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Reducing Cardiac Radiation Dose From Breast Cancer Radiation Therapy With Breath Hold Training and Cognitive Behavioral Therapy

Mayr, Nina A. MD; Borm, Kai J. MD; Kalet, Alan M. PhD; Wootton, Landon S. PhD; Chadderdon, Alexandra L. Psy D; Combs, Stephanie E. MD; Wang, Waylene MD; Cao, Ning PhD; Lo, Simon S. MD; Sandison, George A. PhD; Meyer, Juergen PhD

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Topics in Magnetic Resonance Imaging: June 2020 - Volume 29 - Issue 3 - p 135-148
doi: 10.1097/RMR.0000000000000241
  • Open



Radiation therapy to the breast and chest wall is one of the most frequently practiced treatments for breast cancer, the most common cancer in women.1 Breast radiation enables breast-conserving therapy by greatly reducing the chance of tumor recurrence within the breast in early-stage breast cancer patients.2,3 In advanced-stage disease, postoperative radiation therapy after mastectomy to the chest wall and regional lymph nodes significantly improves the probability of tumor control, thereby preventing devastating and largely incurable tumor recurrences in the chest wall.4–6 In addition, postmastectomy radiation therapy improves the chance of long-term cancer survival and cure.4–6 Therefore at least half of the more than 260,000 women diagnosed annually with breast cancer in the United States7 undergo radiation therapy as part of their treatment.8


Cardiac Toxicity and Mortality in Breast Radiation

These gains in cancer outcomes have, however, been associated with serious long-term cardiac toxicity and mortality from breast and chest wall radiation, as reported in multiple studies.9–13 These complications of future heart disease can include coronary artery disease, cardiomyopathy, myocardial fibrosis, arrhythmias, valvular disease, pericarditis, pericardial effusions, or constriction, which all can result in significant morbidity, heart failure, and cardiac death.9,14,15

Cardiac toxicity occurs because of the heart's proximity to the treatment target, and the technical challenge of treating the target region to an adequate dose while effectively reducing the unintended radiation dose to the nearby heart. Cardiac complications are directly and quantitatively related to the dose of radiation received by the heart. The probability of major ischemic cardiac events has been reported to increase by 7.4% for each 1 Gy increase in the average radiation dose to the heart (mean heart dose).9 A recent worldwide systematic review of heart doses in left breast radiotherapy reported mean heart doses of 3.6 Gy16 compared to previously 5.4 Gy in 201517; however, the heart dose to sensitive cardiac substructures is heterogeneous and can be substantially higher. More recently, data quantifying the effect of radiation dose to these cardiac substructures, such as coronary vessels, that are particularly close to the radiation therapy target, and correlations with cardiac toxicity have emerged.18,19 Radiation-induced cardiac toxicity thus represents an important and difficult to resolve long-term challenge of breast radiation for both breast-conserving therapy and postmastectomy chest wall radiation, particularly for survivors with left-sided breast cancer.

New Technologies to Mitigate Cardiac Dose in Radiation for Breast Cancer

The urgent need for novel approaches to minimize radiation dose to the heart to reduce cardiac risk has been widely recognized. However, until the development of image guidance and motion tracking technologies in radiation oncology, dose exposure of the heart has been a formidable and largely unavoidable hurdle for radiation therapy in breast cancer. Novel hardware and computer science advances in the radiation therapy delivery technologies have since been in development as promising strategies to reduce cardiac dose.

Cardiac dose reduction can be accomplished by either physically separating the heart from the treatment volume, referred to as deep inspiration breath hold (DIBH) (Fig. 1), the most commonly employed approach; or by means of alternative dose delivery, such as proton therapy, and/or alternative treatment planning strategies.

