Explainable machine learning predicts survival of retroperitoneal liposarcoma: A study based on the SEER database and external validation in China.

OBJECTIVE: We have developed explainable machine learning models to predict the overall survival (OS) of retroperitoneal liposarcoma (RLPS) patients. This approach aims to enhance the explainability and transparency of our modeling results. METHODS: We collected clinicopathological information of RLPS patients from The Surveillance, Epidemiology, and End Results (SEER) database and allocated them into training and validation sets with a 7:3 ratio. Simultaneously, we obtained an external validation cohort from The First Affiliated Hospital of Naval Medical University (Shanghai, China). We performed LASSO regression and multivariate Cox proportional hazards analysis to identify relevant risk factors, which were then combined to develop six machine learning (ML) models: Cox proportional hazards model (Coxph), random survival forest (RSF), ranger, gradient boosting with component-wise linear models (GBM), decision trees, and boosting trees. The predictive performance of these ML models was evaluated using the concordance index (C-index), the integrated cumulative/dynamic area under the curve (AUC), and the integrated Brier score, as well as the Cox-Snell residual plot. We also used time-dependent variable importance, analysis of partial dependence survival plots, and the generation of aggregated survival SHapley Additive exPlanations (SurvSHAP) plots to provide a global explanation of the optimal model. Additionally, SurvSHAP (t) and survival local interpretable model-agnostic explanations (SurvLIME) plots were used to provide a local explanation of the optimal model. RESULTS: The final ML models are consisted of six factors: patient's age, gender, marital status, surgical history, as well as tumor's histopathological classification, histological grade, and SEER stage. Our prognostic model exhibits significant discriminative ability, particularly with the ranger model performing optimally. In the training set, validation set, and external validation set, the AUC for 1, 3, and 5 year OS are all above 0.83, and the integrated Brier scores are consistently below 0.15. The explainability analysis of the ranger model also indicates that histological grade, histopathological classification, and age are the most influential factors in predicting OS. CONCLUSIONS: The ranger ML prognostic model exhibits optimal performance and can be utilized to predict the OS of RLPS patients, offering valuable and crucial references for clinical physicians to make informed decisions in advance.

The effect of married status on cancer-specific mortality in nonmetastatic pelvic liposarcoma patients according to sex.

BACKGROUND: In nonmetastatic pelvic liposarcoma patients, it is unknown whether married status is associated with better cancer-control outcome defined as cancer-specific mortality (CSM). We addressed this knowledge gap and hypothesized that married status is associated with lower CSM rates in both male and female patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), nonmetastatic pelvic liposarcoma patients were identified. Kaplan-Meier plots and univariable and multivariable Cox regression models (CRMs) predicting CSM according to marital status were used in the overall cohort and in male and female subgroups. RESULTS: Of 1078 liposarcoma patients, 764 (71%) were male and 314 (29%) female. Of 764 male patients, 542 (71%) were married. Conversely, of 314 female patients, 192 (61%) were married. In the overall cohort, 5-year cancer-specific mortality-free survival (CSM-FS) rates were 89% for married versus 83% for unmarried patients (Δ = 6%). In multivariable CRMs, married status did not independently predict lower CSM (hazard ratio [HR]: 0.74, p = 0.06). In males, 5-year CSM-FS rates were 89% for married versus 86% for unmarried patients (Δ = 3%). In multivariable CRMs, married status did not independently predict lower CSM (HR: 0.85, p = 0.4). In females, 5-year CSM-FS rates were 88% for married versus 79% for unmarried patients (Δ = 9%). In multivariable CRMs, married status independently predicted lower CSM (HR: 0.58, p = 0.03). CONCLUSIONS: In nonmetastatic pelvic liposarcoma patients, married status independently predicted lower CSM only in female patients. In consequence, unmarried female patients should ideally require more assistance and more frequent follow-up than their married counterparts.

Surgically treated pelvic liposarcoma and leiomyosarcoma: The effect of tumor size on cancer-specific survival.

INTRODUCTION: In soft tissue pelvic liposarcoma and leiomyosarcoma, it is unknown whether a specific tumor size cut-off may help to better predict prognosis, defined as cancer-specific survival (CSS). We tested whether different tumor size cut-offs, could improve CSS prediction. MATERIALS AND METHODS: Surgically treated non-metastatic soft tissue pelvic sarcoma patients were identified (Surveillance, Epidemiology, and End Results 2004-2019). Kaplan-Meier plots, univariable and multivariable Cox-regression models and receiver operating characteristic-derived area under the curve (AUC) estimates were used. RESULTS: Overall, 672 (65 %) liposarcoma (median tumor size 11 cm, interquartile range [IQR] 7-16) and 367 (35 %) leiomyosarcoma (median tumor size 8 cm, IQR 5-12) patients were identified. The p-value derived ideal tumor size cut-off was 17.1 cm, in liposarcoma and 7.0 cm, in leiomyosarcoma. In liposarcoma, according to p-value derived cut-off, five-year CSS rates were 92 vs 83 % (≤17.1 vs > 17.1 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 83.8 to 86.8 % (Δ = 3 %). Similarly, among previously established cut-offs (5 vs 10 vs 15 cm), also 15 cm represented an independent predictor of CSS and improved prognostic ability from 83.8 to 87.0 % (Δ = 3.2 %). In leiomyosarcoma, according to p-value derived cut-off, five-year CSS rates were 86 vs 55 % (≤7.0 vs > 7.0 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 68.6 to 76.5 % (Δ = 7.9 %). CONCLUSIONS: In liposarcoma, the p-value derived tumor size cut-off was 17.1 cm vs 7.0 cm, in leiomyosarcoma. In both histologic subtypes, these cut-offs exhibited the optimal statistical characteristics (univariable, multivariable and AUC analyses). In liposarcoma, the 15 cm cut-off represented a valuable alternative.

Retroperitoneal sarcoma: a 10-year follow-up analysis using hospital-based cancer registry data in Japan.

OBJECTIVES: We sought clinical characteristics, survival outcomes, and prognostic factors for overall survival of retroperitoneal sarcoma in Japan. METHODS: A Japanese hospital-based cancer registry database with a pivotal 10-year follow-up was used to identify and enroll patients, registered from 106 institutions, diagnosed with retroperitoneal sarcoma in 2008-2009. Treating hospitals were divided by hospital care volume; high-volume hospitals and low-volume hospitals were defined as ≥ 4 and < 4 cases/year, respectively. RESULTS: A total of 91 men and 97 women were included, with a median age of 64 years. The most common histological type was liposarcoma in 101 patients, followed by leiomyosarcoma in 38 patients. The 5-year and 10-year overall survival rates were 44.1 and 28.3%. The majority of patients (n = 152, 80.9%) were treated at low-volume hospitals. High-volume hospital patients had higher 10-year overall survival rates than low-volume hospital patients (51.2% vs 23.2%, P = 0.026). Multivariate analysis revealed age over 60 years, treatment in low-volume hospitals and chemotherapy were independent predictors of unfavorable survival while treatment with surgery was an independent predictor of favorable survival. CONCLUSIONS: The possibility of surgical removal was suggested to be the most important prognostic factor for retroperitoneal sarcoma. Better survival was shown in patients treated at high-volume hospitals in our series.

Pronóstico y supervivencia de pacientes diagnosticados de liposarcoma retroperitoneal bien diferenciado y desdiferenciado / Prognosis and survival of patients diagnosed with well-differentiated and dedifferentiated retroperitoneal liposarcoma

