Prior immune-related AEs linked to high radiation pneumonitis risk
medwireNews: Patients with prior immune checkpoint inhibitor (ICI)-induced immune-related adverse events (irAEs) have a very high risk for developing radiation pneumonitis from thoracic radiotherapy, US researchers report.
Writing in the Annals of Oncology, Narek Shaverdian and colleagues from the Memorial Sloan Kettering Cancer Center in New York say: “Careful consideration of the increased risk of [radiation pneumonitis] and efforts to minimize the MLD [mean lung radiation dose] are warranted to mitigate the risk of substantial morbidity.”
Their study included data for 496 consecutive patients treated with atezolizumab, nivolumab, ipilimumab, pembrolizumab, durvalumab, or tremelimumab between 2014 and 2020.
Of these, 41 had a history of irAEs and subsequently received thoracic radiation, typically stereotactic body radiotherapy (n=20) or hypofractionated radiotherapy (n=18).
The majority of the prior irAEs were grade 2 (n=21) or grade 3 (n=19) and the median time from the onset of the irAE to thoracic radiation was 8.1 months. At the time of radiotherapy, 78% of patients had complete resolution of irAE symptoms.
Following treatment, 61% of the 41 patients developed grade 2 or worse radiation pneumonitis at a median of 4 months from radiotherapy and 11 months from onset of irAEs. Grade 3 or worse radiation pneumonitis occurred in 15%.
The researchers report that radiation pneumonitis symptoms persisted for at least 3 months in two-thirds of 24 patients evaluable at this timepoint.
Six patients included in the analysis had prior ICI-related pneumonitis that had resolved at the time of radiotherapy. All but one (83%) of these patients subsequently developed grade 2 or worse radiation pneumonitis.
Shaverdian and team used regression analysis to identify variables that might be associated with radiation pneumonitis. The only significant predictor they found was MLD, with each 2 Gy increase associated with a 49% increased risk.
Furthermore, an area under the receiver operating characteristic curve of 0.85 shows that the “relationship between MLD and [radiation pneumonitis] was strong,” the investigators remark.
Indeed, 81% of patients who received an MLD of more than 5 Gy developed grade 2 or worse pneumonitis.
Taken together these findings support “the use of strategies to reduce the MLD far below current guidelines,” Shaverdian et al remark.
They suggest: “Deep-inspiratory breath hold, margin-reduction and/or proton therapy should be considered as potential technical adjustments to mitigate the risk of [radiation pneumonitis] and the associated morbidity and risk of even mortality in these patients.”
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