Radiotherapy Delivery in Deep Inspiration for Pediatric Patients

Pediatric Cancer Clinical Trial

— TEDDI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03315546
• Other study ID #: H-16035870
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 1, 2017
• Est. completion date: December 31, 2029

Study information

• Verified date: October 2020
• Source: Rigshospitalet, Denmark
• Contact: Maja V Maraldo, MD, PhD
• Email: maja.vestmoe.maraldo[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

TEDDI is a non-randomised phase II trial in Scandinavia. All pediatric patients, referred for radiotherapy in the thorax or abdomen and irrespective of diagnosis, are eligible.

Deep inspiration breath-hold (DIBH) is a simple radiotherapy technique, which could have a dramatic impact on the risk of late effects in children. In DIBH, the radiotherapy is delivered while the patient holds his/her breath (4-6 sequential breath-holds). The anatomy is changed and imaging artifacts from respiratory movement are diminished. DIBH is widely used in adult patients with breast cancer and mediastinal lymphoma to minimize the risk of radiation-induced late effects due to a reduced dose to the healthy organs. Also, the technique is simple and cost-efficient.

For pediatric patients, the investigators aim to:

• Estimate the dosimetric benefit of radiotherapy using DIBH compared to free-breathing

• Establish the compliance of DIBH

• Determine if DIBH is an accurate and reproducible strategy

• Optimize treatment planning considering the risk from loss of tumour control as well as the risk of late effects.

Description:

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.

The investigators hypothesize that TEDDI is a feasible and reproducible strategy which will result in a 25% reduction in the mean radiation dose to the heart in pediatric patients referred for radiotherapy to tumors in the thorax or abdomen. This is expected to be true for all pediatric patients, regardless of age.

Through TEDDI, the investigators specifically aim to:

• Estimate the dosimetric benefit of radiotherapy using DIBH compared to free-breathing in pediatric patients.

• Establish the compliance of DIBH in pediatric patients in all age groups.

• Determine if DIBH is an accurate and reproducible strategy for pediatric patients.

Key research questions:

1. What is the extent of the dosimetric benefit of DIBH compared to free-breathing radiotherapy? For adult patients with breast cancer, malignant lymphoma, and lung cancer, radiotherapy delivered in DIBH compared to free-breathing significantly lowers the dose to the heart, lungs, and stomach. However, for very young patients the anatomical changes (i.e. inflation of the lungs, increased separation of the heart and the tumor) might be less pronounced than for adults hampering the dosimetric advantage of DIBH.

Hypothesis 1 (H1): For more than 75% of patients, treatment in DIBH will be dosimetrically superior to treatment in free-breathing.

2. Is DIBH well tolerated by pediatric patients throughout their treatment? At present, the information material regarding DIBH and the visual feedback equipment (consisting of video goggles) is designed for and aimed at adult patients. In TEDDI, all aspects of the current DIBH workflow will be adapted in order to provide a comfortable setting for pediatric patients. Based on preliminary tests on healthy volunteers, children as young as 5 years are able to comply with the DIBH instructions given by the present visual feedback equipment.

Hypothesis 2 (H2): over 90% of pediatric patients older than 5 years can perform a stable and comfortable DIBH (in the form of 4 to 6 sequential breath-holds of ≥20 sec) through their course of radiotherapy.

3. Can the prescribed radiation dose be delivered accurately and reproducibly to the tumor in DIBH? Interfraction monitoring will ensure reliable treatment between treatment days using the RPM system, and intrafraction monitoring will assess the stability of the patient positioning/breath-hold during the treatment. Image acquisition parameters will be optimized to provide sufficient image quality at the lowest possible radiation exposure.

Hypothesis 3 (H3): The tumor position will be reproducible from day to day, as well as from breath-hold to breath-hold. Variations in position will be less than 5 mm over the whole treatment course.

