Desmoid-type fibromatosis of diaphragm

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Anticancer drugs and molecular targeted therapies are used for refractory desmoid-type fibromatosis (DF), but occasionally cause severe side effects. The purpose of this study was to identify an effective drug with fewer side effects against DF by drug repositioning, and evaluate its efficacy. FDA-approved drugs that inhibit the proliferation of DF cells harboring S45F mutations of CTNNB1 were screened. An identified drug was subjected to the investigation of apoptotic effects on DF cells with analysis of Caspase 3/7 activity. Expression of β-catenin was evaluated with western blot analysis, and immunofluorescence staining. Effects of the identified drug on in vivo DF were analyzed using Apc1638N mice. Auranofin was identified as a drug that effectively inhibits the proliferation of DF cells. Auranofin did not affect Caspase 3/7 activity compared to control. The expression level of β-catenin protein was not changed regardless of auranofin concentration. Auranofin effectively inhibited the development of tumorous tissues by both oral and intraperitoneal administration, particularly in male mice. Auranofin, an anti-rheumatic drug, was identified to have repositioning effects on DF. Since auranofin has been used for many years as an FDA-approved drug, it could be a promising drug with fewer side effects for DF.

Introduction: Desmoid-type fibromatosis (DF) are a group of rare (0.03% of total neoplasms) benign tumours arising from fibroblasts that can exhibit locally aggressive behaviour.1 Single agent oral vinorelbine (90 mg weekly for three consecutive weeks of each 28-day cycle) recently emerged as a simplified, less toxic and more manageable alternative to the standard pharmacological approach with two-weekly IV methotrexate and vinorelbine in patients with aggressive or refractory disease.2,3 This study aimed at describing the efficacy and safety of oral vinorelbine in a cohort of patients with DF in any line of treatment. Methods: This was a single-centre, retrospective study of patients treated with oral vinorelbine for DF over a period of 18 months (Jan 2020 to Jun 2021) within a specialised cancer centre. Patients who received at least 3 cycles of treatment (or until the first documented radiographic assessment, whatever occurred first) were included. The following information was collected from the electronic health care records system (Epic®) patient demographics (age, gender), number of previous treatment lines, and number of number of months on treatment (until closure of observations). Efficacy clinical and radiographic reports were used to determine disease status as per RECIST A subgroup analysis of patients who were transitioned from other pharmacological options was also performed. Safety routine full blood count and biochemistry weekly for the first three cycles, and once monthly thereafter were assessed for blood dyscrasias. Other side effects were also recorded. Results: Twenty-four patients were initially started on oral vinorelbine, of which 19 met the inclusion criteria (baseline and demographic characteristics summarised in table 1). Efficacy Symptomatic improvement was observed in all cases (100%) shortly after initiation. Favourable radiographic findings (SD or better) were documented in 18 cases (94.73%). Only one patient (5.26%) experienced marginal increase in tumour size, but was maintained on treatment until further assessment, as still deriving clinical benefit. Additionally, all subjects in the subgroup who were transitioned from other pharmacologic options (9 patients) showed disease response. Safety one episode of grade 3 neutropenia observed after seven cycles. Full blood counts and biochemistry parameters remained otherwise stable throughout treatment one patient had low haemoglobin requiring multiple blood transfusions;this occurred in the context of poor baseline renal function and remained essentially unchanged throughout. The main reported toxicities were diarrhoea (5 cases), nausea (grade 1 in 7 patients and grade 2 in one), fatigue (8), constipation (grade 2, 4 patients), and headaches and muscle pain (one case each). Discussion/ conclusion: Single agent oral vinorelbine was found to be an effective treatment option for the management of newly diagnosed or refractory DF;this was also true for a subgroup of patients who received this to reduce hospital visits or after failure of a previous treatment line. Safety-wise, patients had stable blood counts and biochemical values throughout treatment, whereas most toxicities were mild and did not require discontinuation. These findings are in line with previous reports and underpin a paradigm shift in the management of DF in the post-COVID era.

