Sorafenib or anthracycline-based chemotherapy for progressive desmoid tumors

Background: Desmoid tumors can cause morbidity due to local invasion, potentially being fatal when fast growth compromises vital structures. In this context, a timely treatment response is required. This study aims to compare the activity of sorafenib and anthracycline-containing regimens during the first year of treatment.

Methods: The authors conducted a multi-institutional retrospective analysis of desmoid tumor patients treated with either sorafenib or an anthracycline-containing regimen over 1 year. The primary end point was the overall response rate (ORR). The secondary end points were time to response (TTR), progression-free survival (PFS), and adverse events.

Results: From 2005 to 2022, 80 patients received sorafenib and 51 received an anthracycline-containing regimen with similar baseline characteristics. The 1-year ORR was 37% for anthracycline and 13% for sorafenib (p = .016). Median best response was -9% (range, -73 to 51) for anthracycline and -4% (range, -69 to 126) for sorafenib. Median TTR was 5.6 months (95% confidence interval [CI], 3.4-7.8) for anthracycline and 8.7 months (95% CI, 6.3-11.1) for sorafenib (p = .2). One-year PFS was 73% (95% CI, 60-86) for anthracycline and 59% (95% CI, 47-71) for sorafenib (p = .3). Common grade 1-2 adverse events for sorafenib were hand-foot syndrome (40%), diarrhea (25%), and fatigue (22%); for anthracycline, they were nausea (31%), fatigue (16%), and rash (14%). Grade 3 events were higher in the anthracycline group, 27% versus 14% (p < .05). Conclusion: Anthracycline-based therapy provided a greater 1-year response rate than sorafenib but was associated with a higher rate of serious adverse events. Higher-risk desmoid tumors, which need a more timely response, might benefit from anthracycline-based therapies, whereas average-risk tumors could benefit from sorafenib.

Purpose: Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas but little is known about molecular variability within locally aggressive tumors such as desmoids.

Experimental design: We performed transcriptomic profiling of 31 specimens from 20 primary desmoid tumors to identify genes predictive of relapse. We also performed multi-omic analysis including DNA methylation, copy number alterations, point mutations and gene expression on 24 specimens from different regions of primary and recurrent desmoid tumors from 3 patients (7-9 specimens per patient).

Results: We observed highly variable expression of transcriptomic prognostic signatures, both in patients who did or did not progress. Signatures associated with favorable and unfavorable outcome were detected in different regions within the same tumor. Further multi-omic studies showed remarkable intra- and inter-tumor heterogeneity of genomic, epigenomic and transcriptomic patterns. The transcriptomic profiles showed the highest degree of variability within tumors and between primary and recurrent tumors from the same patient.

Conclusions: This study shows an unexpected degree of intra- and inter-tumor heterogeneity in desmoid tumors. Our analysis indicates that molecular analysis of a single tumor biopsy may underestimate the magnitude of molecular alterations in desmoid tumors. Our study also shows that recurrent desmoid tumors acquire multiple new molecular alterations. Thus, molecular heterogeneity is an important consideration in drug development and validation of prognostic and predictive biomarkers for desmoid tumors.

Introduction: Desmoid tumor (DT) is a rare, locally aggressive, mesenchymal neoplasm that can arise at any site in the body. Medical therapies play a major role for DT’s patients requiring treatment. A novel systemic approach has recently emerged with Nirogacestat, a γ-secretase inhibitor targeting the NOTCH signaling pathway.

Areas covered: Nirogacestat is the first drug in its class to receive approval from the Food and Drug Administration (FDA) and is the first FDA-approved treatment specifically for DTs. We reviewed the data leading to its discovery, including its mechanism of action, pharmacological properties, clinical efficacy, and its positioning within the current treatment armamentarium for DTs.

Expert opinion: High-quality evidence for systemic therapies in the management of DTs remains an unmet need. Nirogacestat now joins sorafenib as the only drugs with efficacy in DTs demonstrated by randomized phase 3 studies. Currently, there are no comparative trials of the available systemic therapies. Therefore, physicians should consider factors such as drug accessibility, cost, toxicity profile, comorbidities, and patient preferences when selecting treatment. Long-term efficacy and safety data will be essential for evaluating the duration of treatment response and monitoring late-onset side effects of Nirogacestat.

