IntroductionCardiac pacemakers are among the top ten most frequently implanted medical devices in the United States of America. Radiation therapy (RT) can have adverse effects on the performance of cardiac pacemakers. As opposed to a standard subcutaneous pacemaker on the upper chest, we sometimes encounter a leadless pacemaker implanted in the right ventricle of the heart. A leadless pacemaker has the same function as a regular pacemaker but is much smaller in size and has no leads. A Micra AV dual-chamber pacemaker transcatheter leadless pacemaker is 95% smaller than typical pacemakers (Figure 1). The RT dose tolerance should be the same as that of a regular pacemaker2

Medtronic, Inc. (2016). Medical Procedures and EMI Warnings and Precautions for Pacemakers.

, 3Radiotherapy in patients with cardiac pacemakers., 4Marbach JR Sontag MR Van Dyk J Wolbarst A.B. Management of radiation oncology patients with implanted cardiac pacemakers., 5

Miften M, Mihailidis D, Kry SF, et al. (2019). Management of radiotherapy patients with implanted cardiac pacemakers and defibrillators: A Report of the AAPM TG-203. 46(12):e757-788.

, 6Hurkmans CW Knegjens JL Oei BS et al.Management of radiation oncology patients with a pacemaker or ICD: A new comprehensive practical guidelines in The Netherlands., 7Salerno F Gomellini S Caruso C. et al.Management of radiation therapy patients with cardiac defibrillator or pacemaker., 8Wadasadawala T Pandey A Agarwal JP et al.Radiation therapy with implanted cardiac pacemaker devices: a clinical and dosimetric analysis of patients and proposed precautions., 9Chan MF Song Y Dauer L et al.Estimating dose to implantable cardioverter-defibrillator outside the treatment fields using a skin QED diode, OSLD, and TLD dosimeters.. Based on the published guidelines, if the patient undergoes RT and the average dose rate at the device is > 1 cGy/min, the pacemaker should be programmed into asynchronous pacing mode, the permissible cumulative dose should be less than 500 cGy (the authors follow the institutional limit of 200 cGy), and the beam energy should be 2

Medtronic, Inc. (2016). Medical Procedures and EMI Warnings and Precautions for Pacemakers.

, 3Radiotherapy in patients with cardiac pacemakers., 4Marbach JR Sontag MR Van Dyk J Wolbarst A.B. Management of radiation oncology patients with implanted cardiac pacemakers., 5

Miften M, Mihailidis D, Kry SF, et al. (2019). Management of radiotherapy patients with implanted cardiac pacemakers and defibrillators: A Report of the AAPM TG-203. 46(12):e757-788.

, 6Hurkmans CW Knegjens JL Oei BS et al.Management of radiation oncology patients with a pacemaker or ICD: A new comprehensive practical guidelines in The Netherlands., 7Salerno F Gomellini S Caruso C. et al.Management of radiation therapy patients with cardiac defibrillator or pacemaker., 8Wadasadawala T Pandey A Agarwal JP et al.Radiation therapy with implanted cardiac pacemaker devices: a clinical and dosimetric analysis of patients and proposed precautions., 9Chan MF Song Y Dauer L et al.Estimating dose to implantable cardioverter-defibrillator outside the treatment fields using a skin QED diode, OSLD, and TLD dosimeters.. A leadless pacemaker is sometimes considered a favorable alternative for patients with tumors of the upper chest/lower neck but even then it can be too close to the treatment fields. As such, the management of a leadless pacemaker in RT poses its unique challenges, in that it is not easily further relocated, and in-vivo dosimetry is not possible.

FIGURE 1Left: A leadless pacemaker relative size to a penny; Right: A leadless pacemaker implanted directly into the right ventricle. Reprint with permission of Medtronic, Inc.

