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)

Association Between Ageing and Short-Term Survival Outcomes in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma.

BACKGROUND: As the population ages, more elderly patients are receiving surgery for retroperitoneal sarcoma (RPS). However, high-quality data investigating associations between ageing and prognosis are lacking. Our study aimed to investigate whether ageing is associated with inferior short-term survival outcomes after RPS surgery. PATIENTS AND METHODS: Patients undergoing surgery for primary RPS between 2008 and 2019 at two tertiary sarcoma centres were analysed. The primary outcome was 1-year mortality, and the primary explanatory variable was patient age, classified as: < 55, 55-64, 65-74 or 75+ years. RESULTS: The 692 patients undergoing surgery (mean age 60.8 ± 13.8 years) had a 1-year mortality rate of 9.4%, which differed significantly by age (p < 0.001), with rates of 7.2%, 6.9%, 8.7% and 22.8% for the < 55, 55-64, 65-74 and 75+ years groups, respectively. The distribution of causes of death also differed significantly by age (p = 0.023), with 22% and 28% of deaths in the 65-74 and 75+ years groups caused by post-operative complications, versus none in the < 55 and 55-64 years groups. On multivariable analysis, age of 75+ years (versus < 55 years) was a significant independent predictor of 1-year mortality [odds ratio (OR) 7.05, 95% confidence interval (CI) 2.63-18.9, p < 0.001]; no significant increase in risk was observed in the 55-64 (OR 0.72, 95% CI 0.28-1.87) or 65-74 (OR 0.89, 95% CI 0.37-2.15) years groups. CONCLUSIONS: Post-operative complications are an important cause of deaths in elderly patients. These findings are relevant to decision-making and counselling when surgery is considered for patients with RPS.

Adjuvant therapy for retroperitoneal sarcoma: a meta-analysis.

BACKGROUND: Adjuvant therapy is a promising treatment to improve the prognosis of cancer patients, however, the evidence base driving recommendations for adjuvant radiotherapy (ART) or chemotherapy (ACT) in retroperitoneal sarcomas (RPS) primarily hinges on observational data. The aim of this study was to evaluate the effectiveness of adjuvant therapy in the management of RPS patients. METHODS: We searched PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane Library for comparative studies (until December 2020) of adjuvant therapy versus surgery alone. Data on the following endpoints were evaluated: overall survival (OS), local recurrence (LR), recurrence-free survival (RFS), and metastasis-free survival (MFS). Data were summarized as hazard ratios (HR) with 95% confidence intervals (CI). Risk of bias of studies was assessed with Begg's and Egger's tests. RESULTS: A total of 15 trials were eligible, including 9281 adjuvant therapy and 21,583 surgery alone cases (20 studies for OS, six studies for RFS, two studies for LR, and two studies for MFS). Meta-analysis showed that ART was associated with distinct advantages as compared to surgery alone, including a longer OS (HR = 0.80, P < 0.0001), a longer RFS (HR = 0.61, P = 0.0002), and a lower LR (HR = 0.31, P = 0.005). However, this meta-analysis failed to demonstrate a benefit of ACT for RPS patients, including OS (HR = 1.11, P = 0.19), RFS (HR = 1.30, P = 0.09) and MFS (HR = 0.69, P = 0.09). In the sensitivity analysis, ACT was associated with a worse OS (HR = 1.19, P = 0.0002). No evidence of publication bias was observed. CONCLUSIONS: Overall, the quality of the evidence was moderate for most outcomes. The evidence supports that ART achieved a generally better outcome as compared to surgery alone.

Longitudinal prognostication in retroperitoneal sarcoma survivors: Development and external validation of two dynamic nomograms.

PURPOSE: The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS). METHODS: Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts. RESULTS: Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (TLM), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM, histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes. CONCLUSION: Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors.

Clinical characteristics, treatment strategies and oncologic outcomes of primary retroperitoneal tumours: a retrospective analysis in the Chinese population.

