Retroperitoneal Soft Tissue Sarcoma Research Articles

Defining Which Patients Are at High Risk for Recurrence of Soft Tissue Sarcoma.

Several studies have investigated the prognosis of soft tissue sarcomas and the influence of a variety of factors, such as size, histology subtype, malignancy grade, site, margins, on overall survival, recurrence-free survival, incidence of local and distant spreading. The impact of genomic and expression profiling on long-term outcomes of patients with sarcomas has been also evaluated in order to fill the knowledge gap of this heterogeneous disease. Nomograms represent a prognostic tool that extends the standard staging systems on an individualized basis, taking into account tumor- and patient-related factors. They are used to assist the health provider and the patients in the decision-making process, for patient counseling, treatment decision-making, follow-up scheduling, and clinical trial eligibility determination. None of the available nomograms include molecular characterization of sarcomas. In the future, omics signatures might be incorporated into prognostic nomograms possibly improving their performance. In the present review, we focus on the complexity of prognostic and predictive factors for extremity and trunk wall as well as for retroperitoneal soft tissue sarcomas, while exploring the available prognostic models.

Soft-tissue sarcoma in adults: An update on the current state of histiotype-specific management in an era of personalized medicine.

Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.

Variations in Retroperitoneal Soft Tissue Sarcoma Outcomes by Hospital Type: A National Cancer Database Analysis.

Surgical resection remains the cornerstone of retroperitoneal soft tissue sarcoma (RPS) treatment. Patient- and sarcoma-related factors are well known to influence survival outcomes. The effect of hospital-related factors on long-term survival, however, are not well understood. We sought to assess the relative contribution of hospital-level factors to mortality after surgical treatment of RPS. The 2004-2015 National Cancer Database was used to identify 10,113 patients who underwent surgical treatment of RPS. Patient-, sarcoma-, hospital-, and treatment-level factors were compared by increasing survival times. Stepwise multivariable Cox regression was performed that controlled for covariates to measure the relative contributions of these factors on overall survival (OS). Effect modification analyses ascertained how hospital type modulates the volume relationship with respect to RPS mortality. Factors predictive of worsening OS were older age, nonprivate insurance, low income, presence of comorbidities, tumor histology, high grade or stage, and R2 resection (for all, P < .05). Increasing hospital surgical volume predicted decreasing risk of death across all survival times. However, analysis by hospital type demonstrated that compared with academic centers, the risk of death at community centers increased significantly as surgical volume increased (hazard ratio, 1.26; 95% CI, 1.03 to 1.53). Hospital factors affect mortality after surgical treatment of RPS. Specifically, hospital type alters the surgical volume-outcome relationship for RPS mortality such that community centers perform worse with increasing volumes. Recommendations that higher surgical volume improves outcomes cannot be applied universally and must be re-examined in other complex surgical cancers.

Fusion imaging to evaluate the radiographic anatomical relationship between primary tumors and local recurrences in retroperitoneal soft tissue sarcoma

BackgroundLocal recurrence (LR) of retroperitoneal soft tissue sarcoma (RPS) is a common and life-threatening event. The evaluation of the exact anatomical patterns of local recurrence might help to improve local treatment in RPS. MethodsOf our local database we extracted ten patients with LR of RPS with axial MRI and/or CT datasets of the primary tumor (PT) and the LR. Using the Osirix DICOM viewer Version v.3.9.4 64-bit (Pixmeo, Geneva, Switzerland) we performed a three-step fusion algorithm consisting of: a) 3-point co-registration of the axial datasets depicting the PT and the LR using three abdominal landmarks b) re-orientation of the datasets and c) image fusion. We evaluated the feasibility of this technique with regard to categorizing the localization of LR as within or distant from the PT. ResultsFusion imaging was feasible in seven out of ten patients. In the other three patients anatomical shifting of organs after surgery led to a relevant mismatch of anatomical landmarks and impeded interpretation of the fused images. In five of seven patients with successful fusion imaging, local recurrences were located within the anatomical borders of the primary tumor, in two out of seven patients local recurrences were distant to the primary. ConclusionsFusion imaging of primary tumors and local recurrences is feasible in most patients with RPS. Most local recurrences occurred within the anatomical localization of the primary tumor. For further investigations validation of the technique in larger patient cohorts is required.

