Secondary Logo

Journal Logo

Review Articles

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

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

Abstract

IMPORTANCE OF RADIATION THERAPY IN BREAST CANCER

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 INJURY AND DEEP INSPIRATION BREATH HOLD PROCEDURE

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.

FIGURE 1
FIGURE 1:
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.

FIGURE 2
FIGURE 2:
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.

TABLE 1
TABLE 1:
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.

TABLE 2
TABLE 2:
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.

ANXIETY AND STRESS IN RADIATION THERAPY

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.

NONMEDICAL APPROACH: EDUCATIONAL AND PHYSICAL TRAINING

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.

NONMEDICAL APPROACH: INTEGRATIVE HEALTH: COGNITIVE BEHAVIORAL THERAPY

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).

TABLE 3
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.

NONMEDICAL APPROACH: INTEGRATIVE HEALTH: HYPNOSIS AND HYPNOSIS + COGNITIVE THERAPY

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

TABLE 4
TABLE 4:
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.

CONCLUSION

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.

REFERENCES

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68:394–424.
2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347:1233–1241.
3. Vinh-Hung V, Verschraegen C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 2004; 96:115–121.
4. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet (London, England) 2005; 366:2087–2106.
5. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997; 337:949–955.
6. Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 2005; 97:116–126.
7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69:7–34.
8. American Cancer Society: Cancer Treatment & Survivorship Facts & Figures 2019-2021. Available at: https://wwwcancerorg/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-treatment-and-survivorship-facts-and-figures/cancer-treatment-and-survivorship-facts-and-figures-2019-2021pdf, page 8. (Accessed March 1, 2020)
9. Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 2013; 368:987–998.
10. Taylor C, McGale P, Bronnum D, et al. Cardiac structure injury after radiotherapy for breast cancer: cross-sectional study with individual patient data. J Clin Oncol 2018; 36:2288–2296.
11. Correa CR, Litt HI, Hwang WT, et al. Coronary artery findings after left-sided compared with right-sided radiation treatment for early-stage breast cancer. J Clin Oncol 2007; 25:3031–3037.
12. Paszat LF, Mackillop WJ, Groome PA, et al. Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. J Clin Oncol 1998; 16:2625–2631.
13. Cuzick J, Stewart H, Rutqvist L, et al. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol 1994; 12:447–453.
14. Darby SC, Cutter DJ, Boerma M, et al. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys 2010; 76:656–665.
15. Jordan JH, Todd RM, Vasu S, et al. Cardiovascular magnetic resonance in the oncology patient. JACC Cardiovasc Imaging 2018; 11:1150–1172.
16. Drost L, Yee C, Lam H, et al. A systematic review of heart dose in breast radiotherapy. Clin Breast Cancer 2018; 18:e819–e824.
17. Taylor CW, Wang Z, Macaulay E, et al. Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiati Oncol Biol, Phys 2015; 93:845–853.
18. Nilsson G, Holmberg L, Garmo H, et al. Distribution of coronary artery stenosis after radiation for breast cancer. J Clin Oncol 2012; 30:380–386.
19. Wennstig AK, Garmo H, Isacsson U, et al. The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiat Oncol 2019; 14:40.
