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Objective Metaplastic breast cancer (MpBC) is an aggressive subtype of all breast cancer. We aimed to investigate the clinicopathological features, treatments and prognoses of MpBC patients. Methods We collected the data from MpBC patients diagnosed at Tianjin Medical University Cancer Hospital from 2010 to 2017. Kaplan Meier curves and Cox regression model were used to evaluating clinical outcomes and prognostic factors. After removing baseline differences by propensity score matching (PSM), we analyzed the prognosis between MpBC patients and invasive ductal carcinomas of no special type (IDC-NST) patients. Results A total of 217 MpBC patients were subsumed. Of all histological subtypes, 45.1% were mixed subtypes, followed by with mesenchymal differentiation (27.2%), pure squamous (15.2%) and pure spindle (12.4%) subtypes. 69.6% of MpBC were triple-negative, 25.3% and 6.5% were HR-positive and HER2-positive. MpBC patients had worse survival compared to IDC-NST patients, with 5-year RFS of 73.8 and 83.6% (HR = 1.177 95%CI (1.171–2.676) P = 0.0068), and 5-year BCSS of 79.0% and 89.7% (HR = 2.187 95%CI (1.357–3.523) P = 0.0013). In the multivariate COX model, AJCC stage, mixed subtype and chemotherapy were independent prognostic factors. Mixed MpBC is more aggressive than pure and with heterologous mesenchymal differentiation subtypes. And whether squamous or spindle MpBC, mixed forms have shorter outcomes than pure forms. Conclusions MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.

Objective: Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, showed promising efficacy and manageable safety profiles in the treatment of HER-2 positive breast cancer. Diarrhea is the most common adverse event associated with pyrotinib. This study aimed to evaluate the incidence and management of diarrhea secondary to pyrotinib in Chinese patients with HER-2 positive breast cancer. Methods: In this prospective real-world study, consecutive patients aged over 18 with HER-2 positive breast cancer and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 who planned to receive pyrotinib-based regimens for at least 21 days were included. Pyrotinib-treated patients and those with preexisting gastrointestinal conditions were excluded. There were no planned management strategy or primary prophylaxis for diarrhea, while loperamide, montmorillonite powder or Golden Bifid (a live combined Bifidobacterium, Lactobacillus and Streptococcus Thermophilus tablet) were recommended. Treatment was given in accordance with routine clinical practice by investigators. For patients developed grade 3 or higher diarrhea, pyrotinib was suspended until the diarrhea improving to grade 1 or less, and secondary prophylaxis (such as loperamide, loperamide plus montmorillonite powder, or loperamide plus Golden Bifid) was administrated before pyrotinib resumption. The baseline characteristics of patients and details of diarrhea (onset time, duration, severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03, treatment and prognosis) were collected. Results: Between August, 2020 and April, 2022, a total of 107 eligible patients were included, with a median age of 54 (range: 25-81) years old. Most patients (93.5%) had an ECOG PS of 0-1, and 51 patients (47.7%) were hormone receptor positive. A total of 46 patients (43.0%) received pyrotinib in the early stage and 61 (57.0%) in the advanced stage. Sixty-nine cases (64.5%) used pyrotinib-containing combination therapy (including 40 combined with capecitabine, 13 combined with trastuzumab, and 16 combined with other regimens), and 38 (35.5%) received pyrotinib alone. Ninety-eight cases (91.6%) reported diarrhea of any grade. Grade 1, 2 and 3 diarrhea occurred in 78 (72.9%), 9 (8.4%) and 11 (10.3%) patients, respectively. The median time to first onset of diarrhea of any grade was 2.5 (1-12) days, and the duration of first onset was 4 (1-24) days. The cumulative duration of diarrhea was 10 (1-60) days. Sixty-four, two, thirty, two patients used loperamide alone, montmorillonite powder alone, loperamide plus montmorillonite powder and loperamide plus Golden Bifid for the treatment of diarrhea, respectively. Eleven (10.3%) and seven (6.5%) patients experienced pyrotinib dose reduction and pyrotinib discontinuation. For 11 patients suffered grade 3 diarrhea, the median time to first onset of grade 3 diarrhea was 9 (4-14) days. Two, four and five patients administrated loperamide, loperamide plus Golden Bifid and loperamide plus montmorillonite powder as their secondary prophylaxis. Ten of eleven had grade 1 or 2 diarrhea after secondary prophylaxis, while one patient still suffered grade 3 diarrhea. All of them (11/11) held the pyrotinib dose. The incidence rate of constipation of all patients was 3.7%, which did not increase after treatment or secondary prophylaxis for diarrhea. Conclusion: In this study, the majority of patients developed pyrotinib associated diarrhea, and most of them were grade 1. About 10% patients reported grade 3 diarrhea, which can be managed by loperamide-based treatment and secondary prophylaxis. Table 1. Baseline characteristics of patients ECOG PS: Eastern Cooperative Oncology Group performance status; HER-2: human epidermal growth factor receptor 2. Table 2. Summary of patients developed diarrhea Table 3. Summary of patients developed grade 3 diarrhea Citation Format: Hong Liu, Li Ma, Xu Wang, Xinzhong Chang, Qi Yu, Qingfeng Huang, Chunfang Hao, Jun Liu, Jing Zhao, Shufen Li, Zhongsheng Tong, Yehui Shi, Ning Lu, Weipeng Zhao, Tong Wang, Xuchen Cao, Chen Wang, Juntian Liu, Ying Zhao, Lina Zhang, Baoliang Guo, Xin Wang, Xu Di, Chunhui Gao, Zongzhan Liu, Shuo Sun, Linwei Li. Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-11.

