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REVIEW ARTICLE
Year : 2013  |  Volume : 9  |  Issue : 2  |  Page : 193-198

Cancer patients with cardiac pacemakers needing radiation treatment: A systematic review


1 Department of Radiation Oncology, Fortis Memorial Research Institute, Gurgaon, Haryana, India
2 Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India
3 Government Medical College, Haldwani, Uttarakhand, India

Date of Web Publication13-Jun-2013

Correspondence Address:
Anusheel Munshi
Department of Radiation Oncology, Fortis Memorial Research Institute, Gurgaon, Haryana-122002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.113348

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 > Abstract 

With improving average life expectancy of individuals in most countries, there has been increase in the incidence of cardiovascular diseases and cancers. Radiation oncologists therefore are likely to encounter an increasing number of cancer patients with in situ cardiac pacemaker devices needing radiation treatments. Pacemaker technology has advanced rapidly in recent years. As a result, the potential interactions of these devices with radiation therapy have changed since American Association of Physicists in Medicine (AAPM) issued guidelines in 1994. Current approaches to treatment in patients who have these devices vary among radiation oncology centers. Furthermore, the recommendations given by the devices' manufacturers differ considerably. Common knowledge about pacemaker in radiation oncology community is vital as radiation management needs to be tailored to individual patients in accordance to the information of available for the device. Some general practical guidelines can be gleaned from the literature. It is felt that more robust information is required using web based database sharing to develop total safe practice guidelines in such patients. This article reviews the information available to help create such guidelines and presents recommendations for treatment in this increasingly common clinical situation.

Keywords: Cancer, radiotherapy, pacemaker


How to cite this article:
Munshi A, Agarwal JP, Pandey KC. Cancer patients with cardiac pacemakers needing radiation treatment: A systematic review. J Can Res Ther 2013;9:193-8

How to cite this URL:
Munshi A, Agarwal JP, Pandey KC. Cancer patients with cardiac pacemakers needing radiation treatment: A systematic review. J Can Res Ther [serial online] 2013 [cited 2019 Dec 5];9:193-8. Available from: http://www.cancerjournal.net/text.asp?2013/9/2/193/113348


 > Introduction Top


In most regions of the world, cancer incidence is on a rise. [1] Also, the average life expectancy of individuals is improving in most countries. [2] Increasing life expectance in turn can increase the incidence of diseases related to elderly age and cardiovascular disease is one such important condition. [3] In view of this, radiation oncologists are likely to encounter an increasing number of patients with in situ cardiac pacemaker (PM) devices.

We collected all the data regarding the cancer patients treated with radiation and having in situ PM reported in literature from 1985 to 2011. The key words used for search included "Pacemaker", "Cardiac", "Radiotherapy", "irradiation or radiation" and "artificial pacing". The search was done in Pubmed, Medline and Embase databases. We also collected reports on experimental irradiation of pacemakers to assess their malfunction. No randomized trials related to this subject could be identified. In the end, our study included case series and isolated case reports.


 > Cardiac Pacemakers: What are they? Essentials for Radiation Oncologists Top


Permanent pacemakers provide electrical stimuli for cardiac contraction when intrinsic myocardial electrical activity is inappropriately slow or absent. The first implantation of permanent pacing started in the 1950s. [4] Since then, many advances in technology have resulted in a present modern pacemaker which is miniaturized, has increased longevity of pulse generators, including improvement in leads. [5] They are indicated for several clinical reasons usually symptomatic bradycardia (slow heart rate). Some patients are pacemaker dependent [6] (i.e., without continuous or nearly continuous pacemaker activation, the patient would suffer life-threatening symptoms). Other patients are pacemaker independent meaning that the patient's escape rhythm is enough to sustain an adequate blood pressure. These devices sense intrinsic cardiac electric potentials, and, if too infrequent or absent, they transmit impulses to the heart to stimulate myocardial contraction.

