Safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic bone and soft-tissue sarcomas: a retrospective institutional study

Safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic bone and soft-tissue sarcomas: a retrospective institutional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic bone and soft-tissue sarcomas: a retrospective institutional study Lina Pang, Shengli Zhang, Liye Wang, Shuai Gong, Xiaoke Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3869541/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This retrospective institutional study analyzed the safety and efficacy of anlotinib-chemotherapy combination as a first-line therapy in patients with unresectable or metastatic bone and soft tissue sarcomas (BSTSs). The clinical data of 92 patients with sarcoma treated with chemotherapy combined with or without anlotinib at the First Affiliated Hospital of Zhengzhou University from January 2018 to September 2020 were collected and analyzed. To determine the short-term efficacy, the objective response rate (ORR) and disease control rate (DCR) were analyzed. Long-term survival was assessed using the Kaplan–Meier method, including median progression-free survival (mPFS) and overall survival (mOS). Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the primary pathological subtypes of the 92 patients. The median patients’ age was 46 (range, 11–75) years. The ORR and DCR of the anlotinib–chemotherapy combination used as first-line therapy were 31.9% and 85.1%, respectively. However, the ORR and DCR were only 6.7% and 57.8% in the chemotherapy alone (the control group), respectively. Compared with the control group, improvements were observed in the mPFS and mOS with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months). Anlotinib-associated adverse events were well tolerated and mainly occurred in grades I and II. New anlotinib-related adverse reactions were not noted. Anlotinib-based regimen as a first-line therapy showed a positive effect on the treatment of unresectable or metastatic BSTSs. The anlotinib-associated adverse events were minor and well tolerated. Health sciences/Oncology Health sciences/Oncology/Cancer Health sciences/Oncology/Cancer/Cancer therapy Health sciences/Oncology/Cancer/Cancer therapy/Targeted therapies Bone and soft tissue sarcoma Anlotinib Prognosis Efficacy Adverse event Figures Figure 1 Introduction Sarcomas, including bone and soft tissue sarcomas (BSTSs), are rare heterogeneous malignancies that originate from the mesenchyme and can occur in various tissues and organs throughout the body. Currently, there are > 70 histological subtypes, and different molecular subtypes may be identified in the future [1, 2]. Soft tissue sarcomas (STSs) account for approximately 1.0% of all human malignancies, with the annual rate of approximately 3–5/100,000 globally [3, 4]. Osteosarcoma, chondrosarcoma (CS), and Ewing’s sarcoma are common bone sarcomas, with a person-year incidence of approximately 0.8 per 100,000 [5, 6]. To date, complete surgical resection remains the primary method for treatment; however, local recurrence or distant metastasis occurs following 30–50% of surgeries [7]. The rate of advanced sarcomas in primary diagnosis is approximately 20%, and approximately 50% localized diseases develop metastases [8, 9]. Despite decades of bench and clinical research attempting to improve outcomes of unresectable or metastatic sarcomas, the 5-year overall survival rate remains unsatisfactory [10]. Anthracyclines remain the backbone of the standard treatment for advanced sarcomas; however, they have poor safety, limited efficacy, and a low remission rate [11]. Tumor occurrence and development are inseparable from tumor angiogenesis (TA), which is regulated by several types of cytokines in the tumor microenvironment, such as vascular endothelial growth factor (VEGF) [12–16]. Studies have shown that VEGF receptor overexpression is correlated with poor prognosis in patients with sarcoma, which may benefit from antiangiogenic therapy [17, 18]. Anlotinib is an oral small-molecular receptor tyrosine kinase inhibitor that can play the role of an antiangiogenesis and proliferation inhibitor by targeting c-Kit, PDGFR-α, FGFR, and VEGFR. Basic research has confirmed that anlotinib inhibits tumor cell proliferation, migration, and TA in vitro and vivo through these pathways [19]. A phase IIb trial (ALTER0203) showed that anlotinib had an antitumor effect in patients with advanced STSs who failed in standard chemotherapy, and it has been approved in China for patients with alveolar soft part sarcomas (ASPSs), clear cell sarcomas, and STSs with failed anthracycline treatment [20]. In China, anlotinib has been used for some patients with sarcoma as a first-line therapy. National comprehensive cancer network (NCCN) guidelines 2021 recommended that TKIs (eg: pazopanib) could be used for advanced or metastatic sarcoma patients ineligible for IV systemic therapy as first-line therapy. Correlational studies about anlotinib-based regimen in patients with unresectable or metastatic BSTSs as first-line therapy were included in Chinese society of clinical oncology (CSCO) Guidelines 2022. And this guideline's views are as follows: For advanced BSTSs, not suitable for or unwilling to accept intensive chemotherapy, there are not any approved treatments, anlotinib-based regimen is an effective and safe treatment. Therefore, this study aimed to evaluate the real-world efficacy and safety of anlotinib-based regimen as a first-line therapy and explore its impact in patients with sarcoma. Materials and methods Clinical data Clinical data of patients with unresectable or metastatic BSTSs treated with chemotherapy combined with anlotinib or not as a first-line therapy at the First Affiliated Hospital of Zhengzhou University from January 2018 to September 2020 were collected and analyzed. The final follow-up date was September 30, 2022, and the median follow-up time was 46.0 months. Additional survival statistics would be obtained in the future. The following were the main inclusion criteria: (1) histologically proven BSTSs, (2) confirmed ineligibility for surgical treatment or other local treatments, (3) treatment with chemotherapy combined with anlotinib or not for at least two cycles, (4) at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and (5) an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients with sarcoma without follow-up data were excluded. Considering these criteria, data from 92 patients with BSTSs were included. The sample size which was computed by Two-Sample T-Text in PASS 15.0 was 81 individuals with a significance level of 5%. So 92 individuals included in this study were enough. Patient information on age, sex, ECOG performance status, surgical history, reduction of anlotinib, adverse reactions, metastasis or not, tumor location, and pathological subtypes was collected and analyzed. Treatment methods Anlotinib was provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., with a product lot number of National Drug Code H20180002. Treatment included oral administration of one tablet of 8–12 mg anlotinib taken once daily for 2 weeks and stopped for 1 week. The dose was adjusted according to patient tolerance. Anlotinib was continuously administered until intolerable toxic side reaction, progressive disease (PD), or death occurred. As a retrospective study, the chemotherapy regimen was determined by clinicians according to related guidelines. Whether patients received chemotherapy alone or chemotherapy combination anlotinib was decided by clinicians and patients' wishes. Outcome The treatment efficacy was evaluated using RECIST 1.1. Efficacy evaluation included complete response (CR), partial response (PR), stable disease (SD), or PD. The objective response rate (ORR) was the sum of CR and PR, and the disease control rate (DCR) was the sum of CR, PR, and SD. The median progression-free survival (mPFS) was the time from the start of antitumor therapy to PD or death due to any cause. Similarly, the median overall survival (mOS) was the time from the confirmed disease to the date of death from any cause. Patients who were event-free or were lost to follow-up were censored at the time of the last visit. Anlotinib-related adverse events (AEs) were recorded and assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Statistical methods Median (range) or number of patients (percentage) was used for quantitative variables. IBM SPSS Statistics for Windows, version 21.0 was implemented for statistical analyses. The chi-square test was performed for rate comparison, the Kaplan–Meier method for survival analysis, 95% confidence interval for mPFS and mOS, and the GraphPad Prism 5.0 (La Jolla, CA, USA) for survival curves. Survival time in different groups was compared using the log-rank test, and Cox regression was used for multivariate analysis. P -value < 0.05 was considered statistically significant. Results Baseline characteristics The baseline characteristics of all 92 patients are presented in Table I. The median age was 46 (range, 11–75) years. Male patients showed higher than female patients (male-to-female ratio, 1.8:1). The ECOG performance status of 84 participants (91.3%) was 0 or 1. The extremities (31.5%) were the most common site of sarcoma, followed by the retroperitoneal space (16.3%) and head and neck regions (13.0%). Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the main pathological subtypes. Of the participants, 55 (59.8%) had history of surgery. The percentage of anlotinib–chemotherapy combination was 51.1%, whereas that of chemotherapy alone was 48.9%. Baseline characteristics were well balanced between the two arms (see Table I for further information). Other treatments with a small number of patients such as local treatments, including radiotherapy or combination immunotherapy were excluded from this study. Short-term efficacy Treatment efficacy was evaluated in all participants. One1 patient showed CR, and 14 patients showed PR in the combination group, which had ORR and DCR of 31.9% and 85.1%, respectively. However, the only chemotherapy group had ORR and DCR of 6.7% and 57.8%, respectively. The ORR and DCR of anlotinib-based regimen were better ( p < 0.05) (Table II). Survival analysis At the time of follow-up visit, disease progression occurred in 59 patients (64.1%), and the overall mPFS was 6.0 months; 54 patients (58.7%) reached the end of the study, and the overall mOS was 25.0 months. The detailed univariate survival analysis results are shown in Table III and Fig. 1 . In our study, CS, fibrosarcoma (FS), leiomyosarcoma (LMS), undifferentiated pleiomorphic sarcoma (UPS), and ASPS indicated a more favorable prognosis than the others; therefore, the two groups were further categorized into good or poor histology. Tumor location, surgery history, adverse reactions, and metastasis or not showed no statistical differences in mPFS and mOS ( p > 0.05) using univariate analyses. 11–42 years, anlotinib–chemotherapy combination or good histology was a favorable factor for mPFS ( p < 0.05); however only the mPFS of anlotinib–chemotherapy combination or good histology transformed the mOS benefit ( p < 0.05). Compared with the control group, improvements in the mPFS and mOS were observed with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months) (the details are shown in Table III and Fig. 1 ). Multivariate analyses showed that age, sex, and the therapy method were independent prognostic factors for mPFS ( p < 0.05); however, mOS was affected by the pathological subtype only ( p < 0.05) (Table IV). Adverse events of anlotinib Regardless of grade, the main AEs of anlotinib included hypertension (39.1%), fatigue (29.3%), proteinuria (28.3%), hand–foot syndrome (26.1%), and ALT/AST elevation (21.7%). The incidence of grade 3 and above AEs of anlotinib was 4.3%, 4.3%, 3.3%, 3.3%, and 2.2% for hand–hand-foot syndrome, ALT/AST elevation, hypertension, proteinuria, and fatigue, respectively. Only two patients discontinued anlotinib treatment owing to intolerable AEs (proteinuria and hand–foot syndrome) (Table V). AEs were mainly grades I and II and were well tolerated. Furthermore, new anlotinib-related adverse reactions were not observed. Discussion Unresectable or metastatic BSTSs are mainly treated with systemic therapy, and single-agent or combination chemotherapy based on anthracyclines was the most common therapy. Owing to its low efficacy rate, chemotherapy is hard to cure. Owing to the low incidence rate and several pathological subtypes of sarcoma, a large clinical trial for a specific subtype is difficult to perform. Additionally, different pathological subtypes have different sensitivities to systemic therapies. For decades, with a deep understanding of tumor pathogenesis and the prevalence of genetic testing, molecular targeted therapy is rapidly evolving for several tumor types, including BSTSs [21]. In recent years, anti-angiogenesis–targeted therapies have unlocked several achievements in sarcoma. Anlotinib, a novel multi-targeting tyrosine, is a representative antiangiogenic agent [19]. Owing to various reasons, including poor physical condition, some patients following failure of first-line chemotherapy experience no therapeutic opportunities and poor tolerance of full-dose chemotherapy; in China, anlotinib was frequently used as the first-line therapy for BSTSs. Therefore, this study aimed to evaluate the real-world safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic BSTSs as the first-line therapy and explore better treatment plans and related prognostic factors. It was noted that patients with sarcomas treated with anlotinib-based regimen as the first-line therapy benefited with significantly longer survival, particularly for some histological subtypes (CS, FS, LMS, UPS, and ASPS). A previous study reported that anlotinib had an antitumor effect on patients with advanced refractory solid tumors, including STSs [22]. Subsequently, a multicenter phase II study (NCT01878448) [20]) was conducted to observe anlotinib’s antitumor effect on STSs. A total of 166 patients with STSs following failure of first-line chemotherapy with anthracyclines were included. Treatment included oral administration of one tablet of 8–12 mg anlotinib once daily for 2 weeks and stopped for 1 week. The results showed that the ORR, mPFS, and mOS were 13%, 5.6 months, and 12.0 months, respectively. In our study, the ORR, mPFS, and mOS of anlotinib combined with chemotherapy as the first-line therapy were 31.9%, 8.3 months, and 59.0 months, respectively, which were much better than those of the phase II study. Several studies have shown that the mPFS of patients with metastatic STSs who failed standard treatments was approximately 3–6 months, and the mOS was approximately 6–12 months [20]. Although anthracycline and ifosfamide remain the cornerstones of systemic first-line therapy, the mOS is only 12 months in patients with advanced BSTSs [23]. Furthermore, the AEs of anthracyclines particularly cardiotoxicity limit the effectiveness [24, 25]. The mPFS with pazopanib and regorafenib treatment as the second-line therapy and beyond was 4.6 and 4.0 months, respectively. These two agents demonstrated a significant improvement in PFS; however, OS was not better than that of the placebo [26, 27]. The survival benefit of anlotinib-based regimen as the first-line therapy in our study was longer than that in the aforementioned phase II data. These results suggest that patients with BSTSs have an increased survival benefit from anlotinib combined with standard treatment as the first-line therapy (Table III and Fig. 1 ). Multi-targeted anti-angiogenic therapy is a significant treatment for sarcomas and may be more effective when administered as early as possible. In the ALTER0203 clinical trial, patients aged > 40 years and females had much longer mPFS [28]. In our study, females showed a similar result; however, the mPFS was longer in participants aged 11–42 years, which was relevant to the study group. Several histological types of STSs showed high sensitivity to anlotinib-based regimen, including LMS, CS, FS, UPS, and ASPS, which had longer mPFS (18.0 vs. 5.0 months, p = 0.049) and mOS (NR vs. 24.0 months, p = 0.005) than other subtypes. Multiple factor analysis showed that the histological type was the only independent prognostic factor for mOS (Table IV). These findings are similar to those of the ALTER0203 trial [28]. The others showed no statistical differences in mPFS and mOS ( p > 0.05). In the present study, only eight patients had an ECOG performance status 2, and seven patients had reduced anlotinib levels; however, more data are needed to explore these effects. The number of patients included in our study was nearly twice as much than then Zhiyong Liu's study [29]. The treatment plan is different, our study is anlotinib combined chemotherapy versus chemotherapy alone, which was conformed to the actual situation; the plan of Zhiyong Liu's study was only anlotinib. Our statistical methods was more consummate and scientific with single-factor and multivariate analysis. And overall survival was also observed in our study. In our study, the treatment-related AEs of anlotinib were consistent with those of previous studies on anlotinib and other multi-kinase inhibitors [30, 31]. Although anlotinib was frequently used in combination with other antitumor agents, such as anthracyclines and platinum, our study indicated that it did not increase the occurrence of anlotinib-related AEs. This study had some limitations. First, there may have been a selection bias owing to the characteristics of a single-center retrospective study. Therefore, exploring the benefits of anlotinib therapy in patients with sarcoma using prospective clinical studies is necessary. Second, all participants in our study were from China, which may impact the universality to other races. Lastly, the sample size of 92 was small; however, sarcomas were an unusual kind of tumor. In conclusion, anlotinib-based regimen as the first-line therapy resulted in a favorable antitumor activity in short-term efficacy and survival in patients with unresectable or metastatic BSTSs. The AEs of anlotinib were minor and well tolerated, and the effect of anlotinib in specific sarcoma subtypes warrants further investigation. Declarations Funding This work was supported by the Key Scientific