The implementation of the urban underground logistics system (ULS) can effectively mitigate the contradiction between the surging logistics demand and the increased negativity of urban logistics. The widespread implementation of ULS still suffers from a lack of research into its operation in the marketplace, although the research on ULS system technology and network design appears to be sufficient. A new supply chain for logistics service based on ULS (ULS-SSC) was proposed, as ULS embedded in the urban logistics system could lead to the evolution of the role of supply chain participants. This article analyzed the organizational structure and operation characteristics of ULS-SSC and designed a top-down ULS-SSC operation process model based on the designed functional structure and subsystems relationship using the hierarchical colored Petri net (HCPN). The simulation results show that the integrated information management platform based on ULS can integrate urban logistics service supply chain resources and operate effectively under the two main service modes designed. The high-time delay intermediate links can be upgraded by system optimization, and the links with initial pickup and terminal distribution can be improved through outsourcing and supply chain collaboration. The findings provide new insights into the feasibility of the operation of ULS in the market and help stimulate the implementation of ULS.

Background This study aims to evaluate the clinicopathological features, prognosis, and related prognosis factors of triple-positive breast cancer, to develop more scientific and individualized treatment plans. Methods We collected pathological and clinical data from 960 patients with early-stage triple-positive breast cancer who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital (2012–2017). The Cox regression model was used for prognostic univariate analysis and multifactor analysis. Kaplan-Meier was used to plot survival curves, and the log-rank test was used to analyze survival differences between groups. Results T-stage, N-stage, whether to receive adjuvant targeted therapy, and whether to receive adjuvant endocrine therapy were independent influencing factors of prognosis (P P P > 0.05). The prognosis of T1abN0M0 patients was not significantly altered by the use of trastuzumab or not (P = 0.439). There was no significant difference in OS with or without trastuzumab in the HR ≥ 30% group (P = 0.212) and in DFS and OS in the HR ≥ 50% group (P = 0.082, P = 0.978). Conclusions Our findings indicate that HR expression influences the biological behavior and treatment outcome of TPBC. We should choose individualized, targeted treatment programs, based on patients’ HR expression and pathological staging to benefit patients with TPBC.

Purpose Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is still unclear that the mechanisms by which long non-coding RNA (lncRNA) regulates tumorigenesis of TNBC. In this study, we explored the function and regulation of lncRNA in TNBC. Methods The differentially expressed and overlapped lncRNAs were obtained from two microarray datasets of breast cancer. The cancer genome atlas (TCGA) data was applied to validate the roles of top differentially expressed lncRNAs. The potential relationship among lncRNAs, miRNAs, and mRNAs and the effects of them on the TNBC tumorigenesis were further explored through multiple bioinformatic methods. Results Long intergenic non-protein coding RNA 1351 (LINC01351) was first discovered to play an oncogenic role in TNBC. The highly expressed LINC01351 was significantly related to aggressive subtypes, advanced stages and metastasis of breast cancer. The overexpressed LINC01351 was associated with adverse prognosis of patients with TNBC. LINC01351 was found to negatively regulate ELK4 which was involved in the transcriptional regulation in cancer. The high expression of ELK4 showed favorable prognosis of patients with basal-like 1 subtype and luminal androgen receptor subtype of TNBC. Conclusion The dysregulation of LINC01351 played an important role in triple-negative breast cancer. LINC01351 could be a poor prognostic marker and a potential target for patients with TNBC.

Aberrant expression of histone deacetylase 6 (HDAC6) is greatly involved in neoplasm metastasis, which is a leading cause of colon cancer related death. Thus, deep understanding of the regulatory mechanisms of HDAC6 in the metastasis of colon cancer is warranted. In this study, we firstly found that HDAC6 expression was highly expressed in metastatic colon cancer tissues and inhibition or knockdown of HDAC6 suppressed colon cancer metastasis. Next, based on proteomic analysis we uncovered A-kinase anchoring protein 12 (AKAP12) was a novel substrate of HDAC6. HDAC6 interacted with AKAP12 and deacetylated the K526/K531 residues of AKAP12. Moreover, deacetylation of AKAP12 at K531 by HDAC6 increased its ubiquitination level, which facilitated AKAP12 proteasome-dependent degradation. Importantly, we observed an inverse correlation between AKAP12 and HDAC6 protein levels with human colon cancer specimens. Further deletion of AKAP12 in HDAC6 knockdown cells restored the cell motility defects and reactivated the protein kinase C isoforms, repression of which were responsible for the inhibition of cancer metastasis of AKAP12. Our study identified AKAP12 was a new interactor and substrate of HDAC6 and uncovered a novel mechanism through which HDAC6-dependent AKAP12 deacetylation led to its ubiquitination mediated degradation and promoted colon cancer metastasis.

The soil discharged by an earth pressure balanced (EPB) shield machine reflects ground loss and controls surface settlement. In engineering, the discharge was mainly estimated by weighing the tunnelling spoil, however, human disturbance and information lag bring serious hidden security risks to tunnel construction. Through the analysis of conveying flow and force of screw conveyor, an energy model of interaction between screw conveyor and soil discharged was proposed and verified experimentally. Then, the energy model was combined with the discharge equation and the force balance equation, and a semi-analytical method to fast estimate the soil discharged of the EPB shield machine was proposed. Taking an EPB shield construction project as an example, according to the data of earth pressure, the torque and the rotation of the screw conveyor recorded by EPB shield machine, the real-time soil discharged of EPB shield machine can be accurately estimated. The mean absolute error (MAE) of this method is 3.177 × 103 kg compared with the measured weight of tunnelling spoil, which verifies the rationality of the method and provides a method for further effective evaluation and control of ground loss.

