The role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma

Abstract

Background: To investigate the role of combined ion-beam radiotherapy (CIBRT) with protons and carbon ions in a multimodal treatment strategy of inoperable osteosarcoma; final analysis of a one-armed, single center phase I/II trial. Methods: Between August 2011 until September 2018, 20 patients with primary (N = 18), metastatic (N = 3), or recurrent (N = 2) inoperable pelvic (70%) or craniofacial (30%) osteosarcoma were treated with protons up to 54 Gy (RBE) and a carbon ion boost of 18 Gy (RBE) and followed until May 2019. A Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before CIBRT in search for a prognostic factor. The primary endpoint was toxicity. Secondary endpoints included treatment response, global, local and distant progression free survival (PFS, LPFS and DPFS) and overall (OS), among others. Results: The median age was 20; all patients finished treatment per protocol. LPFS, DPFS, PFS and OS were 73%, 74%, 60% and 75% after one year and 55%, 65% 65.3%, 45% and 68% after two years, respectively. The median clinical target volume (CTV) was 1042 cc and 415 cc for the primary and boost plan, respectively. Craniofacial localization, lower uptake of FDG in PET/CT and boost plan CTV median were associated with improved overall survival (p = 0.039, p = 0.016 and p = 0.0043, respectively). No acute toxicities > grade III were observed. We observed one case of secondary acute myeloid leukemia (AML) seven months after CIBRT for recurrent disease and one case of hearing loss. Conclusion: CIBRT shows a favorable toxicity profile and promising results particularly for patients with inoperable craniofacial osteosarcoma.

Carbon-ion Radiotherapy for Inoperable Head and Neck Bone and Soft-tissue Sarcoma: Prospective Observational Study

“…Most adverse events were grade 2 or lower, and the reasonably high OS suggests particle beam therapy (carbon and proton) for BSS-HN might be a possibility in the future. However, despite the proton and C-ion boost intervention, the OS in the previous study (15) was slightly lower than that of our study. Lower OS might be related to lower LC and PFS.…”

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

“…Currently, the event-free survival of OS patients is about 60–70% after neoadjuvant CT comprising cisplatin, doxorubicin followed by high-dose methotrexate, and surgical removal of the tumor often followed by adjuvant CT. EBRT plays no or only a minor role due to the high radioresistance of OS and is only applied on rare occasions when surgical margins are limited by tumor localization with an additional positive impact on prognosis, but high doses up to 80 Gy may be required to achieve some additional benefit [ 390 ]. Here, recent studies using highly localized combined ion-beam EBRT for inoperable OS showed promising results and may represent a treatment option with a favorable toxicity profile [ 364 ].…”

Bone sarcoma: Success through interdisciplinary collaboration

“… 10 Modern radiotherapy techniques such as proton therapy may save the occasional patient when complete surgery is not an option. 11 , 12 However, complete surgery must remain the first choice in all cases.…”