Esophageal squamous cell carcinoma (ESCC) shows considerable variation in incidence across different regions and is affected by various risk factors, including smoking and HPV infection. This article presents a rare case of ESCC that metastasized to the anal region, illustrating the effectiveness of whole-exome sequencing and clonal evolution analysis in identifying the origins of the metastasis. The findings reveal distinct clonal characteristics between the primary tumor and the metastatic site. This underscores the importance of molecular profiling for developing effective treatment strategies.

IntroductionPrimary malignant melanoma of the esophagus (PMME) is a rare malignancy of the esophagus. The main treatment is esophagectomy, but the recurrence and metastasis rate are very high, and the prognosis is very poor. Here, we report a case of locally advanced PMME that rapidly developed intracranial metastases after surgery and adjuvant therapy.Case presentationThe patient was a 47-year-old male with dysphagia. Endoscopy revealed multiple cauliflower-like lesions in the middle esophagus, confirmed as malignant melanoma via biopsy with positive immunohistochemical staining for SOX-10 and Melan-A, with regional lymph node metastases. The patient was diagnosed with PMME and was treated with radical esophagectomy. The adjuvant therapy used tislelizumab combined with lenvatinib. Five months after surgery, follow-up magnetic resonance imaging (MRI) indicated multiple intracranial metastases. The patient underwent a tumor resection of the left cerebellar lesion, and stereotactic radiosurgery for other lesions, and received oral temozolomide. One month after radiotherapy, his condition deteriorated rapidly, showing systemic progression, and he eventually passed away ten months after diagnosis.ConclusionDespite surgical resection and adjuvant therapy, this case of PMME rapidly progressed with multiple intracranial metastases, highlighting the highly aggressive nature and poor prognosis of this malignancy.

BACKGROUND:Several high-quality clinical trials have shown promising results compared with neoadjuvant chemotherapy (NCT) or chemoradiotherapy, further supporting the efficacy of neoadjuvant immunochemotherapy (NICT) for locally advanced esophageal cancer (AEC). This study evaluated the efficacy of NICT in different segments of esophageal squamous cell carcinoma (ESCC) and aimed to identify potential prognostic factors. METHODS:A retrospective cohort study analyzed 248 patients. Before undergoing radical surgery, the patients received two to four cycles of NICT. The relationship between different segments of ESCC and both clinical and pathologic characteristics were evaluated. RESULTS:The patients with tumors in the upper thoracic esophagus had a higher proportion of lower tumor regression grade (TRG) scores. A significantly higher proportion of patients with TRG 0-1 was observed in the upper and middle thoracic tumor groups than in the lower thoracic group (P = 0.001). In esophageal cancer, TRG 2-3 was significantly associated with lower thoracic tumor location (odds ratio [OR], 3.298; P = 0.003), clinical T3 stage (OR, 2.834; P < 0.001), and clinical N2 stage (OR, 2.557; P = 0.045). CONCLUSIONS:The patients with upper-third ESCC appeared to derive greater clinical benefits from NICT than those with tumors located in the lower third of the esophagus in this post hoc analysis. This could potentially serve as a predictor of NICT efficacy.

