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Proton Beam Therapy Interference With Implanted Cardiac Pacemakers
Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 3, pp. 723–727, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter
doi:10.1016/j.ijrobp.2008.01.062
CLINICAL INVESTIGATION
Heart
PROTON BEAM THERAPY INTERFERENCE WITH IMPLANTED CARDIAC PACEMAKERS YOSHIKO OSHIRO, M.D.,* SHINJI SUGAHARA, M.D.,* MIO NOMA, M.D.,y MASATO SATO, M.D.,y YUZURU SAKAKIBARA, M.D.,y TAKEJI SAKAE, PH.D.,z YASUTAKA HAYASHI, M.D.,* HIDETSUGU NAKAYAMA, M.D.,*z KOJI TSUBOI, M.D.,*z NOBUYOSHI FUKUMITSU, M.D.,*z AYAE KANEMOTO, M.D.,* TAKAYUKI HASHIMOTO, M.D.,x AND KOICHI TOKUUYE, M.D.*z Department of *Radiation Oncology and y Cardiovascular Surgery, z Proton Medical Research Center, University of Tsukuba, Ibaraki, Japan; and x Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function. Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33–77 gray equivalents (GyE) in dose fractions of 2.2–6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT. Results: The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course. Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT. Ó 2008 Elsevier Inc. Cardiac pacemaker, Proton beam therapy, Neutron.
INTRODUCTION
ineligible for surgical resection or conventional radiotherapy owing to limited liver or lung function and pacemaker implantation and were referred to PMRC for cancer therapy.
Recent increases in pacemaker use have resulted in a growing population of patients with both cancer and implanted cardiac pacemakers (1). During the past few decades, the number of pacemaker implants in Japan increased by 3–10% each year. It has been suggested that pacemaker malfunction can occur during treatment with conventional photon radiotherapy. Proton Medical Research Center (PMRC) of the University of Tsukuba has been engaged in proton beam therapy (PBT) since 2001. A modality proving excellent dose localization, PBT differs from conventional radiotherapy because the former is based on high-energy protons associated with very low levels of incidental neutrons. Uncertainties with regard to the potential effect of proton irradiation on pacemaker function prompted us to initiate a study to establish guidelines for management of this unique subset of patients. After performing a phantom study to ensure the safety of our patients, we investigated the effect of PBT on pacemaker function in 8 oncology patients. All 8 patients were considered
METHODS AND MATERIALS Phantom study Before initiating PBT in these patients, a phantom study was carried out to measure the extent of the effect of PBT on pacemakers (Fig. 1). Two acrylic phantoms, 25 25 12.5 cm in size and 1.16 g/mL density, (Unitek, Tsukuba, Japan), were placed on the treatment bed, and the lead of a pacemaker (Kappa KSR 703; Medtronic, Minneapolis, MN) was placed between the two phantoms. The generator of the pacemaker (TPS-451C; Aloka, Tokyo, Japan) was placed behind the phantom, which did not allow penetration of 250-MeV proton beams. A collimated 200-MeV proton beam of 10 cm was delivered through the phantom to the pacing lead, which was located at the center of a 10-cm s pread-out brag peak. A total dose of 35 gray (Gy) was delivered to the pacing lead. The lead was exposed to the atmosphere for the first 20 Gy to determine the effect of PBT on unshielded leads. For the remaining 15 Gy, the lead was
from the Ministry of Health, Labor and Welfare of the Japanese Government. Conflict of interest: none. Received Sept 12, 2007, and in revised form Jan 25, 2008. Accepted for publication Jan 28, 2008.
Reprint requests to: Yoshiko Oshiro, M.D., Tennodai 1-11, Tsukuba, Ibaraki, 305-8575, Japan. Tel: (+81) 0-29-8530604; Fax: (+81) 0-29-853-7102; E-mail: ooyoshiko@pmrc. tsukuba.ac.jp Supported in part by a Grant-in-Aid for Cancer Research 15-9 723
I. J. Radiation Oncology d Biology d Physics
724
Gantry
Pacemaker Phantom
Aperture
Fig. 1. Experimental scheme. A pacemaker lead was exposed to proton beams while the generator of a pacemaker was completely shielded. However, the generator received a small amount of scattered neutrons. placed in saline to simulate the in vivo environment. Pulse voltages and intervals generated by the pacemaker were measured during irradiation.
