Exploring Current U.S. Physician Preferences for the Treatment of Patients with Desmoid Tumors

Desmoid tumors are rare, locally invasive soft-tissue tumors characterized by a heterogeneous clinical course. Currently, there are no FDA approved therapies for the treatment of desmoid tumors, but a number of agents are used off-label along with locoregional interventions, such as surgery. The identification of physicians who treat these patients and the therapies used is rendered challenging by the lack of a current dedicated ICD-10 code for desmoid tumors. This prevents the utilization of resources, such as claims data, that are typically used to characterize treatment preferences.  Recent joint global consensus guidelines recommend an initial active surveillance period followed by a surgical intervention for abdominal wall tumors and systemic therapies for other locations upon progression. However, in practice, U.S. physician treatment preferences remain unclear.Â
SpringWorks Therapeutics, which is developing a gamma secretase inhibitor for the treatment of desmoid tumors, sought to better understand how U.S. physicians currently treat patients with desmoid tumors. We designed a physician survey to assess past and current therapies used along with a series of hypothetical case studies to evaluate future treatment preferences. The goals of the survey included understanding whether physicians preferred a watchful waiting approach to an active intervention as a front-line therapy, which active treatments (i.e., locoregional or systemic therapies) physicians preferred, and whether patient presentation and etiology altered treatment preferences. The results of the case study portion of the survey were presented at the 2020 American Association for Cancer Research Virtual Annual Meeting II and are described below.

In this paper, the aim was to report our experience with three-dimensional reconstruction (3DR) modeling to determine resection and plan the surgical reconstruction in a patient with a desmoid tumor of the chest wall. A 68-year-old, non-smoking man presented at our outpatient department with painless swelling of the right anterobasal chest wall. A thorax-abdomen-brain CT scan revealed homogenous solid tissue with a dense mass measuring 80 mm × 62 mm. The final 3D model was evaluated by the surgical team (three medical doctors), who found the model to be powerful. Based on the results and the accuracy of the model, the multidisciplinary team decided that the tumor was resectable. The patient underwent right anterolateral thoracotomy at the seventh intercostal space, which confirmed the CT scan findings and revealed infiltration of the serratus muscle and medial portion of the diaphragm. A radical tumor en bloc resection with chest wall and diaphragm resection was performed. The full-thickness chest wall and diaphragm defects were reconstructed using two separate biological patches of a porcine dermal collagen implant (Permacol™ Surgical Implant). Postoperative X-ray revealed unremarkable findings; the patient had an uneventful recovery and was discharged 6 days after surgery.

This study aimed to establish a specified magnetic resonance imaging (MRI) signal and size criterion for assessing the response of desmoid-type fibromatosis (DF). This retrospective study included 129 patients with DF who received non-surgical therapy. All patients underwent pretreatment and 6-month-interval follow-up MRI for >3 years (6 follow-up visits). Signal grade and size among three response groups (partial response [PR], stable disease [SD], progression disease [PD]) were compared. The specified signal and size criterion was established, used to assess tumour response at each follow-up, and compared with the reference. The Response Evaluation Criteria in Solid Tumours (RECIST)1.1 criterion at the end of the 3rd year was considered the reference. MRI signals were moderately correlated with size changes (r = -0.56 and -0.41 for T2 grade and contrast-enhanced T1 grade, respectively). Changes in T2 grade and size in the three response groups were significantly different (all p < 0.01). The signal and size criterion accurately predicted 95% of PR patients at 2nd follow-up and 81.2% of PD patients at the 3rd follow-up, while only 13.1% of PR and 56.3% of PD patients were predicted by RECIST1.1. However, the accuracy of the signal & size criterion for predicting SD was lower than that of RECIST1.1. MRI signal is useful in assessing the response of DF. Signal & size criterion can identify patients with PR and PD earlier than RECIST1.1.

