Background The aim of the study is to assess whether transcatheter rectal arterial chemoembolization (TRACE) with oxaliplatin could increase the pathologic complete response (pCR) rate of locally advanced rectal cancer (LARC) and improve survival outcomes, while minimizing adverse events compared to preoperative chemoradiotherapy (CRT) alone. Methods Eligible LARC patients who received TRACE with oxaliplatin plus chemoradiotherapy (the NATRACE-CRT group) or preoperative CRT alone (the NA-CRT group) were retrospectively selected from the database of our institution. Pathological results, treatment-related adverse events and survival in the two groups were compared. Results A total of 236 patients were enrolled. The pCR rates were 18.38% in the NATRACE-CRT group and 14.00% in the NA-CRT group, with a non-significant difference of 4.38% (P=0.473). The median follow-up time was 42 months. The 5-year DFS (75.7% vs. 73.2%; P=0.879) and OS (73.4% vs. 70.3%; P=0.855) rates were comparable between the NATRACE-CRT group and the NA-CRT group. However, the NATRACE-CRT group had significantly fewer patients achieving TRG3 compared to the NA-CRT group (16.18% vs. 35.00%; P=0.001). Furthermore, TRG3 patients in the NATRACE-CRT group exhibited significantly longer OS compared to those in the NA-CRT group (5-year OS: 88.9% vs 59.5%; P=0.016). Conclusions TRACE with oxaliplatin demonstrates potential in improving treatment response and prognosis of LARC patients with chemoradiotherapy resistance.

BackgroundPreoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified.MethodsThe comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results.ResultsThe top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-β and TP53 pathways were significantly associated with worse DFS.ConclusionsResected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-β and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Background: Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity. Method: This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles. Results: Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3-4 adverse events (AEs). All immune-related AEs were grade 1-2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred. Conclusion: This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy. Trial registration: ClinicalTrials.gov Identifier: NCT05957016.

Abstract Background Recent evidence suggests that patients with mismatch repair-deficient/microsatellite instability-high LARC are exceptionally sensitive to immune checkpoint inhibitors (ICIs), However, the majority of LARC patients are microsatellite-stable. Therefore, there is an urgent need to enhance the effectiveness of ICIs in this population. Hence, we propose a novel neoadjuvant protocol for LARC patients: chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), followed by concurrent chemoradiotherapy and programmed cell death 1 (PD-1) immunotherapy. Methods This prospective, single-arm, phase II clinical trial is designed to evaluate the effectiveness and safety of CIETAI in the management of LARC. The trial will consecutively recruit at least 37 stage II/III LARC patients from Daping hospital in China whose distal tumor are ≤ 15 cm from the anal verge. Enrolled patients will receive a sequential arterial infusion of oxaliplatin (100 mg) and PD-1 monoclonal antibody tislelizumab (200 mg) and subsequent embolization of the major rectal tumor-feeding artery using gelatin sponge particles and iodixanol. The dose of oxaliplatin was calculated according to body surface area (BSA; 130 mg/m2), of which 100 mg was infused and the remaining dose was administered intravenously. Tislelizumab will be administered intravenously every 3 weeks for an additional two cycles. Additionally, all enrolled patients will receive LCRT (45 Gy in 25 fractions: 1.8 Gy per fraction, 5 days/week), along with two 21-day cycles of capecitabine (1000 mg/m2, bid, po, day1–14). The TME surgery will be scheduled for 4 to 8 weeks after the completion of radiotherapy. Trial accrual opened on January, 2023, and scheduled to end on June, 2026. Discussion We will explore if the addition of CIETAI to chemoradiotherapy as part of neoadjuvant therapy in LARC will be safe and improve the pathological complete response rate. This study protocol is pioneering in its approach, as it introduces the administration of an anti-PD-1 antibody through tumor-feeding arteries within the neoadjuvant treatment framework, which may help reverse the immune desertification observed in LARC and their resistance to immunotherapy. Trial registration ClinicalTrials.gov Identifier: NCT05957016

Rationale:Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide, and approximately 50% of patients with early-stage disease develop metastases. A critical limitation for successful management of CRC is early disease detection and identification of progression. Next-generation sequencing-based circulating tumor DNA (ctDNA) profiling has emerged as a promising biomarker for the assessment of minimal or molecular residual disease in CRC. Patient concerns:The patient was initially diagnosed with resectable CRC with uncertain small lung nodules. Diagnoses:The patient was diagnosed with sigmoid colon adenocarcinoma placed at 15 to 20 cm above the anal verge (ypT4N1R0). Lung nodules were found in the apical part of the upper lobe of the right lung and the dorsal segment of the lower lobe of the left lung. Interventions:The patient received systemic therapy and local treatment and plasma ctDNA-MRD detection was performed for monitoring the molecular disease status after surgery. Outcomes:The patient achieved a complete response after treatment. However, he presented with disease recurrence in liver lesions. The postoperative ctDNA detection suggested the possibility of micrometastatic pulmonary disease, and that was confirmed by follow-up examination. Serial ctDNA detection revealed disease relapse ahead of radiologic imaging by a lead time of 9 months. This case demonstrated the potential of ctDNA analysis to be a sensitive and specific tool for the detection of micrometastatic disease and prediction of recurrence.