Background:Esophageal squamous cell carcinoma (ESCC) presents significant therapeutic challenges due to limited treatment options. While immune checkpoint inhibitors (ICIs) combined with chemotherapy have demonstrated efficacy, variable response rates underscore the necessity for enhanced therapeutic approaches. Anlotinib, a multi-target tyrosine kinase inhibitor, has shown synergistic effects with ICIs in clinical practice. However, its influence on the tumor immune microenvironment (TIME) in ESCC requires further elucidation. This study aimed to investigate anlotinib's effects on the TIME. Methods:In our phase II trial (NCT04471480), we analyzed 8 advanced ESCC patients who achieved operability following treatment with anlotinib, camrelizumab, and chemotherapy (TCAC group). A control group (TCC group) comprised 8 patients from a separate neoadjuvant trial who received identical treatment, excluding anlotinib. Tumor-infiltrating immune cell populations (CD4+, CD8+, CD20+, CD68+, FOXP3+) were evaluated using multiplex immunofluorescence. Additional mechanistic insights were obtained through RNA sequencing (RNA-seq) and enzyme-linked immunosorbent assay (ELISA). Results:Baseline immune cell profiles showed no significant intergroup differences. Post-treatment analysis revealed the TCAC group had significantly elevated CD8+ cell proportions and reduced FOXP3+ cell proportions compared to controls (P<0.05). Within the TCAC cohort, pretreatment immune cell distributions were comparable between pathological complete response (pCR) and non-pCR patients. However, post-treatment pCR patients demonstrated significantly higher CD8+ and lower FOXP3+ cell levels versus non-pCR cases (P<0.05). RNA-seq and ELISA analyses suggested anlotinib's potential to enhance the immune microenvironment through C-C motif chemokine ligand 5 (CCL5) upregulation. Conclusions:The combination of anlotinib with camrelizumab and chemotherapy appears to modify the ESCC immune microenvironment by promoting cytotoxic CD8+ T cell infiltration while suppressing FOXP3+ regulatory T cells, possibly mediated through CCL5 induction. These results warrant further investigation of anlotinib's immunomodulatory potential in ESCC combination therapies.

Advanced esophageal squamous cell carcinoma (ESCC) patients exhibit a ~ 50% objective response rate (ORR) and median progression-free survival (mPFS) of just 5-7 months when undergoing first-line immune-chemotherapeutic treatment, underscoring pronounced unmet clinical need. We assessed the efficacy and safety of Anlotinib plus Camrelizumab and chemotherapy for advanced, unresectable, or metastatic ESCC. This is an open-label, investigator-initiated, phase 2, non-randomized clinical trial enrolled patients from August 3, 2020, to August 10, 2022. Patients with treatment-naive unresectable stage III or IV ESCC received treatment which was patient-selected, including chemotherapy + camrelizumab + Anlotinib (TCAC group) or chemotherapy + Camrelizumab (TCC group) induction therapy for 4-6 cycles, followed by maintenance therapy. The primary endpoint was ORR, while secondary endpoints included mPFS, median overall survival (mOS), disease control rate (DCR), and treatment-related adverse events (TRAEs). 30 patients were included in each group. Over a median 14.5-month follow-up period, the ORR was 90.0%, 43.3%(P < 0 0.001) and the mPFS was 16.03, 7.30 months (HR 0.35, 95%CI, 0.19-0.65; P < 0 0.001) in TCAC and TCC groups, respectively. Grade 3 TRAEs were experienced by 12 patients (40.0%) in TCAC group, including decreased neutrophil counts (5 [16.7%]), decreased white blood cell counts (4 [13.3%]), reduced platelet counts (3 [10%]), and hypertension (2 [6.7%]). No patients experienced grade 4-5 TRAEs. The combination of Anlotinib plus Camrelizumab and chemotherapy had promising efficacy among patients with advanced ESCC in this study, which may be a promising first-line treatment regimen.Trial registration: Registered with ClinicalTrials.gov, NCT04471480. 15/07/2020.

Esophageal squamous cell carcinoma (ESCC) is a severe malignant tumor of the digestive system that poses a significant threat to human health. Despite its significance, the complex molecular mechanism regulating the occurrence and development of ESCC remain elusive. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) members constitute a pivotal subfamily of the APOBEC family that possess cytidine deaminase activity. In recent years, APOBEC3s (A3s) have received increasing attention due to their pivotal roles in the occurrence, development, and prognosis of ESCC. This comprehensive review systematically summarizes the latest research progress on the mechanisms of action of A3s in ESCC and discusses their impact on the development and therapeutic considerations for ESCC, with a particular focus on their potential role in immunotherapy. These insights may be of great value in continued exploration of ESCC pathogenesis and provides a theoretical foundation for the development of clinical treatment strategies for ESCC.

