Challenging aggressive surgical strategies in extraabdominal desmoid tumors: Is tumor volume the missing key?

Objective: Desmoid tumors are fibroblast-derived rare soft tissue neoplasms with unclear borders that invade the surrounding structures. Despite the non-metastasizing nature, these tumors often relapse due to strong local aggressive behavior. The aim of this study was to analyze the demographic and clinical characteristics of patients with extraabdominal desmoid tumor, who underwent surgery between 2012 and 2022 and to determine the risk factors affecting recurrence.

Methods: Thirty-five patients (14 males, 21 females; mean age 41.2 years (range: 11-80) underwent operation between the years 2012 and 2022 and followed up for a mean of 52 months. The diagnosis was confirmed with biopsy, and the plan for surgery and adjuvant radiotherapy was decided by the multidisciplinary tumor council. Demographic, radiologic, and management data of the patients were collected. Potential effects of surgical margin status, estimated tumor volume (ETV), and radiotherapy on recurrence were investigated. Estimated tumor volume was calculated from dimensions on pathologic specimens.

Results: While wide surgical resection was aimed for all patients, R0 margins were achieved only in 40%, whereas R1 and R2 margins were obtained in 22.9% and 37.1% of these patients respectively. The local recurrence rate was 40%. No significant correlation was observed between surgical margin positivity and the recurrence or progression of the tumor, when patients with R0 margin are sta-tistically compared with the rest (P = .067). On the other hand, when R0 and R1 margins were compared with each other in terms of recurrence or progression, there was a statistically significant difference (P = .006). While the impact of radiotherapy on recurrence or pro-gression could not be determined due to inadequate sample size, the recurrence rate increased significantly with increasing ETV (P = .01).

Conclusion: Extraabdominal desmoid tumors are ill-defined locally aggressive neoplasms with an unpredictable and challenging clinical course. When the disease-free and recurring patients were compared, the recurrence rate increased significantly as the ETV increased. Achieving negative margins is still the benchmark for surgery; however, the risks and benefits of an aggressive surgery should always be reevaluated when there is a high possibility of a complex reconstructive surgery that has the capability to affect the functional outcome adversely.

We present the update of the recommendations of the Société française de radiothérapie oncologique (the French society for radiation oncology) on soft tissue sarcomas. Currently, the initial management of sarcomas is very important as it may impact on patients’ quality of life, especially in the case of limb soft tissue sarcomas, and on overall survival in trunk sarcomas. Radiotherapy has to be discussed within a multidisciplinary board meeting with results of biopsy, eventually re-examined by a dedicated sarcoma pathologist. The role of radiotherapy varies according to localization of soft tissue sarcomas; the use of intensity-modulated radiotherapy has become standard of care. It is part of the standard treatment for grade 2 and 3 sarcomas of the extremities and superficial trunk at least 5cm. Preoperative radiotherapy is generally preferred to postoperative irradiation in expert soft tissue sarcomas centres. In the case of incomplete resection, re-excision should be discussed. In such cases, radiation may be delivered preoperatively (50Gy in 25 fractions of 2Gy) or postoperatively. For retroperitoneal sarcomas, preoperative intensity-modulated radiotherapy cannot be proposed systematically following the results of STRASS trial. Concomitant chemoradiotherapy cannot be considered a standard treatment. All other soft tissue sarcomas sites will be addressed as well as as desmoid tumours, and other techniques that may be used such as brachytherapy and proton therapy. Hypofractionated radiotherapy for soft tissue sarcomas has also been adressed.

Purpose: To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in the treatment of desmoid tumors (DTs).

Patients and methods: In this investigator-initiated, double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with advanced or refractory DTs to receive either PLD (50 mg/m² intravenously) or placebo every 4 weeks for 6 cycles. Crossover from placebo to PLD was permitted upon disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response and safety.