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 .

The aim of this study was to investigate the mutations in mucinous adenocarcinoma of the appendix (MAA). SNV was detected in 15 patients with MAA, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and reactome pathway analyses were performed. Tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), microsatellite instability (MSI) was analysis. Finally, the human leukocyte antigen (HLA) typing of the samples was detected. The results showed that TP53 (27 %) and KRAS (20 %) were the highest mutation frequency in the sample, mainly occur in p53 pathway and RTK-RAS pathway. GO analysis reveals mutated genes are closely related to the regulation of GTPase activity, regulation of small GTPase mediated signal transduction and other BP, related to the CC and MF. Analysis of KEGG pathways indicated that the top canonical pathways associated with SNV was Wnt signaling pathway. Reactome pathway analysis further revealed that the mutant genes were closely related to muscle contraction. Only one patient had moderate TMB level and one patient with high MSI. In conclusion, the most common mutated genes and the signaling pathways closely related to MAA development were detected in this study, which will contribute to the development of immunotherapy for patients with MAA.

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

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 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 ).

Abstract Background: The prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), neuron-specific enolase (NSE), Glycogen Antigen 153, Glycogen Antigen 199 has been investigated in Lung Adenocarcinoma (LUAD). However, few studies have directly focused on the association between serum tumor markers and epidermal growth factor receptor (EGFR) mutation status.Material and Method: 146 patients with stage IIIB and IV LUAD were enrolled between 2008 and 2018. Correlations between serum tumor marker levels, EGFR mutations and survival were analyzed and prognostic factors were identified.Result: Of eligible 90 patients with EGFR-mutant LUAD, CA 15-3 (7 versus 9 months, 0.037 for PFS; 25 months versus 36 month, P = 0.003 for OS, ) and Cyfra21-1 (7.0 versus 9.0 months, P =0.010 for PFS, 25 months versus 36 months, P=0.044 for OS,showed negatively significant correlation with overall survival and Progression free survival. For parents without EGFR-mutation, CA125 (month versus 8 months, P = 0.013 for DFS, 18 months versus 24 month, P = 0.016 for OS) also showed negatively significant correlation with overall survival and Progression free survival.Conclusion: CA153 and Cyfra21-1 was a prognostic serum biomarker in EGFR-mutant LUAD patient, coincide with CA125 in EGFR-WT LUAD group.Cyfra21-1 levels was also a predictive serum biomarker for in EGFR-mutant LUAD patient who received EGFR-TKI treatment.

BACKGROUND:Metastasis is a major challenge in cervical cancer treatment. Previous studies have shown that the dual functional protein apurinic/apyrimidinic endonuclease 1 (APE1) promotes tumor metastasis and is overexpressed in cervical cancer. However, the biological role and mechanism of APE1 in cervical cancer metastasis have rarely been studied.METHODS:We used gene set enrichment analysis (GSEA) to determine the APE1-related signaling pathways in cervical cancer. To investigate the role and mechanism of APE1 in cervical cancer metastasis and invasion, immunohistochemistry, immunofluorescence, western blotting, secondary structure prediction, coimmunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were performed. The inhibitory effects of the APE1 redox function inhibitor APX3330 on cervical cancer metastasis were evaluated using animal models.RESULTS:Clinical data showed that high expression of APE1 was associated with lymph node metastasis in cervical cancer patients. GSEA results showed that APE1 was associated with epithelial to mesenchymal transition (EMT) in cervical cancer. Ectopic expression of APE1 promoted EMT and invasion of cervical cancer cells, whereas inhibition of APE1 suppressed EMT and invasion of cervical cancer cells in a redox function-dependent manner. Notably, APE1 redox function inhibitor APX3330 treatment dramatically suppressed cervical cancer cell lymph node and distant metastasis in vivo. Furthermore, we found that APE1 enhanced the interaction between ZEB1 and the E-cadherin promoter by binding to ZEB1, thereby suppressing the expression of E-cadherin, a negative regulator of EMT.CONCLUSION:Our findings help to elucidate the role played by APE1 in cervical cancer metastasis and targeting APE1 redox function may be a novel strategy for inhibiting cervical cancer metastasis.