NME1 is a metastatic suppressor inconsistently reported to have multiple roles as both a promoter and inhibitor of cancer metastasis. Nevertheless, the specific mechanism behind these results is still unclear.We observed that A549 cells with stable transfer of NME1 into the nucleus (A549-nNm23-H1) exhibited significantly increased migration and invasion activity compared to vector control cells, which was further enhanced by over-expressing CYP24A1 (P<0.001). NME1 demonstrated the ability to safely attach to and amplify the transcription activation of JUN, consequently leading to the up-regulation of CYP24A1. Analysis of clinical data showed a positive relationship between nuclear NME1 levels and CYP24A1 expression. Furthermore, they were positively associated with postoperative distant metastasis and negatively correlated with prognosis in those with early-stage lung adenocarcinoma.In conclusion, the data presented provides a new understanding of the probable pathways by which nuclear NME1 facilitates tumor metastasis, establishing the groundwork for future prediction and treatment of tumor metastasis.

Background:Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and malignant form of esophageal tumor associated with high rates of patient mortality for which there remains a persistent lack of effective targets for therapeutic interventional efforts. This study was developed with the goal of exploring the expression and functional role of RBM15 in ESCC. Methods:This study was developed with the goal of exploring the expression and functional role of RBM15 in ESCC. To establish the prognostic and therapeutic significance of RBM15 in this cancer, data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and UCSC Xena databases were leveraged. Immunohistochemical analyses were used to assess RBM15 expression in postoperative ESCC tumor tissue samples, and the correlations between such expression and patient outcomes were assessed. The effects of RBM15 on ESCC cell proliferative, migratory, and invasive activity were assessed with Cell Counting Kit-8 (CCK8) and Transwell assay approaches. Together, these experiments revealed RBM15 upregulation in ESCC relative to paracancerous tissues, while confirming that it was associated with favorable patient outcomes. RBM15 was also found to suppress ESCC cell proliferation, migration, and invasivity. Results:We suggest that RBM15 may be a clinically relevant prognostic factor in ESCC such that new therapeutic interventions based on low levels of RBM15 have the potential to be developed for the improved management of ESCC in the future. Conclusions:The results of the present study provide confirmation that high levels of RBM15 expression are protective and associated with better ESCC patient prognostic outcomes. Pan-cancer analyses performed herein also revealed the correlations between RBM15 expression and prognosis in various cancers.

395 Background: The combination of anti-PD-1 mAb with chemotherapy is one of the standard first-line therapies for advanced esophageal cancer. Recent studies have shown that anti-PD-1 mAb combined with chemotherapy or targeted treatment can improve the efficacy of immunotherapy. The purpose of this study was to evaluate the efficacy and safety of paclitaxel and carboplatin (TC) combined with anlotinib, an anti-angiogenic TKI, and anti-PD-1 mAb, in the treatment of advanced esophageal cancer. Methods: This study was a parallel, single-center, open-label, phase II trial. A total of 90 patients (pts) with previously untreated, advanced or metastatic ESCC, with an age ranging from 18-75 years old, and an ECOG performance status ≤ 1 were planned to be enrolled into three arms with an allocation ratio of 1:1:1. Arm A received paclitaxel (175 mg/m2, IV, d1, q3w) /nab-paclitaxel (260mg/m2, IV, d1, q3w) + carboplatin (AUC 4-6, IV, d2, q3w) + anti-PD-1 mAb + anlotinib (8mg, PO, d1-14, q3w); Arm B received TC with anti-PD-1 mAb; Arm C received TC only. After 4-6 cycles of induction therapy, arm A and arm B would receive anti-PD-1 mAb plus anlotinib or anti-PD-1 mAb as maintenance therapy until disease progression or intolerable adverse events, respectively. The primary endpoint was ORR. Secondary endpoints included PFS, OS and safety. Results: At data cut-off date (Sep. 20, 2022), a total of 90 pts were enrolled and 88 pts were available for efficacy assessment. 25 of 28 pts achieved partial response (PR) in arm A, 13 of 30 pts PR in arm B, and 7 of 30 pts PR in arm C. The ORR (95% CI) were 89.3% (71.8-97.7) in arm A, 43.3% (25.5-62.6) in arm B, and 23.3% (9.9-42.3) in arm C. The DCR (95% CI) were 100% (87.7-100.0) in arm A, 96.7% (82.8-99.9) in arm B, and 83.3% (65.3-94.4) in arm C. The median PFS was not reached. The rate of treatment related adverse events (TRAEs) of any grade was 100% in all three groups, and grade 3 TRAEs were 23.3%, 16.7% and 13.3%, respectively. The most common grade 3 TRAEs were thrombocytopenia (6.7%), leukopenia (5.6%), neutropenia (5.6%). No grade 4 or 5 TRAEs occurred. Conclusions: The addition of anlotinib to immunotherapy plus chemotherapy as first-line therapy for ESCC demonstrated a high ORR (89.3%), and a manageable safety profile. Clinical trial information: NCT04471480 .

