Derivation of a comprehensive semi-empirical proton RBE model from published experimental cell survival data collected in the PIDE database.

We aimed to develop a comprehensive proton relative biological effectiveness (RBE) model based on accumulated cell survival data in the literature. Our approach includes four major components: (1) Eligible cell survival data with various linear energy transfers (LETs) in the Particle Irradiation Data Ensemble (PIDE) database (72 datasets in four cell lines); (2) a cell survival model based on Poisson equation, with and defined as the ability to generate and repair damage, respectively, to replace the classic linear-quadratic model for fitting the cell survival data; (3) hypothetical linear relations of and on LET, or and ; and (4) a multi-curve fitting (MCF) approach to fit all cell survival data into the survival model and derive the , , , and values for each cell line. Dependences of these parameters on cell type were thus determined and finally a comprehensive RBE model was derived.

Interpretable deep learning insights: Unveiling the role of 1 Gy volume on lymphopenia after radiotherapy in breast cancer.

Background: Lymphopenia is known for its significance on poor survivals in breast cancer patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in breast cancer.

Material And Methods: Patients with breast cancer treated with adjuvant RT were eligible in this multicenter study.

Dosimetric Effect of Thymus and Thoracic Duct on Radiation-Induced Lymphopenia in Patients With Primary Lung Cancer Who Received Thoracic Radiation.

Purpose: Radiation-induced lymphopenia is a well-recognized factor for tumor control and survival in patients with cancer. This study aimed to determine the role of radiation dose to the thymus and thoracic duct on radiation-induced lymphopenia.

Methods And Materials: Patients with primary lung cancer treated with thoracic radiation therapy between May 2015 and February 2020 with whole blood count data were eligible.

Potential Determinants for Radiation-Induced Lymphopenia in Patients With Breast Cancer Using Interpretable Machine Learning Approach.

Radiation-induced lymphopenia is known for its survival significance in patients with breast cancer treated with radiation therapy. This study aimed to evaluate the impact of radiotherapy on lymphocytes by applying machine learning strategies. We used Extreme Gradient Boosting (XGboost) to predict the event of lymphopenia (grade≥1) and conduced an independent validation.

Radiation Induced Lymphopenia Is Associated With the Effective Dose to the Circulating Immune Cells in Breast Cancer.

Background: Lymphopenia is a known significant factor for treatment outcome in cancer patients, with underlying risk factor poorly understood in breast cancer. We hypothesize that the effective dose to the circulating immune cells (EDIC) which was related with lymphopenia in lung cancer will also have significant effect for radiation induced lymphopenia (RIL) in patients with breast cancer.

Material And Methods: Patients treated with adjuvant radiotherapy (RT) and with complete blood tests within one week from RT end/start (post/preRT) were eligible in this study.

Prospect of radiotherapy technology development in the era of immunotherapy.

Radiotherapy (RT) is one of the important modalities for cancer treatments. Mounting evidence suggests that the host immune system is involved in the tumor cell killing during RT, and future RT technology development should aim to minimize radiation dose to the immune system while maintaining a sufficient dose to the tumor. A brief history of RT technology development is first summarized.

Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617.

: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). : This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect.

Monte Carlo Dose Calculation Using MRI Based Synthetic CT Generated by Fully Convolutional Neural Network for Gamma Knife Radiosurgery.

The aim of this work is to study the dosimetric effect from generated synthetic computed tomography (sCT) from magnetic resonance (MR) images using a deep learning algorithm for Gamma Knife (GK) stereotactic radiosurgery (SRS). The Monte Carlo (MC) method is used for dose calculations. Thirty patients were retrospectively selected with our institution IRB's approval.

Risk factors for radiation induced lymphopenia in patients with breast cancer receiving adjuvant radiotherapy.

Background: This study aimed to investigate radiation-induced lymphopenia and its potential risk factors in patients with breast cancer receiving adjuvant radiotherapy.

Methods: Breast cancer patients received adjuvant radiotherapy (RT) at our hospital with peripheral lymphocyte counts (PLC) at pre-and immediately after RT (post-RT) were eligible. The primary endpoints were any grade of lymphopenia post-RT and nadir-PLC/pre-PLC <0.

Genetic Variations in the Transforming Growth Factor-β1 Pathway May Improve Predictive Power for Overall Survival in Non-small Cell Lung Cancer.

Transforming growth factor-β1 (TGF-β1), a known immune suppressor, plays an important role in tumor progression and overall survival (OS) in many types of cancers. We hypothesized that genetic variations of single nucleotide polymorphisms (SNPs) in the TGF-β1 pathway can predict survival in patients with non-small cell lung cancer (NSCLC) after radiation therapy. Fourteen functional SNPs in the TGF-β1 pathway were measured in 166 patients with NSCLC enrolled in a multi-center clinical trial.

Impact of effective dose to immune cells (EDIC) on lymphocyte nadir and survival in limited-stage SCLC.

Background: Effective dose to immune cell (EDIC), an estimated radiation dose to the circulating lymphocytes, is of significance for overall survival (OS) in non-small cell lung cancer. This study aimed to validate the EDIC's OS effect on limited-stage small cell lung cancer (LS-SCLC).

Method And Materials: This study included LS-SCLC patients received definitive chemo-radiation in one single center from 2012 to 2017.

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

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 (%ΔALC) and suggests spleen dose constraints to reduce RIL risk.

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients.

Background: Radiation-induced lung fibrosis (RILF) is an important late toxicity in patients with non-small-cell lung cancer (NSCLC) after radiotherapy (RT). Clinically significant RILF can impact quality of life and/or cause non-cancer related death. This study aimed to determine whether pre-treatment plasma cytokine levels have a significant effect on the risk of RILF and investigate the abilities of machine learning algorithms for risk prediction.

Significance of radiation esophagitis: Conditional survival assessment in patients with non-small cell lung cancer.

Purpose: This study aimed to examine the effect of radiation esophagitis (RE) and the dynamics of RE on subsequent survival in non-small cell lung cancer (NSCLC) patients who underwent radiotherapy.

Experimental Design: Patients with NSCLC treated with fractionated thoracic radiotherapy enrolled in prospective trials were eligible. RE was graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE) v3.

Risk factors for symptomatic radiation pneumonitis after stereotactic body radiation therapy (SBRT) in patients with non-small cell lung cancer.

Background And Purpose: Radiation pneumonitis (RP) can be a potential fatal toxicity of stereotactic body radiation therapy (SBRT) for medically inoperable non-small cell lung cancer (NSCLC). This study aimed to examine the risk factors that predict RP and explore dosimetric tolerance for safe practice in a large institutional series of NSCLC patients.

Materials And Methods: Patients with early-stage and locally recurrent NSCLC who received lung SBRT between 2002 and 2015 formed the study population.

Central Airway Toxicity After High Dose Radiation: A Combined Analysis of Prospective Clinical Trials for Non-Small Cell Lung Cancer.

Purpose: To study the dosimetric risk factors for radiation-induced proximal bronchial tree (PBT) toxicity in patients treated with radiation therapy for non-small cell lung cancer (NSCLC).

Methods And Materials: Patients with medically inoperable or unresectable NSCLC treated with conventionally fractionated 3-dimensional conformal radiation therapy (3DCRT) in prospective clinical trials were eligible for this study. Proximal bronchial tree (PBT) and PBT wall were contoured consistently per RTOG 1106 OAR-Atlas.

Ultra-high dose rate effect on circulating immune cells: A potential mechanism for FLASH effect?

Purpose: "FLASH" radiotherapy (RT) is a potential paradigm-changing RT technology with marked tumor killing and normal tissue sparing. However, the mechanism of the FLASH effect is not well understood. We hypothesize that the ultra-high dose rate FLASH-RT significantly reduces the killing of circulating immune cells which may partially contribute to the reported FLASH effect.

