Upright Image-Guided Proton Therapy for Thoracic Re-Irradiation: Interim Results of Prospective Clinical Trial
Abstract
Purpose
Thoracic re-irradiation (reRT) for locally recurrent non-small cell lung cancer is constrained by cumulative dose limits to mediastinal organs at risk (OARs). Proton therapy enables improved dose conformity compared with photon techniques, while upright patient positioning may further enhance thoracic geometry by increasing lung volume, displacing mediastinal structures, and enabling gantry-less beam delivery. This interim analysis evaluates the feasibility, dosimetric performance, and early clinical outcomes of upright image-guided intensity-modulated proton therapy (IMPT) for thoracic reRT, with comparisons to supine IMPT and photon volumetric-modulated arc therapy (VMAT).
Methods
Ten patients with locally recurrent thoracic malignancies previously treated with radiotherapy were prospectively enrolled. Nine patients underwent both upright and supine CT simulation; one patient completed the upright workflow only. All treatments employed a free-breathing internal target volume (ITV) approach. Comparative treatment plans were generated for upright IMPT, supine IMPT, and VMAT using identical target and OAR definitions. Changes in lung volume between supine and upright positioning were quantified. Acute toxicity was graded using CTCAE_v5.0, and early metabolic response was assessed at three months post-treatment.
Results
Upright IMPT achieved target coverage comparable to both supine IMPT and VMAT. Compared with VMAT, IMPT significantly reduced dose to all evaluated mediastinal and pulmonary OARs. Upright positioning resulted in a mean lung volume increase of 9.8% relative to supine positioning (p < 0.01). No statistically significant dosimetric differences were observed between upright and supine IMPT plans. At three months, most patients demonstrated metabolic response, with only grade 1–2 acute toxicities reported and no grade ≥3 events.
Conclusion
Upright IMPT for thoracic re-irradiation is technically feasible and provides substantial OAR sparing compared with photon VMAT, while maintaining equivalent dosimetric performance to conventional supine IMPT. Increased lung volume and favorable early tolerance support upright positioning as a viable and physics-driven strategy for thoracic reRT.