TEDDI: radiotherapy delivery in deep inspiration for pediatric patients - a NOPHO feasibility study

Anni Young Lundgaard, Lisa Lyngsie Hjalgrim, Laura Ann Rechner, Mirjana Josipovic, Morten Joergensen, Marianne Camille Aznar, Anne Kill Berthelsen, Lise Borgwardt, Christoffer Johansen, Annika Loft, Akmal Safwat, Leila Vaalavirta, Lena Specht, Maja Vestmoe Maraldo, Anni Young Lundgaard, Lisa Lyngsie Hjalgrim, Laura Ann Rechner, Mirjana Josipovic, Morten Joergensen, Marianne Camille Aznar, Anne Kill Berthelsen, Lise Borgwardt, Christoffer Johansen, Annika Loft, Akmal Safwat, Leila Vaalavirta, Lena Specht, Maja Vestmoe Maraldo

Abstract

Background: Radiotherapy (RT) delivered in deep inspiration breath-hold (DIBH) is a simple technique, in which changes in patient anatomy can significantly reduce the irradiation of the organs at risk (OARs) surrounding the treatment target. DIBH is routinely used in the treatment of some adult patients to diminish the risk of late effects; however, no formalized studies have addressed the potential benefit of DIBH in children.

Methods/design: TEDDI is a multicenter, non-randomized, feasibility study. The study investigates the dosimetric benefit of RT delivered in DIBH compared to free breathing (FB) in pediatric patients. Also, the study aims to establish the compliance to DIBH and to determine the accuracy and reproducibility in a pediatric setting. Pediatric patients (aged 5-17 years) with a tumor in the mediastinum or upper abdomen with the possible need of RT will be included in the study. Written informed consent is obligatory. Prior to any treatment, patients will undergo a DIBH training session followed by a diagnostic PET/CT- or CT-staging scan in both DIBH and FB. If the patient proceeds to RT, a RT planning CT scan will be performed in both DIBH and FB and two separate treatment plans will be calculated. The superior treatment plan, i.e. equal target coverage and lowest overall dose to the OARs, will be chosen for treatment. Patient comfort will be assessed daily by questionnaires and by adherence to the respiratory management procedure.

Discussion: RT in DIBH is expected to diminish irradiation of the OARs surrounding the treatment target and thereby reduce the risk of late effects in childhood cancer survivors.

Trial registration: The Danish Ethical Committee (H-16035870, approved November 24th 2016, prospectively registered). The Danish Data Protection Agency (2012-58-0004, approved January 1st 2017, prospectively registered). Registered at clinicaltrials.gov ( NCT03315546 , October 20th 2017, retrospectively registered).

Keywords: Deep inspiration breath-hold; Pediatric patients; Radiotherapy.

Conflict of interest statement

Ethics approval and consent to participate

The study has been approved by The Danish Ethical Committee (H-16035870) and by The Danish Data Protection Agency (2012–58-0004). The study has been registered at Consent for publication

Consent for publication of fig. 1 obtained.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
A six year old healthy volunteer perform deep inspiration breath-hold using the Real-time Position Management system from Varian Medical Systems (Palo Alto, USA). The screen provides a visual feed-back and helps guide the volunteer’s  respiration. Notice how the immobilization device does not support the volunteer sufficiently; if the volunteer was to receive radiotherapy a custom made fixation device should be constructed
Fig. 2
Fig. 2
Chart of estimated workflow during accrual and treatment planning. Abbreviations: CT = computed tomography; DIBH = deep inspiration breath-hold; FB = free breathing; PET = positron emission tomography; RT = radiotherapy