Background: FCN-437c is a second-generation CDK4/6 inhibitor. Phase 1b clinical results indicated improved antitumor activity in patients (pts) with HR+, HER2– advanced breast cancer (ABC), treated with FCN-437c + letrozole. Methods: This Phase 2, multicenter, open-label clinical study evaluated the antitumor activity, pharmacokinetics (PK), and safety of FCN-437c + fulvestrant in post-menopausal pts (Cohort 1, treatment-naïve or 2L), FCN-437c + letrozole + goserelin in pre-menopausal pts (Cohort 2, treatment-naïve). Pts received FCN-437c (200 mg QD) in a 21-day-on and 7-day-off schedule either in combination with fulvestrant (500 mg D1) or letrozole (2.5 mg QD) + goserelin (3.6 mg once per cycle) in 28-day cycles. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), PK, and safety. Results: At study cutoff (Feb 7, 2022), 36 pts were enrolled in Cohort 1 and 31 pts were in Cohort 2; 42 (62.7%) pts had visceral metastases and 9 (13.4%) pts had bone-only metastases. In Cohort 1, 18 pts were treatment-naïve, 15 pts had received 1L treatment, and 3 pts had received ≥2L treatment. In Cohort 2, 25 pts were treatment-naïve and 6 pts had received 1L treatment. Overall, 27 pts in the per-protocol set achieved partial response (PR), resulting in an ORR of 40.9% (95% CI, 29.0-53.7). Median follow-up was 12.8 months, and median PFS (mPFS), OS, and DOR were not reached. However, at 12 months, the PFS rate was 67.7% (95% CI, 53.2-78.6) and the OS rate was 95.9% (95% CI, 84.5-99.0); the 6-month DOR rate was 96.0% (95% CI, 74.8-99.4). In Cohort 1 (n=35), 11 pts achieved PR: the ORR was 31.4% (16.9-49.3%) and mPFS was 12.9 months (95% CI, 9.2-NR); the 6-month DOR rate was 100%. In Cohort 2 (n=31), 16 pts achieved PR: the ORR was 51.6% (95% CI, 33.1-69.9%). mPFS, OS, and DOR were not reached; the 6-month DOR rate was 92.9% (95% CI, 59.08-98.96) (Table). Treatment-emergent adverse events (TEAEs) were observed in all pts. Majority of AE were G1 or 2 except for hematological TEAE. 58 (86.6%) pts reported grade ≥3 TEAEs, mainly neutropenia (74.6%), leukopenia (49.3%), hypertriglyceridemia (6.0%), lymphocyte count decrease (4.5%), and γ-glutamyltransferase increase (3.0%): most were reversed through dose interruption and symptomatic therapy. Steady-state PK parameters were analyzed after 15-21 days of QD administration: Cohort 1: median Tmax was 3 h, geomean T1/2 was 44.6 h, geomean Cmax was 1650.7 ng/mL, and geomean AUC0-24h was 29,148.08 h*ng/mL; the geomean accumulation ratios of AUC0-24h and RCmax were 2.18 and 1.74, respectively, compared with first dose. Cohort 2: median Tmax was 4 h, geomean T1/2 was 35.7 h, geomean Cmax was 1314.34 ng/mL, and geomean AUC0-24h was 22,889.96 h*ng/mL; the geomean accumulation ratios of AUC0-24h and RCmax were 1.95 and 1.63, respectively, compared with first dose. Conclusion: FCN-437c in combination with fulvestrant or letrozole + goserelin demonstrates antitumor activity and safety and is well tolerated in pts with HR+, HER2– ABC. This combination therapy will be further investigated in 2 ongoing Phase 3 trials (NCT05438810 and NCT05439499). Clinical trial number: NCT05004142. Research Sponsor: Avanc Pharmaceutical Co., Ltd Table. Clinical outcomes for patients in the per-protocol set. Citation Format: JiaJie Shi, Wei Li, Zhongsheng Tong, Aimin Zang, Xiaohua Zeng, Shui Wang, Tao Huang, Ying Wang, Yanqiu Song, Lihua Kang, Zheng Lv, Yehui Shi, Hua Yang, Jing Wu, Yongmei Yin, Yan Liang, Jie Tan, Jie Ming, Yaping Yang, Simin Luo, Xiujuan Gui, Ai-Min Hui, Zhuli Wu, Ling Tian, Yuchen Yang, Lei Diao, Wenjing Zhang, Yongjiao Zhang, Yunjiang Liu. Phase 2 Study of the CDK4/6 Inhibitor FCN-437c in Combination With Fulvestrant or Letrozole and Goserelin in Patients With HR+, HER2– Advanced Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-21.

Recently, programmed cell death 1(PD-1) inhibitors have shown a significant curative effect in the treatment of most solid cancers and some hematological malignancies. The effects of PD-1 inhibitors in recurrent head and neck squamous cell carcinoma (HNSCC) have also been confirmed. However, there is a lack of reliable clinical evidence to confirm the safety and efficacy of PD-1 inhibitors in patients after allogeneic hematopoietic stem cell transplantation, especially when the patient has a second primary cancer. Generally, graft-versus-host disease (GVHD) is unpredictable among these patients. Here we report the case of a patient who successfully used nivolumab without any GVHD or other immune-related adverse events for HNSCC after allogeneic bone marrow transplantation because of the Philadelphia chromosome-positive T cell acute lymphoblastic leukemia.

Objective Fluzoparib (SHR3162) is a novel, potent poly(ADP-ribose) polymerases (PARP)1, 2 inhibitor that showed anti-tumor activity in xenograft models. We conducted a phase I, first-in-human, dose-escalation and expansion (D-Esc and D-Ex) trial in patients with advanced solid cancer. Methods This was a 3+3 phase I D-Esc trial with a 3-level D-Ex at 5 hospitals in China. Eligible patients for D-Esc had advanced solid tumors refractory to standard therapies, and D-Ex enrolled patients with ovarian cancer (OC). Fluzoparib was administered orally once or twice daily (bid) at 11 dose levels from 10 to 400 mg/d. Endpoints included dose-finding, safety, pharmacokinetics, and antitumor activity. Results Seventy-nine patients were enrolled from March, 2015 to January, 2018 [OC (47, 59.5%); breast cancer (BC) (16, 20.3%); colorectal cancer (8, 10.1%), other tumors (8, 10.1%)]; 48 patients were treated in the D-Esc arm and 31 in the D-Ex arm. The maximum tolerated dose (MTD) was 150 mg bid, with a half-life of 9.14 h. Grade 3/4 adverse events included anemia (7.6%) and neutropenia (5.1%). The objective response rate (ORR) was 30% (3/10) in patients with platinum-sensitive OC and 7.7% (1/13) in patients with BC. Among patients treated with fluzoparib ≥120 mg/d, median progression-free survival (mPFS) was 7.2 [95% confidence interval (95% CI), 1.8-9.3] months in OC, 9.3 (95% CI, 7.2-9.3) months in platinum-sensitive OC, and 3.5 (range, 2.0-28.0) months in BC. In patients with germline BC susceptibility gene mutation (gBRCA Mut) (11/43 OC; 2/16 BC), mPFS was 8.9 months for OC (range, 1.0-23.2; 95% CI, 1.0-16.8) and 14 and 28 months for BC (those two patients both also had somaticBRCA Mut). Conclusions The MTD of fluzoparib was 150 mg bid in advanced solid malignancies. Fluzoparib demonstrated single-agent antitumor activity in BC and OC, particularly in BRCA Mut and platinum-sensitive OC.

