New Sarculator Prognostic Nomograms for Patients With Primary Retroperitoneal Sarcoma: Case Volume Does Matter.

OBJECTIVE: To update the current Sarculator retroperitoneal sarcoma (RPS) prognostic nomograms considering the improvement in patient prognosis and the case volume effect. BACKGROUND: Survival of patients with primary RPS has been increasing over time, and the volume-outcome relationship has been well recognized. Nevertheless, the specific impact on prognostic nomograms is unknown. METHODS: All consecutive adult patients with primary localized RPS treated at 8 European and North American sarcoma reference centers between 2010 and 2017 were included. Patients were divided into 2 groups: high-volume centers (HVC, ≥13 cases/year) and low-volume centers (LVC, <13 cases/year). Primary end points were overall survival (OS) and disease-free survival (DFS). Multivariable analyses for OS and DFS were performed. The nomograms were updated by recalibration. Nomograms performance was assessed in terms of discrimination (Harrell C index) and calibration (calibration plot). RESULTS: The HVC and LVC groups comprised 857 and 244 patients, respectively. The median annual primary RPS case volume (interquartile range) was 24.0 in HVC (15.0-41.3) and 9.0 in LVC (1.8-10.3). Five-year OS was 71.4% (95% CI: 68.3%-74.7%) in the HVC cohort and 63.3% (56.8%-70.5%) in the LVC cohort ( P =0.012). Case volume was associated with both OS (LVC vs. HVC hazard ratio 1.40, 95% CI: 1.08-1.82, P =0.011) and DFS (hazard ratio 1.93, 95% CI: 1.57-2.37, P <0.001) at multivariable analyses. When applied to the study cohorts, the Sarculator nomograms showed good discrimination (Harrell C index between 0.68 and 0.73). The recalibrated nomograms showed good calibration in the HVC group, whereas the original nomograms showed good calibration in the LVC group. CONCLUSIONS: New nomograms for patients with primary RPS treated with surgery at high-volume versus low-volume sarcoma reference centers are available in the Sarculator app.

Surgical Outcome in Retroperitoneal Sarcoma Surgery: Accuracy of P-POSSUM, ACS-NSQIP, and Inflammatory Biomarkers Prognostic Index (IBPI) Risk-Calculators for Prediction of Severe and Overall Morbidity.

INTRODUCTION: Retroperitoneal sarcoma often requires comprehensive resection, leading to severe postoperative morbidity. The lack of disease-procedure specific tools for morbidity risk and the questionable accuracy of existing tools (ACS-NSQIP and P-POSSUM) in RPS surgery drove this study to assess these calculators' accuracy. METHODS: Retrospective analysis of primary RPS cases undergoing surgery at two sarcoma-referral centers was conducted. Predicted morbidity/mortality rates at 90 days postsurgery, classified by Clavien-Dindo (CD) and Comprehensive Complication Index (CCI), were compared with observed data. Accuracy was assessed by Brier Score and area under the curve (AUC). Inflammatory Biomarkers Prognostic Index (IBPI) also was tested. RESULTS: A total of 567 patients (median age 62 years; 53.6% male) with a median of four resected organs were included. 59% experienced surgical complications by 90 days postoperation, graded CD ≥ 3 in 30.5%, median CCI 20.9, with a mortality rate of 1.6% (8/567). Reoperation was required in 68 of 567 patients (12%). Thirty-day mortality was 1.1%. Severe complications occurred after 30th postoperative day in 3.5% cases. ACS-NSQIP predicted below-average complication for 65.1%, average for 16.9%, and above-average for 18% of patients. P-POSSUM predicted a 66% rate of morbidity and 4% mortality. None of the prediction tools were accurate, with Brier scores ranging 0.155-0.231 and no AUC ≥ 0.7. IBPI accuracy for predicting severe infective complication was low (AUC 0.58, Brier 0.161). CONCLUSIONS: The significant morbidity burden after MVR necessitates reliable evaluation, especially in frail patients. Given the limitations of ACS-NSQIP and P-POSSUM, a dedicated prediction tool for perioperative events in RPS candidates for MVR needs urgent development.

Pleomorphic Liposarcoma of the Extremity and Trunk: Multimodality Therapy for Some but Not All?

