Favorable control of rapidly progressive retroperitoneal pleomorphic leiomyosarcoma with multimodality therapy: a case report.
ABSTRACT: 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: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:Background: Retroperitoneal sarcomas (RPS) are rare and primarily managed with surgery, which improves local recurrence-free and overall survival. Radiation can improve local control or provide palliation for inoperable or metastatic RPS by eliciting tumor cell death via irreparable DNA damage. In extraordinary circumstances radiation-induced cell death promotes immune-mediated regression of non-irradiated lesions in a process termed the abscopal effect. Abscopal effects are rare and incompletely understood, involving a balance of radiation's immunogenic and immunosuppressive effects. There are currently no methods to predict abscopal responses following radiotherapy. Case reports documenting post-radiotherapy abscopal effects provide additional information to better characterize these responses and to inform ongoing and future clinical trials attempting to harness radiation-induced immune responses to improve outcomes with systemic therapy, such as SARC-032, a cooperative group trial of pre-operative radiation ± pembrolizumab. We present a case of inoperable metastatic RPS treated with proton radiotherapy with complete responses of un-irradiated metastases. Case Presentation: A 67 year-old female with inoperable metastatic unclassified round cell RPS was treated with palliative proton radiotherapy only to the primary tumor. Following completion of radiotherapy, the patient demonstrated complete regression of all un-irradiated metastases, and near complete response of the primary lesion without additional therapy. Conclusions: Metastatic RPS is typically managed with first-line chemotherapy, with objective response rates <50%. We present a case of inoperable metastatic RPS treated with palliative proton radiotherapy for rapidly progressive disease who had complete regression of non-irradiated metastases consistent with the abscopal effect. To our knowledge this is the first case report describing abscopal effects in inoperable metastatic RPS treated with proton radiation and is among the first case reports of an abscopal effect in a patient treated with proton therapy regardless of disease site. Further investigation is warranted regarding the benefit of proton radiation to primary tumors for inoperable metastatic RPS.
Project description:Leiomyosarcoma is a soft tissue sarcoma whose outcome has historically been confounded by the inclusion of gastrointestinal stromal tumors. Thus, we sought to determine the factors that predict survival and recurrence in patients with primary leiomyosarcoma alone.During 1982-2006, a total of 353 patients with primary resectable leiomyosarcoma were identified from a prospective database. Multivariate analysis was used to assess clinicopathologic factors for association with disease-specific survival (DSS). Competing risk survival analysis was used to determine factors predictive for local and distant recurrence.Of 353 patients, 170 (48 %) presented with extremity, 144 (41 %) with abdominal/retroperitoneal, and 39 (11 %) with truncal tumors. Median age was 57 (range, 18-88) years, and median follow-up was 50 (range, 1-270) months. Most tumors were high grade (75 %), deep (73 %), and completely resected (97 %); median size was 6.0 (range, 0.3-45) cm. Abdominal/retroperitoneal location was associated with worse long-term DSS compared to extremity or trunk (P = 0.005). However, by multivariate analysis, only high grade and size were significant independent predictors of DSS. Overall, 139 patients (39 %) had recurrence: 51 % of those with abdominal/retroperitoneal, 33 % of extremity, and 26 % of truncal disease. Significant independent predictors for local recurrence were size and margin, whereas predictors for distant recurrence were size and grade. Site was not an independent predictor of recurrence; however, late recurrence (>5 years) occurred in 9 % of abdominal/retroperitoneal and 4 % of extremity lesions.Grade and size are significant independent predictors of DSS and distant recurrence. Long-term follow-up in leiomyosarcoma is important, as late recurrence continues in 6-9 % patients.
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:BACKGROUND:Retroperitoneal sarcomas (RPS) are heterogeneous. No previous study has investigated the impact of specialized surgery, evaluated locoregional relapse (LRR), abdominal sarcomatosis and distant metastatic relapse as separate events, or considered histological subtypes separately. This study addresses these specific points in a homogeneous cohort of patients with completely resected primary RPS. PATIENTS AND METHODS:We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 and eventually referred to one of 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist. RESULTS:Five hundred eighty-six patients were included. Median follow-up was 6.5 years [95% confidence interval (CI) 5.9-7.1]. Five hundred thirty-seven patients had localized disease and 389 patients (76%) had macroscopically complete resection of the tumor. In this latter group, the 5-year LRR-free survival rate was 46% [41-52] and the 5-year overall survival (OS) rate was 66% [61-71]. In multivariate analysis, gender, adjacent organ involvement, specialization of the surgeon, piecemeal resection and perioperative radiotherapy were independently associated with LRR. Specialization of the surgeon and piecemeal resection were independently associated with abdominal sarcomatosis whereas histology and adjacent organ involvement were independently associated with distant metastasis. Age, gender, grade, adjacent organ involvement and piecemeal resection were significantly associated with OS. Prognostic factors for LRR and OS were analyzed in well-differentiated and dedifferentiated liposarcomas and leiomyosarcomas. Grade 3 was an independent prognostic factor for OS of dedifferentiated liposarcomas. CONCLUSION:This study underlines the crucial role of pretherapeutic assessment and meticulous histological examination of RPS as well as the need to consider histological subtypes separately. Surgery in a specialized center and avoidance of piecemeal resection stand out as the two most important prognostic factors for RPS and highlight the importance of treating these patients in specialized centers.
