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

Front Immunol. 2022 Jan 13:12:828858. doi: 10.3389/fimmu.2021.828858. eCollection 2021.

Abstract

Purpose: Dosimetric 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 materials: All 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.

Results: Median 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).

Conclusions: This 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.

Keywords: dosimetry; immune checkpoint inhibitor; pneumonitis; radiotherapy; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / diagnosis
  • Acute Lung Injury / epidemiology*
  • Acute Lung Injury / etiology*
  • Aged
  • Disease Susceptibility*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Incidence
  • Male
  • Middle Aged
  • Odds Ratio
  • ROC Curve
  • Radiation Pneumonitis / diagnosis
  • Radiation Pneumonitis / epidemiology*
  • Radiation Pneumonitis / etiology*
  • Radiotherapy / adverse effects
  • Radiotherapy / methods
  • Radiotherapy Dosage
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index

Substances

  • Immune Checkpoint Inhibitors