Background Her-2 positive subtype breast cancer is characterized as Her-2 gene amplification with poor survival and increased invasiveness accounting for 20–30% of invasive infiltrated breast cancer. A lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network is constructed to detect Her-2 specific RNAs in the development and progression of HER-2 positive breast cancer which may overcoming the anti-HER-2 therapy resistance of breast cancer cells. Methods One thousand one hundred and nine breast cancer samples obtained from The Cancer Genome Atlas (TCGA) database were classified into two cohorts including ER+/PR+ (n=461) and ER-/PR- breast cancer (n=152). Differently expressed mRNAs, lncRNAs and miRNAs were screened in ER+/PR+ and ER-/PR- breast cancer cohorts, respectively. lncRNA-miRNA interactions were preformed to predicted and verified by miRcode. miRNA-mRNA interactions were selected to predict targeted mRNAs of miRNAs by miRanda, Targetscan and miRTarBase. Results lncRNA-miRNA-mRNA ceRNA network was constructed by retained lncRNAs, miRNAs and mRNAs. Fifteen DEmiRNAs, 129 DElncRNAs and 269 DEmRNAs were retained in ER+/PR+ cohort after intersection with DEmiRNAs, DElncRNAs and DEmRNAs between breast cancer and normal tissues. Six hundred and ninety-three DEmRNAs, 25 DEmiRNAs and 364 DElncRNAs were retained in ER-/PR- cohort. ceRNA network in ER+/PR+ breast cancer cohort was constructed of the interactions of 4 DElncRNA–DEmiRNA pairs and 2 DEmiRNA–DEmRNA pairs included 4 DElncRNAs, 1 DEmiRNAs, and 2 DEmRNAs. ceRNA network in ER-/PR- breast cancer cohort was constructed of the interactions of 24 DElncRNA–DEmiRNA pairs and 1 DEmiRNA–DEmRNA pairs included 19 DElncRNAs, 4 DEmiRNAs, and 1 DEmRNA. MIR7-3HG- hsa-mir-204-NTRK2 axis was identified in both ER+/PR+ and ER-/PR- cohort in our study. Conclusions Based on the ceRNA hypothesis, a potential Her-2 related regulatory ceRNA networks are constructed which may provide novel insights into the mechanism underlying the biological processes of Her-2 positive breast cancer.

Contaminated soil management and renovation is one of the major environmental geotechnical issues in China. Due to their special strength and stiffness properties, contaminated soil has attracted extensive attention in foundation and slope stability design. For the differentiated influence of acidic/alkaline contamination on the geotechnical physical and mechanical characteristics of soil, this study mainly introduced a remodeled silty clay sample contaminated by acidic and alkaline solutions in the laboratory and conducted research into its basic physical properties, compressive properties, shear strength, and microstructure. It was shown that when the hydrochloric acid concentration increased from 1% to 7%, the density and specific gravity decreased by 7.07% and 3.11%, respectively. The void ratio showed a descending trend with increasing concentration of acid. The acidic solution concentration was negatively correlated with the cohesion of the soil, but the internal friction angle remained constant with a concentration of 1–5%. Alternatively, when the sodium hydroxide concentration increased from 1% to 7%, the density and specific gravity increased by 1.88% and 2.67%, respectively. The void ratio decreased linearly with the increase in consolidation pressure. Alkaline concentration could affect the internal friction angle and cohesion in a positive correlation. Through the observation of microstructure, the surface of acidified soil particles was smooth and flat, while the surface of alkalized soil particles was rough and uneven. The results can provide reference for the evaluation of the mechanical properties of soil contaminated by acid and alkali.

The reliability of liquid rocket engines (LREs), which are the main propulsion device of launch vehicles, cannot be overemphasised. The development of fault detection and diagnosis (FDD) technology for LREs can effectively improve the safety and reliability of launch vehicles, which has important theoretical and engineering significance. With the rapid development of artificial intelligence technologies such as machine learning and artificial neural network, data-driven FDD methods have gained increasing attention. However, the scarcity of engine fault samples limits the application of this methods. We proposed a method combining Wasserstein generative adversarial nets (WGANs) and multilayer perceptron (MLP) to perform FDD for LREs with sample imbalance. Wasserstein generative adversarial nets were trained using the fault data from the actual hot-firing ground test of a large LRE. Considerable fault data were generated to expand the data set to balance the ratio of positive and negative samples. Subsequently, the expanded data set was used to train the MLP for FDD of a large LRE. The results showed that the samples generated by the WGAN were authentic, confirming the application of the proposed method as a novel and effective tool for establishing a complete LRE fault database. Furthermore, the diagnosis times of the proposed method on five fault tests were advanced by 0.66, 15.82, 0.24, 0.14 and 1.08 s in relation to those of the conventional red-line cut-off system. Compared with support vector machine and adaptive threshold algorithm, the proposed method also performed better.