Patients We have treated 1,095 patients with PBT since Sept 2001. Eight patients had pacemakers implanted in the anterior chest wall or the supraclavicular fossa: 4 patients for sick-sinus syndrome, 3 for atrioventricular block, and 1 for bradycardia with atrial fibrillation. One patient depended on a pacemaker 40% of the time, whereas the remaining 7 patients were dependent more than 80% of the time. Models of pacemakers varied. There were 7 men and 1 woman, and median age was 79 years (range, 75–85 years). Seven patients had hepatocellular carcinoma and 1 had squamous cell lung cancer (Table 1).
Treatments All 8 patients received a total tumor dose of 33–77 gray equivalents (GyE) with a daily fraction dose of 2.2–6.6 GyE given 5 days a week. The proton energy used was 155–250 MeV, and the relative biologic effectiveness of the beam was calculated to be 1.1. All pulse generators were placed outside the treatment field. Before the first day of PBT, a cardiologist assessed each patient’s cardiac conditions and pacemaker status. All patients were monitored by means of an electrocardiogram (ECG) during PBT treatment. Pacemakers were checked weekly by manufacturers’ personnel. Clinical symptoms, ECGs, maximum cumulative proton dose to the pacing lead, neutron dose to the generator, median dose rate, and the distance between generators and the irradiation field were evaluated for each patient.
Volume 72, Number 3, 2008
cm on the portal image or X-ray films. The computed proton dose to the generator was zero in all cases, and the dose to the pacing lead was 0–69 GyE. The median proton dose rate was 2.45 GyE min1, ranging from 2.06–3.00 GyE min1. No clinical symptoms were observed in our patients during or after PBT. However, pacemaker malfunction occurred three times (2.4%) in two cases. These two cases are described next. Case 1. This patient (Patient 7) with HCC was dependent on pacemaker activity more than 99% of the time because of AV block. The planned dose was 66 GyE in 10 fractions, with a median dose rate of 2.42 GyE min1. The distance between the field and the generator was 30 cm, the farthest of all patients. The pacemaker (Affinity DR; St. Jude Medical, St. Paul, MN) was originally programmed to provide dualchamber pacing (DDD) at a rate of 60 beats/min and bipolar pulse configurations for the atrium and ventricle (Fig. 3a). Weekly evaluation of the pacemaker by the manufacturer’s personnel showed a programming error after the seventh fraction (46 GyE), resulting in reliance on a ‘‘safety backup program.’’ The backup program was set at 65 beats/min for single-chamber pacing (VVI) with a unipolar ventricular configuration (Fig. 3b). After this event, we recorded ECGs on this patient before and after every PBT treatment. Case 2. This patient (Patient 8) with squamous cell lung carcinoma was dependent on pacemaker activity 40% of the time for sick-sinus syndrome. This patient received 72.6 GyE in 22 fractions, with a median dose rate of 2.83 GyE min1. The distance between the field and the generator was 6 cm, the shortest for all patients. The pacemaker (Phillos SR; Biotronik, Berlin, Germany) was originally programmed to VVI pacing at a rate of 60 beats/min (Fig. 4a). Pacemaker malfunctions occurred twice. The first occurred after the seventh treatment (cumulative total dose of 23 GyE) and was characterized by slowing of the pacing rate from 60 to 54 beats/min (Fig. 4b). Re-initialization was found to be required according to weekly evaluation of the pacemaker after the eighth fraction (26 GyE), at which time the pacing rate was noted to be 54 beats/min (Fig. 4c). The second malfunction occurred after the last treatment, at which time the pacing rate increased from 60 to 63 beats/min (Fig. 4d). This pacemaker was equipped with three safety backup pacing systems (53, 63, and 70 beats/min) in addition to its baseline rate of 60 beats/min. Because the change in pacing mode was clinically negligible in both cases, the patients did not experience symptoms during pacemaker malfunction. Also, after re-initialization, it was noted that the pacemakers functioned normally.
