Efficacy and safety of apatinib for patients with advanced extremity desmoid fibromatosis: a retrospective study

The aim of this study was to investigate the efficacy and safety of apatinib, a novel multi-target angiogenesis inhibitor, in patients with desmoid fibromatosis (DF). We retrospectively analyzed the medical records of patients with advanced extremity DF regularly treated with apatinib between October 2017 and January 2020 in our center. Apatinib was initially administered with a dose of 250 mg daily and the dose was adjusted according to the toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. The primary endpoint was progression-free survival (PFS); objective response rates and drug-related adverse events were also evaluated. A total of 22 (6 male, 16 female) patients with advanced extremity DF were included. The mean medication time was 17 months. None of the patients reached a complete response, but ten (45.5%) patients achieved partial response, and 11 patients (50%) achieved stable disease. One (4.5%) patient developed progressive disease, and the 1-year PFS rate was 95.2%. The disease control rate was 95.4% (21/22) and the objective response rate was 45.5% (10/22). Meanwhile, 18 (81.8%) patients with a tumor shrinkage were accompanied by a decreased signal intensity of lesions in T2-weighted magnetic resonance imaging. The most frequent adverse events included hand-foot syndrome (n = 7, 31.8%), fatigue (n = 6, 27.2%), local pain (n = 4, 18.1%), diarrhea (n = 4, 18.1%). Apatinib is an effective and well-tolerated option for patients with advanced extremity DF. Indeed, further prospective, randomized studies with larger cases are required to fully explore the clinical utility of apatinib in DF.

We present here a 35-year-old male patient with chest wall aggressive fibromatosis, who was treated with surgery followed by adjuvant radiation therapy. The patient is doing well following 12 months of follow-up without local recurrence. Radical surgical resection is the main treatment for desmoid tumors (DTs). The adjuvant treatment, either chemotherapy or radiotherapy, can be considered when radical resection could not be achieved and if reoperation for a recurrence is not applicable. Close follow-up is essential in such patients.

Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of desmoid tumours (DT) to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients’ prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies.

A 42-year-old man visited our clinic for routine follow-up 1 year after left upper lobe lingular segmentectomy for lung adenocarcinoma. Chest computed tomography showed a pleural mass adherent to the thoracotomy site. Positron emission tomography revealed mildly increased metabolism with a maximal standardized uptake value of 2.7 within the tumor, suggesting local recurrence of the previous neoplasm. Exploratory thoracotomy and en bloc resection of the tumor revealed spindle cells in a massive collagenous tissue consistent with a desmoid tumor. Next-generation sequencing (NGS) was performed to confirm the diagnosis and to identify any genetic alterations that might be relevant to the prognosis of this tumor. The tumor harbored an S45F mutation in CTNNB1, which has been correlated with a high recurrence rate. Therefore, we performed adjuvant radiotherapy on the resection bed at a dose of 56 Gy. The patient experienced no postoperative or radiotherapy-related complications. Periodic follow-up examinations using computed tomography were performed every 3 months, and no evidence of recurrence of either tumor was observed during the 38 months after the last surgery. To the best of our knowledge, this is the first case reporting the clinical application of NGS and aggressive treatment based on the genotyping results for the management of a desmoid tumor.

Desmoid tumours which present to CoRSU rehabilitation hospital in Kampala are frequently managed surgically. This study compares the demographics and management of patients presenting to CoRSU hospital with that of other centres against best practice. The CoRSU database was searched for any patients diagnosed with “desmoid tumour” or “fibromatosis”. Fourteen patients with suitable histology were found. There were six males in the cohort and eight females. The median age at diagnosis was 12 (range 5-35). The most common tumour sites were the extremities, limb girdles and chest wall. Four patients had at least one recurrence, and of these all of them had a primary tumour in the extremities or limb girdles. The patient demographics at CoRSU are similar to those demonstrated in the literature. The study supported the idea that younger patients are more likely to develop extra-abdominal tumours, and older patients may present with abdominal tumours. Most patients were managed surgically, in line with current recommendations.

A 15-year-old boy presented with a painless, progressively growing swelling of his right arm. The swelling was firm, non-tender and with restricted mobility. MRI imaging revealed a well-defined, heterogenous, lobulated swelling extending beneath arm and shoulder muscles. Wide local excision of the swelling was done under general anesthesia and pathologic examination revealed aggressive fibromatosis of the arm. Adjuvant radiotherapy was provided to the patient to reduce the risk of local recurrence of the tumor. Aggressive fibromatosis of the upper limb presents as a painless, progressively growing swelling. Assessment with MRI is imperative for making a preliminary diagnosis. Wide local excision with safety margin with adjuvant radiotherapy is the main line of treatment to minimize the incidence of recurrence and preserve the limb.