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

Daniel Buergy; Florian Würschmidt; Eleni Gkika; Juliane Hörner-Rieber; Stefan Knippen; Sabine Gerum; Panagiotis Balermpas; Christoph Henkenberens; Theresa Voglhuber; Christine Kornhuber; Steffen Barczyk; Barbara Röper; Ali Rashid; Oliver Blanck; Andrea Wittig; Hans Ulrich Herold; Thomas Baptist Brunner; Reinhart A. Sweeney; Klaus Henning Kahl; Ilja Frank Ciernik; Annette Ottinger; Victor Izaguirre; Florian Putz; Laila König; Michael Hoffmann; Stephanie Elisabeth Combs; Matthias Guckenberger; Judit Boda-Heggemann

doi:10.1002/ijc.34017

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

Daniel Buergy, Florian Würschmidt, Eleni Gkika, Juliane Hörner-Rieber, Stefan Knippen, Sabine Gerum, Panagiotis Balermpas, Christoph Henkenberens, Theresa Voglhuber, Christine Kornhuber, Steffen Barczyk, Barbara Röper, Ali Rashid, Oliver Blanck, Andrea Wittig, Hans Ulrich Herold, Thomas Baptist Brunner, Reinhart A. Sweeney, Klaus Henning Kahl, Ilja Frank CiernikAnnette Ottinger, Victor Izaguirre, Florian Putz, Laila König, Michael Hoffmann, Stephanie Elisabeth Combs, Matthias Guckenberger, Judit Boda-Heggemann

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	412-421
Number of pages	10
Journal	International Journal of Cancer
Volume	151
Issue number	3
DOIs	https://doi.org/10.1002/ijc.34017
State	Published - 1 Aug 2022

Bibliographical note

Funding Information:
Daniel Buergy reports personal fees from NB Capital ApS, personal fees from Nordic Biotech, personal fees from Siemens AG, personal fees from b.e. Imaging GmbH, outside the submitted work; Juliane Hörner‐Rieber received speaker fees and travel reimbursement from ViewRay Inc, as well as travel reimbursement form IntraOP Medical and Elekta Instrument AB and grants from IntraOP Medical and Varian Medical Systems outside the submitted work; Florian Putz received research grants and speaker fees from Siemens Healthcare AG outside the submitted work; Laila König received speaker fees and travel reimbursement from Accuray and Novocure outside the submitted work; Klaus Henning Kahl is on the advisory board of Bristol Myers Squibb (BMS), MSD, and AstraZeneca; received travel and speakers fees from Varian, Elekta, Zeiss Meditec, Merck, Bristol Myers Squibb (BMS), AstraZeneca and fees from Medical Intelligence outside the submitted work. All the other authors reported no potential conflicts of interest.

Publisher Copyright:
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Keywords

SBRT
adrenal
dose-finding
oligometastases

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10.1002/ijc.34017

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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., ... Boda-Heggemann, J. (2022). Stereotactic body radiotherapy of adrenal metastases—A dose-finding study. International Journal of Cancer, 151(3), 412-421. https://doi.org/10.1002/ijc.34017

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abstract = "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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note = "Publisher Copyright: {\textcopyright} 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.",

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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, HU, Brunner, TB, Sweeney, RA, Kahl, KH, Ciernik, IF, Ottinger, A, Izaguirre, V, Putz, F, König, L, Hoffmann, M, Combs, SE, Guckenberger, M & Boda-Heggemann, J 2022, 'Stereotactic body radiotherapy of adrenal metastases—A dose-finding study', International Journal of Cancer, vol. 151, no. 3, pp. 412-421. https://doi.org/10.1002/ijc.34017

TY - JOUR

T1 - Stereotactic body radiotherapy of adrenal metastases—A dose-finding study

AU - Buergy, Daniel

AU - Würschmidt, Florian

AU - Gkika, Eleni

AU - Hörner-Rieber, Juliane

AU - Knippen, Stefan

AU - Gerum, Sabine

AU - Balermpas, Panagiotis

AU - Henkenberens, Christoph

AU - Voglhuber, Theresa

AU - Kornhuber, Christine

AU - Barczyk, Steffen

AU - Röper, Barbara

AU - Rashid, Ali

AU - Blanck, Oliver

AU - Wittig, Andrea

AU - Herold, Hans Ulrich

AU - Brunner, Thomas Baptist

AU - Sweeney, Reinhart A.

AU - Kahl, Klaus Henning

AU - Ciernik, Ilja Frank

AU - Ottinger, Annette

AU - Izaguirre, Victor

AU - Putz, Florian

AU - König, Laila

AU - Hoffmann, Michael

AU - Combs, Stephanie Elisabeth

AU - Guckenberger, Matthias

AU - Boda-Heggemann, Judit

PY - 2022/8/1

Y1 - 2022/8/1

N2 - 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.

AB - 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.

KW - SBRT

KW - adrenal

KW - dose-finding

KW - oligometastases

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U2 - 10.1002/ijc.34017

DO - 10.1002/ijc.34017

M3 - Artículo

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AN - SCOPUS:85129178326

SN - 0020-7136

VL - 151

SP - 412

EP - 421

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

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