RESULTS Phantom study Direct proton beam exposure to the pacing lead did not affect pulse voltage or pulse intervals. Neutron scatter did not affect the pacemaker generator. (Fig. 2). Case reviews Eight patients received a total of 127 PBT sessions (Table 2). The distance between the fields and the generator was 6–30
DISCUSSION The electromagnetic interference of mobile phones and security and kitchen gadgets with pacemakers is well known. Additionally, many electromagnetic sources in the medical environment can result in pacemaker dysfunction. However, knowledge about radiation interference with pacemakers is limited (2). Conventional photon radiotherapy has been reported to affect pacemaker function when doses of 0.5–40 Gy
725
Abbreviations: VVI = single-chamber pacing; VDD and DDD = dual-chamber pacing; Af = Atrial fibriration; SSS = Sick sinus syndrome; AV block = atrial ventricle block. * Segment: Liver was divided into 8 parts according to the Couinard classification (17).
VVI VVI VDD VVI VVI VVI DDD VVI Kappa KDR721 Kappa KSR700 Kappa KDR721 Discovery II VIRTUS PLUS II SR Solus-mini Affinity DR Philos SR Medtronic Medtronic Medtronic Guidant Intermedics Jude medical Jude medical Biotronik 2003 1984 2004 1995 1995 1989 2004 1994 >99% >99% 98% 90% 88% >99% >99% 40% 1 2 3 4 5 6 7 8
Male Male Male Male Male Male Male Female
78 80 76 81 85 66 79 75
liver (VIII) liver (II/III) liver (VIII) liver (VIII) liver (VIII) liver (VIII) liver (VIII) left upper lobe of the lung
66 42.9 77 66 36.3 66 66 72.6
10 19 35 10 11 10 10 22
Af SSS AV block SSS AV block SSS AV block SSS
Maker Year implanted Pacemaker dependency rate Reason for pacemaker Number of fractions Total dose (GyE) Tumor location (*segment) Age Sex Patient
Table 1. The list of patients
Model
Mode
Proton therapy interference with pacemakers d Y. OSHIRO et al.
Fig. 2. This figure shows pulse voltage and pulse interval according to the proton dose. Pulse voltage and pulse interval were stable over proton dose. Pulse voltage decreased to almost half after the lead was inserted to the saline at the proton dose of 20 Gy.
are used (3–11). Direct radiation exposure to a pacemaker should be avoided and the total dose delivered to a pacemaker should be less than 2 Gy (2, 12, 13). Mouton et al. (14) reported that pacemaker malfunction was not observed with dose rates lower than 0.2 Gy min1, and that the risk of pacemaker failure was high with doses in excess of 8 Gy min1. The effect of PBT on pacemaker function has not been described in the literature. The PBT differs from conventional radiotherapy in that a small amount of neutrons are released during treatment when the proton beam strikes nozzle of components. Tayama et al. (15) measured neutron doses outside the treatment field at PMRC and found that neutrons were homogeneously distributed in the area within 30 cm from the field. An absorbed dose of only 2 mSv/Gy was noted. In our phantom study, a proton dose of 35 Gy did not impact on pulse voltage or intervals, although the pacing lead was directly irradiated and the generator was located within 30 cm on the target isocenter. In our small series, minor pacemaker malfunctions occurred three times (2.4%) in two cases. Although the proton dose to the generator was computed to be 0 Gy in both cases, a small amount of neutron scatter may have been responsible for the pacemaker dysfunction that occurred. Raitt et al. (16) reported that severe pacemaker malfunction occurred with high-energy neutron therapy at a dose of only 0.9 Gy, suggesting that neutron beams can cause catastrophic pacemaker dysfunction. In conventional photon irradiation, a linear energy transfer value less than 0.6 keV/mm is considered a threshold for latch-up in a complementary metal-oxide semiconductor conductor. Modern multiprogrammable pacemakers using a complementary metal-oxide semiconductor are very sensitive to neutron irradiation, and the safety threshold is unknown (2). In our study, a small amount of scattered neutrons, calculated to 0.012 Sv (0.002 Sv 6) in Patient 1