Types and function [7],[8]

There are several types of pacemakers. Classically, comprising of a pulse generator and pacing leads. A generator (or "can") is a hermetically (air tight) sealed canister housing the electronics and the battery. From the can, one or more leads are connected to the heart. The generator is usually implanted subcutaneously in the right or left infraclavicular region above the pectoral muscles, although several other locations are used for both cosmetic and technical reasons. There are both endocardial (inside the heart) and epicardial (outside the heart) leads. Endocardial leads are by far the most common and are placed via a transvenous approach without the need for surgery.

The internal circuitry of a pacemaker starts with DC-DC converters that multiply or divide the battery (usually Lithium) voltage to charge a capacitor. A sense amplifier that includes gain amplifiers and frequency filters monitors cardiac depolarization to control timing. A telemetry circuit with an internal antenna communicates with an external programmer. This programmer can interrogate the pacemaker and adjust its setting. Also on board the pacemaker are a voltage/current reference circuit and a measurement circuit for battery capacity, lead resistance and analog to digital conversion.

Pacemakers are divided into single chamber (one lead, either into the right atria or ventricle), dual chamber (two leads, usually to the right atria and right ventricle) and biventricular pacemakers. Biventricular pacemakers allow for the simultaneous stimulation of both the left and right ventricles. One lead is placed in the right ventricle and the other from the right atrium and into the coronary sinus, which traverses the lateral wall of the left ventricle. Many manufactures have a variety of pacemakers with optional defibrillator capabilities for patients that require elements of both devices.

Decoding the code system [8],[7]

Regardless of the type of pacemaker (single or dual chamber), a standard system to describe the programmed characteristics of the device is employed. The four letter code system begins with the letter of the chamber being paced (A=atria, V=ventricle, D=dual or both, O=none), the second letter for the chamber being sensed, the third for the chamber that is inhibited. A fourth optional letter "R" is added if the pacemaker is rate responsive. Responsive pacemakers increase or decrease firing rates based on a piezoelectric transducer that detects movement from either patient activity or respiration. This allows for a more natural increase in heart rate during the activities of daily living

Pulse generators can be set to fixed-rate (asynchronous) or demand (synchronous) modes. The asynchronous mode, impulses are produced at a set rate independent of intrinsic cardiac activity and carries a small but inherent danger of producing lethal dysrhythmias when dysregulated.


 > Interaction of Radiation with Pacemaker: Who is at Risk? Why is there a Risk? Top


The operation of the pacemakers can be disturbed by electromagnetic interferences. The usual electromagnetic sources which can be of significant disturbance to function of pacemakers include many sources like MRI, lancet, radio frequency and devices of the everyday life like the hotplates to induction, cell phones. The use of radiotherapy especially for sites in and around implanted pacemaker can cause malfunction or failure of the PM device either due to its ionizing effect or via electromagnetic interference or dysfunction. [6],[7],[8] These include breast, lung, head and neck, lymphomas, thyroid and esophageal cancers.

Ionizing radiation interferes with electrical circuits in permanent pacemakers. The complementary metal-oxide (CMOS) has silicon in combination with other very sensitive transistors and are in particular susceptible leading to permanent damage. [9] The reasons for the damage to the pacemaker are 1) Destruction of electrical components (most often with direct irradiation) 2) Effects on the random access memory (most often secondary to scatter radiation or electromagnetic irradiation. 3) Loading of the silicon dioxide insulator with excess of electron-hole pairs which may persist to accumulate a net positive charge on the insulator. [7],[10],[11],[12],[13],[14] The resultant formation of aberrant electrical pathways within the insulator leads to transient or permanent changes in the PM function. In a relevant study 18 multi programmable pacemakers were tested to establish any pattern by which these pacemakers are affected. Temporary change lasts for the duration of the irradiation only and is self-recoverable. More sustained change which are usually permanent require reprogramming of the pacemaker. In this case the pacemaker stops generating pulses and recovery may occur a long time after the end of the treatment which is mostly incomplete needing reprogramming or a replacement. [14]


