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.

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.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Desmoid Tumors in Familial Adenomatous Polyposis Patients: Favorable Outcomes with Multidisciplinary Management.

OBJECTIVE: In this study, we aimed to describe the clinical features, management, and outcomes of desmoid tumors (DTs) in familial adenomatous polyposis (FAP) patients at a high-volume sarcoma center. METHODS: Consecutive patients with FAP and DTs were identified from our institutional databases (1985-2021). Patient demographics, treatment, and outcomes were described. Categorical data were compared using Fisher's exact test, and Kaplan-Meier curves were used to estimate progression-free survival (PFS). RESULTS: Forty-five patients with 67 DTs were identified: 39 mesenteric or retroperitoneal (58.2%), 17 abdominal wall (25.4%), 4 extremity (6%), 4 breast (6%) and 3 back (4.4%). Severe DT symptoms were present in 12 patients (26.7%). Initial treatments per tumor were observation in 30 (44.8%) DTs, chemotherapy in 15 (22.4%) DTs, surgery in 10 (14.9%) DTs, and other systemic therapies in 10 (14.9%) DTs. The majority of DTs remained stable with observation or a single intervention (77.8%). Median PFS was 23.4 years (95% confidence interval 7.6-39.2). In the 12 severely symptomatic patients, four patients required more than two interventions for DT control. At a median follow-up of 6.0 years (range 0.7-35.8 years), 33 (73.3%) patients were alive with disease, 7 (15.6%) were alive without disease, and 5 (11.1%) died of other causes. No patients died of DT-related complications. CONCLUSIONS: The majority of DTs in FAP patients remained stable with observation or a single intervention. There were no DT-related deaths; however, 12 of 45 patients (26.7%) experienced significant tumor morbidity and required more interventions for disease control. Further studies on quality of life are required.

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. METHODS: Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. RESULTS: The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed local recurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. DISCUSSION AND CONCLUSION: Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.

Multidisciplinary Intervention in Radiation-Associated Angiosarcoma of the Breast: Patterns of Recurrence and Response to Treatment.

BACKGROUND: Radiation-associated angiosarcoma (RAAS) of the breast is an aggressive malignancy affecting 1 in 1000 breast cancer patients. This study aimed to determine differences in treatments and outcomes for RAAS initially managed through a sarcoma multi-disciplinary team (SMDT) compared with an outside center (OC) and to describe outcomes after recurrence. METHODS: Patients with a diagnosis of breast RAAS between 2004 and 2019 were identified from our sarcoma database. Clinicopathologic characteristics, recurrence patterns, and factors predictive of survival were assessed. Differences in local recurrence-free survival (LRFS) and disease-specific survival (DSS) were estimated using Kaplan-Meier and compared using the log-rank test. RESULTS: Surgery was performed for 49 women with RAAS, who had a median age of 74 years (range 41-89 years). Primary management was performed by SMDT for 26 patients and by OC for 23 patients. Radical mastectomy and reconstruction were performed for 96% of the SMDT group versus 17% of the OC group (p = 0.00001). The proportion patients who received chemotherapy, radiation, or both was 42.3% in the SMDT group and 0% in the OC group. During a median follow-up period of 26 months, recurrence was experienced by 38% (10/26) of the SMDT cohort and 83% (19/23) of the OC cohort (p = 0.002). The 3-year LRFS was better in the SMDT cohort (59.3% vs 31.8%; p = 0.019). Of the 29 recurrences 16 received chemotherapy and 6 received radiation, surgery, or both. At the last follow-up visit, 20 patients were in first remission, 1 patient was in second remission, 8 patients were alive with disease, and 20 patients had died of disease. CONCLUSION: Initial treatment by SMDT was associated with more extensive surgery, multimodal treatments, and a better 3-year LRFS. Patients with breast RAAS likely benefit from early referral and treatment by an SMDT.

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.

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.

Has the Outcome for Patients Who Undergo Resection of Primary Retroperitoneal Sarcoma Changed Over Time? A Study of Time Trends During the Past 15 years.

