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HancockSLDonaldsonSSHoppeRTCardiac disease following treatment of Hodgkin's disease in children and adolescentsJ Clin Oncol19931171208158315419HancockSLDonaldsonSSHoppeRTCardiac disease following treatment of Hodgkin's disease in children and adolescentsJ Clin Oncol19931171208158315419, HancockSLDonaldsonSSHoppeRTCardiac disease following treatment of Hodgkin's disease in children and adolescentsJ Clin Oncol19931171208158315419
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IkaheimoMJEarly cardiac changes related to radiation therapyAm J Cardiol19855615943610.1016/0002-9149(85)90409-64072928IkaheimoMJEarly cardiac changes related to radiation therapyAm J Cardiol19855615943610.1016/0002-9149(85)90409-64072928, IkaheimoMJEarly cardiac changes related to radiation therapyAm J Cardiol19855615943610.1016/0002-9149(85)90409-64072928
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HostHBrennhovdIOLoebMPostoperative radiotherapy in breast cancer--long-term results from the Oslo studyInt J Radiat Oncol Biol Phys19861257273210.1016/0360-3016(86)90029-53519550HostHBrennhovdIOLoebMPostoperative radiotherapy in breast cancer--long-term results from the Oslo studyInt J Radiat Oncol Biol Phys19861257273210.1016/0360-3016(86)90029-53519550, HostHBrennhovdIOLoebMPostoperative radiotherapy in breast cancer--long-term results from the Oslo studyInt J Radiat Oncol Biol Phys19861257273210.1016/0360-3016(86)90029-53519550
Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature. Background knowledge, this is the first report of the successful treat- Anaplastic thyroid carcinoma (ATC) is a rare, aggressive ment of cardiac metastases from from ATCs, and of malignancy with a median survival of 6 months. Distant mural metastases encasing the leads of a pacemaker. metastases - usually to lungs and bone - present early in thecourseofdisease [1].ATC is also oneofthe few Case cancers known to metastasize to the heart [2]. The patient is an 80 year old male with a past medical Secondary cardiac tumors are usually reported at history of atrial fibrillation with sinus block with dual autopsy, and can involve various anatomic structures of chamber pacemaker placed in November 2006, and a the heart. While cardiac metastases can be treated with complicated oncologic history including breast cancer in external beam radiation, cardiac toxicity remains dose- the 1970s treated with left-sided mastectomy and axil- limiting and must be taken into consideration during lary lymph node dissection; prostate cancer treated with radiation treatment planning for patients with poor car- intensity modulated radiation therapy (IMRT) in 2001; diac function and pacemaker dependence. mucosal melanoma with metastases to small bowel trea- We report the case of a patient with ATC who pre- ted with small bowel resection in 2005; and multiple sented with intraventricular metastases encasing the skin cancers. He was treated with a total thyroidectomy electrical leads of his pacemaker. After a course of pal- for anaplastic thyroid carcinoma in March 2008, fol- liative radiation therapy to his right atrium and ventri- lowed by post-operative cisplatin-based chemo-radiation cle, the patient survived to demonstrate radiographic therapy to the surgical bed and the draining lymph response to treatment. nodes. Asubsequentleftlung nodulewas treatedwith As cardiac metastases are increasing in incidence, we thoracotomy and wedge resection in December 2008, detail the radiation methods used to treat these intracar- with documented metastatic anaplastic thyroid carci- diac metastases, including specific precautions taken for noma on pathology. He also received one cycle of the pacemaker leads within the field of radiation. To our Abraxane and Bevacizumab in February 2009. The patient had been asymptomatic and in his usual state of health until July 2009 when he presented with a * Correspondence: dasguptat@radonc.ucsf.edu; MRoach@radonc.ucsf.edu 2 month history of decreased exercise tolerance and From the Department of Radiation Oncology, 1600 Divisadero Street, Suite H1031, San Francisco, California - 94102-1708, USA © 2011 Dasgupta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Dasgupta et al. Radiation Oncology 2011, 6:16 Page 2 of 7 http://www.ro-journal.com/content/6/1/16 orthostatic hypotension. Workup revealed a loss of atrial reprogramming of the device. Transcutaneous pacer was function, leaving the patient