Title
The Cardiac Radiation Therapy Sparing (HEARTS) for Thoracic Cancers

Description
This clinical trial, The cARdiac Radiation Therapy Sparing (HEARTS) trial, will compare MR-guided adaptive radiation therapy (MRgART) with substructure sparing to standard of care x-ray based linac RT with whole-heart dose metrics for patients with cancer in the thoracic region based on longitudinal changes in cardiac function using MRI, quality of life, cardiac waveforms, and blood biomarkers.

Objective
Primary

To evaluate Left Ventricular Ejection Fraction (LVEF) using cardiac MRI in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To evaluate left and right ventricular (LV/RV) volume using cardiac MRI in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To evaluate myocardial strain using cardiac MRI in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To evaluate quantitative T1, T2,and extracellular volume fraction (ECV) mapping using cardiac MRI in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To evaluate semi-quantitative perfusion using cardiac MRI in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To evaluate late gadolinium enhancement interpreted by expert readers using cardiac MRI in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To estimate quality of life in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To evaluate acute toxicity of MRgART compared to that of standard of care x-ray based linac with whole heart dose/volume assessments in subjects with thoracic cancers.

To monitor heart rhythm in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To characterize early changes in biomarkers for fibrosis and left ventricular dysfunction in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

To characterize early changes in biomarkers for myocardial injury and stress (high-sensitivity cardiac troponin T [hs-cTnT]), inflammation, and oxidative stress in subjects with thoracic cancers treated with MRgART coupled with substructure sparing as compared to subjects treated with standard of care x-ray based linac with whole heart dose/volume assessments.

Treatment The goal of this clinical trial is to compare a new way of using magnetic resonance-guided adaptive radiation therapy (MRgART) to the standard of care linear accelerator (LINAC) radiation treatment in people with cancer in the thoracic region near the heart.

The main question it aims to answer is whether MRgART affects the heart differently than LINAC.

Participants will:

-Receive radiation therapy
-Undergo MRIs and bloodwork
-Complete quality of life questionnaires

Key Eligibility Inclusion Criteria:

Age > 18 years at the time of consent.

Dosimetric eligibility criteria met using endpoints from QUANTEC (>10% of heart receives > 25 Gy) as determined through rapid auto-planning

Participants with histologically or cytologically proven AJCC, 8th edition including:



Stage IIIA,IIIB, or IIIC non-operable non-small cell lung cancer

Stage I-III N0-2 disease esophageal/esophagogastric cancer

Stage II or III thymoma/thymic carcinoma

Other cancers in the thoracic region that meet the dosimetric and other clinical trial criteria.



Participants must have a definitive course of daily fractionated RT planned of at least 15 treatment fractions, typically ranging from 1.8 to 4 Gy/fraction

Definitive clinical or radiologic evidence of metastatic disease with life expectancy <12 months

Prior thoracic radiotherapy significantly overlapping the heart region

Contraindications to MRI

Severe, active co-morbidity defined as follows: New York Heart Association Functional Classification III/IV are not eligible.

Applicable Disease Sites
Esophagus; Lung

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital