Radiation Pneumonitis after Yttrium-90 Radioembolization: A Systematic Review and Meta-Analysis

The current radioembolization guidelines are based on external beam radiation data of 25 patients (1) and a case series of 5 patients with Yttrium-90 (Y90) radiation pneumonitis (RP) where lung doses were estimated from planar scintigraphy (2,3). Post-Y90 dosimetry was not performed, and the actual lung doses were unknown. Therefore, the guideline regarding the maximum tolerated lung dose for Y90 radioembolization is an expert opinion (level 5 evidence) based on a case series of 5 patients and recommends keeping the radiation dose to the lungs below 30 Gy per treatment and 50 Gy in a lifetime to prevent RP. The current understanding of the risks of RP is minimal despite its debilitating nature and high mortality rate. This systematic review and meta-analysis evaluates the available evidence of lung dosimetry and RP.

Materials and Methods:

A literature review was conducted in PubMed, Embase, Cochrane, and Google Scholar for reported cases of RP. 24 publications were identified including 13 articles, 7 case reports and 4 conference abstracts which reported cases of Y90-related RP. Two articles and one case report were excluded because these were duplicate reports of published cases. A database of 48 RP cases was compiled and analyzed.

Results:

Thirty patients were treated with resin and 16 patients with glass Y90-microspheres. The treatment device was not reported in 2 cases. RP developed a median of 3 months after radioembolization. The mortality rate was 40%. The hepatopulmonary shunt was not significantly different between the glass and the resin group (21.2±14% vs. 15.6±7.5%, p=0.24). The radiation dose to the lungs was significantly higher in patients treated with glass compared to resin Y90-microspheres (41.4±18.4 Gy vs. 21.5±9.9 Gy, p=0.003). In the glass Y90 group 20% and in the resin Y90 group 69% of patients received less than 30 Gy lung dose but developed RP.

Conclusion:

The lung dose toxicity threshold for resin is lower than that of glass microspheres. The established 30 Gy dose limit may not be uniformly applicable in all cases and for both devices. To improve the radioembolization guideline the maximum tolerable lung dose needs to be defined and the shortcomings of the current hepatopulmonary shunt calculation need to be corrected. Because RP rarely occurs, further investigation and dose escalation experiments in large animals are required to precisely define the radiation tolerance of lung parenchyma. In the meantime, the maximum tolerable lung dose for resin microspheres should be revised to a lower threshold.