Dataset Information

Patient-Specific Lymphocyte Loss Kinetics as Biomarker of Spleen Dose in Patients Undergoing Radiation Therapy for Upper Abdominal Malignancies.

ABSTRACT:

Purpose

Radiation therapy (RT)-induced lymphopenia (RIL) is linked with inferior survival in esophageal and pancreatic cancers. Previous work has demonstrated a correlation between spleen dose and RIL risk. The present study correlates spleen dose-volume parameters with fractional lymphocyte loss rate (FLL) and total percent change in absolute lymphocyte count (%?ALC) and suggests spleen dose constraints to reduce RIL risk.

Methods and materials

This registry-based study included 140 patients who underwent RT for pancreatic (n = 67), gastroesophageal (n = 61), or biliary tract (n = 12) adenocarcinoma. Patient-specific parameters of lymphocyte loss kinetics, including FLL and %?ALC, were calculated based on serial ALCs obtained during RT. Spearman's rho was used to correlate spleen dose-volume parameters with %?ALC, end-treatment ALC, and FLL. Multivariable logistic regression was used to identify predictors of ?grade 3 and grade 4 RIL.

Results

Spleen dose-volume parameters, including mean spleen dose (MSD), all correlated with %?ALC, end-treatment ALC, and FLL. Controlling for baseline ALC and planning target volume (PTV), an increase in any spleen dose-volume parameter increased the odds of developing ?grade 3 lymphopenia. Each 1-Gy increase in MSD increased the odds of ?grade 3 RIL by 18.6%, and each 100-cm³ increase in PTV increased the odds of ?grade 3 lymphopenia by 20%. Patients with baseline ALC < 1500 cells/?L had a high risk of ?grade 3 RIL regardless of MSD or PTV. FLL was an equally good predictor of ?grade 3 lymphopenia as any spleen dose-volume parameter.

Conclusions

In patients undergoing RT for upper abdominal malignancies, higher spleen dose is associated with higher per-fraction lymphocyte loss rates, higher total %?ALC, and increased odds of severe lymphopenia. Spleen dose constraints should be individualized based on baseline ALC and PTV size to minimize RIL risk, although our findings require validation in larger, ideally prospective data sets.

SUBMITTER: Yalamanchali A

PROVIDER: S-EPMC7897770 | biostudies-literature | 2021 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Patient-Specific Lymphocyte Loss Kinetics as Biomarker of Spleen Dose in Patients Undergoing Radiation Therapy for Upper Abdominal Malignancies.

Yalamanchali Anirudh A Zhang Hong H Huang Ke Colin KC Mohan Radhe R Lin Steven H SH Zhu Cong C Grossman Stuart A SA Jin Jian-Yue JY Ellsworth Susannah G SG

Advances in radiation oncology 20200810 1

<h4>Purpose</h4>Radiation therapy (RT)-induced lymphopenia (RIL) is linked with inferior survival in esophageal and pancreatic cancers. Previous work has demonstrated a correlation between spleen dose and RIL risk. The present study correlates spleen dose-volume parameters with fractional lymphocyte loss rate (FLL) and total percent change in absolute lymphocyte count (%ΔALC) and suggests spleen dose constraints to reduce RIL risk.<h4>Methods and materials</h4>This registry-based study included ...[more]

PMID: 33665481

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Project description:BackgroundCesium-137 (137Cs) is one of the major and most clinically relevant radionuclides of concern in a radiological dispersal device, "dirty bomb" scenario as well as in nuclear accidents and detonations. In this exposure scenario, a significant amount of soluble radionuclide(s) may be dispersed into the atmosphere as a component of fallout. The objectives of the present study were to investigate the effect of protracted 137Cs radionuclide exposures on DNA damage in mouse blood and spleen mononuclear cells (MNCs) in vivo using the γ-H2AX biomarker, and to develop a mathematical formalism for these processes.ResultsC57BL/6 mice were injected with a range of 137CsCl activities (5.74, 6.66, 7.65 and 9.28 MBq) to achieve total-body committed doses of ~ 4 Gy at Days 3, 5, 7, and 14. Close to 50% of 137Cs was excreted by day 5, leading to a slower rate of decay for the remaining time of the study; 137Cs excretion kinetics were independent of activity level within the tested range, and the absorbed radiation dose was determined by injected activity and time after injection. Measurements of γ-H2AX fluorescence in blood and spleen MNCs at each time point were used to develop a new biodosimetric mathematical formalism to estimate injected activity based on γ-H2AX fluorescence and time after injection. The formalism performed reasonably well on blood data at 2-5 days after injection: Pearson and Spearman's correlation coefficients between actual and predicted activity values were 0.857 (p = 0.00659) and 0.929 (p = 0.00223), respectively.ConclusionsDespite the complicated nature of the studied biological system and the time-dependent changes in radiation dose and dose rate due to radionuclide excretion and other processes, we have used the γ-H2AX repair kinetics to develop a mathematical formalism, which can relatively accurately predict injected 137Cs activity 2-5 days after initial exposure. To determine the assay's usefulness to predict retrospective absorbed dose for medical triage, further studies are required to validate the sensitivity and accuracy of the γ-H2AX response after protracted exposures.

Dataset Information

Patient-Specific Lymphocyte Loss Kinetics as Biomarker of Spleen Dose in Patients Undergoing Radiation Therapy for Upper Abdominal Malignancies.

Purpose

Methods and materials

Results

Conclusions

Publications

Patient-Specific Lymphocyte Loss Kinetics as Biomarker of Spleen Dose in Patients Undergoing Radiation Therapy for Upper Abdominal Malignancies.

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