The impact of the effective dose to immune cells on lymphopenia and survival of esophageal cancer after chemoradiotherapy.

Purpose: To test the hypothesis that effective dose to circulating immune cells (EDIC) impacts the severity of radiation-induced lymphopenia and clinical outcomes of esophageal cancer patients treated with concurrent chemoradiotherapy (CCRT).

Material And Methods: 488 esophageal cancer patients treated with CCRT with and without surgery were analyzed. The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose (MLD), mean heart dose (MHD), mean liver dose (MlD), and integral dose (ITD) of the body region scanned, calculated as: EDIC=0.

An Integrated Framework Based on Full Monte Carlo Simulations for Double-Scattering Proton Therapy.

Purpose: We developed an integrated framework that employs a full Monte Carlo (MC) model for treatment-plan simulations of a passive double-scattering proton system.

Materials And Methods: We have previously validated a virtual machine source model for full MC proton-dose calculations by comparing the percentage of depth-dose curves, spread-out Bragg peaks, and lateral profiles against measured commissioning data. This study further expanded our previous work by developing an integrate framework that facilitates its clinical use.

A framework for modeling radiation induced lymphopenia in radiotherapy.

Introduction: Associations between radiation-induced lymphopenia (RIL) and survival have been extensively reported. However, the immune system is not considered as an organ-at-risk (OAR) in radiotherapy. This study aimed to develop the framework of an immune OAR model that may be utilized to predict and minimize RIL.

Comprehensive Analysis of the Kinetics of Radiation-Induced Lymphocyte Loss in Patients Treated with External Beam Radiation Therapy.

Radiation-induced lymphopenia (RIL) is associated with worse survival in patients with solid tumors, as well as lower response rates to checkpoint inhibitors. While single-fraction total-body irradiation is known to result in exponential decreases in the absolute lymphocyte count (ALC), the kinetics of lymphocyte loss after focal fractionated exposures have not previously been characterized. In the current study, lymphocyte loss kinetics was analyzed among patients undergoing focal fractionated radiotherapy for clinical indications.

A Validation Study on IDO Immune Biomarkers for Survival Prediction in Non-Small Cell Lung Cancer: Radiation Dose Fractionation Effect in Early-Stage Disease.

Purpose: We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is significantly correlated with more distant metastasis and worse survival. The present study examined whether radiotherapy (RT) dose fractionation correlates with IDO-mediated immune activity in patients with early-stage NSCLC. Patients with newly diagnosed stage I-II NSCLC treated with either conventionally fractionated 3-dimensional conformal radiotherapy (3DCRT) or stereotactic body radiotherapy (SBRT) were analyzed.

Machine Learning to Build and Validate a Model for Radiation Pneumonitis Prediction in Patients with Non-Small Cell Lung Cancer.

Purpose: Radiation pneumonitis is an important adverse event in patients with non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy. However, the risk of radiation pneumonitis grade ≥ 2 (RP2) has not been well predicted. This study hypothesized that inflammatory cytokines or the dynamic changes during radiotherapy can improve predictive accuracy for RP2.

Doses of radiation to the pericardium, instead of heart, are significant for survival in patients with non-small cell lung cancer.

Background And Purpose: Higher cardiac dose was associated with worse overall survival in the RTOG0617 study. Pericardial effusion (PCE) is a common cardiac complication of thoracic radiation therapy (RT). We investigated whether doses of radiation to the heart and pericardium are associated with PCE and overall survival in patients treated with thoracic radiation for non-small cell lung cancer (NSCLC).

Pretreatment PET/CT imaging of angiogenesis based on F-RGD tracer uptake may predict antiangiogenic response.

Purpose: To explore the relationship between metabolic uptake of the F-ALF-NOTA-PRGD (F-RGD) tracer on positron emission tomography/computerized tomography (PET/CT) and the antiangiogenic effect of apatinib in patients with solid malignancies.

Materials And Patients: Patients with measurable lesions scheduled for second- or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial. All patients underwent F-RGD PET/CT examination before the start of treatment.