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Buergy, D.* ; Würschmidt, F.* ; Gkika, E.* ; Hörner-Rieber, J.* ; Knippen, S.* ; Gerum, S.* ; Balermpas, P.* ; Henkenberens, C.* ; Voglhuber, T.* ; Kornhuber, C.* ; Barczyk, S.* ; Röper, B.* ; Rashid, A.* ; Blanck, O.* ; Wittig, A.* ; Herold, H.U.* ; Brunner, T.B.* ; Sweeney, R.A.* ; Kahl, K.H.* ; Ciernik, I.F.* ; Ottinger, A.* ; Izaguirre, V.* ; Putz, F.* ; König, L.* ; Hoffmann, M.* ; Combs, S.E. ; Guckenberger, M.* ; Boda-Heggemann, J.*

Stereotactic body radiotherapy of adrenal metastases-A dose-finding study.

Int. J. Cancer 151, 412-421 (2022)

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Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

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