Highly effective and less effective DIBH. Coregistration images of the heart from radiation therapy planning imaging (CT simulation) acquired in DIBH and in free-breathing mode for dosimetry are shown. The position of the heart in the free-breathing CT is shown in the color wash (orange and brown areas). The heart in DIBH position is outlined with a pink contour and the area of the heart in DIBH position is shown in gray scale (orange + grey areas). Axial (A), coronal (B) and sagittal (C) images in a patient with highly successful DIBH demonstrate the heart position during free breathing (orange + brown areas) and DIBH (orange + gray areas). Compared to the heart position during the free breathing, the heart in DIBH effectively moved away from left anterior chest wall, where the radiation (multiple colored isodose lines) was delivered for the treatment of the left breast cancer. In DIBH the heart (orange + gray) moves toward the right (A, B) and inferior (B, C) compared to the heart position during free breathing (orange + brown). The heart position during free breathing is more toward the left (A, B) and superior (B, C), and clearly crosses the multiple isodose lines (radiation treatment field). Both the right and inferior displacement of the heart in DIBH create more distance between the heart and the left chest wall and radiation volume, resulting in lesser dose exposure to the heart in DIBH than in free breathing. In contrast, the axial (D), coronal (E), and sagittal (F) images of a patient with poor DIBH demonstrate that the heart position in DIBH is only minimally different from the heart position in free breathing with respect to the right lateral (D, E) and inferior movement (E, F). This results in less distance gains between the heart and the treatment target (multiple colored isodose lines in D, E and F) and insufficient dose reduction to the heart from the DIBH.

Deep Inspiration Breath Hold to Reduce Unintended Radiation Dose to the Heart

The DIBH method delivers each radiation treatment during an extended controlled deep breath hold that is actively performed by the patient. During deep inspiration the chest cavity and lung volume expand, and as a result the heart shifts to the right and inferiorly in most patients. This displacement of the heart increases the distance between the radiation therapy target structures (breast, chest wall) and the heart. The increased distance between heart and target structures, in conjunction with meticulous 3D-conformal or intensity-modulated imaging-based radiation dose planning, can reduce the dose to the heart while maintaining adequate dose coverage to the breast or chest wall target structures (Fig. 1).

Deep Inspiration Breath Hold technologies

The technical implementation of DIBH is complex, and aggravated by the repetitive need for a reproducible DIBH on each day of the 3½- to 5½-week radiation treatment course. Stringent quality assurance to precisely determine and daily reproduce the patient-specific DIBH are necessary and achieved through 2 major approaches: (1) external chest wall motion tracking and (2) breath hold volume tracking.

The simplest method of external chest wall motion tracking, which illustrates its principles, is the placement of an external visual surrogate, such as a line drawn on the patient's chest, relative to a fixed reference point such as in-room lasers. This external surrogate for the chest and heart position is placed while the patient is in DIBH at the time of the radiation therapy planning procedure, and the surrogate is realigned for daily treatment to assure that the DIBH is reproduced precisely on each treatment day. Radiation therapists visually monitor the depth of the breath hold and, based on the surrogate marker, manually control beam on/off to ensure that radiation is delivered only while the patient is in the precise DIBH position. More recently DIBH motion tracking has advanced to more reliable and automated approaches, including mechanical tracking of the patient's inspiration20camera-based tracking through infrared reflectors placed on the patient's skin,21 and electromagnetic tracking, such as radiofrequency transponder beacons.22–24

Currently the most sophisticated and common method for motion tracking in DIBH is surface imaging, also referred to as surface-guided radiation therapy. Here the entire patient surface is mapped and tracked in real time in 3D space with an array of cameras. The systems use invisible or near-visible light to project patterns onto the patient, which are captured with the cameras. A mathematical reconstruction, based on triangulation, allows the patient's chest surface to be reconstructed (Fig. 2).25–27 This real-time surface can then be compared with a reference surface to infer the depth of the breath hold, ensuring reproducible breath holds as well as patient positioning during treatment. Also, any posture difference including deformations can be visualized and corrected.28 The systems can automatically turn the radiation beam on, referred to as gating, when the patient is within a predefined gating window. Visual or audiovisual feedback options for patients are also available.

Surface-guided radiation therapy for DIBH. In this system the entire surface of the patient's chest is 3-dimensionally reconstructed and mapped using an in-room camera and tracking system (C-RAD, Uppsala, Sweden) at the time of the initial CT simulation for treatment planning. A, The treatment positioning for breast or chest wall radiation, as performed during the initial CT simulation (treatment planning) process and reproduced precisely during each daily treatment. Both arms are elevated above the head and the left chest wall is contoured on the skin (faint yellow lines). B, The patient's chest mapping in treatment position in DIBH at the time of treatment planning (reference). C, The patient's reconstructed chest surface map (live image) at the time of daily radiation (1 daily image shown). In the Overlay (D) the planning map (B) and the map in treatment position (C) are coregistered. Registration corrections based on triangulation are displayed to aid in positional and DIBH adjustments until optimal overlay is achieved that matches the parameters from the initial planning imaging (B). Registration corrections are displayed in (E). Color codes visually display real-time the regions with optimal overlay (green) and those with positional discrepancies (blue) to guide positional adjustments.