INTRODUCTION: Primary retroperitoneal tumours (PRTs) are rare soft tissue tumours originating from the retroperitoneum. Although there has been considerable progress recently in diagnosis and treatment, the overall survival rate has not improved qualitatively. This study aimed to explore the clinical features, therapeutic strategies and prognosis of PRTs. METHODS: Retrospective analysis of clinical data for 121 PRT patients admitted to Peking University Shenzhen Hospital from April 2003 to February 2017. RESULTS: A total of 113 patients underwent surgery and 8 chose nonsurgical palliative treatment. There were 53 males and 68 females (ratio, 1:1.3; average age, 40.75 years), and the average tumour diameter was 9.69(2-40)cm. A total of 104 patients (92.04%) underwent complete resection, 5 (4.42%) underwent palliative resection and 21 (18.58%) underwent combined visceral resection. The pathological diagnosis was benign in 88 cases (72.73%) and malignant in 33 cases (27.27%). A total of 101 patients (83.47%) were followed for an average of 5.82 years. At the end of follow up, the recurrence and survival rates were 2.63% and 93.42% for benign tumours, respectively, and 24.00% and 60.00% for malignant tumours (p<0.01). CONCLUSIONS: Imaging plays important roles in localising and characterising tumours, guiding treatment strategies. Complete tumour resection is key to reducing postoperative recurrence and improving survival. According to the postsurgical pathological results, combinations including radiotherapy, chemotherapy or targeted therapy are beneficial for improving prognosis.

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.

The impact of postoperative radiological surveillance intensity on disease free and overall survival from primary retroperitoneal, abdominal and pelvic soft-tissue sarcoma.

AIM: This observational study aimed to evaluate the impact of intensity of radiological surveillance on survival following resection of retroperitoneal sarcoma. METHOD: Retrospective cohort study of patients undergoing primary resection of soft tissue sarcoma arising in the retroperitoneum, abdomen or pelvis at a single, high-volume sarcoma centre. Intensity of follow-up regimes up to 5 postoperative years were categorized as 'European Society for Medical Oncology (ESMO) compliant' (intense), or 'non-ESMO compliant' (less-intense). The primary outcome measure was overall survival (OS). The secondary outcome measures were disease-free survival (DFS) and reoperation rate. Analyses were stratified by high (grade 2 or 3) or low (grade 1) tumour grade. RESULTS: Of 168 patients, 67.1% had high-grade and 32.9% had low-grade disease. Overall, 40.0% of patients had ESMO-compliant radiological follow-up (high-grade:25.7%, low-grade:66.7%). 41.7% of patients died and 48.2% suffered local or distant recurrence by cessation of follow up. Upon univariable analysis for high-grade tumours, ESMO compliance reduced DFS (p = 0.066) but had no impact on OS. There was no significant difference in the reoperation rate in patients with ESMO-compliant and non-compliant follow-up (p = 0.097). In low-grade tumours, ESMO compliance significantly reduced DFS (p < 0.001), but without effecting OS. In risk-adjusted models for high-grade tumours, ESMO compliant follow-up was associated with reduced OS (HR:3.47, 1.40-8.61, p = 0.007) and no difference in DFS. In low-grade tumours, there was no association between overall ESMO compliance and OS or DFS. CONCLUSION: This study did not find a benefit for high-intensity radiological surveillance and overall survival in patients undergoing primary resection for high or low-grade retroperitoneal sarcoma.

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.

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.

Primary mesenteric sarcomas: Collaborative experience from the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

BACKGROUND: Primary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function. OBJECTIVES: To determine the overall survival (OS) and recurrence-free survival (RFS) for patients undergoing primary resection for mesenteric STS. METHODS: The Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019. RESULTS: Fifty-six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher-grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery. CONCLUSION: Primary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging.

Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes. METHODS: Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared. RESULTS: Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma. CONCLUSIONS: In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated.

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.

Treatment Factors Associated With Overall Survival in Retroperitoneal Sarcoma: An Institutional Review.

