Impact of Respiratory Maneuvers on Cardiac Volume Within Left-Breast Radiation Portals
Background Late cardiac morbidity and mortality have been reported among left-breast cancer survivors treated with radiation therapy. Radiation-induced cardiotoxicity is affected by the volume of myocardium included in the radiation portals. We hypothesize that simple respiratory maneuvers may alter the position of the heart relative to the portals without altering the radiation dose delivered to the breast.
Methods and Results Fourteen healthy female adult volunteers underwent cardiac MRI to determine the cardiac volume included in the typical left-breast radiation field during respiratory maneuvers. Cardiac volume within the radiation portals was assessed from a transverse stack of 14 1-cm-thick contiguous slices covering the entire heart, obtained during breath holding at end-tidal volume (baseline), deep inspiration, and forced expiration. Thirteen subjects (92%) had inclusion of a portion of the heart within the radiation portals at end-tidal volume (median, 20.9 cm3; range, 1.3 to 88.4 cm3). In these subjects, inspiration decreased the cardiac volume included within the radiation portals (median change: −10.7 cm3 [−40.2%], P<.001 versus end-tidal volume), whereas expiration increased the cardiac volume included (median change: 4.0 cm3 [21.5%]; P<.001 versus end-tidal volume).
Conclusions Inclusion of a portion of the heart in the left-breast radiation field is common. The use of simple inspiratory maneuvers significantly decreases cardiac volume within the radiation portals. Such an approach during delivery of radiation therapy may allow for preservation of radiation dosage to the breast while reducing cardiac involvement and subsequent mortality.
Late cardiac morbidity and mortality have been reported among left-breast cancer survivors treated with older techniques of radiation therapy.1–8 Long-term follow-up studies of breast cancer patients have found increased cardiovascular deaths.1–8 In contrast, tangent fields to the right breast are not associated with increased risk of cardiotoxicity.1–8 The long-term effects of modern techniques of breast radiation therapy on cardiac function have not been established. Radiation factors that influence the extent of cardiotoxicity include total radiation dose, volume of the radiation field, configuration of the field, beam energy, and daily dose fraction size.9,10
The position of the heart within the chest cavity in a supine individual is determined by chest size, cardiac size, and phase of the respiratory cycle. Respiratory maneuvers such as inspiration pull the diaphragm and heart inferiorly while expanding the chest cavity, thereby increasing the distance between breast tissue and the heart. Given that radiation-induced cardiotoxicity relates to cardiac volume included in the radiation portals,9 simple respiratory maneuvers that alter the position of the heart relative to these portals offer the potential to reduce radiation delivered to the heart without altering the dose delivered to the breast. We hypothesized that deep inspiration would minimize the volume of heart included in the left-breast radiation field. To the best of our knowledge, such an approach has not been studied previously.
Fourteen healthy women volunteers (age, 23 to 47 years; weight, 95 to 185 lb) in sinus rhythm and without contraindication to MRI were studied.
MRI-visible markers (0.2% copper sulfate solution) were positioned on the chest at the beginning of the study to delineate the typical radiation portals for left-breast radiation therapy. The medial entrance of the radiation portals was at the midline. We modified the MRI scanning table with a flat-top table surface to reproduce the radiation therapy patient treatment setup position. For 8 of 14 subjects, a radiation therapy breast cast immobilization device was used to hold the subject’s arms above her head, precisely replicating the radiation therapy treatment position. The other 6 subjects were scanned with their arms at their sides. Respiratory maneuvers were explained to the subjects, who practiced the maneuvers before entering the magnetic field; these were sustained breath holding at end-tidal volume, full inspiration, and forced expiration. Total breath-hold duration for each maneuver was ≈16 seconds.
With the subjects in a supine position, MR was performed in a 1.5-T Gyroscan NT (Philips Medical Systems) with a 20-cm circular surface coil (C1) as a radiofrequency receiver. MR images were acquired with the use of an ECG-gated turbo-field echo sequence (total acquisition time=500 ms, field-of-view=300 mm, 64×256 matrix, repetition time=7.8 ms, echo time=3.4 ms, flip angle=15°). MRI-compatible ECG leads were placed on the patient’s anterior chest.
Thoracic scout images in the coronal, transverse, and sagittal planes were obtained to confirm visualization of the markers and location of the heart with respect to other thoracic structures. A transverse (axial) stack of 14 1-cm-thick contiguous slices, covering the entire heart, were obtained during each of the three respiratory maneuvers. Position of the radiation portals with respect to their projection on the transverse stack was delineated by the MRI markers. The entire setup and imaging portion of the protocol took less than 1 hour.