References

    1. Gatta G, Zigon G, Capocaccia R, Coebergh JW, Desandes E, Kaatsch P, et al. Survival of European children and young adults with cancer diagnosed 1995-2002. Eur J Cancer. 2009;45:992–1005. doi: 10.1016/j.ejca.2008.11.042.
    1. Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER Cancer statistics review, 1975–2014. Bethesda: National Cancer Institute; 2010.
    1. de Fine LS, Rugbjerg K, Gudmundsdottir T, Bonnesen TG, Asdahl PH, Holmqvist AS, et al. Long-term inpatient disease burden in the adult life after childhood Cancer in Scandinavia (ALiCCS) study: a cohort study of 21,297 childhood cancer survivors. PLoS Med. 2017;14:e1002296. doi: 10.1371/journal.pmed.1002296.
    1. Gudmundsdottir T, Winther JF, de Fine Licht S, Bonnesen TG, Asdahl PH, Tryggvadottir L, et al. Cardiovascular disease in adult life after childhood Cancer in Scandinavia: a population-based cohort study of 32,308 one-year survivors. Int J Cancer. 2015;137:1176–1186. doi: 10.1002/ijc.29468.
    1. Oeffinger KC, Mertens AC. Sklar C a, Kawashima T, Hudson MM, meadows AT, et al. chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572–1582. doi: 10.1056/NEJMsa060185.
    1. Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the childhood Cancer survivor study cohort. BMJ. 2009;339:b4606. doi: 10.1136/bmj.b4606.
    1. Tukenova M, Guibout C, Oberlin O, Doyon F, Mousannif A, Haddy N, et al. Role of cancer treatment in long-term overall and cardiovascular mortality after childhood cancer. J Clin Oncol. 2010;28:1308–1315. doi: 10.1200/JCO.2008.20.2267.
    1. Castellino SM, Geiger AM, Mertens AC, Leisenring WM, Tooze JA, Goodman P, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma : a report from the childhood Cancer survivor study. Blood. 2016;117:1806–1817. doi: 10.1182/blood-2010-04-278796.
    1. Mulrooney DA, Armstrong GT, Huang S, Ness KK, Ehrhardt MJ, Joshi VM, et al. Cardiac outcomes in adult survivors of childhood cancer exposed to cardiotoxic therapy. Ann Intern Med. 2016;164:93–101. doi: 10.7326/M15-0424.
    1. Bhatia S. High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin’s disease: report from the late effects study group. J Clin Oncol. 2003;21:4386–4394. doi: 10.1200/JCO.2003.11.059.
    1. De Bruin ML, Sparidans J, Van’t Veer MB, Noordijk EM, Louwman MWJ, Zijlstra JM, et al. Breast cancer risk in female survivors of Hodgkin’s lymphoma: lower risk after smaller radiation volumes. J Clin Oncol. 2009;27:4239–4246. doi: 10.1200/JCO.2008.19.9174.
    1. Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B, et al. Lung cancer following chemotherapy and radiotherapy for Hodgkin’s disease. J Natl Cancer Inst. 2002;94:182–192. doi: 10.1093/jnci/94.3.182.
    1. Armstrong GT, Chen Y, Yasui Y, Leisenring W, Gibson TM, Mertens AC, et al. Reduction in late mortality among 5-year survivors of childhood Cancer. N Engl J Med. 2016;374:833–842. doi: 10.1056/NEJMoa1510795.
    1. Korreman SS, Pedersen AN, Nøttrup TJ, Specht L, Nyström H. Breathing adapted radiotherapy for breast cancer: comparison of free breathing gating with the breath-hold technique. Radiother Oncol. 2005;76:311–318. doi: 10.1016/j.radonc.2005.07.009.
    1. 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. doi: 10.1016/j.radonc.2012.10.016.
    1. Petersen PM, Aznar MC, Berthelsen AK, Loft A, Schut DA, Maraldo M, et al. Prospective phase II trial of image-guided radiotherapy in Hodgkin lymphoma: benefit of deep inspiration breath-hold. Acta Oncol. 2014:1–7. 10.3109/0284186X.2014.932435.
    1. Josipovic M, Persson GF, Håkansson K, Damkjær SMS, Bangsgaard JP, Westman G, et al. Deep inspiration breath hold radiotherapy for locally advanced lung cancer: comparison of different treatment techniques on target coverage, lung dose and treatment delivery time. Acta Oncol. 2013;52:1582–1586. doi: 10.3109/0284186X.2013.813644.
    1. Aznar MC, Maraldo MV, Schut DA, Lundemann M, Brodin NP, Vogelius IR, et al. Minimizing late effects for patients with mediastinal Hodgkin lymphoma: deep inspiration breath-hold, IMRT, or both? Int J Radiat Oncol Biol Phys. 2015;92:169–174. doi: 10.1016/j.ijrobp.2015.01.013.
    1. Claude L, Malet C, Pommier P, Thiesse P, Chabaud S, Carrie C. Active breathing control for Hodgkin’s disease in childhood and adolescence: feasibility, advantages, and limits. Int J Radiat Oncol Biol Phys. 2007;67:1470–1475. doi: 10.1016/j.ijrobp.2006.11.008.
    1. Demoor-Goldschmidt C, Chiavassa S, Josset S, Mahé M, Supiot S. Respiratory-gated bilateral pulmonary radiotherapy for Ewing’s sarcoma and nephroblastoma in children and young adults: Dosimetric and clinical feasibility studies. Cancer/Radiothérapie. 2017;21:124–129. doi: 10.1016/j.canrad.2016.11.003.
    1. Damkjær SMS, Aznar MC, Pedersen AN, Vogelius IR, Bangsgaard JP, Josipovic M. Reduced lung dose and improved inspiration level reproducibility in visually guided DIBH compared to audio coached EIG radiotherapy for breast cancer patients. Acta Oncol (Madr) 2013;52:1458–1463. doi: 10.3109/0284186X.2013.813073.
    1. Specht L. Berthelsen AK. PET/CT in Radiation Therapy Planning. 10.1053/j.semnuclmed.2017.09.006.
    1. Girinsky T, van der Maazen R, Specht L, Aleman B, Poortmans P, Lievens Y, et al. Involved-node radiotherapy (INRT) in patients with early Hodgkin lymphoma: concepts and guidelines. Radiother Oncol. 2006;79:270–277. doi: 10.1016/j.radonc.2006.05.015.
    1. Hodgson DC, Dieckmann K, Terezakis S, Constine L, International Lymphoma Radiation Oncology Group Implementation of contemporary radiation therapy planning concepts for pediatric Hodgkin lymphoma: guidelines from the international lymphoma radiation oncology group. Pract Radiat Oncol. 2015;5:85–92. doi: 10.1016/j.prro.2014.05.003.
    1. Hodapp N. The ICRU report 83: prescribing, recording and reporting photon-beam intensity-modulated radiation therapy (IMRT) Strahlenther Onkol. 2012;188:97–99. doi: 10.1007/s00066-011-0015-x.
    1. Bartlett FR, Colgan RM, Carr K, Donovan EM, McNair HA, Locke I, et al. The UK HeartSpare study: randomised evaluation of voluntary deep-inspiratory breath-hold in women undergoing breast radiotherapy. Radiother Oncol. 2013;108:242–247. doi: 10.1016/j.radonc.2013.04.021.
    1. Huijskens SC, Van Dijk IWEM, Visser J, Rasch CRN, Alderliesten T, Bel A. Magnitude and variability of respiratory-induced diaphragm motion in children during image-guided radiotherapy. Radiother Oncol. 123:263–9. 10.1016/j.radonc.2017.03.016.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj