Treatment Of Unresectable Osteosarcoma With Proton Therapy

En bloc resection is the primary approach for local control (LC) of osteosarcoma (OSA), unless the anatomical site precludes primary curative surgery. To achieve local control of macroscopic disease with radiotherapy (RT), high doses of radiation are necessary. Proton therapy (PT) delivers highly conformal treatment of doses exceeding 70 CGE while optimally sparing neighboring structures, such as the spinal cord, the brain, or the viscera. We reviewed 18 cases of unresectable or incompletely resected OSA who received either PT alone or in combination with photons and concomitant chemotherapy following induction chemotherapy from 1990 until 2009. All cases were treated after 3D planning and PT was delivered with 160 MeV protons via a fixed beam line from 1990–2001 and then with 230 MeV protons via a rotational gantry from 2002–2009. The median follow-up was 29 months (mean 43). Overall survival (OS), disease-free survival (DFS), LC and potential risk factors were assessed. Univariate analysis was used to assess factors associated with outcome. OSA occurred <= 18 years of age in 11 (61%), 19 to 45 in 2 (11%), and > 45 in 5 (28%). Five cases (27.5%) presented with disease in the head and neck or base of skull, 5 cases (27.5%) presented with disease localized to the cervical spine, and 10 cases (55%) with mid to lower spine or sacro-pelvic disease. The male-to-female ratio was 2:7. The mean total radiation dose was 70.2 Gy +/- 5.8 Gy (SD) (range, 63 to 88 Gy). 14 patients (78%) were started on photons (3D or IMRT), receiving a mean dose of 16.7 Gy +/- 11.1 Gy (SD) prior to PT. High dose volumes treated with >70 CGE (cobalt Gy equivalent) ranged from 16 to 637 mL. Because of short follow-up in 2 patients, outcome analysis is reported for 16 patients. At 2 years, the LC rate was 72 % (CI 4–88%), DFS was 49% (21–72%), and OS was 100%. At 4 years, the LC rate was 57% (22–81%), DFS was 39% (14–64%), and OS was 45% (15–71%). Univariate analysis identified shorter treatment duration (53 days versus 62 days) as the only prognostic factor for improved survival (p = 0.04). In unresectable osteosarcoma, induction chemotherapy followed by definitive radiotherapy, primarily protons, can be an effective and appropriate treatment strategy.