Objetivos: El objetivo principal es determinar la supervivencia global y la supervivencia libre de enfermedad de pacientes intervenidos de liposarcoma retroperitoneal, comparándolos en función de los subtipos histológicos bien diferenciado y desdiferenciado. Los objetivos secundarios son analizar descriptivamente las características clínicas de estos pacientes e identificar otras variables independientes que puedan modificar significativamente estos perfiles de supervivencia.MétodosSe realiza un estudio observacional y analítico mediante una cohorte histórica retrospectiva, seguida prospectivamente. Los criterios de inclusión fueron: cirugía de liposarcoma de localización retroperitoneal, subtipos histológicos bien diferenciado y desdiferenciado, entre enero de 2002 y mayo de 2019. Se incluyeron un total de 32 pacientes. Se utilizó el estimador de Kaplan-Meier para resumir los datos y la prueba log-rank para el análisis comparativo.ResultadosLa supervivencia global a los 5 años fue del 59%. No se encontraron diferencias entre los pacientes con subtipo bien diferenciado con respecto al desdiferenciado (p=0,834). La supervivencia libre de enfermedad a los 2 años fue del 59% en los bien diferenciados y del 26% en los desdiferenciados, siendo estas diferencias estadísticamente significativas (p=0,005). Ninguna de las otras variables estudiadas modificó significativamente estos perfiles de supervivencia.ConclusionesLa supervivencia libre de enfermedad de los liposarcomas retroperitoneales desdiferenciados es significativamente menor que en los bien diferenciados, pero no puede afirmarse que haya diferencias en la supervivencia global (AU)

Objectives: The main objective is to establish the overall survival and disease-free survival profiles regarding the patients with retroperitoneal liposarcoma, making a comparison based on the well-differentiated and dedifferentiated histological subtypes. The secondary objectives are to descriptively analyze the clinical characteristics of said patients and to identify and analyze other independent variables that might modify these survival profiles significantly.MethodsAn observational and analytical study was performed using a retrospective historical cohort that was followed prospectively. The inclusion criteria consisted of: the procedure of liposarcoma located in the retroperitoneum, the well-differentiated and dedifferentiated histological subtypes, between January 2002 and May 2019. As a result, 32 patients took part in this study's sample. Kaplan–Meier estimator was used to summarize the results and log-rank test was used in the comparative analysis.ResultsThe overall survival at 5 years was around 59%. No differences were found between the patients with a well-differentiated subtype compared to the dedifferentiated ones (p=0.834). The disease-free survival at 2 years was 59% regarding the well-differentiated and 26% regarding the dedifferentiated, with these differences being statistically significant (p=0.005). None of the other studied variables modified these survival profiles significantly.ConclusionsDedifferentiated retroperitoneal liposarcomas show less disease-free survival than well-differentiated liposarcomas. However, regarding overall survival no differences can be claimed (AU)

Resection Status Does Not Impact Recurrence in Well-Differentiated Liposarcoma of the Extremity.

BACKGROUND: Well-differentiated liposarcoma (WDLPS) is a low-grade soft tissue sarcoma with a propensity for local recurrence. The necessity of obtaining microscopically free surgical margins (R0) to minimize local recurrence is not clear. This study evaluates recurrence-free survival (RFS) of extremity WDLPS in relation to resection margin status. METHODS: A retrospective review of adult patients with primary extremity WDLPS at seven US institutions from 2000 to 2016 was performed. Patients with recurrent tumors or incomplete resection (R2) were excluded. Clinicopathologic factors were analyzed to assess impact on local RFS. RESULTS: 97 patients with primary extremity WDLPS were identified. The majority of patients had deep, lower extremity tumors. Mean tumor size was 18.2±8.9cm. Patients were treated with either radical (76.3%) or excisional (23.7%) resections; 64% had R0 and 36% had microscopically positive (R1) resection margins. Ten patients received radiation therapy with no difference in receipt of radiation between R0 vs R1 groups. Thirteen patients (13%) developed a local recurrence with no difference in RFS between R0 vs R1 resection. Five-year RFS was 59.5% for R0 vs 85.2% for R1. Only one patient died of disease after developing dedifferentiation and distant metastasis despite originally having an R0 resection. DISCUSSION: In this large multi-institutional study of surgical resection of extremity WDLPS, microscopically positive margins were not associated with an increased risk of recurrence. Positive microscopic margin resection for extremity WDLPS may yield similar rates of local control while avoiding a radical approach to obtain microscopically negative margins.

Dedifferentiation within well-differentiated liposarcoma of the extremity or trunk: Implications for clinical management.

