The optimal assessment of the risk-to-benefit ratio of a new treatment, particularly in oncology, has always been based on the results of prospective randomized trials, ideally carried out in a ...double-blind manner with a large sample size and overall survival as the primary endpoint. This is still the best level of evidence available and has been an indisputable metric for discussing approval and reimbursement with health authorities for decades. This remains true in clinical oncology. However, it is no longer an appropriate standard in personalized medicine, particularly when focusing on rare subtypes. Indeed, molecular screening can categorize common diseases into several ultra-rare pathologies, each grouping a limited number of patients. For example, patients with NTRK-rearranged tumors are textbook cases. They could be identified and receive personalized treatment; but, in some countries, access to treatment is suspended pending the results of randomized trials. However, the demand is insurmountable.
To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out.
Patients with inoperable progressive ...disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect.
Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients.
Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.
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