Desmoid tumor: A focus set on a challenging but understudied rare disease

Desmoid tumor (DT) is a rare disease characterized by a locally aggressive, monoclonal, fibroblastic proliferation leading to a variable and often unpredictable clinical course. The incidence is estimated to be 5 to 6 cases per 1 million per year, with a peak age of 30 to 40 years and a female predominance. Although DTs are not life-threatening in the vast majority of cases, patients often suffer from chronic pain, functional deficits, psychological problems, and a general decrease in quality of life. DT is a clearly understudied disease, and until recently no level 1 or 2 evidence existed in terms of clinical studies; there were only a few prospectively conducted studies or meta-analyses. Therefore, an effort has been made in the last 5 years to bring together adult and pediatric sarcoma experts from different disciplines with patients and patient advocates initially from Europe, more recently also from North America and Japan to harmonize the DT treatment strategy among clinicians. In 2018, an evidence-based, joint global consensus guideline approach to the management of this disease has been undertaken, focusing on molecular genetics, indications for active treatment, and available systemic therapeutic options. Consensus was reached by 1) an initial evidence-based systematic literature search that was performed by an independent institute involving methodological experts and an analysis of the identified literature according to GRADE (Grading of Recommendations Assessment, Development and Evaluation) followed by 2) the consensus meeting. This 1-day meeting was held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for Rare Solid Adult Cancers (EURACAN) and the European Organization for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with the support of the patient advocacy groups “sos desmoid” from Germany, Sarcoma Patients EuroNet (SPAEN), and The Desmoid Tumor Research Foundation (DTRF). The consensus paper will be published soon. In recent years, there has been a paradigm shift toward more conservative DT management. Immediate surgery is no longer the standard treatment, and available systemic therapies have moved more and more into the focus of interest. In this respect, tyrosine kinase inhibitors such as imatinib, pazopanib, and sorafenib have emerged as promising therapeutic options. Sorafenib has been evaluated in a randomized phase 3 trial (NCT02066181), the first of its kind for DT. This double-blind trial randomly assigned 87 patients with progressive, symptomatic, or recurrent DT to receive either sorafenib 400 mg/day or matching placebo with a possible crossover to the treatment arm in case of progression. The 2-year progression-free survival rate was 81% in the sorafenib group and 36% in the placebo group (hazard ratio, 0.13; 95% confidence interval, 0.05-0.31; P < .001). The objective response rate was 33% in the sorafenib group and 20% in the placebo group. The most frequently reported adverse events for sorafenib were grade 1/2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). Taken together, these results show that sorafenib significantly prolonged progression-free survival and induced durable responses in DT patients; DT did not grow for 1 year in twice as many patients who received therapy with sorafenib compared with those who received a placebo. The work of Mrinal Gounder has been featured as an advance of the year for rare cancers in Clinical Cancer Advances 2019: ASCO’s Annual Report on Progress against Cancer, showcasing major breakthroughs in clinical cancer research and care as well as emerging trends in oncology (https://www.conquer.org/advancing-clinical-research). Before this trial, many DT patients were often given off-label treatments. In this context, the article by Braggio et al in this issue of Cancer is current and of great interest. The authors have conducted a comprehensive analysis of sorafenib efficacy in a large panel of DT cell strains and could confirm in vitro the potent anti-DT activity of sorafenib by inhibiting proliferation, colony formation, migration, and invasion. The