Management Of Retroperitoneal Sarcoma Research Articles

Comparison of Estimated Late Toxicities between IMRT and IMPT when Treating Retroperitoneal Sarcoma Preoperatively with Ultra-Hypofractionation

While preoperative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. The risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. Thus, finding methods to mitigate the issues of delaying surgery and irradiating normal tissue may provide a path towards affording the benefits of radiation while limiting its downside. One potential solution involves the use of hypofractionation to limit delay from radiation initiation to surgery, and proton therapy to limit dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of preoperative ultra-hypofractionated intensity-modulated photon radiotherapy (IMRT) and proton therapy (IMPT) for RPS, comparing estimated rates of late toxicity using published normal tissue complication probability (NTCP) models. Volumetric modulated arc therapy IMRT and IMPT plans were generated on 10 RPS patients previously treated with preoperative radiation. The prescription was 25 Gy radiobiological equivalent (GyE) to the clinical target volume (CTV) and 30 GyE to the margin-at-risk, all in five fractions. Proton doses were calculated using a radiobiological effective dose of 1.1. NTCPs were calculated for each OAR as a function of equivalent uniform dose. The ΔNTCP (difference in absolute NTCP between IMRT and IMPT plans) for each of the toxicity domains was calculated. Student T-tests were used to compare differences in dosimetric and NTCP outcomes. CTV coverage was met for all IMRT and IMPT plans with >99% of CTVs receiving ≥100% of prescription doses. The following endpoints were significantly lower with IMPT than IMRT: mean doses to liver, bone, and all analyzed genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. No OAR endpoint was significantly higher with IMPT. The average ΔNTCP for grade 3 bowel ulceration/perforation and renal toxicity was 1.9% (p = .037) and 43.0% (p = .023), respectively, favoring IMPT. Using a model-based selection threshold of any ΔNTCP >10%, 50% (n = 5) of patients would be eligible for IMPT. IMPT maintained target coverage while significantly reducing dose to adjacent OARs and integral dose compared to IMRT. This translated to significantly lower risks of estimated late gastrointestinal and renal toxicities with IMPT. Further investigation is warranted to validate these findings and potential clinical benefit in the management of RPS. A prospective trial treating RPS with preoperative ultra-hypofractionated IMPT at our institution is currently being pursued (NCT05302570).

In Silico Dosimetric Comparison of Intensity-Modulated Proton Radiotherapy (IMPT) vs. Intensity-Modulated Photon Radiotherapy (IMRT) in the Preoperative Treatment of Retroperitoneal Sarcoma

<h3>Purpose/Objective(s)</h3> With the results of the randomized STRASS trial, the benefit of preoperative radiation has been called into question in the treatment of retroperitoneal sarcoma. Given the large amount of normal tissue which often resides in close proximity to retroperitoneal sarcomas, the risk of radiation-associated toxicity is substantial, with 77% of irradiated patients experiencing grade ≥3 lymphopenia in STRASS. The exit dose and integral exposure associated with photon irradiation limits its therapeutic ratio. Our purpose was to evaluate a dosimetric comparison between ultra-hypofractionated modern scanning beam intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) for the preoperative treatment of retroperitoneal sarcoma. We hypothesized that IMPT would significantly reduce dose to the to the liver, bowel and kidneys without sacrificing clinical target volume (CTV) coverage. <h3>Materials/Methods</h3> Ultra-hypofractionated IMRT and IMPT plans were generated using TPS on 10 patients previously treated with conventionally fractionated preoperative photon irradiation for retroperitoneal sarcoma. The prescription was 25 Gy radiobiological equivalent (GyE) to the entire CTV and 30 GyE to the margin-at-risk (CTV_Boost), all in five fractions. IMPT doses are reported in GyE = 1.1 Gy. Target coverage goals, OAR constraints, and integral dose were compared by student T-test with <i>p</i> < .050 considered significant. <h3>Results</h3> Target coverage goals, OAR constraints, and integral dose are reported in Table 1. Mean dose to liver, bowel, and ipsilateral and contralateral kidneys were all significantly lower with IMPT than IMRT, as was integral dose. <h3>Conclusion</h3> IMPT maintained target coverage while significantly reducing integral dose and mean dose to nearby OARs compared to IMRT. Further investigation is warranted to validate these dosimetric findings and potential clinical benefit in the management of retroperitoneal sarcoma.

