Observation of acute toxicity events in lung cancer patients treated concurrently with a tyrosine kinase inhibitor

Abstract

Introduction

Tyrosine kinase inhibitors (TKIs) have led to improvements in the management of non-small-cell lung cancer (NSCLC), though toxicity profiles of combined TKI and radiation therapies remains unclear. We set out to determine if concurrent TKI therapy increases risk for acute esophageal or pulmonary toxicity following thoracic radiation.

Materials & methods

We performed a retrospective study of patients receiving thoracic radiation for NSCLC from March 2011–December 2021. Concurrent TKI use included drug use within three months of radiation. Patients receiving concurrent therapy were compared to those receiving radiation alone for CTCAE acute toxicity within 12 months of radiation. Probit models were generated to derive normal tissue complication probability (NTCP) curves for toxicity outcomes.

Results

95 patients received lung radiation with a median follow-up of 12 months (range=5–114 months) of which 15.8 % (n = 15/95) patients received concurrent TKI. The rate of grade 2–3 acute esophagitis was 21.3 % (17/80) and 53.3 % (8/15) for patients receiving radiotherapy without and with concurrent TKI, respectively (p = 0.010). Concurrent TKI use was associated with more grade 2–3 esophagitis (OR=4.24, 95 % CI=1.34–3.34, p = 0.014). NTCP analysis showed concurrent TKI was associated with lower TD50 values for all dosimetric constraints for ≥ grade 2 esophagitis. There were no differences in pulmonary toxicity.

Conclusions

Concurrent TKI therapy may contribute to radiosensitization of the esophagus during thoracic radiotherapy. However, there were no grade 4–5 toxicity outcomes, suggesting feasibility of this approach. Further investigation is warranted to determine potential complications and identify approaches to mitigate risk in multimodality therapy.