Current Management of Desmoid Tumors: A Review.

Importance: Desmoid tumor (DT) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Previously, surgery was the standard primary treatment modality; however, within the past decade, a paradigm shift toward less-invasive management has been introduced and an effort to harmonize the strategy among clinicians has been made. To update the 2020 global evidence-based consensus guideline on the management of patients with DT, the Desmoid Tumor Working Group convened a 1-day consensus meeting in Milan, Italy, on June 30, 2023, under the auspices of the European Reference Network on Rare Adult Solid Cancers and Sarcoma Patient Advocacy Global Network, the Desmoid Foundation Italy, and the Desmoid Tumor Research Foundation. The meeting brought together over 90 adult and pediatric sarcoma experts from different disciplines as well as patients and patient advocates from around the world. Observations: The 2023 update of the global evidence-based consensus guideline focused on the positioning of local therapies alongside surgery and radiotherapy in the treatment algorithm as well as the positioning of the newest class of medical agents, such as γ-secretase inhibitors. Literature searches of MEDLINE and Embase databases were performed for English-language randomized clinical trials (RCTs) of systemic therapies to obtain data to support the consensus recommendations. Of the 18 full-text articles retrieved, only 4 articles met the inclusion criteria. The 2023 consensus guideline is informed by a number of new aspects, including data for local ablative therapies such as cryotherapy; other indications for surgery; and the γ-secretase inhibitor nirogacestat, the first representative of the newest class of medical agents and first approved drug for DT. Management of DT is complex and should be carried out exclusively in designated DT referral centers equipped with a multidisciplinary tumor board. Selection of the appropriate strategy should consider DT-related symptoms, associated risks, tumor location, disease morbidities, available treatment options, and preferences of individual patients. Conclusions and Relevance: The therapeutic armamentarium of DT therapy is continually expanding. It is imperative to carefully select the management strategy for each patient with DT to optimize tumor control and enhance quality of life.

Factors Impacting Clinically Relevant RNA Fusion Assays Using Next-Generation Sequencing.

CONTEXT.­: RNA-based next-generation sequencing (NGS) assays are being used with increasing frequency for comprehensive molecular profiling of solid tumors. OBJECTIVE.­: To evaluate factors that might impact clinical assay performance. DESIGN.­: A 4-month retrospective review of cases analyzed by a targeted RNA-based NGS assay to detect fusions was performed. RNA extraction was performed from formalin-fixed, paraffin-embedded tissue sections and/or cytology smears of 767 cases, including 493 in-house and 274 outside referral cases. The types of samples included 422 core needle biopsy specimens (55%), 268 resection specimens (35%), and 77 cytology samples (10%). RESULTS.­: Successful NGS fusion testing was achieved in 697 specimens (90.9%) and correlated positively with RNA yield (P < .001) and negatively with specimen necrosis (P = .002), decalcification (P < .001), and paraffin block age of more than 2 years (P = .001). Of the 697 cases that were successfully sequenced, 50 (7.2%) had clinically relevant fusions. The testing success rates and fusion detection rates were similar between core needle biopsy and cytology samples. In contrast, RNA fusion testing was often less successful using resection specimens (P = .007). Testing success was independent of the tumor percentage in the specimen, given that at least 20% tumor cellularity was present. CONCLUSIONS.­: The success of RNA-based NGS testing is multifactorial and is influenced by RNA quality and quantity. Identification of preanalytical factors affecting RNA quality and yield can improve NGS testing success rates.

Radiation-Associated Undifferentiated Pleomorphic Sarcoma is Associated with Worse Clinical Outcomes than Sporadic Lesions.

BACKGROUND: Radiation therapy is used increasingly as a component of multidisciplinary treatment for many solid tumors. One complication of such treatment is the development of radiation-associated sarcoma (RAS). Undifferentiated pleomorphic sarcoma (UPS), previously termed "malignant fibrous histiocytoma" (MFH) is the most common histologic subtype of RAS. This study investigated the clinical outcomes for patients with radiation-associated UPS (RA-UPS/MFH). METHODS: The study identified 1068 patients with UPS/MFH treated at the authors' institution. Patient and tumor factors were collected and compared. Regression analysis was performed to identify independent predictors of survival. A matched-cohort survival and recurrence analysis was performed for radiation-associated and sporadic UPS/MFH. RESULTS: The findings showed that RA-UPS/MFH comprised 5.1 % of the UPS population. The median latency to the development of RA-UPS/MFH was 9.3 years. The 5-year disease-specific survival (DSS) was 52.2 % for patients identified with RA-UPS/MFH (n = 55) compared with 76.4 % for patients with unmatched sporadic UPS/MFH (n = 1,013; p < 0.001). A matched-cohort analysis also demonstrated that the 5-year DSS was significantly worse for RA-UPS/MFH (52.2 vs 73.4 %; p = 0.002). Furthermore, higher local recurrence rates were observed for patients with RA-UPS/MFH than for patients with sporadic lesions (54.5 vs 23.5 %; p < 0.001). Radiation-associated status and incomplete resection were identified as independent predictors of local recurrence. CONCLUSION: This study demonstrated worse clinical outcomes for patients with RA-UPS/MFH than for patients with sporadic UPS/MFH. Local recurrence was significantly higher for patients with RA-UPS/MFH, suggesting a unique tumor biology for this challenging disease.

Familial multiple pilomatrixomas as a presentation of attenuated adenomatosis polyposis coli.

Pilomatrixomas are benign follicular tumors that occur most commonly in children. Rare multiple or familial pilomatrixomas have been associated with myotonic dystrophy and other disorders. Although sporadic pilomatrixomas and hybrid cutaneous cysts with pilomatrixoma-like features have been observed in some kindreds with Gardner syndrome, an autosomal dominant form of familial adenomatous polyposis, no definitive association has been made with multiple or familial pilomatrixomas. Here we describe two siblings with multiple pilomatrixomas who were also found to have a family history of colonic adenocarcinoma. Genetic testing revealed a mutation in the 5' portion of the adenomatous polyposis coli (APC) gene, in a region associated with an attenuated APC phenotype. These findings show that multiple pilomatrixomas may be the presenting symptom of patients with APC gene mutations.