Main Session
Sep
29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care
3646 - Proton Therapy in Locally Advanced NSCLC: Decreased Side Effects and Mortality Compared to VMAT
Presenter(s)
Lisanne van Dijk, PhD - University Medical Center Groningen, Groningen 9700 GZ, Texas
L. V. van Dijk1, R. van de Wal1, O. Chouvalova1, J. van Loon2, K. van Keeken2, F. F. Ubbels1, S. A. de Boer1, A. C. Hessels1, E. W. Korevaar1, P. R. Deseyne1, A. Gawryszuk1, S. Both1, J. A. Langendijk1, and R. Wijsman1; 1Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, the Netherlands, Groningen, Netherlands, 2Department of Radiation Oncology (MAASTRO), Grow-School for Oncology and Developmental Biology, Maastricht University, The Netherlands, Maastricht, Netherlands
Purpose/Objective(s):
This study compared observed rates after intensity-modulated proton therapy (IMPT) with corresponding model-predicted rates for photon radiotherapy (VMAT) of 2-year mortality, radiation pneumonitis (RP), and acute esophageal toxicity (AET) in patients with non–small cell lung cancer (NSCLC).Materials/Methods:
This study prospectively enrolled consecutive patients with stage IIB–IV locally advanced NSCLC treated with curative-intent IMPT (25×2.4 Gy) between 2019 and 2025. Exclusion criteria included prior thoracic surgery or irradiation, presence of a second primary tumor, or >5 fractions of the total treatment delivered with VMAT. Prior to treatment, comparative VMAT and IMPT plans were generated for each patient. Planning comparisons evaluated dose, predicted mortality and toxicity risks. Predicted risks were prospectively estimated using externally validated models [1-3]. Observed IMPT outcome rates - AET grade=2 (CTCAE), RP =2 (CTCAE) and 2-year mortality - were compared with predicted rates for both IMPT and VMAT. Patients with <2 years of follow-up were excluded from mortality analyses. A photon treated cohort (2013–2024) meeting identical inclusion criteria was used to assess the reliability of VMAT-predicted NTCP values. This cohort was not used as a direct comparator due to selection bias and treatment evolution.Results:
In total, 259 NSCLC patients were treated with IMPT. IMPT achieved significantly lower mean doses to the lungs-GTV, esophagus, and heart compared with VMAT plans (p<0.0001), as well as lower corresponding predicted risks (Table 1). The observed 2-year mortality rate after IMPT was 41%, compared with a predicted rate of 51% for VMAT, corresponding to an absolute reduction of 10%. Observed RP rates were 15% for IMPT versus 22% predicted for VMAT (absolute reduction 7.2%), while AET rates showed a smaller difference (40% vs 43%). Observed IMPT rates matched predicted risks for 2-year mortality (41% vs 43%) and RP (15% vs 15%) and were slightly higher for AET (40% vs 37%). In the photon cohort (n=689), observed mortality was higher than predicted (47% vs 44%) and RP rates were comparable (13% vs 14%), supporting the use of predicted VMAT rates as a comparator for IMPT. Observed AET rates were lower than predicted (33% vs 37%).Conclusion:
IMPT was associated with a 10% reduction in 2-year mortality and 7% in RP compared with model-predicted VMAT rates for locally advanced NSCLC patients. The consistency between observed and predicted outcomes supports the comparison of observed and model-predicted rates.| IMPT mean dose [IQR] | VMAT mean dose [IQR] | ?mean dose [IQR] | |
| Heart | 4.5 [1.9-6.3] Gy | 11.1 [5.3-15.8] Gy | -6.6 [-9.4--2.9] Gy |
| Lungs | 9.8 [7.4-12.2] Gy | 13.6 [11-15.8] Gy | -3.8 [-4.5--2.8] Gy |
| Esophagus | 17.2 [8.6-24.5] Gy | 19.8 [11.6-27.1] Gy | -2.6 [-3.9--0.6] Gy |
| IMPT | IMPT | VMAT | |
| Observed rates | Predicted risk | Predicted risk | |
| 2 year survival | 41.0 ±3.4% | 43.6 ±8.7% | 51.0 ±10.2% |
| Pneumonitis | 14.7 ±2.2% | 14.6 ±9.1% | 21.9 ±12.7% |
| Esophageal toxicity | 40.2 ±3.0% | 37.4 ±21.2% | 42.8 ±18.7% |