dependent on his pace- available during treatment should failure of the primary maker. An outpatient echocardiogram was concerning pacing device occur. Echocardiograms during radiation for “intracavitary irregular densities” in the right ventri- treatment showed that the intracardiac mass had not cle and right atrium. CT Chest with contrast revealed a increased in size. The patient required platelet transfu- 5.1 × 4.8 cm right atrial mass, with a broad base of sions approximately every 48 hours, and his platelet attachment at the right atrial posterior wall and exten- count held steadily around 18 to 20. Given his leukope- sion into both the inferior and superior vena cava. nia and sepsis, Abraxane was withheld after two courses. There was a notable displacement of pacemaker leads. After discharge, the patient participated in regular The right ventricle also demonstrated an irregular lobu- activities of daily living, including work-related meet- lated 6.8 × 2.5 cm mass attached to the ventricular sep- ings and exercise on the treadmill, but experienced tum. Retrospective evaluation of a prior PET-CT from persistent dyspnea on exertion. His pacemaker contin- June 2009 confirmed increased FDG uptake within the ued to demonstrate full capture without evidence of right atrium and right ventricle. dysfunction. In mid-July 2009, the patient was admitted to University In late August 2009, less than one month after com- of California San Francisco Moffitt Hospital for cardiac pletion of treatment, a PET-CT showed decreased FDG telemetry and management of this intracardiac mass. uptake right atrium (maximum SUV decreased from Admission labs showed thrombocytopenia with platelets 27.9 to 7.8) and stable FDG uptake within the right ven- ranging between 20 and 35. The differential diagnosis for tricle (Figure 2). There was some questionable uptake in right heart masses included metastases from anaplastic the interventricular septum, representing normal physio- thyroid carcinoma or melanoma, a new primary cardiac logic uptake or residual disease. Unfortunately, multiple malignancy, or a thrombus. pulmonary and chest wall metastases were subsequently A Fibrinogen level was within normal limits, and detected. hematology smears were negative for schistocytes. The patient completed one additional course of pallia- A bone marrow biopsy demonstrated a normocellular tive radiation therapy to a symptomatic left chest wall marrow for the patient’s age with mixed trilineage metastasis. He died in his home two months after com- hematopoesis and no evidence of lymphoma or throm- pletion of radiation therapy. bus. A trial of dexamethasone for suspected idiopathic thrombocytic purpura (ITP) did not impact the Conclusions thrombocytopenia. The differential diagnosis for the I. Secondary cardiac tumors are increasing in incidence, thrombocytopenia therefore remained a consumptive have various methods of spread and can affect any coagulopathy secondary to tumor, versus tumor- anatomic region of the heart associated immune thrombocytopenia. There have been several reports of cardiac metastases in After careful consideration at a multi-institutional the the literature [3,4]. Intracardiac metastases are tumor board, it was decided to treat these intracardiac reported from several different primary cancers, includ- metastases with radiation therapy. A pre-treatment elec- ing melanoma, bladder[4], sarcoma[5], lung, lymphoma, trophysiologic interrogation showed intermittent loss of breast carcinoma[6] and cervix [7]. Cardiac metastases capture by the pacemaker, most likely secondary to from primary anaplastic thyroid carcinoma are rare - an growth of the intracardiac mass. Therefore, a new pace- autopsy series has reported the rate as 0 to 2% [2]. maker with epicardial leads was emergently placed. Dur- Different routes of cancer spread have been reported, ing this procedure, biopsy of the intracardiac mass was and include hematogenous, lymphatic, and direct exten- performed, confirming metastatic anaplastic thyroid sion to the heart or thoracic duct [2,8]. Retrograde lym- carcinoma. phatic spread is predominant. The majority of lymphatic Radiation therapy to the right atrium and part of the ducts of the heart are located on the pericardial surface, right ventricle was initiated at 2.5 Gy per fraction for 15 where they coalesce adjacent to the aortic root; obstruc- fractions to a total dose of 37.5 Gy, with an intended tion of these channels leading to