Individualised Multimodal Therapy of Retroperitoneal Soft Tissue Sarcomas

Retroperitoneal soft tissue sarcomas make up a diverse group of malignant tumours of mesenchymal origin with diverse histo- and molecular pathology. Liposarcoma and leiomyosarcoma are the predominant subentities - followed by the substantially less frequent solitary fibrous tumors, malignant peripheral nerve-sheath tumors and unclassified pleomorphic sarcomas. The biological behaviour of retroperitoneal soft tissue sarcomas is highly variable, depending on the histopathological subtype. A differentiated therapeutic approach is therefore essential. There is only marginal therapeutic evidence that multimodal therapies improve patients' outcomes, yet neoadjuvant and adjuvant strategies should be discussed, depending on tumour topography, histopathology and patient-specific factors. There has been intense debate in the last 10 years about the appropriate surgical strategy. The core issue is whether long-term follow-up is improved after more radical, compartmental resection that includes adjacent organs and tissues that appear not to be infiltrated, as judged by clinical and radiological evidence. This procedure should then be generally recommended as standard of care. The available data appears to answer this question - nonetheless a differentiated approach is mandatory. Therefore entities exhibiting low local recurrence rates and/or more benign biology should be resected with the aim of organ preservation, while tumours with high local recurrence rates and unfavourable biological behaviour should undergo more radical, compartimental resection. A balanced approach should be considered in entities with high metachronic systemic dissemination rates.

Inoperable Primary Retroperitoneal Sarcoma: Clinical Characteristics And Reasons Against Resection At A Single Referral Institution

Background: surgery is the standard and only curative treatment for localized primary retroperitoneal soft tissue sarcomas (rps). However, some patients (pts) are not offered surgical resection. The aim of our study was to determine the rate and reasons of inoperable primary rps at a large referral institution.

Perioperative Residual Adrenal Function After Extended Resection for Retroperitoneal Soft Tissue Sarcomas

Perioperative Residual Adrenal Function After Extended Resection for Retroperitoneal Soft Tissue Sarcomas

Significance of intraoperative radiation therapy and high cumulative radiation doses in retroperitoneal soft tissue sarcoma

IntroductionIn retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates remain high despite more aggressive surgical approaches. Since wide resection margins cannot be achieved in all patients, application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear. Material and methodsPatients undergoing resection of primary or recurrent retroperitoneal STS at the University of Heidelberg Department of General, Visceral and Transplantation Surgery were retrospectively analyzed. Univariate Kaplan-Meyer and multivariate Cox regression analyses were performed to identify predictors of LR-free survival and to investigate the impact of IORT and high cumulative radiation doses. Analyses with propensity-score matched subgroups for IORT and cumulative radiation dose were performed to control for selection bias. Subgroup analyses for patients with retroperitoneal liposarcoma were likewise performed. Results272 patients were identified. Recurrent tumors, histology of dedifferentiated liposarcoma or unclassified sarcoma and microscopically incomplete resection were associated with decreased LR-free survival. In liposarcoma, only recurrent and dedifferentiated tumors were confirmed as poor prognostic factors concerning LR. IORT and cumulative radiation doses exceeding 60 Gy did not influence LR rates (estimated 5-year LR-free survival: IORT: 39%, non-IORT: 46%; p = 0.79). ConclusionIn this retrospective evaluation, additional application of IORT does not significantly influence oncological outcome in retroperitoneal soft tissue sarcoma. Randomized trials are needed to clarify the benefit of IORT.

Identifying the Minimum Volume Threshold for Retroperitoneal Soft Tissue Sarcoma Resection: Merging National Data with Consensus Expert Opinion

The complexity of retroperitoneal soft tissue sarcoma (RPS) surgery has prompted international recommendations to regionalize it to high-volume hospitals (HVHs). A minimum procedural volume threshold for RPS is not yet defined, hampering effective referral and regionalization in the US. This multihospital study sought to establish an HVH threshold informed by national data and international expert opinion. The 2004-2015 National Cancer Database identified 8,721 surgically treated RPS patients. Multivariable models, using linear splines, identified annual volume thresholds predictive of overall and 90-day mortality. Transatlantic Australasian Retroperitoneal Soft Tissue Sarcoma Working Group members (n= 48) completed a 15-item survey regarding these data. Overall mortality risk was reduced by 4% per additional case (hazard ratio [HR] 0.96, 95% CI 0.95 to 0.98) up to a threshold of 13 cases/year; no further reduction was observed over 13 (HR 0.99, 95% CI 0.97 to 1.01). After revealing the results from our statistical analysis, 71.4% of respondents who initially chose >30 cases/year as a cutoff shifted their response to a lower value. More than 56% cited 11 to 20 procedures/year as the cutoff for an HVH. Median survival in hospitals with <13 vs >13 cases/year was 94 vs 139 months, respectively (p < 0.001). Forty percent of respondents cited 1% to 2% as an acceptable90-day mortality. This was achieved with a minimum of 13 cases/year based on risk-adjusted survival analysis. This is the first multicenter analysis to merge data-driven RPS surgery volume thresholds to clinically meaningful sarcoma expert opinions. These findings will help inform national/international consensus recommendations, a practical volume threshold, trial design, and motivate evidence-based hospital referral.

