Pulmonary fibrosis and pulmonary function in patients with metastatic testicular cancer during and after combination chemotherapy : the BLEOTOX study

Abstract

Background and objective: Metastatic testicular germ cell tumors (mTGCTs) are treated with combination chemotherapy (Cx) containing bleomycin (BEP [bleomycin, etoposide, and cisplatin]). Bleomycin-induced pulmonary toxicity (BPT) is a serious Cx-associated complication. This study aimed to investigate the association between radiographic changes in computed tomography of the chest (CT-T) and pulmonary function tests (PFTs) during, shortly after, and long term after BEP. Methods: In this nonrandomized, monocentric cohort study, we included patients with mTGCT who were treated with a minimum of two cycles of BEP. Pulmonary changes associated with BPT were extracted from CT-T scans performed before the first (baseline CT-1), after the second cycle (CT-2), and after the last cycle (CT-3) of BEP. Corresponding PFTs were performed before each new cycle. A current PFT was used to evaluate long-term toxicity. Statistical analyses were carried out using the McNemar test, the Fisher exact test, the Wilcoxon signed-rank test, and multivariable regression analyses. Key findings and limitations: We identified 85 patients (38 had seminomas, and 47 had nonseminomas). Thirty-two patients received a current PFT. After two cycles of BEP, 21% of the patients showed radiographic BPT and 20% PFT deterioration. The association between CT and PFT changes was significant (odds ratio [OR] = 10.65 [95% confidence interval {CI} = 3.1–37.6]; p < 0.001). During BEP, the proportion of patients with deterioration in PFTs increased from 7.1% to 22% (Δ = 0.176 [95% CI = 0.076 – 0.277]; p = 0.0046). All patients with current PFT deterioration showed BPT after the second BEP cycle (CT-2); however, the association was not significant (OR = 6.25 [95% CI = 0.68–57.9]; p = 0.14). Conclusions and clinical implications: BPT is a common radiographic finding during and after BEP. Radiographic changes in CT-2 were significantly associated with reduced PFT. However, in most patients, PFT recovered over time with no radiographic correlation to any time point of CT-T during BEP. Therefore, routine CT-T during ongoing BEP should not be performed for BPT detection and should only be considered in patients who are clinically symptomatic.