3504 - Spatially Fractionated Radiotherapy for Large Thoracic Malignancies: Early Clinical Outcomes

Purpose/Objective(s): Spatially fractionated radiation therapy (SFRT) delivers heterogeneous dose distributions within tumors and has shown promise for large, radioresistant malignancies. However, dedicated thoracic-specific data remain limited. This study evaluated the technical feasibility, dosimetric characteristics, and early clinical outcomes of lattice-based SFRT in patients with large thoracic malignancies.

Materials/Methods: We retrospectively analyzed patients with histologically confirmed thoracic malignancies (maximum tumor diameter =4.5 cm or GTV =50 cc) treated with SFRT between October 2024 and June 2025 at a single institution. SFRT was delivered once weekly (1–5 fractions, 6–15 Gy/fraction) using VMAT with 6-MV flattening filter-free beams, integrated into a hybrid regimen where conventional radiotherapy (1.8–3.0 Gy/fraction) was administered on remaining weekdays to a total conventional dose of 27–60 Gy (median 50 Gy). Lattice vertex parameters were individualized per tumor geometry and adjacent anatomy. The primary endpoint was objective response rate (ORR) and local control (LC) rate per RECIST v1.1; secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related toxicity graded by CTCAE v5.0.

Results: Twenty-seven patients were included (median age 66 years; 70.4% male). Histologies comprised squamous cell carcinoma (44.4%), adenocarcinoma (37.1%), small cell carcinoma (14.8%), and sarcomatoid carcinoma (3.7%). The majority were stage III (81.4%). Median GTV was 154.8 cc (range, 52.2–756.3). SFRT dosimetric parameters included a median peak dose of 34.2 Gy, valley dose of 23.9 Gy, and peak-to-valley dose ratio (PVDR) of 1.46 (range, 1.17–2.99). No significant correlation was observed between GTV and PVDR (r = 0.20, p = 0.329). OAR exposure from SFRT was minimal: median lung V20 was essentially 0%, mean lung dose 1.28 Gy, and heart V30/V40 were 0% in all patients. At a median follow-up of 6.7 months, the ORR was 59.3% (1 CR, 15 PR) and the LC rate was 88.9%. The 6-month PFS and OS rates were 92.3% (95% CI, 72.6–98.0) and 95.7% (95% CI, 72.9–99.4), respectively. Two patients (7.4%) experienced grade 2 radiation pneumonitis; no grade =3 acute or late toxicity occurred. Lymphocyte counts decreased by 54.2% post-treatment (p < 0.001).

Conclusion: Lattice-based SFRT is feasible and well-tolerated for large thoracic malignancies, achieving favorable early local control with minimal OAR exposure and low acute toxicity. Prospective trials are warranted to validate these findings and refine patient selection criteria.