An observational study in Non-small Cell Lung Cancer and Radiation Toxicity, sponsored by London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's. Status unknown at 1 site in Canada. Per ClinicalTrials.gov, last updated 2018-01-31.
Sponsored by London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's · Observational
Lung cancer is the most common cause of cancer death in Canada. For approximately 30% of patients that present with locally-advanced non-small cell lung cancer (NSCLC), the standard treatment is curative-intent concurrent chemoradiotherapy. Outcomes remain poor, with 5-year survival of only 20%. Despite the long-held belief that higher radiation doses lead to improved overall survival (OS), the landmark randomized trial (RTOG 0617) showed the opposite. The investigators hypothesize that the inferior survival observed may be due to unexpected heart toxicity as secondary analysis revealed that the heart dose was a strong predictor of inferior OS. Up to now, change in heart function is typically detected histologically, requiring autopsy tissue. Therefore, a non-invasive marker of early heart damage is required. Hybrid PET-MRI has become available in Canada only recently. The ability to simultaneously perform metabolic imaging with functional and tissue imaging allows for novel assessment of heart toxicity. The primary objective is to examine the utility of hybrid PET-MRI and DCE-CT to assess acute changes in heart function and to measure inflammation before, and six weeks after NSCLC radiotherapy. A pilot of 20 patients with Stage I-III NSCLC will be enrolled. The findings of this study will aid in the design of new studies to reassess dose escalation for locally advanced NSCLC while limiting the risk of heart toxicity. FDG PET will be used to simultaneously assess both cardiac inflammation and tumour response. Quantitative DCE-CT will also be used to measure ventilation and perfusion changes in the normal lung and tumour after radiotherapy, providing image data that can comprehensively assess both tumour response and potential toxicity in both the heart and lungs. Such information is crucial in understanding the disease and its response to treatment. This data will also aid in the design of radiation techniques that spare the heart in other patients with any thoracic malignancies, including breast cancer, lymphoma, and esophageal cancer.
The investigators propose a longitudinal imaging pilot study composed of 20 Stage I-III NSCLC patients before, and six weeks after standard radiotherapy using a hybrid 3T-PET/MRI system (Biograph mMR, Siemens Healthcare) and a GE Revolution 256-slice CT scanner. The imaging protocol is designed to detect acute changes in myocardial perfusion, inflammation, edema, left ventricular ejection fraction, normal lung and tumour perfusion, and tumour metabolism. During each imaging session, patients will receive an 18F-FDG PET scan to image macrophage-related inflammation and tumour metabolism, MRI to identify edema, mature fibrosis or scar, and Dynamic contrast enhanced CT (DCE-CT) imaging to image perfusion and (LVEF). All images will be fused and rendered with radiation treatment planning dose distributions. Parameters such as Standard Uptake Value (SUV) will be used to compare PET scans, while heart volume and presence of Gadolinium enhancement will be used to compare MRI scans. Blood flow, blood volume, and permeability will be used to compare CT scans. Blood tests including Erythrocyte Sedimentation Rate (ESR), high sensitivity C-reactive protein, and troponin at each timepoint will also be performed to detect cardiac inflammation. Comparisons between Stage I/II and Stage III patients will allow us to determine whether our metrics for heart changes is radiation related. Relative differences from the six-week time point to baseline will be correlated with the radiation dose distribution to attempt to define a dose-response relationship between radiation dose and cardiac toxicity.
Ultimately, the sample size was based upon practical considerations and that 20 NSCLC patients (10 Stage I/II and 10 Stage III) could be accrued relatively easily from new patient clinics, while sufficiently providing enough evidence to validate the imaging techniques to be used as a non-invasive measure for future clinical trials aimed at reducing or mitigating radiation-induced cardiac toxicity.
Exclusion Criteria:
Stage I/II NSCLC patients receiving standard stereotactic body radiation therapy and Stage III patients receiving Standard platinum-based chemoradiotherapy will receive PET/MRI, DCE-CT, ECG/EKG, and bloodwork before and six weeks post treatment.
Radiation: Standard platinum-based chemoradiotherapy
Stage III patients: Standard platinum-based chemotherapy, total radiation dose 60 Gy in 30 fractions. Stage I/II patients: Standard radiotherapy, total radiation dose of 54 Gy in 3 fractions (peripheral), 55 Gy in 5 fractions (near chest wall), or 60 Gy in 8 fractions (central).
Detection of Imaging Biomarkers of acute cardiac inflammation
FDG-PET imaging to detect increase in cardiac inflammation compared to baseline with corresponding blood markers (Erythrocyte Sedimentation Rate (ESR), high sensitivity C-reactive protein, and troponin levels in blood (inflammation)).
Time frame: 6 weeks
Detection of Imaging Biomarkers of acute cardiac perfusion changes
DCE-CT imaging to detect changes in acute cardiac perfusion changes compared to baseline.
Time frame: 6 weeks
Detection of Imaging Biomarkers of acute changes in Left-ventricular ejection fraction (LVEF)
Contrast-enhanced CT imaging to detect acute changes in LVEF compared to baseline.
Time frame: 6 weeks
Detection of cardiac fibrosis
Gadolinium Enhanced MR imaging to detect cardiac fibrosis compared to baseline
Time frame: 6 weeks
Tumour Response (metabolism)
FDG-PET imaging to detect tumour metabolism changes compared to baseline.
Time frame: 6 weeks
Tumour Response (perfusion)
DCE-CT imaging to detect changes in tumour perfusion compared to baseline
Time frame: 6 weeks
Acute Changes in Lung Ventilation
4D-CT imaging to detect changes in lung ventilation compared to baseline
Time frame: 6 weeks
Acute Changes in Lung Perfusion
DCE-CT imaging to detect changes in lung perfusion compared to baseline
Time frame: 6 weeks
Plan to share: No
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London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's