The role of standard and novel radiotherapy approaches in management of retroperitoneal sarcomas

Primary non-metastatic retroperitoneal soft tissue sarcoma patients can be cured by radical surgery. However there remains a risk for patients to develop a local recurrence. To minimize this risk, patients with low grade liposarcomas might benefit from preoperative radiotherapy. This review summarizes all issues that should be considered for the irradiation of patients with retroperitoneal soft tissue sarcoma.

The management of retroperitoneal sarcoma: The experience of a single institution and a review of the literature

ObjectivesRetroperitoneal sarcomas (RPSs) are rare mesenchymal tumors. The objective of this study was to discuss the different clinical, therapeutic and prognostic aspects of RPS in our institution. MethodsThis was a retrospective study conducted at the Department of Medical Oncology in the Habib Bourguiba University Hospital in Sfax, including 19 patients who were treated for RPSs between 1999 and 2016. ResultsThe median age was 49 years (range: 18–83 years); 68.4% of the patients were female. The commonest symptom was abdominal pain (88%) and the median tumor size was 15 cm (range: 4–30 cm). Complete resection was achieved in only five cases (26.3%). The most common histological subtypes were liposarcoma (47.4%) and leiomyosarcoma (26.3%). Eight patients had a high-grade tumor (G2 = 2 or G3 = 6). Adjuvant radiotherapy was administered in 5 patients (26%). Seventeen patients were treated with chemotherapy; six received chemotherapy in an adjuvant treatment, three as a neoadjuvant treatment, and eight were treated during the palliative phase. Relapse was observed in 58% of cases. For all patients, the overall survival (OS) was 89.5% at 1 year and 40.3% at 5 years. Prognostic factors influencing OS were sex (p = 0.037), resection margins (p = 0.02), recurrence (p = 0.042), and radiotherapy (p = 0.023). In multivariate analysis, radiotherapy (p = 0.031) and histological subtype (p = 0.028) were independent factors influencing OS and disease-free survival (DFS) respectively. ConclusionWe showed that the treatment of RPSs relies on surgery with complete resection. Other factors, such as radiotherapy and the occurrence of relapse, also have an impact on OS. To facilitate surgery and to obtain negative resection margins, preoperative radiotherapy is indicated in selected patients with a high risk of relapse. Further prospective trials are warranted to select optimal therapies with less toxicity and better efficacy in reducing recurrences, mainly at a local level.

Adjuvant therapy for retroperitoneal sarcoma: a meta-analysis

BackgroundAdjuvant 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.MethodsWe searched PubMed, Web of Science, Embase, ASCO s, 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.ResultsA 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.ConclusionsOverall, 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.

ASO Author Reflections: Standardization in the Management of Retroperitoneal Sarcoma Through International Collaboration.

ASO Author Reflections: Standardization in the Management of Retroperitoneal Sarcoma Through International Collaboration.

A critical narrative review of radiotherapy for retroperitoneal soft tissue sarcoma.

Retroperitoneal sarcomas (RPSs) are rare diseases, and the 5-year overall survival rate remains low. Management of RPSs is challenging, and the quality of treatment strategy is a crucial prognostic factor. Treatment decisions and the treatment department to which the patients is referred must be centralized. Overall survival rate is positively correlated with the number of patients treated in the centers. En bloc surgery is the standard of care for effective treatment and potential for cure, whereas perioperative chemotherapy or radiotherapy has not yet been validated. Pre- or postoperative radiotherapy was considered controversial, but the STRASS trial publication illustrated that preoperative radiation could be useful in some conditions. Retroperitoneal liposarcoma might become a future target of prospective trials. Furthermore, some retrospective studies have shown that preoperative radiotherapy increases the rate of R0-R1 resections. This article reviews the role of external beam radiotherapy in the management of RPS and highlights the optimal volumes, doses, and radiotherapy techniques for the treatment of RPS. As accurately predicting prognosis in patients with RPS is challenging, we also emphasize the utility of nomograms in the field of radiotherapy. However, these nomograms do not include radiotherapy as a predictive factor. Although some authors could conclude that use of radiotherapy should be avoided based on the results of the STRASS trial, some data argue that radiotherapy still has utility in select cases.

