Amanda J. Cannell

Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients From the Multi-institutional Collaborative RPS Working Group

Background:Retroperitoneal sarcomas (RPS) are rare tumors composed of several well defined histologic subtypes. The aim of this study was to analyze patterns of recurrence and treatment variations in a large population of patients, treated at reference centers. Methods:All consecutive patients with primary RPS treated at 6 European and 2 North American institutions between January 2002 and December 2011 were included. Five, 8, and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were calculated. Multivariate analyses for OS, CCI of LR, and DM were performed. Results:In all, 1007 patients were included. Median follow-up was 58 months (first and third quartile range 36–90). The 5, 8, and 10-year OS were 67% [95% confidence interval (CI), 63, 70), 56% (95% CI, 52, 61), and 46% (95% CI, 40, 53). The 5, 8, and 10-year CCI of LR and DM were 25.9 (95% CI, 23.1, 29.1), 31.3 (95% CI, 27.8, 35.1), 35% (95% CI, 30.5, 40.1), and 21% (95% CI, 18.4, 23.8%), 21.6 (95% CI, 19.0, 24.6), and 21.6 (95% CI, 19.0, 24.6), respectively. Tumour size, histologic subtype, malignancy grade, multifocality, and completeness of resection were significant predictors of outcome. Patterns of recurrence varied depending on histologic subtype. Different treatment policies at participating institutions influenced LR of well differentiated liposarcoma without impacting OS, whereas discrepancies in adjuvant systemic therapies did not impact LR, DM, or OS of leiomyosarcoma. Conclusions:Reference centers are critical to outcomes of RPS patients, as the management strategy requires specific expertise. Histologic subtype predicts patterns of recurrence and should inform management decision. A prospective international registry is under preparation, to further define our understanding of this disease.

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.

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.

Post‐relapse outcomes after primary extended resection of retroperitoneal sarcoma: A report from the Trans‐Atlantic RPS Working Group

Despite a radical surgical approach to primary retroperitoneal sarcoma (RPS), many patients experience locoregional and/or distant recurrence. The objective of this study was to analyze post‐relapse outcomes for patients with RPS who had initially undergone surgical resection of their primary tumor at a specialist center.

External validation of a multi-institutional retroperitoneal sarcoma nomogram

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.

Postoperative Morbidity After Radical Resection of Primary Retroperitoneal Sarcoma: A Report From the Transatlantic RPS Working Group

Andrea J. MacNeill, MD, y Alessandro Gronchi, MD,y Rosalba Miceli, PhD,z Sylvie Bonvalot, MD, PhD,§ Carol J. Swallow, MD, PhD, Peter Hohenberger, MD, Frits Van Coevorden, MD,jj Piotr Rutkowski, MD, Dario Callegaro, MD,y Andrew J. Hayes, MD, PhD,yy Charles Honoré, MD,zz Mark Fairweather, MD,§§ Amanda Cannell, BSc, Jens Jakob, MD, Rick L. Haas, MD,jjjj Milena Szacht, MD, Marco Fiore, MD,y Paolo G. Casali, MD, Raphael E. Pollock, MD, PhD,yyy Francesco Barretta, PhD,z Chandrajit P. Raut, MD, MSc,§§ and Dirk C. Strauss, MDyy