Clinico-radiological outcomes after discontinuation of sorafenib in non-abdominal desmoid-type fibromatosis: Final results from a phase-II SORASTOP study from India

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.

In the early 2010s, a paradigm shift in the management of DTs emerged, with a ‘wait-and-see’ strategy becoming the preferred initial approach for the majority of the patients. Prospective data have since shown that up to 30% experience spontaneous disease regression, and approximately two-thirds remain treatment-free at five years. As a result, surgery is now reserved as an upfront option only for selected cases, while most individuals who are symptomatic, have life-threatening disease, or show clear radiological or clinical progression are primarily managed with systemic therapies.

Before 2023, no medical therapy had been approved for DTs, although agents such as multitargeted tyrosine kinase inhibitors, including sorafenib and pazopanib, and conventional chemotherapy, were used in clinical practice. In this context, gamma-secretase inhibitors (GSIs) have recently emerged as one of the most compelling pharmacotherapeutic approaches investigated in DTs, supported by a biologically sound rationale and the most robust clinical evidence to date in this disease.

Orbital desmoid fibromatosis (DF) is a rare, non-metastasizing, locally destructive fibroblastic neoplasm, posing diagnostic and therapeutic challenges. There are only 12 reports of orbital DF in the literature. Herein is a case of an infantile orbital DF refractory to multiple chemotherapeutic agents, which was treated with a combination of sorafenib and cryoablation. This case highlights the importance of combination molecular profiling in establishing correct diagnosis, especially with low or equivocal intranuclear β-catenin staining. This case also highlights the efficacy of sorafenib and adjuvant cryoablation as non-surgical treatment options of recalcitrant DF when complete surgical excision is not an option. To the authors knowledge, this is the first report demonstrating the use of cryoablation for orbital DF.

Desmoid tumors are rare locally aggressive soft tissue tumors that can occur anywhere in the body and have a varying imaging appearance.