Primary iliocaval leiomyosarcomas: The path beyond surgery

IntroductionIliocaval leiomyosarcoma (ICLM) is a rare and aggressive form of sarcoma within the retroperitoneum. Surgery is the mainstay of treatment, with no consensus on the benefit of chemoradiotherapy in the neo/adjuvant setting. This study aims to describe the natural history of a chemotherapy-naïve ICLM treated in a tertiary cancer centre and to explore potential directions to improve oncological outcome. Materials and methodsA prospective database was used to identify patient demographics, clinicopathological variables and oncological outcomes in 30 patients who underwent surgical resection in our institution for primary non-metastatic ICLM between 2003 and 2018. ResultsThere was no 90-day mortality. With a median follow-up time of 70.0 months (95% CI 52.6–87.4), 5/30 patients (16.7%) developed local recurrence while 11/30 (36.7%) developed distant metastatic disease. 1 patient (3.3%) developed both local and distant recurrence. Median overall survival of our cohort was 41.0 months (95% CI 33.6–48.4) and 5-year overall survival rate was 32.1%. Multivariate survival analysis using the Cox proportional hazard model identified tumour grade and blood loss of more than 600 mL as key prognostic factors in our model. ConclusionManagement of ICLM should be centralised in high-volume sarcoma centres with expertise in the management of retroperitoneal sarcomas. Integration of tumour biology with a concerted effort to conduct conclusive multi-centre phase III in histological and molecularly defined sarcoma subgroups is necessary to improve patient outcome. We eagerly await the results of STRASS 2 study to gain more insights to the efficacy of neoadjuvant chemotherapy on patient prognosis.

Update in Pelvic and Retroperitoneal Sarcoma Management: The Role of Compartment Surgery

Surgery for retroperitoneal sarcomas should be “enbloc” compartmental, which involves resection of unaffected organs. Its upfront use is key, providing a high percentage of resections with negative margins, resulting in a better local control and increased survival in many patients. Preservation of organs should be done in an individualized manner, especially in the pelvic location, and adapted to the histological aggressiveness of the tumor. Preoperative biopsy is able to establish the diagnosis of sarcoma subtype and consequently an adequate perioperative strategy. These patients should be managed by expert surgeons at referral centers with multidisciplinary units and oncology committees. The use of chemotherapy and radiotherapy is not yet well defined, so it is only recommended at referral centers with clinical trials. Currently, this is the only option to offer the best morbidity and mortality rates, as well as possible improvements in the survival of these patients.

Impact of centralization of services on outcomes in a rare tumour: Retroperitoneal sarcomas

Background and aimThe retroperitoneal tumor (RPT) service in the North West costal region of England was centralized in May 2011 by the merger of the Merseyside, Cheshire and Lancashire, Cumbria sarcoma networks. Our aim was to analyze the impact of centralization of services on patient outcomes. MethodsAn analysis from 01/12/2004 to 30/11/2017 was undertaken from prospectively maintained database and electronic patient records; follow-up was until 30/04/2018. This time period encompassed 6.5 years before and after centralization of services took place. Survival analysis was done for Retroperitoneal Sarcomas (RPS) and also compared the impact of centralization. Results72 patients (27 men), median age 69 (21–90) years) underwent 95 operations with an intention to excise RPS. Overall there were 52 (54.7%) multi-visceral resections (MVR). 91/95 (95.8%) patients with primary tumors had surgery with a curative (R0/1) intent. 30-day and 90-day operative mortality was 3.2% (n = 3) and 4.2% (n = 4) respectively. The 5-year survival for patients undergoing resection for RPTs was 51.3%. 79 (83.1%) of the resections in this series occurred in the 6.5-years post-centralization with an increase in MVR between the two time points (p < 0.0006). Despite the more radical nature of surgery post-centralization, there was no difference in 5-year survival for RPS patients when compared to pre-centralization, p = 0.575. However the 5-yr survival post-centralization compared favorability to national outcomes. ConclusionCentralization in the management of RPS has resulted in an increase in resection rates and more complex MVRs, without compromising R0/1 resection rates; peri-operative mortality or overall survival.

Systemic therapy in retroperitoneal sarcoma management.

There is paucity of randomized controlled data on the role of systemic therapy in retroperitoneal sarcomas. The type of systemic therapy used is guided by the histological subtype. The majority of retroperitoneal sarcomas comprising liposarcomas and leiomyosarcomas are by and large chemotherapy insensitive. There is an urgent need for more efficacious systemic therapies in the management of early and advanced stage retroperitoneal sarcomas.

Radiation therapy in retroperitoneal sarcoma management.

Surgery is potentially curative for primary non-metastatic retroperitoneal soft tissue sarcomas (RPS), although patients remain at risk for local recurrence. To reduce this risk, the addition of radiotherapy to radical surgery may be considered. Nevertheless, level I evidence to support radiotherapy is currently lacking. The results from the EORTC-STBSG 62092-22092 studying this question are awaited. This manuscript addresses issues to consider when radiation-oncologists engage in a multidisciplinary treatment approach for RPS patients, including radiotherapy.

