|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3634-3636 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.288
Cardiac Toxicity of Mediastinal Radiotherapy: Which Are the Critical Structures?Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany
Department of Cardiology, University of Wuerzburg, Germany To the Editor: We read with great interest the recent article by Adams et al1 on late cardiovascular toxicity in patients treated with mediastinal radiotherapy for Hodgkin’s disease between 1970 and 1990, showing by echocardiography and ECG a high prevalence of significant valvular defects (42%), conduction defects (75%), and findings suggestive of restrictive cardiomyopathy (22%). All radiation treatments were performed as mantle technique with a median dose of 40 Gy, using equally weighted anterior and posterior 4- or 6-MV photon beams. The present study, as have previous reports,2,3 raises the question of which cardiac structures are causative of the above abnormalities and may benefit from protection in future radiotherapy concepts. Such protection can be achieved by limiting the irradiated volume4 or technical advances in delivery of radiotherapy.5 Based on our experience from an ongoing analysis of late cardiac toxicity in Hodgkin’s disease survivors treated between 1978 and 1985, we would like to comment on some details of former and current principles of radiotherapy planning and delivery that are of relevance for an association of radiation dose to particular cardiac structures and specific late effects. The authors state that the actual dose to particular cardiac structures in their patient cohort is unknown. We think that it is difficult but not impossible to reconstruct the radiation dose received by specific cardiac structures during mediastinal radiotherapy in the 1970s and 1980s. Previous investigators of cardiac radiation damage have either estimated the heart portion exposed to radiotherapy from two-dimensional simulation films and calculated the dose within this area at a defined depth3 or attempted three-dimensional dose reconstruction.6 As part of our ongoing study of cardiac toxicity, our group has reconstructed dose distributions of patients treated between 1978 and 1985 by matching simulation films of previously treated patients to digital radiographic reconstructions of computed tomography (CT) scans of current patients with comparable thoracic anatomy. Matching these two imaging modalities on the basis of heart contours using state-of-the-art radiotherapy treatment planning software permits calculation of radiation dose to previously contoured heart structures in the test patient. Additionally, the ability of cardiac magnetic resonance imaging (CMRI) to detect myocardial, valvular, and coronary disease,7 opens up the possibility to generate axial images of the heart anatomy and pathology in previously irradiated patients and reconstruct the radiotherapy technique directly in these magnetic resonance imaging (MRI) scans. Although the density information provided by CT is usually required for calculation of radiation dose distribution, use of an MRI study alone for radiotherapy planning is possible.8 Secondly, it should be noted that a large proportion of Hodgkin’s disease patients treated worldwide in the 1970s and 1980s were irradiated with less sophisticated techniques than employed at the Harvard Joint Cancer for Radiation Therapy during this period, as described by Adams et al. The anterior/posterior opposing-beam mantle technique has evolved from techniques using an anterior mediastinal field only, with or without boost dose to the posterior mediastinum, often using lower energies with resulting overdosage near the surface, corresponding to anterior portions of the heart. In our patient series, three-dimensional dose reconstruction of anterior mantle field technique using cobalt-60 (mean energy, 1.25 MV) typically resulted in relative maximum doses in the anterior heart region of 150% (without boost) and 120% (with boost). Related to a median prescribed mediastinal dose of 40 Gy, this corresponds to 60 Gy and 48 Gy, respectively, in the anterior cardiac structures, in particular the right atrium, the right ventricle, and the right coronary artery. In a recent review, radiation tolerance doses for several late effects including pericarditis, cardiomyopathy, coronary artery disease, and valvular disease have been estimated to be between 30 and 40 Gy.9 In fact, a high risk of complications (eg, severe constrictive pericarditis) has been observed with such anterior mantle field technique.10 Not only the treatment of the mediastinum through an anterior beam only but also the treatment with opposing photon beams of 4 to 6 MV energy, as described in the present report, can result in significant overdosage of the anterior heart structures, depending on the anterior-posterior diameter of the patient. Computer-calculated doses in the anterior cardiac region were described as being 2.5% to 6% higher than the manually calculated dose used for treatment prescription.11 Interestingly, the group of Adams et al identified an RSR' pattern in the right precordial lead as the most common conduction defect, occurring in 60% of patients, and concluded that the most anterior structures of the intracardiac conduction system were at most risk for fibrosis from mediastinal radiotherapy, a finding that may be explained by the presence of radiation dose peaks in this area. In summary, we would like to encourage attempts to link toxicity data to the anatomic radiation dose distribution within the heart and draw attention to a possible overdosage to anterior heart structures even with current mediastinal irradiation techniques. Authors' Disclosures of Potential Conflicts of Interest The following authors or their immediate family members have indicated a finanical interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Consultant: Christiane Angermann, Pfizer, AstraZeneca, Novartis. Honoraria: Christiane Angermann, AstraZeneca, Novartis, Pfizer, Aventis, Roche, Bayer. Research Funding: Christiane Angermann, Novartis, Pfizer, Marck, Sanofi. For a detailed description of these types of categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Delcaration and the Disclosure of Potential Conflicts of Interest section of Information for Contributors found in the front of every issue. REFERENCES
1. Adams MJ, Lipsitz SR, Colan SD, et al: Cardiovascular status in long-term survivors of Hodgkin's disease treated with chest radiotherapy. J Clin Oncol 22
: 3139
-3148, 2004
2. Knobel H, Loge JH, Lund MB, et al: Late medical complications and fatigue in Hodgkin's disease survivors. J Clin Oncol 19
: 3226
-3233, 2001 3. Glanzmann C, Kaufmann P, Jenni R, et al: Cardiac risk after mediastinal irradiation for Hodgkin's disease. Radiother Oncol 46 : 51 -62, 1998[CrossRef][Medline]
4. Engert A, Schiller P, Josting A, et al: Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: Results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol 21
: 3601
-3608, 2003 5. Stromberg JS, Sharpe MB, Kim LH, et al: Active breathing control (ABC) for Hodgkin's disease: Reduction in normal tissue irradiation with deep inspiration and implications for treatment. Int J Radiat Oncol Biol Phys 48 : 797 -806, 2000[CrossRef][Medline] 6. Rutqvist LE, Lax I, Fornander T, et al: Cardiovascular mortality in a randomized trial of adjuvant radiation therapy versus surgery alone in primary breast cancer. Int J Radiat Oncol Biol Phys 22 : 887 -896, 1992[Medline] 7. Constantine G, Shan K, Flamm SD, et al: Role of MRI in clinical cardiology. Lancet 363 : 2162 -2171, 2004[CrossRef][Medline] 8. Petersch B, Bogner J, Fransson A, et al: Effects of geometric distortion in 0.2 T MRI on radiotherapy treatment planning of prostate cancer. Radiother Oncol 71 : 55 -64, 2004[CrossRef][Medline] 9. Adams MJ, Hardenbergh PH, Constine LS, et al: Radiation-associated cardiovascular disease. Crit Rev Oncol Hematol 45 : 55 -75, 2003[Medline] 10. Coltart RS, Roberts JT, Thom CH, et al: Severe constrictive pericarditis after single 16 MeV anterior mantle irradiation for Hodgkin's disease. Lancet 1 : 488 -489, 1985[Medline] 11. Glanzmann C, Huguenin P, Lütolf UM, et al: Cardiac lesions after mediastinal irradiation for Hodgkin's disease. Radiother Oncol 30 : 43 -54, 1994[CrossRef][Medline]
Related Reply
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
