Immune Checkpoint Inhibitor and Radiotherapy-Related Pneumonitis: An Informatics Approach to Determine Real-World Incidence, Severity, Management, and Resource Implications.

Sumeet Hindocha,Anna Minchom,Fiona Mcdonald,Des Campbell,Merina Ahmed,Wanyuan Cui,Jaishree Bhosle,Michael Davidson,Mary O'Brien,Richard W Lee,Bhupinder Sharma,Sanjay Popat,Kyriaki Giorgakoudi,Benjamin Hunter,Imogen Locke,Nadia Yousaf,Hardeep Kalsi,Philip Molyneaux

doi:10.3389/fmed.2021.764563

Abstract

Pneumonitis is a well-described, potentially life-threatening adverse effect of immune checkpoint inhibitors (ICI) and thoracic radiotherapy. It can require additional investigations, treatment, and interruption of cancer therapy. It is important for clinicians to have an awareness of its incidence and severity, however real-world data are lacking and do not always correlate with findings from clinical trials. Similarly, there is a dearth of information on cost impact of symptomatic pneumonitis. Informatics approaches are increasingly being applied to healthcare data for their ability to identify specific patient cohorts efficiently, at scale. We developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT report text to identify cases of ICI and radiotherapy pneumonitis between 1/1/2015 and 31/12/2020. Further data on severity, investigations, medical management were also acquired from the electronic health record. We identified 248 cases of pneumonitis attributable to ICI and/or radiotherapy, of which 139 were symptomatic with CTCAE severity grade 2 or more. The grade ≥2 ICI pneumonitis incidence in our cohort is 5.43%, greater than the all-grade 1.3–2.7% incidence reported in the literature. Time to onset of ICI pneumonitis was also longer in our cohort (mean 4.5 months, range 4 days-21 months), compared to the median 2.7 months (range 9 days−19.2 months) described in the literature. The estimated average healthcare cost of symptomatic pneumonitis is £3932.33 per patient. In this study we use an informatics approach to present new real-world data on the incidence, severity, management, and resource burden of ICI and radiotherapy pneumonitis. To our knowledge, this is the first study to look at real-world incidence and healthcare resource utilisation at the per-patient level in a UK cancer hospital. Improved management of pneumonitis may facilitate prompt continuation of cancer therapy, and improved outcomes for this not insubstantial cohort of patients.

Highlights

Pneumonitis is a well-described, potentially life-threatening and disabling adverse effect of several cancer therapies including immune checkpoint inhibitor (ICI) drugs and thoracic radiotherapy
Using our integrated data warehouse and electronic health record (EHR) systems, we developed a Structured Query Language (SQL)-based informatics algorithm which we applied to CT Thorax report text to identify scans performed between 01/01/2015 and 31/12/2020 that contained key terms determined by radiology and respiratory expertise: “pneumonitis,” “pulmonary toxicity,” “lung toxicity,” “lung injury,” “interstitial lung disease” and “pneumonia”
We identified 450 CT reports indicating a pneumonitis in patients who had previously received ICI and/or radiotherapy, and which was possibly attributable to ICI/RT amongst other causes (Figure 1)

Summary

Introduction

Pneumonitis is a well-described, potentially life-threatening and disabling adverse effect of several cancer therapies including immune checkpoint inhibitor (ICI) drugs and thoracic radiotherapy. The advent of ICI drugs, such as those targeting the Programmed Cell Death 1 receptor or its ligand (PD1/PD-L1), have transformed cancer treatment over the last decade. The numbers of patients receiving such drugs either alone or in combination therapy for various cancers continues to increase and an abundance of clinical trials elaborate upon further applications [1, 2]. Radiotherapy continues to be a major treatment modality for lung cancer and with an ageing and increasingly comorbid population, the number of patients treated curatively with radiotherapy rather than surgery is likely to increase. As pneumonitis is observed in up to 5% of patients treated with ICI [3,4,5] and 40% following radiotherapy [6], it is likely to present a growing problem in cancer care. As pneumonitis can result in significant morbidity, preclusion of further treatment and even death [7], it is important for clinicians to have an awareness of its incidence and severity

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Results

Conclusion