Radiotherapy Delivery in Deep Inspiration for Pediatric Patients: TEDDI - a NOPHO Feasibility Study

Background:

The majority (approximately 80%) of pediatric patients with cancer become long-term survivors. Long-term follow-up of childhood cancer survivors has documented a substantial treatment-induced increased mortality and morbidity, primarily from cardiovascular disease and second cancers. Specifically, cardiac mortality has been shown to be 5-fold higher, cardiac morbidity 2-fold to 6-fold higher, and the incidence of second cancers 8-fold higher in childhood cancer survivors compared to the general population or siblings. Due to the young age at diagnosis and corresponding long life expectancy of pediatric patients the impact of late effect(s) on patient quality of life, morbidity, and ultimately mortality is non-trivial.

Radiotherapy-induced late effects are severe, yet difficult to assess and quantify as they occur late and, therefore, often are the results of treatment regimens now considered outdated. Nonetheless, the risk of radiation-induced late effects is known to be influenced by both the radiation dose and the volume of irradiated tissue. In adults, the use of more conformal radiotherapy delivery techniques and breathing adaptation has been introduced in order to limit the irradiation of the surrounding healthy organs. However, there has been a reluctance to implement new radiotherapy delivery techniques in the treatment of pediatric patients as late effects data are not available for these new techniques and for the fear of a low compliance with breathing instructions.

Deep inspiration breath-hold (DIBH) is a simple radiotherapy technique, which could have a dramatic impact on late effects in children. In DIBH, the radiotherapy is delivered while the patient holds his/her breath (defined as 4 to 6 sequential breath-holds of ≥20 sec). In deep inspiration, the patient anatomy is changed and imaging artifacts from respiratory movement are diminished as the organs are not moving. Radiotherapy in DIBH can reduce the irradiation of the heart, breasts, and lungs without impacting the delivered radiation dose to the tumor and with no detriment to other healthy organs. Also, the technique is simple and cost-efficient. DIBH is widely used throughout the world in adult patients with left-sided breast cancer and with mediastinal lymphoma to minimize the risk of radiation-induced late effects.

The Department of Radiation Oncology at Rigshospitalet has pioneered the use of DIBH in the treatment of patients with breast cancer and mediastinal lymphoma [Korreman et al., Pedersen et al.] and is currently prospectively testing the DIBH technique in a more frail population of lung cancer patients. The department has extensive experience in the daily delivery and patient coaching of adult patients. While the experience from several centers confirms that the compliance of adult patients to DIBH is excellent, no reports exist of the applicability of DIBH to pediatric patients, especially the very young.