Currently there are limited reports with regard to implanted leadless pacemakers in RT. For example, there was one case report published in Europace[10]Martinez-Sande JL Garcia-Seara J Rodriguez-Manero M. Radiotherapy in a leadless pacemaker. of a patient with a mediastinal mass who underwent RT with a leadless pacemaker partially in the field; this case documented no remarkable dysfunctions to the leadless pacemaker which received a mean dose of 243 cGy and maximum point dose of 1159 cGy. In this study, we report a case of RT to a patient with left breast cancer whose standard subcutaneous pacemaker was changed to a leadless pacemaker (Micra, Medtronic, Minneapolis, MN) after RT simulation but before RT started.Case PresentationThe patient is a 69-year-old female with a cardiac pacemaker; she is not pacing dependent. The patient presented with a stage IIA (cT2N0) triple negative left breast invasive ductal carcinoma status post lumpectomy and sentinel node biopsy. Three[3]Radiotherapy in patients with cardiac pacemakers. months prior to the treatment of her breast cancer, she had received concurrent chemoradiotherapy for a locally advanced unresectable pancreatic head adenocarcinoma at our institution. The pancreas RT dose was 4500 cGy in 25 fractions with a simultaneously integrated boost of 7500 cGy to the gross tumor. The abdominal RT was considered to have marginal overlap with her breast RT. The original pacemaker, implanted subcutaneously on her chest, was estimated to have received a cumulative dose of 14 cGy from the pancreas RT based on in-vivo dosimetry. For the left breast RT, following the “Fast-Forward” protocol[11]Brunt AM Havilan JS Wheatley DA et al.Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial., the radiation oncologist prescribed 2600 cGy in 5 fractions to the whole breast followed by 1040 cGy boost in 2 fractions to the lumpectomy cavity. The patient was simulated in the supine position utilizing deep inspiration breath-hold (DIBH) technique. The Medtronic cardiac pacemaker (model A2DR01) was visible in the planning CT images located in the left superior thorax (Figure 2) and contoured. It was positioned approximately 3 cm superior to the current lumpectomy contour. Due to the pacemaker's proximity to the lumpectomy site, the whole breast could not be adequately treated without exceeding the institutional cumulative pacemaker limit of 200 cGy (including the previous 14 cGy from pancreatic RT). Closing the superior field border in the initial treatment planning did not help decrease the pacemaker exposure. The case was presented to the institutional Breast Chart Rounds. After considering alternative options such as intensity-modulated radiotherapy (IMRT) and partial breast irradiation (PBI), it was decided that the best approach would be to relocate the pacemaker further away from the breast treatment site. The patient's cardiologist, at a different institution, was then consulted. Four[4]Marbach JR Sontag MR Van Dyk J Wolbarst A.B. Management of radiation oncology patients with implanted cardiac pacemakers. workdays before the scheduled start date of breast RT, the patient had her subcutaneous pacemaker removed and replaced with a leadless Micra AV pacemaker (Medtronic, MN). She stayed in the hospital overnight and was discharged the next day.

FIGURE 2Initial planning CT image showing the original pacemaker location relative to the left breast lumpectomy site. Pink: Lumpectomy contour.

The day after the cardiology procedure, the procedure report was obtained from the cardiologist's office; radiological images were not obtained due to the procedure being performed in a different hospital. Based on the reading of the cardiology procedure report, it was presumed that the leadless pacemaker would not be in proximity to the breast fields. Treatment planning therefore continued without re-simulation but CBCT verification was recommended before the start of treatment.

In order to verify the actual location of the pacemaker, a CBCT was acquired prior to delivery of the first fraction of treatment. CBCT confirmed no anatomical changes in the treatment site due to the original pacemaker explantation. The CBCT was saved and registered to the treatment planning CT in the Treatment Planning System (TPS), so that the leadless pacemaker on CBCT could be blended into the treatment plan. The planned 200 cGy isodose line was evaluated on the CBCT (Figure 3).

FIGURE 3CBCT image blended in the treatment planning system with a display with 200 cGy isodose color-wash: A 0.58 cm distance was measured between the leadless pacemaker and 200 cGy isodose line.

As can be seen from Figure 3, this treatment plan gave little room for setup errors as the 200 cGy isodose line was only measured approximately 0.6 cm (0.58 cm in Figure 3) from the pacemaker edge. The calculated dose to the pacemaker, without considering setup uncertainty, would be 165 cGy. Additionally, even though the multileaf collimators (MLCs) were blocking the pacemaker, the pacemaker was within the jaws of the initial fields thus allowing for leakage dose, potentially further increasing the dose to the pacemaker. The physician was alerted to these concerns and decided not to proceed with the treatment as planned. The treatment was re-planned to further reduce the potential dose to the leadless pacemaker.The pacemaker was contoured on CBCT and this contour was copied to the planning CT so that the physician could create new fields with more tangential posterior field edges by choosing new gantry angles, collimator angles, and jaw positions, to keep the pacemaker well outside of the field without dose degradation at the treatment site. The revision plan was generated and the maximum pacemaker dose as planned was calculated to be 102 cGy. Subsequent CBCT verification was done again on the first treatment day of treatment using the revised treatment plan. On CBCT, the pacemaker was measured to be approximately 1.1 cm from the 200 cGy isodose line and 0.5 cm from the field edge, as shown in Figure 4. These distances were considered to have met the safe margin, based on the anecdotally observed typical setup error of

