Abstract 422P
Background
Pneumonitis is a known adverse event of both radiation therapy and immune checkpoint inhibitors (ICIs). This study aims to investigate occurrence and dosimetric factors influencing the risk of acute pnuemonitis in patients treated with thoracic radiotherapy (TRT) with prior receipt of ICIs.
Methods
Patients treated at two Institutions with TRT after systemic treatment with ICIs were retrospectively analyzed. Acute events are defined as those occurring within 6 months after TRT and defined as per CTCAE 5.0. Outcomes of interest included pneumonitis occurrence and type of acute pneumonitis [radiation pneumonitis (RP) and any pneumonitis (AP)]. Association with dosimetric parameters [including mean lung dose (MLD), percentage of normal lung volume receiving ≥20 Gy (V20), ≥5 Gy (V5); and mean heart dose (MHD)] was evaluated. Considering the heterogeneity in dose/fractionation schedules, all plans were standardized using equivalent dose in 2 Gy (EQD2) doses.
Results
A total of 83 patients treated from January 2018 to June 2024 were included. Most common primary malignancy was lung (94%). ICIs were PD1 54 (65%) or PD-L1 29 (35%) inhibitors, administered for a median of 6 cycles (range 1–47) prior TRT. Median EQD2 radiation dose and planning target volume were 48.8 Gy (range 31.3–62.5 Gy) and 259 cc (range 17–1025 cc), respectively. Acute RP and AP occurred in 63.9% and 65.1% of patients, respectively, at a median time of 2 months (95% CI 2–3 months) from TRT completion. Overall, RP G≥2 rate was 32.5%, higher than 20% expected according to normal tissue complication probability model (QUANTEC). Dosimetric variables associated with G≥2 RP were lungs V20, MLD and MHD (Table), while PTV volume was associated with G5 RP. Variables associated with G≥2 AP were MLD and MHD, while lung V5 was associated with ≥G3 and G5 AP.
Table 422PAnalysis of dosimetric and volumetric parameters among patients with acute pneumonitis versus patients without
| Parameter, median (range) | P-value | ||
| G>2 RP (n=27) | No G≥2 RP (n=56) | ||
| V20 GyEQD2 (%) | 11.5 (0.5–41.4). | 7.6 (0.0–32.5) | 0.029 |
| MLD (GyEQD2) | 9.0 (0.8–71.7) | 6.7 (0.2–19.6) | 0.018 |
| MHD (GyEQD2) | 7.5 (0.3–22.2) | 2.8 (0.0–17.0) | 0.001 |
| G5 RP (n=4) | No G5 RP (n=79) | ||
| PTV volume (cc) | 468(344–825) | 224 (17.5–1025) | 0.050 |
| G>2 AP (n=30) | No G≥2 AP (n=53) | ||
| MLD (GyEQD2) | 8.5 (0.8–71.7) | 6.9 (0.2–19.6) | 0.031 |
| MHD (GyEQD2) | 7.1 (0.2–22.5) | 2.7 (0.0–17.1) | 0.030 |
| G>3 AP (n=15) | No G≥3 AP (n=68) | ||
| V5 GyEQD2 (%) | 48.9 (11.1–77.6) | 31.4 (0.2–73.9) | 0.023 |
| G5 AP (n=7) | No G5 AP (n=76) | ||
| V5 GyEQD2 (%) | 63.0 (33.2–77.6) | 33.1 (0.2–74.6) | 0.019 |
Conclusions
In this study, incidence and severity of RP and AP in patients treated with TRT after ICI was higher than expected according to pre-ICI defined dose constraints.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Tiseo: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Roche, Amgen, Takeda, MSD, Merck, BMS, Pfizer, Eli Lilly, Novartis, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche. All other authors have declared no conflicts of interest.