For the breath hold volume tracking method, the volume of air inhaled and exhaled by the patient is employed as a surrogate for the breath hold using spirometers.29,30 In such systems the patient inhales until a volume of air established at the treatment planning procedure has passed through the spirometer. The subsequent breath hold can either be voluntary, based on therapist and/or device coaching and feedback, or involuntary wherein the spirometer has a valve system that stops the flow of air once a threshold has been reached. Many of these tracking technologies can interface with the treatment delivery unit through gating to ensure the beam is only turned on when the patient is in the specified DIBH position.

Alternative non-DIBH treatment planning and delivery strategies for cardiac sparing, such as proton therapy31 are much less common, more costly and less widely available for breast cancer. Therefore in the vast majority of breast cancer patients DIBH is the method of choice for heart dose reduction.

Clinical outcome of Deep Inspiration Breath Hold

Multiple studies in clinical patients have demonstrated that DIBH measurably decreases the heart dose in left-sided breast radiation compared to treatment in normal respiration (free-breathing) (Table 1).32–35 Parameters to identify patients who may benefit most from DIBH based on their anatomical co-location of heart and chest wall structures have also been developed.36 DIBH technique has thus become an important and increasingly practiced technique of advanced radiation therapy in patients with left breast cancer32 and holds the promise to achieve better long-term cardiac health in breast cancer survivors.

Studies of Heart Dose Reduction Achieved in Deep Inspiration Breath Hold (vs Free Breathing)

However, even with DIBH, mean heart doses as high 5 Gy are still observed44. In addition, the dose to cardiac substructures, specifically, coronary vessels, which are closely approximated to the radiation target structures, must be minimized. Recent correlation studies of coronary artery dose and cardiac morbidity have shown that a reduction of the dose to the coronary vessels to 5 Gy or less is needed to reduce the cardiac risk to baseline.19 Maximal performance of the DIBH by the patient is therefore critical.

Deep Inspiration Breath Hold procedure and challenge

However, the procedural success in the individual patient and the clinical protocols for DIBH have been highly variable (Table 2).32,45 Active and precise on-demand cooperation from the patient is eminently important for the effectiveness of each daily DIBH because a sustained, stable, consistent and deep inspiration breath hold is critical to continuously maintain the required distance of the heart from the radiation beam target. Patients have to hold their breath for approximately 30 to 40 seconds several times during each of the daily radiation treatment procedures, and do so for each of the 16 to 28 daily treatments (3½–5 ½-week treatment course). To ensure accuracy, the chest position is tracked real-time during the DIBH while the radiation therapy is delivered (Fig. 2), and chest excursions are monitored on a submillimeter basis. Stringent motion parameters are set.23,28,32,41 If these parameters are exceeded, the radiation beam is stopped and radiation treatment is not resumed until the parameters are within limits, signifying an adequate DIBH that sufficiently displaces the heart from the chest wall.

Comprehensive Summary of Training and Practice Methods Reported in Studies of Deep Inspiration Breath Hold in Breast Cancer

Although aiming to reduce the radiation dose to the heart, subjecting breast cancer patients to these complex daily procedures often augments their preexisting cognitive stress, distress and anxiety.


Baseline Stress and Anxiety

Among patients with breast cancer in general 12% to 47% report baseline anxiety, and 11% to 16% experience both, anxiety and depression.72–74 Emotional stress is felt by at least half of all breast cancer patients,75 and one fourth of patients will experience clinically significant psychological disorders.76 Anxiety, stress, and distress related to medical procedures can arise from fear for health, uncertainty about outcome, combined with a profound loss of control.77