Advances in soft-tissue sarcoma - There are no mistakes, only lessons to learn!

Background:In this decade the treatment of advanced sarcoma has seen many highs and lows in terms of successful trials and failed trials. This is possible due to great collaborations, newer therapies and histology focused trials.Methods:In ASCO 2019 many sarcoma trials were presented and we chose 3 challenging clinical trials that widen our perspective on soft tissue sarcoma. We have critically analyzed the data and have discussed the implications of these trials on current practice. First trial was ANNOUNCE trial which was done to confirm the efficacy of olaratumab after its dramatic success in advanced soft tissue sarcoma in a phase 2 trial. Another trial STRASS trial, which was unique because of being first successfully conducted randomized trial addressing preoperative radiotherapy in retroperitoneal soft tissue sarcoma. Third trial was phase 2 trial SARC 028 trial exploring the role of immunotherapy in pleomorphic undifferentiated sarcoma and liposarcoma subgroup.Result:ANNOUNCE trial failed to show OS benefit in olaratumab/doxorubicin arm as compared to doxorubicin/placebo arm. Based upon this FDA has revoked the approval of olaratumab leading to nihilism and disappointment amongst oncologists. In STRASS trial failed to meet the primary end point though there was a benefit in the liposarcoma subgroup in terms of abdominal recurrence free survival. There are several reasons that this trial might have failed. First, RPSs are not homogeneous population. RPSs might behave very differently as per the histopathology ranging from well differentiated LPS to leiomyosarcoma. Since the event rate in well-differentiated liposarcoma might happen late, the median follow-up of 43 months might not be sufficient. In SARC trial ORR in pleomorphic undifferentiated sarcoma (PUS) cohort was 9/40 (22.5%), while response rates in liposarcoma cohort were 4/39 (10.2%). There was poor correlation between the response and the tumor cells' PD-L1 positivity. Simultaneously, we must not take for granted the role of pembrolizumab in PUS as the previous study (PEMBROSARC) had also showed dismal outcomes with immunotherapy.Conclusion:In this paper we discuss the intricacies of these trials and how they affect the rapidly changing landscape in advanced soft tissue sarcoma.

Identifying the Minimum Volume Threshold for Retroperitoneal Soft Tissue Sarcoma Resection: Merging National Data with Consensus Expert Opinion

Identifying the Minimum Volume Threshold for Retroperitoneal Soft Tissue Sarcoma Resection: Merging National Data with Consensus Expert Opinion

Role of radiation therapy for retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.

The use of radiation therapy in the treatment of retroperitoneal sarcomas has increased in recent years. Its impact on survival and recurrence is unclear. A retrospective propensity score matched (PSM) analysis of patients with primary retroperitoneal soft tissue sarcomas, who underwent resection from 2000 to 2016 at eight institutions of the US Sarcoma Collaborative, was performed. Patients with metastatic disease, desmoid tumors, and palliative resections were excluded. Total 425 patients were included, 56 in the neoadjuvant radiation group (neo-RT), 75 in the adjuvant radiation group (adj-RT), and 294 in the no radiotherapy group (no-RT). Median age was 59.5 years, 186 (43.8%) were male with a median follow up of 31.4 months. R0 and R1 resection was achieved in 253 (61.1%) and 143 (34.5%), respectively. Overall 1:1 match of 46 adj-RT and 59 neo-RT patients was performed using histology, sex, age, race, functional status, tumor size, grade, resection status, and chemotherapy. Unadjusted recurrence-free survival (RFS) was 35.9 months (no-RT) vs 33.5 months (neo-RT) and 27.2 months (adj-RT), P = .43 and P = .84, respectively. In the PSM, RFS was 17.6 months (no-RT) vs 33.9 months (neo-RT), P = .28 and 19 months (no-RT) vs 27.2 months (adj-RT), P = .1. Use of radiotherapy, both in adjuvent or neoadjuvent setting, was not associated with improved survival or reduced recurrence rate.