Results: From November 2020 to March 2023, a total of 73 patients were assigned to receive PLD (49 patients) or placebo (24 patients). With a median follow-up of 16.1 months, PLD had a significantly longer PFS over placebo (not reached vs. 4.3 months), with a hazard ratio (HR) of 0.05 (95% CI, 0.01-0.17; P<0.001). The 2-year PFS rates were 90.4% with the PLD group and 19.6% with placebo. PFS benefit favored PLD across most prespecified subgroups. The confirmed objective response was observed in 19 (40.4%) patients in the PLD group and 1 (4.3%) in the placebo group (P=0.002). Common grade 3 or higher adverse events with PLD included neutrophil count decreased (10.6%), mucositis oral (6.4%), and white-cell decreased (4.3%). Significant between-group differences in certain patient-reported toxicities were observed (P<0.05). Conclusions: PLD significantly prolonged PFS and induced durable responses than placebo, with a favorable safety profile, for patients with progressive or symptomatic desmoid tumors.

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colorectal cancer (CRC) syndrome caused by germline pathogenic variants in the adenomatous polyposis coli (APC) gene. FAP is typically characterized by the development of hundreds to thousands of adenomatous polyps throughout the colon and rectum, with a nearly 100% chance of developing CRC if left untreated. Duodenal cancer is the second leading cause of cancer for patients with FAP; however, gastric cancer has become more prevalent in recent years with improved surveillance of the colon, rectum, and duodenum. Patients frequently develop other extracolonic manifestations including desmoid disease, which holds the highest extracolonic mortality risk, and thyroid nodules, which are more frequently associated with the cribriform morular variant of papillary thyroid cancer. Management of FAP is complex, and patients require frequent and lifelong surveillance. This review will discuss the current understanding and clinical management of FAP as well as innovations and challenges in clinical practice.

Background: Intra-abdominal desmoid tumours (IADT) can closely mimic gastrointestinal stromal tumours (GISTs), particularly in recurrence and metastases. However, differentiating these two diseases using radiological methods remains challenging. This study aimed to investigate the value of [18F]FAPI-42 PET/CT in differentiating IADT and GISTs compared to [18F]FDG PET/CT.

Methods: This study retrospectively included a total of 24 patients (12 patients with IADT and 12 patients with recurrent/metastatic GISTs) who underwent two separate PET/CT scans using [18F]FAPI-42 and [18F]FDG, respectively. The differences in tumour SUVmax on [18F]FAPI-42 PET/CT (SUVmax-FAPI) and [18F]FDG PET/CT (SUVmax-FDG) and the ratio of tumour SUVmax on FAPI PET/CT to SUVmax on FDG PET/CT [SUVmax ratio (FAPI/FDG)] were compared between IADT and GISTs. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of these parameters in differentiating IADTs from GISTs. Immunohistochemistry was used to verify FAP expression in all IADT lesions and GISTs lesions.

Results: The SUVmax of IADTs on [18F]FAPI-42 PET/CT was significantly higher than that of GISTs [8.8 (7.2, 10.6) vs. 3.9 (2.8, 7.6), P = 0.045], whereas the SUVmax of IADTs on [18F]FDG PET/CT was significantly lower than that of GISTs [2.5 (1.9, 3.5) vs. 6.1 (3.6, 8.3), P = 0.007]. The SUVmax ratio (FAPI/FDG) of IADTs was significantly higher than that of GISTs [3.3 (2.2, 4.1) vs. 0.8 (0.3, 1.4), P < 0.001]. SUVmax-FAPI, SUVmax-FDG, and the SUVmax ratio (FAPI/FDG) achieved AUCs of 0.743, 0.819, and 0.896, with corresponding accuracies of 75.0%, 83.3%, and 87.5%, respectively, for distinguishing IADT from GISTs. Immunohistochemistry revealed significantly higher FAP expression in IADTs compared to GISTs (P = 0.002), with most IADTs showing strong (3+) staining (8/12, 66.7%), while GISTs primarily demonstrated weak (1+) or no staining (7/12, 58.3%). Conclusion: The distinct uptake characteristics of [18F]FAPI-42 and [18F]FDG observed in IADTs and GISTs provide preliminary evidence that these two tracers may offer complementary diagnostic information when evaluating desmoid tumours that mimic recurrent or metastatic GISTs.

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort.

Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments.

Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS.

Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management.