1033 Background: In 15% to 30% of breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed, this is related to aggressive disease and poor prognosis. Although important clinical benefits for patients have been achieved by the use of the HER2 antibody trastuzumab, 50% to 74% of patients with metastatic disease have no response to treatment, and approximately 75% progress within one year. The purpose of this study was to evaluate the efficacy and safety of oral pyrotinib in combination with oral metronomic vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. Methods: This prospective phase 2 study enrolled patients aged 18-75 years with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy, and had an Eastern Cooperative Oncology Group performance score of 0-2. Patients received pyrotinib 400 mg once daily and vinorelbine 40 mg once on Monday, Wednesday, Friday of each week until disease progression or unacceptable toxicity. Both pyrotinib and vinorelbine were orally administered 30 min after meals. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease remission rate (DCR), overall survival (OS), quality of life (QoL) and safety (CTCAE 5.0). The follow-up of this study is ongoing, but enrolment is closed. This study is registered on Clinical Trials.gov, number NCT04903652. Results: Between Oct 21, 2019, and Jan 21, 2022, 36 patients were enrolled and all of them were included in the intent-to-treat (ITT) population. 20 of 36 patients had disease progress or death. Median follow-up was 16.23 months. The median PFS (mPFS) was 14.23 months (95% CI 8.13-20.33). The ORR and DCR were 38.9% and 83.3%, respectively. The median OS was not reached. Grade 3 adverse events (AEs) occurred in 17 of 36 patients, the most common were diarrhea 27.8% and stomachache 5.6%. No grade 4 AEs were observed. Conclusions: Pyrotinib combined with metronomic oral vinorelbine showed promising efficacy and manageable safety in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. This study might represent a potential treatment option for these patients. Clinical trial information: NCT04903652..

1077 Background: Gemcitabine plus capecitabine (GX) regimen is still lack of phase Ⅲ clinical trial evidence for the first-line treatment of advanced triple-negative breast cancer (TNBC). We designed this phase Ⅲ trial to compare the efficacy and safety of GX with gemcitabine plus carboplatin (GC) in patients with advanced TNBC. We also explored the correlation between tumor infiltrating lymphocytes (TILs) and the prognosis in TNBC treated with different chemotherapy regimen. Methods: Patients with advanced TNBC were randomly assigned to receive gemcitabine (1,000 mg/m2) on days 1 and 8 plus oral capecitabine (1,000 mg/m2 twice a day) on days 1 through14; or, to receive gemcitabine (1,000 mg/m2) on days 1 and 8 plus carboplatin (AUC = 2) on days 1 and 8. The primary end point was progression free survival (PFS), and secondary end points were objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and safety. Immunohistochemistry was performed with antibodies against CD3, CD4, CD8, and CD 19 antigens on tissue sections of 52 TNBC patients. The margin used to establish non-inferiority was 1.2. This study is registered on Clinical Trials.gov, number NCT02207335. Results: From Jan 2014, to Dec 2020, 187 patients underwent eligibility assessment and were randomly assigned (93 in GX and 94 in GC). The ORRs in GX arm and GC arm were 37.6%, and 39.4%, respectively ( P = 0.808). The CBRs in GX arm and GC arm were 78.5% and 79.8%, respectively ( P = 0.828). Median PFS was 6.1 months for GX arm compared with 6.3months for GC arm (log-rank P = 0.348; HR = 1.148, 95% CI: 0.856 to 1.539, P = 0.357). The median OS in GX arm and GC arm was 21.0 months and 21.5 months, respectively (log-rank P = 0.992; HR = 1.002, 95% CI: 0.717 to 1.400, P = 0.992). Hematologic adverse events (AEs) were commonly observed in both arms, especially in GC arm. Non-hematological AEs such as hand-foot syndrome, diarrhea, and peripheral sensory neuropathy were more common observed in GX arm, while alopecia, nausea, vomiting, fatigue, decreased appetite, infusion related reaction, and hyperglycemia were more common in GC arm. Patients with high CD8+ TILs had a significantly longer PFS (HR = 0.559; 95% CI: 0.314 to 0.993, P = 0.047) and OS (HR = 0.436; 95% CI: 0.226 to 0.843, P = 0.014) compared with patients with low CD8+ TILs. In the high CD8+ group，patients treated with GC had prolonged PFS (HR = 0.322; 95% CI: 0.127 to 0.816, P = 0.017) and OS (HR = 0.300; 95% CI: 0.094 to 0.957, P = 0.042) compared with GX. Conclusions: The trial did not meet the prespecified criteria for the primary end point of PFS in the ITT population. Compared with GC, GX demonstrated lower toxicity. Compared to patients with low CD8+ TILs, patients with high CD8+ TILs showed better outcomes, and in these patients, GC regimen could improve survival compared with GX regimen. Clinical trial information: NCT02207335.

TPS2694 Background: Folate-receptor 1 (FOLR1) and prostate specific membrane antigen (PSMA) are overexpressed on tumor and angiogenic endothelial cells in solid tumors, including prostate cancer, renal cell cancer and lung cancer. CBP-1018 is a first-in-class bi-ligand drug conjugate targeting to both FOLR1 and PSMA, with a tubulin inhibitor payload, monomethyl auristatin E (MMAE). We herein introduce its first-in-human study which is designed based on the significant anti-tumor potency and acceptable safety profile in nonclinical studies. Methods: This study is a phase Ⅰa/Ⅰb, multicenter, open-label study enrolling patients with advanced solid tumor relapsed after previous standard therapies. The primary objective is to assess CBP-1018 safety, tolerability, dose limiting toxicity and maximum tolerated dose. Preliminary efficacy including objective response rate, duration of response and progression-free survival will be observed. Pharmacokinetics, immunogenicity and biomarkers will be also evaluated. This study includes 2 parts: Ⅰa (Dose Escalation) and Ⅰb (Dose Expansion). CBP-1018 is administrated iv Q2W (4 weeks/cycle) in Ⅰa, with accelerated titration at lower doses (0.03 mg/kg and 0.06 mg/kg) and an i3+3 design at following doses (0.08 mg/kg, 0.10 mg/kg, 0.12 mg/kg and 0.14mg/kg, etc.). Subjects will be enrolled in 4 cohorts in Ⅰb: metastatic castration resistant prostate cancer, advanced renal cell cancer, advanced lung squamous cell cancer, and other advanced solid tumors. Efficacy will be assessed every 8 weeks (±7days) according to RECIST 1.1, PCWG3 and PSA assessment (only for prostate cancer). Treatment will be continued untill disease progression or intolerable toxicity. Enrollment has been started in Nov. 2021 and is ongoing. Clinical trial information: NCT04928612.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is still unclear that the mechanisms by which long non-coding RNA (lncRNA) regulates tumorigenesis of TNBC. In this study, we explored the function and regulation of lncRNA in TNBC. Methods: The differentially expressed and overlapped lncRNAs were obtained from two microarray datasets of breast cancer. The Cancer Genome Atlas data was applied to validate the roles of top differentially expressed lncRNAs. The potential relationship among lncRNAs, miRNAs, and mRNAs and the effects of them on the TNBC tumorigenesis were further explored through multiple bioinformatic methods. Results: Long intergenic non-protein coding RNA 1351 (LINC01351) was first discovered to play an oncogenic role in TNBC. The highly expressed LINC01351 was significantly related to poor prognosis, aggressive subtypes, advanced stages and metastasis of breast cancer. LINC01351 was found to negatively regulate ELK4 which was involved in the transcriptional regulation in cancer. The high expression of ELK4 showed favorable prognosis of patients with basal-like 1 subtype and luminal androgen receptor subtype of TNBC.Conclusion: The dysregulation of LINC01351 played an important role in triple-negative breast cancer. LINC01351 could be a poor prognostic marker and a potential target for patients with TNBC.