malignant pericardial maximum dose in the tumor areas just exceeding 40 Gy effusions [8]. The coronary arteries are the primary con- (see below) (Figure 1). Paclitaxel (50 mg/m ) was admi- duits of hematogenous spread. As metastatic cancer nistered concurrently on days 1 and 8ofradiation cells are filtered in the hepatic and pulmonary circula- treatment. tion, metastases are unlikely to reach cardiac tissue During the course of his radiation treatment, the pace- without metastatic disease in other organs [8]. maker demonstrated full capture. A single episode of Metastatic lesions may involve any anatomic region of ventricular undersensing with pacing stimuli during the heart, including most commonly the epicardium and T-waves was successfully addressed by the pericardium. Metastases within the cardiac chambers Dasgupta et al. Radiation Oncology 2011, 6:16 Page 3 of 7 http://www.ro-journal.com/content/6/1/16 Figure 1 Radiation treatment plan for patient with right atrial and ventricular metastases from anaplastic thyroid carcinoma. The PTV is delineated in red and received 37.50 Gy in 15 fractions, prescribed to the 87% isodose line. The median left ventricle (purple) and lateral left ventricle (beige) were delineated as avoidance structures in this IMRT treatment plan. The 1875 cGy (18.7 Gy) isodose line is shown in light blue; the 3500 cGy (35 Gy) isodose line, in yellow; the 3750 cGy (37.5 Gy) isodose line, in green; and the 4100 cGy (41 Gy) isodose line, in pink. arerare[6,9,10]. In primaryanaplasticthyroid carci- dose 6300-7400 rads delivered with 4 fields in the noma, cardiac metastases have been reported in the 1960’s. The patient remained asymptomatic for myocardium and pericardium, as well as within the ven- 8 months, and autopsy identified no residual cardiac tricles [2]. tumor[11]. Cases of leukemic infiltration of the myocar- dium presenting with arrhythmia [12], and interventri- II. Secondary cardiac tumors have been successfully cular septum metastases with malignant pleural effusion treated with external beam radiation responding to radiation have also been reported [13]. In Various cardiac tumors have been reported to respond a case of cardiac metastases from cervical carcinoma, to radiation. These include a primary cardiac sarcoma one patient with right ventricular and intraventricular involving right ventricular outflow track treated with a septum metastases was treated with chemoradiation Dasgupta et al. Radiation Oncology 2011, 6:16 Page 4 of 7 http://www.ro-journal.com/content/6/1/16 Figure 2 PET Response to treatment of an intracardiac metastases in the R ventricle and atrium. The top panel demonstrates a PET-CT scan of the hypermetabolic tumor mass prior to treatment on June 8 2009; the lower panel shows the tumor mass with notably decreased FDG uptake after treatment on August 30 2009. Dasgupta et al. Radiation Oncology 2011, 6:16 Page 5 of 7 http://www.ro-journal.com/content/6/1/16 (2/60 Gy with concurrent 5-fluorouracil and cisplatin) portals [24]), late toxicity is typically manifested as early and survived 7 months after presentation[10]. A recent or aggravated coronary artery disease [19,25-32]. How- report also demonstrated response of intraventricular ever, modern radiation methods have reduced inci- metastases from small cell lung cancer to chemotherapy dences of both acute and late pericardial toxicity [9]. and radiation (carboplatin and etoposide followed by The patient in this case report experienced no acute IMRT to 60 Gy to the lung mass, mediastinal LNs and toxicity secondary to radiation. cardiac metastases). Two months after treatment, fol- low-up PET CT showed no residual uptake in the R IV. The radiation of cardiac metastases encasing ventricle or mediastinal LNs, but persistent uptake in pacemaker leads has not been previously reported the lungs [14]. Until 1978, pacemakers based on bipolar technology From these case studies, no consensus on the dose were commonly used, and capable of withstanding required to control a secondary cardiac tumor can be cumulative radiation doses of up to 300 Gy without dys- established. In radiosensitive tumors like lymphoma, function. However, the metal oxide semiconductors of doses of even 20 Gy may be sufficient. However, more modern pacemakers render them more sensitive to radioresistant tumors may require higher doses like radiation[33]. There are only nine reported cases of 45 Gy with apossible additionalboostof10to15Gy radiation-related pacemaker