1.四川省绵阳市中医医院 普通外科，四川 绵阳 621000;2.四川省绵阳市中心医院 2. 血管外科 3. 肿瘤科，四川 绵阳 621000
王晋， Email: email@example.com
1.Department of General Surgery, Mianyang Hospital of TCM, Mianyang, Sichuan 621000, China;2.Department of Vascular Surgery, 3. Department of Oncology, Mianyang Central Hospital, Mianyang, Sichuan 621000, China
背景与目的 腹膜后脂肪肉瘤是一种罕见的软组织肉瘤，其发病率低，预后差，治疗手段有限，不同病理学类型之间患者的预后差异较大，缺少针对该类患者的大样本临床研究证据，临床个体化治疗方案制定困难。本研究旨在探讨不同病理学类型腹膜后脂肪肉瘤患者预后的影响因素，并分别探讨手术、放射、化疗在他们中的应用价值。方法 从SEER数据库提取1975—2016年期间经病理学确诊且有完整随访记录的腹膜后脂肪肉瘤患者资料，根据纳入和排除标准严格筛选病例，依据ICD-O-3分为高分化脂肪肉瘤、去分化脂肪肉瘤、黏液样/圆细胞脂肪肉瘤、多形性脂肪肉瘤、混合脂肪肉瘤5类，比较不同病理学类型患者间肿瘤特异生存（CSS）和总生存（OS）的差异，并分析患者CSS与OS的影响因素。结果 共纳入2 296例腹膜后脂肪肉瘤患者，其中，高分化脂肪肉瘤917例，去分化脂肪肉瘤847例，黏液样/圆细胞脂肪肉瘤302例，多形性脂肪肉瘤135例，混合脂肪肉瘤95例。中位随访42个月（IQR：13~90个月）。估算的5年OS分别为高分化脂肪肉瘤74.99%（95% CI=71.65%~78.01%）、去分化脂肪肉瘤42.83%（95% CI=38.87%~46.73%）、黏液样/圆细胞脂肪肉瘤50.13%（95% CI=47.02%~58.86%）、多形性脂肪肉瘤34.69%（95% CI=26.39%~43.11%）、混合脂肪肉瘤57.67%（95% CI=46.43%~67.37%），Log-rank检验显示，组间差异有统计学意义（χ2=211.54，P<0.000 1）。估算的5年CSS分别为高分化脂肪肉瘤87.98%（95% CI=85.23%~90.25%）、去分化脂肪肉瘤57.78%（95% CI=50.46%~61.85%）、黏液样/圆细胞脂肪肉瘤64.99%（95% CI=58.64%~70.62%）、多形性脂肪肉瘤46.02%（95% CI=36.22%~55.25%）、混合脂肪肉瘤67.33%（95% CI=55.71%~76.53%），Log-rank检验显示，组间差异有统计学意义（χ2=227.92，P<0.000 1）。不同病理学类型Cox多因素分析显示，年龄是各病理学类型患者预后的独立影响因素（均P<0.05）。在高分化组脂肪肉瘤患者中，根治性和非根治性手术均能提高OS（根治性：HR=0.42，95% CI=0.19~0.92，P=0.031；非根治性：HR=0.40，95% CI=0.18~0.88，P=0.023）和CSS（根治性：HR=0.32，95% CI=0.16~0.63，P=0.001；非根治性：HR=0.23，95% CI=0.12~0.44，P=0.001）；化疗会降低患者的OS（HR=2.29，95% CI=1.54~3.40，P<0.001）和CSS（HR=3.55，95% CI=2.16~5.83，P<0.001）。在去分化脂肪肉瘤患者中，根治性和非根治性手术均能提高OS（根治性：HR=0.25，95% CI=0.18~0.35，P<0.001；非根治性：HR=0.34，95% CI=0.24~0.47，P<0.001）和CSS（根治性：HR=0.22，95% CI=0.15~0.33，P<0.001；非根治性：HR=0.31，95% CI=0.21~0.45，P<0.001）；放疗能提高CSS（HR=0.75，95% CI=0.57~0.99，P=0.043）；化疗会降低OS（HR=1.33，95% CI=1.05~1.69，P=0.018）和CSS（HR=1.64，95% CI=1.24~2.18，P=0.001）。放疗能提高黏液样/圆细胞脂肪肉瘤患者的OS（HR=0.66，95% CI=0.47~0.92，P=0.015）和CSS（HR=0.54，95% CI=0.34~0.84，P=0.007）。结论 年龄是影响不同病理学类型腹膜后脂肪肉瘤患者预后的独立危险因素。腹膜后脂肪肉瘤患者的治疗，应以病理学分类为导向制定个体化治疗方案。手术切除是高分化和去分化脂肪肉瘤最佳适应证。对于手术方式的选择，应综合评价患者全身情况。在高分化脂肪肉瘤患者中R0切除不是必须的，R1切除或者局部治疗（包括微波、射频等）也能达到提高患者OS和CSS的作用。而对于去分化脂肪肉瘤，则应争取达到R0切除。放疗是黏液样/圆形细胞脂肪肉瘤的最佳适应证，同时也是去分化脂肪肉瘤患者治疗手段的重要补充。在高分化和去分化病理学类型中，化疗会增加患者的死亡风险。
Background and Aims Retroperitoneal liposarcoma is a rare type of soft tissue sarcoma with low incidence, poor prognosis, and limited treatment options. The prognosis of patients with different pathological types is quite different, and there is a lack of large sample clinical research evidence for this group of patients. So, the clinical individualized treatment plan is difficult to establish. The purpose of this study was to explore the prognostic factors for patients with different pathological types of retroperitoneal liposarcoma, and to determine the application values of surgery, radiotherapy and chemotherapy for them.Methods The data of patients with retroperitoneal liposarcoma diagnosed by pathology and with complete follow-up record from 1975 to 2016 were retrieved from the SEER database, and the eligible cases were selected according to the inclusion and exclusion criteria. Using the ICD-O-3 classification, the patients were divided into five types that included well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid/round cell liposarcoma, pleomorphic liposarcoma and mixed liposarcoma. The differences of cancer-specific survival (CSS) and overall survival (OS) among patients with different pathological types were compared. The influencing factors for CSS and OS of the patients were analyzed.Results A total of 2 296 patients with