20. Lee HY, Chang JS, Lee IJ, et al. The deep inspiration breath hold technique using Abches reduces cardiac dose in patients undergoing left-sided breast irradiation. Radiat Oncol J 2013; 31:239–246.
21. Pedersen AN, Korreman S, Nystrom H, et al. Breathing adapted radiotherapy of breast cancer: reduction of cardiac and pulmonary doses using voluntary inspiration breath-hold. Radiother Oncol 2004; 72:53–60.
22. Kalet A, Kim A, Cao N, et al. Impact of breath hold coaching and home practice on surface-tracked deep inspiratory breath-hold (DIBH) radiotherapy in patients with left-sided breast cancer. AAPM 2017.
23. Kalet AM, Cao N, Smith WP, et al. Accuracy and stability of deep inspiration breath hold in gated breast radiotherapy—a comparison of two tracking and guidance systems. Phys Med 2019; 60:174–181.
24. Remouchamps VM, Huyskens DP, Mertens I, et al. The use of magnetic sensors to monitor moderate deep inspiration breath hold during breast irradiation with dynamic MLC compensators. Radiother Oncol 2007; 82:341–348.
25. Alderliesten T, Sonke JJ, Betgen A, et al. Accuracy evaluation of a 3-dimensional surface imaging system for guidance in deep-inspiration breath-hold radiation therapy. Int J Radiat Oncol Biol Phys 2013; 85:536–542.
26. Djajaputra D, Li S. Real-time 3D surface-image-guided beam setup in radiotherapy of breast cancer. Medical physics 2005; 32:65–75.
27. Rong Y, Walston S, Welliver MX, et al. Improving intra-fractional target position accuracy using a 3D surface surrogate for left breast irradiation using the respiratory-gated deep-inspiration breath-hold technique. PLoS One 2014; 9:e97933.
28. Meyer J, Smith W, Geneser S, et al. Characterizing a deformable registration algorithm for surface-guided breast radiotherapy. Med Physics 2020; 47:352–362.
29. Fassi A, Ivaldi GB, Meaglia I, et al. Reproducibility of the external surface position in left-breast DIBH radiotherapy with spirometer-based monitoring. J Appl Clin Med Phys 2014; 15:130–140.
30. Moran JM, Balter JM, Ben-David MA, et al. Short-term displacement and reproducibility of the breast and nodal targets under active breathing control. Int J Radiat Oncol Biol Phys 2007; 68:541–546.
31. Mast ME, Vredeveld EJ, Credoe HM, et al. Whole breast proton irradiation for maximal reduction of heart dose in breast cancer patients. Breast Cancer Res Treat 2014; 148:33–39.
32. Boda-Heggemann J, Knopf A-C, Simeonova-Chergou A, et al. Deep inspiration breath hold-based radiation therapy: a clinical review. Int J Radiat Oncol Biol Phys 2016; 94:478–492.
33. Sixel KE, Aznar MC, Ung YC. Deep inspiration breath hold to reduce irradiated heart volume in breast cancer patients. Int J Radiat Oncol Biol Phys 2001; 49:199–204.
34. Lin A, Sharieff W, Juhasz J, et al. The benefit of deep inspiration breath hold: evaluating cardiac radiation exposure in patients after mastectomy and after breast-conserving surgery. Breast Cancer 2017; 24:86–91.
35. Korreman SS, Pedersen AN, Nottrup TJ, et al. Breathing adapted radiotherapy for breast cancer: comparison of free breathing gating with the breath-hold technique. Radiother Oncol 2005; 76:311–318.
36. Cao N, Kalet AM, Young LA, et al. Predictors of cardiac and lung dose sparing in DIBH for left breast treatment. Phys Med 2019; 67:27–33.
37. Walston S, Quick AM, Kuhn K, et al. Dosimetric considerations in respiratory-gated deep inspiration breath-hold for left breast irradiation. Technol Cancer Res Treat 2017; 16:22–32.
38. Swanson T, Grills IS, Ye H, et al. Six-year experience routinely using moderate deep inspiration breath-hold for the reduction of cardiac dose in left-sided breast irradiation for patients with early-stage or locally advanced breast cancer. Am J Clin Oncol 2013; 36:24–30.
39. Tanguturi SK, Lyatskaya Y, Chen Y. Prospective assessment of deep inspiration breath-hold using 3-dimensional surface tracking for irradiation of left-sided breast cancer. Pract Radiat Oncol 2015; 5:358–365.