Liquid rocket engines are complex equipment with long maintenance cycles and high fault diagnosis costs. Therefore, hardware-in-the-loop simulation combining software and hardware has become the best choice. A hardware-in-the-loop simulation platform framework is proposed based on a V-type development model and related digital twin technology, and the main content of the framework is introduced. Based on the development process of the platform, a certain type of liquid rocket engine is taken as the object to verify the results. The results show that the platform can well simulate the engine changes under different faults, and has versatility and high real-time performance.

In the risk assessment of water inrush in karst tunnel, it is most important to provide an available theoretical model for qualifying the epistemic uncertainties due to a lack of knowledge and information. Firstly, a mechanical model dependent on geology is introduced associating with four parameters, i.e., the elastic modulus E, the Poisson ratio μ, the water differential pressure q, and the tunnel radius a. Then, a mathematical model representing epistemic uncertainty is represented with probability theory and possibility theory. The methodology was computerized to calculate the distribution of the margin and uncertainty and then to determine the ratio of “margin/uncertainty.” Analyses involving possibility theory and possibility theory are illustrated with the same engineering example used in the presentation indicated above to illustrate the use of probability to represent aleatory and epistemic uncertainty in QMU analyses. The comparison between the uses of possibility theory and probability theory for the representation of aleatory and epistemic uncertainty indicates that the possibility is not only has a better mathematical structure than probability theory but also has some challenges.

Rock masses can be regarded as a blocky rock system. After a disturbance load is applied, the anomalously low friction phenomenon may take place and cause geological disasters. A series of impact experiments on granite blocks were conducted to investigate the anomalously low friction phenomena. Vertical vibration, Fourier frequency spectrum, and horizontal motions were investigated. It can be found that the tensile phases of vertical vibration can reduce the maximum static friction force, namely, the shear strength. The quasi-resonance operating mode of the rock blocks was observed. During the stress wave propagation, the vibration in the loading direction tends to transfer from high frequency to low frequency and the modes of stress wave propagation do not depend on disturbance energies. The observed translational and rotational motions were due to the initial shear force, which is less than the friction force with no disturbance load. Stability of the blocky rock system is very sensitive to the initial stress state. In the subcritical state, friction force reduction can easily break the equilibrium of forces along the contact surface and even a slight disturbance may make the horizontal motions happen, which may lead to geological disasters with great energy release.

Romidepsin (FK228), a histone deacetylase inhibitor (HDACi), has anti-tumor effects against several types of solid tumors. Studies have suggested that HDACi could upregulate PD-L1 expression in tumor cells and change the state of anti-tumor immune responses in vivo. However, the influence of enhanced PD-L1 expression in tumor cells induced by romidepsin on anti-tumor immune responses is still under debate. So, the purpose of this study was to explore the anti-tumor effects and influence on immune responses of romidepsin in colon cancer. The results indicated that romidepsin inhibited proliferation, induced G0/G1 cell cycle arrest and increased apoptosis in CT26 and MC38 cells. Romidepsin treatment increased PD-L1 expression in vivo and in vitro via increasing the acetylation levels of histones H3 and H4 and regulating the transcription factor BRD4. In subcutaneous transplant tumor mice and colitis-associated cancer (CAC) mice, romidepsin increased the percentage of FOXP3+ regulatory T cells (Tregs), decreased the ratio of Th1/Th2 cells and the percentage of IFN-γ+ CD8+ T cells in the peripheral blood and the tumor microenvironment. Upon combination with an anti-PD-1 antibody, the anti-tumor effects of romidepsin were enhanced and the influence on CD4+ and CD8+ T cells was partially reversed. Therefore, the combination of romidepsin and anti-PD-1 immunotherapy provides a more potential treatment for colon cancer.

S-1 is a multicomponent capsule containing tegafur, gimeracil, and oteracil potassium that has shown anticancer activity against numerous tumor types. However, S-1 capsules from different manufacturing companies have shown variations in pharmacokinetics and safety. Therefore, this multicenter, single-dose, randomized-sequence, open-label, two-way, self-crossover study was conducted to evaluate the bioequivalence of a newly developed generic S-1 (New Times Pharmaceutical Co., Ltd., Shandong, China) and the original brand-name S-1 capsule (Taiho Pharmaceutical Co., Ltd., Japan). Furthermore, the safety profiles of both products were compared. A total of 70 patients with 18 types cancer including breast, lung, gastric, and colorectal recruited at 5 hospitals who were randomly and alternatively administered 50 mg of the reference and test S-1 with a 7-day interval. Plasma concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), oteracil potassium, and 5-fluorouracil were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters, including maximum drug concentration (Cmax), time to achieve Cmax (Tmax), half-life (t1/2, area under the concentration-time curve from 0–time t (AUC0–t), and AUC from 0–infinity (AUC0–∞) were determined using non-compartmental analysis with DAS2.0 software. Bioequivalence of the reference and test S-1 was evaluated according to 90% confidence intervals (CIs) for ratios of AUC and Cmax of S-1. Adverse events were evaluated by monitoring symptoms, physical and laboratory examinations, electrocardiogram, and subject interviews. No significant difference was observed in plasma concentrations and pharmacokinetic profiles of tegafur, CDHP, oteracil potassium, or 5-fluorouracil (p > 0.05) among cancer patients treated with the reference or test S-1 formulation. The 90% CIs of Cmax, AUC0–t, and AUC0–∞ ratios were within the 80%–125% limit. The generic S-1 caused eight mild adverse events including liver dysfunction, diarrhea, nausea, fatigue, abnormal blood electrolytes, hyperglycemia, and dermal toxicity. Similarly, 18 mild adverse events were observed including dysarteriotony, diarrhea, nausea, fatigue, fever, hematotoxicity, abnormal blood electrolytes, hyperglycemia, dermal toxicity, and joint pain. There were no differences in the adverse event incidence between the two formulations. In conclusion, the newly developed generic S-1 showed similar pharmacokinetics to those of an original brand-name S-1 in cancer patients, thereby indicating bioequivalence. Furthermore, both treatments were well tolerated, suggesting that the cost-effective generic S-1 should be considered as a feasible option when treating patients.