BACKGROUND: In extremity or trunk liposarcoma, the implications of a dedifferentiated (DD) component within a well-differentiated (WD) tumor are unclear. We evaluated outcomes after surgery and identified potential predictors of survival in these patients compared to those with an entirely WD tumor. METHODS: Retrospective data were collected for patients who underwent complete resection from 2009 to 2019. Cumulative incidences of local recurrence (LR) and distant metastasis (DM) were calculated, and overall survival (OS) was estimated. Associations between OS and clinicopathologic variables were evaluated by univariable models. RESULTS: A total of 210 patients with MDM2-verified tumors were studied, including 58 (27.6%) with DD. In primary disease, LR occurred only in DD and worse OS was observed versus WD (p < 0.001). In recurrent disease, the LR incidences were similar between WD and DD (p = 0.559); however, worse OS persisted in DD (p = 0.004). The incidence of DM was extremely low (3.8%) and limited to DD. Higher grade (p < 0.001) and DD size (p = 0.043), but not overall tumor size were associated with worse OS. CONCLUSIONS: In extremity or trunk liposarcoma, the presence of DD leads to significantly worse outcomes in both primary and recurrence diseases. Further study is needed to determine if these patients benefit from adjunct therapies (e.g., radiation).

Retroperitoneal Dedifferentiated Liposarcoma.

OBJECTIVES: We aimed to test the hypothesis that in retroperitoneal dedifferentiated liposarcoma (DDLS) the presence of the dedifferentiated (DD) component at the resection margin is associated with adverse outcome. METHODS: We retrospectively searched the archive for primary resections of retroperitoneal DDLS performed at our institution between 1990 and 2017. Slides were rereviewed for diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer grade, myogenic differentiation, and the presence of the well-differentiated (WD) or DD component at the resection margin. The medical records were reviewed for patient age, sex, tumor size, tumor focality, adjuvant/neoadjuvant therapy, local recurrence, distant metastases, local recurrence-free survival (LRFS), overall survival (OS), and follow-up duration. RESULTS: The presence of the DD component at the resection margin was associated with worse LRFS compared with cases without the DD component at the margin (P = .002). However, OS was not significantly affected (P = .11). CONCLUSIONS: LRFS is significantly shorter in cases with the DD component at the margin compared with cases without DD tumor at the margin, while there is no association with OS. We recommend reporting the presence or absence of DD tumor at the margin in retroperitoneal DDLS, as it adds meaningful prognostic information.

Pharmacotherapy for liposarcoma: current and emerging synthetic treatments.

Liposarcomas are rare tumors arising from adipocytic tissue and accounting for approximately 15-20% of all soft tissue sarcomas. Liposarcoma can be further classified into histopathological subtypes with variable chemosensitivity according to subtype. Decisions regarding management should be made on an individual basis, but surgery for localized disease and systemic chemotherapy remain the mainstay of treatment. Currently, only doxorubicin and trabectedin have robust Phase III data to support their use in the management of advanced liposarcoma. However, in the subgroup analysis of a Phase III trial comparing eribulin with dacarbazine, there was a greater than 7-month improvement in median overall survival in those treated with eribulin. There are also promising results from emerging studies in novel and targeted agents for the treatment of liposarcoma.

Survival analysis and treatment strategies for limb liposarcoma patients with metastasis at presentation.

ABSTRACT: Limited data exist on patients with limb liposarcoma (LLS) with metastasis at presentation Moreover, the potential prognostic factors of this patient population are poorly documented because of its rarity. Therefore, we conducted this study to evaluate the clinicopathologic characteristics and prognostic factors for patients with metastatic LLS.All patients with LLS with metastasis at presentation from 1975 to 2016 were identified by using the Surveillance, Epidemiology, and End Results (SEER) database. The following clinical data were derived from this clinical database: age, sex, histologic grade, subtype, size of tumor, surgery, radiotherapy, chemotherapy, vital status, cause of death, and survival duration. The Kaplan-Meier method was performed to calculate median survival time and draw survivorship curves. Cox-proportional hazards regression model was used to reveal the statistical independence between various variables.The present study collected 184 cases from SEER database for survival analysis. Mean age was 57.8 years with 63.6% (n = 117) men. The 3-year overall survival (OS) and cancer-specific survival (CSS) rates of this population were 27.8% and 30.1%, respectively. Univariate analysis revealed that age, tumor grade, and surgery were significantly correlated with survival. Sex and tumor size did not reach significant predictor status of survival. Multivariate analysis revealed that age at diagnosis <60, low tumor grade, and local surgery were significantly correlated with improved OS and CSS.Patients with LLS with metastasis at diagnosis experienced quite poor prognosis. Currently, surgery for the primary tumor significantly prolonged the survival of those patients, whereas chemotherapy and radiotherapy need to be further confirmed.

Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study.

BACKGROUND: Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Very few studies have presented data on pleomorphic liposarcoma specifically, often including a limited number of cases and short-term follow-up. As a result, the survivorship and prognostic characteristics of this tumor remain incompletely identified. STUDY DESIGN AND SETTING: Cross-sectional analysis of the Surveillance Epidemiology and End Results database (1996-2015). RESULTS: Overall survival for the entire series was 54% (95% confidence interval [CI], 49-58%) and 40% (95% CI, 35-45%) at 5 and 10 years, respectively. Disease-specific survival for the entire series was 60% (95% CI, 56-65%) and 53% (95% CI, 48-58%) at 5 and 10 years, respectively. Patients who survived 10 years or more were more likely to die of events unrelated to pleomorphic liposarcoma. Univariate and multivariate analysis demonstrated that not receiving cancer-directed surgery was an independent poor prognostic factor. Older age (≥ 65 years old) was associated with worse overall survival but not disease-specific survival. Tumor stage and radiotherapy showed different impact on survival depending on tumor size. In comparison to localized staged tumors, regional stage only predicts poor survival in patients with tumor size less than 5 cm, while distant stage is an independent worse prognosis factor. Radiotherapy only benefits patients with tumor size larger than 10 cm. These results were confirmed in competing risk analysis. CONCLUSION: Survival rates of patients with pleomorphic liposarcoma has not changed over the past 20 years. Patients with distant stage have poor prognosis; regional stage indicates worse survival in patients with tumor size less than 5 cm. Receiving surgery could prolong the survival, while radiotherapy only benefits patients with large tumor size (> 10 cm). Older age is associated with poor overall survival but not disease-specific survival. Routine patient surveillance following initial diagnosis should at least be 10 years for pleomorphic liposarcoma.

Liposarcoma in children and young adults: a clinicopathologic and molecular study of 23 cases in one of the largest institutions of China.

The incidence of pediatric liposarcoma is rare and most published cases lack systematic genetic analyses. We present clinicopathologic and genetic features of 23 liposarcomas aged <22 years. The study cohort comprised 10 males and 13 females (M:F=1:1.3) aged 11-21 years (median 17 years). The tumors predominantly occurred at the extremities (16/23; 69.6%), followed by the head/neck (2/23; 8.7%), chest (2/23; 8.7%), waist (2/23, 8.7%), and retroperitoneum (1/23; 4.3%). The tumor subtypes were sixteen myxoid liposarcoma (ML), one well-differentiated liposarcoma (WDL), two dedifferentiated liposarcoma (DDL), one pleomorphic liposarcoma (PL), and three myxoid pleomorphic liposarcoma (MPL) cases. Fluorescence in situ hybridization analysis identified MDM2/CDK4 amplification in all WDL/DDL cases (3/3; 100%) and DDIT3 rearrangement in all ML cases (13/13; 100%). Whole-exome sequencing indicated that one PL case and one MPL case exhibited RB1 loss. The two tested MPL cases had TP53 mutation and one of them harbored a TP53 germline mutation. Follow-up information was available for 20 patients (20/23; 87.0%) with a median follow-up duration of 42.5 months (range, 13-120 months). Three patients exhibited tumor progression (3/20;15.0%). Seventeen patients (17/20; 85.0%) survived with no evidence of disease. One MPL case (1/20; 5.0%) died of the disease. In conclusion, despite some overlaps, the occurrence, distribution of subtype, and prognosis of liposarcoma are overall different in children and adults. Most MLs and ALT/WDL/DDLs showed similar genetic aberrations with adult counterparts. Molecular features of MPL overlapped with those of conventional PL. The genetic characteristics including Tp53 status of MPL need further investigation.