40. Nissen HD, Appelt AL. Improved heart, lung and target dose with deep inspiration breath hold in a large clinical series of breast cancer patients. Radiother Oncol 2013; 106:28–32.
41. Kim A, Kalet AM, Cao N, et al. Effects of preparatory coaching and home practice for deep inspiration breath hold on cardiac dose for left breast radiation therapy. Clin Oncol (R Coll Radiol) 2018; 30:571–577.
42. Comsa D, Barnett E, Le K, et al. Introduction of moderate deep inspiration breath hold for radiation therapy of left breast: initial experience of a regional cancer center. Pract Radiat Oncol 2014; 4:298–305.
43. Eldredge-Hindy H, Lockamy V, Crawford A, et al. Active breathing coordinator reduces radiation dose to the heart and preserves local control in patients with left breast cancer: report of a prospective trial. Pract Radiat Oncol 2015; 5:4–10.
44. Osman SO, Hol S, Poortmans PM, et al. Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation. Radiother Oncol 2014; 112:17–22.
45. Remouchamps VM, Letts N, Yan D, et al. Three-dimensional evaluation of intra- and interfraction immobilization of lung and chest wall using active breathing control: a reproducibility study with breast cancer patients. Int J Radiat Oncol Biol Phys 2003; 57:968–978.
46. Bruzzaniti V, Abate A, Pinnaro P, et al. Dosimetric and clinical advantages of deep inspiration breath-hold (DIBH) during radiotherapy of breast cancer. J Exp Clin Cancer Res 2013; 32:88.
    47. Lawler G, Leech M. Dose sparing potential of deep inspiration breath-hold technique for left breast cancer radiotherapy organs-at-risk. Anticancer Res 2017; 37:883–890.
    48. Stranzl H, Zurl B, Langsenlehner T, et al. Wide tangential fields including the internal mammary lymph nodes in patients with left-sided breast cancer. Influence of respiratory-controlled radiotherapy (4D-CT) on cardiac exposure. Strahlenther Onkol 2009; 185:155–160.
    49. Zhao F, Shen J, Lu Z, et al. Abdominal DIBH reduces the cardiac dose even further: a prospective analysis. Radiat Oncol 2018; 13:116.
    50. Hayden AJ, Rains M, Tiver K. Deep inspiration breath hold technique reduces heart dose from radiotherapy for left-sided breast cancer. J Med Imaging Radiat Oncol 2012; 56:464–472.
    51. Stranzl H, Zurl B. Postoperative irradiation of left-sided breast cancer patients and cardiac toxicity. Does deep inspiration breath-hold (DIBH) technique protect the heart? Strahlenther Onkol 2008; 184:354–358.
    52. Mulliez T, Veldeman L, Speleers B, et al. Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation. Radiother Oncol 2015; 114:79–84.
    53. Mast ME, Van Kempen-Harteveld L, Heijenbrok MW, et al. Left-sided breast cancer radiotherapy with and without breath-hold: does IMRT reduce the cardiac dose even further? Radiother Oncol 2013; 108:248–253.
    54. Reardon KA, Read PW, Morris MM, et al. A comparative analysis of 3D conformal deep inspiratory-breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer. Med Dosim 2013; 38:190–195.
    55. McIntosh A, Shoushtari AN, Benedict SH, et al. Quantifying the reproducibility of heart position during treatment and corresponding delivered heart dose in voluntary deep inhalation breath hold for left breast cancer patients treated with external beam radiotherapy. Int J Radiat Oncol Biol Phys 2011; 81:e569–e576.
    56. Yeung R, Conroy L, Long K, et al. Cardiac dose reduction with deep inspiration breath hold for left-sided breast cancer radiotherapy patients with and without regional nodal irradiation. Radiat Oncol 2015; 10:200.
    57. Hjelstuen MH, Mjaaland I, Vikstrom J, et al. Radiation during deep inspiration allows loco-regional treatment of left breast and axillary-, supraclavicular- and internal mammary lymph nodes without compromising target coverage or dose restrictions to organs at risk. Acta Oncol 2012; 51:333–344.
