Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG).
ABSTRACT: Introduction:Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1%-0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. Methods:The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. Results:All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. Conclusions:This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.
Project description:Retroperitoneal soft tissue sarcomas (RPS) are rare tumors. Surgery is the mainstay of curative therapy, but local recurrence is common. No recommendations concerning the best management of recurring disease have been developed so far. Although every effort should be made to optimize the initial approach, recommendations to treat recurring RPS will be helpful to maximize disease control at recurrence.An RPS transatlantic working group was established in 2013. The goals of the group were to share institutional experiences, build large multi-institutional case series, and develop consensus documents on the approach to this difficult disease. The outcome of this document applies to recurrent RPS that is nonvisceral in origin. Included are sarcomas of major veins, undifferentiated pleomorphic sarcoma of psoas, ureteric leiomyosarcoma (LMS). Excluded are desmoids-type fibromatosis, angiomyolipoma, gastrointestinal stromal tumors, sarcomas arising from the gut or its mesentery, uterine LMS, prostatic sarcoma, paratesticular/spermatic cord sarcoma, Ewing sarcoma, alveolar/embryonal rhabdomyosarcoma, sarcoma arising from teratoma, carcinosarcoma, sarcomatoid carcinoma, clear cell sarcoma, radiation-induced sarcoma, paraganglioma, and malignant pheochromocytoma.Recurrent RPS management was evaluated from diagnosis to follow-up. It is a rare and complex malignancy that is best managed by an experienced multidisciplinary team in a specialized referral center. The best chance of cure is at the time of primary presentation, but some patients may experience prolonged disease control also at recurrence, when the approach is optimized and follows the recommendations contained herein.International collaboration is critical for adding to the present knowledge. A transatlantic prospective registry has been established.
Project description:<h4>Background</h4>There is currently no consensus on optimal management of patients with primary or recurrent non-resectable/residual retroperitoneal sarcomas (RPS). The objective of this study was to document the outcomes of patients with primary or recurrent non-resectable/residual RPS treated in our center with definitive radiotherapy (RT) and to perform a systematic review on the topic.<h4>Methods</h4>A retrospective analysis of consecutive RPS patients treated in our center between 2000 and 2019 was performed. All consecutive patients who underwent definitive conformal RT with image guidance for primary or recurrent non-resectable or macroscopically residual RPS were included. Additionally, a systematic review compliant with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed.<h4>Results</h4>The study enrolled 14 patients who met the aforementioned criteria. Data on clinicopathological characteristics, RT and response to treatment were assessed. RT allowed achieving prolonged local control of the disease, i.e. no local progression of the disease for more than 12 months after RT in 10 patients. Local control lasted more than 24 months in 6 cases, with minimal or no toxicity. A systemic review of 11 studies revealed concordance of our results with previous reports of primary or recurrent non-resectable/residual RPS.<h4>Conclusions</h4>RT provided satisfactory local disease control with acceptable treatment tolerance in patients with primary or recurrent non-resectable/residual RPS and represents a valuable treatment modality in the selected group of patients. Additional RT modalities i.e. BT, particle therapy, MRI-guided RT, or GRID/Lattice RT may be introduced to improve local control and further minimize toxicity.
Project description:Retroperitoneal sarcomas (RPS) are rare cancers whose management can be challenging due to various presentation patterns, multiple organ involvement, and a high local and distant recurrence rate. Histopathology and prognostic factors analysis are essential to predict the behaviour of the disease and plan the best therapeutic strategy. To date, surgery is still the main therapeutic option that guarantees a chance of cure from the primary disease. While chemotherapy and radiotherapy seem to be good options for controlling metastatic and recurrent irresectable disease, their role in the treatment of primary RPS remains unclear. This literature review aims to provide a comprehensive overview of the multidisciplinary aspects of RPS management in high-volume centres, summarising the diagnostic path, the prognostic factors, and the most suitable therapeutic options.
Project description:The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists.Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics.Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate.For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.
Project description:Introduction. Retroperitoneal sarcomas are uncommon large malignant tumors. Methods. Forty-one consecutive patients with localized retroperitoneal sarcoma were retrospectively studied. Results. Median age was 58 years (range 20-91 years). Median tumor size was 17.5 cm (range 4-41 cm). Only 2 tumors were <5 cm. Most were liposarcoma (44%) and high-grade (59%). 59% were stage 3 and the rest was stage 1. Median followup was 10 months (range 1-106 months). Thirty-eight patients had an initial complete resection; 15 (37%) developed recurrent sarcoma and 12 (80%) had a second complete resection. Patients with an initial complete resection had a 5-year survival of 46%. For all patients, tumor grade affected overall survival (P = .006). Complete surgical resection improved overall survival for high-grade tumors (P = .03). Conclusions. Tumor grade/stage and complete surgical resection for high-grade tumors are important prognostic variables. Radiation therapy or chemotherapy had no significant impact on overall or recurrence-free survival. Complete surgical resection is the treatment of choice for patients with initial and locally recurrent retroperitoneal sarcoma.
