Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

doi:10.1016/j.zemedi.2019.05.002

Zeitschrift für Medizinische Physik

Volume 30, Issue 1, February 2020, Pages 17-23

https://doi.org/10.1016/j.zemedi.2019.05.002 Get rights and content

Abstract

Purpose

Total body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.

Material and methods

Forty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.

Results

For all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.

Conclusions

Total body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.

Introduction

Besides chemotherapy total body irradiation (TBI) is an important part for conditioning of allogeneic stem cell transplantation in patients with lymphatic malignancies as acute lymphatic leukemia (ALL) or chronic lymphatic leukemia (CLL) etc. The treatment protocols provide total radiation doses up to 12 Gy delivered in mostly hyperfractionated regimes (2 × 2 Gy/day) according i.e. GMALL 7/2003 GMALL 08/12 study protocol [1]. These doses are required to achieve total immunological suppression and best conditions for stem cell transplantation. Especially intensity modulated radiotherapy (IMRT) techniques allow us to optimize dose distribution to target volume with simultaneous sparing to relevant organs at risk. IMRT is already established for nearly all radiotherapy treatments. The current treatment protocols of conditioning for stem cell transplantation mainly refer to experiences form conventional radiation therapy era. Due to technical improvements it has already been shown that Tomotherapy using helical beam delivery increases conformity and homogeneity in target dose distribution and allows dose sparing in organs at risk [2]. In our department Tomotherapy is regularly used for TBI treatment.

In this study we were interested in maximum lung sparing that can be achieved in TBI patients with helical Tomotherapy to reduce radiogenic side effects.

Section snippets

Materials and methods

This study does not contain any treatment of human participants and is a retrospective planning study. As such no recommendation of our institutional ethic committee is required.

Whole body radiotherapy plans with Tomotherapy HiART II (version) were the basis of this study. Included were forty consecutive adult patients treated between 2012 and 2016 (for demographics see Table 1).

To achieve comparable data we assumed an application dose of 12 Gy in 6 fractions (2 × 2 Gy/day) for all patients.

The

Results

In all 40 patients the prescribed planning criteria D99 for heart and ribs (minimum 10.86 Gy, average 11.22 Gy +/− 0.15 Gy) could be met.

This required between 89 and 322 (mean 153) iterations. The set up planning modulation factor was calculated to an actual modulation factor of 2.532.

For the first treatment position (head to middle femoral third) treatment time ranged from 2281 and 2940 s (mean 2686.63 = 44.77 min).

Treatment of the second part (“rest” body volume) took from 407.3 to 951.8 s (mean 678.5 s =

Discussion

Total body irradiation or total marrow radiation is a commonly used conditioning in patients before bone marrow or hematopoietic stem cell transplantation [1]. Patients who are planned for stem cell transplantation are treated with combined radio chemotherapy regimes leading to systemic elimination of cancer cells in the blood circulation and bony structures. TBI is additionally used to eliminate malignant cells and stem cells in the patients tissue to prepare for optimal conditions for stem

Conclusion

This planning study demonstrates that total body irradiation with helical Tomotherapy offers an excellent opportunity of highly conformal and homogenous dose delivery in extensive target volumes. Compromise in PTV dose might only occur in patients with high BMI. All predefined constraints are reachable in an acceptable planning time. To our knowledge we showed for the first time, that total body irradiation with a hyperfractionated total dose of 12 Gy can be delivered simultaneously with maximum

Disclosure of conflicts of interests of interest

The authors have no relevant conflicts of interest to disclose.

