Dosimetric Risk Factors for Acute Radiation Pneumonitis in Patients With Prior Receipt of Immune Checkpoint Inhibitors.

Jianping Bi,Tingting Nie,Ying Li,Lu Sun,Guang Han,Vivek Verma,Jing Qian,Shouyu Lin,Xudong Xue,Dongqin Yang

doi:10.3389/fimmu.2021.828858

Abstract

PurposeDosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far.Methods and MaterialsAll included patients underwent thoracic intensity-modulated radiotherapy, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis.ResultsMedian follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Neither the number of prior ICI cycles nor the delivery of concurrent systemic therapy significantly associated with aRP risk. Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD (continuous variables).ConclusionsThis is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. However, these data should not be extrapolated to patients without pre-radiotherapy receipt of prior ICIs, or to evaluate the risk of chronic pulmonary effects. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.

Highlights

Immune checkpoint inhibitors (ICIs) have revolutionized oncologic care throughout the world and represent the standard of care for many metastatic or locally advanced cancers
We conducted a retrospective review of all patients who received thoracic intensity-modulated radiotherapy (IMRT) at our institution from March 2020 to July 2021
Patients with a variety of thoracic cancers were included, so workup and follow-up were individualized, but pre-RT workup always involved chest computed tomography (CT) or positron emission tomography (PET)-CT imaging, and follow-up after RT generally consisted of follow-up chest CT one month after RT and every 3 months thereafter

Summary

Introduction

Immune checkpoint inhibitors (ICIs) have revolutionized oncologic care throughout the world and represent the standard of care for many metastatic or locally advanced cancers. It is well recognized that ICIs can cause adverse events that may be additive with those caused by RT. One such example is pneumonitis, which can be caused independently by ICIs as well as from RT [2,3,4]. Some reports have observed relatively high rates of radiation pneumonitis (RP) in patients with combined ICI and RT, including fatal events [5, 6]. The safety of combined therapy remains poorly understood owing to 1) the relatively recent adoption of ICIs as well as 2) the rise in RT delivered to suprapalliative doses for metastatic cancers (e.g. for oligometastatic or oligoprogressive disease)

Objectives

Methods

Results

Discussion

Conclusion