and Technological Project of Henan Province (212102310126), Key Scientific Research Project of Henan Province Education Department (21A320030), and National Natural Science Foundation of China (82102715). Acknowledgements Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author or first author on reasonable request. Authors' contributions Wei He and Lina Pang conceived and designed the experiments. Lina Pang, Shengli Zhang, Xiaoke Zhang, Liye Wang and Shuai Gong performed the experiments. Lina Pang and Shengli Zhang analyzed the data. Lina Pang and Wei He wrote the manuscript. All authors read and approved the manuscript and agree to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work are appropriately investigated and resolved. Ethical Approval The study was conducted in accordance with the principles of the Declaration of Helsinki, and the study protocol was approved by the ethics committee of the First Affiliated Hospital of Zhengzhou University. Because of the retrospective nature of the study, the Ethics Committee did not require written informed consent provided by participants. Informed consent was waived by the ethics committee of the First Affiliated Hospital of Zhengzhou University. Patient consent for publication Not applicable. Conflict of interest statement All authors (Lina Pang, Shengli Zhang, Liye Wang, Shuai Gong, Xiaoke Zhang and Wei He) declare no conflicts of interest. References Sbaraglia, M., E. Bellan, and A.P. Dei Tos, The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica, 2021. 113 (2): p. 70-84. Chi, Y., et al., Safety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients with Refractory Metastatic Soft-Tissue Sarcoma. Clin Cancer Res, 2018. 24 (21): p. 5233-5238. Yang, Z., et al., Incidence, distribution of histological subtypes and primary sites of soft tissue sarcoma in China. Cancer Biol Med, 2019. 16 (3): p. 565-574. Siegel, R.L., K.D. 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Characteristics N(%) Anlotinb + Chemotherapy(%) Chemotherapy alone(%) χ2 value value P Sex Male 59(64.1) 30(63.8) 29(64.4) 0.004 0.951 Female 33(35.9) 17(36.2) 16(35.6) Age(years) Median 46 41 43 Range 11–75 12–75 11–69 Average 42 41 38 11–42 40(43.5) 21(44.7) 19(42.2) 1.902 0.296 43–75 52(56.5) 26(55.3) 26(57.8) ECOG 0,1 84(91.3) 45(95.7) 39(86.7) 2.386 0.122 2 8(8.7) 2(4.3) 6(13.3) Tumor location Head and neck region 12(13.0) 4(8.5) 8(17.8) 4.593 0.204 Retroperitoneal space 15(16.3) 11(23.4) 4(8.9) Extremities 29(31.5) 14(29.8) 15(33.3) Others 36(39.1) 18(38.3) 18(40.0) Surgery history Yes 55(59.8) 27(57.4) 28(62.2) 0.218 0.641 No 37(40.2) 20(42.6) 17(37.8) Presence or absence of metastasis No 41(44.6) 25(53.2) 26(57.8) 0.196 0.658 Yes 51(55.4) 22(46.8) 19(42.2) Reduction of anlotinib Yes 7(7.6) 4(8.5) 3(6.7) 0.111 0.739 No 85(92.5) 43(91.5) 42(93.3) Adverse reaction Yes 68(73.9) 30(63.8) 38(84.4) 5.067 0.024 No 24(26.1) 17(36.2) 7(15.6) Histology OS 2(2.2) 1(2.1) 1(2.2) 17.971 0.303 CS 3(3.3) 2(4.3) 1(2.2) ES 8(8.7) 3(6.4) 5(11.1) SS 14(15.2) 6(12.8) 8(17.8) LMS 5(5.4) 5(10.6) 0(0) FS 6(6.5) 5(10.6) 1(2.2) UPS 3(3.3) 1(2.1) 2(4.4) LPS 12(13.0) 6(12.8) 6(13.4) ASPS 2(2.2) 2(4.3) 0(0) CCS 1(1.1) 0(0) 1(2.2) RMS 18(19.6) 7(14.9) 11(24.5) HSA 6(6.5) 4(8.5) 2(4.4) Others 12(13.0) 5(10.6) 7(15.6) (Osteosarcoma OS, Chondrosarcoma CS, Ewing‘s sarcoma ES, Synovial sarcoma SS, Leiomyosarcoma LMS, Fibrosarcoma FS, Undifferentiated pleomorphic sarcoma UPS, Liposarcoma LPS, Alveolar soft-part sarcoma ASPS, Clear cell sarcoma CCS, Rhabdomyosarcoma RMS, Haemangiosarcoma HAS) Table II. The objective response rate and disease control rate of patients in different groups. Anlotinb + Chemotherapy Chemotherapy alone χ2 value value P Cases (%) 47(51.1) 45(48.9) CR 1(2.1) 0(0) 0.968 0.325 PR 14(29.8) 3(6.7) 8.158 0.004 SD 25(53.2) 23(51.1) 0.040 0.842 PD 7(14.9) 19(42.2) 8.469 0.004 ORR(%) 15(31.9) 3(6.7) 9.312 0.002 DCR(%) 40(85.1) 26(57.8) 8.469 0.004 (Complete response CR, Partial response PR, Stable disease SD, Progressive disease PD, Objective response rate ORR, Disease control rate DCR) Table III. Univariate survival analysis. Characteristics Groups mPFS(m) 95%CI χ2 value value P mOS(m) 95%CI χ2 value value P Sex male 5.0 1.6–8.4 1.939 0.164 40.0 20.6–59.4 2.138 0.144 female 8.0 2.6–13.4 24.0 20.0–28.0 Age(years) 11–42 8.3 5.5–11.1 3.904 0.048 36.0 8.9–63.1 1.296 0.255 43–75 3.6 0.9–6.3 24.0 17.5–30.5 ECOG 0,1 7.0 4.6–9.4 1.832 0.176 25.0 16.8–33.2 0.035 0.853 2 2.5 NR-5.3 40.0 10.5–69.5 Tumor location Head and neck region 3.0 NR-6.9 1.122 0.772 22.0 13.4–30.6 0.880 0.830 Retroperitoneal space 6.0 NR-12.6 40.0 20.7–59.3 Extremities 6.0 0.6–11.4 48.0 25.1–70.9 Others 7.0 3.6–11.4 25.0 3.5–46.5 Therapy method Anlotinb + Chemotherapy 8.3 5.6–11.0 9.661 0.002 59.0 13.2-104.8 4.191 0.041 Chemotherapy alone 3.0 2.5–3.5 22.0 15.9–28.1 Surgery history Yes 6.0 2.9–9.1 0.010 0.921 40.0 18.2–61.8 2.628 0.105 No 7.0 1.8–12.1 21.0 13.1–28.9 Reduction of anlotinib Yes 18.0 2.4–33.6 0.732 0.392 NR NR 2.758 0.097 No 6.0 3.0-8.9 24.0 14.6–33.4 Adverse reaction Yes 7.0 3.2–10.8 0.001 0.976 25.0 10.8–39.2 0.032 0.859 No 6.0 1.3–10.7 31.0 4.0–58.0 Presence or absence of metastasis No 6.0 2.2–9.8 0.006 0.936 22.0 17.7–26.3 1.368 0.242 Yes 7.0 2.4–11.6 41.0 19.7–62.3 Histology Good histology 18.0 7.4–28.6 3.878 0.049 NR NR 7.889 0.005 Poor histology 5.0 2.2–7.8 24.0 19.7–28.3 CI, Confidence Interval; NR, Not Reached; P value less than 0.05 were shown in bold. Table IV. Cox regression analysis of progression-free survival and overall survival. Groups PFS OS p value HR 95%CI p value HR 95%CI Therapy method: Anlotinb + Chemotherapy vs Chemotherapy alone 0.011 0.463 0.256–0.835 0.195 0.648 0.337–1.248 ECOG:0,1 vs 2 0.489 1.399 0.541–3.622 0.599 1.296 0.494–3.398 Sex: Female vs Male 0.018 2.127 1.136–3.983 0.589 0.848 0.466–1.544 Age:11–42 vs 43-75years 0.024 0.507 0.281–0.914 0.351 0.764 0.434–1.345 Histology: Good histology vs Poor histology 0.056 0.486 0.232–1.019 0.017 0.313 0.121–0.814 Table V. Incidence of adverse reactions. Adverse reaction Any grade (%) Grade 3/4 (%) Fatigue 27(29.3) 2(2.2) Hand-foot syndrome 24(26.1) 4(4.3) Hypertension 36(39.1) 3(3.3) ALT/AST elevation 20(21.7) 4(4.3) Loss of appetite 18(19.6) 1(1.1) Proteinuria 26(28.3) 3(3.3) Hemorrhage 13(14.1) 2(2.2) Oral mucositis 11(12.0) 1(1.1) Hematological toxicity 5(5.4) 0(0) Thrombotic events 3(3.3) 1(1.1) Joint pain 2(2.2) 0(0) Poor wound healing 1(1.1) 0(0) Prolonged Q-T interval 0(0) 0(0) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3869541","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":269686714,"identity":"b0b9a5aa-1e81-47a0-a56b-e1d1b608b1ed","order_by":0,"name":"Lina Pang","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lina","middleName":"","lastName":"Pang","suffix":""},{"id":269686715,"identity":"b8f480f2-7056-4b52-8749-45c266d14066","order_by":1,"name":"Shengli Zhang","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shengli","middleName":"","lastName":"Zhang","suffix":""},{"id":269686716,"identity":"9e0607d1-906a-440b-a4a1-1ffe0229590f","order_by":2,"name":"Liye Wang","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liye","middleName":"","lastName":"Wang","suffix":""},{"id":269686717,"identity":"1a387476-62d3-42d2-970c-f3dabd7cc10c","order_by":3,"name":"Shuai Gong","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shuai","middleName":"","lastName":"Gong","suffix":""},{"id":269686718,"identity":"85828390-255f-4388-9fd3-ac744758bfdb","order_by":4,"name":"Xiaoke Zhang","email":"","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaoke","middleName":"","lastName":"Zhang","suffix":""},{"id":269686719,"identity":"6e554a2c-ab4e-4518-a6ad-7b1c9c2305ed","order_by":5,"name":"Wei He","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIiWNgGAWjYBACAxCR+M9Gjh/CZyZSSwJbmrFkA0laGNgOJxocIFaLOXuP4YMHPMwJxuePP5NgqLBObGA/ewCvFsueM8YGCRJseWYHDqRJMJxJT2zgyUvA77AbudskEgx4is0ONhyTYGw7nNggwWOAX8v9t9t/JCRIJG5uZmyTYPxHjJYbvNsYEg4YJG5gY2aTYGwgRsuZ/M8SiQ0JxhJn2JgtEo6lG7fx5BDQcvxY4sefDf/l+PuPP7zxocZatp/9DH4tqCABiNlIUD8KRsEoGAWjAAcAAP8hRE3+9zfuAAAAAElFTkSuQmCC","orcid":"","institution":"the First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"He","suffix":""}],"badges":[],"createdAt":"2024-01-16 10:53:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3869541/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3869541/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50452886,"identity":"5be5e2be-d74b-4c04-b02c-dc6a40d82af5","added_by":"auto","created_at":"2024-01-31 17:52:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":683295,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Kaplan-Meier plot of progression-free survival (PFS) among different groups; (B) Kaplan-Meier plot of overall survival (OS) among different groups; (C) Kaplan-Meier plot of PFS among different ages; (D) Kaplan-Meier plot of OS among different ages; (E) Kaplan-Meier plot of PFS among different histology; (F) Kaplan-Meier plot of OS among different histology.