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Pulmonary Hemorrhage in Patients Treated With Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents. International journal of radiation oncology, biology, physics Lau, B., No, H. J., Wu, Y. F., Ko, R. B., Devine, M., Das, M., Neal, J. W., Ramchandran, K. J., Wakelee, H. A., Shaheen, S., Diehn, M., Chin, A. L., Loo, B. W., Vitzthum, L. 2021; 111 (3S): e423

Abstract

PURPOSE/OBJECTIVE(S): Hemoptysis is a rare but potentially fatal toxicity associated with thoracic stereotactic ablative radiotherapy (SABR). Prior studies have suggested that vascular endothelial growth factor inhibitors (VEGFI) may potentiate the risk for pulmonary hemorrhage in patients treated with SABR for centrally located lung tumors. To what degree the risk of toxicity varies by timing of therapies or tumor location is uncertain. The purpose of this study is to evaluate the combined toxicity of VEGFIs and SABR for peripheral, central, or ultra-central tumors.MATERIALS/METHODS: We evaluated patients with primary or metastatic lung tumors treated with SABR between 2008 and 2018 at a single institution. Baseline patient, tumor and treatment characteristics were evaluated. Pulmonary bleeding events were graded using CTCAE version 5.0. Rates of a grade three or higher (G3+) or any ipsilateral pulmonary hemorrhage at three years were estimated using the Kaplan-Meier method. We compared rates of bleeding by tumor location, treatment with a VEGFI, sequence of therapy and VEGFI within 90 days of SABR using the log-rank test.RESULTS: This retrospective cohort study included a total of 925 pulmonary tumors treated with SABR in 691 patients. There were 44 patients treated with a VEGFI (bevacizumab, sorafenib, pazopanib, sunitinib or ramucirumab), with the majority receiving bevacizumab (n?=?38, 86.3%). Among those treated with a VEGFI, the median interval between VEGFI therapy and SABR was 16 weeks, ranging from zero days to 3.7 years, with 15 (34.0%) patients treated within 90 days of SABR. Patients were treated with SABR to peripheral (738, 79.8%), central (137, 14.8%) and ultra-central (50, 5.4%) locations with a median BED10 of 87.5 Gy. Median follow-up was 32.2 months for the overall cohort and 46.4 months for VEGFI patients. The rate of G3+ hemorrhage was significantly higher in patients treated with a VEGFI (7.3 vs 0.8%, P < 0.01). The rate of any grade hemorrhage did not significantly vary between groups (9.4 vs 2.7%, P?=?0.1). When stratified by location, both central/ultra-central tumors (21.1 vs 3.2%, P?=?0.03) and peripheral tumors (3.4 vs 0.1%, P?=?0.03) had increased rates of G3+ hemorrhage when treated with a VEGFI. Among patients treated with SABR and VEGFI, there was no significant difference in rates of hemorrhage when the interval was > or = 90 days (12.0 vs 0.0%, P?=?0.17). Similarly, there was no significant difference between rates of G3+ hemorrhage when VEGFI was given before (12.9%), after (8.3%), or before and after SABR (0.0%).CONCLUSION: VEGFI therapy was associated with an increased rate of high-grade hemorrhage in patients undergoing SABR to pulmonary tumors. Rates of high-grade hemorrhage were increased with VEGFI for both central/ultra-central and peripheral tumors although the absolute rate was low for peripheral tumors. While limited by low sample size and event rate, there was no correlation observed between interval or sequence of VEGFI and SABR and rate of high-grade hemorrhage.

View details for DOI 10.1016/j.ijrobp.2021.07.1208

View details for PubMedID 34701419