    58. Schönecker S, Walter F, Freislederer P, et al. Treatment planning and evaluation of gated radiotherapy in left-sided breast cancer patients using the CatalystTM/SentinelTM system for deep inspiration breath-hold (DIBH). Radiat Oncol 2016; 11:143.
    59. Kunheri B, Kotne S, Nair SS, et al. A dosimetric analysis of cardiac dose with or without active breath coordinator moderate deep inspiratory breath hold in left sided breast cancer radiotherapy. J Cancer Res Ther 2017; 13:56–61.
      60. Wiant D, Wentworth S, Liu H, et al. How important is a reproducible breath hold for deep inspiration breath hold breast radiation therapy? Int J Radiat Oncol Biol Phys 2015; 93:901–907.
      61. Verhoeven K, Sweldens C, Petillion S, et al. Breathing adapted radiation therapy in comparison with prone position to reduce the doses to the heart, left anterior descending coronary artery, and contralateral breast in whole breast radiation therapy. Pract Radiat Oncol 2014; 4:123–129.
      62. Vikstrom J, Hjelstuen MHB, Mjaaland I. Cardiac and pulmonary dose reduction for tangentially irradiated breast cancer, utilizing deep inspiration breath-hold with audio-visual guidance, without compromising target coverage. Acta Oncol 2011; 50:42–50.
      63. Wang W, Purdie TG, Rahman M, et al. Rapid automated treatment planning process to select breast cancer patients for active breathing control to achieve cardiac dose reduction. Int J Radiat Oncol Biol Phys 2012; 82:386–393.
      64. Bolukbasi Y, Saglam Y, Selek U, et al. Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy. Tumori 2014; 100:169–178.
      65. Joo JH, Kim SS, Ahn SD, et al. Cardiac dose reduction during tangential breast irradiation using deep inspiration breath hold: a dose comparison study based on deformable image registration. Radiat Oncol 2015; 10:264.
        66. Mohamad O, Shiao J, Zhao B, et al. Deep inspiration breathhold for left-sided breast cancer patients with unfavorable cardiac anatomy requiring internal mammary nodal irradiation. Pract Radiat Oncol 2017; 7:e361–e367.
        67. Johansen S, Vikstrom J, Hjelstuen MH, et al. Dose evaluation and risk estimation for secondary cancer in contralateral breast and a study of correlation between thorax shape and dose to organs at risk following tangentially breast irradiation during deep inspiration breath-hold and free breathing. Acta Oncol 2011; 50:563–568.
          68. Rochet N, Drake JI, Harrington K, et al. Deep inspiration breath-hold technique in left-sided breast cancer radiation therapy: Evaluating cardiac contact distance as a predictor of cardiac exposure for patient selection. Pract Radiat Oncol 2015; 5:e127–e134.
          69. Borst GR, Sonke JJ, Den Hollander S, et al. Clinical results of image-guided deep inspiration breath hold breast irradiation. Int J Radiat Oncol Biol Phys 2010; 78:1345–1351.
          70. Oonsiri P, Wisetrinthong M, Chitnok M, et al. An effective patient training for deep inspiration breath hold technique of left-sided breast on computed tomography simulation procedure at King Chulalongkorn Memorial Hospital. Radiat Oncol J 2019; 37:201–206.
          71. Borm KJ, Oechsner M, Combs SE, et al. Deep-inspiration breath-hold radiation therapy in breast cancer: a word of caution on the dose to the axillary lymph node levels. Int J Radiat Oncol Biol Phys 2018; 100:263–269.
            72. Brintzenhofe-Szoc KM, Levin TT, Li Y, et al. Mixed anxiety/depression symptoms in a large cancer cohort: prevalence by cancer type. Psychosomatics 2009; 50:383–391.
            73. Eskelinen M, Ollonen P. Assessment of general anxiety in patients with breast disease and breast cancer using the Spielberger STAI self evaluation test: a prospective case-control study in Finland. Anticancer Res 2011; 31:1801–1806.