INTRODUCTION: Retroperitoneal sarcoma (RPS) is a rare malignancy, and curative resection is considered the main therapy. Use of chemotherapy and/or radiation in addition to surgery (multimodality therapy) is controversial. OBJECTIVE: To determine treatment factors that influence overall survival in RPS. METHODS: This retrospective Institutional Review Board-approved study identified patients with RPS treated at a single institution between 2000 and 2017. Patient, tumor, and treatment modalities were collected. Prism (v.8.2.1) was used to calculate Kaplan-Meier survival curves. RESULTS: There were 695 patients with sarcoma between 2000 and 2017, and 61 adults had RPS. The mean age was 59 (range 31-86) years, with 57.4% females (n = 35). Patients were 68.9% Caucasian (n = 42), 21.3% Hispanic (n = 13), 8.2% black (n = 5), and 1.6% Asian (n = 1). There were 4 patients who had neoadjuvant therapy (chemotherapy, n = 3; radiation, n = 2) and 17 who had adjuvant therapy (chemotherapy, n = 6; radiation, n = 14). There was no significant difference in survival between the groups who received multimodality therapy compared to surgery alone. There was a significant improvement in the median overall survival for patients who underwent one or multiple surgeries (P < .05). CONCLUSIONS: These institutional data suggest that treatment factors associated with overall survival included multiple resections. Use of multimodality therapy was low and did not influence overall survival in patients with RPS compared to surgery alone.

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

BACKGROUND: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). METHODS: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. RESULTS: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. CONCLUSIONS: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.

Innate inflammatory markers for predicting survival in retroperitoneal sarcoma.

INTRODUCTION: Existing prognostic tools for retroperitoneal sarcomas (RPS) utilize parameters that can be accurately determined only postoperatively. This study evaluated the application of the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels for predicting prognosis in primary RPS. MATERIALS AND METHODS: We retrospectively analyzed our database of patients with primary RPS operated between 2008 and 2018. The NLR was calculated from preoperative blood tests and its association with outcomes was determined. RESULTS: The NLR values of 78 suitable patients were analyzed. Patients were classified in the NLR-high group if the NLR was ≥2.1. High-grade tumors were more common in the NLR-high group (71.6% vs 48%, P = .02). NLR-high patients had impaired overall survival (OS) and progression-free survival (PFS) compared to NLR-low patients (median OS not reached vs 74 months 95% confidence interval [CI]: 21.6-126.4, P = .03; median PFS not reached vs 48 months 95% CI: 6.5-98.6, P = .06, respectively). Multivariate analysis showed statistical significance only for PFS but not for OS (hazard ratio [HR] = 4.1, P = .03; HR = 2.3, P = .3). Patients with low CRP levels had improved OS and PFS. CONCLUSIONS: The NLR may serve as a preoperative, easily derived marker for prognosis in RPS. Serum biomarkers may prove useful in these large and spatially heterogeneous tumors.

Metastases of soft tissue sarcoma to the liver: A Historical Cohort Study from a Hospital-based Cancer Registry.

BACKGROUND: Hepatic metastasis of soft tissue sarcoma is rare compared to lung metastasis, and the literature is scarce. We examined the risk of hepatic metastasis according to the site of occurrence and histological type. METHODS: From a Hospital-based Cancer Registry, 658 patients registered between 2007 and 2017 with soft tissue sarcomas were evaluated. The exclusion criteria were gastrointestinal stromal tumors, tumors of unknown origin, and follow-up periods of less than 1 month. SPSS 25 was used for statistical analysis. RESULTS: The risk of hepatic metastasis was significantly higher in the retroperitoneum (HR, 5.981; 95% CI, 2.793-12.808) and leiomyosarcoma (HR, 4.303; 95% CI, 1.782-10.390). Multivariate analysis showed that the risk of hepatic metastasis as first distant metastasis was high in leiomyosarcoma (HR, 4.546; 95% CI, 2.275-9.086) and retroperitoneal onset (HR, 4.588; 95% CI, 2.280-9.231). The 2-year survival rate after hepatic metastasis was 21.7%. CONCLUSIONS: The onset of hepatic metastasis indicates a poor prognosis. However, hepatic metastasis from retroperitoneal sarcoma and leiomyosarcoma may be the first distant metastasis in some cases. For retroperitoneal sarcoma and leiomyosarcoma, additional screening for hepatic metastasis such as contrast CT should be considered during staging and follow-up after treatment.