Project description:Peri-operative radiation of retroperitoneal sarcomas (RPS) is an important component of multidisciplinary treatment. All retrospective series thus far included patients treated with older radiation therapy (RT) techniques including 2D and 3DRT. Intensity modulated radiation therapy (IMRT) allows for selective dose escalation while sparing adjacent organs. We therefore report the first series of patients with RPS treated solely with IMRT, surgery and chemotherapy. We hypothesized that IMRT would permit safe dose escalation and superior rates of local control (LC) in this high-risk patient population.Thirty patients with RPS treated with curative intent between 2006 and 2015 were included in this retrospective study. RT was administered either pre- or post-operatively and IMRT was used in all patients. Statistical comparisons, LC, distant metastasis (DM), and overall survival (OS) were calculated by Kaplan-Meier analysis and univariate Cox regression.Median follow-up time after completion of RT was 36 months (range 1.4-112). Median tumor size was 14 cm (range 3.6 - 28 cm). The most prevalent histologies were liposarcoma in 10 (33%) patients and leiomyosarcoma in 10 (33%) with 21 patients (70%) having high-grade disease. Twenty-eight (93%) patients had surgical resection with 47% having positive margins. Chemotherapy was administered in 9 (30%) patients. RT was delivered pre-operatively in 11 (37%) patients, and post-operatively in 19 (63%) with 60% of patients receiving a simultaneous integrated boost. Pre-operative median RT dose to the high-risk area was 55 Gy (range, 43-66 Gy) while median post-operative dose was 60.4 Gy (range, 45-66.6 Gy). There was one acute grade 3 and one late grade 3 toxicity and no grade 4 or 5 toxicities. Three year actuarial LC, freedom from DM, and OS rates were 84%, 64%, and 68% respectively. Positive surgical margins were associated with a higher risk of local recurrence (p?=?0.02) and decreased OS (p?=?0.04). Pre-operative RT was associated with improved LC (p?=?0.1) with a 5-year actuarial LC of 100%. Administration of chemotherapy, timing of RT, histology or grade was not predictive of OS.Patients with RPS treated with peri-operative IMRT at our institution had excellent local control and low incidences of toxicity.
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>Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy.<h4>Patients and methods</h4>We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy.<h4>Results</h4>With a median follow-up of 24 months (2-114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, <i>p</i> = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2.<h4>Conclusions</h4>Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.
Project description:<h4>Background</h4>Retroperitoneal sarcomas (RPS) are heterogeneous. Advanced stages include unresectable locoregional (LR) disease, abdominal sarcomatosis and distant metastasis. There is no available report assessing palliative chemotherapy in advanced RPS. This study analyzes management and outcome in a large cohort of patients with advanced RPS, considering main histological subtypes separately.<h4>Patients and methods</h4>We conducted a retrospective analysis of adult patients diagnosed with a RPS between 1 January 1988 and 31 December 2008 across 12 centers of the French Sarcoma Group. All cases were centrally reviewed by an expert pathologist.<h4>Results</h4>Five-hundred eighty-six patients were included, 299 patients received palliative chemotherapy, with a median of two lines (range 0-8). Fifty patients underwent palliative surgery. Two hundred fifty-five patients (85%) were assessable for response after first line of chemotherapy. Among them, 69 patients (27%) had progressive disease, 145 (57%) had stable disease, 37 (14.5%) had partial response and 4 (1.5%) complete response. Median time from first line of palliative chemotherapy to progression was 5.9 months [4.9-7.3] and median overall survival (OS), 15.8 months [13-18]. In multivariate analysis, prognosis factors independently associated with poor OS were male gender, performance status (PS) >1 and grade >1. There was no difference according to stage of disease. Palliative surgery did not appear to add any survival benefit.<h4>Conclusion</h4>These results emphasize the scarcity of available options for RPS in the advanced setting and the urgent need to develop new strategies. Patients with good PS should be included in clinical trials and best supportive care should be considered in those with poor PS.