Stress and Anxiety in Radiation Therapy

Specifically to radiation therapy, it has been widely recognized that the process of radiation therapy in itself can generate anxiety and emotional distress78–81 and persistent anxiety during radiation therapy occurs in up to half of patients.78,80 The causes for anxiety and stress regarding radiation therapy can be multifaceted and related to: (1) Overall negative perceptions about radiation, such as nuclear disasters that remain a common perspective. (2) There is still a lingering perception that radiation therapy is associated with end-stage cancer and cancer death. Both generate fear of cancer and cancer death. (3) A sensation of confinement and claustrophobia, similar to that described for imaging procedures by Nguyen et al82 and Ajam et al83 in this Special Edition, can arise during the radiation therapy procedure from the bulky intimidating technical equipment and the need for immobilization for prolonged time in an exposed treatment position (Fig. 2A). (4) In breast cancer patients, these challenges are often further aggravated by the physical discomfort related to the preceding surgical procedure with residual pain and immobility, or residual chemotherapy-related toxicities, such as fatigue, and their apprehension regarding body image and disfigurement. Later during the radiation therapy course, the increasing skin and soft tissue irritation from the radiation can augment the overall discomfort.

The prevalence of anxiety during radiation therapy is underscored by the observations in a study of curable early-stage breast cancer patients receiving radiation therapy in the United States and Europe. The rate of psychological supportive care visits was nearly a third in both countries, and 44% of U.S. patients received prescription psychotropic drugs.84 Furthermore, complementary and alternative medicine is frequently used by patients and self-administered without involvement of their health care team, to alleviate toxicities and anxieties related to cancer treatment, as described in the article by Borm et al85 in this Special Edition. These observations underscore the need for a better understanding of patients’ anxiety and stress and for broadened options to manage these.

Deep Inspiration Breath Hold Procedural Stress and Anxiety

In DIBH, general and radiation therapy-related anxiety and stress reaction are further augmented by the demanding physical performance required from the patient for the breath hold, thereby creating challenges that are both cognitive/emotional and physical.

Patients are frequently unaccustomed to the stringent physical requirements associated with prolonged breath holding maneuvers. DIBH demands complex coordination of thoracoabdominal muscles to achieve a deep, prolonged, and stable breath hold that is not intuitive to patients. The rapid on-demand cooperation, strictly timed within a stressful procedure sequence (set-up, filming, motion tracking, treatment delivery), within a hectic treatment schedule and with little time to prepare, pose additional challenges to cancer patients’ coping mechanisms. Stress-induced detrimental effects on breathing pattern have been well established. Anxiety and stress are associated shallower and faster breathing patterns,86,87 giving rise to a vicious cycle of anxiety/stress that interferes with optimal breath hold performance. Such pressures can make DIBH challenging to perform for the patient, and likely contribute to the variability of success and the wide range of achieved heart dose reduction.

While the wide array of radiation therapy technologies with sub-millimeter-precision have been deployed to assist with DIBH, there has been much less emphasis on the “human factor”, the emotional psychological aspects of cognitive stress, distress and mechanisms of coping with treatment. Easily applicable and sustainable means to optimize DIBH performance, alleviating anxiety and stress, are needed to reduce patients’ distress and enhance their ability to cooperate and perform DIBH optimally.

There is ample evidence that in cancer patients effective anxiety and stress management is associated not only with improvements in quality of life, psychological adjustment and improved decision making, but also with adherence to treatment.88,89

The following sections review the emerging experience on both training/practice and psychotherapeutic strategies and interventions aimed at addressing anxiety, stress, and distress, while facilitating patients’ ability to engage and cooperate optimally with their treatment and its required technologies and techniques, while improving emotional well-being and quality of life during this challenging phase of breast cancer therapy.


Because the success of DIBH depends inevitably on patients’ ability to hold their breath in deep inspiration, training and conditioning of patients before the radiation therapy planning (CT simulation) and treatment procedures is expected to be an important step in DIBH. The very few recent studies on this subject indicate that training has a direct impact on both dose reduction during DIBH and duration of the DIBH procedure.41,70 Despite the importance of training, recommendations regarding instruction, training and practice for DIBH are sparse. Hence, in previous DIBH studies the methods and approaches for instructing and conditioning patients for DIBH have been either ill-defined or highly variable, ranging from no instruction to instructions just before the first DIBH in the CT simulation procedure (Table 2). The vast majority of publications report the timing of the instruction and practice to be on the same day as the actual CT simulation procedure (Table 2). Only very few centers initiate the patient training process in advance of the radiation therapy planning procedure by providing instruction sheets and tutorial videos or by DIBH coaching performed by a physician.35,41,70

In contrast, in other areas of medicine, such as rehabilitation medicine and exercise science, there is ample experience in respiratory training for both, patients with respiratory illnesses or presurgical patients needing preconditioning,90–93 and in normal subjects such as athletes.94 To apply this experience to breast cancer patients, the existing time window from patient evaluation to the first radiation therapy/DIBH procedure can be leveraged to insert a training program to prepare patients for DIBH.

