Desmoid-type Fibromatosis Research Articles

Efficacy and Safety of Auranofin for Progressive Desmoid-Type Fibromatosis: The Study Protocol of an Open-Label Phase II Trial.

Background As desmoid-type fibromatosis (DF) exhibits a high recurrence rate after surgery, initial active surveillance followed by medical therapy is the mainstay of the treatment. However, there are few effective drugs with acceptable side effects. Methodology Among drugs that have been used for a long period and possess a known safety profile, auranofin was observed to be effective in suppressing DF using the drug repositioning method in our laboratory. This clinical study has been designed to examine the efficacy and safety of auranofin, an approved anti-rheumatic drug, in patients with progressive DF. Results This study is conducted as a single-center, single-arm, open-label study. Auranofin 3 mg tablets will be administered twice daily to DF patients with progressive disease. The primary endpoint is progression-free survival at 26 weeks after starting treatment. Secondary endpoints include response rate, T2-weighted MRI evaluation, pain intensity, quality of life (QOL), and safety assessment. Conclusions This is the first clinical trial of auranofin in patients with aggressive DF. The study will allow an in-depth understanding of the efficacy of auranofin for response rate as well as for changes in MRI findings, pain, and QOL in patients with aggressive DF.

Giant intra-abdominal desmoid-type fibromatosis infiltrating into the pancreas

Abstract: Intra-abdominal desmoid-type fibromatosis is a proliferative fibroblastic lesion that constitutes 8% of all desmoid tumors and 0.03% of all neoplasm. It is histologically benign with a local aggressive nature and recurs even after excision. It can occur sporadically and or associated with familial adenomatous polyposis mutation. The present case is a 25-year-old female admitted with a chief complaint of abdominal mass gradually increasing in size in the last 6 months. Ultrasound of the whole abdomen initially suggested it to be a uterine/ovarian mass, which is further detailed by the contrast-enhanced computerized tomography (CT) scan. The CT scan showed a large heterodense intraperitoneal mass lesion measuring 34 cm × 25 cm × 16 cm with foci of calcification and necrosis. The mass extended superomedially. It displaced and compressed the stomach wall. It was abutting the peritoneum and was associated with diffuse peritoneal thickening anterolaterally. Posteriorly it was abutting small bowel loops and inferiorly extending into the pelvis and compressing the urinary bladder wall. Posterosuperiorly seems to abut the left kidney and spleen. Desmoid tumor and gastrointestinal stromal tumor (GIST) remained as differentials radiologically and then the patient underwent laparotomy. Histology and immunohistochemistry confirmed it to be fibromatosis. It is, therefore, justified to describe the tumor by considering its rarity, difficulties in diagnosis, and therapeutic ambit.

Different Shades of Desmoid-Type Fibromatosis (DTF): Detection of Noval Mutations in the Clinicopathologic Analysis of 32 Cases.

Desmoid-type fibromatosis (DTF) is a locally aggressive myofibroblastic/fibroblastic neoplasm with a high risk of local recurrence. It has a variety of histologic features that might confuse diagnosis, especially when detected during core needle biopsy. The Wnt/β-catenin pathway is strongly linked to the pathogenesis of DT fibromatosis. This study examined 33 desmoid-type fibromatoses (DTFs) from 32 patients, analyzing its clinical characteristics, histologic patterns, occurrence rates, relationship with clinical outcomes, immunohistochemical and molecular findings. The DTFs exhibit a range of 1 to 7 histologic patterns per tumor, including conventional, hypercellular, myxoid, hyalinized/hypocellular, staghorn/hemangiopericytomatous blood vessels pattern, nodular fasciitis-like, and keloid-like morphology. No substantial association was found between the existence of different histologic patterns and the clinical outcome. All thirty-three (100%) samples of DTF had a variable percentage of cells that were nuclear positive for β-catenin. An NGS analysis detected novel non-CTNNB1 mutations in two DTFs, including BCL10, MPL, and RBM10 gene mutations. This study reveals a diverse morphology of DTFs that could result in misdiagnosis. Therefore, surgical pathologists must comprehend this thoroughly. Also, the importance of the newly identified non-CTNNB1 gene mutations is still unclear. More research and analyses are needed to completely grasp the clinical implications of these mutations.

Real-life experience with sorafenib for advanced and refractory desmoid-type fibromatosis.