Background: The prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), neuron-specific enolase (NSE), Glycogen Antigen 153, Glycogen Antigen 199 has been investigated in Lung Adenocarcinoma (LUAD). However, few studies have directly focused on the association between serum tumor markers and epidermal growth factor receptor (EGFR) mutation status.Material and Method: 146 patients with stage IIIB and IV LUAD were enrolled between 2008 and 2018. Correlations between serum tumor marker levels, EGFR mutations and survival were analyzed and prognostic factors were identified.Result: Of eligible 90 patients with EGFR-mutant LUAD, CA 15-3 (7 versus 9 months, 0.037 for PFS; 25 months versus 36 month, P = 0.003 for OS, ) and Cyfra21-1 (7.0 versus 9.0 months, P =0.010 for PFS, 25 months versus 36 months, P=0.044 for OS,showed negatively significant correlation with overall survival and Progression free survival. For parents without EGFR-mutation, CA125 (month versus 8 months, P = 0.013 for DFS, 18 months versus 24 month, P = 0.016 for OS) also showed negatively significant correlation with overall survival and Progression free survival.Conclusion: CA153 and Cyfra21-1 was a prognostic serum biomarker in EGFR-mutant LUAD patient, coincide with CA125 in EGFR-WT LUAD group.Cyfra21-1 levels was also a predictive serum biomarker for in EGFR-mutant LUAD patient who received EGFR-TKI treatment.

Background Lung cancer is increasingly common as a second primary malignancy. However, the clinical characteristics of second primary non-small cell lung cancer after cervical cancer (CC-NSCLC) compared with first primary non-small cell lung cancer (NSCLC1) is unknown. Methods The Surveillance, Epidemiology, and End Results (SEER) cancer registry between 1998 and 2010 was used to conduct a large population-based cohort analysis. The demographic and clinical characteristics, as well as prognostic data, were systematically analyzed. The overall survival (OS) in the two cohorts was further compared. The risk factors of second primary lung cancer in patients with cervical cancer were also analyzed. Results A total of 557 patients (3.52%) developed second primary lung cancer after cervical cancer, and 451 were eligible for inclusion in the final analyses. Compared with NSCLC1, patients with CC-NSCLC had a higher rate of squamous cell carcinoma (SCC) (36.59% vs 19.07%,P< 0.01). The median OS was longer for CC-NSCLC than for NSCLC1 before propensity score matching (PSM) (16 months vs. 13 months) but with no significant difference after PSM (16 months vs. 17 months). The high-risk factors for the development of cervical cancer to CC-NSCLC include age 50-79 years, black race [odds ratio (OR) 1.417; 95% confidence interval (CI) 1.095-1.834;P< 0.05], and history of radiotherapy (OR 1.392; 95% CI 1.053-1.841;P< 0.05). Conclusion Age 50-79 years, black race, and history of radiotherapy were independent risk factors for second primary lung cancer in patients with cervical cancer. Patients with CC-NSCLC had distinctive clinical characteristics and better prognosis compared with patients with NSCLC1.

Summary Background The 5-year survival rate for extensive-disease small-cell lung carcinoma (ED-SCLC) is only 1%. Recently, apatinib exerted promising effects on cancer patients after failure of first-line chemotherapy. Methods This study enrolled 24 ED-SCLC patients to study the efficacy and toxicity of apatinib in combination with chemotherapy and maintenance therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib was given 250 mg/day during the chemotherapy interval, and as maintenance therapy after 4–6 cycles until the patient progressed, died, or was intolerant to drug toxicity. The study further evaluated the cytotoxicity, cell-cycle arrest and apoptotic induction of apatinib in A549 and H446 cells. Results There was no difference in short-term efficacy between combined and chemotherapy groups. Long-term efficacy showed that the median PFS was 7.8 months and 4.9 months in combination and chemotherapy groups, respectively [ p = 0.002, HR(95%CI): 0.18(0.06–0.60)]. The median OS was 12.1 months and 8.2 months in combination and chemotherapy groups, respectively [ p = 0.023, HR(95%CI): 0.38 (0.16–0.90)]. Multivariate Cox regression analysis showed that apatinib combined with chemotherapy was an independent prognostic factor for OS and PFS. The ECOG score was an independent prognostic factor affecting OS. In vitro analysis showed that apatinib inhibited cell proliferation and caused cell-cycle arrest and apoptosis. Conclusion Apatinib combination/maintenance therapy showed promising efficacy and safety to extend OS/PFS in ED-SCLC and will be a potent therapeutic option in future practice. Although the scale of this study is small, further research on large sample sizes is needed.