The role of 18 F-FDG PET/CT in retroperitoneal sarcomas-A multicenter retrospective study.

BACKGROUND: The role of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) in the evaluation of retroperitoneal sarcomas is poorly defined. We evaluated the correlation of maximum standardized uptake value (SUVmax) with pathologic tumor grade in the surgical specimen of primary retroperitoneal dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). METHODS: Patients with the above histological subtypes in three participating institutions with preoperative 18 F-FDG PET/CT scan and histopathological specimen available for review were included. The association between SUVmax and pathological grade was assessed. Correlation between SUVmax and relapse-free survival (RFS) and overall survival (OS) were also studied. RESULTS: Of the total 58 patients, final pathological subtype was DDLPS in 44 (75.9%) patients and LMS in 14 (24.1%) patients. The mean SUVmax was 8.7 with a median 7.1 (range, 2.2-33.9). The tumors were graded I, II, III in 6 (10.3%), 35 (60.3%), and 17 (29.3%) patients, respectively. There was an association of higher histological grade with higher SUVmax (rs = 0.40, p = .002). Increasing SUVmax was associated with worse RFS (p = .003) and OS (p = .003). CONCLUSION: There is a correlation between SUVmax and pathologic tumor grade; increasing SUVmax was associated with worse OS and RFS, providing a preoperative noninvasive surrogate marker of tumor grade and biological behavior.

Histologic Subtype Defines the Risk and Kinetics of Recurrence and Death for Primary Extremity/Truncal Liposarcoma.

OBJECTIVE: We sought to define the prognostic significance of histologic subtype for extremity/truncal liposarcoma (LPS). BACKGROUND: LPS, the most common sarcoma, is comprised of 5 histologic subtypes. Despite their distinct behaviors, LPS outcomes are frequently reported as a single entity. METHODS: We analyzed data on all patients from a single-institution prospective database treated from July 1982 to September 2017 for primary, nonmetastatic, extremity or truncal LPS of known subtype. Clinicopathologic variables were tested using competing risk analyses for association with disease-specific death (DSD), distant recurrence (DR), and local recurrence (LR). RESULTS: Among 1001 patients, median follow-up in survivors was 5.4 years. Tumor size and subtype were independently associated with DSD and DR. Size, subtype, and R1 resection were independently associated with LR. DR was most frequent among pleomorphic and round cell LPS; the former recurred early (43% by 3 years), and the latter over a longer period (23%, 3 years; 37%, 10 years). LR was most common in dedifferentiated LPS, in which it occurred early (24%, 3 years; 33%, 5 years), followed by pleomorphic LPS (18%, 3 years; 25%, 10 years). CONCLUSIONS: Histologic subtype is the factor most strongly associated with DSD, DR, and LR in extremity/truncal LPS. Both risk and timing of adverse outcomes vary by subtype. These data may guide selective use of systemic therapy for patients with round cell and pleomorphic LPS, which carry a high risk of DR, and radiotherapy for LPS subtypes at high risk of LR when treated with surgery alone.

The importance of the margin of resection and radiotherapy in retroperitoneal liposarcoma.