FIGURE 4CBCT image blended in the treatment planning system with a display with 200 cGy isodose color-wash in the revised plan: The leadless pacemaker is about 1.15 cm to 200 cGy dose and 0.54 cm to the field edges.

Based on the location of the leadless pacemaker on this CBCT, the cumulative pacemaker dose was estimated to be 101cGy for the entire course of breast RT treatment which was in alignment with the calculated dose in the revised plan. Note that for treatment planning we are making the reasonable assumption that the Anisotropic Analytical Algorithm (AAA) algorithm in the TPS is accurate for out-of-field doses at this relatively short distance from the field edge. The authors are aware that in a TPS calculated doses beyond a few centimeters outside the treatment field edge are less accurate. AAPM TG-158 Report is a good reference in cases where the pacemaker is far from the field edge[12]Kry SF Bednarz B Howell RM et al.AAPM TG 158: Measurement and calculation of doses outside the treated volume from external-beam radiation therapy..CBCT was performed before Fraction 1 and Fraction 2 to verify the pacemaker location (though not used for patient positioning); subsequent fractions used 2D KV images to confirm the position of the leadless pacemaker. Based on an estimate from quality assurance data, CBCT and KV imaging added no more than 20 cGy total dose. The maximum inter-fractional position variation for the pacemaker was found to be 1.0 cm, dominantly in the cranial-caudal direction, and the estimated cumulative dose, considering inter-fraction setup errors, deviated from the plan estimate by no more than 5 cGy. Electrocardiogram (EKG) was performed during the first fraction of treatment. The breast RT completed successfully without dysfunctions noticed in the pacemaker. Patient had her follow-up visit six[6]Hurkmans CW Knegjens JL Oei BS et al.Management of radiation oncology patients with a pacemaker or ICD: A new comprehensive practical guidelines in The Netherlands. weeks after the breast RT, and reported good recovery and noted no issues with cardiac functions. Figure 5 shows the timeline of the patient in the entire RT process from the simulation to completion.

FIGURE 5Timeline of the entire RT process

DiscussionThere have been widely adopted guidelines for management of cardiac implanted devices by the British Journal of Radiology[3]Radiotherapy in patients with cardiac pacemakers., the American Association of Physicists in Medicine[4]Marbach JR Sontag MR Van Dyk J Wolbarst A.B. Management of radiation oncology patients with implanted cardiac pacemakers.,[5]

Miften M, Mihailidis D, Kry SF, et al. (2019). Management of radiotherapy patients with implanted cardiac pacemakers and defibrillators: A Report of the AAPM TG-203. 46(12):e757-788.

as well as the Dutch Society of Radiotherapy and Oncology[6]Hurkmans CW Knegjens JL Oei BS et al.Management of radiation oncology patients with a pacemaker or ICD: A new comprehensive practical guidelines in The Netherlands.. This case report will not revisit the details of such guidelines. Instead, this report shares the experience at the authors’ institution of a single case that presented unique challengers associated with a leadless pacemaker: location verification and inability to perform in-vivo dosimetry.

Ideally the patient should have been re-simulated after the pacemaker was replaced, but in order to prevent a delay in start of RT we used the original simulation for treatment planning.

Additionally, since the leadless pacemaker sat deep inside the heart, it was impossible to obtain conventional in-vivo dosimetry, which is typically done by placing a thermoluminescence dosimeter (TLD) or an optically-stimulated luminescence dosimeter (OSLD), on the skin surface above the subcutaneous pacemaker. Instead, we obtained verification images prior to start of each treatment to verify the location of the leadless pacemaker and to calculate dose exposure. In the case reported here CBCT was obtained at set up and prior to the first fraction of treatment to verify the leadless pacemaker location and calculate dose exposure. This technique should be considered for future cases presenting with similar planning challenges.