Whole Lung Irradiation in Patients with Osteosarcoma and Ewing Sarcoma

Whole lung irradiation (WLI) represents standard therapy for patients with pulmonary metastases from Ewing sarcoma although the impact on clinical outcomes and toxicity is still unclear. The aim of this study was to evaluate toxicity after WLI in patients with Ewing sarcoma and osteosarcoma as well as overall survival (OS) and event-free survival (EFS).

A systematic review of studies on bilateral pulmonary irradiation treatments for prophylactic or curative therapy was performed based on PRISMA methodology. Data base searches on PubMed and Cochrane Library from the earliest time possible through 31st March 2018 were carried out. Combination with other treatments, such as chemotherapy and surgery were allowed. Only articles published in English were considered.

Toxicity was evaluated in 13 of the 14 analyzed studies (640 patients). Reported lung acute toxicity grade ≥3 ranged between 0.0 and 12.2%. Three studies reported 12 cases (1.8%) of severe pneumonitis. Grade ≥2 late toxicity was mainly recorded in patients who received boost irradiation, previous thoracic surgery, chemotherapy or who were smokers. Lack of a significant impact of WLI on OS was reported in comparative studies although patients treated with WLI showed higher survival in most individual studies.

Although the rate of severe toxicity was very low, the real impact of WLI on patients' outcomes remains unproven, probably due to the narrow dose limits that can be delivered to the whole lung parenchyma. New strategies to prevent or treat lung metastases in these patients should be tested. Ultra-fractionated radiotherapy concurrent with modern chemotherapy protocols could be tested in this setting due to the chemo-sensitizing effect and negligible radio-induced toxicity of fraction doses <0.5 Gy.