Cardiac volume included within the radiation field for each of the respiratory maneuvers was determined by use of a multislice summation (modified Simpson’s rule) technique. Area of the heart within the radiation portals was manually traced in each slice by use of standard system software, and cardiac volume within the radiation field (50% isodose line) was calculated for each of the three respiratory positions: ETid, Insp, and Exp.
Inspiratory changes (Insp Δ) and expiratory changes (Exp Δ) in cardiac volume from baseline ETid were calculated (Equations 1, and 2): Percentage inspiratory change (% Insp Δ) and percentage forced expiratory change (% Exp Δ) from ETid were calculated with the use of Equations 3, and 4, respectively: AP diameter from the posterior aspect of the sternum to the anterior spine was measured in all patients at the transverse level corresponding to the four-chamber view of the heart.
All data are presented as median (range). Comparisons among respiratory maneuvers were performed with use of the Wilcoxon paired test. All tests were two-tailed, and a value of P<.05 was considered significant. The 95% CI used the exact binomial calculation.
Thirteen (92%; 95% CI, 66% to 100%) of the 14 subjects had inclusion of a portion of the heart within the simulated left-breast radiation portals (median, 20.9 cm3; range, 1.3 to 88.4 cm3) at ETid. Respiratory maneuvers were performed in each subject who had cardiac inclusion within the radiation portals at ETid. Fig 1⇓ shows images from a representative subject at ETid and at deep inspiration. In the 13 subjects, inspiration decreased cardiac volume within the radiation portals (−10.7 cm3; P<.001 versus ETid), whereas expiration significantly increased cardiac volume (4.0 cm3; P<.001 versus ETid). The change in cardiac volume from ETid with respiratory maneuvers for each subject is shown in Fig 2⇓. Similarly, inspiration also decreased the percentage of cardiac volume within the radiation portals (−40.2%; P<.001 versus ETid), and expiration increased the percentage of cardiac volume (21.5%; P<.001 versus ETid).
For the 13 women with cardiac inclusion within the radiation portals, end-tidal chest AP diameter (median, 8.4 cm; range, 6.6 to 9.7 cm) increased with inspiration (1.3 cm; 0.6 to 2.0 cm; P<.001 versus end-tidal) and decreased with expiration (−0.5 cm; −0.1 to −1.3 cm; P<.001 versus end-tidal).
We found that a portion of the heart is commonly included in the left-breast radiation therapy field. In subjects with cardiac inclusion, inspiration increased the AP chest diameter and resulted in a decrease in cardiac volume included in the left-breast radiation portals. The converse was true for forced expiration. Because geometric alterations in cardiac position may result from various thoracic orientations, we sought to replicate the radiation therapy treatment position with a flat-top table surface, a radiation therapy breast cast immobilization device, and overhead arm position in most subjects. Gagliardi et al11 demonstrated that arm position affects the position of radiation therapy tattoos and therefore the target volume that is irradiated. The absolute magnitude of cardiac volume within left-breast radiation portals with different respiratory maneuvers may be affected by arm position differences between MRI scanning and radiation therapy treatment position; however, our finding that deep inspiration decreases cardiac volume in all subjects was maintained regardless of arm position.
Our finding that cardiac involvement within the radiation field is common is consistent with the report by Plunkett et al.12 It is well established that the volume of heart irradiated is directly correlated with the risk of radiation-related side effects.9 Possible mechanisms of radiation-induced cardiotoxicity are direct myocardial damage, damage to the coronary artery, and damage to the coronary microvasculature.13,14 Although the current study does not evaluate the mechanism of radiation-induced cardiotoxicity, overlapping field arrangements that expose a larger volume of the heart to higher doses of radiation have been clearly linked to excess cardiovascular mortality.10 Rutqvist et al4 demonstrated the importance of using limited radiation therapy treatment volumes and doses in 960 patients with breast cancer. Patients treated with left-sided tangent fields, which included the internal mammary nodes, received the highest dose of radiation to the myocardium and had a threefold greater relative risk of death due to heart disease than counterparts who received surgery alone (no radiation) or right-sided tangent fields that included one or both internal mammary chains. Death due to cardiovascular diseases other than ischemia was not increased in any of the groups.