BACKGROUND: Pleomorphic liposarcoma (PLPS) is an ultra-rare malignancy distinct from well-differentiated/dedifferentiated and myxoid liposarcoma. In this study, we sought to (1) assess outcomes after surgery for primary, non-metastatic PLPS and (2) explore potential indications for multimodality therapy. METHODS: Clinicopathologic data were retrospectively collected for patients treated from 2002 to 2019 at our sarcoma referral center. Descriptive data were summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR), and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest on outcome. RESULTS: Forty-four pathology-verified PLPS cases were included in this study. Median tumor size was 8.5 cm; 75% were FNCLCC Grade 3. All patients underwent complete resection, including 15 patients (34%) who required re-excision to secure microscopic negative margins. Radiation therapy was given to 75% of patients, chemotherapy in 36%. At 5 years, OS was 75.3%; CCI of DSD, LR, and DM were 17.5%, 2.3%, and 32.5%. Larger tumor size was strongly associated with worse OS (p = 0.028) and DSD (p ≤ 0.001). A subgroup of patients (n = 10, 23%) with smaller, predominantly Grade 2 tumors underwent surgery alone without any LR or DM event at a median follow-up of 7.9 years. CONCLUSIONS: In PLPS, aggressive surgery and when appropriate, radiation therapy, results in excellent local control. Chemotherapy can be considered for larger tumors. Patients with smaller, Grade 2 tumors may be potentially cured with surgery alone.

Extent of macroscopic vascular invasion predicts distant metastasis in primary leiomyosarcoma of the inferior vena cava.

BACKGROUND: In retroperitoneal leiomyosarcoma (RP LMS), the predominant issue is distant metastasis (DM). We sought to determine variables associated with this outcome and disease-specific death (DSD). METHODS: Data were retrospectively collected on patients with primary RP LMS treated at a high-volume center from 2002 to 2023. For inferior vena cava (IVC)-origin tumors, the extent of macroscopic vascular invasion was re-assessed on each resection specimen and correlated with preoperative cross-sectional imaging. Crude cumulative incidences were estimated for DM and DSD and univariable and multivariable models were performed. RESULTS: Among 157 study patients, median tumor size was 11.0 cm and 96.2% of cases were intermediate or high grade. All patients underwent complete resection, 56.7% received chemotherapy (43.9% neoadjuvant) and 14.6% received radiation therapy. Only tumor size and grade and not site of tumor origin (e.g., IVC vs. other) were associated with DM and DSD (p < 0.05). Among 64 patients with IVC-origin tumors, a novel 3-tier classification was devised based on the level of intimal disruption, which was associated with both DM (p = 0.007) and DSD (0.002). CONCLUSION: In primary RP LMS, only tumor size and grade are predictive of DM and DSD. In IVC-origin tumors, the extent of macroscopic vascular invasion is also strongly predictive of these outcomes.

Opportunities and Challenges in Soft Tissue Sarcoma Risk Stratification in the Era of Personalised Medicine.

OPINION STATEMENT: Soft tissue sarcomas (STS) are a rare and heterogeneous group of cancers. Treatment options have changed little in the past thirty years, and the role of neoadjuvant chemotherapy is controversial. Accurate risk stratification is crucial in STS in order to facilitate clinical discussions around peri-operative treatment. Current risk stratification tools used in clinic, such as Sarculator, use clinicopathological characteristics and may be specific to anatomical site or to histology. More recently, risk stratification tools have been developed using molecular or immunological data. Combining Sarculator with other risk stratification tools may identify novel patient groups with differential clinical outcomes. There are several considerations when translating risk stratification tools into widespread clinical use, including establishing clinical utility, health economic value, being applicable to existing clinical pathways, having strong real-world performance, and being supported by investment into infrastructure. Future work may include incorporation of novel modalities and data integration techniques.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

BACKGROUND: To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). METHODS: All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. RESULTS: Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p = .09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. CONCLUSION: In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

Preoperative Radiotherapy in Patients With Primary Retroperitoneal Sarcoma: EORTC-62092 Trial (STRASS) Versus Off-trial (STREXIT) Results.

OBJECTIVE: The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma. BACKGROUND: The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S). METHODS: All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first. RESULTS: STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival. CONCLUSIONS: In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

Six Surgical Stages in the Resection of Primary Right Retroperitoneal Liposarcoma: A Standardized Comprehensive Approach.