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Volume 72, Number 3, 2008
Table 2. Treatment results Patient no. 1 2 3 4 5 6 7 8
Pacemaker malfunction
Field-to-generator distance (cm)
Presence of leads in the field
Dose rate (GyE/min)
Maximal lead wire dose (GyE)
None None None None None None Yes Yes
Not measured 17 10 20 10 16 30 6
No Yes Yes No Yes No No Yes
2.87 2.45 2.45 2.18 2.06 3.00 2.42 2.83
— 13 63 — 0 — — 6.6
and 0.006 Sv (0.002 Sv 3) in Patient 2, may have resulted in pacemaker malfunctions, although these doses were considerably smaller than doses reported in neutron irradiation (16). Pacemaker backup mechanisms were successful in preventing adverse events in our series. Pacemakers are usually equipped with several backup mechanisms to prevent them from suddenly stopping. However, a relatively high frequency of minor changes in pacemaker setup may result in significant damage to the pacemaker itself, with potentially life-threatening results. At present, we recommend PBT with cardiac monitoring only when PBT is deemed advantageous over other options, including photon radiotherapy. Additionally, under no circumstance should there be direct PBT exposure to the generator. To reduce neutron contamination
in the future, pencil beam scanning will be necessary, not only to reduce radiation effect on pacemaker function, but also to reduce radiation exposure to normal tissue structures, such as liver, lung, and bone marrow.
Fig. 3. (a) Pretreatment, normal DDD pacing when ventricular activation is synchronized with atrial activation, and the duration between P and QRS waves was stable at 2.5 seconds. (b) Posttreatment, the preset program was changed to a backup mode of VVI pacing in which ventricle and atrium were activated discretely. Durations between P and QRS were also altered.
Fig. 4. (a) Electrocardiogram (ECG) before the seventh treatment. The pacing rate was 60 beats/min, an initially programmed rate. (b) ECG after the seventh treatment. The pacing rate slowed down to 54 beats/min. (c) ECG after the eighth treatment. The pacing rate was still 54 beats/min, and re-initialization was required. (d) ECG after the 22nd treatment. The pacing rate gained to 63 beats/min.
CONCLUSIONS Minor malfunctions of implanted cardiac pacemakers occurred in 2 of 8 patients receiving relatively high-rate PBT. Electrocardiographic monitoring is recommended for all patients with cardiac pacemakers during PBT.
Proton therapy interference with pacemakers d Y. OSHIRO et al.
727
REFERENCES 1. Gregoratos G, Abrams J, Epstein AE, et al. ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices: Summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/NASPE Committee to Update the 1998 Pacemaker Guidelines). J Cardiovasc Electrophysiol 2002;13:1183–1199. 2. Sundar S, Symonds RP, Deehan C. Radiotherapy to patients with artificial cardiac pacemakers. Cancer Treat Rev 2005;31: 474–486. 3. Ngu SL, O’Meley P, Johnson N, et al. Pacemaker function during irradiation: in vivo and in vitro effect. Australas Radiol 1993;37:105–107. 4. Katzenberg CA, Marcus Fl, Heusinkveld RS, et al. Pacemaker failure due to radiation therapy. Pace 1982;5:156–159. 5. Pourhamidi AH. Radiation effect on implanted pacemakers. Chest 1983;84:499–500. 6. Quertermous T, Megahy MS, Das Gupta DS, et al. Pacemaker failure resulting from radiation damage. Radiology 1983;148: 257–258. 7. Lewin AA, Serago CF, Schwade JG, et al. Radiation induced failures of complementary metal oxide semiconductor containing pacemakers: A potentially lethal complication. Int J Radiat Oncol Biol Phys 1984;10:1967–1969. 8. Lee RW, Huang SK, Mechling E, et al. Runaway atrioventricular sequential pacemaker after radiation therapy. Am J Med 1986;81:883–886. 9. Brooks C, Mutter M. Pacemaker failure associated with therapeutic radiation. Am J Emerg Med 1988;6:591–593.