In recent years, there has been a change in the therapeutic landscape of desmoid-type fibromatosis (DF). Watchful waiting is now preferred over initial local treatments such as surgery and radiotherapy. Systemic treatment is considered for progressive or symptomatic disease. The aim of this study is to review real-life data on the use of sorafenib in DF. We established a retrospective dataset of patients treated with sorafenib in our centre, Ghent University Hospital, for progressive DF. Patient demographics, disease characteristics, response to therapy using Response Evaluation Criteria in Solid Tumours 1.1 criteria and toxicity according to CTCAE v5.0 were assessed. Eleven patients with DF were treated with sorafenib between 2020 and 2024. Median treatment duration was 20.4 months (95% confidence interval [CI], 10.0-NR). 36.4% achieved partial response, 54.5% stable disease and 9.1% progressive disease. For three patients, the treatment is ongoing. The median time to objective response rate is 15.0 months (95% CI, 8.8-NR). The majority (81.8%) experienced grade 2 toxicity, and one third of patients grade 3 toxicity (36.4%). The most common all-grade adverse event was skin toxicity (hand-foot syndrome, pruritus and rash) (90.9%). Nine patients (81.8%) needed dose reduction with a median time to first reduction of 1.1 months (95% CI, 0.5-NR). One patient stopped treatment due to toxicity. Real-life data on the use of sorafenib in the treatment of DF is consistent with published data in clinical trial setting. Sorafenib is an effective treatment option for progressive DF although associated with significant toxicity and the need for rapid dose reduction.

Desmoid Type of Fibromatosis of Ureter: A Rare Case

Abstract This study presents a rare case of desmoid-type fibromatosis (DTF) in the ureter of a young adult, highlighting its unusual occurrence within the urinary tract. The patient experienced right flank pain, leading to the discovery of gross hydroureteronephrosis with a suspicious distal ureteric mass. Surgical intervention revealed a well-defined tumor displaying characteristic histological features of DTF. Immunohistochemistry confirmed the diagnosis. Despite the absence of nuclear β-catenin expression, the patient underwent wide local excision. This case highlights the need for individualized treatment plans for DTF and emphasizes its consideration in cases of obstructive uropathy with atypical mass presentations.

Desmoid fibromatosis tumor of the buttock, mimicking a man face on MRI

Desmoid-type Fibromatosis (DF) is a rare and locally aggressive tumor that occurs predominantly between puberty and 40 years, with female predominance. The aim is to clarify the DF management.

Incidental discovery of unilateral hydronephrosis unveiling psoas major desmoid-type fibromatosis in a 24-year-old male: A case report with a 5-year follow-up.

Desmoid-type fibromatosis (DTF), also known as aggressive fibromatosis, is a rare neoplasm originating from the fascial or musculoaponeurotic tissues. While benign and characterized by slow growth, it exhibits local aggressiveness and lacks specific clinical characteristics. However, in a considerable percentage of patients, it could be asymptomatic and discovered by accident during routine clinical examinations. Only a few cases of DTF arising from the psoas major muscle have been reported in the medical literature. A 24-year-old male, asymptomatic and without significant personal or family medical history, was diagnosed with grade 2 hydronephrosis by abdominal ultrasonography during a routine physical examination. This diagnosis was made 15 days after undergoing uncomplicated open-heart surgery to repair an atrial septal defect. Intravenous pyelogram revealed hydronephrosis with dilation of the pelvicalyceal system. Ureteroscopy ruled out any intrinsic lesions of the ureter. Contrast-enhanced computed tomography identified a 3.5 × 2 × 5.2 cm mass in the retroperitoneum, closely associated with the psoas muscle and enveloping the ureter adjacent to the iliac artery. Postoperative pathological analysis confirmed a definitive diagnosis of sporadic DTF. The patient underwent exploratory abdominal surgery, during which the tumor was resected without any intraoperative complications. After close monitoring over a 5-year follow-up period, which included periodic physical examinations, magnetic resonance imaging, and ultrasonography, no local recurrence was detected. Achieving an accurate preoperative diagnosis presents a challenge in cases involving retroperitoneal tumors originating from the psoas major muscle and encasing the ureter. However, the insertion of a double J stent is deemed a crucial step in the surgical process, facilitating the dissection and isolation of the ureter from the tumor while preserving kidney function.