BACKGROUND: Surgery is the treatment mainstay in retroperitoneal sarcoma (RPS), a frontline comprehensive approach based on tumor removal en bloc with adherent viscera is mandatory especially for liposarcoma, where the normal retroperitoneal fat is undistinguishable from the well-differentiated tumor component.1-5 In this video, a reproducible and standardized six-stage approach to a primary right retroperitoneal liposarcoma is presented. PATIENT AND METHODS: A 23-cm right retroperitoneal, well-differentiated liposarcoma was diagnosed in a 68-year-old female patient in December 2021. The tumor involved the right kidney and adrenal gland; displacing anteriorly the right colon, the duodenum, and the pancreatic head; and invading part of the ipsilateral psoas muscle. After the publication of the STRASS trial and STREXIT results,6,7 neoadjuvant radiotherapy was delivered to a total dose of 50.4 Gy in 28 fractions with stable disease. Virtual 3D reconstruction of regional anatomy by Visible Patient was performed preoperatively. RESULTS: The patient underwent right retroperitoneal mass resection en bloc with ipsilateral kidney and adrenal gland, colon, psoas muscle, and portion of ipsilateral diaphragm. Of note, the resection of the psoas muscle was performed to obtain a safe posterior margin and accomplish a better clearance of fat of the posterior abdominal wall. This can be limited to the psoas fascia whenever the tumor is not adherent to it. A six-stage approach was performed, as described in the supplementary video file. CONCLUSIONS: RPS resection is complex and requires a broad range of surgical expertise. A staged approach that can be followed in virtually all cases is highly recommended to achieve an optimal tumor resection.

Organ Infiltration and Patient Risk After Multivisceral Surgery for Primary Retroperitoneal Liposarcomas.

BACKGROUND: The extent of histological organ involvement (HOI) to organs and structures of a retroperitoneal liposarcoma may have prognostic implications. This study investigated incidence, characteristics, and risk association of HOI in these patients. PATIENTS AND METHODS: Data of patients who underwent multivisceral resection for primary liposarcoma (2009-2014) were retrospectively analyzed. HOI was the variable of interest and was classified into four degrees: absent (HOI-0), perivisceral (HOI-1), initial (HOI-2), and advanced (HOI-3). Primary endpoint was overall survival (OS). Secondary endpoint was disease-free survival (DFS). The prognostic value of HOI was adjusted for preoperative treatment and the Sarculator nomogram score. RESULTS: A total of 109 patients were included. HOI-0, HOI-1, HOI-2, and HOI-3 were detected in 9 (8.3%), 11 (10.1%), 43 (39.4%), and 46 (42.2%) patients. Median follow-up was 8.4 years [interquartile range (IQR) 7.2-9.6 years]. There were 68 recurrences and 50 patient deaths observed, resulting in a 10-year OS and DFS of 51.1% [95% confidence interval (CI) 41.9-62.1%] and 34.1% (95% CI 25.2-46.1%), respectively. Clinically relevant HOIs (HOI-2 and HOI-3) were found in 35/45 (77.8%) and 54/64 (84.4%) cases of well- and de-differentiated liposarcomas, respectively. On multivariable survival analysis, patients with HOI-3 had significantly shorter OS (HOI-3 vs HOI-0/HOI-1 HR 2.92; p = 0.012) and DFS (HOI-3 vs HOI-0/HOI-1 HR 2.23; p = 0.045), independently of the nomogram score (OS: HR 2.93; p < 0.001; DFS: HR 1.78; p = 0.003). CONCLUSIONS: Initial and advanced HOIs are frequently detected in both well-differentiated and de-differentiated liposarcomas, supporting that multivisceral resection may be needed. HOI stratifies the risk of patients with primary retroperitoneal liposarcoma.

Sentinel Lymph Node Biopsy for Extremity and Truncal Soft Tissue Sarcomas: A Systematic Review of the Literature.