BACKGROUND: This study aimed to investigate changes in treatment strategy and outcome for patients with primary retroperitoneal sarcoma (RPS) undergoing resection at referral centers during a recent period. METHODS: The study enrolled consecutive adult patients with primary non-metastatic RPS who underwent resection with curative intent between 2002 and 2017 at 10 referral centers. The patients were grouped into three periods according to date of surgery: t1 (2002-2006), t2 (2007-2011), and t3 (2012-2017). Five-year overall survival (OS), disease-specific survival (DSS), and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariable analyses for OS and DSS were performed. RESULTS: The study included 1942 patients. The median follow-up period after resection varied from 130 months (interquartile range [IQR], 124-141 months) in t1 to 37 months (IQR, 35-39 months) in t3. The 5-year OS was 61.2% (95% confidence interval [CI], 56.4-66.3%) in t1, 67.0% (95 CI, 63.2-71.0%) in t2, and 71.9% (95% CI, 67.7-76.1%) in t3. The rate of macroscopically incomplete resection (R2) was 7.1% in t1 versus 4.7% in t3 (p = 0.066). The median number of resected organs increased over time (p < 0.001). In the multivariable analysis resection during t3 was associated with better OS and DSS. The 90-day postoperative mortality improved over time (4.3% in t1 to 2.3% in t3; p = 0.031). The 5-year CCI of LR and DM did not change significantly over time. CONCLUSIONS: The long-term survival of patients who underwent resection for primary RPS has increased during the past 15 years. This increased survival is attributable to better patient selection for resection, quality of surgery, and perioperative patient management.

Management of Primary Retroperitoneal Sarcoma (RPS) in the Adult: An Updated Consensus Approach from the Transatlantic Australasian RPS Working Group.

BACKGROUND: Retroperitoneal soft tissue sarcomas comprise a heterogeneous group of rare tumors of mesenchymal origin that include several well-defined histologic subtypes. In 2015, the Transatlantic Australasian RPS Working Group (TARPSWG) published consensus recommendations for the best management of primary retroperitoneal sarcoma (RPS). Since then, through international collaboration, new evidence and knowledge have been generated, creating the need for an updated consensus document. METHODS: The primary aim of this study was to critically evaluate the current evidence and develop an up-to-date consensus document on the approach to these difficult tumors. The resulting document applies to primary RPS that is non-visceral in origin, with exclusion criteria as previously described. The relevant literature was evaluated and an international group of experts consulted to formulate consensus statements regarding the best management of primary RPS. A level of evidence and grade of recommendation were attributed to each new/updated recommendation. RESULTS: Management of primary RPS was considered from diagnosis to follow-up. This rare and complex malignancy 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, and an individualized management plan should be made based on the 29 consensus statements included in this article, which were agreed upon by all of the authors. Whenever possible, patients should be enrolled in prospective trials and studies. CONCLUSIONS: Ongoing international collaboration is critical to expand upon current knowledge and further improve outcomes of patients with RPS. In addition, prospective data collection and participation in multi-institution trials are strongly encouraged.

Patterns of recurrence and survival probability after second recurrence of retroperitoneal sarcoma: A study from TARPSWG.

BACKGROUND: In this series from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), the authors examined longitudinal outcomes of patients with a second recurrence of retroperitoneal sarcoma (RPS) after complete resection of a first local recurrence (LR). METHODS: Data from patients undergoing resection of a first LR from January 2002 to December 2011were collected from 22 sarcoma centers. The primary outcome was overall survival (OS) after second recurrence. RESULTS: Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first locally recurrent RPS. Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55 patients (13.75%), and both LR and DM in 22 patients (5.5%). The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001): 45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM. The only factors found to be associated with improved OS on multivariable analysis were both time between second surgery and the development of the second recurrence (32 months vs 8 months: hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P < .001]). The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the patients not deemed suitable for surgical resection. CONCLUSIONS: Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and treatment. Durable disease-free survivors were identified after surgery for second LR in patients selected for this intervention.

Early and Late Complications of Percutaneous Core Needle Biopsy of Retroperitoneal Tumors at Two Tertiary Sarcoma Centers.

BACKGROUND: Concern persists regarding percutaneous core needle biopsy (CNB) of a potentially malignant lesion of the retroperitoneum due to the perceived risk of immediate complications and adverse oncologic outcomes, including needle tract seeding (NTS). OBJECTIVE: The aim of this study was to evaluate the incidence of (1) early complications and (2) NTS following CNB of suspected retroperitoneal sarcoma (RPS). METHODS: Patients who underwent CNB of an RP mass with pre-biopsy suspicion of sarcoma were identified from a prospective database at two centers: (1) Princess Margaret Cancer Centre/Mount Sinai Hospital, Toronto (2009-2015); and (2) The Ottawa Hospital (1999-2015). Early complications, including bleeding, pain, infection, and organ injury, were recorded. Instances of NTS were identified from long-term follow-up of patients who underwent resection of primary RPS at these two centers after initial CNB (1996-2013). RESULTS: Of 358 percutaneous CNBs of suspected RPS performed over the study period, 7 (2.0%) resulted in minor bleeding with no transfusion, 3 (0.8%) resulted in significant pain, 1 (0.3%) resulted in unplanned admission to hospital for observation, and 1 (0.3%) resulted in a pneumothorax. There were no infections. In 203 patients who underwent resection of RPS following CNB, crude cumulative local recurrence was 24% at 5 years. At a median follow-up of 44 months, there was one case of NTS (approximately 0.5%). CONCLUSION: This large bi-institutional experience with CNB of an RP mass demonstrates that both the early complication rate and the incidence of NTS are very low. Physicians and patients can be reassured that the benefits of CNB in diagnosing sarcoma and determining its histologic subtype and grade far outweigh the risks.

