Old drug, new data: Broadening the therapeutic armamentarium for desmoid tumors

Desmoid tumours are a locally invasive neoplasm that can exhibit unpredictable clinical behaviour. While treatment options are numerous, few are supported by level 1 evidence. A recent phase 3 trial evaluated the efficacy of long-used pegylated liposomal doxorubicin in patients with progressive desmoid tumours.

Desmoid-type fibromatosis (DTF) is a rare, benign but locally aggressive fibroblastic neoplasm that lacks metastatic potential yet may cause significant morbidity due to local invasion and mechanical complications; intra-abdominal or mesenteric involvement is uncommon and may rarely present with acute intestinal obstruction or volvulus. We report a 30-year-old female who presented with a 3-day history of severe abdominal pain, progressive abdominal distension, and absolute constipation, in whom contrast-enhanced CT demonstrated a large mesenteric soft-tissue mass measuring approximately 16 × 12 cm associated with twisting of small-bowel loops around the mesenteric pedicle, consistent with small-bowel volvulus and closed-loop obstruction; emergency laparotomy with derotation and complete excision was performed, and histopathology confirmed mesenteric DTF, with no recurrence at 6-month follow-up. This case highlights that mesenteric DTF, although benign, can present dramatically with life-threatening mechanical complications and emphasizes the importance of prompt CT diagnosis, urgent surgical management, and histopathologic confirmation, as well as awareness of this rare presentation among radiologists and surgeons to reduce morbidity in acute settings.

Desmoid Tumors (DT) are rare fibromatoses that are locally invasive. These are described as being monoclonal, and they tend to recur. Their clinical features are also different, and the prognoses of these tumors are not predictable. The recent achievements made in molecular genetics and the encouragement of multidisciplinary treatment modes have made a tremendous contribution to the diagnosis, treatment strategies, and qualityof-life measures of patients with DT. This is a narrative review that summarizes clinical, molecular pathology, conventional, and new areas of treatment, prognosis, and the current research on quality of life assessment tools in DT. It specifically highlights the uses and opportunities of targeted therapies, such as the secretase inhibitor nirogacestat (DeFi trial, NCT03785964) and tyrosine kinase inhibitors, such as sorafenib, reporting substantial disease progression, and critically reviews the role of surgery, in the context of high recurrence rates of marginpositive or even margin-negative resection. The study indicates the significance of personalized treatment that varies treatment options with proper risk-benefit analysis of each patient. This review also explains that the heterogeneous nature of DT and the absence of a standard-of-care predetermine the necessity of such an individual approach. Future areas of research that would offer a more powerful scientific foundation for individual guidance are also mentioned.

Introduction: The SORASTOP study reports long-term outcomes following planned sorafenib discontinuation in responding patients with extremity desmoid-type fibromatosis (DTF).

Materials and methods: In this prospective, single-arm phase 2 Simon’s two-stage trial, adults with non-progressive, extremity DTF, ESAS pain < 2, after ≥ 12 months of sorafenib were enrolled. Sorafenib was stopped and patients were monitored with MRI, ESAS, and EORTC QLQ-C30, ACE-III. Progression was defined as ≥ 20 % tumour increase or ≥ 10 % increase with ESAS pain score > 5. The primary endpoint was 1-year PFS.

Results: 33 patients (median age 30 years; 54.5 % female) were enrolled between 2021-2023. At 12 months, 31 (93.9 %) were evaluable; at 24 months, 30 (90.9 %). After 12 months of discontinuation, 4/31 (12.9 %) had PR, 24/31 (77.4 %) SD and 3/31 (9.6 %) PD and at 24 months 8/30 (26.6 %) had PR, 16/30 (53.3 %) SD and 6/30 (20 %) PD (RECIST v1.1). ESAS pain showed a transient rise: pain-free patients (ESAS=0) decreased from 69.7 % at baseline to 35.5 % at 12 months, recovering to 66.7 % at 24 months. Nine patients (27 %) progressed; four required sorafenib re-initiation and five were managed conservatively, all ultimately achieving disease stabilisation. PFS at 12, 24 and 36 months were 90.8 %, 74.5 % and 74.5 % respectively; with median follow-up of 37 months. EORTC QLQ-C30 showed stable global health status and improvements in emotional, physical, and cognitive functioning, with reductions in fatigue and pain.

Conclusion: Planned sorafenib discontinuation in responding extremity DTF patients is feasible, yields durable disease control, and improves QoL. Patients who progressed were successfully managed with sorafenib re-challenge or observation.

Cortical desmoids, also known as distal femoral cortical irregularities, are benign bone lesions typically arising at the posteromedial aspect of the distal femur. These lesions are thought to result from repetitive traction stress at the insertion of the adductor magnus or medial gastrocnemius tendons. Although nonaggressive in nature, their radiographic appearance can mimic malignancy, requiring careful clinical and radiologic correlation to avoid unnecessary interventions such as biopsy or surgery.

Background: Pazopanib, a multi-targeted tyrosine kinase inhibitor, is employed in the treatment of various malignancies, including metastatic non-adipocytic soft tissue sarcoma.

Methods: This systematic review and meta-analysis adhered to PRISMA guidelines to evaluate the efficacy and toxicity of pazopanib monotherapy in treating sarcomas. A comprehensive search of PubMed/MEDLINE and Scopus/ELSEVIER databases was conducted, covering the period from 2009 to 2025. The included studies were evaluated for quality using the MINORS, Newcastle-Ottawa Scale, and RoB2 tools. The spectrum of toxicities and responses in sarcoma types was described. A meta-analysis was performed to compare the efficacy of pazopanib with non-placebo treatments, using both fixed-effect and random-effect models to calculate pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS).

Results: A total of 40 studies were included, encompassing a wide range of study designs and quality. The analysis revealed variable objective response rates (ORR) across different sarcoma types, with the highest ORRs by RECIST observed in desmoid tumors (37.0%) and alveolar soft part sarcoma (35.5%). Common toxicities included hypertension, liver function test abnormalities, and fatigue, with significant variability in dose reductions and treatment interruptions across studies. The pooled HRs for PFS and OS were 1.10 (95% CI: 0.69-1.25) and 0.99 (95% CI: 0.63-1.35), respectively, indicating no significant advantage of non-placebo treatments respect to pazopanib.

Conclusions: Pazopanib demonstrated histology-specific efficacy in sarcomas, with a manageable toxicity profile. Furthermore, it does not appear inferior to non-placebo interventions, highlighting the need for further comparative studies to clarify its role in the therapeutic landscape of advanced sarcomas.