Target therapy with celecoxib in pediatric recurrent desmoid tumors. A case report

We present a pediatric case of a mediastinal desmoid tumor in which CTNNB1 mutation was detected, a genetic mutation which predicts sensitivity to celecoxib, a COX-2 inhibitor.We present the case of a 6 year old girl with a recurrent mediastinal desmoid tumor.Surgical resection was conducted due to the high risk of hemodynamic impairment.The histopathological study confirmed the diagnosis of desmoid-type fibromatosis.Close follow-up was performed with thoracic MRI, identifying tumor recurrence at 18 and 24 months after diagnosis, which are surgically resected. A somatic mutation in CTNNB1 (c.121A>G; p.T41A) is identified. Target treatment with celecoxib and sorafenib was administered. Secondary effects associated to sorafenib appear and treatment with sorafenib is interrupted. Celecoxib in monotherapy is maintained. After 2 years of treatment, the patient remains in complete remission. The generation of therapeutic guidelines is complex. Spontaneous regression has been described in a 20-30% of the cases, recommending “watch and wait strategies”.In symptomatic cases or with risk of functional impairment, surgical or systemic treatment must be considered. If there is a known molecular target such as CTNNB1,target therapy with NSAIDs (i.e. celecoxib) is recommended. Our case demonstrates the efficacy of celecoxib in monotherapy. The identification of molecular targets through genetic study is highly advisable,especially in unresectable, progressive or recurrent desmoid tumors.Treatment with celecoxib in monotherapy could be a secure and effective therapeutic alternative

Desmoid-type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm without metastatic potential. Here, we report a very rare sporadic case of an intracranial supratentorial extradural DTF measuring 82 mm in a 1-year-old girl, that recurred twice following surgery over the course of 16 months, requiring two other surgeries. In three surgeries, we resected a huge tumor with the dura which was thought to be tumor origin and removed this tumor infiltrated the frontal skull base by drilling widely. Furthermore, we treated the tumor invading the bone flap using liquid nitrogen for 20 minutes, and subsequently used it to perform a cranioplasty. This tumor has not recurred for past 8 months. DTF invading the skull base is prone to recurrence, and liquid nitrogen treatment is considered to be effective in pediatric patients, who need cranioplasty with tumor-infiltrating autologous bone flaps.

Differential responses to tamoxifen may be due to inter-patient variability in tamoxifen metabolism into pharmacologically active Z-endoxifen. Z-endoxifen administration was anticipated to bypass these variations, increasing active drug levels, and potentially benefitting patients responding sub-optimally to tamoxifen. Patients with treatment-refractory gynecologic malignancies, desmoid tumors, or hormone receptor-positive solid tumors took oral Z-endoxifen daily with a 3+3 phase 1 dose escalation format over 8 dose levels (DLs). Thirty-four of 40 patients were evaluable. No maximum tolerated dose was established. DL8, 360 mg/day, was used for the expansion phase and is higher than doses administered in any previous study; it also yielded higher plasma Z-endoxifen concentrations. Three patients had partial responses and 8 had prolonged stable disease (? 6 cycles); 44.4% (8/18) of patients at dose levels 6-8 achieved one of these outcomes. Six patients who progressed after tamoxifen therapy experienced partial response or stable disease for ? 6 cycles with Z-endoxifen; one with desmoid tumor remains on study after 62 cycles (nearly 5 years). Evidence of antitumor activity and prolonged stable disease are achieved with Z-endoxifen despite prior tamoxifen therapy, supporting further study of Z-endoxifen, particularly in patients with desmoid tumors.

Surgery is an important treatment option for desmoid tumor (DT) patients, but how to decrease and predict the high recurrence rate remains a major challenge. Desmoid tumor patients diagnosed and treated at Tianjin Cancer Institute & Hospital were included, and a web-based nomogram was constructed by screening the recurrence-related risk factors using Cox regression analysis. External validation was conducted with data from the Fudan University Shanghai Cancer Center. A total of 385 patients were identified. Finally, after excluding patients without surgery, patients who were lost to follow-up, and patients without complete resection, a total of 267 patients were included in the nomogram construction. Among these patients, 53 experienced recurrence, with a recurrence rate of 20.15%. The 3-year and 5-year recurrence-free survival (RFS) rates were 82.5% and 78%, respectively. Age, tumor diameter, admission status, location, and tumor number were correlated with recurrence in univariate Cox analysis. In multivariate Cox analysis, only age, tumor diameter and tumor number were independent risk factors for recurrence and were then used to construct a web-based nomogram to predict recurrence. The concordance index (C-index) of the nomogram was 0.718, and the areas under the curves (AUCs) of the 3-year and 5-year receiver operating characteristic (ROC) curves were 0.751 and 0.761, respectively. In the external validation set, the C-index was 0.706, and the AUCs of the 3-year and 5-year ROC curves are 0.788 and 0.794, respectively. Age, tumor diameter, and tumor number were independent predictors of recurrence for DTs, and a web-based nomogram containing these three predictors could accurately predict RFS (https://stepforward.shinyapps.io/Desmoidtumor/).

We retrospectively analyzed the data from 24 patients treated in the First Hospital of China Medical University from January 2011 to June 2019 and discussed the characteristic of this disease after a review of literature worldwide. Most patients were female (91.7%) with a mean age of 33 years (range 26-56 years). The most common symptom was progressive abdominal wall discomfort (ie, abdominal pain) in 16 patients (66.7%). Twelve patients (50%) had a history of cesarean section. All 24 patients underwent surgical R0 resection due to progression of disease or pain, including 12 patients treated with simple tumor resection and 12 patients treated with tumor resection followed by abdominal wall tension-free repair using synthetic mesh. The local recurrence rate was 12.5%. Aggressive fibromatosis of the abdominal wall mainly occurs in young women after cesarean section or other surgeries, with a high recurrence rate. Radical resection is an optimal treatment for the patients with progressive cases, and the restoration of extensive defects of the abdominal wall can be achieved with synthetic mesh, which leads to a good restoration of abdominal wall integrity.

We present a case of an aggressive fibromatosis in a 28-year-old male patient with no previous medical history. The tumor was in the retroperitoneum and eventually caused perforation of the coecum. During the operation, no metastasis was found; however, local lymphadenopathy was seen. After the surgical resection, no adjuvant therapy (radio or chemotherapy) was given to the patient and on follow-up (after three years), no recurrence was observed.