Project description:Retroperitoneal sarcomas (RPS), such as pleomorphic leiomyosarcoma, often invade or displace vital organs in the abdominal cavity and exhibit an aggressive clinical course. Complete surgical resection of the tumor and preoperative radiotherapy and chemotherapies can be used for non-metastatic RPS. However, in case of huge retroperitoneal sarcoma fully occupying the abdominal cavity, surgical resection tends to be insufficient, resulting in poor outcomes. This report describes a case of rapidly progressive retroperitoneal pleomorphic leiomyosarcoma that was favorably controlled by debulking surgery followed by combination chemotherapy and radiotherapy.A 65-year-old Japanese woman developed abdominal discomfort due to a huge retroperitoneal tumor fully occupying the abdominal cavity. The immunohistochemical diagnosis was pleomorphic leiomyosarcoma with high-grade malignancy and aggressive proliferative features. Debulking surgery could be performed, but the small residual tumor had rapidly grown to an approximately 22 cm in length on the major axis within 38 days after the operation. The patient's general condition progressively declined. Combination chemotherapy, consisting of doxorubicin and ifosfamide, was successfully administered for six cycles while maintaining dose intensity. The best objective response was a partial response, and the chemotherapy was well tolerated. Approximately 50 Gy of radiotherapy was delivered to the remaining tumor. This multimodal strategy resulted in progression-free survival for more than 17 months and achieved sustained symptomatic relief.Multimodal therapy with debulking surgery, combination chemotherapy and radiotherapy controlled a rapidly progressive retroperitoneal pleomorphic leiomyosarcoma. Maintaining dose intensity of the chemotherapy and radiotherapy might contribute to overall tumor control.
Project description:<b>Background:</b> Retroperitoneal sarcomas are rare neoplasms that occur in the retroperitoneum. Complete surgical resection is the only effective treatment option. The prediction of prognosis by histological diagnosis has not yet been established. The purpose of this study was to identify the usefulness of [18-F] fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging for validating the prognosis of retroperitoneal sarcoma (RPS) established by histological diagnosis. <b>Methods:</b> We retrospectively reviewed 201 patients with RPS treated at the Osaka International Cancer Institute between 2010 and 2021. We extracted the clinical data, including standardized uptake values (SUVs), evaluated with FDG-PET, and statistically analyzed the data. <b>Results:</b> The median age of patients was 64 years (range, 31-85 years). A total of 101 (50.2%) patients were men, and 100 (49.8%) were women. Surgical resection was performed in 155 (77.1%) patients. On histological analysis, 75 (37.3%), 52 (25.9%), and 29 (14.4%) patients were diagnosed with dedifferentiated liposarcoma, well-differentiated liposarcoma, and leiomyosarcoma, respectively. The median survival time for patients with high maximum SUV (SUVmax) (≥4) or low SUVmax (<4) was 275.8 months and 79.5 months, respectively. Furthermore, among the patients with dedifferentiated liposarcoma, the overall survival rate for patients with high SUVmax (≥4) was significantly lower than that of those with low SUVmax (<4). <b>Conclusions:</b> The present study demonstrated that SUVmax calculated with FDG-PET was useful as a prognostic factor in RPS, especially in dedifferentiated liposarcoma and Grade2 RPS. To devise a treatment strategy for RPS, SUVmax during FDG-PET scan may be considered for clinical assessment.
