Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Lung Neoplasms

Cardiotoxicity

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

All Drugs and Chemicals

Immunomodulating Agents

Patients with locally advanced non-small cell lung cancer

Patients will be treated with definitive concurrent chemoradiation with curative intent as determined by their medical and radiation oncologists. We will consider timing of initiation and discontinuation, type, and cumulative dose of platinum based chemotherapy. We will also consider dose, duration, and type of immunotherapy. Radiation therapy will be delivered via proton or proton therapy. Our primary radiation therapy dose-volume exposures are whole heart volumetric dose. As secondary exposures, we will comprehensively define radiation therapy dose parameters to the right ventricle, entire left ventricle, left ventricle segments, coronary arteries, and mean heart dose.

Chemoradiation

Bonnie Ky, MD, MSCE

This observational cohort will evaluate the cardiovascular effects of chemoradiation used to treat locally advanced, non-small cell lung cancer. Patients will be enrolled prior to the start of therapy and followed during and for at least 2 years after therapy with echocardiograms, nuclear stress tests, blood sampling, and quality of life surveys.

Lung cancer is both the most common malignancy worldwide and the leading cause of cancer death in the US. While radiation therapy is highly effective for many solid tumors, thoracic radiation therapy carries a risk of cardiovascular morbidity and mortality that limits critical gains in cancer control and survival. The investigators will perform detailed cardiovascular phenotyping using biologic and imaging markers to define functional and physiologic perturbations that occur with radiation therapy. The study will provide insights into how cardiovascular risk factors and disease impact these biologic and functional changes. The investigators will also determine which radiotherapy dose-volume metrics are indicative of subclinical cardiotoxicity.

Plasma, Serum, and Buffy coat will be collected for planned biomarker analysis. Patients may optionally consent to have remaining blood banked for future analysis.

Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy

Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy: A Prospective Longitudinal Cohort

Participants may opt in to allowing data and/or banked samples to be used for future research and shared with other researchers. A detailed plan for sharing IPD will be finalized at a later date, and may depend in part on how many participants elect this option. Additional supporting information may be shared, including the study protocol and informed consent form.

All Cause Mortality assessed by National Death Index Search performed 5 years after the last patient is enrolled.

Cardiovascular Specific Mortality by National Death Index Search performed approximately 5 years after the final patient is enrolled.

Incidence of 5-Year MCE by EMR review and patient interview

Incidence of symptomatic adverse events as assessed by NCI's PRO-CTCAE

Change in echo-derived measures of LV peak systolic strain (longitudinal) from baseline

Change in echo-derived measures of ventricular-arterial coupling (Ea/Ees) from baseline

Change in PET/CT derived CFR from baseline

All-cause mortality assessed by electronic medical record (EMR) review

Cardiovascular specific mortality assessed by EMR review

Incidence of MCE assessed by EMR review and patient interview

Change in echo-derived LVEF from baseline

Change in echo-derived RV longitudinal strain from baseline

Change in echo-derived circumferential strain from baseline

Change in echo-derived measures of diastolic function from baseline

Change in echo-derived measures of valvular disease (degree of regurgitation or stenosis) from baseline

Change in 3D echocardiography derived LVEF from baseline

Change in 3D echocardiography derived measures of LV systolic strain from baseline

Change in 3D echocardiography derived measures of LV twist and torsion from baseline

Change in PET/CT derived measures of global and regional myocardial blood flow at rest from baseline

Change in PET/CT derived measures of global and regional myocardial blood flow at stress from baseline

Change in FACIT Fatigue score from baseline. Score ranges from 0-52. Higher scores indicated less fatigue.

Change in FACIT Dyspnea score from baseline. Score ranges from 0-30. Higher scores indicate more dyspnea.

Change in Godin Leisure Time Exercise Score from baseline. Higher scores indicate higher levels of physical activity.

Abramson Cancer Center at Penn Medicine

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

No Intervention: Subjects will be followed before, during and for up to 1 year after radiation with echocardiogram, blood draw, and symptoms and activity survey.

Assignment to proton vs photon by randomization on RadComp parent study.

Proton vs Photon Radiation

This is a companion study to the "Pragmatic Randomized Trial of Proton vs Photon Therapy for Patients with non-Metastatic Breast Cancer Receiving Comprehensive Nodal Radiation: A Radiotherapy Comparative Effectiveness (RadComp) Consortium Trial" (NCT02603341). The investigators will collect cardiovascular (CV) biomarkers and echocardiograms prior to, during, and for up to 1 year following radiation for a subset of patients enrolled on RadComp and to evaluate the impact of proton vs photon radiation therapy (RT) on CV function and structure.

The study population of the companion study will consist of newly enrolled RadComp trial participants. Patients on this ancillary will be consented prior to RadComp randomization to decrease the bias secondary to RT type and enhance internal validity. The study will define the early changes in biomarkers, imaging measures, and RT dose volume metrics and long-term (5-10 year) CV clinical outcomes using the RadComp parent study's infrastructure for clinical data collection and long-term follow-up. Blood samples, echocardiograms, and questionnaires are obtained at baseline (between end of chemotherapy and start of RT), immediately after the end of RT, and at 6 months and 12 months after the end of RT. An additional blood sample will be collected at 4 weeks after the start of RT. Clinical, demographic, and patient reported outcomes data are collected as part of the RadComp parent study. In addition to data collected by RadComp, we will collect a limited set of clinical data and two additional quality of life instruments for the companion study.

Plasma, Serum, and Buffy coat are collected.

Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study

Change in 3d echocardiography derived LVEF from baseline

Change in 3D echocardiography derived longitudinal and circumferential strain from baseline

Collected, defined, and adjudicated by the RadComp study team

Change in echocardiography derived LVEF from baseline

Change in echocardiography derived RV FAC from baseline

Change in 2D echocardiography derived LV global longitudinal strain and circumferential strain from baseline

Change from baseline in ventricular arterial coupling as defined by end systolic elastance divided by effective arterial elastance

Change in E/e' from baseline as measured by echocardiogram

Change in high-sensitivity TnT levels from baseline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy	NCT04305613	Cardiotoxicity Lung Cancer Sta... Lung Cancer Sta... Radiation Toxic...	Chemoradiation	18 Years -	Abramson Cancer Center at Penn Medicine
Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study	NCT04361240	Breast Cancer Cardiotoxicity	Proton vs Photo...	21 Years -	Abramson Cancer Center at Penn Medicine
Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study	NCT04361240	Breast Cancer Cardiotoxicity	Proton vs Photo...	21 Years -	Abramson Cancer Center at Penn Medicine
Cardiotoxicity in Locally Advanced Lung Cancer Patients Treated With Chemoradiation Therapy	NCT04305613	Cardiotoxicity Lung Cancer Sta... Lung Cancer Sta... Radiation Toxic...	Chemoradiation	18 Years -	Abramson Cancer Center at Penn Medicine
Cardiotoxicity in Breast Cancer Patients Treated With Proton or Photon Radiotherapy: A RadComp Companion Study	NCT04361240	Breast Cancer Cardiotoxicity	Proton vs Photo...	21 Years -	Abramson Cancer Center at Penn Medicine

Spots Global Cancer Trial Database for radiation therapy cardiotoxicity