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.

External validation of a multi-institutional retroperitoneal sarcoma nomogram.

BACKGROUND: A multi-institutional nomogram for predicting disease-free survival (DFS) and overall survival (OS) in patients with primary retroperitoneal sarcoma (RPS) incorporating relevant prognostic factors not included in the American Joint Committee on Cancer staging system for soft tissue sarcoma has been reported. The authors validated this nomogram with an independent, transatlantic cohort. METHODS: Data from patients with RPS who were undergoing definitive resection at 1 of 6 sarcoma centers in Europe and North America ("validation set") were used to validate a RPS nomogram developed from 3 other centers ("development set"). The nomogram incorporated 6 variables: age, tumor size, grade, histologic subtype, multifocality, and quality of surgery. Nomogram-predicted probabilities were stratified into 6 subgroups and compared with observed outcomes. Discriminative ability was quantified by Harrell C statistics. RESULTS: The validation and development sets included 631 and 523 patients, respectively, all of whom underwent surgical resection at the institutions represented. The 7-year DFS and OS rates for the validation set were 38% (95% confidence interval, 34%-43%) and 58% (95% confidence interval, 53%-63%), respectively. All 6 nomogram variables were found to be independently prognostic. The corrected Harrell C statistics concordance index values for the validation set were 0.69 for DFS and 0.73 for OS, which were similar to those for the development set, suggesting good calibration of the nomogram in the validation cohort. CONCLUSIONS: The RPS nomogram was externally validated using a larger, independent cohort. The nomogram can be generalized to patients undergoing surgery for RPS by specialized sarcoma surgeons at sarcoma centers. The nomogram provides a more individualized and disease-relevant estimation of OS compared with the American Joint Committee on Cancer classification. Cancer 2016;122:1417-1424. © 2016 American Cancer Society.

Impact of Major Complications on Patients' Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for selected patients with peritoneal surface malignancies (PSM). Although it can have significant morbidity, perioperative mortality is low. Little is known about whether major complications after CRS/HIPEC have a lasting impact on patients' quality of life (QOL). METHODS: We retrospectively reviewed data from a prospectively collected database on patients treated with CRS/HIPEC for PSM (2011-2014). Patients with CRS/HIPEC and 6-month QOL evaluation were included. Major perioperative complications (Clavien-Dindo grade 3/4) were the primary independent variable. QOL was evaluated using the validated EORTC QLQ-C30 score. The primary outcome was 6-month global health score. Secondary outcomes were individual functional and symptom domains. RESULTS: Forty-two patients were analyzed. Median age was 57.5; 64 % were female. Origin of PSM was appendix (55 %), colorectal (38 %), mesothelioma (5 %), and small bowel (2 %). Fourteen patients (33 %) had major (grade 3/4) complications. Median length of stay was 16 days; patients experiencing major complications had significantly increased length of stay (35.5 vs. 13 days, p < 0.01). Major complications included intra-abdominal abscess (9.5 %), bleeding (9.5 %), symptomatic pleural effusion (7.1 %), anastomotic leaks (7.1 %), and renal failure (2.4 %). The average global health score at 6 months was 68.1. The worst-rated symptom scores at 6 months were diarrhea (39.8) and fatigue (35.4). There were no significant differences in 6-month QOL scores between patients with and without major complications, globally or in specific domains. CONCLUSIONS: Although major complications are common after CRS/HIPEC, QOL at 6 months recovers and is similar to those without major complications.

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.

Trabectedin for inoperable or recurrent soft tissue sarcoma in adult patients: a retrospective cohort study.