BACKGROUND: Regional lymph node metastasis (RLNM) occurs infrequently in patients with soft tissue sarcoma (STS), although certain STS subtypes have a higher propensity for RLNM. The identification of RLNM has significant implications for staging and prognosis; however, the precise impact of node-positive disease on patient survival remains a topic of controversy. Although the benefits of sentinel lymph node biopsy (SLNB) are well documented in patients with melanoma and breast cancer, whether this procedure offers a benefit in STS is controversial. METHODS: A systematic literature search was performed and articles reviewed to determine if SLNB in patients with extremity/truncal STS impacts disease-free or overall survival. RESULTS: Six studies were included. Rates of sentinel lymph node positivity were heterogeneous (range 4.3-50%). The impact of SLNB on patient outcomes remains unclear. The overall quality of available evidence was low, as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system. CONCLUSIONS: The literature addressing the impact of nodal basin evaluation on the staging and management of patients with extremity/truncal STS is confounded by heterogeneous patient cohorts and clinical practices. Multicenter prospective studies are warranted to determine the true incidence of RLNM and whether SLNB could benefit patients with clinically occult RLNM at diagnosis.

Effect of Preoperative Treatment on the Performance of Predictive Nomograms in Primary Retroperitoneal Sarcoma.

BACKGROUND: Retroperitoneal sarcoma (RPS)-specific nomograms provide estimates of survival and recurrence risk following resection in the individual patient. The effect of preoperative treatment on nomogram performance has not been previously examined. Our aim was to evaluate the predictive accuracy of existing RPS-specific nomograms in patients managed at our center, where the majority of patients received preoperative radiation. PATIENTS AND METHODS: All patients who underwent curative treatment for primary RPS at Mount Sinai Hospital/Princess Margaret Hospital between 1996 and 2016 were identified. The performance of four previously published nomograms was assessed by measuring the agreement between nomogram-predicted and observed outcomes using Harrell's C-Index and level of calibration. Outcomes included in each of the nomograms [overall survival (OS), disease-free survival (DFS), disease-specific death (DSD), local recurrence (LR), distant recurrence (DR)] at each of the specified post-resection timepoints were examined. RESULTS: In total, 253 patients were included. When observed outcomes were compared with those predicted by each of the four nomograms, the C-Index ranged from 0.60 to 0.81, representing a wide range of predictive accuracy. The lowest C-Index was for prediction of LR. Calibration plots revealed that the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicted a 5-year LR of 45%, whereas the observed LR was 24%. Overprediction of LR was detected in patients who had undergone preoperative radiotherapy, but not in patients treated with surgery alone. CONCLUSIONS: Preoperative radiotherapy appeared to preclude the use of the LR component of existing nomograms for primary RPS. Updated nomograms should be created to reflect this variable, particularly in light of the recently published STRASS trial results.

Sarculator is a Good Model to Predict Survival in Resected Extremity and Trunk Sarcomas in US Patients.

BACKGROUND: Sarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown. PATIENTS AND METHODS: Patients from the National Cancer Data Base (NCDB) (2006-2016) with resected stage I-III primary extremity or trunk sarcoma were included. Predicted overall survival (pOS) was calculated using the Sarculator algorithm, which includes patient age, tumor size (cm), grade (1-3), and histology, and compared with actual overall survival (aOS). Harrell's C-index was calculated to determine the discriminatory ability of Sarculator (0.7 = good, 0.8 = strong, 1.0 = perfect model), and calibration plots were created. RESULTS: In total, 9738 patients were included. Five-year pOS was 73.7% compared with aOS of 68.9%. The C-index for the entire cohort was 0.726. By stage, the C-index was 0.730 for stage I, 0.708 for stage II, and 0.679 for stage III. By histology, C-indices were highest for leiomyosarcoma (0.745), myxofibrosarcoma (0.722), and other histologies (0.721). By sociodemographic variables, Sarculator performed better for patients < 50 years (C-index 0.722), of other/unknown race (C-index 0.781), with private insurance (C-index 0.715), treated at a center other than a community cancer programs (C-index > 0.7), and with no comorbidities (C-index 0.716). Outcomes by zip code educational attainment and income were not markedly different (all C-indices > 0.7). CONCLUSIONS: Sarculator is overall a good predictor of aOS and useful tool for clinicians to aid in survival prognostication. However, clinicians should be aware of populations for whom Sarculator's predictions may be less accurate. Future work could focus on enhancing the Sarculator algorithm specifically for US patients by including demographic variables.