            74. Ollonen P, Lehtonen J, Eskelinen M. Anxiety, depression, and the history of psychiatric symptoms in patients with breast disease: a prospective case-control study in Kuopio, Finland. Anticancer Res 2005; 25:2527–2533.
            75. Kornblith AB, Ligibel J. Psychosocial and sexual functioning of survivors of breast cancer. Semin Oncol 2003; 30:799–813.
            76. Glanz K, Lerman C. Psychosocial impact of breast cancer: a critical review. Ann Behav Med 1992; 14:204–212.
            77. Flory N, Martinez Salazar GM, Lang EV. Hypnosis for acute distress management during medical procedures. Int J Clin Exp Hypn 2007; 55:303–317.
            78. Fritzsche K, Liptai C, Henke M. Psychosocial distress and need for psychotherapeutic treatment in cancer patients undergoing radiotherapy. Radiother Oncol 2004; 72:183–189.
            79. Lewis F, Merckaert I, Lienard A, et al. Anxiety and its time courses during radiotherapy for non-metastatic breast cancer: a longitudinal study. Radiother Oncol 2014; 111:276–280.
            80. Mose S, Budischewski KM, Rahn AN, et al. Influence of irradiation on therapy-associated psychological distress in breast carcinoma patients. Int J Radiat Oncol Biol Phys 2001; 51:1328–1335.
            81. Halkett GK, Kristjanson LJ, Lobb EA. ’If we get too close to your bones they’ll go brittle’: women's initial fears about radiotherapy for early breast cancer. Psychooncology 2008; 17:877–884.
            82. Nguyen XV, Tahir S, Bresnahan BW, et al. Prevalence and financial impact of claustrophobia, anxiety, patient motion, and other patient events in magnetic resonance imaging. Top Magn Reson Imaging 2020; 29:125–130.
            83. Ajam AA, Tahir S, Makary MS, et al. Communication and team interactions to improve patient experiences, quality of care, and throughput in MRI. Top Magn Reson Imaging 2020; 29:131–134.
            84. Kaidar-Person O, Meattini I, Deal AM, et al. The use of psychological supportive care services and psychotropic drugs in patients with early-stage breast cancer: a comparison between two institutions on two continents. Med Oncol 2017; 34:144.
            85. Borm KJ, Schiller K, Asadpour R, et al. Complementary and alternative medicine in radiotherapy: a comprehensive review. Top Magn Reson Imaging 2020; 29:149–156.
            86. Masaoka Y, Homma I. Anxiety and respiratory patterns: their relationship during mental stress and physical load. Int J Psychophysiol 1997; 27:153–159.
            87. Paulus MP. The breathing conundrum-interoceptive sensitivity and anxiety. Depress Anxiety 2013; 30:315–320.
            88. Rashid A. Anxiety in cancer patients. MD Anderson Manual of Psychosocial Oncology 2011; New York, NY:McGraw-Hill, Inc, 271–288.
            89. Institute of MedicineCancer Care for the Whole Patient: Ch. 3: Meeting Psychosocial Health Needs. Washington, DC:The National Academic Press; 2008.
            90. Inzelberg R, Peleg N, Nisipeanu P, et al. Inspiratory muscle training and the perception of dyspnea in Parkinson's disease. Can J Neurol Sci 2005; 32:213–217.
            91. Shahin B, Germain M, Kazem A, et al. Benefits of short inspiratory muscle training on exercise capacity, dyspnea, and inspiratory fraction in COPD patients. Int J Chron Obstruct Pulmon Dis 2008; 3:423–427.
            92. Steffens D, Young J, Beckenkamp PR, et al. Feasibility and acceptability of PrE-operative Physical Activity to improve patient outcomes After major cancer surgery: study protocol for a pilot randomised controlled trial (PEPA Trial). Trials 2018; 19:112.
            93. Weiner P, Waizman J, Magadle R, et al. The effect of specific inspiratory muscle training on the sensation of dyspnea and exercise tolerance in patients with congestive heart failure. Clin Cardiol 1999; 22:727–732.