malfunction in the litera- for adequate control[3,15]. ture since 1983[33], with widely varying doses of radia- tion observed to cause pacemaker dysfunction[34,35]. In III. Cardiac toxicity is dose-limiting in the treatment of one study, 6% of devices showed dysfunction at doses cardiac metastases with external beam radiation below 2 Gy [35]. In another study, most devices toler- The dose tolerance of the pericardium is limiting[10], as ated a cumulative dose of more than 90 Gy before fail- the most common manifestation of radiation-induced ing, and only of nineteen studied devices failed with a heart disease (RIHD) is late-onset, chronic pericardial cumulative dose of 20 Gy [34]. Either direct or indirect disease[9]. However, any other anatomic region of the damage to the circuit (if the pacemaker is out of the heart can manifest cardiac damage secondary to radia- treatment field) by the electromagnetic field is the pro- tion, including electrical conduction system, coronary posed mechanism of damage. Therefore, while there is arteries, cardiac valves, myocardium and endocardium no consensus for a safe threshold of radiation for the [9,16]. Therefore, while the dose tolerance of the whole pacemaker within a treatment field, the modern pace- heart - 60 Gy if 25% of the heart is irradiated, and maker seems relatively resistant to radiation-related mal- 45 Gy if 65% of the heart volume is irradiated [17] - is function[34]. For our case subject, the cumulative mean dose to the usually taken into consideration, the different anatomic subsites must be considered. Risk of RIHD increases pacemaker was 0.2615 Gy with a maximum dose with doses > 40 Gy over 4 weeks for pericardial disease, 0.37 Gy. TLDs (thermoluminescent dosimeters) placed > 35-60 Gy for myocardial disease, > 30 Gy for valvular during the first fraction showed the effective dose to the disease, and > 30 Gy for coronary artery disease (espe- superior aspect of the pacemaker was (0.862 +/- cially in younger patients, with concomitant chemother- 0.104 Gy). The treatment plan was modified to ensure apy), though doses as low as 5 Gy have been associated that the cumulative dose to the device itself was less with increased risk of coronary artery disease[9,17]. than 0.50 Gy (0.461 Gy +/- 0.41 Gy). Because of the the- Beam energy, dose per fraction [18,19], concurrent che- oretical possibility that treatment response of the tumor motherapy - especially with anthracyclines[16] - affect encasing the pacemaker leads could result in a loss of cardiac toxicity from radiation. Most patients experien- electrical capture, the pacemaker was interrogated cing severe complications had 60% or more of their car- before and upon completion of every treatment. The diac silhouette irradiated, and risk of RIHD ranged from irradiation was carried out under continuous EKG mon- 6.6 to 29%. Preclinical trials suggest that cardiac gating itoring via transcutaneous pads which could also be [20] may reduce the incidence of RIHD. used for external pacing in case of the primary pacer RIHD is additionally divided into early and late toxi- failure or loss of primary capture. city. Early toxicity, presenting within 2 to 6 months, is most frequently pericarditis [21-23]. Radiation induced V. Radiation therapy can successfully palliate cardiac valvular disease manifests within ten to fifteen years of metastases while preserving quality of life irradiation and management is similar to other types of We decided to treat this patient with IMRT to limit the valvular disease[9]. In younger patients who have cardiac dose and result in less cardiac toxicity. The received mediastinal irradiation for either Hodgkin’s patient was treated in a supine position immobilized lymphoma or breast cancer (even if the heart waspurpo- with a wing board. A CT simulation with 4D respiratory sefully blocked or omitted from the treatment gating in 8 phases of respiration was acquired in both Dasgupta et al. Radiation Oncology 2011, 6:16 Page 6 of 7 http://www.ro-journal.com/content/6/1/16 free-breathing and breath hold positions, with 1.55 mm and left ventricle. This treatment was well-tolerated by slice reconstruction and no contrast. The Gross Tumor the patient, with preservation of quality of life. Volume (GTV) was defined as the right atrial and right In their review of secondary cardiac tumors, Cham ventricular tumor. An Internal Tumor Volume (ITV) et al. suggest that “cardiac metastases should be strongly (with