Introduction: Percutaneous cryoablation is a first-line therapeutic option for primary neoplasms and metastatic lesions of the musculoskeletal system. Treatment of abdominal wall tumors is challenging as surgical resection can be highly morbid and necessitate complex reconstructive surgery; the efficacy of cryoablation for abdominal wall tumors may be limited by inadequate posterior margins owing to the proximity of intra-abdominal organs. With laparoscopy and insufflation, peritoneal structures can be safely mobilized away from the abdominal wall, allowing for adequate deep margin freeze and visualization of the ice ball. We present two patients with abdominal wall soft tissue tumors treated with a novel approach of laparoscopic-assisted, percutaneous ultrasound-guided cryoablation.

Patients and methods: Patient 1 is a 65-year-old female with metastatic extraskeletal myxoid chondrosarcoma, stable on systemic therapy, who presented with a new soft tissue metastasis to the abdominal wall. Resection would have necessitated a highly morbid complex abdominal wall reconstruction with mesh. Patient 2 is a 35-year-old female with a large abdominal wall desmoid tumor, diagnosed after miscarriage. Resection was relatively contraindicated owing to the morbidity of a complex abdominal wall reconstruction and concerns regarding potential future pregnancies after surgery.

Results: Both patients underwent procedures in the outpatient setting after discussion at multidisciplinary sarcoma tumor board. Laparoscopic enterolysis was performed to mobilize the bowel away from the abdominal wall, to allow direct visualization of the peritoneal aspect of the tumor, and to confirm adequacy of the posterior margin freeze of the lesion. Laparoscopic transversus abdominus preperitoneal (TAPP) blocks with local anesthetic were performed for postoperative pain control. Interventional radiology performed an ultrasound-guided cryoablation consisting of two freeze and thaw cycles. Both patients recovered well without complications and were without radiographic evidence of persistent or recurrent disease at 12 and 18 months postoperatively, respectively.

Conclusion: We report a novel approach of laparoscopic-assisted cryoablation for the treatment of abdominal wall soft tissue tumors. This allowed for successful minimally invasive local control of these large tumors that would have otherwise required highly morbid resections with complex abdominal wall reconstruction and mesh repair.

Cervical aggressive fibromatosis is a rare intermediate tumor characterized by invasive growth. Aggressive fibromatosis (AF), also referred to as desmoid-type fibrosarcoma or grade I fibrosarcoma, is a clonal proliferative lesion of fibroblasts located in deep soft tissues. While many cases have been reported, there are relatively few involving aggressive fibromatosis in the anterior inferior margin muscle space of the neck trapezius muscle. We present a case of pathologically confirmed left cervical aggressive fibromatosis, admitted to the Fourth Affiliated Hospital of Zhejiang University. The initial ultrasound and magnetic resonance imaging (MRI) scan of the patient revealed a mass in the left cervical dorsal muscle space, which slowly increased after one year. An enhanced MRI scan initially diagnosed the mass as a left cervical schwannoma. The patient underwent neck soft tissue lesion resection surgery, with postoperative confirmation of cervical aggressive fibromatosis. Our case suggests that fibromatosis cannot be ruled out, and the low-signal cord-like non-enhanced areas, representing collagen fiber characteristics after enhanced scanning, are significant imaging features in diagnosing cervical fibromatosis. Based on the available literature, we have conducted preliminary research on the clinical presentation, imaging manifestations, diagnosis, and differential diagnosis of cervical aggressive fibromatosis to improve clinical understanding and ensure timely clinical treatment.

Introduction and importance: Desmoid-type fibromatosis is an uncommon tumor characterized by its local invasiveness, with shoulder involvement being notably infrequent. The optimal treatment strategy for this tumor remains a topic of ongoing debate.

Case presentation: A 47-year-old Tunisian woman with a history of hypothyroidism, presented with pain and swelling in her left shoulder for a year. Examination revealed a firm, painful 4 cm mass, and MRI showed a poorly defined intramuscular tumor in the deltoid muscle, initially suspected to be rhabdomyosarcoma. However, surgical biopsy confirmed desmoid-type fibromatosis of the shoulder. The patient underwent surgical wide en-bloc resection of the tumor. The patient’s recovery was uneventful, and she received physical therapy. At the three-year follow-up, she reported residual shoulder pain after heavy lifting, improving with analgesics. Examination showed no neurological deficits and a Constant score of 83 out of 100.

Clinical discussion: Due to their deep-seated nature and infiltrative growth patterns into neighboring subcutaneous tissues or muscles, along with the presence of myxoid or fibrotic components, desmoid-type fibromatosis can present challenges in distinguishing them from malignant soft tissue neoplasms based on imaging characteristics.

Conclusions: While radiologic evaluations may indicate characteristics suggestive of a malignant soft tissue tumor, histological confirmation is imperative prior to initiating surgical intervention. Continued research into the optimal treatment approaches for desmoid-type fibromatosis is essential for improving future patient outcomes and quality of life.