RESULTS
We identified 7 patients with metastatic RMS and no known primary tumor, who accounted for 2.5% of the population enrolled in the MTS 2008 study. We identified 3 more patients whose data were available in the MTS2008 database, but they had been excluded from the analysis conducted for the MTS 2008 study because their diagnosis was established on cytology alone in 1 case, and by center decision in 2. We decided to also include these 3 patients in the present analysis, and the characteristics of all 10 patients are listed in Table 1.
No gender-related difference was noted. Patients were mainly adolescents (median age 15.8 years, range 4.6-20.4). Symptoms were nonspecific and a diagnosis of lymphoma had been suspected in 3 cases (patients 1, 4 and 8) because their symptoms at onset were asthenia, weight loss and lymphadenopathy. One patient presented with disseminated leptomeningeal disease and was diagnosed as RMS NOS based on cell morphology and immunohistochemistry. All other patients had fusion-positive alveolar RMS, positive for PAX3-FOX1 in 8, and for PAX7-FOX1 in 1. Multiple organ involvement was identified in 7 patients, while 2 only had bone marrow disease, and 1 only had leptomeningeal dissemination. The most often involved organs were: bone marrow in 6 cases; and distant nodes in 5. Applying the Oberlin score, which identifies age (<1or>0 years old), unfavorable primary sites (extremity, other site and unknown primary site) bone or bone marrow involvement, and >3 metastatic sites as correlating with a negative prognosis, our series included 1 patient with 1 of these risk factors, 3 patients with 2, 4 patients with 3, and 2 patients with 4 (2). The diagnosis was established from bone marrow aspirates in 4 patients, peritoneal nodules in 2, lymph nodes in 2, a bone biopsy in 1, and cerebrospinal fluid in 1. All patients underwent staging investigations according to the protocol, and 8 were also investigated with FDG-PET/CT (patients x-y and z-a). It emerged that the extremities were not fully investigated with FDG-PET/CT and/or MRI in 3 cases, (patients 3, 4 and 9 in Table 1).
All patients received chemotherapy according to the protocol. After the first three cycles, 4 patients were in CR, and 3 were in PR, while 1 patient had SD and 1 had PD. One patient with intracardiac tumor died of cardiac arrest before being assessed for tumor response. Radiotherapy was administered to 5 patients (in doses ranging from 41.4 to 50.4 Gy). In particular, the patient with leptomeningeal dissemination received craniospinal irradiation, one patient with peritoneal dissemination received whole abdominal irradiation, two children had radiotherapy to bone lesions and one patient received lymph node irradiation. No patients had surgery. Three patients received an allogeneic bone marrow transplant at the local center’s discretion (after bone marrow progression in one case).
At the time of this analysis, 2 patients are alive in CR, 94 and 101 months after their diagnosis. Of the 8 who died, 4 had tumor progression, 2 developed new metastases (1 during treatment), 1 had a cardiac arrest after the first cycle of chemotherapy, and 1 died of transplant-related toxicity (not further specified). One of the two patients still alive received radiotherapy.