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Dosimetric Predictors of Radiation Pneumonitis for Stage III NSCLC Treated With Neoadjuvant Immuno-chemotherapy and
Yang Liu1, YunXiang Qi2, Wenyan Pan3
1Department of Pathology, The Third Xiangya Hospital of Central South University, Central South University, Changsha, China.
Background:
For patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with neoadjuvant immuno-chemotherapy followed by definitive radiotherapy, the risk of radiation pneumonitis (RP) may be elevated. This multicenter study aimed to validate established dose-volume predictors in this specific treatment context.
Methods:
We analyzed 372 stage III NSCLC patients from 9 institutions who received neoadjuvant (NEO) or adjuvant immunotherapy. RP was graded per CTCAE v5.0. Univariable and multivariable logistic regression identified factors associated with grade ≥ 2 (RP2) and grade ≥ 3 (RP3) RP within the NEO cohort. Optimized dosimetric thresholds were derived using ROC curves.
Results:
In the NEO cohort, multivariable analysis showed lung V20 independently predicted RP2 (odd ratio [OR]: 1.09, 95% confidence interval [CI]: 1.05-1.14, P < .001), while mean lung dose (MLD) independently predicted RP3 (OR: 1.11, 95% CI, 1.02-1.22, P = .018). The optimal cutoffs were V20 ≤ 24% and MLD ≤ 14 Gy. A composite constraint (V20 ≤ 24% and MLD ≤ 14 Gy) significantly reduced RP2 (20.8% vs. 49.5%) and RP3 (8.2% vs. 23.1%) incidence compared to non-compliant plans. This new constraint showed significant net reclassification improvement for RP2 (NRI = 17.4%, P = .027) over conventional criteria (V20 ≤ 35%, MLD ≤ 20 Gy).
Conclusion:
Stricter dosimetric constraints (V20 ≤ 24%; MLD ≤ 14 Gy) are critical for mitigating RP risk in stage III NSCLC patients treated with neoadjuvant immuno-chemotherapy and radiotherapy, providing tailored guidance for planning in the immunotherapy era.