Long-Term Quality of Life of Retroperitoneal Sarcoma Patients Treated with Pre-Operative Radiotherapy and Surgery.

Purpose: Retroperitoneal sarcomas (RPS) are connective tissue cancers that are often large and anatomically in close proximity to critical and radiation-sensitive normal structures and organs within the abdomen and pelvis. The management of RPS may include preoperative radiotherapy (RT) and surgery. We aimed to examine how treatment-related toxicities affect patient quality of life (QOL). Methods and materials: Within two prospective cohort studies, 48 RPS patients who were treated with preoperative RT from 1998-2012 were recruited and assessed for QOL (EORTC-QLQ-C30) and to determine toxicities potentially related to RT and surgery (graded using CTCAE V.4). Baseline and prospective QOL was available for 11 patients. In the other 37 patients, prospective data were obtained at different time points during their follow-up. Unless stated otherwise, all scores refer to the global QOL subscale.Results: The patients' median age was 57 (38-82) and RT was administered to a median dose of 45 Gy (41.4-50.4). The median maximum tumor dimension was 16.0 cm (5.7-28) and the majority (35/48) were liposarcomas. The mean pre-RT QOL was 48.5/100. At one month post-RT, the mean QOL improved to 54.2; however, the mean diarrhea symptom scale worsened from baseline (78.3 vs. 18.2, p<0.001). Correspondingly, 54% of patients had gastrointestinal toxicities (92% G1-2 and 8% G3) by the end of RT. At 36 months post-RT, 88% of patients had chronic toxicities (19% G3). RPS patients who survived and are free of recurrence ≥ 36 months had significantly (mean: 75.0; p=0.001) better QOL than at diagnosis. The number of toxicities was significantly (p=0.001) associated with QOL. RT dose, tumor size, patient age, and patient gender were not associated with 36-month QOL. Conclusions: Treatment toxicities seem to contribute to QOL recovery during the first 36 months. QOL at 36 months was better than at diagnosis.

Feasibility of spacers to facilitate postoperative radiotherapy for retroperitoneal sarcomas.

The role and timing of postoperative radiotherapy (PORT) in the management of retroperitoneal sarcoma (RPS) remains controversial. This is a retrospective cohort review of patients undergoing curative resection for RPS at a single institution between January 2011 and July 2016. Patient selection was through the South Australian Soft Tissue Tumour Multidisciplinary Group (MDT) based at Royal Adelaide Hospital. An individualised approach, including assessment of resectability, histopathological grade and subtype, and radiotherapy considerations, was taken for each patient. Patients offered preoperative radiotherapy or palliation were excluded. A saline-filled spacer was inserted following operative resection. Radiotherapy commenced postoperatively. Patients underwent laparotomy to remove the device approximately 6 weeks post completion of PORT. Primary endpoints were technical feasibility, perioperative morbidity and radiation toxicity. Secondary endpoints were local recurrence (LR), distant recurrence (DR) and death. During the study period, 40 patients with RPS were managed through the MDT. Twelve patients (ages 33-78) underwent PORT utilising spacers. Radiotherapy toxicity was reported in four patients and extensive adhesions observed in another four patients during spacer removal. Median follow-up was 35 months (range 4-60). Seven patients remain alive and disease free. Four patients developed LR, three developed DR. Three patients died; two with DR and one with LR. Two patients with recurrent/progressive disease are alive; one with DR and one with LR. Use of intraoperative spacers to facilitate PORT is feasible, with acceptable toxicity following resection of RPS. Patient selection for this approach remains to be determined.

Tumor biology remains the main determinant of prognosis in retroperitoneal sarcomas: a 14-year single-center experience.

To review our experience in the management of retroperitoneal sarcomas (RPSs) in a single institution, with a predominantly Asian population, and identify associated prognostic factors for overall survival (OS), disease-free survival (DFS) and local recurrence. All RPSs diagnosed and managed at our center between January 2000 and March 2014 were included. Exclusion criteria included patients whose medical records were untraceable and patients who underwent biopsy but did not undergo resection. The variables studied were age, gender, histological subtype, tumor size, tumor grade, surgical margins, type of presentation of tumor (primary or recurrent) and presence of contiguous organ resection. The primary outcome measured was OS. Eighty-five patients underwent resection of RPS with curative intent. Eight patients underwent adjuvant chemotherapy and 15 patients underwent radiotherapy. The median DFS was 21 months (range: 0-146) and median OS was 45 months (range: 1-233). On univariate analysis, resection margin (P = 0.04), tumor grade (P = 0.011) and type of presentation of tumor (P = 0.007) were found to significantly affect OS. Patients with tumor adherent to contiguous organs had a greater OS as compared to patients with tumor invasive into the contiguous organs (P = 0.02). An aggressive surgical approach in primary and recurrent RPS is associated with good OS. Complete resection, with contiguous organ resection if necessary should be performed to achieve microscopically negative surgical margins to allow for long-term survival. However, tumor biology remains the main determinant for OS.