Clinicopathological and molecular genetic features of neuromuscular choristoma-associated desmoid type fibromatosis

Objective: To investigate the clinicopathological and genetic characteristics of neuromuscular choristoma-associated desmoid type fibromatosis (NMC-DF). Methods: The clinical morphological and immunohistochemical features of 7 NMC-DF cases diagnosed from January 2013 to January 2023 in Beijing Jishuitan Hospital were retrospectively analyzed. A series of neuromuscular choristoma and neuromuscular choristoma-associated desmoid type fibromatosis were evaluated for CTNNB1 mutations, and hotspot mutations for CTNNB1 were tested in 4 NMC-DF cases using Sanger sequencing. Results: The tumors were collected from 3 females and 4 males, aged 1 to 22 years (mean 7.1 years), involving the sciatic nerve (n=4), brachial plexus (n=2) or multiple nerves (n=1). The course of the disease spanned from 3 months to 10 years. Two cases were recurrent tumors. All the 7 NMC cases showed endoneurial intercalation of mature skeletal muscle fibers among the peripheral nerve fascicles, and the histologic features of the NMC-DF were strikingly similar to the conventional desmoid-type fibromatosis. By immunohistochemistry, all NMC and NMC-DF cases showed aberrant nuclear staining of β-catenin (7/7), the muscle cells in NMC were intensely immunoreactive for desmin, and the admixed nerve fibers were highlighted by NF and S-100 (7/7). Four NMC and NMC-DF had CTNNB1 mutations, 3 c.121A>G (p.T41A) and 1 c.134C>T (p.S45F). Follow-up of the 7 cases, ranging from 22 to 78 months, showed tumor recurrence in 2 patients at 3 and 8 months respectively after the first surgical resection, of which 1 patient underwent above-knee amputation. No recurrence occurred in other cases with tumor excision and neurological reconstruction surgery. There was no metastasis occurred in the 7 cases. Conclusions: NMC is a rare congenital lesion with differentiated mature skeletal muscle tissue found in peripheral nerve fascicles, and approximately 80% of patients with NMC develop a soft tissue fibromatosis. CTNNB1 mutation in the Wnt signaling pathway may be involved in the pathogenesis of NMC and NMC-DF, and S45F mutations seems to have a higher risk of disease progression.

Identifying intra-abdominal desmoid type fibromatosis mimicking recurrence/metastasis of GISTs using FAPI PET/CT.

e23516 Background: Intra-abdominal desmoid tumor (IADT) can mimic the recurrence/metastases of gastrointestinal stromal tumors (GISTs). However, it is difficult to radiologically differentiate IADT and recurrence/metastases of GISTs. This study aims to investigate the value of 18F fibroblast activation protein inhibitor ( [18F]FAPI-42) PET/CT in identifying intra-abdominal desmoid type fibromatosis mimicking recurrence/metastases of GISTs by comparing it to [18F]FDG PET/CT. Methods: This study retrospectively included a total of 24 patients (12 patients with IADT and 12 patients with recurrent/metastatic GISTs). The differences in [18F]FAPI-42 PET/CT parameters (SUVmax-FAPI and SUVTLR-FAPI ), [18F]FDG PET/CT parameters (SUVmax-FDG and SUVTLR-FDG), SUVfapi/SUVfdg ratio of IADT and GISTs were compared. The difference in PET/CT parameters (SUVmax, SUVTLR) of IADT between FDG PET/CT and FAPI PET/CT were compared. Immunohistochemical verification was performed on IADT lesions of all 12 patients and expression profiles of GEO datasets were analyzed to validate the FAP expression of IADT. Results: Both [18F]FAPI-42 PET/CT parameters, SUVmax-FAPI [8.8 (2.0, 16.0) vs 1.9 (1.0, 6.0), P< 0.001]and SUVTLR-FAPI [7.3 (2.0, 15.8) vs 1.7 (0.5, 6.9), P< 0.001], of IADT was significantly higher than that of GISTs, while there was no statistically significant difference in [18F]FDG PET/CT parameters, SUVmax-FDG and SUVTLR-FDG, between this two group. The ratio (SUVfapi/SUVfdg) of IADT was significantly higher than that of GISTs [3.3 (1.5, 8.0) vs 0.5 (0.1, 3.9), P= 0.001]. The SUVmax and SUVTLR of FAPI PET/CT of IADT were significantly higher than that of FDG PET/CT [8.8 (2.0, 16.0) vs 2.5 (1.1, 6.2), P< 0.001; 7.3 (2.0, 15.8) vs 0.9 (0.4, 2.7), P< 0.001; respectively]. FAP expression was found to be expressed in all the examined tissues and highly expressed in most of them. GEO database analysis shows that the FAP gene expression in DT is significantly higher than that in GISTs. Conclusions: FAPI PET/CT is a promising method in differentiating IADT from recurrence/metastases of GISTs compared with FDG PET/CT since FAP expression in DT is significantly higher than that in GISTs.