BACKGROUND: Prior studies evaluating the impact of adjuvant or neoadjuvant radiotherapy on clinical outcomes in retroperitoneal liposarcoma have been underpowered. METHODS: We queried the National Cancer Database for patients undergoing resection of retroperitoneal liposarcoma from 2004 to 2016. Cox proportional hazards modeling stratified by tumor size was used to identify factors associated with overall survival. RESULTS: 4018 patients met inclusion criteria. 251 had small (<5 cm), 574 intermediate (5-10 cm), and 3193 large (>10 cm) tumors. Positive surgical margins were correlated with risk of death across all tumor size categories (<5 cm HR 2.33, CI [1.20, 4.55]; 5-10 cm HR 1.49, CI [1.03, 2.14]; >10 cm HR 1.30, CI [1.12, 1.51]). Adjuvant radiotherapy was associated with improved survival for patients with large tumors only (HR 0.75, CI [0.64, 0.89]). CONCLUSIONS: In retroperitoneal liposarcoma, adjuvant radiation is associated with improved survival only for patients with tumors larger than 10 cm. Radiation should be used sparingly in patients with smaller tumors. SUMMARY: The use of radiotherapy in the management of retroperitoneal sarcoma remains controversial. We isolated retroperitoneal liposarcomas only and identified a survival benefit from radiotherapy treatment only in tumors larger than 10 cm and only in the adjuvant setting.

Clinical features of multiply recurrent retroperitoneal liposarcoma: A single-center experience.

BACKGROUND: To elucidate the clinicopathological features of multiply recurrent retroperitoneal liposarcoma referred to a tertiary center. METHODS: We retrospectively analyzed the clinical data of 40 patients with pathologically proven primary retroperitoneal liposarcoma treated between January 2015 and June 2019. RESULTS: The initial pathology was well-differentiated liposarcoma (WDLS) in 23 patients, dedifferentiated liposarcoma (DDLS) in 15 patients, and myxoid liposarcoma in two patients. Before and after referral to our hospital, the patients underwent 142 surgeries (median number of surgeries: 3) for initial and recurrent tumors. Of these, 35 (87.5%) patients underwent surgeries for recurrent tumors. In 11 (47.8%) of the 23 patients with initial WDLS, pathological progression (PP) to DDLS was observed in recurrent tumors at the median interval of 7.8 years. In eight patients (72.7%), the PP occurred at the first recurrence. In contrast, all 15 patients with DDLS recurred as DDLS. Distant metastases developed in eight patients (34.8%) with WDLS and five patients (29.4%) with DDLS/myxoid subtype. All eight WDLS patients who developed metastasis were alive with disease at the median interval of 3.6 years, whereas four of the five patients with primary diagnosis of DDLS/myxoid subtype died at the median interval of 5.6 months from the development of metastasis. The 5-year overall survival of the patients with initial WDLS and those with DDLS/myxoid subtype were 100% and 67.4% (p = 0.0006), respectively. CONCLUSIONS: The prognosis of the initial-WDLS patients was favorable despite multiple recurrences. In WDLS patients, if distant metastases develop, it is possible to remain alive with disease for years.

A Proposed Staging System for Improved Prognostication of MDM2-amplified Liposarcoma.

Despite the release of anatomic site-specific staging systems for soft tissue sarcomas in the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, the algorithms for sarcomas arising in the extremities/trunk and retroperitoneum differ only in the staging of lymph node metastasis. The retroperitoneum not only provides a larger potential space for tumor growth before the clinical presentation, but its anatomic complexities complicate surgical resection and adversely affect disease-free survival. Here, we propose a new staging system for MDM2-amplified liposarcomas (well-differentiated and dedifferentiated subtypes) that properly emphasizes retroperitoneal localization, degree of differentiation (histologic subtype), and presence of distant metastasis. A retrospective cohort of 4146 adult patients with surgically resected liposarcoma was extracted from the SEER database to compare the natural history of MDM2-amplified liposarcomas arising in the extremities/trunk or retroperitoneum. Separate training and validation datasets were created, and Cox proportional hazard regression, multivariable nonlinear regression, and nomographic analyses determined the most significant parameters in predicting sarcoma-specific death. A new staging system was derived and its predictive accuracy was compared with the AJCC, eighth edition system using areas under receiver operating characteristic curves and multiple concordance indices. Multivariable analysis showed that dedifferentiation (hazard ratio [HR]=3.7±0.5; P<0.0005), retroperitoneal location (HR=3.2±0.5; P<0.0005), and distant metastasis (HR=2.4±0.6; P=0.002), but not categorized tumor size (pT category), had the largest effects on sarcoma-specific survival. A new staging system based on these predictive factors demonstrated better discrimination between tumor stages, higher concordance with clinical outcomes, and greater predictive accuracy than the AJCC eighth edition staging system (86±1% vs. 83±2%; P=0.005). Statistical analysis of a large national cohort failed to confirm that categorized tumor size is a useful criterion by which to stage MDM2-amplified liposarcoma. A simplified staging system based on anatomic location and dedifferentiation outperforms the current AJCC staging system. Anatomic localization and histologic grade, and not tumor size, should be included in any future liposarcoma-specific staging system.