Refining the Approach to Patients with Primary Soft Tissue Sarcoma of the Extremities and Trunk Wall: Outcome Improvement Over Time at a Single Institution.

BACKGROUND: The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients' cohort to assess changes in outcomes over time for extremity and superficial trunk soft tissue sarcoma (ESTSTS) treated at a single referral center. METHODS: All consecutive patients with primary localized adult-type ESTSTS surgically treated at the authors' institution between 1987 and 2017 were included and divided into group 1 (1987-2002) and group 2 (2003-2017) according to primary surgery year. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local recurrence (LR), and distant metastases (DM) were calculated in a competing-risks framework. DM-free survival (DMFS) and post-DM survival were also assessed. RESULTS: The study identified 2382 patients. The median follow-up was 104 months (range, 63-127 months), and the post-DM follow-up was 76 months (range, 37-126 months). Since 2003, an increased adoption of preoperative treatments was observed: the use of chemotherapy, radiotherapy and combined chemoradiotherapy went from 10.5% to 23.7%, from 1.7% to 17.8%, and from 1% to 11.8% respectively. This change in treatment strategies was associated to an improvement in CCI-SSM (27.8% vs 19.5%; P < 0.001), CCI-LR (14.1 vs 7.5%; P < 0.001), DMFS (57.9% vs 65.8%; P = 0.004), and post-DM (12.2% vs 20.1%; P = 0.012), but not in CCI-DM. CONCLUSIONS: Increased adoption of preoperative treatments and greater availability of medical agents in the recent years were associated to better outcomes. New treatments are eagerly awaited for further improvement of outcome for ESTSTS patients because no major changes have been observed since 2003.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

The evolution of adjuvant/neoadjuvant trials for resectable localized sarcoma.

Soft-tissue sarcomas are rare tumors arising from mesenchymal tissues. As a heterogeneous group comprising more than 50 types, the development of clinical trials remains challenging. Decision-making for neoadjuvant or adjuvant chemotherapy and radiation therapy is based on the available evidence of contemporary trials and multidisciplinary clinical judgment.

Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities.

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. RESULTS: It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. CONCLUSIONS: Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.

Retroperitoneal sarcoma: the Transatlantic Australasian Retroperitoneal Sarcoma Working Group Program.

PURPOSE OF REVIEW: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is a bottom-up clinical network established in 2013 with the goal of improving the care and outcomes of patients with retroperitoneal sarcoma (RPS). Here, we review the knowledge produced by this collaborative effort and examine the future potential of this group. RECENT FINDINGS: TARPSWG has produced retrospective studies focused on patients with primary and recurrent RPS allowing a better understanding of patient prognosis, treatment outcomes and tumor biology. The group has played a pivotal role in a phase III randomized STudy of preoperative RAdiotherapy plus Surgery versus surgery alone for patients with Retroperitoneal Sarcoma (STRASS) trial, favoring patient recruitment and trial completion. A prospective registry for patients with primary RPS populated by TARPSWG members is ongoing. TARPSWG has created consensus papers with recommendations regarding the management of patients with primary, recurrent and metastatic RPS that collated the views of representatives of sarcoma centers from Europe, North America, Asia and Australia. SUMMARY: Since its inception, TARPSWG has become a leading network in the field of RPS. It has made a major contribution to the world of RPS research and cares allowing to overcome the limitations related to the rarity of the disease through collaboration.

Unplanned Excision of Extremity and Trunk Wall Soft Tissue Sarcoma: To Re-resect or Not to Re-resect?

PURPOSE: The need for systematic reexcision in patients who underwent unplanned excision (UE) for extremity and superficial trunk soft tissue sarcoma (ESTSTS) has been questioned. We investigated the outcome of patients who underwent reexcision for ESTSTS compared with primarily resected at our institution and the prognostic impact of microscopic residual disease (MR) in the reexcision specimen. METHODS: Primary ESTSTS patients surgically treated at our institution between 1997 and 2017 were divided in three groups: primarily resected (A), reexcised after macroscopically complete UE (B), and incomplete UE (C). Weighted overall survival (OS), crude cumulative incidence of local relapse (CCI-LR), and distant metastasis (CCI-DM) were calculated and compared. In group B, multivariable models were performed to assess factors associated with the outcomes. RESULTS: A total of 1962 patients were identified: 1076, 697 and 189 in groups A, B, and C, respectively. Overall median follow-up was 85 months. Seven-year weighted-OS was 73.8%, 84.1%, and 80.7% (p < 0.001) for groups A, B, and C respectively. Seven-year CCI-LR and DM were 5.0% and 25.3%, 12.1% and 15.8%, and 13.6% and 29.4% (both p < 0.001) for groups A, B, and C, respectively. At multivariable analysis, the presence MR was associated with LR (p < 0.001) but not with OS nor CCI-DM. CONCLUSIONS: UE and the presence of MR at pathology in reexcision specimen are associated to a higher risk of LR but not to a higher risk of DM or lower OS. After macroscopic complete UE, postponing reexcision until a LR occurs may be considered on an individualized basis.

Inoperable Primary Retroperitoneal Sarcomas: Clinical Characteristics and Reasons Against Resection at a Single Referral Institution.

BACKGROUND: The outcome of patients with retroperitoneal sarcomas (RPS) depends mainly on tumor biology and completeness of surgical resection. However, some patients are deemed not resectable for various reasons. This study analyzed a series of primary RPS patients to describe rate and reasons of primary inoperability at a large referral center. METHODS: All consecutive patients affected by primary localized RPS referred for surgical treatment at our institution between January 1, 2013 and December 31, 2017 were analyzed. Patients were split in two groups: those who underwent surgical resection with curative intent, and those who were not resected. RESULTS: A total of 322 patients were available for the current analysis: 285 (88.5%) underwent resection with curative intent, and 37 (11.5%) did not. Twenty of 322 (6.2%) patients who did not undergo resection had a technically unresectable tumor, whereas the remaining 18 of 322 (5.6%) were not amenable to a major surgical procedure due to comorbidities/poor performance status. The dominant technical reason was involvement of the celiaco-mesenteric vessels. At a median follow-up from the diagnosis of 34 months, 24 of 37 (64.9%) nonoperated and 48 of 285 (16.8%) operated patients died. The corresponding 4-year overall survival were 10.3% and 83.4%, respectively (p < 0.001). CONCLUSIONS: Roughly, 10% of patients who presented with localized primary RPS at a large referral institution were not resected. An attempt to standardize the definition of resectability for primary localized RPS should be made considering anatomic, biologic, and patient-related factors.

A Prospective Observational Study of Multivisceral Resection for Retroperitoneal Sarcoma: Clinical and Patient-Reported Outcomes 1 Year After Surgery.

BACKGROUND: Primary retroperitoneal sarcoma (RPS) may require multivisceral resection (MVR). Clinical outcome (morbidity and renal function) and quality of life (QoL) are not as well reported as the oncologic outcome. METHODS: Patients with primary RPS who underwent surgery between 2014 and 2016 were prospectively enrolled in an observational longitudinal study. At baseline, then at 4 and 12 months, the study measured Clavien-Dindo morbidity, estimated glomerular filtration rate (EGFR), EORTC QLQ-C30, QLQ-CR29, DN4 (neuropathic pain [NP]), lower-extremity functional scale (LEFS), and the brief pain inventory. The primary end point was the difference in global health status (GHS/QoL). The secondary end points were EGFR changes, difference in other QLQ-C30 scales, pain intensity, NP, and LEFS. The study is registered at ClinTrials.gov (NCT03480399). RESULTS: Of 74 patients, 58 were evaluable. Morbidity grade 3 or higher was 24.1%, and mortality was 1.3%. After nephrectomy, the mean 1-year EGFR change was -33.9%. The GHS/QoL at baseline was 58.6 and had increased of 6.9 points at 1 year, comparable with that of the general population. A transient worsening in pain and diarrhea had recovered at 12 months. Average pain was mild and did not differ at 12 months. However, NP was found in 41.4% of the patients and was significantly associated with resection of the psoas muscle. At baseline, LEFS was already lower than the normative value, and worsening after surgery was not clinically relevant. CONCLUSION: A QoL measure after MVR in primary RPS is complex and requires multiple tools. Whereas overall MVR is safe and associated with an improvement in GHS/QoL, chronic NP is frequent and deserves specific attention. Pre-surgery rehabilitation tracks may help to prevent or reduce chronic NP.