Patients with left-sided breast cancers have an increased risk of heart damage from adjuvant radiation therapy given after lumpectomy or mastectomy.
To minimize cardiotoxicity from incidental cardiac irradiation in these patients, radiation oncologists at The University of Texas MD Anderson Cancer Center are using a technique called “deep inspiration breath hold” during radiation delivery.
“Radiation to the heart is not a good thing, and any effort to keep the dose to the heart as low as reasonably achievable should be in our patients’ best interests,” said Benjamin Smith, M.D., an associate professor in the Department of Radiation Oncology. “Deep inspiration breath hold is an elegant innovation to help keep that dose as low as possible.”
The majority of breast cancer patients who undergo lumpectomy for early-stage disease, as well as many breast cancer patients who undergo mastectomy for more extensive disease, receive adjuvant radiation therapy.
In patients with left-sided breast cancers, radiation delivered to the target volumes—the tumor bed and/or regional lymph nodes—can also intersect the heart. The potential complications arising from this incidental cardiac irradiation depend on which part of the heart is irradiated. Possible complications include ischemic heart disease, heart failure, valvular disease, or even death from heart disease. In patients with left-sided breast cancers who receive adjuvant radiation therapy, the heart usually receives a glancing blow of radiation, with the superficial portions of the heart—the pericardium and the coronary arteries—receiving the highest radiation dose. The pericardium is generally fairly tolerant of radiation, and radiation-induced pericarditis is uncommon among patients with left-sided breast cancers. Much more susceptible to the adverse effects of radiation are the coronary arteries.
“Radiation to the arteries increases the risk of atherosclerotic disease, and this can be a very late effect of radiation,” Dr. Smith said. “It’s been reasonably well established that there’s a radiation dose–response relationship; the higher the dose to those blood vessels, the more likely the patient will have a late effect. So trying to minimize the dose to those blood vessels is very meaningful for minimizing a patient’s long-term risk of heart damage.”
To illustrate this point, Dr. Smith described a breast cancer patient who in 1980 was one of the first treated with lumpectomy and radiation; 34 years later, she had a heart attack that was at least partially attributable to her radiation therapy. “So radiation causes this injury that can be silent for decades, but after some time, the patient reaches a critical tipping point and begins having clinical manifestations of the injury,” Dr. Smith said.
Patients with preexisting cardiac risk factors or coronary heart disease may be more likely to develop radiation-related heart problems later in life. In addition, many systemic agents used to treat breast cancer are potentially cardiotoxic—including traditional chemotherapy drugs such as doxorubicin, targeted agents such as trastuzumab, and hormonal therapies such as tamoxifen—and they may act in synergy with radiation to damage heart tissue.
Minimizing the radiation dose
Several techniques can be used to minimize the radiation dose to the heart. One strategy is to use a cardiac block—essentially placing a slab of lead in front of the heart to shield it from radiation. Now achieved with a multileaf collimator integrated with the radiation delivery system, a cardiac block can be used effectively in most patients with upper-quadrant breast tumors but may compromise the dose to the target volume in patients with lower-quadrant breast tumors.
Another common approach is to use intensity-modulated radiation therapy to shape the radiation beam to the target volume while avoiding the heart; however, such treatment may also result in a higher radiation dose to other organs at risk in the thorax.
A third option is to use respiratory gating—synchronizing the delivery of radiation with the patient’s breathing to limit the amount of tissue beyond the target volume that receives radiation. One type of respiratory gating is deep inspiration breath hold, in which the patient takes a deep breath to inflate the lingula of the left lung. The inflated lingula temporarily displaces the heart inferiorly and posteriorly, thereby increasing the distance between the heart and the chest wall and moving the organ out of the radiation beam’s path. Dr. Smith says he employs the technique in almost all of his patients with left-sided breast cancers.
“With other techniques, you sometimes have to decide whether to protect the heart or adequately treat the tumor bed to minimize the risk of recurrence,” Dr. Smith said. “But with deep inspiration, you can usually have the best of both worlds. It allows us not only to lower the dose of radiation to the heart—and the dose can be lowered pretty dramatically—but also to deliver enough radiation to treat the tumor bed effectively.”
Planning and delivering radiation
When the deep inspiration breath hold technique is used, radiation treatment is planned meticulously to ensure a minimal radiation dose to the heart while allowing a sufficient dose to the target volume. During treatment simulation, the patient lies on her back, and a reflector box is taped to her abdomen. An infrared camera mounted at the foot of the treatment couch tracks the up-down movement of the box as the patient breathes. The patient wears video goggles showing a yellow bar moving up (representing her inhalation) and down (exhalation) below a blue “target” rectangle. When the patient inhales deeply, the yellow bar rises into the blue rectangle and turns green. The patient then holds her breath for about 15 seconds while computed tomography images are taken to map the patient’s anatomy for treatment planning.