 > Risk Assessment Top


Risk stratification is based on PM dependency, location of the PM with respect to the radiation beam and estimated cumulative dose to the PM. [13] The definition of pacemaker dependency (PD) has long been a source of controversy and confusion. Broadly, PD can be defined as the risk of serious injury or death from sudden pacemaker failure, an event more dangerous than progressive rate decrease. PM dependency is categorised into three classes. [11] Class 1 : Patients in whom abrupt cessation of pacing results in bradycardia related symptoms or signs that create an emergent or urgent clinical situation, or in whom there is a history of similar symptoms or signs in the absence of pacing. These require continuous cardiac monitoring during radiotherapy from an outside room and trained on call cardiac team to tackle emergency. Class 2 : Patients who are asymptomatic even when the intrinsic ventricular rate is less than 30 beats per minute. Class 3 : Patients whose intrinsic ventricular rate exceeds 30 beats per minute but who have never experienced an emergent or urgent clinical situation related to bradycardia. These are not pacemaker dependent.


 > In Vivo; Case Series and Case Reports in Literature Top


Till date, the largest clinical study with regards to radiotherapy treatment in patients with in situ PM has been done by Ferrara et al. [16] Forty-five irradiated patients, implanted with pacemakers or implantable cardioverter-defibrillators were prospectively investigated from 1999 to 2007. The authors carried out an analysis of radiation damage to pacemakers, depending on the geometric and dosimetric characteristics of the radiation beams. The electric and magnetic fields of linear accelerators (LINACs) were measured to evaluate any interference. No dysfunctions were observed in any pacemaker, nor were the substitution times negatively affected. They did not find problems with the devices due to the interaction with the electromagnetic fields. Dose-volume histograms showed an average maximum dose of 2.5 Gy for head and neck and 1.8 Gy for the thoracic region. Acute (3 cases) and late (2 cases) cardiac events were observed only in 5 patients who underwent chemoradiation treatment, but no pacemaker dysfunction was observed in any of the patients. The study confirmed the safety of carefully planned radiotherapy for patients implanted with pacemakers but suggested that chemoradiation represents a probable risk factor for cardiac toxicity. [Table 1] gives a summary of all the case series and reports in literature.
Table 1: Case reports and case series of radiation therapy with implanted cardiac PM

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 > In Vitro Studies Top


Many authors have considered an alternative approach of directly irradiating the pacemakers with photons or electrons. In 2002, Mouton, et al. [29] tested Ninety-six various pacemakers irradiated in water phantom to high dose levels by 18 MV photons. The failure was observed at a cumulative dose of only 15 cGy for one pacemaker, at <100 cGy for two pacemakers and at <200 cGy for nine. A maximum dose rate of only 20 cGy/ min was considered "safe". Thus, no pacemaker must ever be directly irradiated in a conventional radiotherapy setting because conventional daily dose rates is about 2 Gy/min at which 15% of the tested pacemakers had a clinically important failure.

These tests have been done in vitro and provide a reasonable estimate of the threshold tolerance dose of the packemaker [Table 2]. However studies such as these have two inherent errors and bias a) Varying makes of pacemaker lead to inhomegenity in comparison. b) Upgradation of pacemaker technology over the years. Wide variation in the threshold doses and unpredictable failure mechanisms of different commercially available PM models from various manufacturers further prohibits individual testing.
Table 2: Reports of in vitro irradiation of pacemakers with photons or electrons

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 > Guidelines in Literature Top


  1. In 1994, American Association of Physicists in Medicine (AAPM) issued guidelines for pacemaker irradiation after an extensive review by Marbach, et al. [13] Their specific recommendations include:

    1. Patients with implanted pacemaker should not be treated with a betatron.
    2. Pacemakers should not be in direct line of radiotherapy beam.
    3. The absorbed dose to be received by the pacemaker should be estimated before treatment.
    4. Pacemaker function should be checked if the total estimated dose to the pacemaker might exceed 2 Gy.
    5. Most of the studies till dated have dealt with linear accelerators, betatrons, and cobalt irradiators only. The interaction of pacemakers with other units should be evaluated on an individual basis and approached with caution.
  2. In 1997 Last et al. [12] reviewed the solid-state damage to pacemakers from ionizing radiation and gave recommendations as below:

