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OBJECTIVE: This meta-analysis (PROSPERO CRD42018100653) uses individual patient data (IPD) to assess the association between recurrence and CTNNB1 mutation status in surgically treated adult desmoid-type fibromatosis (DTF) patients.SUMMARY OF BACKGROUND DATA: The majority of sporadic DTF tumors harbor a CTNNB1 (ß-catenin) mutation: T41A, S45F, and S45P or are wild-type (WT). Results are conflicting regarding the recurrence risk after surgery for these mutation types.METHODS: A systematic literature search was performed on June 6th, 2018. IPD from eligible studies was used to analyze differences in recurrence according to CTNNB1 mutation status using Cox proportional hazards analysis. Predictive factors included: sex, age, mutation type, tumor site, tumor size, resection margin status, and cohort. The PRISMA-IPD guideline was used.RESULTS: Seven studies, describing retrospective cohorts were included and the IPD of 329 patients were used of whom 154 (46.8%) had a T41A mutation, 66 (20.1%) a S45F mutation, and 24 (7.3%) a S45P mutation, whereas 85 (25.8%) patients had a WT CTNNB1. Eighty-three patients (25.2%) experienced recurrence. Multivariable analysis, adjusting for sex, age, and tumor site yielded a P-value of 0.011 for CTNNB1 mutation. Additional adjustment for tumor size yielded a P-value of 0.082 with hazard ratio's of 0.83 [95% confidence interval (CI) 0.48-1.42), 0.37 (95% CI 0.12-1.14), and 0.44 (95% CI 0.21-0.92) for T41A, S45P and WT DTF tumors compared to S45F DTF tumors. The effect modification between tumor size and mutation type suggests that tumor size is an important mediator for recurrence.CONCLUSIONS: Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.

OBJECTIVE The Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) 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, 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 while 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 following resections while recurrences were observed in 4 (1.9%) patients. CONCLUSION 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.

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.The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S).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.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.In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

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.To investigate the possible relationship between DF and pregnancy.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.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.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.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the gastrointestinal tract. In most series before the imatinib era, some advanced patients were offered surgical resection of their liver or peritoneal disease, with reportedly poor results.1 Currently, imatinib mesylate (IM) has become the standard therapy for recurrent/metastatic disease.2–4 Two large, randomized, phase III trials have reported the activity and efficacy of IM in advanced GIST patients, both in terms of progression-free and overall survival.5,6 The major limitation of such a highly effective therapy has been the development of secondary resistance. Primary resistance refers to patients who do not achieve any response, or stable disease. There is clear evidence that tumors with KIT mutations other than to exon 11, such as mutations to exon 9, 13, and 17, or no detectable kinase mutation (wild-type kit), are overrepresented in this group of nonresponders.7,8 Secondary progression is often related to acquired mutations, which differ in type from the primary ones.9,10 Progressing patients have undergone surgery of evolving disease as from the earliest cases observed, even because progression often seemed to affect only a portion of the disease. Then, the idea was to anticipate surgery of residual disease at a time in which progression has not developed yet, under the assumption that it might prevent, or delay, the occurrence of resistant clones. Surgery of residual disease has therefore been progressively more and more used as from 2002. This retrospective analysis provides data about the outcome of patients undergoing surgery of residual disease at our institution.