To investigate differential imaging features of intra-abdominal desmoid tumors and peritoneal seeding in patients with history of cancer surgery. Thirty-two patients who had a single pathologically proven intra-peritoneal lesion that developed after cancer surgery were enrolled between January 2000 and June 2019. There were 16 desmoid tumors and 16 peritoneal seeding lesions. Portal phase CT and/or 18F-FDG PET findings were analyzed by two radiologists in consensus for the following items: location, size, shape, margin, contour, homogeneity, necrosis, adjacent organ invasion, calcification, intra-lesional fat, peritoneal infiltration, mass effect, and degree of enhancement. Hounsfield units (HU) and maximum standardized uptake values (SUVmax) of the lesions were measured. Desmoid tumors frequently showed well-defined margins (9/16) and smooth contours (12/16), whereas peritoneal seeding had ill-defined margins (13/16) and lobulated contours (11/16) (P = 0.028 and 0.013, respectively). Intra-lesional fat was found more frequently in desmoid tumors (7/16) than peritoneal seeding (1/16) (P = 0.014). Desmoid tumors showed iso-attenuation (13/16) compared to psoas muscle in portal phase, while peritoneal seeding depicted high attenuation (12/16) (P = 0.002). Mean HU was significantly lower in desmoid tumors (64.3) than peritoneal seeding lesions (95.1) (P = 0.001). However, the mean SUVmax of desmoid tumors (4.1) did not significantly differ from peritoneal seeding lesions (5.2) (P = 0.519). Several CT features including iso-attenuation in portal phase and presence of intra-lesional fat can be helpful in differentiating desmoid tumors from peritoneal seeding in patients with history of intra-abdominal cancer surgery.

The clinical data of 32 patients with desmoid-type fibromatosis (DTF) in the shoulder girdle admitted between June 2003 and December 2016 were retrospectively analyzed, including 14 males and 18 females, aged 14-56 years with an average age of 36.8 years. The maximum diameter of the tumor was 7-19 cm, with an average of 11.1 cm. According to the “West China Classification” of DTF in the shoulder girdle, there were 4 cases of region I, 3 cases of region II, 6 cases of region III, 3 cases of region IV, 5 cases of regions I+II, 5 cases of regions II+III, and 6 cases of regions I+II+III. In addition, the involvement of blood vessels and nerves was also taken into consideration for choosing a surgical approach. Finally, 12 cases were operated via anteroposterior approach (group A), 14 via posterior approach (group B), and 6 via combined anterior-posterior approach (group C). The 1993 Musculoskeletal Tumor Society (MSTS93) score (including pain, limb function, satisfaction, hand position, hand flexibility, and lifting ability), Japanese Orthopedic Association (JOA) score, range of motion (ROM) of shoulder joint (including flexion, extension, abduction, and adduction), and complications of patients in the 3 groups were recorded and compared. All the 32 patients were followed up 30-190 months, with an average of 94.6 months. At last follow-up, complications occurred in 5 cases (15.6%), including 2 cases (16.6%) in group A, 2 (14.3%) in group B, and 1 (16.6%) in group C. There was no significant difference in the incidence of complications among the 3 groups ( P=1.000). Tumor recurrence occurred in 5 (15.6%) cases, including 1 (8.3%) case in group A, 2 (14.3%) in group B, and 1 (16.6%) in group C. No significant difference was found in the recurrence rate among the 3 groups ( P=1.000). At last follow-up, MSTS93 score of pain, limb function, satisfaction, hand flexibility, and hand position in groups A and B were significantly better than those in group C ( P<0.05), even though no significant difference existed between group A and group B ( P>0.05). The lifting ability score in group C was significantly lower than in group A ( P<0.05), and no significant difference was found between other groups ( P>0.05). The JOA score and flexion, extension, abduction, and adduction activities of shoulder in groups A and B were significantly better than those in group C ( P<0.05). The extension activity in group A was significantly better than that in group B ( P<0.05), the flexion activity in group B was significantly better than that in group A ( P<0.05). There was no significant difference in other indexes between groups A and B ( P>0.05). Taking a rational approach to fully expose and completely remove the tumor is the key point of surgical treatment for patients with DTF in the shoulder girdle. At the same time, preservation of vital structures and reconstruction of soft tissues should also be taken into consideration. Overall, surgical treatment under the guidance of “West China Classification” of DTF in the shoulder girdle has achieved satisfactory long-term effectiveness.

A 73-year-old Japanese male complained of a painless, left anterior neck mass of 3-month duration. Computed tomography revealed the mass measured 9 × 7 × 6 cm and extended to the anterior mediastinum, with invasion of the left clavicle. En bloc resection of the tumor with the left sternoclavicular joint and the medial portion of the left clavicle was performed by cervico-thoracic approach with L-shaped partial sternotomy. Histopathologic examination showed fascicular growth of spindle-shaped cells separated by abundant collagen. Immunohistologic examination revealed nuclear staining of Beta-catenin and cytoplasmic staining of vimentin. Genetic analysis of 160 cancer-related genes by next-generation sequencing (NGS) demonstrated only a missense mutation in the CTNNB1 gene (c.133T>C, p.S45P). DF extending from the neck to the anterior mediastinum is rare. We report the complete resection of a large-sized DF with the clavicular invasion. A low-frequency CTNNB1 mutation of DF was identified. Genetic analysis with NGS was beneficial for the diagnosis.