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3869541/v1/13e721a70916ca7a150b59cb.jpg"},{"id":55265673,"identity":"39c4325d-9020-4327-85ad-8b2048c290ed","added_by":"auto","created_at":"2024-04-25 02:13:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":984912,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3869541/v1/0f13c400-c123-4a06-8194-abf86a296ad6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic bone and soft-tissue sarcomas: a retrospective institutional study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSarcomas, including bone and soft tissue sarcomas (BSTSs), are rare heterogeneous malignancies that originate from the mesenchyme and can occur in various tissues and organs throughout the body. Currently, there are \u0026gt;\u0026thinsp;70 histological subtypes, and different molecular subtypes may be identified in the future [1, 2]. Soft tissue sarcomas (STSs) account for approximately 1.0% of all human malignancies, with the annual rate of approximately 3\u0026ndash;5/100,000 globally [3, 4]. Osteosarcoma, chondrosarcoma (CS), and Ewing\u0026rsquo;s sarcoma are common bone sarcomas, with a person-year incidence of approximately 0.8 per 100,000 [5, 6]. To date, complete surgical resection remains the primary method for treatment; however, local recurrence or distant metastasis occurs following 30\u0026ndash;50% of surgeries [7]. The rate of advanced sarcomas in primary diagnosis is approximately 20%, and approximately 50% localized diseases develop metastases [8, 9]. Despite decades of bench and clinical research attempting to improve outcomes of unresectable or metastatic sarcomas, the 5-year overall survival rate remains unsatisfactory [10]. Anthracyclines remain the backbone of the standard treatment for advanced sarcomas; however, they have poor safety, limited efficacy, and a low remission rate [11]. Tumor occurrence and development are inseparable from tumor angiogenesis (TA), which is regulated by several types of cytokines in the tumor microenvironment, such as vascular endothelial growth factor (VEGF) [12\u0026ndash;16]. Studies have shown that VEGF receptor overexpression is correlated with poor prognosis in patients with sarcoma, which may benefit from antiangiogenic therapy [17, 18]. Anlotinib is an oral small-molecular receptor tyrosine kinase inhibitor that can play the role of an antiangiogenesis and proliferation inhibitor by targeting c-Kit, PDGFR-α, FGFR, and VEGFR. Basic research has confirmed that anlotinib inhibits tumor cell proliferation, migration, and TA in \u003cem\u003evitro\u003c/em\u003e and \u003cem\u003evivo\u003c/em\u003e through these pathways [19]. A phase IIb trial (ALTER0203) showed that anlotinib had an antitumor effect in patients with advanced STSs who failed in standard chemotherapy, and it has been approved in China for patients with alveolar soft part sarcomas (ASPSs), clear cell sarcomas, and STSs with failed anthracycline treatment [20]. In China, anlotinib has been used for some patients with sarcoma as a first-line therapy. National comprehensive cancer network (NCCN) guidelines 2021 recommended that TKIs (eg: pazopanib) could be used for advanced or metastatic sarcoma patients ineligible for IV systemic therapy as first-line therapy. Correlational studies about anlotinib-based regimen in patients with unresectable or metastatic BSTSs as first-line therapy were included in Chinese society of clinical oncology (CSCO) Guidelines 2022. And this guideline's views are as follows: For advanced BSTSs, not suitable for or unwilling to accept intensive chemotherapy, there are not any approved treatments, anlotinib-based regimen is an effective and safe treatment. Therefore, this study aimed to evaluate the real-world efficacy and safety of anlotinib-based regimen as a first-line therapy and explore its impact in patients with sarcoma.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eClinical data\u003c/h2\u003e \u003cp\u003eClinical data of patients with unresectable or metastatic BSTSs treated with chemotherapy combined with anlotinib or not as a first-line therapy at the First Affiliated Hospital of Zhengzhou University from January 2018 to September 2020 were collected and analyzed. The final follow-up date was September 30, 2022, and the median follow-up time was 46.0 months. Additional survival statistics would be obtained in the future. The following were the main inclusion criteria: (1) histologically proven BSTSs, (2) confirmed ineligibility for surgical treatment or other local treatments, (3) treatment with chemotherapy combined with anlotinib or not for at least two cycles, (4) at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and (5) an Eastern Cooperative Oncology Group (ECOG) performance status of 0\u0026ndash;2. Patients with sarcoma without follow-up data were excluded. Considering these criteria, data from 92 patients with BSTSs were included. The sample size which was computed by Two-Sample T-Text in PASS 15.0 was 81 individuals with a significance level of 5%. So 92 individuals included in this study were enough. Patient information on age, sex, ECOG performance status, surgical history, reduction of anlotinib, adverse reactions, metastasis or not, tumor location, and pathological subtypes was collected and analyzed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eTreatment methods\u003c/h2\u003e \u003cp\u003eAnlotinib was provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd., with a product lot number of National Drug Code H20180002. Treatment included oral administration of one tablet of 8\u0026ndash;12 mg anlotinib taken once daily for 2 weeks and stopped for 1 week. The dose was adjusted according to patient tolerance. Anlotinib was continuously administered until intolerable toxic side reaction, progressive disease (PD), or death occurred. As a retrospective study, the chemotherapy regimen was determined by clinicians according to related guidelines. Whether patients received chemotherapy alone or chemotherapy combination anlotinib was decided by clinicians and patients' wishes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcome\u003c/h2\u003e \u003cp\u003eThe treatment efficacy was evaluated using RECIST 1.1. Efficacy evaluation included complete response (CR), partial response (PR), stable disease (SD), or PD. The objective response rate (ORR) was the sum of CR and PR, and the disease control rate (DCR) was the sum of CR, PR, and SD. The median progression-free survival (mPFS) was the time from the start of antitumor therapy to PD or death due to any cause. Similarly, the median overall survival (mOS) was the time from the confirmed disease to the date of death from any cause. Patients who were event-free or were lost to follow-up were censored at the time of the last visit. Anlotinib-related adverse events (AEs) were recorded and assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical methods\u003c/h2\u003e \u003cp\u003eMedian (range) or number of patients (percentage) was used for quantitative variables. IBM SPSS Statistics for Windows, version 21.0 was implemented for statistical analyses. The chi-square test was performed for rate comparison, the Kaplan\u0026ndash;Meier method for survival analysis, 95% confidence interval for mPFS and mOS, and the GraphPad Prism 5.0 (La Jolla, CA, USA) for survival curves. Survival time in different groups was compared using the log-rank test, and Cox regression was used for multivariate analysis. \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics\u003c/h2\u003e \u003cp\u003eThe baseline characteristics of all 92 patients are presented in Table I. The median age was 46 (range, 11\u0026ndash;75) years. Male patients showed higher than female patients (male-to-female ratio, 1.8:1). The ECOG performance status of 84 participants (91.3%) was 0 or 1. The extremities (31.5%) were the most common site of sarcoma, followed by the retroperitoneal space (16.3%) and head and neck regions (13.0%). Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the main pathological subtypes. Of the participants, 55 (59.8%) had history of surgery. The percentage of anlotinib\u0026ndash;chemotherapy combination was 51.1%, whereas that of chemotherapy alone was 48.9%. Baseline characteristics were well balanced between the two arms (see Table I for further information). Other treatments with a small number of patients such as local treatments, including radiotherapy or combination immunotherapy were excluded from this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eShort-term efficacy\u003c/h2\u003e \u003cp\u003eTreatment efficacy was evaluated in all participants. One1 patient showed CR, and 14 patients showed PR in the combination group, which had ORR and DCR of 31.9% and 85.1%, respectively. However, the only chemotherapy group had ORR and DCR of 6.7% and 57.8%, respectively. The ORR and DCR of anlotinib-based regimen were better (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table II).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eSurvival analysis\u003c/h2\u003e \u003cp\u003eAt the time of follow-up visit, disease progression occurred in 59 patients (64.1%), and the overall mPFS was 6.0 months; 54 patients (58.7%) reached the end of the study, and the overall mOS was 25.0 months. The detailed univariate survival analysis results are shown in Table III and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In our study, CS, fibrosarcoma (FS), leiomyosarcoma (LMS), undifferentiated pleiomorphic sarcoma (UPS), and ASPS indicated a more favorable prognosis than the others; therefore, the two groups were further categorized into good or poor histology. Tumor location, surgery history, adverse reactions, and metastasis or not showed no statistical differences in mPFS and mOS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) using univariate analyses. 