10. Muller-Runkel R, Orsolini G, Kalokhe UP. Monitoring the radiation dose to a multiprogrammable pacemaker during radical radiation therapy: A case report. Pacing Clin Electrophysiol 1990;13:1466–1470. 11. Solan AN, Solan MJ, Bednarz G, et al. Treatment of patients with cardiac pacemakers and implantable cardioverter-defibrillators during radiotherapy. Int J Radiat Oncol Biol Phys 2004; 59:897–904. 12. Marbach JR, Sontag MR, Van Dyk J, et al. Management of radiation oncology patients with implanted cardiac pacemakers: Report of AAPM Task Group No.34. American Association of Physicists in Medicine. Med Phys 1994;21:85–90. 13. Last A. Radiotherapy in patients with cardiac pacemakers. Br J Radiol 1998;71:4–10. 14. Mouton J, Haug R, Bridier A, et al. Influence of high-energy photon beam irradiation on pacemaker operation. Phys Med Biol 2002;47:2879–2893. 15. Tayama R, Fujita Y, Tadokoro M, et al. Measurement of neutron dose distribution for a passive scattering nozzle at the Proton Medical Research Center (PMRC). Nucl Instr Methods A 2006;564:532–536. 16. Raitt MH, Stelzer KJ, Laramore GE, et al. Runaway pacemaker during high-energy neutron radiation therapy. Chest 1994;106: 955–957. 17. Fischer L, Thorn M, Neumann JO, et al. The segments of the hepatic veins—Is there a spatial correlation to the Couinaud liver segments? Eur J Radiol 2005;53:245–255.
doi:10.1016/j.ijrobp.2008.01.062
CLINICAL INVESTIGATION
Heart
PROTON BEAM THERAPY INTERFERENCE WITH IMPLANTED CARDIAC PACEMAKERS YOSHIKO OSHIRO, M.D.,* SHINJI SUGAHARA, M.D.,* MIO NOMA, M.D.,y MASATO SATO, M.D.,y YUZURU SAKAKIBARA, M.D.,y TAKEJI SAKAE, PH.D.,z YASUTAKA HAYASHI, M.D.,* HIDETSUGU NAKAYAMA, M.D.,*z KOJI TSUBOI, M.D.,*z NOBUYOSHI FUKUMITSU, M.D.,*z AYAE KANEMOTO, M.D.,* TAKAYUKI HASHIMOTO, M.D.,x AND KOICHI TOKUUYE, M.D.*z Department of *Radiation Oncology and y Cardiovascular Surgery, z Proton Medical Research Center, University of Tsukuba, Ibaraki, Japan; and x Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function. Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33–77 gray equivalents (GyE) in dose fractions of 2.2–6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT. Results: The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course. Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT. Ó 2008 Elsevier Inc. Cardiac pacemaker, Proton beam therapy, Neutron.
INTRODUCTION
ineligible for surgical resection or conventional radiotherapy owing to limited liver or lung function and pacemaker implantation and were referred to PMRC for cancer therapy.
Recent increases in pacemaker use have resulted in a growing population of patients with both cancer and implanted cardiac pacemakers (1). During the past few decades, the number of pacemaker implants in Japan increased by 3–10% each year. It has been suggested that pacemaker malfunction can occur during treatment with conventional photon radiotherapy. Proton Medical Research Center (PMRC) of the University of Tsukuba has been engaged in proton beam therapy (PBT) since 2001. A modality proving excellent dose localization, PBT differs from conventional radiotherapy because the former is based on high-energy protons associated with very low levels of incidental neutrons. Uncertainties with regard to the potential effect of proton irradiation on pacemaker function prompted us to initiate a study to establish guidelines for management of this unique subset of patients. After performing a phantom study to ensure the safety of our patients, we investigated the effect of PBT on pacemaker function in 8 oncology patients. All 8 patients were considered
METHODS AND MATERIALS Phantom study Before initiating PBT in these patients, a phantom study was carried out to measure the extent of the effect of PBT on pacemakers (Fig. 1). Two acrylic phantoms, 25 25 12.5 cm in size and 1.16 g/mL density, (Unitek, Tsukuba, Japan), were placed on the treatment bed, and the lead of a pacemaker (Kappa KSR 703; Medtronic, Minneapolis, MN) was placed between the two phantoms. The generator of the pacemaker (TPS-451C; Aloka, Tokyo, Japan) was placed behind the phantom, which did not allow penetration of 250-MeV proton beams. A collimated 200-MeV proton beam of 10 cm was delivered through the phantom to the pacing lead, which was located at the center of a 10-cm s pread-out brag peak. A total dose of 35 gray (Gy) was delivered to the pacing lead. The lead was exposed to the atmosphere for the first 20 Gy to determine the effect of PBT on unshielded leads. For the remaining 15 Gy, the lead was
from the Ministry of Health, Labor and Welfare of the Japanese Government. Conflict of interest: none. Received Sept 12, 2007, and in revised form Jan 25, 2008. Accepted for publication Jan 28, 2008.