Management of Retroperitoneal Sarcomas With Intensity Modulated Radiation Therapy, Surgery, and Chemotherapy: A Single-Institution Experience

Management of Retroperitoneal Sarcomas With Intensity Modulated Radiation Therapy, Surgery, and Chemotherapy: A Single-Institution Experience

A huge retroperitoneal liposarcoma

The aim of the presentation is to show the value of the radical excision of an interesting case of the retroperitoneal liposarcoma. Retroperitoneal sarcomas are malignant tumours arising from mesenchymal cells, which are usually located in muscle, fat, and connective tissues. One-third of malignant tumours located in the retroperitoneum are sarcomas, and approximately 15% of soft tissue sarcomas arise in the retroperitoneum.Complete resection is mandatory for the cure of liposarcoma. The authors reported a 65-year old male that presented with complaints of painless progressive distension of abdomen for the last 10 years, which was associated with. significant weight loss and loss of appetite. Contrast Enhanced Computed Tomography of abdomen and CT angiography showed the features likely suggestive of liposarcoma. Patient underwent exploratory laparotomy with complete resection of the tumor. Histopathology of resected specimen revealed it to be a well differentiated liposarcoma. The management of retroperitoneal sarcomas consists of complete resection of the tumour, followed by adjuvant radiotherapy, reduces local recurrence but does not affect overall survival, and, combined with surveillance for early detection of recurrence or metastases, in our case.therapeutic embolization, proved to be useful preoperatively, allowing tumour shrinkage, and reduced blood loss during resection.

Place de la radiothérapie dans la prise en charge des sarcomes rétropéritonéaux

The management of retroperitoneal sarcoma can be very challenging, and the quality of initial treatment strategy appears to be a crucial prognostic factor. En bloc surgery is currently the standard of care for these rare tumours and perioperative treatments such as chemotherapy or radiotherapy have not been validated yet. However, local-regional relapse constitutes the most common disease course. While adjuvant radiotherapy is less and less common due to gastrointestinal toxicities, preoperative radiation therapy offers numerous advantages and is being evaluated as part of a national multicentre phase II study (TOMOREP trial) and is the subject of a European randomized phase III study (STRASS trial). The objective of this article is to present data on preoperative irradiation in terms of dose, volumes and optimal radiotherapy techniques for the treatment of this rare disease.

Retroperitoneal Sarcoma - A Diagnostic Challenge with Only a Surgical Cure

Sarcomas are solid tumours of mesenchymal cell origin and account for 1% of all adult malignancies. Retroperitoneal sarcomas more commonly affect people in their 50’s who can present to a general surgeon for assessment of non-specific abdominal symptoms. This nature of their presentation and anatomical location provides a diagnostic challenge and initial investigations may be normal. Patients can therefore present late when the tumour is locally advanced. Complete surgical resection with negative macroscopic margins is the treatment of choice and the only proven modality to improve survival and reduce disease recurrence. Extensive resection of multiple organs may be necessary to offer any chance of cure. The benefits of other treatments such as radiotherapy and chemotherapy are less certain. We will present the case of a 63-year-old man who presented with a chronic history of non-specific abdominal symptoms and outline the results of his investigations and subsequent management. We will briefly discuss some of the issue relating to the diagnosis and management of retroperitoneal sarcomas in general.

Giant retroperitoneal liposarcoma: A very rare case report

Soft-tissue sarcomas are very rare entity, seen in <1% of all malignancies. Sarcoma accounts for about one-third of all retroperitoneal malignancies. Management of retroperitoneal sarcoma is challenge for surgeons because of its rare presentation and no standard guidelines for it. A 65-year-old male presented to surgery out-patient department with the complaints of abdominal distention and pain in abdomen since 3 years. On imaging, he was diagnosed as case of retroperitoneal tumor and managed by radical surgery including resection of the tumor with left kidney, spleen, and descending colon. Postoperative period was uneventful.