Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo-or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12 patients who were controlled for more than 6 months failed locally, yielding a 5-year local control rate of 59% for 15 patients. Overall, 4 patients (27%) developed distant metastasis (two in patients with uncontrolled primary); 4 patients succumbed to their disease, 3 patients died of intercurrent disease, resulting in overall survival of 44% at 5 years. Group 3 (giant cell tumors, osteo- and chondroblastoma): One of 8 patients with giant cell tumor failed locally, 1 patient distantly, and all patients are alive. Three of 4 patients with osteo- or chondroblastoma are alive and well. One patient suffered local recurrence and died of disease. Local control rate and overall survival for this group of 12 patients was 76% and 87% and local control for patients with giant cell tumors 83% at 5 years. In the majority of cases radiotherapy was well tolerated. However, one patient with a large base of skull tumor developed retinopathy, one patient required enucleation of a previously blind eye, and another patient with sacral tumor developed chronic diarrhea. Combined proton and photon radiation therapy optimized by 3D treatment planning, allows the delivery of higher radiation doses to tumors of the axial skeleton, while respecting normal tissue constraints. High radiation doses can result in improved long-term local control.