            94. Vašíčková J, Neumannová K, Svozil Z. The effect of respiratory muscle training on fin-swimmers’ performance. J Sports Sci Med 2017; 16:521–526.
            95. Van den Bogaard VA, Ta BD, Van der Schaaf A, et al. Validation and modification of a prediction model for acute cardiac events in patients with breast cancer treated with radiotherapy based on three-dimensional dose distributions to cardiac substructures. J Clin Oncol 2017; 35:1171–1178.
            96. Parkes MJ, Green S, Kilby W, et al. The feasibility, safety and optimization of multiple prolonged breath-holds for radiotherapy. Radiother Oncol 2019; 141:296–303.
            97. Parkes MJ, Green S, Stevens AM, et al. Safely prolonging single breath-holds to >5 min in patients with cancer; feasibility and applications for radiotherapy. Br J Radiol 2016; 89:20160194.
            98. Yue GH, Cole KJ, Darling WG, et al. Imagined muscle contraction training increases voluntary neural drive to muscle. J Psychophysiol 1996; 10:198–208.
            99. Yao WX, Ranganathan VK, Allexandre D, et al. Kinesthetic imagery training of forceful muscle contractions increases brain signal and muscle strength. Front Hum Neurosci 2013; 7:561.
            100. Sharma N, Baron JC. Does motor imagery share neural networks with executed movement: a multivariate fMRI analysis. Front Hum Neurosci 2013; 7:564.
            101. Jacobsen P, Donovan K, Swaine Z. Chang A, Ganz P, Hayes D, et al. Management of anxiety and depression in adult cancer patients: Toward an evidence-based approach. Oncology: An Evidence-based Approach. New York, NY:Springer-Verlag; 2006. 1552–1579.
            102. Chadderdon AL, Carns DR, Pudalov LR. Underlying mechanisms of psychological interventions in magnetic resonance imaging and image-guided radiology procedures. Top Magn Reson Imaging 2020; 29:157–163.
            103. Matthews H, Grunfeld EA, Turner A. The efficacy of interventions to improve psychosocial outcomes following surgical treatment for breast cancer: a systematic review and meta-analysis. Psychooncology 2017; 26:593–607.
            104. Hulbert-Williams NJ, Beatty L, Dhillon HM. Psychological support for patients with cancer: evidence review and suggestions for future directions. Curr Opin Support Palliat Care 2018; 12:276–292.
            105. National Breast Cancer Centre and National Cancer Control Initiative AustraliaClinical Practice Guidelines for the Psychosocial Care of Adults With Cancer. 2003; Camperdown, NSW:https://canceraustralia.gov.au/sites/default/files/publications/pca-1-clinical-practice-guidelines-for-psychosocial-care-of-adults-with-cancer_504af02682bdf.pdfhttps://canceraustralia.gov.au/sites/default/files/publications/pca-1-clinical-practice-guidelines-for-psychosocial-care-of-adults-with-cancer_504af02682bdf.pdf (Accessed May 11, 2020).
            106. Trijsburg RW, van Knippenberg FC, Rijpma SE. Effects of psychological treatment on cancer patients: a critical review. v 1992; 54:489–517.
            107. Tatrow K, Montgomery GH. Cognitive behavioral therapy techniques for distress and pain in breast cancer patients: a meta-analysis. J Behav Med 2006; 29:17–27.
            108. Lang EV, Benotsch EG, Fick LJ, et al. Adjunctive non-pharmacological analgesia for invasive medical procedures: a randomised trial. Lancet 2000; 355:1486–1490.
            109. Lang EV, Yuh WT, Ajam A, et al. Understanding patient satisfaction ratings for radiology services. AJR Am J Roentgenol 2013; 201:1190–1195.
            110. Norbash A, Yucel K, Yuh W, et al. Effect of team training on improving MRI study completion rates and no-show rates. J Magn Reson Imaging 2016; 44:1040–1047.