Desmoplastic small round cell tumor (DSRCT) is a rare undifferentiated malignant soft tissue tumor with a poor prognosis and a lack of consensus on treatment. This study's objective was to build a nomogram based on clinicopathologic factors and an online survival risk calculator to predict patient prognosis and support therapeutic decision-making. A retrospective cohort analysis of the Surveillance, Epidemiology and End Results (SEER) database was performed for patients diagnosed with DSRCT between 2000 and 2019. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to identify the individual variables related to overall survival (OS) and cancer-specific survival (CSS), as well as to construct online survival risk calculators and nomogram survival models. The nomogram was employed to categorize patients into different risk groups, and the Kaplan-Meier method was utilized to determine the survival rate of each risk category. Propensity score matching (PSM) was used to assess survival with different therapeutic approaches. A total of 374 patients were included, and the median OS and CSS were 25 (interquartile range 21.9-28.1) months and 27 (interquartile range 23.6-30.3) months, respectively. The nomogram models demonstrated high predictive accuracy. PSM found that patients with triple-therapy had better CSS and OS than those who received surgery plus chemotherapy (median survival times 49 vs 34 months and 49 vs 35 months, respectively). The nomogram successfully predicted the DSRCT patients survival rate. This approach could assist doctors in evaluating prognoses, identifying high-risk populations, and implementing personalized therapy.

目的 探讨改良型流体头皮止血带对化疗诱导的脱发(CIA)的预防作用.方法 前瞻性纳入173例进行化疗的乳腺癌患者,分为试验组89例和对照组84例,试验组给予改良型流体头皮止血带处理,对照组对CIA的预防和治疗不作任何的处理,通过WH O抗癌药物急性和亚急性毒性分级标准评估改良型流体头皮止血带对CIA的预防作用,并评估生活质量的相关变化.结果 173例患者中位年龄52岁(31～74岁),试验组患者中有38例发生Ⅲ～Ⅳ度脱发,发生率为42.70％(38/89),而对照组为64.29％(54/84),试验组Ⅲ～Ⅳ度脱发发生率较对照组降低(P<0.05).在2组生活质量评分,最后1个化疗周期结束后及化疗结束后1个月时试验组得分明显低于对照组(P<0.05).结论 改良型流体头皮止血带可减少CIA的发生,提高患者的生活质量,重塑生活信心.

Objective To analyze the clinical features of primary appendiceal mucinous adenocarcinoma (AMAC), and investigate the diagnosis and treatment principles of the disease. Methods Thirty cases of primary AMAC from October 2011 to September 2019 in Daping Hospital of the Army Medical University were retrospectively analyzed, including demography, imaging, hematology, pathology and treatment method. Results The main clinical features of the 30 cases were right lower abdominal pain. Of whom 12 cases were diagnosed as acute or chronic appendicitis before operation, and 8 cases were as combined with ovarian space occupying. Preoperative routine abdominal B ultrasonography combined with other imaging examinations (including abdominal CT, MRI and PET/CT) obviously improved the diagnostic accuracy (68.2%) than that with B ultrasonography alone (25.0%, P=0.049). Carcinoembryonic antigen (CEA) and carbohydrate antigens (CA199, CA125 and CA242) were the most common tumor markers, which had the highest diagnostic value for AMAC. Intestinal obstruction occured in four patients undergoing stage Ⅱ extended surgery, while in only three patients without undergoing stage Ⅱ extended surgery (Fisher's exact test, P=0.181). The mean survival time of patients with R0 resection was (57.5±9.5) months and the median survival time was 59.0 months. The mean survival time of patients without R0 resection was (29.8±4.1) months and the median survival time was 33.0 months (χ2=1.255, P=0.263). Conclusions Appendiceal B ultrasound combined with abdominal enhanced MRI, CT or PET/CT can significantly improve the diagnostic rate of appendiceal mucinous adenocarcinoma. The monitoring of CEA, CA199, CA125, CA242 is helpful for the preoperative diagnosis of appendiceal mucinous adenocarcinoma. DOI: 10.11855/j.issn.0577-7402.2021.01.08

