Vertebral body and splenic irradiation are associated with lymphopenia in localized pancreatic cancer treated with stereotactic body radiation therapy

Abstract

Objectives: The purpose of this study was to determine if vertebral body and splenic dosimetry was associated with the development of lymphopenia in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation therapy (SBRT).

Methods: Patients with BRPC/LAPC who were treated with SBRT and who had lymphocyte counts and radiation treatment plans available for review were included in the study. Vertebral body levels T11-L3 and the spleen were retrospectively contoured for each patient. Univariate (UVA) and multivariable analyses (MVA) were performed to identify associations between vertebral body and splenic dosimetric parameters with absolute lymphocyte count (ALC) and grade ≥ 2 lymphopenia. Receiver operator characteristic curves were generated to identify dose-volume thresholds in predicting grade ≥ 2 lymphopenia.

Results: A total of 132 patients were included in the study. On UVA and MVA, vertebral V15 (regression coefficient [β]: - 0.026, 95% CI - 0.044 to - 0.009, p = 0.003), vertebral V2.5 (β: - 0.011, 95% CI - 0.020 to - 0.002, p = 0.015), and log₁₀PTV (β: - 0.15, 95% CI - 0.30 to - 0.005, p = 0.042) were associated with post-SBRT ALC. On UVA and MVA, vertebral V15 (odds ratio [OR]: 3.98, 95% CI 1.09-14.51, p = 0.027), vertebral V2.5 (OR: 1.04, 95% CI 1.00-1.09, p = 0.032), and spleen V10 (OR: 1.05, 95% CI 1.09-1.95, p = 0.004) were associated with development of grade ≥ 2 lymphopenia. Development of grade ≥ 2 lymphopenia was more likely in patients with vertebral V15 ≥ 5.84% (65.5% vs 34.0%, p = 0.002), vertebral V2.5 ≥ 48.36% (48.9% vs 23.8%, p = 0.005), and spleen V10 ≥ 4.17% (56.2% vs 26.9%, p < 0.001).

Conclusions: Increasing radiation dose to vertebral bodies and spleen were associated with the development of lymphopenia in BRPC/LAPC treated with SBRT. Optimization of vertebral body and splenic dosimetry may reduce the risk of developing lymphopenia and improve clinical outcomes in this population.

Keywords: Pancreatic adenocarcinoma; Pancreatic cancer; Radiation induced lymphopenia; SBRT; Spleen dose; Splenic irradiation; Stereotactic body radiation therapy; Vertebral body dose; Vertebral body irradiation.

Fig. 1

Receiver operating characteristic curves showing optimal thresholds for vertebral V15 (a), vertebral V2.5 (b), and spleen V10 (c) in predicting development of grade ≥ 2 lymphopenia

Fig. 2

Radiation treatment plan with isodose lines on axial, coronal, and sagittal planning images for a initial plan which exceeded vertebral body and splenic thresholds and b optimized plan which met vertebral body and splenic constraints. Turquoise colorwash represents PTV, orange colorwash represents spleen, and red colorwash represents vertebral bodies. Isocenter represented by green crosshair on axial image

Fig. 3

Dose-volume histograms for a vertebral body and b spleen for the initial (solid line) and optimized (dashed line) plans