Heart protection from toxicity and enhanced wellbeing in breast cancer therapy

Heart toxicity challenge in breast cancer therapy

In patients with breast cancer, the most common cancer in women, radiation therapy to the breast or chest is frequently needed to control the tumor and improve the chance of survival.  Despite advances radiation therapy for breast cancer, there are two challenges: 1. Cardiac injury from scattered radiation to the heart that can result in long-term morbidity and mortality in breast cancer survivors [1, 2], and 2. Patients’ cognitive distress and anxiety that often interfere with their ability to tolerate novel heart-protecting radiation therapy techniques aimed at reducing the radiation dose to the heart. The aim of the Focus Group is to develop and test innovative approaches to alleviate both these challenges.

Advanced radiation delivery technologies and the human factor

Respiratory motion management is the most promising such advanced technique for heart-protecting radiation therapy in breast cancer. By delivering radiation therapy in a highly targeted/focused technique and during an extended controlled deep inspiration breath hold (DIBH), greater physical separation between the radiation target (breast, chest wall) and the heart can be achieved.  With greater distance of the heart from the target, the radiation dose spillage to the heart is reduced, and this dose reduction holds the promise to achieve better cardiac health in breast cancer survivors.  DIBH requires the patient to perform a precisely timed and sustained voluntary breath hold for each daily radiation treatment in the three- to four-week course of treatment.  However, the DIBH procedure is often poorly tolerated and poorly performed by patients, resulting in variable success; and clinical protocols of DIBH vary widely.

Patients who undergo radiation therapy for breast cancer generally experience significant cognitive distress and anxiety, augmented by the added burden of recovery from preceding surgery and chemotherapy. This is aggravated by the repetitive stringent treatment procedures demanded by advanced radiation techniques and the confining, threatening therapy equipment, which frequently intensifies patients’ anxiety and leaves them unprepared and unable to cooperate with the treatment.

“High-tech and gentle-touch”

Our Focus Group has been investigating a new approach combining the novel heart-protecting (heart-sparing) radiation therapy technologies and techniques with targeted preparatory training and anxiety-reducing cognitive interventions that leverage physical conditioning for DIBH while promoting anxiety and stress reduction through rapport, reframing, and relaxation techniques.  We leverage this combined advanced technology (“high-tech”) and integrative health (“gentle-touch”) approach to improve patients’ skill and compliance with radiation therapy procedures in DIBH, and to improve physical and emotional well-being, both and in the short term by alleviating physical and cognitive distress during cancer therapy, and in the long term by reducing therapy-induced cardiac toxicities.

DIBH training and cognitive interventions

Leveraging and synergizing the leading-edge technical advancements in breast cancer at TUM Radiation Oncology, embedded in the Comprehensive Cancer Center (CCC-M and RHCCC), the EU clinical trial environment, Molecular Cardiac Imaging, and Molecular Biology, the Focus Group has been working to apply novel patient-directed cognitive and training interventions in combination with the further developed advanced DIBH radiation therapy technologies and techniques to derive a cohesive integrated strategy for DIBH and heart dose optimization.

The TUM Radiation Oncology Team ­(Stephanie Combs, Jan Wilkens, Daniel Habermehl, Franz Pfeiffer, Markus Oechsner, Fridtjof Nüsslin, Kai Borm), is focused on understanding underlying mechanisms of radiation-induced cardiac toxicities and unraveling the relevance of dose to different heart structures [3-6].  The Focus Group’s work builds on the TUM faculty’s investigations aimed at understanding which heart sub-structures are the most critical targets for dose reduction to prevent cardiac toxicities [3].

Investigations at the University of Washington, Seattle, are exploring novel strategies to improve DIBH procedure performance by patients through coached patient self-training interventions [7, 8]. The team developed an in-advance coaching and preparatory home practice regimen that improved patients’ ability to perform DIBH ...and further reduced the dose to the heart (maximal cardiac dose: 13.1 Gy), compared to patients who performed DIBH without coaching (19.4 Gy, p=0.004) [8]. The Focus Group's work also builds on the Alumna Fellow's prior investigations at Ohio State University demonstrating that advanced rapport, reframing, and relaxation techniques, applied before medical procedures, enhanced patients’ comfort with distressing medical imaging procedures [10, 11].  The Focus Group has been developing applications of both the targeted training and the anxiety-reducing cognitive interventions to augment the heart-dose reducing effectiveness of DIBH.

Clinical trial development

The existing clinical trial entitled GATing at TUM (GATTUM), currently open to accrual at TUM Radiation Oncology, provides an outstanding platform for implementing and testing the effect of the training and cognitive interventions. The trial employs image-guided targeted radiation therapy and collects precise chest wall motion tracking, respiratory monitoring, and imaging data in DIBH radiation therapy to establish DIBH quality performance metrics. Imaging and radiomics analyses will ultimately provide data to guide dose optimization and dose reduction strategies for critical normal tissue organ sparing of the heart and adjacent organs.

The Focus Group is implementing the developed training modules at TUM and within GATTUM.  The cognitive rapport, reframing, and relaxation techniques, which have to date been applied in imaging and interventional procedures but not in radiation oncology, are being adapted to the specific needs of breast cancer patients and to the  ­physical and cognitive demands and process of DIBH. These techniques are integrated  with targeted respiratory training to enhance each patient’s physical DIBH capability and tolerance. Script development for the  ­integrative health rapport, reframing, and relaxation techniques continue to evolve, and team training in the educational and cognitive techniques is planned. Oncologic quality-of-life survey tools have been adapted to the specific needs of breast cancer, DIBH, and radiation therapy.

Studies and projects in 2020

While the Covid-19 pandemic prevented us from interacting in person in 2020 due to restrictions, remote collaborations have flourished.

The randomized clinical trial proposal “Respiratory Training and Relaxation Techniques to Improve Adjuvant Radiation Therapy in DIBH in Breast Cancer” (PI: Stephanie Combs) was submitted to the Deutsche Krebshilfe and has received favorable preliminary reviews.We undertook a major effort in 2020 at the University of Washington, with major collaboration by TUM faculty, to assemble a 13-article, two-issue Special Edition of the journal TMRI entitled “Human Touch for High-Tech Imaging and Imaging-guided Procedures: Integrative Medicine Strategies for Patient-Centered Nonpharmacologic Approaches” (Guest Editors: Nina A. Mayr, William T.C. Yuh) [12, 13]. The diverse multi-institutional and multi-disciplinary teams laid out a broad spectrum of integrative medicine and technology-based approaches in radiation oncology, imaging and other complex medical procedures for reducing patient anxiety to improve patient cooperation, quality of care and safety. Breast cancer was a major focus area in this effort [14].

Additional study of the preparatory training regimen in 2020 showed that the targeted training program not only reduced cardiac radiation dose through patients’ ability to perform an extended (i.e., “deeper”) DIBH, but also stably sustained the extended DIBH throughout treatment, particularly in challenging patients with pre-existing cardio-pulmonary disease [9].

New collaborative projects between the University of Washington, TUM (Stephanie Combs, Kai Borm), and the University of Colorado (Alexandra Chadderdon, Psy D) to systematically evaluate patient anxiety in the radiation oncology environment are ongoing and will further inform the Focus Group’s program, the trial, and future strategies.