Desmoid-type Fibromatosis of the Breast. A Literature Review Based on 2 Case Reports

Desmoid-type Fibromatosis of the Breast. A Literature Review Based on 2 Case Reports

Rare desmoid-type fibromatosis of the breast in young female patients: a description of three cases and literature analysis.

Rare desmoid-type fibromatosis of the breast in young female patients: a description of three cases and literature analysis.

Anterior abdominal wall desmoid tumors: Reconstructive considerations and challenges in an oncoplastic unit in a low- and middle-income country: A case report

Desmoid tumors (DTs) are rare, locally aggressive tumors. When left untreated, DT can rapidly proliferate and occupy a significant portion of the anterior abdomen, making postresection reconstruction challenging. We present a 32-year-old female with a previous history of cesarean section and a 10-month history of two rapidly growing anterior abdominal wall (AAW) masses. There was no clinical or radiologic evidence of distant metastases. Abdominopelvic computed tomography scan showed no intra-abdominal extension. She had a wide local excision of the masses using an “abdominoplasty” technique and reconstruction of the extensive musculofascial defect with fascia lata grafts and polypropylene mesh. A histologic diagnosis of desmoid-type fibromatosis was made. The patient is scheduled for adjuvant radiotherapy and desires future pregnancies. This case report highlights the reconstructive considerations and challenges associated with surgical resection of huge AAW DT in an oncoplastic unit in a low- and middle-income country.

Utility of LEF1 to differentiate desmoid fibromatosis from its histologic mimics.

Diagnosis of desmoid-type fibromatosis (DF) may be challenging on biopsy due to morphologic overlap with reactive fibrosis (scar) and other uniform spindle cell neoplasms. Evaluation of nuclear β-catenin, a surrogate of Wnt pathway activation, is often difficult in DF due to weak nuclear expression and high background membranous/cytoplasmic staining. Lymphoid enhancer-factor 1 (LEF1) is a recently characterized effector partner of β-catenin which activates the transcription of target genes. We investigated the performance of LEF1 and β-catenin immunohistochemistry in a retrospective series of 156 soft tissue tumors, including 35 DF, 3 superficial fibromatosis, and 121 histologic mimics (19 soft tissue perineurioma, 8 colorectal perineurioma, 4 intraneural perineurioma, 26 scars, 23 nodular fasciitis, 6 low-grade fibromyxoid sarcomas, 6 angioleiomyomas, 5 neurofibromas, 5 dermatofibrosarcoma protuberans, 3 low-grade myofibroblastic sarcomas, 3 synovial sarcomas, 3 inflammatory myofibroblastic tumors, 2 schwannomas, and 1 each of Gardner-associated fibroma, radiation-associated spindle cell sarcoma, sclerotic fibroma, dermatofibroma, and glomus tumor). LEF1 expression was not only seen in 33/35 (94%) of DF but also observed in 19/23 (82%) nodular fasciitis, 7/19 (37%) soft tissue perineurioma, 2/3 (66%) synovial sarcoma, and 6/26 (23%) scar, as well as in 1 radiation-associated spindle cell sarcoma. The sensitivity and specificity of LEF1 IHC for diagnosis of DF were 94% and 70%, respectively. By comparison, β-catenin offered similar sensitivity, 94%, but 88% specificity. Positivity for LEF1 and β-catenin in combination showed sensitivity of 89%, lower than the sensitivity of β-catenin alone (94%); however, the combination of both LEF1 and β-catenin improved specificity (96%) compared to the specificity of β-catenin alone (88%). Although LEF1 has imperfect specificity in isolation, this stain has diagnostic utility when used in combination with β-catenin.