Single centre 30-year experience in treating retroperitoneal liposarcomas.

BACKGROUND AND OBJECTIVES: Liposarcomas form a diverse group of tumors that represent the majority of retroperitoneal soft tissue sarcomas. Radical excision of these retroperitoneal liposarcomas is often challenging due to their large size and proximity to visceral organs and major vessels. Here we present the 30-year experience of our multidisciplinary sarcoma team in the treatment of these tumors and analysis of factors influencing survival. METHODS: Patients with retroperitoneal liposarcomas treated in Helsinki University Hospital from 1987 to 2017 were reviewed. Local recurrence-free survival, metastases-free survival, and disease-specific survival were assessed with Kaplan-Meier analysis, and factors influencing survival were evaluated with Cox regression. RESULTS: A total of 107 patients were identified. The median follow-up time was 5.4 years (interquartile range: 2.2-8.8 years). Local recurrence developed in 72% and metastases in 15% during follow-up. The 5-year disease-free survival was 31% and disease-specific survival was 66%. The multifactorial analysis revealed histological type and grade as predictors of disease-specific survival (P < .01) while multifocality carried a poor prognosis for local recurrence (P = .02) and higher histological grade for metastases (P < .01). CONCLUSIONS: Retroperitoneal liposarcomas rarely metastasize but tend to recur locally. For tumors that have been resected with macroscopically clear margins, histological, type, and grade are significant predictors of survival.

Identification of TYMS as a promoting factor of retroperitoneal liposarcoma progression: Bioinformatics analysis and biological evidence.

Retroperitoneal liposarcoma (RLPS) is one of the most common types of retroperitoneal sarcomas, and has a high recurrence rate. There is an urgent need to further explore its pathogenesis and develop more effective treatment strategies. The aim of the present study was to identify potential driver genes of RLPS through bioinformatics analysis and molecular biology to elucidate potential targets that are suitable for further analysis for the treatment of RLPS. Differentially expressed genes (DEGs) between liposarcoma and normal fatty (NF) tissues were identified based on microarray data through bioinformatics analysis, and thymidylate synthase (TYMS) was selected from the DEGs, based on high content screening (HCS). TYMS expression was evaluated in RLPS tumor tissues and cell lines. A total of 21 RLPS tissues and 10 NF frozen tissues were used for reverse transcription­quantitative PCR, and 47 RLPS formalin­fixed specimens were used for immunohistochemical analysis. The effect of TYMS downregulation on cell proliferation, apoptosis, cell cycle progression, and cell migration and invasion were evaluated using lentivirus­mediated short hairpin RNA. The underlying mechanisms of TYMS in RLPS were examined by protein microarray and verified by western blotting. A total of 855 DEGs were identified. TYMS knockdown had the most notable effect on the proliferative capacity of RLPS cells according to the HCS results. TYMS mRNA expression levels were higher in RLPS tissues compared with NF tissues (P<0.001). TYMS expression was higher in high­grade RLPS tissues compared with low­grade RLPS tissues (P=0.003). The patients with positive TYMS expression had a worse overall survival (OS) and disease­free survival (DFS) compared with the patients with negative TYMS expression (OS, P=0.024; DFS, P=0.030). The knockdown of TYMS reduced proliferation, promoted apoptosis, facilitated cell cycle progression from G1 to S phase, and reduced cell migration and invasion of RLPS cells. Protein microarray analysis and western blotting showed that the Janus Kinase/Signal transducers and activators of transcription pathway was downregulated following TYMS knockdown. In conclusion, TYMS expression is upregulated in RLPS tissues, and downregulation of TYMS reduces RLPS progression.