    1. Discuss actively with cardiologist regarding pacemaker dependence.
    2. It is reasonable to assume a 2 Gy threshold for absorbed dose tolerance.
    3. If possible, a 3 cm margin should be kept from the radiation field edge.
    4. Consider TLD or diode measurement on day one of radiation therapy.
    5. Do high-level monitoring if dose >2 Gy or pacemaker-dependent patient.
    6. If cumulative dose >10 Gy, consider repositioning the pacemaker.
  3. Manufacturer's Specifications and Guidelines
In 2003, Guidant pacemaker's literature [35] stated that no level of cumulative radiation dose is "safe". Due to radiation damage of the on-board software of PM, bad memory locations can be detected and corrected up to a point and if the amount alteration is too great, the device will invoke its ROM-based operating mode ("Safety Mode"), which gives only basic pacing at a preset mode and rate. The Medtronic [36] lists specific, minor radiation damage as low as 5 Gy, and they recommend monitoring after each therapy session when this limit is reached. The possibly of replacement at the conclusion of the therapy course has been recommended. The St. Jude Medical [37] states that its pacemakers (Programalith III® , Phoenix® , Paragon® , Synchrony® , Trilogy® , Tempo® , Affinity® , Entity® , Integrity® and Identity® ) have been tested to 30 Gy cumulative dose without adverse effect. The Biotronik [38] states that functional disturbances occur at 20 Gy cumulative doses and less severe damage at 5 Gy. They indicate that the current consumption of the pacemaker may be an indirect assessment of radiation damage to circuit elements. If current consumption is >15%, then radiation damage can be assumed. High current consumption also puts a pacemaker with a low battery at risk of having its voltage supply decrease below the minimum and stop.

A decade ago, Last et al. reviewed old and new in-vitro and in-vivo studies of PM irradiation and suggested safe dose threshold of 10 Gy as clinically significant failure was rare below this dose. [8] Since then different manufacturers have recommended different dose values and safety precautions. [6],[7],[8],[9] In view of lack of uniform and firm guidelines, it is important for the radiation oncologist to take utmost safety precautions for all patients, identify high risk group and make services available from well equipped expert cardiac team (comprising of cardiologist and PM manufacturer personnel for monitoring the cardiac status, addressing inadvertent adverse situation and providing advanced life support) for these high risk patients.

Shortcomings in current literature

The respective tolerance of the pacemaker device, the lead and the electrode is not known. Intuitively, the body of the pacemaker, which houses most of the electrical circuitry, should be most susceptible to radiation induced damage. However, there is no definite evidence from literature with regard to difference in tolerance of thresholds of these components of the pacemaker. Firm clinical answers would require more patients, more mature follow up and perhaps an analysis of pacemakers removed or replaced after malfunction.

The exact dose of malfunction depends on the brand of PM according to material and circuits sensitivity. But variable in vitro testing show that manufacturer should probably test thresholds for individual PM and label safe doses for each before marketing. Also as few radiation oncology centers will see large number of pacemaker patients per year, a method to share data through the internet database would be most appropriate. A website can be generated where one could leave data on successful and unsuccessful irradiations including model and conditions of treatment, measurements of electromagnetic irradiation at isocentre on various models of accelerators and various miscellaneous notes and comments.

In view of the heterogeneity of the existing evidence, which essentially consists of case reports and small series, it is difficult to set a list of precautionary measures for the departmental personnel involved in direct patient care. Overall, similar to radiation protection issues; "As low as reasonably achievable (ALARA)" seems appropriate for implanted cardiac PM too.

