Rhabdomyosarcoma of parameningeal sites

Rhabdomyosarcoma arising in the skull base has a feature of its natural history that is unique in oncology: by virtue of parameningeal location and invasive behavior, it can extend intracranially and produce neoplastic meningitis. The four anatomic sites with this potential are the nasopharynx/nasal cavity, the middle ear, the paranasal sinuses, and the infratemporal fossa/pterygopalatine space. Patients with these primary sites comprise 41% of patients with head and neck sites and 15% of all patients with rhabdomyosarcoma. Most are under 10 years old at diagnosis (72%) and are Intergroup Rhabdomyosarcoma Study (IRS) Clinical Group III (76%). IRS protocols over the last 20 years have lead to a gradual improvement in outcome while refining radiation treatment parameters to allow for restricted indications for (and then the elimination of) whole cranial radiotherapy ports. The current guidelines (Group III) are for a dosage of 1.8 Gy/d up to a total of 50.4 Gy using 2-cm margins around the gross tumor volume at diagnosis. The timing of radiotherapy in relation to combination chemotherapy is based on assessment of three risk factors that predict tumor access to the cranial subarachnoid space: skull base erosion, cranial nerve palsy, and intracranial extension. Patients with one or more factors begin radiotherapy concurrently with chemotherapy. The remaining one third of patients begin radio-therapy after induction chemotherapy (week 9). The 5-year failure-free survival rate for patients with Group III parameningeal rhabdomyosarcoma on IRS-III was 71%. In the absence of the three risk factors, 5-year survival was 97%. The local failure rate was 15%. Among patients who achieved a complete or partial response (IRS-III), 5% had contiguous (nonhematogenous) central nervous system failure. Late effects of radiotherapy in these young patients are protean and include growth inhibition, cataracts, impaired dentition and hearing, and facial bone asymmetry. The promise of improvement of the therapeutic ratio may be realized from treatment refinements, which include chemotherapy response-based portal reduction, hyperfractionation, and conformal radiation therapy.