We found that simple respiratory maneuvers significantly alter cardiac volume within the radiation field. Radiation therapy is typically delivered in a continuous administration over an ≈45-second period during quiet breathing. End-tidal volume was chosen as the baseline for all our analyses because it most closely approximates a patient breathing quietly during continuous delivery of radiation therapy. Because the pericardium is firmly attached to the diaphragm, full inspiration pulls both the diaphragm and heart inferiorly while expanding the chest cavity; as a result, cardiac volume involvement in the radiation field decreases. In contrast, forced expiration elevates the diaphragm, moving the heart superiorly and anteriorly toward the chest wall, thereby increasing cardiac volume in the radiation portals.
To the best of our knowledge, no previous studies have examined the use of respiratory maneuvers during delivery of radiation therapy as a mechanism for decreasing cardiac volume and potential cardiotoxicity for breast cancer patients. These respiratory maneuvers are simple and thus easy to implement.
The results of the present study may lead to the use of respiratory-gated radiation therapy delivery, such as short bursts of radiation while the patient holds her breath rather than longer, continuous delivery of radiation during normal breathing. The breath-hold duration of the MR studies was shorter than that which might be required for radiation therapy treatments. Therefore, multiple breath holds or respiratory-gating techniques ultimately may be needed for clinical application of this technique. Respiratory gating may not work as well, however, as deep inspiration because the latter yields the maximal difference in cardiac volume from end-tidal respiration. Despite this limitation, use of respiratory maneuvers may minimize radiation dose to the heart while not altering the dose of radiation delivered to the breast.
We compared the effects of respiratory maneuvers on cardiac volume included in left-breast radiation portals. Myocardial volume rather than cardiac volume (myocardium plus blood pool) is likely to be of greater clinical relevance. Implementation of “black blood” MRI techniques that improve myocardium–blood pool contrast relative to the TFE sequences used in the present study may be advantageous; this remains to be studied. Of note, the subjects in the present study are younger in age than the average breast cancer patient. Therefore, further studies to confirm these results in older patients are under way to increase the generalizability of our results.
In conclusion, we found that inclusion of cardiac volume in the left-breast radiation therapy field is common. Use of inspiratory maneuvers significantly decreases cardiac volume within the radiation portals. We believe all attempts to minimize cardiotoxicity are especially relevant for long-term breast cancer survivors because cardiovascular disease remains the leading cause of mortality in women after menopause.15 The implementation of simple inspiratory breath holding during delivery of radiation therapy may preserve radiation dosage to the breast while reducing cardiac involvement and deserves further study.
Selected Abbreviations and Acronyms
|ETid||=||end-tidal cardiac volume|
|Exp||=||forced expiratory cardiac volume|
|Insp||=||inspiratory cardiac volume|
Dr Chen is supported in part by the Clinical Investigator Training Program, Beth Israel Deaconess Medical Center–Harvard/MIT Division of Health Sciences and Technology, in collaboration with Pfizer, Inc, Boston, Mass. The authors would like to thank Lois Rhodes, RTT, department of radiation therapy, for her technical assistance in replicating the radiation treatment position in the volunteers during MRI scanning.
- Received August 15, 1997.
- Revision received September 4, 1997.
- Accepted September 15, 1997.
- Copyright © 1997 by American Heart Association
Haybittle JL, Brinkley D, Houghton J, A’Hern RP, Baum M. Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer. Br Med J. 1989;298:1611–1614.
Cuzick J, Stewart H, Rutqvist L, Houghton J, Edwards R, Redmond C, Peto R, Baum M, Fisher B, Host H, Lythgoe L, Ribeiro G, Scheurlen H. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol. 1994;12:447–453.
Fuller SA, Haybittle JL, Smith RE, Dobbs HJ. Cardiac doses in post-operative breast irradiation. Radiother Oncol. 1992;25: 19–24.
Corn BW, Trock BJ, Goodman RI. Irradiation-related ischemic heart disease. J Clin Oncol. 1990;8:741–750.
Fuller SA, Haybittle JL, Smith RE, Dobbs HJ. Cardiac doses in post-operative breast irradiation. Radiother Oncol. 1992;25:9–24.
Plunkett ME, Bornstein BA, Costello P, Kijewski PK, Harris JR. Use of spiral CT in the assessment of cardiac structures for planning 3D volumetric radiation treatment of the breast. Radiology. 189(suppl):355.
DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. Philadelphia, Pa: JB Lippincott Co; 1997:2747–2750.
Gyenes G, Fornander T, Carlens P, Glas U, Rutqvist L. Myocardial damage in breast cancer patients treated with adjuvant radiotherapy: a prospective study. J Radiother Oncol. 1996;36:899–905.
Eaker E, Chesebro JH, Sacks FM, Wenger NK, Whisnant JP, Winston M. Cardiovascular disease in women. Circulation. 1993;88(pt 1):1999–2009.