BACKGROUND: Trabectedin is an antineoplastic agent used for patients with soft tissue sarcoma (STS) who fail standard-of-care treatment. Real-world data of its performance is scarce. This study evaluates the safety and effectiveness of trabectedin for patients with advanced STS who were treated at a high-volume sarcoma center. METHODS: A retrospective chart review was performed on 77 patients treated with trabectedin (24 h infusion q3w) between 01/2005 and 05/2014. Data regarding safety, objective radiological response, progression-free and overall survival were analyzed. RESULTS: Median age at treatment onset was 52y [interquartile range (IQR): 45-61y]. Tumors included leiomyosarcoma (41.6%), liposarcoma (18.2%), and synovial sarcoma (13%). Trabectedin was provided as ≥ third-line chemotherapy in 71.4%. Median number of cycles was 2 (range: 1-17). Dose reduction and treatment delays occurred in 19.5 and 40.3%, respectively. Toxicities occurred in 78%, primarily for neutropenia or elevated liver enzymes. Two patients died secondary to trabectedin-induced rhabdomyolysis. Treatment was discontinued because of disease progression (84.7%), toxicity (10%), and patient preference (5%). Partial response or stable disease occurred in 14.1 and 33.8%, respectively, while 52.1% developed progressive disease. Median progression-free survival was 1.3 m (IQR: 0.7-3.5 m) and was significantly higher in patients lacking severe toxicities or progressive disease. Median overall survival was 6.7 m (IQR: 2.3-12.7 m) and was significantly higher in patients with leiomyosarcoma or liposarcoma relative to other histologies. CONCLUSIONS: Trabectedin has an acceptable safety profile as an anti-tumor agent. Our data further suggest there may be some benefit in using trabectedin particularly in patients with leiomyo- or liposarcoma who failed standard-of-care agents.

Desmoid-type fibromatosis and pregnancy: a multi-institutional analysis of recurrence and obstetric risk.

BACKGROUND: Many women who present with desmoid-type fibromatosis (DF) have had a recent pregnancy. Long-term data about disease behavior during and after pregnancy are lacking. OBJECTIVE: To investigate the possible relationship between DF and pregnancy. PATIENTS AND METHODS: A cohort of women with DF and pregnancy was identified from 4 sarcoma centers. Four groups were identified: diagnosis during pregnancy (A); diagnosis after delivery (B); DF clinically evident during pregnancy (C); and DF resected before pregnancy (D). Progression/regression rates, recurrence rates after resection, and obstetric outcomes were analyzed. RESULTS: Ninety-two women were included. Forty-four women (48%) had pregnancy-related DF (A + B), whereas 48 (52%) had a history of DF before conception (C + D). Initial treatment was resection in 52%, medical therapy in 4%, and watchful waiting in 43%. Postsurgical relapse rate in A + B was 13%, although progression during watchful waiting was 63%. Relapse/progression in C + D was 42%. After pregnancy, 46% underwent treatment of DF, whereas 54% were managed with watchful waiting. Eventually, only 17% experienced further progression after treatment. Spontaneous regression occurred in 14%. After further pregnancies, only 27% progressed. The only related obstetric event was a cesarean delivery. CONCLUSIONS: Pregnancy-related DF has good outcomes. Progression risk during pregnancy is high, but it can be safely managed. DF does not increase obstetric risk, and it should not be a contraindication to future pregnancy.

Combined management of retroperitoneal sarcoma with dose intensification radiotherapy and resection: long-term results of a prospective trial.

BACKGROUND: Late failure is a challenging problem following resection of retroperitoneal sarcoma (RPS). We investigated the effects of preoperative XRT plus dose escalation with early postoperative brachytherapy (BT) on long-term survival and recurrence in RPS. METHODS: From June 1996 to October 2000, eligible patients with resectable RPS were entered onto a phase II trial of preoperative XRT (45-50 Gray) plus postoperative BT (20-25 Gray). Kaplan Meier survival curves were constructed and compared by log rank analysis (SPSS 21.0). RESULTS: All 40 patients had preoperative XRT and total gross resection as part of the prospective trial, nineteen received BT (48%). Median follow-up was 106 months. For the entire cohort, OS at 5 and 10 years was 70% and 64%, respectively; RFS at 5 and 10 years was 69% and 63%. RFS was significantly reduced in high versus low grade RPS at 5 years (53% vs. 88%, p=0.016), but not at 10 years (53% vs. 75%, p=0.079). RFS and OS at 10 years were reduced in patients who presented with recurrent compared to primary disease (RFS 30% vs. 74%, p=0.015; OS 36% vs. 76%, p=0.036). At 10 years, neither RFS nor OS was improved in patients who received BT compared to those who did not (RFS 56% vs. 69%, p=0.54; OS 52% vs.76%, p=0.23). CONCLUSIONS: In this prospective trial with mature follow-up, long-term OS and RFS in patients who underwent combined preoperative XRT plus resection of RPS compare favourably with those reported in retrospective institutional and population-based series. Postoperative BT was associated with unacceptable toxicity and did not contribute to disease control. CONDENSED ABSTRACT: In a prospective trial with mature follow-up, preoperative radiation combined with complete resection of retroperitoneal sarcoma resulted in favourable long-term RFS and OS compared to historical controls. Dose escalation with postoperative brachytherapy was not associated with better disease control.