 
 > References Top

1.http://www.mondofragilis.net/Portfolio/International-Agency-for-Research-on-Cancer/World-Cancer-Report-2008.   Back to cited text no. 1
    
2.Kalache A, Keller I. The greying world : A challenge for the twenty-first century. Sci Prog 2000;83 (Pt 1):33-54.  Back to cited text no. 2
    
3.Sanderson JE, Mayosi B, Yusuf S, Reddy S, Hu S, Chen Z, et al. Global burden of cardiovascular disease. Heart 2007;93:1175.  Back to cited text no. 3
    
4.Hori M. [History of cardiac pacing and pacemaker update]. Nihon Rinsho 1990;48:227-32.  Back to cited text no. 4
    
5.Pollak WM, Simmons JD, Interian A Jr, Castellanos A, Myerburg RJ, Mitrani RD. Pacemaker diagnostics : A critical appraisal of current technology. Pacing Clin Electrophysiol 2003;26:76-98.  Back to cited text no. 5
    
6.Lelakowski J, Majewski J, Bednarek J, Ma³ecka B, Zabek A. Pacemaker dependency after pacemaker implantation. Cardiol J 2007;14:83-6.  Back to cited text no. 6
    
7.2011. Available from : http://www.nlm.nih.gov/medlineplus/ency/article/007369.htm.   Back to cited text no. 7
    
8.2011. Available from : http://emedicine.medscape.com/article/780825-overview.   Back to cited text no. 8
    
9.Lewin AA, Serago CF, Schwade JG, Abitbol AA, Margolis SC. Radiation induced failures of complementary metal oxide semiconductor containing pacemakers : a0 potentially lethal complication. Int J Radiat Oncol Biol Phys 1984;10:1967-9.  Back to cited text no. 9
    
10.Munshi A, Wadasadawala T, Sharma PK, Sharma D, Budrukkar A, Jalali R, et al. Radiation therapy planning of a breast cancer patient with in situ pacemaker--challenges and lessons. Acta Oncol 2008;47:255-60.  Back to cited text no. 10
    
11.Solan AN, Solan MJ, Bednarz G, Goodkin MB. Treatment of patients with cardiac pacemakers and implantable cardioverter-defibrillators during radiotherapy. Int J Radiat Oncol Biol Phys 2004;59:897-904.  Back to cited text no. 11
    
12.Last A. Radiotherapy in patients with cardiac pacemakers. Br J Radiol 1998;71:4-10.  Back to cited text no. 12
    
13.Marbach JR, Sontag MR, Van Dyk J, Wolbarst AB. 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.  Back to cited text no. 13
    
14.Tondato F, Ng DW, Srivathsan K, Altemose GT, Halyard MY, Scott LR. Radiotherapy-induced pacemaker and implantable cardioverter defibrillator malfunction. Expert Rev Med Devices 2009;6:243-9.  Back to cited text no. 14
    
15.Souliman SK, Christie J. Pacemaker failure induced by radiotherapy. Pacing Clin Electrophysiol 1994;17:270-3.  Back to cited text no. 15
    
16.Croshaw R, Kim Y, Lappinen E, Julian T, Trombetta M. Avoiding mastectomy : A ccelerated partial breast irradiation for breast cancer patients with pacemakers or defibrillators. Ann Surg Oncol 2011;18:3500-5.  Back to cited text no. 16
    
17.Ferrara T, Baiotto B, Malinverni G, Caria N, Garibaldi E, Barboni G, et al. Irradiation of pacemakers and cardio-defibrillators in patients submitted to radiotherapy : A clinical experience. Tumori 2010;96:76-83.  Back to cited text no. 17
    
18.Wadasadawala T, Pandey A, Agarwal JP, Jalali R, Laskar SG, Chowdhary S, et al. Radiation therapy with implanted cardiac pacemaker devices : A clinical and dosimetric analysis of patients and proposed precautions. Clin Oncol (R Coll Radiol) 2011;23:79-85.  Back to cited text no. 18
    
19.Kikuchi D, Iizuka T, Hoteya S, Miyata Y, Mitani T, Ochiai Y, et al. [Safe and successful chemoradiotherapy for a patient with cardiac pacemaker and triple cancers]. Gan To Kagaku Ryoho 2009;36:1025-7.  Back to cited text no. 19
    
20.Zweng A, Schuster R, Hawlicek R, Weber HS. Life-threatening pacemaker dysfunction associated with therapeutic radiation : A case report. Angiology 2009;60:509-12.  Back to cited text no. 20
    