Background Although much progress has been made in the diagnosis of early-stage lung adenocarcinoma (ES-LUAD), the prognosis for ES-LUAD patients with rapid recurrence is still poor. Importantly, there is currently no effective and precise method to screen patients who may develop rapid recurrence. Therefore, it is necessary to identify potential differentially expressed genes (DEGs) in ES-LUAD patients with rapid recurrence and non-rapid recurrence. Methods Affymetrix GeneChip Human Transcriptome Array was used to identify DEGs between ES-LUAD patients with rapid recurrence and non-rapid recurrence. Rapid recurrence was defined as recurrence-free survival (RFS) ≦ 1 year and non-rapid recurrence was defined as RFS ≧ 3 years. The biological functions of the DEGs were analyzed by GO and KEGG pathway enrichment analyses. The protein–protein interaction (PPI) network of identified DEGs was conducted by STRING and Cytoscape software. The expression level of crucial hub genes and tumor-infiltrating lymphocytes (TILs) was verified by immunohistochemistry (IHC). Results A total of 416 DEGs were identified between ES-LUAD patients with and without rapid recurrence. The results of GO analysis revealed that 2 of the top 10 categories in the domain of cellular component, 2 of the top 10 in the domain of molecular function, and 9 of the top 10 in the domain of biological process were functionally related to immunity. The results of KEGG analysis showed that 6 of the top 8 pathways were functionally involved in immune regulation and inflammatory response. The PPI network analysis identified ten crucial nodal protein, including EGFR, MMP9, IL-1β, PTGS2, MMP1, and 5 histone proteins, which constituted 25 key interactions. IL-1β and PTGS2 expression were closely related to immunity and IHC analysis further revealed that low expression of IL-1β and PTGS2 is associated with rapid recurrence. Kaplan–Meier analysis further revealed that LUAD patients with lower IL-1β or PTGS2 expression had a worse RFS. When the TIL density of CD3 + , CD4 + , CD8 + and CD20 + subsets was less than 20%, ES-LUAD patients have a higher probability of rapid recurrence. Conclusion There were significant differences in the expression of immune-related genes between patients with rapid recurrence and patient with non-rapid recurrence. Immune-related genes such as IL-1β and PTGS2 and TIL density (20%) play important roles in rapid recurrence of ES-LUAD. This study provided a theoretical basis for distinguishing the two types of patients from an immunological perspective.

The diagnosis and treatment for multiple primary cancers have been a great challenge in clinical practice. Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA that circulates in the blood. Herein we report a case that ctDNA facilitated the diagnosis of synchronous urothelial carcinoma (UC) and lung adenocarcinoma. A 58-year-old male patient was diagnosed with UC initially. Computed tomography (CT) revealed multiple metastases without the brain after surgery and adjuvant chemotherapy. However, the patient had a progressively worsened headache symbol during system therapy. We explored the genome variations using next-generation sequencing (NGS). HRAS and TP53 mutations were detected from UC surgical tissue and postoperative ctDNA. Unexpectedly, the epidermal growth factor receptor (EGFR) exon 19 deletion (19del) mutation, which is common in non-small cell lung cancer (NSCLC), was also identified in ctDNA. Pathological analysis of a neck lymph node confirmed adenocarcinoma derived from the lung. Meanwhile, EGFR 19del was detected in neck lymph node biopsy. The ctDNA contained both UC and lung adenocarcinoma-derived mutations. Thus, the diagnosis was modified into synchronous UC and lung adenocarcinoma. Interestingly, the lung adenocarcinoma-derived lesions responded well to osimertinib (80mg, once daily), while the UC did not. His headache rapidly subsided and disappeared. This case demonstrates that ctDNA analysis may better capture the molecular heterogeneity harbored by multiple primary tumors in a patient and can facilitate the diagnosis and therapy of patients with simultaneous cancers.

设计一套模拟发射筒内建压过程的装置,使之能够模拟不同建压速度、不同终值压强时的发射筒内建压过程,进而对导弹弹射过程中导弹尾罩和其他结构受到的气体冲击载荷进行地面冷实验.分别对四种不同初始条件下的建压过程进行了实验,并对一种情况进行了数值模拟仿真.结果 显示,实验设备通过调节柱塞两侧初始压力差和高压气缸初始压力,可以实现对不同建压速率、不同终值压强的模拟;在建压过程中模拟发射筒内存在明显涡流,尾罩中间部位受压更大,变形时间相较于升压时间存在明显滞后.