11\u0026ndash;42 years, anlotinib\u0026ndash;chemotherapy combination or good histology was a favorable factor for mPFS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05); however only the mPFS of anlotinib\u0026ndash;chemotherapy combination or good histology transformed the mOS benefit (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with the control group, improvements in the mPFS and mOS were observed with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months) (the details are shown in Table III and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMultivariate analyses showed that age, sex, and the therapy method were independent prognostic factors for mPFS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05); however, mOS was affected by the pathological subtype only (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table IV).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events of anlotinib\u003c/h2\u003e \u003cp\u003eRegardless of grade, the main AEs of anlotinib included hypertension (39.1%), fatigue (29.3%), proteinuria (28.3%), hand\u0026ndash;foot syndrome (26.1%), and ALT/AST elevation (21.7%). The incidence of grade 3 and above AEs of anlotinib was 4.3%, 4.3%, 3.3%, 3.3%, and 2.2% for hand\u0026ndash;hand-foot syndrome, ALT/AST elevation, hypertension, proteinuria, and fatigue, respectively. Only two patients discontinued anlotinib treatment owing to intolerable AEs (proteinuria and hand\u0026ndash;foot syndrome) (Table V). AEs were mainly grades I and II and were well tolerated. Furthermore, new anlotinib-related adverse reactions were not observed.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eUnresectable or metastatic BSTSs are mainly treated with systemic therapy, and single-agent or combination chemotherapy based on anthracyclines was the most common therapy. Owing to its low efficacy rate, chemotherapy is hard to cure. Owing to the low incidence rate and several pathological subtypes of sarcoma, a large clinical trial for a specific subtype is difficult to perform. Additionally, different pathological subtypes have different sensitivities to systemic therapies. For decades, with a deep understanding of tumor pathogenesis and the prevalence of genetic testing, molecular targeted therapy is rapidly evolving for several tumor types, including BSTSs [21]. In recent years, anti-angiogenesis\u0026ndash;targeted therapies have unlocked several achievements in sarcoma. Anlotinib, a novel multi-targeting tyrosine, is a representative antiangiogenic agent [19]. Owing to various reasons, including poor physical condition, some patients following failure of first-line chemotherapy experience no therapeutic opportunities and poor tolerance of full-dose chemotherapy; in China, anlotinib was frequently used as the first-line therapy for BSTSs. Therefore, this study aimed to evaluate the real-world safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic BSTSs as the first-line therapy and explore better treatment plans and related prognostic factors. It was noted that patients with sarcomas treated with anlotinib-based regimen as the first-line therapy benefited with significantly longer survival, particularly for some histological subtypes (CS, FS, LMS, UPS, and ASPS).\u003c/p\u003e\n\u003cp\u003eA previous study reported that anlotinib had an antitumor effect on patients with advanced refractory solid tumors, including STSs [22]. Subsequently, a multicenter phase II study (NCT01878448) [20]) was conducted to observe anlotinib\u0026rsquo;s antitumor effect on STSs. A total of 166 patients with STSs following failure of first-line chemotherapy with anthracyclines were included. Treatment included oral administration of one tablet of 8\u0026ndash;12 mg anlotinib once daily for 2 weeks and stopped for 1 week. The results showed that the ORR, mPFS, and mOS were 13%, 5.6 months, and 12.0 months, respectively. In our study, the ORR, mPFS, and mOS of anlotinib combined with chemotherapy as the first-line therapy were 31.9%, 8.3 months, and 59.0 months, respectively, which were much better than those of the phase II study.\u003c/p\u003e\n\u003cp\u003eSeveral studies have shown that the mPFS of patients with metastatic STSs who failed standard treatments was approximately 3\u0026ndash;6 months, and the mOS was approximately 6\u0026ndash;12 months [20]. Although anthracycline and ifosfamide remain the cornerstones of systemic first-line therapy, the mOS is only 12 months in patients with advanced BSTSs [23]. Furthermore, the AEs of anthracyclines particularly cardiotoxicity limit the effectiveness [24, 25]. The mPFS with pazopanib and regorafenib treatment as the second-line therapy and beyond was 4.6 and 4.0 months, respectively. These two agents demonstrated a significant improvement in PFS; however, OS was not better than that of the placebo [26, 27]. The survival benefit of anlotinib-based regimen as the first-line therapy in our study was longer than that in the aforementioned phase II data. These results suggest that patients with BSTSs have an increased survival benefit from anlotinib combined with standard treatment as the first-line therapy (Table III and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Multi-targeted anti-angiogenic therapy is a significant treatment for sarcomas and may be more effective when administered as early as possible.\u003c/p\u003e\n\u003cp\u003eIn the ALTER0203 clinical trial, patients aged\u0026thinsp;\u0026gt;\u0026thinsp;40 years and females had much longer mPFS [28]. In our study, females showed a similar result; however, the mPFS was longer in participants aged 11\u0026ndash;42 years, which was relevant to the study group. Several histological types of STSs showed high sensitivity to anlotinib-based regimen, including LMS, CS, FS, UPS, and ASPS, which had longer mPFS (18.0 vs. 5.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049) and mOS (NR vs. 24.0 months, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) than other subtypes. Multiple factor analysis showed that the histological type was the only independent prognostic factor for mOS (Table IV). These findings are similar to those of the ALTER0203 trial [28]. The others showed no statistical differences in mPFS and mOS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the present study, only eight patients had an ECOG performance status 2, and seven patients had reduced anlotinib levels; however, more data are needed to explore these effects. The number of patients included in our study was nearly twice as much than then Zhiyong Liu\u0026apos;s study [29]. The treatment plan is different, our study is anlotinib combined chemotherapy versus chemotherapy alone, which was conformed to the actual situation; the plan of Zhiyong Liu\u0026apos;s study was only anlotinib. Our statistical methods was more consummate and scientific with single-factor and multivariate analysis. And overall survival was also observed in our study.\u003c/p\u003e\n\u003cp\u003eIn our study, the treatment-related AEs of anlotinib were consistent with those of previous studies on anlotinib and other multi-kinase inhibitors [30, 31]. Although anlotinib was frequently used in combination with other antitumor agents, such as anthracyclines and platinum, our study indicated that it did not increase the occurrence of anlotinib-related AEs.\u003c/p\u003e\n\u003cp\u003eThis study had some limitations. First, there may have been a selection bias owing to the characteristics of a single-center retrospective study. Therefore, exploring the benefits of anlotinib therapy in patients with sarcoma using prospective clinical studies is necessary. Second, all participants in our study were from China, which may impact the universality to other races. Lastly, the sample size of 92 was small; however, sarcomas were an unusual kind of tumor.\u003c/p\u003e\n\u003cp\u003eIn conclusion, anlotinib-based regimen as the first-line therapy resulted in a favorable antitumor activity in short-term efficacy and survival in patients with unresectable or metastatic BSTSs. The AEs of anlotinib were minor and well tolerated, and the effect of anlotinib in specific sarcoma subtypes warrants further investigation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Key Scientific and Technological Project of Henan Province (212102310126), Key Scientific Research Project of Henan Province Education Department (21A320030), and National Natural Science Foundation of China (82102715).