21.Oshiro Y, Sugahara S, Noma M, Sato M, Sakakibara Y, Sakae T, et al. Proton beam therapy interference with implanted cardiac pacemakers. Int J Radiat Oncol Biol Phys 2008;72:723-7.  Back to cited text no. 21
    
22.Kapa S, Fong L, Blackwell CR, Herman MG, Schomberg PJ, Hayes DL. Effects of scatter radiation on ICD and CRT function. Pacing Clin Electrophysiol 2008;31:727-32.  Back to cited text no. 22
    
23.Li DM, Xu B, Xu XN. [Radiotherapy of tumor patients implanted with permanent cardiac pacemaker: 4 cases report]. Ai Zheng 2004;23:722-3.  Back to cited text no. 23
    
24.Nibhanupudy JR, de Jesus MA, Fujita M, Goldson AL. Radiation dose monitoring in a breast cancer patient with a pacemaker : A case report. J Natl Med Assoc 2001;93:278-81.  Back to cited text no. 24
    
25.Brooks C, Mutter M. Pacemaker failure associated with therapeutic radiation. Am J Emerg Med 1988;6:591-3.  Back to cited text no. 25
    
26.Raitt MH, Stelzer KJ, Laramore GE, Bardy GH, Dolack GL, Poole JE, et al. Runaway pacemaker during high-energy neutron radiation therapy. Chest 1994;106:955-7.  Back to cited text no. 26
    
27.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;13:1466-70.  Back to cited text no. 27
    
28.Quertermous T, Megahy MS, Das Gupta DS, Griem ML. Pacemaker failure resulting from radiation damage. Radiology 1983;148:257-8.  Back to cited text no. 28
    
29.Mouton J, Haug R, Bridier A, Dodinot B, Eschwege F. Influence of high-energy photon beam irradiation on pacemaker operation. Phys Med Biol 2002;47:2879-93.  Back to cited text no. 29
    
30.Hurkmans CW, Scheepers E, Springorum BG, Uiterwaal H. Influence of radiotherapy on the latest generation of implantable cardioverter-defibrillators. Int J Radiat Oncol Biol Phys 2005;63:282-9.  Back to cited text no. 30
    
31.Hurkmans CW, Scheepers E, Springorum BG, Uiterwaal H. Influence of radiotherapy on the latest generation of pacemakers. Radiother Oncol 2005;76:93-8.  Back to cited text no. 31
    
32.Wilm M, Kronholz HL, Schütz J, Koch T. [The modification of programmable pacemakers by therapeutic irradiation]. Strahlenther Onkol 1994;170:225-31.  Back to cited text no. 32
    
33.Venselaar JL, Van Kerkoerle HL, Vet AJ. Radiation damage to pacemakers from radiotherapy. Pacing Clin Electrophysiol 1987;10:538-42.  Back to cited text no. 33
    
34.Venselaar JL. The effects of ionizing radiation on eight cardiac pacemakers and the influence of electromagnetic interference from two linear accelerators. Radiother Oncol 1985;3:81-7.  Back to cited text no. 34
    
35.Guidant Corp., The Impact of Therapeutic Radiation on Guidant Implantable Pacemakers (imps) and Implantable Cardioverter Defibrillators (icds). Cardiac Rhythm Management Technical Services, St. Paul, MN., 2/13/2003.  Back to cited text no. 35
    
36.Medtronic Inc., Radiation and ICDs. 1 pg, 7/9/2002 and Radiation and Pacemakers. 1 pg, 10/96, Technical Services, Redmond, WA.  Back to cited text no. 36
    
37.St. Jude Medical, Radiation. 1-3, 9/02 and Electromagnetic Interference. 1-6, no date, Cardiac Rhythm Management Division, Sylmar, CA.  Back to cited text no. 37
    
38.Biotronick, Produkt information 512, Radiation Exposure of Implanted Pacemakers. 1-2, Berlin, Germany, 5/18/2001; 2001. p. 1-2.w  Back to cited text no. 38
    



 
 
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  [Table 1], [Table 2]


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