Rhabdomyosarcoma associated with germline TP53 alteration in children and adolescents: The French experience.

OBJECTIVE: To describe the clinical characteristics and outcome of patients with Li-Fraumeni-associated rhabdomyosarcoma (RMS). METHOD: Retrospective analysis of data from 31 French patients with RMS diagnosed before the age of 20 years associated with a TP53 pathogenic germline variant. Cases were identified through the French Li-Fraumeni database. Central histologic review was performed in 16 cases. RESULTS: The median age at diagnosis was 2.3 years, and the median follow-up was 9.1 years (0.3-34.8). The main tumor sites were head and neck (n = 13), extremities (n = 8), and trunk (n = 8). The local pathology report classified the 31 tumors in embryonal (n = 26), alveolar (n = 1), pleomorphic (n = 1), and spindle-cell (n = 1) RMS (missing = 2). After histological review, anaplasia (diffuse or focal) was reported in 12/16 patients. Twenty-five patients had localized disease, three had lymph node involvement, and three distant metastases. First-line therapy combined surgery (n = 27), chemotherapy (n = 30), and radiotherapy (n = 14) and led to RMS control in all, but one patient. Eleven patients relapsed, and 18 patients had second malignancies. The 10-year event-free, progression-free, and overall survival rates were 36% (95% CI: 20-56), 62% (95% CI: 43-77) and 76% (95% CI: 56-88), respectively. The 10-year cumulative risk of second malignancies was 40% (95% CI: 22-60). CONCLUSION: The high incidence of multiple primary tumors strongly influences the long-term prognosis of RMS associated with TP53 pathogenic germline variants. Anaplastic RMS in childhood, independently of the familial history, should lead to TP53 analysis at treatment initiation to reduce, whenever possible, the burden of genotoxic drugs and radiotherapy in carriers and to ensure the early detection of second malignancies.

Long-term results of the transmanubrial osteomuscular-sparing approach for pediatric tumors.

BACKGROUND: The complete and safe resection of pediatric cervicothoracic tumors, mostly represented by neurogenic tumors, remains a surgical challenge because of the complex anatomy of this region. The transmanubrial osteomuscular-sparing approach (TOSA) is an alternative to isolated or combined cervical and thoracic approaches enabling the control of supra-aortic vessels and nerves through the thoracic inlet. METHODS: We retrospectively reviewed the tumor characteristics, completeness of resection, morbidity, and long-term outcome of patients with cervicothoracic tumors removed by TOSA between 2000 and 2012 in our institution. RESULTS: Thirteen patients (7 males, 6 females) underwent surgery at a median age of 72 months (4-188) for neuroblastoma (n = 6), ganglioneuroblastoma (n = 3), rhabdoid tumor (n = 1), melanotic schwannoma (n = 1), chordoma (n = 1), and malignant peripheral nerve sheath tumor in one patient with type 1 neurofibromatosis. The median duration of the procedure was 215 minutes (110-315). Two children presented with postoperative chylothorax that resolved spontaneously. The median duration of hospitalization was 7 days (4-22). At a median follow-up of 39 months (2-159), four patients had died of metastatic relapse (n = 2), locoregional progression (n = 1), and chemotoxicity (n = 1). The patient with melanotic schwannoma was lost to follow-up after a local relapse at 5 months. Long-term morbidity revealed homolateral Claude-Bernard Horner sign and upper limb vasomotor dysfunction in disease-free patients due to mandatory resection of the stellate ganglia. CONCLUSIONS: TOSA is a valuable surgical approach for all cervicothoracic tumors with acceptable long-term morbidity when compared with its complexity. We can therefore recommend TOSA for tumors involving the thoracic inlet.