Evaluation of AJCC staging system and proposal of a novel stage grouping system in retroperitoneal liposarcoma: the Fudan Zhongshan experience.

Background: Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. Methods: The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. Results: A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Conclusion: Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.

Clinical and surgical effectiveness of the multi-disciplinary standardized management model in the treatment of retroperitoneal liposarcoma: Evidence-based clinical practice experience from Fudan Zhongshan.

BACKGROUND: To assess the correlation between clinical outcomes and diagnostic accuracy of evaluations carried out by a preoperative multidisciplinary team versus standard surgical care for patients with retroperitoneal liposarcoma undergoing surgery. METHODS: This comparative study was conducted retrospectively at a specialist assessment center within Zhongshan Hospital, Fudan University, China, between April 2011 and March 2021. Patients were assigned to a multidisciplinary team or nonmultidisciplinary team cohort based on referral to the multidisciplinary team. The primary outcome measured was long-term clinical prognosis, with other outcomes including diagnostic accuracy, 30-day reoperation, duration of stay, perioperative mortality, and medical complications. To mitigate selection bias, we conducted propensity-score matching. Uni- and multivariable Cox proportional hazard models were then used to evaluate the effect of multidisciplinary teams on postoperative survival. The previously specified questionnaire was used to measure the enhancement of awareness and treatment adherence facilitated by multidisciplinary team management. Data analysis was carried out between January 2023 and August 2023. RESULTS: Of the 521 records that were screened, 139 patients were deemed eligible for inclusion and defined as the multidisciplinary team cohort. At the same time, 382 patients without multidisciplinary team management were also included during that period and defined as the nonmultidisciplinary team cohort. The multidisciplinary team cohort exhibited lower numbers of primary retroperitoneal liposarcoma but a higher tumor grade and a greater proportion of R2 resection. After propensity-score matching, the 1-, 3-, and 5-year overall survival rates were 89.5%, 70.5%, and 62.9%, respectively, in the multidisciplinary team cohort, and 77.1%, 49.8%, and 45.1% in the nonmultidisciplinary team cohort. The diagnostic consistency of the multidisciplinary team group was significantly superior to that of the nonmultidisciplinary cohort (92.5% vs 83.6%, P = .042). Although no significant links were shown with duration of stay (P = .232) and 30-day reoperation (P = .447), the multidisciplinary team participation was linked to a substantial decrease in perioperative mortality (P = .036) and postoperative complications (P = .002). Additionally, the multidisciplinary team group indicated stronger illness awareness and postoperative adherence among individuals with retroperitoneal liposarcoma. CONCLUSION: The study's findings indicate that multidisciplinary team management could result in improved clinical outcomes, higher diagnostic accuracy, and reduced duration of postoperative stays, complications, and perioperative mortality. The intervention may also enhance disease awareness and postoperative compliance in retroperitoneal liposarcoma patients who undergo surgery. However, evidence quality was deemed low, and prospective studies with robust designs are required. Nonetheless, these results are worth considering.

Insight of a lipid metabolism prognostic model to identify immune landscape and potential target for retroperitoneal liposarcoma.

Introduction: The exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model. Methods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis. Results: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings. Discussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.