Desmoid tumors are benign fibroblastic neoplasms, with locally invasive features and a tendency of recurrence. They are considered an aggressive non-metastatic fibromatosis. The retroperitoneal location is extremely rare. Their exact mechanism of occurrence is still controversial, but could be related to a genetic predisposition, hormonal factors or traumatic factors, including surgery. This entity faces management difficulties due to its rarity, the variable circumstances of its discovery, and the non-specific clinical manifestations. Their sensitivity to chemotherapy and radiotherapy is limited and surgery remains the only curative treatment in symptomatic cases, however observational waiting could consist the most appropriate management in selected asymptomatic patients, moreover it could avoid unnecessary morbidity from surgery or radiotherapy, which makes the management of this condition a multidisciplinary decision and should be adapted to fit the patients individually. We report a case of a retroperitoneal desmoid tumor in a 31-year-old woman with a history of familial adenomatous polyposis, through which we will discuss this extremely rare neoplastic entity.

Desmoid tumors are rare formations of fibroblastic origin thought benign and slow growing, but could be aggressive in behaviour invading the surrounding areas. The aim of this report is to present a case of a patient with desmoid tumor located in anterior cervical region mimicking malignant formation. A 69-year-old female patient with previous history of surgery due to multinodular goiter as well as primary hyperparathyroidism caused by parathyroid adenoma was scheduled to ultrasound of the neck due to hoarseness. Ultrasound revealed extremely hard, isoechoic, poorly defined nodule with calcification in thyroid bed suggestive of malignant tissue. The finding of fine needle aspiration cytology report showed rare spindle cells but was inconclusive. Other imaging techniques like computed tomography and magnetic resonance imaging were suggestive for paraganglioma or parathyroid adenoma, but another etiology could not be ruled out with certainty and complete surgical resection was recommended. Pathology report was consistent with fibromatosis, leading to the final diagnosis of extra-abdominal desmoid tumor. Although desmoid tumor is generally a benign disease, it can sometimes be locally aggressive invading the surrounding tissue and mimicking the picture of a malignant process with difficulties to remove surgically, as in our case. Moreover, even after complete excision, recurrence of the disease often occurs that should be kept in mind and such patients should be monitored periodically.

Background: Desmoid tumors (DT) or aggressive fibromatosis are rare growths of fibroblastic connective tissue that can be locally aggressive but without metastatic potential. Most cases are sporadic, but 5-20% of cases are associated with Familial adenomatous polyposis (FAP). Despite numerous systemic options, optimal choice is unclear, and there is a paucity of studies comparing efficacy based on tumor site. Liposomal doxorubicin (LD) can be an appealing option for DT patients (pts) given its favorable schedule and toxicity profile. In this study, we compared outcomes in pts with intra-abdominal (IA) and extra-abdominal (EA) DT who received LD. Methods: We identified pts with DT who were treated with LD between 1/2010 – and 2/2022 at two sarcoma centers. Tumor and pt characteristics and outcomes were clinically (symptom improvement) and radiologically (RECIST 1.1) assessed. Results: 40 pts with DT treated with LD were identified; 58% female and 42% male. Pt characteristics and outcomes are summarized in Table 1. Primary tumor site was IA in 21 (53%) pts. FAP was present more commonly in pts with IA vs EA DT, 8/21 (43%) and 4/19 (21%), respectively. In the IA cohort, LD was given as first (15/21, 71%), second (10%) or third (19%) line therapy. LD was used more commonly as a later line in the EA cohort with 16%, 52%, 16%, and 16% receiving it in first, second, third, and fourth lines, respectively. 37 pts were evaluable for response. Response rate in the IA cohort treated in first-line was 50% (8 of 16) and 10 of 12 evaluable pts had symptomatic improvement. No first-line responses were seen in the EA cohort. As later lines of therapy, 7/12 pts had disease control in the second line, 6/8 pts in the third line, and 1/2 pts in the fourth line with LD in the IA cohort. 1 patient had fourth line response to LD in the EA cohort. Disease control rate with LD was 72.5% across all pts. Reasons for early discontinuation of LD included progression or lack of symptom improvement (20%), allergic reaction (12.5%), adverse effects (7.5%), or infection (2.5%). No acute or long-term cardiotoxicity was reported. 2 pts had no signs of recurrence or symptoms at follow-up, 33 pts were alive with symptomatic DT, 1 patient died from disease, and 3 were lost to follow-up. Conclusions: In our study, LD provided tumor response, disease control, and symptomatic improvement regardless of location or prior therapy, with responses most frequently seen in IA DT in first line setting. Further studies should include comparison of efficacy, adverse effects, and patient-reported outcomes while accounting for tumor location and line of therapy.