an additional 1 to 1.5 cm cardiac margin) was suspected in the cancer patient with sudden onset of generated from the Maxiumum Intensity Projection unexplained tachycardia, arrhythmia, or congestive heart (MIP) using the CT simulation data from all 8 phases of failure”[36].Inthe agingUSpopulationwhere theuse respiration, taking into account cardiac motion of the of permanent pacemakers is increasing[37], cancer tumor. A Planning Target Volume (PTV) was defined as patients with pacemakers will only become more com- the ITV with an additional 5 mm margin in all dimen- mon. We recommend evaluation for cardiac metastases sions. In the free-breathing CT scan, which was used for in patients with disseminated disease who experience the final treatment planning, the lateral left ventricle symptoms of unexplained tachyarrhythmias or other and medial left ventricle (including the interventricular cardiac abnormalities. Proper cardiac evaluation may be septum) were contoured as avoidance structures. The warranted in these high-risk patients. Traditional onco- patient was treated with an IMRT plan 2.5 Gy per frac- logic staging techniques are generally not adequate for tion to 87% isodose line delivered in 15 fractions with proper evaluation. For example, the naturally high FDG 8 coplanar beams and 6 mV photons. The actual maxi- uptake of the cardiac muscle on a staging PET/CT scan mum dose to the tumor from all beams was 43.1 Gy may obscure cardiac metastases. As demonstrated by (Figure 1). The patient had previously received radiation our case subject, cardiac metastases can be effectively to the mediastinum, and his prior treatment plan was palliated with radiation therapy to meaningful doses dearchived and reconstructed to avoid overlap of radia- with limited toxicity using modern techniques. Each tion fields and minimize the dose to the lungs. Dosi- case should be individually evaluated for palliative treat- metric paramters are outlined in Table 1. ment giving full consideration to the patient’sand After completing treatment, the patient did not family’s goals of care. experience any significant acute toxicities from the treatment. He remained exceptionally active until his Consent death. Written informed consent was obtained from the patient for publication of this case report and any accompany- VI. Case Summary and Recommendations ing images. A copy of the written consent is available We report a successful PET-proven response to IMRT for review by the Editor-in-Chief of this journal. of a secondary cardiac tumor, which encased the leads of a dual-chamber pacemaker in a pacer-dependent List of Abbreviations patient. The treatment plan was designed to prevent The following abbreviations have been used in this manuscript: 5FU: 5- overlap with the patient’s prior mediastinal radiation fluorouracil; ATC: anaplastic thyroid carcinoma; AED: automated external defibrillator; FDG: fluorodeoxy glucose; GTV: gross tumor volume; IMRT: fields, and also to minimize toxicity to the whole heart intensity modulated radiation therapy; ITP: idiopathic thrombocytic purpura; ITV: integrated target volume; PET-CT: positron emission tomography computed tomography; PTV: planning target volume; RIHD: radiation Table 1 Dosimetric parameters of radiation treamtment induced heart disease; TLD: thermoluminscent dosimetry; V20: percentage of plan tissue receiving ≥ 20 Gy; V37.5: percentage of tissue receiving ≥ 37.5 Gy; V25: percentage of tissue receiving ≥ 25 Gy. Structure Parameter Percentage of tissue receiving threshold dose Authors’ contributions R lung V20 9.7% TD, IJB and MR III were the radiation oncologists involved in caring for the patient discussed in this the case report. They designed and delivered the L lung V20 1.95% radiation treatment plan described above. All authors read and approved GTV V37.5 95.1% the final manuscript. PTV V37.5 69.77% Competing interests Lateral Left V37.5 0.01% The authors declare that they have no competing interests. Ventricle Lateral Left V25 6.14% Received: 10 October 2010 Accepted: 14 February 2011 Ventricle Published: 14 February 2011 Medial Left V37.5 0.95% Ventricle References Medial Left V25 45.7% 1. Kondo T, Ezzat S, Asa SL: Pathogenetic mechanisms in thyroid follicular- Ventricle cell neoplasia. Nat Rev Cancer 2006, 6(4):292-306. 2. 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Radiation Oncology – Springer Journals
Published: Feb 14, 2011
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