Comprehensive immune characterization and T-cell receptor repertoire heterogeneity of retroperitoneal liposarcoma.

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas and lacks effective treatment. This study aimed to provide a thorough profile of immune characteristics of RLPS. This study included 56 RLPS patients. Multisite tumor tissues were collected from 16 patients. Immunohistochemistry was carried out to identify CD4+, CD8+, FoxP3+, CD20+, or programmed cell death‐1 (PD‐1)+ tumor infiltrating lymphocytes (TILs) and Programmed cell death ligand‐1 (PD‐L1) expression in tumor tissues. Ultradeep sequencing of T‐cell receptor (TCR) β‐chain gene was carried out in 42 tumor samples as well as peripheral blood samples collected from 6 patients. In RLPS, TILs were distributed in 3 patterns and T cells were more prevalent than B cells. Generally, the proportion of TILs decreased and PD‐L1 expression increased with tumor progression. Patients with higher PD‐1/PD‐L1 expression tended to have poorer prognosis, whereas patients with tertiary lymphoid structure tended to have a favorable disease‐free survival. Although T‐cell clones in tumors were quite different from those in peripheral blood, TCR sequencing showed low TCR repertoire reads as well as polyclonal status within tumors, which indicated limited T cell response in the tumors. Both TILs distribution and TCR repertoires suggested spatial immune heterogeneity in RLPS. Our research described the immune landscape of RLPS, and suggested RLPS might be a kind of tumor with low T cell infiltration as well as great immune heterogeneity. Therefore, strategies that can facilitate lymphocytic infiltration and immune reactivity need to be developed in the future to improve the efficacy of immunotherapy.

Oncovascular Surgery: Essential Roles of Vascular Surgeons in Cancer Surgery.

For the modern practice of cancer surgery, the concept of oncovascular surgery (OVS), defined as cancer resection with concurrent ligation or reconstruction of a major vascular structure, can be very important. OVS for advanced cancers requires specialized procedures performed by a specialized multidisciplinary team. Roles of oncovascular surgeons are summarized as: a primary surgeon in vesselorigin tumors, a rescue surgeon treating complications during cancer surgery, and a consultant surgeon as a multidisciplinary team for cancer surgery. Vascular surgeons must show leadership in cancer surgery in cases of complex advanced diseases, such as angiosarcoma, leiomyosarcoma, intravenous leiomyomatosis, retroperitoneal soft tissue sarcoma, iatrogenic injury of the major vessels during cancer surgery, pancreatic cancer with vascular invasion, extremity soft tissue sarcoma, melanoma and others.

Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.

Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival. Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated. Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years. Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.

A case of marantic endocarditis with systemic emboli in a patient with metastatic soft tissue sarcoma

Clinical manifestations of cancer can be categorized as resulting from direct tissue injury from the primary tumor, distant metastatic spread, or aberrant biological activity, also known as a paraneoplastic syndrome. Soft tissue sarcomas are a rare group of malignant tumors of mesenchymal origin which typically present with direct tissue injury, exerting their harmful potential by compression and mass effect. We describe a rare case of an occult retroperitoneal soft tissue sarcoma presenting with marantic endocarditis. To date, there is a paucity of available medical literature relating sarcoma to marantic endocarditis.

Retroperitoneal soft tissue sarcoma (RPS): Recent outcome improvement and refinement of treatment strategies at a single institution.