retroperitoneal liposarcoma were included. Of them, 917 cases were well-differentiated liposarcoma, 847 cases were dedifferentiated liposarcoma, 302 cases were myxoid/round cell liposarcoma, 135 cases were pleomorphic liposarcoma and 95 cases were mixed liposarcoma. The median follow-up was 42 months (IQR: 13~90 months). The estimated 5-year OS were 74.99% (95% CI=71.65-78.01) for well-differentiated liposarcoma, 42.83% (95% CI=38.87-46.73) for dedifferentiated liposarcoma, 50.13% (95% CI=47.02-58.86) for myxoid/round cell liposarcoma, 34.69% (95% CI=26.39-43.11) for pleomorphic liposarcoma, and 57.67% (95% CI=46.43-67.37) for mixed liposarcoma, respectively. Log-rank test showed that difference was statistically significant among them (χ2=211.54, P<0.0001). The estimated 5-year CSS were 87.98% (95% CI=85.23-90.25) for well differentiated liposarcoma, 57.78% (95% CI=50.46-61.85) for dedifferentiated liposarcoma, 64.99% (95% CI=58.64-70.62) for myxoid/round cell liposarcoma, 46.02% (95% CI=36.22-55.25%) for pleomorphic liposarcoma, 67.33% (95% CI=55.71-76.53) for mixed liposarcoma, respectively. Log-rank test showed that the difference was statistically significant among them (χ2=227.92, P<0.000 1). Cox multivariate analysis of different pathological types showed that age was an independent factor affecting the prognosis of patients of all pathological types (all P<0.05). In well-differentiated liposarcoma patients, both radical and non-radical operation improved the OS (radical operation: HR=0.42, 95% CI=0.19-0.92, P=0.031; non-radical operation: HR=0.40, 95% CI=0.18-0.88, P=0.023) and CSS (radical operation: HR=0.32, 95% CI=0.16-0.63, P=0.001; non-radical operation: HR=0.23, 95% CI=0.12-0.44, P=0.001); chemotherapy reduced the OS (HR=2.29, 95% CI=1.54-3.40, P<0.001) and CSS (HR=3.55, 95% CI=2.16-5.83, P<0.001). In dedifferentiated liposarcoma patients, both radical and non-radical operation improved the OS (radical operation: HR=0.25, 95% CI=0.18-0.35, P<0.001, non-radical operation: HR=0.34, 95% CI=0.24-0.47, P<0.001) and CSS (radical operation: HR=0.22, 95% CI=0.15-0.33, P<0.001; non-radical operation: HR=0.31, 95% CI=0.21-0.45, P<0.001); radiotherapy improved the CSS (HR=0.75, 95% CI=0.57-0.99, P=0.043); chemotherapy reduced the OS (HR=1.33, 95% CI=1.05-1.69, P=0.018) and CSS (HR=1.64, 95% CI=1.24-2.18, P=0.001). Radiotherapy improved the OS (HR=0.66, 95% CI=0.47-0.92, P=0.015) and CSS (HR=0.54, 95% CI=0.34-0.84, P=0.007) in patients with myxoid/round cell liposarcoma.Conclusion Age is an independent risk factor affecting the prognosis of patients with different pathological types of retroperitoneal liposarcoma. For the treatment of retroperitoneal liposarcoma, individualized treatment should be made under the guidance of pathological classification. Surgical resection is the best treatment for well differentiated and dedifferentiated liposarcoma. For the choice of surgical methods, the general condition of the patients should be comprehensively evaluated. R0 resection is not necessary in patients with well-differentiated liposarcoma. R1 resection or local treatment (including microwave, radiofrequency, etc.) can also improve the OS and CSS in patients with well-differentiated liposarcoma. For dedifferentiated liposarcoma, R0 resection should be achieved. Radiotherapy is the best treatment for myxoid/round cell liposarcoma, and it is also an important supplement to the treatment of dedifferentiated liposarcoma. In well-differentiated and dedifferentiated pathological types, chemotherapy will increase the risk of death.