Project description:<h4>Background</h4>Although well described for gastrointestinal and pelvic cancers, use of minimally invasive surgery (MIS) for the management of retroperitoneal soft tissue sarcoma (RPS) remains unknown. The current study aimed to describe patterns of MIS use and assess the association between MIS and clinical outcomes among patients undergoing surgery for RPS.<h4>Methods</h4>Patients undergoing a primary resection for RPS between 2010 and 2014 were identified using the National Cancer Database. Multivariable logistic and Cox proportional hazards models were used to assess the association between use of MIS and clinical outcomes. Sensitivity analysis was performed using propensity score-matching (PSM).<h4>Results</h4>This study identified 3844 patients who met the inclusion criteria. Of these patients, 89.3% (n = 3432) underwent an open surgery, whereas 10.7% (n = 412) underwent MIS. The patients undergoing MIS were more likely to present with smaller tumors (open vs MIS: median tumor size, 17 cm; interquartile range [IQR, 9.8-26.0] vs 10.5 cm [IQR, 6.5-18.0]) and to undergo surgery at community hospitals (26.8% vs 36.1%; both P < 0.001). Although MIS was associated with a shorter hospital length of stay [LOS] (median LOS, 6 days [IQR, 5-9 days] vs 4 days [IQR, 2-7]; P < 0.001), postoperative mortality and overall survival were comparable between the two treatment groups (all P > 0.05). These findings were confirmed using PSM.<h4>Conclusions</h4>MIS was associated with a shorter LOS, however, postoperative mortality and overall survival were comparable by operative approach. Future research is required to evaluate the use of MIS for the management of RPS. Policies are required to ensure that patients receive care in accordance with best practices and recommended guidelines.
Project description:BACKGROUND:Margin negative resection offers the best chance of long-term survival in retroperitoneal sarcoma (RPS). En-bloc resection of adjacent structures, including the inferior vena cava (IVC), is often required to achieve negative margins. We review our 20-year experience of en-bloc IVC and RPS resection. METHODS:Retrospective review of patients with RPS resection involving the IVC were matched 1:3 by age and histology to RPS without IVC resection. Prognostic factors for overall survival (OS) and disease free survival (DFS) were assessed. RESULTS:Thirty-two patients underwent RPS resection en-bloc with IVC. They were matched with 96 cases of RPS without IVC resection. Median OS of 59 months and DFS 18 months in IVC resection group was comparable to RPS resection without vascular involvement: median OS 65 months, DFS 18 months (P?=?0.519, P?=?0.604). On multivariate analyses, R2 margin (OS: HR?=?6.52 [95%CI: 1.18-36.09], P?=?0.032) was associated with inferior OS. R2 margin and increased number of organs resected (DFS: HR?=?5.07, [1.15-22.27], P?=?0.031, HR?=?1.28 [1.01-1.62], P?=?0.014) were associated with inferior DFS. Reconstructions included graft (n?=?19, 59%), patch (n?=?4, 13%), primary repair (n?=?6, 19%), and ligation (n?=?4, 13%). CONCLUSIONS:RPS resection en-bloc with IVC can achieve equivalent rates of DFS and OS to patients without vascular involvement.
Project description:<h4>Background</h4>Definitive evidence to guide clinical practice on the principles of surgery for retroperitoneal sarcomas (RPSs) is still lacking. This study aims to summarise the available evidence to assess the relative benefits and disadvantages of an aggressive surgical approach with contiguous organ resection in patients with RPS, the association between surgical resection margins and survival outcomes, and the role of surgery in recurrent RPS.<h4>Methods</h4>We searched PubMed, the Cochrane Library, and EMBASE for relevant randomised trials and observational studies published from inception up to May 1, 2021. Prospective or retrospective studies, published in the English language, providing outcome data with surgical treatment in patients with RPS were selected. The primary outcome was overall survival (OS).<h4>Findings</h4>In total, 47 articles were analysed. There were no significant differences in the rates of OS (HR: 0.93; 95% CI: 0.83-1.03; P = 0.574) and recurrence-free survival (HR: 1.00; 95% CI: 0.74-1.27; P = 0.945) between the extended resection group and the tumour resection alone group. Organ resection did not increase postoperative mortality (OR: 1.00; 95% CI: 0.55-1.81; P = 0.997) but had a relatively higher complication rate (OR: 2.24, 95% CI: 0.94-5.34; P = 0.068). OS was higher in R0 than in R1 resection (HR: 1.34; 95% CI: 1.23-1.44; P < 0.001) and in R1 resection than in R2 resection (HR: 1.86; 95% CI: 1.35-2.36; P < 0.001). OS was also higher in R2 resection than in no surgery (HR: 1.26; 95% CI: 1.07-1.45; P < 0.001), however, subgroup analysis showed that the pooled HR in the trials reporting primary RPS was similar between the two groups (HR, 1.14; 95% CI, 0.87-1.42; P = 0.42). Surgical treatment achieves a significantly higher OS rate than does conservative treatment (HR: 2.42; 95% CI: 1.21-3.64; P < 0.001) for recurrent RPS.<h4>Conclusions</h4>For primary RPS, curative-intent en bloc resection should be aimed, and adjacent organs with evidence of direct invasion must be resected to avoid R2 resection. For recurrent RPS, surgical resection should be considered as a priority. Incomplete resection remains to have a survival benefit in select patients with unresectable recurrent RPS.