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ESTRO ACROP and SIOPE recommendations for myeloablative Total Body Irradiation in children
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On the other hand, they require field junctioning, a longer planning and setup time and use fluctuating higher dose rates. Examples are TomoTherapy [16,193–195] and volumetric modulated arc therapy (VMAT) [17,196–199] (Figs. 1 and 3). Since the couch travel of linear accelerators is usually 120–150 cm, a patient rotation from head-first (HF) to feet-first (FF) position is required to be able to irradiate the whole body (Fig. 1).
Myeloablative Total Body Irradiation (TBI) is an important modality in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), especially in children with high-risk acute lymphoblastic leukemia (ALL). TBI practices are heterogeneous and institution-specific. Since TBI is associated with multiple late adverse effects, recommendations may help to standardize practices and improve the outcome versus toxicity ratio for children.
The European Society for Paediatric Oncology (SIOPE) Radiotherapy TBI Working Group together with ESTRO experts conducted a literature search and evaluation regarding myeloablative TBI techniques and toxicities in children. Findings were discussed in bimonthly virtual meetings and consensus recommendations were established.
Myeloablative TBI in HSCT conditioning is mostly performed for high-risk ALL patients or patients with recurring hematologic malignancies. TBI is discouraged in children <3–4 years old because of increased toxicity risk. Publications regarding TBI are mostly retrospective studies with level III–IV evidence. Preferential TBI dose in children is 12–14.4 Gy in 1.6–2 Gy fractions b.i.d. Dose reduction should be considered for the lungs to <8 Gy, for the kidneys to ≤10 Gy, and for the lenses to <12 Gy, for dose rates ≥6 cGy/min. Highly conformal techniques i.e. TomoTherapy and VMAT TBI or Total Marrow (and/or Lymphoid) Irradiation as implemented in several centers, improve dose homogeneity and organ sparing, and should be evaluated in studies.
These ESTRO ACROP SIOPE recommendations provide expert consensus for conventional and highly conformal myeloablative TBI in children, as well as a supporting literature overview of TBI techniques and toxicities.
Two compound techniques for total body irradiation
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Because approximately 80% of the dose is given by large conventional fields, a lower limit exists for doses achievable to the critical organs. This is a drawback of both presented techniques that other techniques such as tomotherapy or full-body VMAT are without [4,14,21-24]. The issue of undertreatment of malignant cells circulating in the bloodstream has been raised regarding tomoterapy and VMAT-based techniques but has not been found to be important [25].
Total body irradiation (TBI) is an important treatment modality that is used in combination with chemotherapy in many stem cell transplantation protocols. Therefore, the quality of the irradiation is important. Two techniques for planning and delivering TBI are presented and compared.
The technique named ExIMRT is a combination of manually shaped conventional fields from an extended SSD and isocentric IMRT fields. The technique named ExVMAT is a combination of conventional and IMRT fields from an extended SSD and isocentric VMAT fields. Dosimetric data from 32 patients who were planned and treated according to one of the two techniques were compared.
When comparing the two techniques, it is determined that the ExVMAT technique is able to significantly reduce the mean total volume overdosed by 120% from 408 to 12 cm³. The dose covering 98% of the total lung volume is significantly increased by this technique from a mean of 9.7 Gy to 10.3 Gy. Additionally, the dose covering 2% of the total kidney volume is significantly decreased from a mean of 12.8 to 12.5 Gy. Furthermore, the population-based variance of the median dose to the total lung volume, the heart and the volume of the body prescribed to 12.5 Gy is significantly reduced. The results are obtained without compromising overall treatment quality as treatment time or dose rate to the lungs.
Using the ExVMAT technique, a superior dose distribution can be delivered both from a patient and a population perspective compared to the ExIMRT technique.
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Whole body irradiation with intensity-modulated helical tomotherapy prior to haematopoietic stem cell transplantation: analysis of organs at risk by dose and its effect on blood kinetics
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¹: These authors contributed equally to this work.

²: These authors also contributed equally to this work.

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Original PaperTotal body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

Abstract

Purpose

Material and methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Conclusion

Disclosure of conflicts of interests of interest

Cancer Radiother

Radiother Oncol

tipsRO

Int J Radiat Oncol Biol Phys

Med Dosim

Radiother Oncol

Int J Radiat Oncol Biol Phys

Cancer Treat Rev

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Original Paper
Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy