Implantable Devices at Risk During During Cancer Radiotherapy

Pacemakers, implantable cardioverter-defibrillators most affected

Cancer patients with cardiovascular implantable electronic devices (CIEDs) who require radiotherapy may be at increased risk of a single-event upset malfunction when higher energy neutron-producing radiotherapy is used, a study now shows.

The retrospective analysis, one of the largest cohorts in which contemporary CIEDs were exposed to photon- and electron-based radiotherapy, demonstrated that more than 10 MV of neutron-producing radiotherapy resulted in a device compromise rate of 21%.

In 178 courses of non-neutron-producing radiotherapy, however, the device compromise rate was 0%, Jonathan D. Grant, MD, department of radiation oncology, University of Texas MD Anderson Cancer Center, Houston, and colleagues said in an online report in JAMA Oncology.

Single-event upsets also occurred during neutron-producing radiotherapy at a rate of 10% in pacemakers and 34% in implantable cardioverter-defibrillators per course, Grant said.

Based on these findings, the investigators recommend that non-neutron-producing radiotherapy be used whenever possible. In cases where higher radiotherapy energies are of clinical benefit, however, they emphasized that "error rates and outcomes that we report will aid clinicians in weighing the risks of using neutron-producing radiotherapy."

Grant noted the resilience of the contemporary CIEDs to radiotherapy. "The contemporary CIEDs in our series tolerated a consistent range of incident radiotherapy doses up to 5.4 Gy with no increase in malfunction risk," he said. "Given the associated expense and potential morbidity, it may be safe to decrease the number of relocations performed."

The resilience of the contemporary CIEDs to direct radiotherapy exposure is in keeping with ex vivo studies reporting malfunction thresholds of up to 150 and 30 Gy for directly incident 6- and 18-MV photons, respectively, said Grant.

Interestingly, among the neutron-producing radiotherapy group, body region was a significant predictor of malfunction, said Grant. Abdominal and/or pelvic radiotherapy was correlated with a higher risk of single-event upset when compared with sites in the head/neck and chest (hazard ratio 5.2, 95% CI 1.2-22.6; P=0.03). "The mechanism behind this finding is presently unclear and is the subject of ongoing investigation," said Grant.

CIED malfunction was characterized as single-event upset such as data loss, parameter resets, and unrecoverable resets. Delayed effects such as signal interference, pacing threshold changes, and premature battery depletion were also included.

Device malfunction was not correlated with incident CIED dose, and no delayed malfunctions were directly attributed to radiotherapy. Signal interference was uncommon and transient, said Grant.

"Basically, these events represent device compromise due to a change in the memory state of the circuitry," said Charles R. Thomas, Jr. MD, PhD, professor and chairman of the department of radiation medicine at Oregon Health and Science University (OHSU) in Portland, Ore., in an accompanying editorial. He also noted that the retrospective analysis did not involve real time or monitoring of cardiac rhythms.

"Hence," said Thomas, who is also chief of radiation oncology services at OHSU Healthcare, "there exists an opportunity to design trials that incorporate next-generation and commercially available electronic monitoring devices in this patient population ... to detect more subtle dysrhythmias, device sensor adjustments, and/or transient threshold alterations."

The study cohort included all patients with a functioning CIED who underwent radiotherapy between August 2005 and January 2014. Some 249 courses of photon- and electron-based radiotherapy were identified in 215 patients. In this group, there were 123 pacemakers (57%) and 92 implantable cardioverter-defibrillators (43%). In 71 courses (29%), substantial neutron production was generated.

Three-dimensional conformal radiotherapy was associated with a higher incidence of single-event upset than intensity-modulated radiotherapy (P=0.001), said Grant. When the cohort was limited to neutron-producing radiotherapy (P>0.99), this association disappeared, he added.

In 203 patients, external-beam photon-only therapy was used; both photon- and electron-based treatments were given in 22 plans. Ten patients were treated with GammaKnife. Therapeutic energies ranged from 6 to 16 MeV for electron-only therapies (n=14), with most of the treatments delivering 6- or 9-MeV energies.

Twenty-three patients received two separate courses of radiotherapy; four patients received three courses; and one patient received four courses. In 176 cases, dosimeter measurement was used to determine incident dose to the CIED, while treatment-planning software was used to determine this in 22 patients and reference data in 51.

Clinical symptoms developed in six patients with a CIED parameter reset, and three patients experienced hypotension and/or bradycardia. Two patients experiencedabnormal chest ticking (pacemaker syndrome) and one developed cardiac failure.

Single-event upsets in CIEDs caused by high-energy radiation were first described in 1998, noted Grant.

When high-energy photons (>10 MV) interact with material in a linear accelerator, neutrons are emitted throughout the treatment room. Thermal neutrons then interact with boron found in the metal oxide semiconductor components contained in contemporary CIEDs and disrupt electric currents.