify the significant differentiating CT features of LMs of poorly-differentiated GEP-NENs from those of well-differentiated GEP-NENs using univariate analysis and a multivariate logistic regression model.RESULTS:The study included 22 patients with LMs of well-differentiated GEP-NENs and 32 patients with LMs of poorly-differentiated GEP-NENs. Univariate analysis revealed statistically significant differences between the LMs of well- and poorly-differentiated GEP-NENs in terms of feeding arteries (36.4% vs. 75.0%, χ2=8.061, P=0.005), intratumoral neovascularity (18.2% vs. 59.4%, χ2=9.047, P=0.003), lymphadenopathy (27.3% vs. 81.2%, χ2=15.733, P<0.001), tumor-to-aortic ratio in the hepatic arterial and portal venous phase (T-A/AP: 0.297±0.080vs. 0.251±0.059, t=2.437, P=0.018; T-A/PVP: 0.639±0.138 vs. 0.529±0.117, t=3.163, P=0.003) and tumor-to-liver ratio in the hepatic arterial phase (T-L/AP: 1.108±0.267 vs. 0.907±0.240, t=2.882, P=0.006). The LMs of poorly-differentiated GEP-NENs showed more feeding arteries, more intratumoral neovascularity, more lymphadenopathy and a lower tumor-to-aortic ratio. Multivariate analysis suggested that intratumoral neovascularity [P=0.015, OR=0.108, 95% confidence interval (95% CI), 0.018-0.646], lymphadenopathy (P=0.001, OR=0.055, 95% CI, 0.009-0.323) and T-A/PVP (P=0.004, OR=5.3E-5, 95% CI, 0.000-0.044) were independent factors for differentiating LMs of poorly-differentiated from well-differentiated GEP-NENs.CONCLUSIONS:Dynamic enhanced CT features (intratumoral neovascularity, lymphadenopathy and T-A/PVP) are useful in the pathological classification of LMs of GEP-NENs.

OBJECTIVE To investigate the accuracy of CT in preoperative discrimination of cT3 from cT4 in patients with Siewert II esophagogastric junction (EGJ) adenocarcinoma according to UICC/AJCC 8th edition and IGCA 4th edition. METHODS CT imaging data of 43 consecutive patients with Siewert II EGJ adenocarcinoma who underwent preoperative CT and were diagnosed as pT3 or pT4 by postoperative pathology were retrospectively analyzed. Inclusion criteria were as follows:(1)no previous history of gastric operation, radiochemotherapy, targeted treatment; no contraindications of CT enhanced scanning; (2) good filling of gastric cavity by CT, clear image without artifacts, all axial-coronal-sagittal 3-plane reconstruction images obtained by abdominal stage 3 enhanced scan; (3) operation within 1 week after CT examination; (4) Siewert II EGJ adenocarcinoma confirmed by operation, pT3 and pT4 by postoperative pathology. Transverse and multiplanar reconstruction images were reviewed by two radiologists in double-blind method. Distance between cancer epicenter and esophagogastric junction line, and the contour of the serosa were retrospectively measured on CT scans. The cT staging judgment was performed according to the UICC/AJCC 8th edition (Siewert II EGJ adenocarcinoma should be staged as esophageal cancer) and IGCA 4th edition (Siewert II EGJ adenocarcinoma should be staged as gastric cancer) respectively. Consistency of cT staging and pathological pT staging was compared between UICC/AJCC and IGCA. RESULTS Preoperative CT revealed that the mean length between tumor epicenter and esophagogastric junction line was(1.5±0.4) cm (0.7-2.5 cm), and such length was ≤2 cm in 41 cases, whose concordance with surgical judgment was 95.3%(41/43). IGCA staging: 18 cases were preoperatively assessed as cT3 and 25 cases as cT4a. UICC/AJCC staging: 41 cases with cancer epicenter locating within 2 cm below esophagogastric junction line were staged as cT3 according to esophageal cancer staging; 2 cases with cancer epicenter locating > 2 cm below esophagogastric junction line were staged according to gastric cancer staging, of whom one was staged as cT3 due to regular serosa and the other was staged as cT4a due to irregular serosa. Postoperative pathology: 33 cases were pT3 and 10 cases were pT4a. The accuracy of preoperative CT in discrimination of T3 from T4a was 74.4%(32/43) with UICC/AJCC criteria and 65.1%(28/43) with IGCA criteria, whose difference was significant(P<0.01). CONCLUSIONS Preoperative CT can accurately localize the 2 cm threshold line of Siewert II esophagogastric junction adenocarcinoma, which is beneficial to the discrimination of cT3 from cT4a EGJ adenocarcinoma. Application of the UICC/AJCC 8th edition criteria to above discrimination has higher accuracy as compared to IGCA 4th edition in cT-staging by CT.

This study proposed to evaluate the feasibility of dynamic enhanced CT in differentiation of liver metastases of gastroenteropancreatic well-differentiated neuroendocrine tumors (GEP NETs) from GEP adenocarcinomas based on their characteristic features. CT images of 23 well-differentiated (G1 or G2) GEP NETs and 23 GEP adenocarcinomas patients with liver metastases were retrospectively reviewed. The distribution type, shape, intra-tumoral neovascularity, enhancement on hepatic artery phase, dynamic enhancement pattern and lymphadenopathy were subjective analyzed. Meanwhile, the size, number, CT value of tumor and adjacent normal liver parenchyma were measured and the metastasis-to-liver ratios were calculated objectively. Compared with GEP adenocarcinomas, the liver metastases of GEP NETs more frequently demonstrated a hyper enhancement on hepatic artery phase, washout dynamic enhancement pattern, absence of lymphadenopathy and higher metastasis-to-liver ratios on both hepatic artery phase and portal venous phase (P=0.017, P<0.001, P =0.038, P <0.001 and P =0.008, respectively). Logistic regression analysis showed that the dynamic enhancement pattern (P=0.012), and the metastasis-to-liver ratios on hepatic artery phase (P=0.009) were independent CT predictors for liver metastases of GEP NETs. The sensitivity and specificity of combing the two predictors in differentiation of liver metastases of GEP adenocarcinomas from GEP NET were 82.6% (19 of 23) and 91.3% (21 of 23), respectively. CT features are helpful in differentiating liver metastases of well-differentiated GEP NETs from that of GEP adenocarcinomas.