Treatment planning:

All diagnostic imaging during treatment and treatment planning will be performed according to national guidelines (as per cancer diagnosis). For the radiotherapy planning, a planning CT scan will be performed in DIBH as well as in free-breathing for each patient. On both scans the gross tumor volume (GTV), the clinical target volume (CTV) which comprises the GTV adjusted for normal tissue, and the planning target volume (PTV) which is the CTV including a planning margin, will be defined. All relevant, healthy organs at risk from radiation exposure will be contoured (e.g. heart, female breasts, lungs, esophagus, thyroid, salivary glands, spinal cord, bone marrow, stomach, spleen, kidneys, liver). A DIBH and a free-breathing radiotherapy plan will be calculated, both with similar planning objectives for the tumor and organs at risk. All DIBH treatment plans will be designed to keep the number of breath-holds per fraction as low as reasonably achievable (including image guidance) for patient comfort.

Whenever a PET scanning is considered an integral part of the radiotherapy planning, a PET scanning should also be performed in the treatment position in both DIBH and in free-breathing for optimal image fusion. However, for institutions where this is not feasible, participation in TEDDI is still possible.

Treatment delivery:

Patients will be treated in DIBH, if the calculated treatment plan in DIBH is superior to the treatment plan in free-breathing with respect to the lowest overall dose to the organs at risk while maintaining acceptable tumor coverage. Coverage of the CTV and PTV will have the highest priority, as per ICRU83 guidelines.

Follow-up:

Enrollment in TEDDI will not affect the standard follow-up program of pediatric patients which is diagnosis specific.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

Inclusion Criteria:

• Age 5-17 years.

• Patients with a tumor in the mediastinum or abdomen with possible need of radiotherapy according to current treatment guidelines, irrespective of cancer diagnosis.

• The ability to perform three sequential breath-holds of 20 seconds each during the coaching session.

• Written informed consent from parents or legal guardians.

Exclusion Criteria:

• Age younger than 5 years or older than 17 years.

• The need for radiotherapy under general anesthesia.

• CNS tumor or pelvic localization.

• Unable to understand coaching information directly or through interpretation.

Related Conditions & MeSH terms

• Pediatric Cancer
• Respiratory Aspiration

Intervention

Radiation:
• radiotherapy delivery in deep-inspiration
Radiotherapy delivery i deep-inspiration versus free-breathing

Locations

Country	Name	City	State
Denmark	Department of Clinical Oncology, Aarhus University Hospital	Aarhus
Denmark	Department of Clinical Oncology, Rigshospitalet	Copenhagen	Danmark
Finland	Department of Radiation Oncology, Comprehensive Cancer Center, Helsinki University Hospital	Helsinki

Sponsors (4)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Aarhus University Hospital, Helsinki University Central Hospital, Tampere University Hospital

Countries where clinical trial is conducted

Denmark,  Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The dosimetric benefit of DIBH	For each patient, the radiation treatment plan calculated in DIBH and in FB will be compared	1 day prior to treatment start, the superior radiation treatment plan is chosen for treatment delivery
Secondary	Patient compliance defined as 1) patient comfort	Patient comfort will be assessed through questionnaires (after first, middle and last treatment fraction) which aim to evaluate the level of information and coaching pre-treatment, the physical treatment environment at the departments, and the health care staff.	Through study completion, an average of 1 month total treatment time
Secondary	Patient compliance defined as 2) breathhold reproducibility	Tumor position will be used to evaluate the ability of patients to maintain the breath-hold during the whole course of treatment and to investigate the possibility that patients might get weaker and/or more tired and, thus, unable to perform a stable DIBH as the treatment course progresses. This will be done using the respiratory motion management system.	Through study completion, an average of 1 month total treatment time
Secondary	The accuracy of the treatment delivery	Treatment accuracy will evaluated based on daily volumetric imaging, planar kV imaging or surface imaging (e.g. Catalyst, VisionRT). If the tumor is not visible on the planar kV images, the sternum (mediastinal tumors) or the diaphragm (abdominal tumors) will be used as a surrogate structure. If the target position appears reproducible within 5 mm, the patient will be deemed compliant. In addition to the daily online positioning at the treatment machine before each fraction, the reproducibility of the target position will be assessed retrospectively by a medical physicist on a weekly basis.	Through study completion, an average of 1 month total treatment time