Lung signet ring cell carcinoma (LSRCC) is a very rare type of lung cancer, the clinical characteristics, and prognosis of which remain to be clarified. In order to explore the clinicopathological and survival-related factors associated with LSRCC, we performed a large population-based cohort analysis of data included in the Surveillance, Epidemiology, and End Results (SEER) registry from 2001- 2015. A total of 752 LSRCC and 7518 lung mucinous adenocarcinoma (LMAC) patients were incorporated into our analysis, with respective mean ages of 63.8 and 67.5 years at the time of diagnosis. LSRCC patients were significantly more likely than LMAC patients to have distant-stage disease (72.1% vs. 45.8%, p<0.0001), tumors of a high pathological grade (40.6% vs. 10.8%, p<0.0001), have undergone chemotherapy (62.1% vs. 39.9%, p<0.0001), be male (52.7% vs. 48.5%, p=0.03), and be < 40 years old (3.3% vs. 1.3%, p=0.022), whereas they were less likely to have undergone surgical treatment (52.4% vs. 77.0%, p<0.0001). LSRCC and LMAC patients exhibited median overall survival (OS) duration of 8 and 18 months (p<0.0001), respectively, although these differences were not significant after adjusting for confounding variables. Independent factors associated with a favorable patient prognosis included a primary site in the middle or lower lung lobe, underwent surgery and underwent chemotherapy. However, age ≥ 80 years, higher grade, distant summary stage disease, and T4 stage disease were linked to poor prognosis. Patient age, tumor grade, primary tumor site, summary stage, T stage, surgery, and chemotherapy were all significantly associated with LSRCC patient prognosis.

e20570 Background: Although the combination of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy (EP) is the preferred first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC), the survival benefit of the addition of ICIs was still modest. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for normalization the immunosuppressive microenvironment and overcoming the low efficacy of ICIs. We reported the efficacy and safety of toripalimab combined with anlotinib and EP in treatment-naïve ES-SCLC. Methods: The eligible ES-SCLC patients (18-75 years, ECOG PS ≤2), with measurable target lesion (RECIST v1.1) received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1-3) plus carboplatin (AUC = 5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1-14) of a 21-day cycle for 4-6 cycles, then patients with CR、PR or SD could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 October and 2020 November, 16 treatment-naïve ES-SCLC patients (14 males, 2 females) were enrolled. The median age is 63 (range, 42-74) years. The median follow-up was 7.6 months. 100% (16/16) patients achieved an objective response (1 CR and 15 PR). The DCR was also 100% (16/16). The median DOR had not been reached (range, 4.8+ to 21.9+ month). 37.5% (6/16) patients had disease progression after six months of treatment, while median PFS was not reached. As of Jan 31, 2021, all patients were still alive. The median OS had not been reached. 62.5% (10/16) patients remained on-treatment. The most common adverse events (AEs) were grade 1-2 anemia (75%), decreased appetite (50%) and neutropenia (43.8%). Seven patients had Grade 3 AEs (5 neutropenia; 1 leukopenia, 1 emesis, and 1 ketoacidosis). No Grade 4/5 AEs occurred. Conclusions: Toripalimab combined with anlotinib and etoposide plus carboplatin/cisplatin showed promising anti-tumor activity and tolerable toxicities in treatment-naïve ES-SCLC. Clinical trial information: NCT04731909.

