Clinical Factors Influencing the Radiation Dose of Circulating Immune Cells during Radiotherapy for Small Cell Lung Cancer

Summary

Here, we present a protocol to evaluate the effects of radiation therapy on immune system lymphocytes in small cell lung cancer.

Abstract

Small cell lung cancer (SCLC) has garnered significant attention due to its high malignancy, propensity for distant metastasis, and poor prognosis. Radiotherapy remains the cornerstone of treatment for limited-stage small cell lung cancer (LS-SCLC). However, outcomes with radiotherapy alone or in combination with chemotherapy remain suboptimal. Radiotherapy can induce lymphopenia by directly irradiating hematopoietic organs or destroying mature circulating lymphocytes, leading to immunosuppression and consequently diminishing therapeutic efficacy. The estimated dose of radiation to immune cells (EDRIC) model integrates factors such as hemodynamics, lymphocyte radiosensitivity, and proliferation capacity. This study employs the EDRIC model with enhancements to calculate the circulating immune cell radiation dose. By utilizing the EDRIC methodology, the study explores the correlation between EDRIC and tumor target size, average lung dose, average heart dose, clinical features, and peripheral blood lymphocytopenia during radiotherapy for LS-SCLC, aiming to inform personalized patient treatment strategies.

This study analyzed data from 64 LS-SCLC patients who met the inclusion criteria at the General Hospital of Ningxia Medical University from January 2023 to January 2024, all of whom received radical thoracic conventional fractionated radiotherapy. Lymphocyte counts were recorded at the following points: before radiotherapy, at the lowest observed value during radiotherapy, at the end of radiotherapy, and one-month post-radiotherapy. Dosimetric data, including average lung, heart, and body doses, were extracted from the treatment planning system, and the circulating EDRIC was calculated using this model. The relationship between EDRIC values and therapeutic outcomes was analyzed. In LS-SCLC, the EDRIC model effectively predicts lymphocyte count reduction, correlating with planning target volume (PTV; cm³), TNM stage, and the percentage of target lesion shrinkage. Post-radiotherapy, there was a significant decrease in peripheral blood lymphocyte counts, with greater EDRIC values indicating more pronounced lymphocyte reduction.

Introduction

Lung cancer remains a leading cause of morbidity and mortality worldwide, with small cell lung cancer (SCLC) comprising 13%-17% of cases^1,2. SCLC is characterized by a high degree of malignancy and a propensity for early distant metastasis, often leading to late-stage diagnosis and poor prognosis. Advances in medical technology and a deeper understanding of the biological characteristics of SCLC have highlighted the potential value of radiotherapy in its treatment. Nonetheless, outcomes with radiotherapy alone or in combination with chemotherapy remain suboptimal. Identifying key factors influencing the effica....

Protocol

Following stringent adherence to this study's inclusion and exclusion criteria, informed consent for radiotherapy was obtained from each patient and their guardian. Clinical staging was conducted in accordance with the American Joint Committee on Cancer (AJCC) TNM staging system (8^th edition). The Ethics Committee of Ningxia Medical University General Hospital (KYLL-2022-0984) granted approval for this study.

NOTE: The inclusion criteria were as follows: (i) pathologically confi.......

Discussion

The immune system plays a pivotal role in tumor control during radiotherapy, yet radiation-induced immunotoxicity, such as lymphocytopenia, is linked to unfavorable survival outcomes^13,14. SCLC is characterized by its high malignancy, often diagnosed in advanced stages with a dismal prognosis. Radiotherapy stands as the cornerstone treatment for LS-SCLC. However, its impact on the immune system is complex. The efficacy of radiotherapy alone or in combination with.......

Materials

Name	Company	Catalog Number	Comments
CT machine	Siemens Healthcare	SOMATOM Force
MRI machine	Siemens Healthcare	MAGNETOM Terra
Varian Clinac_IX Medical electron linear Accelerator	Siemens Healthcare	IX