Breast cancer is a heterogeneous disease highly diverse in different subtypes, including hormone receptor positive and hormone receptor negative subtypes with variable malignancy, therapy regimen, and different prognosis. In this study, we develop a hormone receptor-specific mRNA-miRNA-lncRNA ceRNA network to identify whether several RNAs play fundamental roles in development and metastasis of breast cancer. To understand the association of ceRNA expression profiles in different breast cancer subgroups, the expression profiles and clinical information of 428 HR+/Her-2- breast cancer samples and 113 triple negative breast cancer samples were downloaded from The Cancer Genome Atlas database (TCGA). We comprehensively integrated and compared expression profiles of mRNAs, miRNAs, and lncRNAs between the two subgroups mentioned. Aberrantly expressed hormone receptor specific RNAs were identified, whereas lncRNA-miRNA interactions predicted by miRcode and miRNA-targeted mRNA interactions were validated by miRTarBase, Targetscan, and miRDB database. In this study, mRNA-miRNA-lncRNA ceRNA network was constructed that consisted of 44 miRNA-lncRNA interaction pairs and 2 miRNA-mRNA interaction pairs, and visualized by Cytoscape software. Prognostic markers of HR-specific subtype of breast cancer associated with overall survival were identified by Kaplan-Meier survival analysis. Finally, SFRP1, AC006449.1, and MUC2 were novel clinical predictors that may also provide a new therapeutic target in the future.

Many biosimilars of monoclonal antibodies (mAbs) are becoming increasingly available as anticancer therapies, such as the rituximab, bevacizumab, and trastuzumab biosimilars. However, no comprehensive summary of their efficacy and safety is available. This study synthesized current evidence on the efficacy and safety of mAb biosimilars relative to their reference biologics among cancer patients. We searched PubMed, Embase, the Cochrane library, ClinicalTrials.gov, the ISI Web of Science, and several Chinese databases from their inception dates to December 31, 2018, for randomized controlled trials (RCTs) or comparative observational studies that compared the efficacy and safety of biosimilars with reference biologics used in oncology. The binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs), continuous outcomes using weighted mean difference (WMD) with 95% CIs, and time-to-event outcomes using hazard ratios (HRs). Subgroup and sensitivity analyses were conducted following this. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to rate the quality of the evidence. We did not find any comparative observational studies that fit the criteria. Twenty-three RCTs were identified for biosimilars of three mAbs, of which eight RCTs examined rituximab biosimilars (total N = 1534), six RCTs were for bevacizumab biosimilars (total N = 1897), and nine were for trastuzumab biosimilars (total N = 4953), respectively. The quality of the GRADE evidence for efficacy and safety outcomes was moderate or low. The findings were robust for all pre-specified subgroup and sensitivity analyses. The existing evidence suggests highly comparable efficacy and safety profiles between mAb biosimilars and their reference biologics in oncological drugs.

2044 Background: Management of advanced gliomas including glioblastoma multiforme (GBM) remains as an unmet medical need. Here we report our clinical experience with ACT001, or dimethylamino micheliolide, a synthesized derivative from parthenolide (a natural product of sesquiterpene lactone class), in Han Chinese patients with advanced glioma. Methods: Adult patients were enrolled in a 3+3 dose escalation phase 1 study with the following pre-defined ACT001 cohorts: 100mg, 200mg, 400mg, 600mg and 900mg, twice a day (BID). Pharmacokinetics and adverse events were evaluated during the study. Imaging studies were performed using RANO criteria to assess the therapeutic afficacy. Results: 16 patients with advanced glioma were enrolled in this single agent dose escalation study including 8 primary GBM, 4 astrocytoma (grade 2-3) and 4 other advanced glioma. The median age was 49 years (range: 31-70). Safety evaluation was performed in five cohorts and 13 of the 16 subjecst were evaluable for drug tolerability analysis. ACT001 was tolerated very well and no DLT or MTD was identified. Other than grade 1 adverse reactions (AE) in most cases and grade 2 AEs in other clinical findings, no drug-related grade 3 AE was noted. Pharmacokinetic analysis indicates that there was approximately linear correlate between the drug exposure (Cmax, AUC0-t and AUC0-inf) and study drug dosages evaluated. T1/2 is 4 hours with mean Cmax increased from approximate 300ng/ml to 5000ng/ml in a dose dependent manner with no significant dose accumulation during repeated dosing challenge. Post baseline MRI scans were performed in 11 out of 16 subjects. Among these 11 subjects, 1 GBM patient had a partial response (PR) at end of cycle 2 but had disease progressed at end of cycle 4; two non-GBM patients had a stable disease (SD) lasting for 5 or 6 cycles respectively before being taken off study due to disease pregression (PD) and other 8 patients had a PD. Of note, 9 out of these 11 subjects had stable or even improved clinical performance by the time they were taken off study due to PD. Five other subjects withdrew their consents or were taken off study due to clinical disease progression. Of note, subject S12 with diffusive astrocytoma was taken off study due to PD while still with a stable clinilcal performance and stereotactic biopsies targeting the progressed lesion didn’t reveal viable tumor tissues other than presence of macrophage/microglia. This subject was still alive 666 days after being taken off study. The mode of ACT001 actions is proposed to be at least partially related to its effects on tumor immune microenvironment. Conclusions: ACT001 was safe and tolerated well in patients. Clinical response was observed including a pathologic response in a subset of patients dosed at lower dose cohorts. iRANO criteria will be used in future studies based on its impacts on tumor immune microenvitonment. Clinical trial information: ChiCTR-OIC-17013604.