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author or first author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWei He and Lina Pang conceived and designed the experiments. Lina Pang, Shengli Zhang, Xiaoke Zhang, Liye Wang and Shuai Gong performed the experiments. Lina Pang and Shengli Zhang analyzed the data. Lina Pang and Wei He wrote the manuscript. All authors read and approved the manuscript and agree to be accountable for all aspects of the research in ensuring that the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the principles of the Declaration of Helsinki, and the study protocol was approved by the ethics committee of the First Affiliated Hospital of Zhengzhou University. Because of the retrospective nature of the study, the Ethics Committee did not require written informed consent provided by participants. Informed consent was waived by the ethics committee of the First Affiliated Hospital of Zhengzhou University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors (Lina Pang, Shengli Zhang, Liye Wang, Shuai Gong, Xiaoke Zhang and Wei He) declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSbaraglia, M., E. Bellan, and A.P. Dei Tos, \u003cem\u003eThe 2020 WHO Classification of Soft Tissue Tumours: news and perspectives.\u003c/em\u003e Pathologica, 2021. \u003cstrong\u003e113\u003c/strong\u003e(2): p. 70-84.\u003c/li\u003e\n\u003cli\u003eChi, Y., et al., \u003cem\u003eSafety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients with Refractory Metastatic Soft-Tissue Sarcoma.\u003c/em\u003e Clin Cancer Res, 2018. \u003cstrong\u003e24\u003c/strong\u003e(21): p. 5233-5238.\u003c/li\u003e\n\u003cli\u003eYang, Z., et al., \u003cem\u003eIncidence, distribution of histological subtypes and primary sites of soft tissue sarcoma in China.\u003c/em\u003e Cancer Biol Med, 2019. \u003cstrong\u003e16\u003c/strong\u003e(3): p. 565-574.\u003c/li\u003e\n\u003cli\u003eSiegel, R.L., K.D. Miller, and A. Jemal, \u003cem\u003eCancer statistics, 2018.\u003c/em\u003e CA Cancer J Clin, 2018. \u003cstrong\u003e68\u003c/strong\u003e(1): p. 7-30.\u003c/li\u003e\n\u003cli\u003eWhelan, J. and L. 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Oncology, 2016. \u003cstrong\u003e17\u003c/strong\u003e(12): p. 1732-1742.\u003c/li\u003e\n\u003cli\u003eZhang, R., et al., \u003cem\u003eThe real-world clinical outcomes and treatment patterns of patients with unresectable locally advanced or metastatic soft tissue sarcoma treated with anlotinib in the post-ALTER0203 trial era.\u003c/em\u003e Cancer medicine, 2022. \u003cstrong\u003e11\u003c/strong\u003e(11): p. 2271-2283.\u003c/li\u003e\n\u003cli\u003eLiu, Z., et al., \u003cem\u003eEfficacy and safety of anlotinib in patients with unresectable or metastatic bone sarcoma: A retrospective multiple institution study.\u003c/em\u003e Cancer Med, 2021. \u003cstrong\u003e10\u003c/strong\u003e(21): p. 7593-7600.\u003c/li\u003e\n\u003cli\u003eColosia, A., et al., \u003cem\u003eA Systematic Literature Review of Adverse Events Associated with Systemic Treatments Used in Advanced Soft Tissue Sarcoma.\u003c/em\u003e Sarcoma, 2016. \u003cstrong\u003e2016\u003c/strong\u003e: p. 3597609.\u003c/li\u003e\n\u003cli\u003eLi, J., B. Han, and H. Liu, \u003cem\u003eOutcomes of Anlotinib Maintenance Therapy in Patients With Advanced NSCLC in a Real-World Setting.\u003c/em\u003e Frontiers in oncology, 2022. \u003cstrong\u003e12\u003c/strong\u003e: p. 785865.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable I. The baseline characteristics of all 92 patients.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eN(%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAnlotinb\u0026thinsp;+\u0026thinsp;Chemotherapy(%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eChemotherapy alone(%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026chi;2 value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003evalue \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59(64.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30(63.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29(64.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.951\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33(35.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17(36.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16(35.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMedian\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u0026ndash;75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12\u0026ndash;75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u0026ndash;69\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAverage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u0026ndash;42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40(43.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21(44.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19(42.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.902\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.296\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43\u0026ndash;75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52(56.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26(55.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26(57.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECOG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e84(91.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45(95.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39(86.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.386\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.122\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8(8.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6(13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTumor location\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHead and neck region\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12(13.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8(17.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.593\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.204\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetroperitoneal space\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15(16.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11(23.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(8.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eExtremities\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29(31.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14(29.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15(33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOthers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36(39.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18(38.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18(40.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery history\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55(59.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27(57.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28(62.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.218\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.641\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37(40.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20(42.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17(37.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePresence or absence of metastasis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41(44.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25(53.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26(57.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.196\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.658\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51(55.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22(46.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19(42.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eReduction of anlotinib\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7(7.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.111\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.739\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e85(92.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43(91.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42(93.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAdverse reaction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e68(73.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30(63.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38(84.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5.067\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.024\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24(26.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17(36.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7(15.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistology\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e17.971\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.303\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(3.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eES\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8(8.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(6.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5(11.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14(15.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6(12.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8(17.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5(5.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5(10.