Employing this concept, Kim et al41 reported a regimen of preparatory DIBH training and home self-practice during the 1 to 2 week period before the radiation treatment planning (CT simulation) procedure. Instruction was given in a 10- to 15-minute coaching/training session at the end of a physician office visit (typically the consultation visit upon patient referral when radiation treatment was reviewed with the patient) 1 to 2 weeks before the CT simulation. Patients were instructed to perform DIBH lying supine on the examination table closely matching the treatment position for radiation therapy, which is illustrated in Figure 2A. Patients were coached to maintain a steady deep breath hold for at least 10 seconds. Their DIBH performance was evaluated with respect to maintenance of treatment position, length of the achieved DIBH, and the absence of visible chest wall motion. The technique was adjusted as needed and DIBH practice continued until the patient felt comfortable to reproduce a maximal DIBH. The 1- to 2-week home training included 3 sets of 10 DIBHs to be performed at least 3 times per day, with no upper limit, in the same treatment position, and with the goal to achieve a stable DIBH lasting at least 40 seconds.

Comparison of the coached patient group with a noncoached group, treated during the same time period in the same facility, showed that preparatory coaching and training resulted in significantly reduced heart dose. In the coached/trained patient group the maximal radiation dose to the heart was on average 6 Gy lower than in the group without coaching/training (13.1 vs 19.4 Gy, P = 0.004). Similarly the volume of heart receiving 10 and 5 Gy was lower.41 These findings suggest that the preparatory training intervention enabled patients to deepen their breath hold for better dosimetric outcome. This reduction in radiation dose exposure of the heart occurred in cardiac regions that are closest to the left chest wall. These cardiac regions generally contain the left ventricle and coronary vessels. Increasing evidence is emerging that radiation dose exposure to precisely these cardiac regions strongly correlates with future cardiac toxicity in breast cancer survivors.19,95 Therefore the dose reductions to these cardiac regions, as enabled by the preparatory training program in Kim et al's41 study are likely to be clinically impactful.

In another preparatory training study, Oonsiri et al70 investigated the impact of DIBH training initiated at least 1 week before the simulation procedure in 112 patients. Training comprised an information sheet and/or an instruction video about DIBH that was handed out to the patients for home training purposes. Endpoints of the study were the duration of the treatment planning procedure and the treatment as well as patient satisfaction. A significant reduction of the planning procedure time (from 22.3 to 10.3 minutes) and high levels of satisfaction was observed in the patients who received the training, compared to those who did not. These results are in agreement and further supported by the observations in Kim et al's study41 of a perceived increase in the ease of the treatment planning procedure and treatment in the trained patients.

The role of the training component in addition to modulation of physiologic conditions has also been demonstrated in recent work by Parkes et al96,97 showing that the length of breath holding for radiation therapy can be increased by training as well as preoxygenation and induction of hypocapnia. The investigators studied the ability to prolong the duration of a breath hold in both normal volunteers and breast cancer patients.96,97 Similarly to Kim et al's41 and Oonsiri et al's70 studies, the investigators employed a training regimen over several days. Training alone (in room air) significantly increased the mean breath-hold duration from 42 ± 2 to 58 ± 6 seconds. Remarkably, optimization of the length of breath hold was achieved not only in healthy volunteers96 but also in elderly patients with breast cancer.97 Although the addition of preoxygenation and hypocapnia produced the greatest DIBH prolongation, training alone also increased the duration of the DIBH.