Reprint requests to: Yoshiko Oshiro, M.D., Tennodai 1-11, Tsukuba, Ibaraki, 305-8575, Japan. Tel: (+81) 0-29-8530604; Fax: (+81) 0-29-853-7102; E-mail: ooyoshiko@pmrc. tsukuba.ac.jp Supported in part by a Grant-in-Aid for Cancer Research 15-9 723
I. J. Radiation Oncology d Biology d Physics
724
Gantry
Pacemaker Phantom
Aperture
Fig. 1. Experimental scheme. A pacemaker lead was exposed to proton beams while the generator of a pacemaker was completely shielded. However, the generator received a small amount of scattered neutrons. placed in saline to simulate the in vivo environment. Pulse voltages and intervals generated by the pacemaker were measured during irradiation.
Patients We have treated 1,095 patients with PBT since Sept 2001. Eight patients had pacemakers implanted in the anterior chest wall or the supraclavicular fossa: 4 patients for sick-sinus syndrome, 3 for atrioventricular block, and 1 for bradycardia with atrial fibrillation. One patient depended on a pacemaker 40% of the time, whereas the remaining 7 patients were dependent more than 80% of the time. Models of pacemakers varied. There were 7 men and 1 woman, and median age was 79 years (range, 75–85 years). Seven patients had hepatocellular carcinoma and 1 had squamous cell lung cancer (Table 1).
Treatments All 8 patients received a total tumor dose of 33–77 gray equivalents (GyE) with a daily fraction dose of 2.2–6.6 GyE given 5 days a week. The proton energy used was 155–250 MeV, and the relative biologic effectiveness of the beam was calculated to be 1.1. All pulse generators were placed outside the treatment field. Before the first day of PBT, a cardiologist assessed each patient’s cardiac conditions and pacemaker status. All patients were monitored by means of an electrocardiogram (ECG) during PBT treatment. Pacemakers were checked weekly by manufacturers’ personnel. Clinical symptoms, ECGs, maximum cumulative proton dose to the pacing lead, neutron dose to the generator, median dose rate, and the distance between generators and the irradiation field were evaluated for each patient.