11041 Background: Extended surgery in retroperitoneal sarcoma (RPS) has resulted in less recurrences and better survival. We investigated whether outcome further improved, after the recent understanding of behavior of different RPS subtypes and introduction of multimodal therapies. Methods: Consecutive primary RPS operated at a single center were analyzed comparing 3 periods (2002-2006; 2007-2011; 2012-2016). Primary endpoints were overall survival (OS), crude cumulative incidence (CCI) of local recurrence and distant metastasis (LR, DM) for each subgroup: well differentiated (WDLPS), dedifferentiated G2 (G2DDLPS), G3 (G3DDLPS) liposarcoma, and leiomyosarcoma (LMS). Secondary endpoints: morbidity and post-relapse OS. Fisher/Chi-squared and Cochran–Armitage trends test were used. Survival was analysed by Kaplan-Meier/Cox PH or CCI/Fine Gray models in the competitive risk framework and compared with log-rank/Wald Gray tests. Multivariable analyses were performed. Results: Overall 437 RPS were operated: 82, 128 and 227 in the 1st, 2nd and 3rd period. Median follow-up was 125, 86 and 39 months. Complete resection (R0/R1) improved from 93.9% to 98.2% (p=0.059), median number of resected organs increased from 2 to 4 (p&lt;.0001). Postoperative morbidity did not change (18.3%, 16.4%, 22.5%; p=0.269). Administration of radiotherapy and chemotherapy (CT) differed over time according to different subtypes. 5-yr OS improved (63.2% to 74.7%, p=0.005), along with a non-significant reduction in LR CCI (18.2% to 16.4%, p=0.379) and no change in DM CCI. At multivariable analysis, study period remained an independent prognostic factor for OS among the other known risk factors (3rd vs 1st period HR: 0.33, p&lt;0.001). Subgroup analysis showed the following associations with better prognosis: 1. Improvement in 5-yr OS (from 55.0% to 70.7%, p=0.024) and LR (from 45.0% to 19.8%, p=0.060) in G2DDLPS, associated with more organs resected 2. Improvement in 5-yr OS (from 18.2% to 49.7%, p=0.035) and DM (from 70.0% to 19.8%; p=0.015) in G3DDLPS, associated with more anthracycline-based CT 3. A better 2-yr post-relapse OS (from 46.3% to 65.2%, p=0.122). Conclusions: OS of patients with DDLPS improved over time: in G2 this was associated with a refinement in the surgical approach, while in G3 with a more liberal use of anthracycline-based CT. New available therapies for recurring RPS may also have extended post-relapse OS. Prospective studies on perioperative CT for high risk RPS subtypes are eagerly awaited.

ASO Author Reflections: Minimally Invasive Surgery for Retroperitoneal Soft Tissue Sarcoma.

ASO Author Reflections: Minimally Invasive Surgery for Retroperitoneal Soft Tissue Sarcoma.

Retroperitoneal Dedifferentiated Liposarcoma with Metaplastic Bone Formation : A Case Report and Review of the Literature

A 69-year-old female was introduced to our department for a retroperitoneal mass, 25 mm in diameter, in the right perirenal space indicated by computed tomography (CT). On the basis of magnetic resonance imaging (MRI), retroperitoneal soft tissue sarcoma was suspected. Because she rejected surgical treatment, we continued imaging surveillance. Subsequently, the mass grew larger, but her intention did not change. At 21 months after initial consultation, CT revealed further increase of the above mass and a new lesion with calcification. Ultimately, she underwent mass resection with concomitant resection of the right kidney. Histological examination showed dedifferentiated liposarcoma with metaplastic bone formation and positive surgical margin, but she refused adjuvant chemotherapy. She has survived 7 months since the operation with no evidence of recurrence.

Retroperitoneal soft tissue sarcoma: low-dose neoadjuvant radiation therapy followed by surgery with or without intraoperative radiotherapy and adjuvant radiation therapy.

We describe the clinical history, outcome, and toxicity of five patients with high-grade retroperitoneal soft tissue sarcoma (RSTS) who were treated with neoadjuvant low-dose radiotherapy (RT) followed by resection with or without intraoperative radiotherapy (IORT), followed by adjuvant RT. We aim to provide additional evidence for the various treatment options that exist for this rare tumor entity. Most patients presented with mild abdominal symptoms. Diagnosis was confirmed by biopsy. Additional imaging was done by sonography, magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/computed tomography (CT). All patients were treated with neoadjuvant RT of 19.8 Gy in 1.8-Gy fractions followed by resection and postoperative RT up to 45 Gy with amedian interval between resection and start of postoperative RT of 5weeks. Two patients received additional IORT. Median follow-up was 61months. One patient developed alocal recurrence that was diagnosed 30months after the start of the first therapy. He was treated with asalvage resection and had no evidence of disease at the last follow-up. Another patient developed aright-sided RSTS on the contralateral side from the primary radiation field with pelvic bone infiltration 56months after the start of RT. He was treated again by RT and resection and was without evidence of disease at last follow-up. Radiotherapy was well tolerated without major toxicity. The treatment of RSTS by low-dose neoadjuvant RT, resection with IORT and adjuvant RT seems to be afeasible and effective treatment approach. Further studies comparing neoadjuvant with adjuvant RT are necessary to find the best treatment option.