Efficacy of Vinblastine and Methotrexate in a Childhood Patient with Progressive Desmoid Fibromatosis of the Lower Jaw: A Case Report

Desmoid fibromatosis (DF) is defined as a borderline tumor of the soft tissues with a low malignant potential. The most common tumor sites are the extremity, trunk, abdominal cavity, and head and neck. Surgical resection has been the standard treatment for DF. However, there are concerns regarding long-term cosmetic outcomes or functional morbidity associated with surgery particularly in the head and neck. Recently, the use of the front-line wait-and-see strategy and pharmacologic treatment such as chemotherapy for progression has been proposed as tumors can spontaneously stabilize and regress. Herein, we report the efficacy of vinblastine (VBL) and methotrexate (MTX) in a childhood patients with DF. A 21-month-old female patient with a 4-cm tumor at the left lower jaw was diagnosed with DF. She did not initially receive any therapies (wait-and-see) according to the recent treatment guidelines. However, the tumor gradually progressed, and the patient was managed with COX2 inhibitor. Since the tumor was not controlled with such a treatment and tracheal exclusion caused by the mass was a cause of concern, the patient was managed with chemotherapy with VBL and MTX. VBL and MTX were administered weekly for 26 weeks, every other week, and further for 26 weeks. The tumor size gradually decreased with VBL and MTX. Magnetic resonance imaging revealed no evidence of the disease at the end of chemotherapy. Good cosmetic outcomes were achieved, and recurrence was not observed after 24 months of follow-up.

Objectives: 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.

Methods: 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.

Results: 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). Conclusions: 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.

With increasing multidisciplinary management and emphasis on masterly inactivity for abdominal fibromatosis (AF), the indications for surgery are evolving. This retrospective analysis looked at outcomes following surgery. Two groups of patients who underwent surgery for AF between November 2011 and August 2021 were identified-intra-abdominal fibromatosis (IAF) and abdominal wall fibromatosis (AWF). All treatment-related details and follow-up data were gathered from a database and analyzed. Sixteen patients underwent surgery for IAF. R0 resection (wide margin) was achieved in 13 patients (81.2%). Over a median follow-up period of 51.7 (range 5-103) months, 5 patients developed recurrence (31.2%). The conditional probabilities of OS and DFS at 5 years were 80% (95% CI 58.7-100) and 42.2% (95% CI 20.3-87.8), respectively. Ten patients with AWF underwent surgery. R0 resection was achieved at 70% (7/10). Over a median follow-up period of 54.8 (range 12.9-96.7) months, 2 patients (20%) developed recurrence. The conditional probabilities of OS and DFS at 5 years were 88.9% (95% CI 70.6-100) and 77.8% (95% CI 54.9-87.8), respectively. Surgery has a vital role in the management of AF presenting with progressive/symptomatic lesions, especially when watchful waiting is not an option, and must be considered as one of the first-line active therapy. Timely curative surgery avoids disease progression and its morbidity with acceptable recurrence rates and provides durable remissions.

Diaphragmatic fibromatosis is an exceptionally rare condition, with only 2 previously reported cases in the literature. We present the case of a 23-year-old woman with a left hypochondrial swelling measuring 19×18×13 cm on computed tomography. An endoscopic ultrasound-guided biopsy indicated low-grade papillary proliferation. Surgical exploration revealed a large mass originating from the left hemidiaphragm. Complete excision of the mass and reconstruction of the diaphragm with double-layer mesh were performed. Microscopic examination of the mass revealed a bland-looking spindle cell proliferation. Immunohistochemical staining showed a positive nuclear reaction in tumor cells for β-catenin, a focal positive reaction for SMA, and negative reactions for S100, CD34, and desmin. Diaphragmatic fibromatosis is an extremely rare tumor for which complete excision and reconstruction of the diaphragm is the best suggested modality of treatment.

Introduction: Desmoid tumors (DT) are rare, locally invasive tumors originating from connective tissue. Surgical intervention is no longer the standard treatment for DT, as systemic therapy gradually replaces it due to its superior efficacy. Despite the availability of various treatment modalities, there is a need for a first-line systemic treatment regimen that offers both effective disease control and acceptable safety profiles.

Methods: To assess the efficacy and safety of different systemic treatment agents for DT, we conducted a systematic review and network meta-analysis. Eligible studies were identified through searches of PubMed, Embase, and the Cochrane Library databases, and data were extracted according to predefined inclusion criteria.

Results: Three articles and clinical data from 295 patients with progressive and refractory DT were included in this Bayesian network meta-analysis. When considered by objective response rate (ORR), the efficacy of γ-secretase inhibitor versus placebo (OR 0.12, 95%CI 0.01-1.68) is superior to that of TKI (OR 0.49, 95%CI 0.03-7.62) and chemotherapy (OR 0.90, 95%CI 0.02-40.00). Vascular endothelial growth factor (VEGF)-TKI (OR, 0.09; 95% CI, 0.01-1.79) seemed to have the highest improvement in terms of 1-yr PFS rate, while chemotherapy seemed to have the highest improvement across all therapies in terms of 2-yr PFS rate across all therapies (OR, 0.06; 95 percent CI, 0.01-2.98). In terms of safety, the incidence of AEs is highest for γ-secretase inhibitor versus placebo (OR 0.16, 95%CI 0.02-1.55), while TKI is associated with the least AEs (OR 0.62, 95%CI 0.06-6.97).

Conclusion: γ-secretase inhibitor provides superior local control of tumors, while chemotherapy and TKI may offer better long-term survival benefits. Among the three regimens, TKI demonstrated better treatment-related safety. These findings have important implications for guiding clinical practice in systemic treatment of DT.

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