Zhao et al's49 study represents another of the very few studies employing training at least 1 week before simulation. Twenty-two patients were trained, using audio and visual coaching in both thoracic and abdominal breathing maneuvers, and the effectiveness of DIBH among the 2 different breathing maneuvers on heart dose reduction was compared. Abdominal DIBH achieved significantly lower cardiac doses (by approximately 20%) compared to thoracic DIBH. These results suggest that preparatory coaching and training enable patients to perform in parallel more than one type of breathing maneuver to achieve the best DIBH, broadening the options for individualization of heart-sparing radiation therapy.

In all these studies the brief time window of only 1 to 2 weeks produced measurable improvements in terms of cardiac dose reduction,41 length of sustained DIBH,96,97 performance time during DIBH simulation procedure70 and range of breath-holding maneuvers performed,49 despite the much shorter training time than the typical 1- to 3-month respiratory training regimens used in cardiopulmonary and sports medicine.90–94 This suggests that these improvements in patients’ ability to perform DIBH may not be solely related to simple gains in respiratory muscle strength. Both neurocognitive and psychological factors may contribute to the better DIBH performance.

Improved cortical–muscle coordination, acquired during the short training period, may also play a role. Neurocognitive studies show that increases in voluntary muscle force are generated not only by actual muscle contraction (exercise). Cognitive training effects (even without physical muscle exercise) can alter the activity level of cortical motor control networks, increase excitatory neural output and activation of motor units, thereby increasing muscle strength.98–100

Psychological factors likely also influence DIBH performance, at least in part through the known adverse effects of anxiety on breathing patterns86,87 and thereby on DIBH performance. The targeted coaching/instruction and the opportunity for patients to train gradually over time and in the comfort and privacy and own familiar home environment, likely contributed to reducing anxiety and stress, thereby enabling increased focus and gradual improvement of the patients’ skills in coordinating thoracoabdominal muscle function and resulting in improved DIBH performance.

Such a low-cost easily implementable training intervention is well suited for wide dissemination to community centers and does not require special equipment or personnel. Applicability of DIBH techniques to busy generalist radiation oncology clinics in the wider community is of great importance if cardiac dose reduction in breast radiation is to be impactful on a larger scale, because most of breast cancer patients are treated in smaller community centers that do not have the leading-edge technologies and manpower of large academic institutions.

In a community-based practice within the University of Washington, DIBH is offered to all left-sided breast cancer patients using the training regimen described above.41 The regimen of individualized guided DIBH coaching and practice well before the first radiation procedure with practical home self-training instructions has led to a nearly 100% acceptance of DIBH by patients and high success. Encouragement by the physician, continued education and empathic individualized attention by the therapy staff throughout the treatment course, further endorsed by visualization of the cardiac sparing using the patient's own treatment images (Fig. 1), and overall patient empowerment by fostering their personal initiative and active physical effort to protect an organ with both physical and emotional prominence, has likely contributed to this success and high patient compliance.


Psychotherapeutic interventions have shown clinically significant impact in helping manage anxiety and depression in adult patients with cancer, based on an extensive review by the Institute of Medicine89 that supports incorporation of these interventions into practice guidelines.101 Among these cognitive behavioral therapy (CBT) has been most widely and most robustly studied. CBT generally consists of cognitive interventions, including cognitive restructuring, as well as behavioral interventions, including guided imagery, progressive muscle relaxation, and deep breathing exercises, as reviewed in more detail in the article by Chadderdon et al102 in this Special Edition. Multiple randomized controlled trials have shown CBT to alleviate psychological symptoms of anxiety, distress and depression and physical symptoms of pain, nausea/vomiting, and fatigue in cancer patients.89,103–106

Cognitive Behavioral Therapies in Breast Cancer Patients

These findings for CBT hold true specifically for patients with breast cancer. Two major meta-analyses showed that CBT is efficacious in improving patients’ anxiety, depression, quality of life, and in alleviating stress.103,107 The meta-analysis of 20 studies by Tatrow and Montgomery107 found that distress and pain improved with CBT in more than 60% of patients, regardless of the severity of their breast cancer. CBT interventions included cognitive restructuring, relaxation and (guided) imagery, systematic desensitization, and (coping) skills training. The meta-analysis also included hypnosis and distraction, autogenic training, and biofeedback interventions in various combinations. Most of the studies within the meta-analysis included breast cancer patients with nonmetastatic tumors. Outcome data from these trials are therefore representative of patient populations undergoing definitive radiation therapy to the breast or chest wall.

