3421 - Developing Blood Sparing Radiotherapy Following CAR T for Lymphoma

G. Ntentas^1,2, C. Beekman³, H. Paganetti⁴, S. Sivabalasingham⁵, J. L. Brady⁶, K. Keshwani⁵, J. Woodward⁷, R. Sanderson⁸, C. Roddie⁹, C. Grassberger¹⁰, R. Begum⁶, M. Patel¹¹, A. Kuhnl¹², and G. Mikhaeel¹³; ¹Department of Medical Physics and Clinical Engineering, Guy´s and St Thomas´ Hospital, London, United Kingdom, ²Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom, ³Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁴Massachusetts General Hospital, Harvard Medical School, Boston, MA, ⁵Proton Beam Therapy Centre, University College London Hospitals NHS Trust, London, United Kingdom, ⁶Guys and St Thomas NHS Foundation Trust, London, United Kingdom, ⁷Department of Radiotherapy Physics, University College London Hospitals, London, United Kingdom, London, United Kingdom, ⁸Kings College NHS Trust, London, United Kingdom, ⁹University College London Hospital NHS Trust, london, United Kingdom, ¹⁰Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, ¹¹Department of Clinical Oncology, Guy´s Cancer Centre, Guy´s and St Thomas´ Hospital, London, United Kingdom, London, United Kingdom, ¹²Kings, London, United Kingdom, ¹³School of Cancer and Pharmaceutical Sciences, Kings College London, London, United Kingdom

Purpose/Objective(s): Radiotherapy (RT) is an effective treatment for residual lymphoma early after CD19 chimeric antigen receptor T cell therapy (CAR T). However, there are concerns regarding the effect of RT on CAR T. We investigated the effect of different RT planning techniques on the dose to circulating blood to develop CAR T sparing RT using a published computational framework to compute hematological doses (HEDOS) [1] Materials/

Methods: We analyzed 33 RT treatment plans for 11 lesions. Each lesion was planned with 3 RT techniques. Technique A: a conventional VMAT plan, B: a blood sparing technique with lower number of arcs and dose optimization for blood vessels (BV) and blood rich organs (BRO) and C: the same as B but delivered with Flattening Filter Free (FFF) beams to increase dose rate (DR) and reduce beam on time (BOT). Fractional blood doses were calculated using HEDOS, which simulates individual blood particles as they travel through the body, dictated by intra- and inter-organ blood flow. The % of blood volume that received 0, 0.05 and 0.5 Gy was estimated for each RT technique. Wilcoxon test was used to test for significance.
Results: BV dose was reduced by B & C, with wide variation between different cases. However, the differences between the mean BV dose of the whole group did not reach statistical significance. Techniques B & C reduced BOT, especially C due to its higher DR (1400 vs 600 MU/min). BOT reduction had the largest influence on the volume of irradiated blood and thus C significantly reduced the blood dose compared to A & B (Table 1). The % blood volume receiving 0 Gy was highest for C. C also reduced the blood volume that received > 0.05 Gy / fraction, a dose level that can induce cell death/inactivation due to the highly radiosensitive nature of lymphocytes [2].
Conclusion: This is the first study to develop a blood sparing (and potentially CAR T sparing) RT by modifying treatment parameters to account for the circulating nature of the blood. Using a dynamic dose calculation method, BOT has a large effect compared to other modifications. Reducing BOT to < 60 seconds had the greatest blood dose-sparing effect. This blood sparing RT could have other potential applications such as reducing risk for lymphopenia after RT. Abstract 3421 – Table 1 [1] C. Beekman et al., doi:10.1088/1361-6560/ad02d6 [2] D. Heylmann et al. doi: 10.1038/s41598-021-81058-1

	A	B	C	A vs B	A vs C
Technique	2 full arcs	1 or half arc + BV and BRO optimization	As B plus FFF
Beam on time seconds (range)	98 (67-132)	77 (58-103)	45 (31-60)	-21.2 p=0.02	-52.9 p<0.0001
HEDOS calculation
Blood V0 (%)	12.3	13.9	26.2	+1.6 p=0.22	+13.9 p<0.001
Blood V > 0.05Gy (%)	55.9	51.0	46.5	-4.9 p=0.06	-9.4 p=0.004
Blood V > 0.5Gy (%)	4.0	3.9	4.4	0.1 p=0.71	0.4 p=0.45
Treatment Planning System calculation
Blood Vessels Dmean (Gy)	10.2	8.7	8.9	1.5 p= 0.5	1.3 p= 0.5
BRO Dmean (Gy)	2.8	2.7	2.8	0.1 p=0.98	0.0 p=0.99
BRO: Blood Rich Organs V: Volume FFF: Flattening Filter Free