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6(6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5(10.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUPS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(3.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(4.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLPS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12(13.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6(12.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6(13.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eASPS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCCS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRMS\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18(19.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7(14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11(24.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6(6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(8.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(4.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOthers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12(13.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5(10.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7(15.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e(Osteosarcoma OS, Chondrosarcoma CS, Ewing\u0026lsquo;s sarcoma ES, Synovial sarcoma SS, Leiomyosarcoma LMS, Fibrosarcoma FS, Undifferentiated pleomorphic sarcoma UPS, Liposarcoma LPS, Alveolar soft-part sarcoma ASPS, Clear cell sarcoma CCS, Rhabdomyosarcoma RMS, Haemangiosarcoma HAS)\u003c/p\u003e\n\u003cp\u003eTable II. The objective response rate and disease control rate of patients in different groups.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabb\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAnlotinb\u0026thinsp;+\u0026thinsp;Chemotherapy\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eChemotherapy alone\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026chi;2 value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003evalue \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCases (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e47(51.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45(48.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1(2.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.968\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.325\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e14(29.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.158\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25(53.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23(51.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.040\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.842\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7(14.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19(42.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.469\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eORR(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e15(31.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.312\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDCR(%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40(85.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26(57.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.469\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e(Complete response CR, Partial response PR, Stable disease SD, Progressive disease PD, Objective response rate ORR, Disease control rate DCR)\u003c/p\u003e\n\u003cp\u003eTable III. Univariate survival analysis.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabc\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGroups\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003emPFS(m)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95%CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026chi;2 value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003evalue \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003emOS(m)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95%CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026chi;2 value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003evalue \u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003emale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.6\u0026ndash;8.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.939\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.164\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.6\u0026ndash;59.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.138\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.144\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003efemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.6\u0026ndash;13.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.0\u0026ndash;28.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge(years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u0026ndash;42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.5\u0026ndash;11.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.904\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.9\u0026ndash;63.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.296\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.255\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43\u0026ndash;75\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.9\u0026ndash;6.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.5\u0026ndash;30.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECOG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0,1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.6\u0026ndash;9.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.832\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.176\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16.8\u0026ndash;33.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.035\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.853\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR-5.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.5\u0026ndash;69.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTumor location\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHead and neck region\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR-6.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.122\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.772\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.4\u0026ndash;30.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.880\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.830\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRetroperitoneal space\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR-12.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20.7\u0026ndash;59.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eExtremities\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.6\u0026ndash;11.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.1\u0026ndash;70.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOthers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.6\u0026ndash;11.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.5\u0026ndash;46.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTherapy method\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnlotinb\u0026thinsp;+\u0026thinsp;Chemotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.6\u0026ndash;11.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.661\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.2-104.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.191\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.041\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChemotherapy alone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.5\u0026ndash;3.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.9\u0026ndash;28.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery history\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.9\u0026ndash;9.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.921\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.2\u0026ndash;61.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.628\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.105\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.8\u0026ndash;12.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13.1\u0026ndash;28.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eReduction of anlotinib\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4\u0026ndash;33.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.732\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.392\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.758\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.097\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.0-8.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.6\u0026ndash;33.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAdverse reaction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.2\u0026ndash;10.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.976\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.8\u0026ndash;39.