e15051 Background: Dysregulation of fibroblast growth factor receptor (FGFR) is strongly associated with establishment and progression of cancer. Pemigatinib is a selective FGFR1–3 inhibitor that are active in a targeted manner against cancers with activated FGFR pathway. The study was aimed at evaluating the tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) of pemigatinib in Chinese patients (pts) with advanced malignancy. Moreover, potential efficacy of pemigatinib was explored in a broad spectrum of FGFR alteration in variety of cancer types. Methods: In this phase 1 study, Chinese patients with advanced, recurrent or metastatic malignancy that were histologically or cytologically confirmed and harboring FGF/ FGFR 1-3 variation were enrolled. Pemigatinib was self-administered orally at 13.5 mg QD on a 3-week cycle (2-weeks-on/1-week-off schedule). Adverse events and other safety factors were monitored throughout the study. Blood samples were obtained at prespecified time points for PK and PD analysis and efficacy was assessed every 9 weeks per RECIST v1.1 guideline. Results: As of Jan 31, 2021, 12 patients with 5 different cancer types (colorectal cancer (4 pts), gastric and gastroesophageal junction carcinoma (3 pts), cholangiocarcinoma (2 pts), esophageal carcinoma (2 pts) and breast cancer (1pts)) were enrolled. Documented FGF/ FGFR1-3 alterations were FGFR amplification (6), FGFR point mutation (5), FGFR2 fusion (2) and FGF alteration (4) with 2 subjects had more than one alteration types. All the subjects were failed to at least 1 line of prior standard therapy. All patients had at least 1 treatment related adverse events (TRAE) and the most common ones were hyperphosphatemia (100%), decreased appetite (50%) and diarrhea (33.3%). Two patients (16.7%) reported ≥ grade 3 TRAEs, which were hyponatremia (8.3%) and proteinuria (8.3%). There were no TEAEs leading to death or treatment discontinuation. Among 11 efficacy evaluable patients, 2 of them had partial responses (PR) as evaluated by investigators with 1 cholagiocarcinoma harboring FGFR2 point mutation (p.F276C) and the other esophageal carcinoma carrying FGFR1 mutation (p.A354V). 3 patients had a best overall response of stable disease (SD). The objective response rate (ORR) was 16.7% (95%CI: 2–48%) and disease control rate was 41.7% (95%CI: 15–72%). Conclusions: Pemigatinib had an acceptable and manageable toxicity and demonstrated a possible anti-cancer benefit in Chinese patients with advanced malignancy that accompanied with FGF/FGFR1-3 aberrance. A significant implication of the data is that it extended the population that potentially benefit from pemigatinib other than FGFR2 fusion/rearrangement. Clinical trial information: NCT04258527.

e12569 Background: Breast cancer (BC) is one of the most common malignant tumors among women in the world. Although under 7% of all BC cases, young BC is more difficult to diagnose and can be aggressive and less likely to respond to treatment. Exploring and identifying potential biomarkers for the diagnosis and prognosis of younger BC patients is necessary. Methods: A total of 1,202 BC patients under 35 years old (YD) were enrolled. Deep sequencing targeting 450 cancer genes was performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) for genomic alteration identification. Statistical analysis was performed by Fisher’s exact test. Results: Of 1,202 young BC patients, 3 were under 20 YD, 85 were 20-25 YD, 371 were 26-30 YD, and 747 were 31-35 YD. Based on pathological, there were 899 infiltrative duct carcinomas, 10 infiltrative lobular carcinomas, and 292 BCs with unclear pathological type. According to molecular features, 587 HR+/HER2- (group I), 118 HR+/HER2+ (group II), 75 HR-/HER2+ (group III) and 193 HR-/HER2- (group IV) were included. Chemotherapy, radiotherapy, endocrine therapy and targeted therapy were received and 1074 patients were followed up. The median overall survival (OS) was 76 (5-156) months. There was no significant difference in OS between different treatments. The median OS was 81 (range 5-156) months, 67 (range 10-153) months, 76 (range 14-146) months, and 78 (range 13-151) months for group I, II, III, and IV, respectively. The significantly lower OS was observed in group II ( P=0.044). Although group II and group III had similar proportion of targeted treatment (43.22% vs 43.24%, respectively), the OS rate was different (67 vs 76 months, P=0.064). Samples from 46 young BC patients were performed on deep sequencing targeting 450 cancer genes. The most common mutations were TP53 (56%), GATA3 (29%), ERBB2 (27%), CDK12 (20%), and FGFR1 (20%). Different from previous studies, only 4.35% (2/46) of BRCA1/2 mutations were detected in this cohort. The mutation frequency of GATA3 in group II was significantly lower than that in group III (0% vs 71.43%, P=0.017). Conclusions: The most common pathological type of young BC was infiltrative duct carcinoma. The OS of HR+/HER2+ patients were significantly lower than that of others. Our results showed that GATA3 could be a potential biomarker for OS prediction for BC with HER2+, which help to further guide targeted therapy in young BC patients.

Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P = 0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients., Cancer: Starving sarcomas into submission A drug that inhibits blood vessel growth offers a potentially promising treatment for a class of tumors with a poor prognosis. Sarcomas form in bone and connective tissue, and patients with advanced disease have a five-year survival rate of less than 10%. Researchers led by Jilong Yang of the Tainjin Medical University Cancer Institute & Hospital in China tested apatanib, a drug that starves tumors by preventing blood vessel development, in late-stage sarcoma patients. Strikingly, 15% of the patients experienced tumor reduction after treatment, and more than half overall achieved at least partial disease control. Adverse events were generally mild, but Yang and colleagues observed that patients who experienced certain side-effects achieved a greater survival benefit from treatment. These results support further investigation of this drug, and offer hints of possible biomarkers to predict response.