During the actual radiation treatment, the patient is again outfitted with the reflector box and goggles and asked to inhale until the yellow bar rises into the blue target rectangle and turns green, at which point the radiation beam is activated. For the beam to be activated, the yellow bar must be in the blue rectangle. Because radiation is given only when the patient has inhaled sufficiently, the patient effectively controls the delivery of the radiation, and movements due to coughing or sneezing do not interfere with therapy delivery.
“For the vast majority of patients, we can get good radiation plans,” Dr. Smith said. “And the data we have indicate that these patients’ risk of long-term cardiac side effects from radiation should be very low.”
Benefit in specific scenarios
Deep inspiration breath hold is particularly beneficial in a number of clinical scenarios.
“There is significant variation in patients’ anatomy,” Dr. Smith said. “Some patients have a heart that’s right up against the rib cage, so without deep inspiration breath hold it can be extremely difficult to avoid the heart and still cover the tumor area that needs to be treated.”
Other patients likely to benefit greatly from the breath hold technique are those with tumors in the lower half of the breast. Without this technique, such tumors are difficult to treat effectively while still avoiding irradiation of the heart. Although patients with these tumors may be treated in the prone position, with the affected breast falling down and away from the body, it can still be difficult in some patients to miss the heart.
“When the patient is prone, both the breast and the heart fall forward, and so the heart may be even closer to the tumor bed,” Dr. Smith said. “The prone plan has certain advantages, but in some patients, you can’t reliably deliver a good dose to the tumor bed and be confident that you would also miss the heart at each treatment session.”
Patients who need treatment to the internal mammary nodes, which are close to the heart, also benefit from the breath hold approach.
“For patients who underwent lumpectomy for breast tumors close to the heart, we can routinely get mean heart doses that are less than 1 Gy. And for patients who require treatment of the internal mammary lymph nodes after mastectomy, we can get mean heart doses between 2 Gy and 4 Gy,” Dr. Smith said. “Without breath hold, those mean heart doses are a lot higher.”
There are few contraindications to using deep inspiration breath hold to move the heart out of harm’s way, Dr. Smith said.
“A few patients can’t hold their breath because they have lung issues or they’re anxious, but most patients seem to be able to do it well and reproducibly,” Dr. Smith said. “People who are 80 years old have undergone this procedure, so age doesn’t seem to be a contraindication.”
Deep inspiration breath hold often is not necessary for patients who also have chronic obstructive pulmonary disease. One of the hallmarks of chronic obstructive pulmonary disease is hyperinflation of the lingula, which often displaces the heart just as deep inspiration breath hold would do.
Although deep inspiration breath hold is used primarily in patients with left-sided breast cancers, it can also be used in select patients with tumors in the right breast to help minimize the radiation dose to the lung.
Deep inspiration breath hold is not without its drawbacks. Treatment simulation with deep inspiration breath hold takes about 15 minutes longer than simulation for treatment without the technique, and treatment itself can take 5–10 minutes longer depending on the complexity of the treatment plan. The extra time needed for deep inspiration breath hold could be burdensome for a radiation oncology clinic already operating at full capacity.
“Deep inspiration breath hold also introduces another layer of uncertainty in the setup of patients,” Dr. Smith said. “Particularly with complicated plans with a lot of different fields, there’s some theoretical concern that you might not deliver the radiation to the same place each day.”
Dr. Smith estimates that at MD Anderson, deep inspiration breath hold is used to reduce cardiac irradiation in 300–400 patients with left-sided breast cancers each year. However, widespread adoption of the technique outside major cancer centers has been hindered by the additional time and equipment (and thus cost) it requires.
“There’s also a learning curve to figuring out the process of setting up patients on a daily basis and making sure the setup is accurate,” Dr. Smith said. “At MD Anderson, we have really great therapists and physicists who work through a systematic process to do that, but it takes time to build up that kind of expertise.”
Another potential barrier to widespread use of the technology is that, until recently, deep inspiration breath hold lacked a Current Procedural Terminology code that would enable physicians to be reimbursed for performing the procedure. However, such a code has been introduced, and this should allow radiation oncologists to recoup some of the additional costs associated with the procedure and thus make the procedure more widely available.
Ultimately, Dr. Smith said, it is important to provide patients with the best treatment options available. This may mean referring some patients to institutions that can provide radiation therapy with deep inspiration breath hold. “If I had a family member with left-sided breast cancer, I would definitely want her to have access to this technology,” Dr. Smith said.
Dr. Benjamin Smith contributed to this article.
Smith BD. Reducing incidental cardiac irradiation during breast radiotherapy. The ASCO Post. May 15, 2013.
For more information, contact Dr. Benjamin Smith at 713-563-8495.
OncoLog, September 2014, Volume 59, Issue 9