Characterizing Chemo-Radiotherapy Treatment-Related Cardiac Changes

PRIMARY OBJECTIVE:

I. To determine the 12-month cardiac event rate after radiation or chemo-radiation for the treatment of lung or esophageal cancer.

EXPLORATORY OBJECTIVES:

I. Define the spectrum of cardiac toxicity among chemoradiotherapy (CRT) patients at highest risk of cardiac toxicity.

II. Establish the timeline of cardiac toxicity development and identify early predictive findings of permanent damage.

III. Characterize the areas of the heart at highest risk for persistent cardiac damage.

IV. Identify a dose response threshold for radiotherapy (RT) damage in different areas of the heart.

V. Improve survival by alerting the cardiology team of the need for life-saving standard of care interventions.

VI. Describe medical interventions employed for the cardiac events identified in the study.

OUTLINE:

Patients receive cardiac monitor implants then undergo standard of care RT or CRT at the discretion of the treating physician. Patients also undergo blood sample collection at baseline, 4 weeks, 3, 9, and 12 months.

After completion of study treatment, patients are followed up at 4 weeks, 3, 9 and 12 months post RT.

• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo biospecimen collection
• Cardiac Event Monitor (Device): Receive cardiac monitor
• Chemoradiotherapy (Other), also known as Chemoradiation, CRT, CRTx, Radiochemotherapy, RCTx, RT-CT: Undergo CRT
• Radiation Therapy (Radiation), also known as Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation: Undergo RT

Primary outcomes

• Proportion of Participants With a Cardiac Event at 12 Months [Up to 12 months]: Assessed as any cardiac event after registration, including electrophysiological changes as defined by the continuous insertable cardiac monitor (ICM); congestive heart failure (CHF); myocardial infarction; pericarditis or myocarditis; cardiac ablation or cardiac pacemaker; cardiac stent placement or any coronary procedure for coronary damage; or any cardiac event as defined by the patients' medical records or autopsy if done.

Secondary outcomes

• Loco-regional Recurrence [Up to 12 months]: Loco-regional recurrence is defined as local recurrences of the cancer in the> same location where the disease was found on any diagnostic or> staging study.
• Disease-free Survival [Up to 12 months]: Disease- free survival is defined as the time from study registration until any disease recurrence or death.
• Distant Recurrence [Up to 12 months]: Distant recurrence is defined as metastatic cancer (cancer that has spread to organs or tissues far from the original cancer) that has either been biopsy> confirmed or clinically diagnosed as recurrent.
• Cardiac Event Free Survival [Up to 12 months]: Cardiac event free survival is defined as the time from registration to any cardiac> event or death.
• Cardiac Death [Up to 12 months]: Cardiac death is defined as the time from registration to death due to cardiac> reasons. Cardiac death would include documented congestive heart failure, myocardial infarction, arrhythmia*, heart block*, or any other cardiac cause documented in the medical records, death certificate, or autopsy as one of the major contributing causes of death. *Any lethal electrophysiologic change documented by before death would also be included.
• Overall Survival [Up to 12 months]: Overall survival is defined as the time from registration to death due to any cause.
• Incidence of Acute 3+ Adverse Events (AE) [Within the first 6 months from the date of enrollment]: Adverse Event incidence and severity will be measured by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
• Incidence of Late Grade 3+ Adverse Events [After the first 6 months from the date of enrollment]: Adverse Event incidence and severity will be measured by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
• Cause Specific Survival [Up to 12 months]: Cause specific survival is defined as the time from registration to death due to cancer.

Other outcomes

• Imaging Changes [Baseline up to 12 months]: Imaging changes in the heart substructures associated with occurrence of cardiac events will be an exploratory component of this trial. Changes will be described at each time point using frequency distributions.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age >= 18 years
* Planned standard of care curative thoracic RT or CRT with anticipated heart V40 > 20 cc (At least 20 cc of the heart should receive a dose of 40 gray \[Gy\] or higher)
* Able to follow-up at all specified standard of care time-points
* Patients can receive treatment as part of the standard of care or in a different study
* Receiving radiation treatment to an area close to the heart, for example gastroesophageal junction cancer, hilar lung cancer, or mainstem bronchus lung cancer
* Any type of systemic therapy or surgery before during or after radiation is acceptable
* Prior radiation to other areas is acceptable
* Planned radiation doses equal or higher than 40 Gy

Exclusion Criteria:

* Metastatic disease
* Recurrent disease
* Patient receiving radiation prescription doses lower than 40 Gy
* No prior radiation that included any part of the heart is acceptable
* No thoracic re-irradiation

Participant flow

Outcome results

• Proportion of Participants With a Cardiac Event at 12 Months (Primary), Number, proportion of participants: Observational (Cardiac Monitoring) 0.6818 (0.4513 to 0.8614)
• Loco-regional Recurrence (Secondary), Count of participants, Participants: Observational (Cardiac Monitoring) 3
• Disease-free Survival (Secondary), Number, proportion of participants: Observational (Cardiac Monitoring) 0.832 (0.672 to 1)
• Distant Recurrence (Secondary), Count of participants, Participants: Observational (Cardiac Monitoring) 1
• Cardiac Event Free Survival (Secondary), Number, proportion of participants: Observational (Cardiac Monitoring) .287 (.141 to .585)
• Cardiac Death (Secondary), Count of participants, Participants: Observational (Cardiac Monitoring) 0
• Overall Survival (Secondary), Number, proportion of participants: Observational (Cardiac Monitoring) 0.818 (0.672 to 0.996)
• Incidence of Acute 3+ Adverse Events (AE) (Secondary), Number, adverse events: Observational (Cardiac Monitoring) 3
• Incidence of Late Grade 3+ Adverse Events (Secondary), Count of participants, Participants: Observational (Cardiac Monitoring) 6
• Cause Specific Survival (Secondary), Count of participants, Participants: Observational (Cardiac Monitoring) 1
• Imaging Changes (Other pre specified)

Adverse events

Time frame: Up to 12 months

Serious adverse events by term

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2024-02-12)
• Informed Consent Form (PDF, 2022-10-21)

• Carlos E. Vargas, M.D., Principal investigator, Mayo Clinic