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Immune-sparing lung SBRT planning reduced lymphocyte loss in a randomized phase II trial

Optimizing dose to blood- and immune-rich structures reduced lymphocyte depletion and prevented grade 3 lymphopenia after early-stage lung SBRT.

RadOncToday · ·1 min read

KEY POINTS

  • This single-institution randomized phase II trial included 51 patients with stage IA–IB or IIA node-negative NSCLC who were medically inoperable or declined surgery. Patients received either standard SBRT or additional optimization to reduce dose to circulating blood, lymph-node stations, thoracic vertebrae, heart, and great vessels.
  • Both groups received 45–60 Gy in five fractions using IMRT or VMAT while meeting RTOG 0813/0915 requirements. Blood was collected before treatment, immediately after SBRT, at four weeks, and at six months.
  • Optimized planning reduced low-dose exposure across several immune-rich structures. Compared with standard plans, integral dose, V5, and V10 were reduced by 21–68% for the heart, 37–68% for lymph-node stations, and 57–92% for the thoracic spine, although not every dosimetric comparison was statistically significant.
  • Mean lymphocyte-count changes from baseline were −16%, −22%, and −16% immediately, at four weeks, and at six months with optimized planning, versus −31%, −34%, and −26% with standard planning. The overall adjusted improvement was 13.4 percentage points (95% CI 2.8–24.0; p=0.014).
  • The largest effect occurred in the 15 patients with central tumours. Across the three time points, optimized planning improved lymphocyte preservation by 29.5 percentage points compared with standard planning (95% CI 10.1–48.9; p=0.004).
  • Grade 3 lymphopenia developed in 15.4% of standard-arm patients and none in the optimized arm, corresponding to a risk difference of −15.4 percentage points (95% CI −29.2 to −1.5; p=0.04). Dose to the heart, great vessels, thoracic spine, and lymph nodes correlated with lymphocyte depletion.
  • Two grade ≥3 non-haematological adverse events occurred with optimized planning and four with standard planning. No grade ≥2 pneumonitis or grade ≥4 toxicity occurred; exploratory survival differences favoured optimized planning but were neither powered nor statistically significant.

CLINICAL TAKEAWAY

Immune-aware optimization can be incorporated into conventional lung SBRT planning without compromising protocol constraints and appears to meaningfully reduce treatment-related lymphocyte loss. The strategy is promising, particularly for central tumours, but the small single-centre trial does not establish improved tumour control or survival.

SOURCE

International Journal of Radiation Oncology, Biology, Physics