While the specific interventions and patient/therapist session schedules have varied widely, no significant correlation was found between the frequency and length of patient contact and effect size. This observation suggests that the time intensity of the specific CBT regimen may not play a major role, and therefore short CBT intervention times, which are more achievable in a hectic radiation oncology workflow, are likely effective. This concept is further supported by observations that short preprocedural relaxation and cognitive reframing interventions, often in the range of minutes, significantly reduce patients’ anxiety and pain perception during invasive interventional radiology procedures108 and improve examination completion rates of MRI procedures, while reducing noncompliance rates in subsequent MRI examinations and improving patient satisfaction rates.109,110 Tatrow and Montgomerys107 meta-analysis further suggests that the impact was greater when CBT was done in individual sessions, compared to group sessions, suggesting that personalized patient-centered interventions, focusing on the patient's individual needs, are important. A recent meta-analysis of 32 studies by Matthews et al103 confirms in a meta-analysis that CBT showed significant effect in improving anxiety, distress, and quality of life in breast cancer patients who have undergone surgery. CBT also demonstrated positive effects on relaxation indicators as well as physical correlates (late-afternoon serum cortisol) in women undergoing treatment for nonmetastatic breast cancer.111

Tatrow and Montgomery107 meta-analysis also assessed trials studying pain as an endpoint and found CBT efficacious in reducing chronic pain. This aspect is important because a proportion of breast cancer patients who undergo radiation therapy have residual postsurgical discomfort in the breast, axilla, and/or arm mobility limitations that can cause discomfort with treatment positioning. In addition, radiation reaction of the skin and breast, a toxicity that occurs later in the treatment course, can result in pain.

Comprehensive updated clinical practice guidelines on the evidence-based use of integrative therapies in breast cancer for the management of anxiety/stress, depression/mood disorders, fatigue, quality of life/physical functioning, pain and other symptoms were published in 2018 by the Society for Integrative Oncology,112 and identify a wide array of psychotherapeutic interventions that can serve as effective supportive care strategies during breast cancer treatment.

Cognitive Behavioral Therapies Specific to Radiation Therapy for Breast Cancer

Although information on psychotherapeutic interventions specific to the radiation oncology environment is much sparser, the few available studies also suggest that CBT can reduce stress, tension, depression, fatigue, and anger in patients treated with radiation for various cancers.89,113 Studies specific to CBT in breast cancer patients undergoing radiation therapy are also rare. The results of the few available studies are highly encouraging (Table 3).

Randomized Trials of Cognitive Behavioral Therapy in Radiation Therapy for Curatively Treated Breast Cancer

An early study by Bridge et al114 in 1988 randomized CBT, consisting of relaxation therapy versus relaxation therapy and guided imagery, performed weekly during radiation therapy with home practice versus no intervention. The trial showed that the regimen of both arms, that contained relaxation therapy, significantly decreased mood disturbances, as assessed by the Profile of Mood States, compared to the no-intervention group. Anxiety and depression were, however, unaffected.

Nunes et al116 showed that daily guided relaxation, guided imagery, and meditation in a group setting and home practice during the radiation therapy course significantly reduced stress, anxiety, and depression scores in patients receiving radiation for breast cancer. Furthermore, Kolcaba and Fox115 showed that listening to guided imagery audiotapes resulted in improvements in comfort and was particularly impactful when employed early, within the first 3 weeks of radiation therapy.

Overall, the broad experience with CBT in oncology in general and the emerging data on of CBT in the radiation oncology environment for breast cancer patients,114–117 suggest that these strategies are a yet untapped resource to improve breast cancer patients’ anxiety and stress during radiation therapy. Based on these outcomes, CBT may serve as a promising adjunct to help enhance patients’ ability to cooperate and perform well. This is important because advanced radiation therapy procedures, such as DIBH, increasingly require physically and mentally demanding participation from patients that further elevate their stress and anxiety levels. CBT approaches that have been well validated in radiologic and interventional procedures, such MRI, breast biopsies, and surgical procedures,108–110,118 can be adaptable to the specific needs of advanced radiation therapy, particularly if combined with coaching and training.


Several major studies have also incorporated hypnosis as an adjunct to CBT and have shown improvement in stress, anxiety, and pain in cancer patients.