Gastric cancer (GC) is the fifth-highest ranked cancer for incidence and second for mortality from cancer worldwide. Conversion therapy has recently emerged as an alternative therapy for advanced/metastatic GC patients who are unable to undergo surgical resection at the time of diagnosis. Herein, we present the case of a patient with unresectable stage III GC of high microsatellite instability (MSI), high tumor mutation burden (TMB), and Epstein-Barr virus (EBV) positive. The patient received conversion therapy involving a combination of chemotherapy and immunotherapy regimens. After 3 courses of chemotherapy combined with tislelizumab, the patient underwent laparoscopic radical total gastrectomy. The pathological examination demonstrated that there was no cancerous tissue at the proximal or distal end of the tumor and no lymph node metastases in the lesser or greater curvature, indicating a pathologic complete response. Thereafter, the patient continued tislelizumab treatment to prevent postoperative carcinoma recurrence and metastasis, and to improve prognosis. In conclusion, our study confirmed that chemotherapy combined with immunotherapy is a promising conversion therapy for GC patients with locally unresectable lesions or distant lymph node metastasis, and these findings warrant large-scale clinical studies. This report highlights the clinical importance of next-generation sequencing technology in investigating therapeutic strategy to provide the maximal clinical benefit for patients with GC.

Background Telangiectatic osteosarcoma (TOS) is a rare type of osteosarcoma for which limited clinical data is available. Furthermore, the clinical characteristics and prognosis of TOS remain unclear. Methods A large population-based cohort analysis was conducted using the Surveillance, Epidemiology and End Results (SEER) registry. The data of TOS and conventional osteosarcoma (COS) patients from 2000 to 2017 were collected. The categorical variables were assessed by Chi-squared tests. Kaplan-Meier curves and log-rank (Mantel-Cox) tests were used to examine the survival outcomes between the groups. Cox proportional hazard models were used for univariate and multivariate analyses of TOS patient survival-related variables. Results A total of 141 TOS patients and 2961 COS patients were included in this analysis, and the mean age at diagnosis was 23.5 and 29.4 years, respectively. Compared to COS patients, TOS patients were more likely to be under 20 years old (61.7% vs. 51.7%, P=0.022), and without a second peak of incidence after 60 years of age. The median overall survival (mOS) of TOS patients was not reached compared to a median survival of 84 months for COS patients (hazard ratio 0.75, 95% confidence interval 0.59 to 0.95, P=0.0175). After adjusting these data for age at diagnosis, stage, and surgery at the primary site, no significant differences in mOS were observed between the two groups. In univariate analyses, being under 20 years of age, having localized or regional stage disease, and having undergone surgery were associated with a decreased risk of death. Subsequent multivariate analysis indicated that age at diagnosis, stage, and surgery at the primary site were all independent predictors of prognosis in TOS patients. Conclusions Patients with TOS were younger than patients with COS and did not show a second peak after 60 years of age. Age, summary stage at diagnosis, and surgery at the primary site were independent predictors of survival for TOS patients.

Background This trail is an open-label, single-arm, phase II study that aims to observe the efficacy and safety of toripalimab combined with anlotinib and platinum-etoposide (EP) chemotherapy as first-line treatment in ES-SCLC (Clinical trial information: NCT04731909). The preliminary results of the study have been presented in 2020 ASCO abstract e20570, which demonstrated 100% objective response rate (ORR) and tolerable safety. Here we report PFS analysis results of the study. Methods The study enrolled treatment-naïve ES-SCLC patients (18–75 years, ECOG PS ≤2) who have measurable target lesion evaluated by RECIST v1.1. All enrolled patients received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1–3) plus carboplatin (AUC=5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1–14) of a 21-day cycle. After 4–6 cycles of the treatment, patients who achieved complete response (CR), partial response (PR) or stable disease (SD) could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). ORR, disease control rate (DCR), progression-free survival (PFS) and safety were set as secondary endpoints. Results As of July 16, 2021, the median follow-up was 13.7 months. 9 disease progression events occurred of the enrolled 16 treatment-naïve ES-SCLC patients (14 males, 2 females, median age 63). The investigator-assessed median PFS was 13.3 months (95%CI: 5.0–21.6). The PFS rate at 6 months was 81.3% and the PFS rate at 12 months was 31.3%. 15 patients were still alive and the study treatments for 7 patients were still ongoing. At the data cutoff, there was only 1 patient dead with 37.6 months OS and the median OS was not reached. No new unexpected adverse events were observed. Conclusions Combined with preliminary data at 2020 ASCO, toripalimab combined with anlotinib and EP chemotherapy showed excellent ORR and PFS as well as tolerable safety in treatment-naïve ES-SCLC. The combination therapy is expected to provide clinically meaningful OS benefit and become a promising treatment option. Trial Registration This study is registered with ClinicalTrials.gov (National Institutes of Health), number NCT04731909. Ethics Approval The program was approved by the ethics committee of Army Medical Center (Daping Hospital ).

Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94–3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.

RATIONALE:Non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) have been found as subjects of poor prognosis. Whole-brain radiotherapy (WBRT), surgery, and stereotactic radiosurgery, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), or some combinations are the most commonly employed strategies for the treatment of treatments BMs. However, some patients are resistant to all these treatments. PATIENT CONCERNS:We present an NSCLC patient with progression of BMs after treatment with WBRT and EGFR-TKIs. The patient was diagnosed with multiple metastases on July 9, 2014, and treated with docetaxel plus cisplatin chemotherapy followed with gefitinib as the maintenance therapy. The patient showed recurrence of BMs after 8-months of chemotherapy. WBRT with 30 Gy was administrated in 10 fractions. Tumor progression of the brain was diagnosed with an magnetic resonance imaging scan after 2-months of WBRT. DIAGNOSES:The patient was diagnosed as pulmonary adenocarcinoma with diffuse metastases in both lungs and multiple metastases in bone and brain. Progression of BMs was confirmed through magnetic resonance imaging. INTERVENTIONS:This patient was administered temozolomide (150 mg/m2/d for 5 days every 28-day cycle). As a whole, 6 cycles were performed after the progression of BMs from August 2015. OUTCOMES:The patient got complete brain remission and lived without discomfort. The intracranial lesion did not progress until the progression of the lung lesion and led to death on February 20, 2019. The intracranial progression-free survival was 42 months, whereas the overall survival was 55 months. LESSONS:For patients with NSCLC and BMs, temozolomide can be used as a treatment option, especially in patients with EGFR-TKIs resistance or without driver mutations.

This study sought to assess the relationship between single nucleotide polymorphisms (SNPs) affecting DNA base-excision repair (BER) genes and esophageal squamous cell carcinoma (ESCC) risk in a Han Chinese population. Genes screened for such SNPs included 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1) and X-ray repair cross-complementing group 1 protein (XRCC1). Blood samples that had been collected in a prospective manner were used for DNA extraction, with all DNA samples then being subjected to PCR-restriction fragment length polymorphism genotyping for BER gene SNPs, including APE1 Asp148Glu and -141T/G, OGG1 Ser326Cys, and XRCC1 Arg399Gln. The relationship between these SNPs and ESCC risk was then assessed, with the comparability of the case and control groups being enhanced via propensity score matching (PSM). This study initially included 642 healthy controls and 321 ESCC patients, with PSM optimization leading to a final analyzed total of 311 matched subjects per group (311 total). Factors associated with elevated ESCC risk in this analysis included advanced age, being male and smoking. We further identified that the XRCC1 399 Gln/Gln genotype was associated with a significant reduction in ESCC risk prior to propensity matching (odds ratio=0.48; 95% CI: 0.23-1.00; P<0.05), although this did not remain true following matching. For the remaining analyzed SNPs, no significant associations between genotype and ESCC risk were detected prior to or following propensity matching. A multivariate analysis incorporating patient age, sex, smoking status and drinking status failed to detect any relationship between the four tested genotypes and ESCC risk. In conclusion, being male, a smoker or of advanced age was associated with an elevated ESCC risk. However, we did not detect any significant relationship between ESCC risk and BER polymorphisms in XRCC1, OGG1, APE1 or the APE1 promoter region in a Han Chinese population.