Volume 72, Number 3, 2008
cm on the portal image or X-ray films. The computed proton dose to the generator was zero in all cases, and the dose to the pacing lead was 0–69 GyE. The median proton dose rate was 2.45 GyE min1, ranging from 2.06–3.00 GyE min1. No clinical symptoms were observed in our patients during or after PBT. However, pacemaker malfunction occurred three times (2.4%) in two cases. These two cases are described next. Case 1. This patient (Patient 7) with HCC was dependent on pacemaker activity more than 99% of the time because of AV block. The planned dose was 66 GyE in 10 fractions, with a median dose rate of 2.42 GyE min1. The distance between the field and the generator was 30 cm, the farthest of all patients. The pacemaker (Affinity DR; St. Jude Medical, St. Paul, MN) was originally programmed to provide dualchamber pacing (DDD) at a rate of 60 beats/min and bipolar pulse configurations for the atrium and ventricle (Fig. 3a). Weekly evaluation of the pacemaker by the manufacturer’s personnel showed a programming error after the seventh fraction (46 GyE), resulting in reliance on a ‘‘safety backup program.’’ The backup program was set at 65 beats/min for single-chamber pacing (VVI) with a unipolar ventricular configuration (Fig. 3b). After this event, we recorded ECGs on this patient before and after every PBT treatment. Case 2. This patient (Patient 8) with squamous cell lung carcinoma was dependent on pacemaker activity 40% of the time for sick-sinus syndrome. This patient received 72.6 GyE in 22 fractions, with a median dose rate of 2.83 GyE min1. The distance between the field and the generator was 6 cm, the shortest for all patients. The pacemaker (Phillos SR; Biotronik, Berlin, Germany) was originally programmed to VVI pacing at a rate of 60 beats/min (Fig. 4a). Pacemaker malfunctions occurred twice. The first occurred after the seventh treatment (cumulative total dose of 23 GyE) and was characterized by slowing of the pacing rate from 60 to 54 beats/min (Fig. 4b). Re-initialization was found to be required according to weekly evaluation of the pacemaker after the eighth fraction (26 GyE), at which time the pacing rate was noted to be 54 beats/min (Fig. 4c). The second malfunction occurred after the last treatment, at which time the pacing rate increased from 60 to 63 beats/min (Fig. 4d). This pacemaker was equipped with three safety backup pacing systems (53, 63, and 70 beats/min) in addition to its baseline rate of 60 beats/min. Because the change in pacing mode was clinically negligible in both cases, the patients did not experience symptoms during pacemaker malfunction. Also, after re-initialization, it was noted that the pacemakers functioned normally.
RESULTS Phantom study Direct proton beam exposure to the pacing lead did not affect pulse voltage or pulse intervals. Neutron scatter did not affect the pacemaker generator. (Fig. 2). Case reviews Eight patients received a total of 127 PBT sessions (Table 2). The distance between the fields and the generator was 6–30
DISCUSSION The electromagnetic interference of mobile phones and security and kitchen gadgets with pacemakers is well known. Additionally, many electromagnetic sources in the medical environment can result in pacemaker dysfunction. However, knowledge about radiation interference with pacemakers is limited (2). Conventional photon radiotherapy has been reported to affect pacemaker function when doses of 0.5–40 Gy
725
Abbreviations: VVI = single-chamber pacing; VDD and DDD = dual-chamber pacing; Af = Atrial fibriration; SSS = Sick sinus syndrome; AV block = atrial ventricle block. * Segment: Liver was divided into 8 parts according to the Couinard classification (17).
VVI VVI VDD VVI VVI VVI DDD VVI Kappa KDR721 Kappa KSR700 Kappa KDR721 Discovery II VIRTUS PLUS II SR Solus-mini Affinity DR Philos SR Medtronic Medtronic Medtronic Guidant Intermedics Jude medical Jude medical Biotronik 2003 1984 2004 1995 1995 1989 2004 1994 >99% >99% 98% 90% 88% >99% >99% 40% 1 2 3 4 5 6 7 8
Male Male Male Male Male Male Male Female
78 80 76 81 85 66 79 75
liver (VIII) liver (II/III) liver (VIII) liver (VIII) liver (VIII) liver (VIII) liver (VIII) left upper lobe of the lung
66 42.9 77 66 36.3 66 66 72.6
10 19 35 10 11 10 10 22
Af SSS AV block SSS AV block SSS AV block SSS
Maker Year implanted Pacemaker dependency rate Reason for pacemaker Number of fractions Total dose (GyE) Tumor location (*segment) Age Sex Patient
Table 1. The list of patients
Model
Mode
Proton therapy interference with pacemakers d Y. OSHIRO et al.