Comparison of published risk models for prediction of outcome in patients with extrameningeal solitary fibrous tumour.

AIMS: Solitary fibrous tumours (SFTs) are fibroblastic mesenchymal tumours with a 10-30% metastatic rate. Several risk models have been proposed for extrameningeal SFT, but they have not been evaluated in direct comparison with each other. The aim of this study is to compare the utility of published risk models in a multi-institutional SFT cohort. METHODS AND RESULTS: Clinicopathological data were evaluated for a cohort of extrameningeal SFTs, and used to stratify tumours by the use of five proposed risk models designed for soft tissue and/or pleural SFT [modified Demicco, Pasquali, Salas overall survival (OS), Salas metastasis, and Salas local recurrence (LR)]. Kaplan-Meier and Cox proportional hazards models were used to assess OS, time to first metastasis, time to first LR, and recurrence-free survival (RFS). The study included 303 patients (109 from a referral cancer treatment centre; previously described in the original Demicco model) and an independent cohort from two large hospitals (n = 194). The median patient age was 54 years, and the median clinical follow-up (available for 220 patients) was 37 months. The independent cohort had a 13% risk of metastasis at 5 years and a 16% risk of metastasis at 10 years. In this cohort, the modified Demicco, Salas OS, and Salas metastasis models predicted metastasis and RFS, whereas the Pasquali model had the best correlation with OS. CONCLUSIONS: Multivariate risk models that include mitotic rate and patient age can more accurately predict aggressive behaviour in SFTs, with the modified Demicco and Salas OS risk models showing the best correlation with metastasis and RFS.

Prognostic models for RPS patients-Attempting to predict patient outcomes.

Retroperitoneal sarcoma (RPS) patients can have variable of outcomes after surgery. The chance to recur locally or at distant sites varies according to tumor grade, histologic subtype, and other patient- and tumor-related characteristics. The relative contribution of each prognostic variable on the oncological outcome of RPS patients can be weighted by combining them in prognostic tools such as nomograms. With this review, we critically appraise the available nomograms for RPS patients highlighting pros and cons.

Results of Resection for Recurrent or Residual Retroperitoneal Sarcoma After Failed Primary Treatment.

BACKGROUND: Local recurrence after resection of retroperitoneal sarcoma (RPS) is a common and difficult problem. Gross residual disease after incomplete resection is a particular challenge. The authors reviewed their experience with patients referred for management of recurrent or residual RPS. METHODS: Patients seen at the authors' center from 1996 to 2013 who had undergone resection at an outside institution were identified from a prospective database. Kaplan-Meier survival curves were generated and compared by log-rank analysis. RESULTS: A total of 45 patients were referred with recurrent (n = 33) or residual (n = 12) disease. Before initial surgery elsewhere, cross-sectional imaging (computed tomograpy/magnetic resonance imaging) had been obtained for 30 patients (67 %) and percutaneous biopsy for 8 patients (18 %). At referral to the authors' center, 15 patients were deemed inappropriate for resection, with a subsequent median overall survival (OS) period of 15 months. At the authors' center, 30 patients (22 with recurrent and 8 with residual disease) were resected. The majority received preoperative radiation (77 %). The postoperative mortality rate was 0 % in the recurrent group and 25 % (2/8) in the residual group (p = 0.015). Among the 30 resected patients, the median and 5-year OS was 53 months (50 %), and the OS was better in the recurrent group (median, 77 months) than in the residual group (median, 41 months (p = 0.027). The median time to local re-recurrence was 49 months in the recurrent group and 35 months in the residual group (p = 0.730). CONCLUSIONS: Durable disease control and prolonged survival may be achieved for selected patients with recurrent RPS. In this study, resection after previous grossly incomplete resection was associated with high postoperative mortality and inferior OS. The benefit of extensive surgery for these patients may be limited.

Clinical outcomes in breast angiosarcoma patients: A rare tumor with unique challenges.