The use of hypnosis in medical settings has been defined as “an agreement between a person designated as the hypnotist and a person designated as the client or patient to participate in a psychotherapeutic technique based on the hypnotist providing suggestions for changes in sensation, perception, cognition, affect, mood, or behavior.119 Although well-suited for the medical setting and included into the clinical practice guidelines for integrative therapies112 and despite the level I evidence for statistically significant improvement in stress, anxiety, and pain in cancer patients, hypnosis has not been widely disseminated in oncology practice.

In breast cancer patients, most experience with hypnosis has focused on breast biopsy procedures, surgery and the chemotherapy setting. In a systematic review of randomized trials of hypnosis in breast cancer, hypnosis reduced pain and distress in patients undergoing diagnostic breast biopsy and breast surgery, and additionally positively influenced fatigue and nausea surgical patients.120

In radiation therapy for breast cancer, Montgomery and colleagues121–124 have employed a combination of both, CBT and hypnosis (CBTH), with the premise that a multimodal approach of both CBT combined with hypnosis can yield larger clinical effect sizes than CBT alone125,126 (Table 4). The investigators showed that patients had a significantly lower overall negative affect and higher positive affect, compared to the control group.124 The CBTH regimen included first an individual hypnosis session with a licensed clinical psychologist and home instructions/resources for self-hypnosis before the radiation therapy planning (CT simulation) procedure. This was followed by a CBT session just before the verification procedure day (verification of treatment position and imaging on the day before the first radiation treatment). The CBT component included cognitive reframing, cognitive restructuring, stress management, and stress coping training. The CBTH interventions started before radiation therapy, based on the principle that negative affect related to breast cancer radiotherapy is most intense in the pretreatment phase.127 Interventions during the radiation therapy course included individual twice-weekly review sessions with the psychologist, augmented by a home program and regular discussion sessions that promoted the practice of CBT and self-hypnosis by patients at home. In a follow-up randomized trial of the multimodal CBTH approach, there was significantly reduced emotional distress, as assessed by Profile of Mood States testing (Table 4), in the domains of tension-anxiety, depression-dejection, anger-hostility, vigor-activity, and fatigue-inertia, not only during but beyond the radiation therapy course.128

Randomized Trials of Combined Cognitive Behavioral Therapy and Hypnosis in Radiation Therapy for Curatively Treated Breast Cancer

Although no randomized trials have compared CBT to CBTH, these data suggest that the addition of hypnosis, enhanced by self-hypnosis, may augment the effects of CBT in reducing anxiety in patients with breast cancer who receive radiation therapy.


Overall, psychotherapeutic interventions have proofed to be important and impactful adjuncts to medical cancer therapy. Early results on educational and training strategies to optimize patients’ conditioning for increasingly complex organ-sparing radiation treatment procedures have similarly shown impact and benefit. The evidence laid out in the prior 3 sections strongly suggests that education/training and psychotherapeutic interventions can improve physical conditioning and cooperation, and alleviate emotional distress and anxiety related to radiation therapy, respectively, in breast cancer patients.

To optimize patients’ ability to perform and cooperate physically in anxiety-provoking, stressful, and multirepetitive radiation therapy procedures—while they are still consumed by coping with their cancer diagnosis—is essential for optimal organ sparing during advanced radiation therapy. The ability to address patients’ anxiety and stress, with their known detrimental effects on respiratory patterns, can be an important contributor to optimizing the delivery DIBH in heart-sparing radiation therapy.

Evidence suggests that the addition of hypnotic approaches may further augment the success of CBT. Such multimodal approach tends to be more involved, time-consuming, and resource-intense for the broad range of radiation oncology practitioners who treat a disease as common as breast cancer. At the same time, abbreviated approaches, such as guided self-hypnosis on a framework of CBT may offer additional options.

Although gaps in knowledge exist, leveraging both strategies, education/training and psychotherapeutic interventions, holds the promise that these approaches complement each other to improve physical and emotional well-being, both in the long term by reducing radiation therapy-induced cardiac toxicities, and in the short term by alleviating physical and cognitive distress during cancer therapy.


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            anxiety; breast cancer; cardiac toxicity; cognitive behavioral therapy; deep inspiration breath hold; distress; hypnosis; image guidance; radiation therapy; respiratory training

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