Fig. 2. This figure shows pulse voltage and pulse interval according to the proton dose. Pulse voltage and pulse interval were stable over proton dose. Pulse voltage decreased to almost half after the lead was inserted to the saline at the proton dose of 20 Gy.
are used (3–11). Direct radiation exposure to a pacemaker should be avoided and the total dose delivered to a pacemaker should be less than 2 Gy (2, 12, 13). Mouton et al. (14) reported that pacemaker malfunction was not observed with dose rates lower than 0.2 Gy min1, and that the risk of pacemaker failure was high with doses in excess of 8 Gy min1. The effect of PBT on pacemaker function has not been described in the literature. The PBT differs from conventional radiotherapy in that a small amount of neutrons are released during treatment when the proton beam strikes nozzle of components. Tayama et al. (15) measured neutron doses outside the treatment field at PMRC and found that neutrons were homogeneously distributed in the area within 30 cm from the field. An absorbed dose of only 2 mSv/Gy was noted. In our phantom study, a proton dose of 35 Gy did not impact on pulse voltage or intervals, although the pacing lead was directly irradiated and the generator was located within 30 cm on the target isocenter. In our small series, minor pacemaker malfunctions occurred three times (2.4%) in two cases. Although the proton dose to the generator was computed to be 0 Gy in both cases, a small amount of neutron scatter may have been responsible for the pacemaker dysfunction that occurred. Raitt et al. (16) reported that severe pacemaker malfunction occurred with high-energy neutron therapy at a dose of only 0.9 Gy, suggesting that neutron beams can cause catastrophic pacemaker dysfunction. In conventional photon irradiation, a linear energy transfer value less than 0.6 keV/mm is considered a threshold for latch-up in a complementary metal-oxide semiconductor conductor. Modern multiprogrammable pacemakers using a complementary metal-oxide semiconductor are very sensitive to neutron irradiation, and the safety threshold is unknown (2). In our study, a small amount of scattered neutrons, calculated to 0.012 Sv (0.002 Sv 6) in Patient 1
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Volume 72, Number 3, 2008
Table 2. Treatment results Patient no. 1 2 3 4 5 6 7 8
Pacemaker malfunction
Field-to-generator distance (cm)
Presence of leads in the field
Dose rate (GyE/min)
Maximal lead wire dose (GyE)
None None None None None None Yes Yes
Not measured 17 10 20 10 16 30 6
No Yes Yes No Yes No No Yes
2.87 2.45 2.45 2.18 2.06 3.00 2.42 2.83
— 13 63 — 0 — — 6.6
and 0.006 Sv (0.002 Sv 3) in Patient 2, may have resulted in pacemaker malfunctions, although these doses were considerably smaller than doses reported in neutron irradiation (16). Pacemaker backup mechanisms were successful in preventing adverse events in our series. Pacemakers are usually equipped with several backup mechanisms to prevent them from suddenly stopping. However, a relatively high frequency of minor changes in pacemaker setup may result in significant damage to the pacemaker itself, with potentially life-threatening results. At present, we recommend PBT with cardiac monitoring only when PBT is deemed advantageous over other options, including photon radiotherapy. Additionally, under no circumstance should there be direct PBT exposure to the generator. To reduce neutron contamination
in the future, pencil beam scanning will be necessary, not only to reduce radiation effect on pacemaker function, but also to reduce radiation exposure to normal tissue structures, such as liver, lung, and bone marrow.
Fig. 3. (a) Pretreatment, normal DDD pacing when ventricular activation is synchronized with atrial activation, and the duration between P and QRS waves was stable at 2.5 seconds. (b) Posttreatment, the preset program was changed to a backup mode of VVI pacing in which ventricle and atrium were activated discretely. Durations between P and QRS were also altered.
Fig. 4. (a) Electrocardiogram (ECG) before the seventh treatment. The pacing rate was 60 beats/min, an initially programmed rate. (b) ECG after the seventh treatment. The pacing rate slowed down to 54 beats/min. (c) ECG after the eighth treatment. The pacing rate was still 54 beats/min, and re-initialization was required. (d) ECG after the 22nd treatment. The pacing rate gained to 63 beats/min.
CONCLUSIONS Minor malfunctions of implanted cardiac pacemakers occurred in 2 of 8 patients receiving relatively high-rate PBT. Electrocardiographic monitoring is recommended for all patients with cardiac pacemakers during PBT.
Proton therapy interference with pacemakers d Y. OSHIRO et al.
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