Intra-abdominal fibromatosis following laparoscopic surgery for sigmoid colon cancer: A case report

Introduction: Desmoid tumors, also known as aggressive fibromatosis, are rare, benign, non-inflammatory, and fibroblastic tumors. Characterized by their locally aggressive behavior and the potential for recurrence, these tumors do not metastasize. Intra-abdominal desmoid tumors comprise 8% of all desmoid tumors. Case Report: This paper presents a case of a 50-year-old male, highlighting the diagnostic challenge posed by the incidental discovery of an intra-abdominal mesenteric mass in a patient previously treated for stage I sigmoid colon cancer by laparoscopic proctocolectomy. Multidisciplinary consensus favored surgical intervention, successfully revealing and removing a benign desmoid-type fibromatosis. The occurrence of intra-abdominal desmoid tumors after laparoscopic surgery for colorectal cancer is exceptionally rare, underscoring the unique nature of this case. Conclusion: During post-operative follow-up for colon cancer, the discovery of an intra-abdominal mass is often initially regarded as a sign of cancer recurrence and metastasis. Radiologists and oncologists may not immediately consider alternative causes. The incidentally discovered desmoid-type fibromatosis emphasizes the necessity for vigilant monitoring and consideration of diverse pathologies during follow-up, especially in low-risk scenarios.

Exuberant circumferential fibroproliferative neuromas in lipomatosis of nerve: a unifying theory. Illustrative case.

Lipomatosis of nerve (LN) is a rare disorder characterized by the massive enlargement of peripheral nerves, frequently accompanied by generalized fibroadipose proliferation and skeletal overgrowth. The authors have been routinely following a 20-year-old male for lipomatosis of median nerve at the wrist noted shortly after birth. He had undergone resection of the lesion accompanied by sural nerve grafting at another institution. Clinically, although his neurological loss of function has been stable, he has had continued soft tissue growth. Serial magnetic resonance imaging has revealed persistent LN proximal to the repair sites with evidence of fatty proliferation in the sural grafts and continued LN and fatty proliferation distally. There has been a progressive circumferential pattern of fibrosis around the proximal and distal suture lines, which has a similar radiological pattern to desmoid type fibromatosis (a pattern recently described in neuromuscular choristoma [NMC] desmoid-type fibromatosis). Considering the similar reaction of nerve in both LN and NMC despite differing genetic cascades, the authors believe a unifying process occurs in both lesions. The pattern of circumferential fibroproliferation would be most consistent with neuron-mediated growth from unspecified trophic factors, supporting a previously reported a nerve-derived "inside-out mechanism." The clinical consequences of this unifying process are presented.

Current Treatment Concepts for Extra-Abdominal Desmoid-Type Fibromatosis: A Narrative Review.

Extra-abdominal desmoid-type fibromatosis (EADTF) is a rare neoplastic condition of monoclonal fibroblastic proliferation characterized by local aggressiveness with a distinct tendency to recur. Although EADTF is a benign disease entity, these tumors have a tendency to infiltrate surrounding normal tissues, making it difficult to completely eliminate them without adjacent healthy tissue injury. Surgical excision of these locally aggressive tumors without clear resection margins often leads to local recurrence. The aim of this thorough review was to assess the current treatment concepts for these rare tumors. A comprehensive search of articles published in the Cochrane Library, MEDLINE (PubMed), and EMBASE databases between January 2008 and February 2023 was conducted. Surgical intervention is no longer the first-line approach for most cases; instead, strategies like active surveillance or systemic therapies are used as initial treatment options. With the exception of EADTFs situated near vital structures, a minimum of 6-12 months of active surveillance is currently advocated for, during which some disease progression may be considered acceptable. Non-surgical interventions such as radiation or cryoablation may be employed in certain patients to achieve local control. The currently preferred systemic treatment options include tyrosine kinase inhibitors, low-dose chemotherapy, and gamma-secretase inhibitors, while hormone therapy is not advised. Nonsteroidal anti-inflammatory drugs are utilized primarily for pain management.

Neuromuscular choristoma and circumferential nerve territory desmoid-type fibromatosis: imaging findings supporting a nerve-driven mechanism.