BACKGROUND: Breast angiosarcoma (AS) accounts for less than 1% of all breast cancers. The goal of this study was to determine patient outcomes in radiation-associated angiosarcoma of the breast (RAAS) and sporadic AS. We evaluated patterns of recurrence and predictors of breast AS survival. METHODS: Patients with pathologically confirmed AS from 1994 to 2014 referred to Mount Sinai Hospital/Princess Margaret Cancer Centre were included. Primary outcome was overall survival (OS). Secondary outcomes were disease-free survival (DFS), clinicopathologic characteristics, patterns of recurrence and factors predictive of survival. Kaplan-Meier and log-rank tests were used for OS and DFS. RESULTS: Twenty-six patients were included: 6 with sporadic AS and 20 with RAAS. Median follow-up was 24 months. Five-year OS for RAAS and sporadic subgroups were 44% and 40%, respectively (P = ns). Five-year DFS for RAAS and sporadic subgroups were 23% and 20%, respectively (P = ns). Overall recurrence rate was 67% with median time to recurrence of 11 months. Age, tumor depth, margin status, and tumor size were not statistically significant predictive factors for OS and DFS. DISCUSSION: Breast AS is associated with poor survival and high recurrence rates. Prognosis may be mainly determined by its aggressive biology. Referral to tertiary care centers for multimodality treatment is recommended.

PI3K/AKT/mTOR inhibition in combination with doxorubicin is an effective therapy for leiomyosarcoma.

BACKGROUND: Leiomyosarcoma (LMS) is a common type of soft tissue sarcoma that responds poorly to standard chemotherapy. Thus the goal of this study was to identify novel selective therapies that may be effective in leiomyosarcoma by screening cell lines with a small molecule library comprised of 480 kinase inhibitors to functionally determine which signalling pathways may be critical for LMS growth. METHODS: LMS cell lines were screened with the OICR kinase library and a cell viability assay was used to identify potentially effective compounds. The top 10 % of hits underwent secondary validation to determine their EC50 and immunoblots were performed to confirm selective drug action. The efficacy of combination drug therapy with doxorubicin (Dox) in vitro was analyzed using the Calcusyn program after treatment with one of three dosing schedules: concurrent treatment, initial treatment with a selective compound followed by Dox, or initial treatment with Dox followed by the selective compound. Single and combination drug therapy were then validated in vivo using LMS xenografts. RESULTS: Compounds that targeted PI3K/AKT/mTOR pathways (52 %) were most effective. EC50s were determined to validate these initial hits, and of the 11 confirmed hits, 10 targeted PI3K and/or mTOR pathways with EC50 values <1 µM. We therefore examined if BEZ235 and BKM120, two selective compounds in these pathways, would inhibit leiomyosarcoma growth in vitro. Immunoblots confirmed on-target effects of these compounds in the PI3K and/or mTOR pathways. We next investigated if there was synergy with these agents and first line chemotherapy doxorubicin (Dox), which would allow for earlier introduction into patient care. Only combined treatment of BEZ235 and Dox was synergistic in vitro. To validate these findings in pre-clinical models, leiomyosarcoma xenografts were treated with single agent and combination therapy. BEZ235 treated xenografts (n = 8) demonstrated a decrease in tumor volume of 42 % whereas combining BEZ235 with Dox (n = 8) decreased tumor volume 68 % compared to vehicle alone. CONCLUSIONS: In summary, this study supports further investigation into the use of PI3K and mTOR inhibitors alone and in combination with standard treatment in leiomyosarcoma patients.

Toward Observation as First-line Management in Abdominal Desmoid Tumors.

BACKGROUND: Desmoid tumors (DT) occur sporadically, in familial adenomatous polyposis, or in association with pregnancy. Initial observation has been proposed in the management of DT. An advantage of this approach is to select patients who have indolent disease versus those who require intervention. Here we report our multidisciplinary experience of abdominal DT as it relates to nonoperative management. METHODS: Patients seeking care from 1980 to 2012 with pathologically confirmed DT were identified from clinical research databases. Clinicopathologic data and management strategies were collected, and statistical analyses were performed by Chi square and t tests. RESULTS: A total of 213 patients were identified; DT occurred in abdominal wall (n = 103, 48 %), intra-abdominally (n = 92, 43 %), or at both sites (n = 18, 9 %). Patients were predominantly female (72 %); disease was sporadic (48 %), associated with familial adenomatous polyposis (38 %), or associated with pregnancy (14 %). Patient presentation was stratified into 3 groups: untreated (group A; n = 176), DT resected elsewhere (group B; n = 19), or recurrent DT (group C; n = 18). In group A, 109 patients were initially observed, with 51 patients requiring intervention as a result of progression or symptoms. Of the 58 patients who underwent only observation, 93 % experienced spontaneous regression or stable disease (median follow-up 38 months). Of the 67 patients in group A who underwent resection, 28 % experienced recurrence (median 22 months). Abdominal wall DT >7 cm and intra-abdominal DT were more likely to recur (P < 0.01). CONCLUSIONS: Initial observation has been implemented for abdominal DT at our institution. Over half of patients observed required no intervention with prolonged follow-up. Tumor size and site may predict progression during observation, therefore representing higher-risk groups.