            111. Phillips KM, Antoni MH, Lechner SC, et al. Stress management intervention reduces serum cortisol and increases relaxation during treatment for nonmetastatic breast cancer. Psychosom Med 2008; 70:1044–1049.
            112. Greenlee H, DuPont-Reyes MJ, Balneaves LG, et al. Clinical practice guidelines on the evidence-based use of integrative therapies during and after breast cancer treatment. CA Cancer J Clin 2017; 67:194–232.
            113. Decker TW, Cline-Elsen J, Gallagher M. Relaxation therapy as an adjunct in radiation oncology. J Clin Psychol 1992; 48:388–393.
            114. Bridge LR, Benson P, Pietroni PC, et al. Relaxation and imagery in the treatment of breast cancer. BMJ 1988; 297:1169–1172.
            115. Kolcaba K, Fox C. The effects of guided imagery on comfort of women with early stage breast cancer undergoing radiation therapy. Oncol Nurs Forum 1999; 26:67–72.
            116. Nunes DF, Rodriguez AL, Da Silva Hoffmann F, et al. Relaxation and guided imagery program in patients with breast cancer undergoing radiotherapy is not associated with neuroimmunomodulatory effects. J Psychosom Res 2007; 63:647–655.
            117. Henderson VP, Massion AO, Clemow L, et al. A randomized controlled trial of mindfulness-based stress reduction for women with early-stage breast cancer receiving radiotherapy. Integr Cancer Ther 2013; 12:404–413.
            118. Lang EV, Berbaum KS, Faintuch S, et al. Adjunctive self-hypnotic relaxation for outpatient medical procedures: a prospective randomized trial with women undergoing large core breast biopsy. Pain 2006; 126:155–164.
            119. Montgomery GH, Bovbjerg DH, Schnur JB, et al. A randomized clinical trial of a brief hypnosis intervention to control side effects in breast surgery patients. J Natl Cancer Inst 2007; 99:1304–1312.
            120. Cramer H, Lauche R, Paul A, et al. Hypnosis in breast cancer care: a systematic review of randomized controlled trials. Integr Cancer Ther 2015; 14:5–15.
            121. Montgomery GH, David D, Kangas M, et al. Randomized controlled trial of a cognitive-behavioral therapy plus hypnosis intervention to control fatigue in patients undergoing radiotherapy for breast cancer. J Clin Oncol 2014; 32:557–563.
            122. Montgomery GH, DuHamel KN, Redd WH. A meta-analysis of hypnotically induced analgesia: how effective is hypnosis? Int J Clin Exp Hypn 2000; 48:138–153.
            123. Montgomery GH, Kangas M, David D, et al. Fatigue during breast cancer radiotherapy: an initial randomized study of cognitive-behavioral therapy plus hypnosis. Health Psychol 2009; 28:317–322.
            124. Schnur JB, David D, Kangas M, et al. A randomized trial of a cognitive-behavioral therapy and hypnosis intervention on positive and negative affect during breast cancer radiotherapy. J Clin Psychol 2009; 65:443–455.
            125. Bryant RA, Moulds ML, Guthrie RM, et al. The additive benefit of hypnosis and cognitive-behavioral therapy in treating acute stress disorder. J Consult Clin Psychol 2005; 73:334–340.
            126. Kirsch I, Montgomery G, Sapirstein G. Hypnosis as an adjunct to cognitive-behavioral psychotherapy: a meta-analysis. J Consult Clin Psychol 1995; 63:214–220.
            127. Buick DL, Petrie KJ, Booth R, et al. Emotional and functional impact of radiotherapy and chemotherapy on patients with primary breast cancer. J Psychosoc Oncol 2000; 18:39–62.
            128. Montgomery GH, Sucala M, Dillon MJ, et al. Cognitive-behavioral therapy plus hypnosis for distress during breast radiotherapy: a randomized trial. Am J Clin Hypn 2017; 60:109–122.
            129. Kolcaba KY. A theory of holistic comfort for nursing. J Adv Nurs 1994; 19:1178–1184.
            Keywords:

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

            Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.