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

Abhinav V Reddy,Juan F Jackson,Amol K Narang,Lei Zheng,Jin He,Joseph M Herman,Colin S Hill,Shuchi Sehgal,Jeffrey Meyer,Matthew P Deek

doi:10.1186/s13014-021-01969-1

Abstract

ObjectivesThe 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).MethodsPatients 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.ResultsA 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).ConclusionsIncreasing 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.

Highlights

Pancreatic cancer is currently the third most common cause of cancer related deaths in the United States, responsible for over 48,000 deaths each year [1]
Patients with Borderline resectable pancreatic cancer (BRPC)/locally advanced pancreatic cancer (LAPC) who were treated with stereotactic body radiation therapy (SBRT) and who had lymphocyte counts and radiation treatment plans available for review were included in the study
On UVA and multivariable analyses (MVA), vertebral V15, 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 absolute lymphocyte count (ALC)

Summary

Introduction

Pancreatic cancer is currently the third most common cause of cancer related deaths in the United States, responsible for over 48,000 deaths each year [1]. Treatment related lymphopenia is seen in a wide range of malignancies including esophageal cancer, non-small cell lung cancer (NSCLC), head and neck cancer, and pancreatic cancer [5,6,7,8]. It is associated with poor survival and tumor control outcomes, likely due to the depletion of anti-tumorigenic cytotoxic T cells in both the peripheral blood and tumor microenvironment (TME) [9, 10]. Strategies to minimize lymphopenia should be explored to optimize outcomes in pancreatic cancer

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