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.032\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.859\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.3\u0026ndash;10.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.0\u0026ndash;58.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePresence or absence of metastasis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.2\u0026ndash;9.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.936\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.7\u0026ndash;26.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.368\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.242\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.4\u0026ndash;11.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e41.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.7\u0026ndash;62.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistology\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGood histology\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.4\u0026ndash;28.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.878\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.889\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePoor histology\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.2\u0026ndash;7.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.7\u0026ndash;28.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"10\" align=\"left\"\u003e\n\u003cp\u003eCI, Confidence Interval; NR, Not Reached; \u003cem\u003eP\u003c/em\u003e value less than 0.05 were shown in bold.\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable IV. Cox regression analysis of progression-free survival and overall survival.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabd\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGroups\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003ePFS\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eOS\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95%CI\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e95%CI\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTherapy method: Anlotinb\u0026thinsp;+\u0026thinsp;Chemotherapy vs Chemotherapy alone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.463\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.256\u0026ndash;0.835\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.195\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.648\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.337\u0026ndash;1.248\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eECOG:0,1 vs 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.489\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.399\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.541\u0026ndash;3.622\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.599\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.296\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.494\u0026ndash;3.398\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex: Female vs Male\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.127\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.136\u0026ndash;3.983\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.589\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.848\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.466\u0026ndash;1.544\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge:11\u0026ndash;42 vs 43-75years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.507\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.281\u0026ndash;0.914\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.351\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.764\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.434\u0026ndash;1.345\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHistology: Good histology vs Poor histology\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.056\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.486\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.232\u0026ndash;1.019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.313\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.121\u0026ndash;0.814\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable V. Incidence of adverse reactions.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabe\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAdverse reaction\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAny grade (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eGrade 3/4 (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFatigue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27(29.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHand-foot syndrome\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24(26.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36(39.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(3.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT/AST elevation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20(21.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4(4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLoss of appetite\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18(19.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProteinuria\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26(28.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(3.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemorrhage\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13(14.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOral mucositis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11(12.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHematological toxicity\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5(5.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eThrombotic events\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3(3.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJoint pain\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2(2.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePoor wound healing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1(1.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eProlonged Q-T interval\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0(0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Bone and soft tissue sarcoma, Anlotinib, Prognosis, Efficacy, Adverse event","lastPublishedDoi":"10.21203/rs.3.rs-3869541/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3869541/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis retrospective institutional study analyzed the safety and efficacy of anlotinib-chemotherapy combination as a first-line therapy in patients with unresectable or metastatic bone and soft tissue sarcomas (BSTSs). The clinical data of 92 patients with sarcoma treated with chemotherapy combined with or without anlotinib at the First Affiliated Hospital of Zhengzhou University from January 2018 to September 2020 were collected and analyzed. To determine the short-term efficacy, the objective response rate (ORR) and disease control rate (DCR) were analyzed. Long-term survival was assessed using the Kaplan\u0026ndash;Meier method, including median progression-free survival (mPFS) and overall survival (mOS). Liposarcoma, synovial sarcoma, and rhabdomyosarcoma were the primary pathological subtypes of the 92 patients. The median patients\u0026rsquo; age was 46 (range, 11\u0026ndash;75) years. The ORR and DCR of the anlotinib\u0026ndash;chemotherapy combination used as first-line therapy were 31.9% and 85.1%, respectively. However, the ORR and DCR were only 6.7% and 57.8% in the chemotherapy alone (the control group), respectively. Compared with the control group, improvements were observed in the mPFS and mOS with anlotinib-based regimen (mPFS, 8.3 vs. 3.0 months; mOS, 59.0 vs. 22.0 months). Anlotinib-associated adverse events were well tolerated and mainly occurred in grades I and II. New anlotinib-related adverse reactions were not noted. Anlotinib-based regimen as a first-line therapy showed a positive effect on the treatment of unresectable or metastatic BSTSs. The anlotinib-associated adverse events were minor and well tolerated.\u003c/p\u003e","manuscriptTitle":"Safety and efficacy of anlotinib-based regimen in patients with unresectable or metastatic bone and soft-tissue sarcomas: a retrospective institutional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-31 17:52:54","doi":"10.21203/rs.3.rs-3869541/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"94f587f3-ef80-4bfb-ad55-f1f36f8c605d","owner":[],"postedDate":"January 31st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28410910,"name":"Health sciences/Oncology"},{"id":28410911,"name":"Health sciences/Oncology/Cancer"},{"id":28410912,"name":"Health sciences/Oncology/Cancer/Cancer therapy"},{"id":28410913,"name":"Health sciences/Oncology/Cancer/Cancer therapy/Targeted therapies"}],"tags":[],"updatedAt":"2024-04-30T03:08:56+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-31 17:52:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3869541","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3869541","identity":"rs-3869541","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}