Extreme Heterogeneity Of Myeloablative Total Body Irradiation (TBI) Techniques Across Europe: A Survey Of Acute Leukemia Working Party Of The EBMT
Authors: Giebel Sebastian , Miszczyk Leszek , Slosarek Krzysztof , Moukhtari Leila , Ciceri Fabio , Esteve Jordi , Gorin Norbert Claude , Labopin Myriam , Nagler Arnon , Schmid Christoph , Mohty Mohamad 
Published: October 2019

Background
Total body irradiation (TBI) is widely used for conditioning prior to both allogeneic and autologous hematopoietic stem cell transplantation. Myeloablatitve doses of TBI are considered highly effective but also associated with relevant toxicity. Both, the efficacy and toxicity may depend on many methodological aspects of TBI. The goal of the survey was to explore current practice across centers collaborating in the European Group for Blood and Marrow Transplantation (EBMT).

Methods
The questionnaire sent to all EBMT centers included 19 questions regarding the doses used for myeloabaltive TBI, the way of fractionation, the modes of delivering the dose, type of immobilization, methods of dosimetry and organ shielding. 56 centers from 23 countries responded.

Results
All centers differ with regard at least one of the methodological aspects.
The total dose of TBI used for myeloablative transplantation ranges from 8 to 14.4 Gy, the number of fractions ranges from 1 to 8, while the dose per fraction is 1.65 – 8 Gy. Altogether 16 modalities of dosing/fractionation have been identified with 6 x 2 Gy being the most frequent one (n=36, 64%). The dose rate in the axis of the beam ranges from 4.5 – 30 cGy/min (27 modalities; most frequently 18 cGy/min, 5%).
The treatment unit is regular linac (n=51, 91%) or cobalt unit (n=5, 9%). Beams used for regular linac are 6 to 23 MV (most frequently 6 MV, n=26, 51%).
The most frequent technique used for irradiation is “patient in one field” using two fields per fraction and two patient positions per fraction (n=36, 64%), however, altogether 11 modalities were described with regard to the technique, number of fields and positions per fraction. Source to surface distance is 2 to 5 m (most frequently 4 m; n=10, 18%). In 23 (41%) centers patients are immobilized during TBI, using 9 different types of device.
Fifty-two centers (93%) measure acquired dose of irradiation using 5 types of detectors for in vivo dosimetry (most frequently semiconductors; n=37, 66%). Accepted discrepancy between planned and measured dose ranges from 1.5 to 10%.
In 47 (84%) centers lungs are shielded during irradiation and lung density is considered for treatment planning. Maximum accepted dose for lungs ranges from 6 to 12 Gy. Additionally, in some centers lenses (14%), thyroid gland (7%), larynx (4%), kidneys (4%) and/or salivary glands (2%) are shielded.

Conclusions
TBI is an extremely heterogeneous treatment modality. Differences between centers regard all methodological aspects. Our findings should warrant caution in interpretation of clinical studies involving TBI. Further investigation is needed to evaluate whether differences between treatment modalities influence the efficacy and safety of the TBI procedure. Finally, efforts to standardize the method should be considered.

Disclosures:
No relevant conflicts of interest to declare.