Neuromuscular choristoma (NMC) is a rare developmental malformation of peripheral nerve that is frequently associated with the development of a desmoid-type fibromatosis (DTF). Both NMC and NMC-DTF typically contain pathogenic CTNNB1 mutations and NMC-DTF develop only within the NMC-affected nerve territory. The authors aimed to determine if there is a nerve-driven mechanism involved in the formation of NMC-DTF from the underlying NMC-affected nerve. Retrospective review was performed for patients evaluated in the authors' institution with a diagnosis of NMC-DTF in the sciatic nerve (or lumbosacral plexus). MRI and FDG PET/CT studies were reviewed to determine the specific relationship and configuration of NMC and DTF lesions along the sciatic nerve. Ten patients were identified with sciatic nerve NMC and NMC-DTF involving the lumbosacral plexus, sciatic nerve, or sciatic nerve branches. All primary NMC-DTF lesions were located in the sciatic nerve territory. Eight cases of NMC-DTF demonstrated circumferential encasement of the sciatic nerve, and one abutted the sciatic nerve. One patient had a primary DTF remote from the sciatic nerve, but subsequently developed multifocal DTF within the NMC nerve territory, including 2 satellite DTFs that circumferentially encased the parent nerve. Five patients had a total of 8 satellite DTFs, 4 of which abutted the parent nerve and 3 that circumferentially involved the parent nerve. Based on clinical and radiological data, a novel mechanism of NMC-DTF development from soft tissues innervated by NMC-affected nerve segments is proposed, reflecting their shared molecular genetic alteration. The authors believe the DTF develops outward from the NMC in a radial fashion or it arises in the NMC and wraps around it as it grows. In either scenario, NMC-DTF develops directly from the nerve, likely arising from (myo)fibroblasts within the stromal microenvironment of the NMC and grows outward into the surrounding soft tissues. Clinical implications for patient diagnosis and treatment are presented based on the proposed pathogenetic mechanism.

Full-thickness chest wall reconstruction after resection of recurrent desmoid-type fibromatosis

Introduction. Desmoid-type fibromatosis (DF) is a benign but locally infiltrative soft tissue tumor that develops from fascia and musculoaponeurotic tissue with high local recurrence rate. The aim of this article was to present a case of recurrent DF of the chest wall and chest wall reconstruction after tumor resection. Case outline. A 62-year-old man came for an examination due to a tumor localized on the right anterior chest wall. The previous year, the patient had undergone surgical excision of DF of the abdominal wall. Physical examination found a firm and painless 6?7 cm mass on the right side of the chest wall with no swelling of superficial lymph nodes. A computed tomography scan revealed a homogenous mass of soft tissue density, measuring 7.12 ? 4.23 cm, arising from right anterolateral wall of thoracic cage with adjoining ribs destruction. The patient was taken to surgery, and right thoracotomy was done with excision of tumor along with resection of the eighth, nineth and tenth rib. The results of pathological examination were consistent with the frozen section, and the patient was diagnosed with DF. Despite the absence of postoperative radiotherapy, there was no evidence of local recurrence two years later. Conclusion. Surgical treatment of recurrent DF of the chest wall requires a wide resection with negative margins. Multidisciplinary approach in case of full-thickness defect of the chest wall and combination of pedicled muscle flap and polypropylene mesh are important to provide chest wall stability.

Capturing Patient Voice to Improve Outcomes That Matter to Patients with Desmoid Tumor.

Desmoid tumors (DT) are rare, intermediate-grade sarcomas characterized by locally aggressive growths that commonly occur intra-abdominally, in the abdominal wall, or in the extremities. Desmoid tumors are 2-3-fold more common in females than males, with most patients aged <40 years at diagnosis. Clinical course of DT is highly variable but rarely fatal, with median overall survival >80% at 20 years. However, patient morbidity and DT symptom burden can be high. DT significantly reduce patient quality of life, imposing substantial physical, emotional, and social burdens. Pain, fatigue, and insomnia are common symptoms; disfigurement, mobility restrictions, and, rarely, the need for amputation may also result. Despite its limited impact on survival, patients with DT may have anxiety and depression levels commensurate with those associated with malignant sarcomas. Thus, DT impose an array of significant, long-term morbidities on a young patient population. In order to evaluate the impact of these morbidities, patient-reported outcome (PRO) tools are used, which assess outcomes of importance to patients that extend beyond traditional oncology endpoints. General or oncology-related PROs can be used; although currently, the only DT-specific, validated PRO measure is the GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS©), consisting of an 11-item DT Symptom Scale (DTSS) and a 17-item DT Impact Scale (DTIS). DTSS and DTIS were secondary endpoints in DeFi, a randomized phase 3 trial of nirogacestat; blinded, pooled data from DeFi were used to validate GODDESS reliability and responsiveness as a PRO measure in DT. Another DT-specific PRO measure, the Desmoid-Type Fibromatosis Quality of Life (DTF-QoL) questionnaire, has been developed but not validated. As novel DT therapies continue to be developed, incorporating DT-specific PRO measures into clinical trials will be key to capturing patient voice, improving outcomes of importance to this unique patient population, and assisting patients and providers in selecting optimal treatment.

MRI T2 mapping assessment of T2 relaxation time in desmoid tumors as a quantitative imaging biomarker of tumor response: preliminary results.

Because size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity. This IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters. Median patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12). Analysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability.