Simple Clinical Factors Associated With Radiation-Induced Lung Toxicity After Stereotactic Body Radiation Therapy in Lung Cancer: A Pooled Analysis of 70 Studies: Treatment Toxicity

Abstract

As part of the AAPM Working Group Stereotactic body radiation therapy (SBRT) QUANTEC, we herein present a preliminary analysis from a pooled published data to 1) review radiation induced lung toxicity (RILT) after SBRT; and 2) analyze the relationship between RILT and clinical factors. Eligible studies for pooled analysis provided crude or actuarial risks of RILT. PubMed search criteria included the following keywords: SBRT or SABR, lung toxicity, pneumonitis, lung fibrosis. Data of grade 1 to 5 toxicities by CTCAE were extracted and ≥ grade 2 (G2+) and ≥ grade 3 (G3+) toxicities were summed. Clinical factors of interest included age, gender, tumor location, pathological type, smoking status, PTV, GTV and prescription dose. Linear regression was used to determine the relationship between toxicity rate and continuous clinical variables. All data were collected by one physician and double checked by another physician. Seventy studies (5708 patients) were eligible and analyzed. The median rates of G2+ and G3+ RILT for all studies were 14.4% (range 0-48.9%) and 3.6% (range 0-20.0%), respectively. The rates of G2+ and G3+ RILT for 5708 patients were 10.6% (9.4%-11.3%) and 2.3% (1.2%-3.1%), respectively. The clinical characteristics, reported as medians/percentages (95% CI) are as following: age 72 y (71-74), male/female ratio 2 (1-3), central tumors 30% (29%-32%), lower lobe tumors 38% (33%-43%), adenocarcinoma 41% (33%-48%), smokers 70% (38%-100%), PTV 53 cc (35-71cc), GTV 13cc (5-20cc), and radiation prescription dose 47 Gy (42-52 Gy). None of the above factors were correlated with the rate of G2+ RILT (all P values >.05). Age, gender, tumor location, smoking status, histology tumor type, and prescription dose were not significantly associated with risk of G3+ RILT. PTV was significantly correlated with high rate of G3+ RILT (P=.04): studies with larger PTV had increased rate of G3+ RILT. Interestingly, there was a significant negative linear correlation between G3+ RILT and GTV in the limited reported range (2-16 cc) of GTV (P=.01). The rates of grade ≥2 or ≥3 RILT are relatively limited and generally acceptable in these 70 studies, suggesting safe practice being utilized for SBRT. There were no clear/consistent clinical or treatment parameters associated with RILT. There is a modest trend for slightly higher rates of RILT in studies with smaller GTVs and larger PTVs, though a more detailed dosimetric analysis is needed to better understand this association. Better methods to standardize reporting are needed to facilitate such pooled analyses.