What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities?

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.

Nomogram for predicting the overall survival and cancer-specific survival of patients with extremity liposarcoma: a population-based study.

BACKGROUND: Extremity liposarcoma represents 25% of extremity soft tissue sarcoma and has a better prognosis than liposarcoma occurring in other anatomic sites. The purpose of this study was to develop two nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with extremity liposarcoma. METHODS: A total of 2170 patients diagnosed with primary extremity liposarcoma between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were performed to explore the independent prognostic factors and establish two nomograms. The area under the curve (AUC), C-index, calibration curve, decision curve analysis (DCA), Kaplan-Meier analysis, and subgroup analyses were used to evaluate the nomograms. RESULTS: Six variables were identified as independent prognostic factors for both OS and CSS. In the training cohort, the AUCs of the OS nomogram were 0.842, 0.841, and 0.823 for predicting 3-, 5-, and 8-year OS, respectively, while the AUCs of the CSS nomogram were 0.889, 0.884, and 0.859 for predicting 3-, 5-, and 8-year CSS, respectively. Calibration plots and DCA revealed that the nomogram had a satisfactory ability to predict OS and CSS. The above results were also observed in the validation cohort. In addition, the C-indices of both nomograms were significantly higher than those of all independent prognostic factors in both the training and validation cohorts. Stratification of the patients into high- and low-risk groups highlighted the differences in prognosis between the two groups in the training and validation cohorts. CONCLUSION: Age, sex, tumor size, grade, M stage, and surgery status were confirmed as independent prognostic variables for both OS and CSS in extremity liposarcoma patients. Two nomograms based on the above variables were established to provide more accurate individual survival predictions for extremity liposarcoma patients and to help physicians make appropriate clinical decisions.

Characteristics of primary and repeated recurrent retroperitoneal liposarcoma: outcomes after aggressive surgeries at a single institution.

OBJECTIVE: This study sought to investigate the characteristics of primary and repeated recurrent retroperitoneal liposarcoma. METHODS: Patients treated with primary or recurrent retroperitoneal liposarcoma between 2005 and 2018 were retrospectively reviewed. Survival time analysis of recurrence-free survival and overall survival was conducted using Kaplan-Meier analysis and log-rank test. RESULTS: Fifty-two patients with primary retroperitoneal liposarcoma were analysed. Amongst them, 46 patients (88%) had undergone surgery. Histologic grades included well-differentiated (n = 21), dedifferentiated (n = 21), myxoid (n = 3) and pleomorphic (n = 1) subtypes. The patients undergoing R0 resection in the first surgery had significantly higher recurrence-free survival rates compared with the patients undergoing non-R0 resection (3-year recurrence-free survival: 80 versus 38%; 5-year recurrence-free survival: 49 versus 29%, P = 0.033). Although overall survival rates tended to be higher in the patients undergoing R0 resection compared with the non-R0 resection, it did not reach to a statistical significant difference (5-year overall survival: 93 versus 75%; 10-year overall survival: 93 versus 59%, P = 0.124). The recurrence rates were 65, 67, 73 and 100%, and the median recurrence-free survival times were 46, 20, 9 and 3 months after the first, second, third and fourth surgeries, respectively. The 5-year overall survival rates were 82, 69, 40 and 0% after the first, second, third and fourth surgeries, respectively. CONCLUSIONS: With repeated recurrence and surgeries, the time to recurrence decreased and the recurrence rate increased. R0 resection in the first surgery was considered the most important for longer recurrence-free survival and radical cure.