Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma

Stephanie G C Kroeze; Corinna Fritz; Jana Schaule; Shankar Siva; Klaus H Kahl; Nora Sundahl; Oliver Blanck; David Kaul; Sonja Adebahr; Joost J C Verhoeff; Georgios Skazikis; Falk Roeder; Michael Geier; Franziska Eckert; Matthias Guckenberger

doi:10.1111/bju.15284

Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma

Stephanie G C Kroeze
, Corinna Fritz
, Jana Schaule
, Shankar Siva
, Klaus H Kahl
, Nora Sundahl
, Oliver Blanck
, David Kaul
, Sonja Adebahr
, Joost J C Verhoeff
, Georgios Skazikis
, Falk Roeder
, Michael Geier
, Franziska Eckert
, Matthias Guckenberger

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

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Abstract

OBJECTIVES: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy.

PATIENTS AND METHODS: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03.

RESULTS: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed.

CONCLUSION: Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.

Original language	English
Pages (from-to)	703-711
Number of pages	9
Journal	BJU International
Volume	127
Issue number	6
Early online date	28 Oct 2020
DOIs	https://doi.org/10.1111/bju.15284
Publication status	Published - Jun 2021

Keywords

#KidneyCancer
#kcsm
#uroonc
concurrent
immunotherapy
oligometastases
renal cell carcinoma
stereotactic
targeted therapy

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10.1111/bju.15284

bju.15284Final published version, 1.39 MBLicence: Taverne

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Kroeze, S. G. C., Fritz, C., Schaule, J., Siva, S., Kahl, K. H., Sundahl, N., Blanck, O., Kaul, D., Adebahr, S., Verhoeff, J. J. C., Skazikis, G., Roeder, F., Geier, M., Eckert, F., & Guckenberger, M. (2021). Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma. BJU International, 127(6), 703-711. https://doi.org/10.1111/bju.15284

@article{33440929776e4d68a30dfc495cf7c9a0,

title = "Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma",

abstract = "OBJECTIVES: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy.PATIENTS AND METHODS: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03.RESULTS: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58\% presented with oligometastatic disease (OMD). ICIs and TT were received by 32\% and 68\% of patients, respectively. Twenty patients (37\%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71\%, 75\% and 25\%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46\% of patients. After 1 year, 62\% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83\% vs 36\%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95\% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95\% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95\% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed.CONCLUSION: Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.",

keywords = "\#KidneyCancer, \#kcsm, \#uroonc, concurrent, immunotherapy, oligometastases, renal cell carcinoma, stereotactic, targeted therapy",

author = "Kroeze, \{Stephanie G C\} and Corinna Fritz and Jana Schaule and Shankar Siva and Kahl, \{Klaus H\} and Nora Sundahl and Oliver Blanck and David Kaul and Sonja Adebahr and Verhoeff, \{Joost J C\} and Georgios Skazikis and Falk Roeder and Michael Geier and Franziska Eckert and Matthias Guckenberger",

note = "Funding Information: N. Sundahl reports non‐financial support from Bayer, MSD, Bristol‐Myers Squibb and Astellas, outside the submitted work. S. Siva reports personal fees from the National Health and Medical Research Council and Cancer Council Victoria Colebatch Fellowship outside the submitted work. G. Skazikis reports grants from the University of Zurich, during the conduct of the study. M. Geier reports personal fees from Roche and Bristol‐Myers Squibb outside the submitted work. D. Kaul reports personal fees from Novocure outside the submitted work. S. Adebahr reports personal fees from the German Consortium of Translational Cancer Research (DKTK), during the conduct of the study. K. H. Kahl reports personal fees from Bristol Myers Squibb, MSD, Merck, AstraZeneca, Varian, Elekta and Zeiss Meditec, outside the submitted work. J. J. C. Verhoeff, O. Blanck, M. Guckenberger, J. Schaule, F. Roeder, F. Eckert and C. Fritz declare no conflicts of interest. Funding Information: N. Sundahl reports non-financial support from Bayer, MSD, Bristol-Myers Squibb and Astellas, outside the submitted work. S. Siva reports personal fees from the National Health and Medical Research Council and Cancer Council Victoria Colebatch Fellowship outside the submitted work. G. Skazikis reports grants from the University of Zurich, during the conduct of the study. M. Geier reports personal fees from Roche and Bristol-Myers Squibb outside the submitted work. D. Kaul reports personal fees from Novocure outside the submitted work. S. Adebahr reports personal fees from the German Consortium of Translational Cancer Research (DKTK), during the conduct of the study. K. H. Kahl reports personal fees from Bristol Myers Squibb, MSD, Merck, AstraZeneca, Varian, Elekta and Zeiss Meditec, outside the submitted work. J. J. C. Verhoeff, O. Blanck, M. Guckenberger, J. Schaule, F. Roeder, F. Eckert and C. Fritz declare no conflicts of interest. This work was financially supported by Varian Medical Systems. Varian Medical Systems was not involved in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication. Funding Information: This work was financially supported by Varian Medical Systems. Varian Medical Systems was not involved in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication. Publisher Copyright: {\textcopyright} 2020 The Authors BJU International {\textcopyright} 2020 BJU International Published by John Wiley \& Sons Ltd",

year = "2021",

month = jun,

doi = "10.1111/bju.15284",

language = "English",

volume = "127",

pages = "703--711",

journal = "BJU International",

issn = "1464-4096",

publisher = "John Wiley \& Sons Inc.",

number = "6",

}

Kroeze, SGC, Fritz, C, Schaule, J, Siva, S, Kahl, KH, Sundahl, N, Blanck, O, Kaul, D, Adebahr, S, Verhoeff, JJC, Skazikis, G, Roeder, F, Geier, M, Eckert, F & Guckenberger, M 2021, 'Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma', BJU International, vol. 127, no. 6, pp. 703-711. https://doi.org/10.1111/bju.15284

TY - JOUR

T1 - Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma

AU - Kroeze, Stephanie G C

AU - Fritz, Corinna

AU - Schaule, Jana

AU - Siva, Shankar

AU - Kahl, Klaus H

AU - Sundahl, Nora

AU - Blanck, Oliver

AU - Kaul, David

AU - Adebahr, Sonja

AU - Verhoeff, Joost J C

AU - Skazikis, Georgios

AU - Roeder, Falk

AU - Geier, Michael

AU - Eckert, Franziska

AU - Guckenberger, Matthias

N1 - Funding Information: N. Sundahl reports non‐financial support from Bayer, MSD, Bristol‐Myers Squibb and Astellas, outside the submitted work. S. Siva reports personal fees from the National Health and Medical Research Council and Cancer Council Victoria Colebatch Fellowship outside the submitted work. G. Skazikis reports grants from the University of Zurich, during the conduct of the study. M. Geier reports personal fees from Roche and Bristol‐Myers Squibb outside the submitted work. D. Kaul reports personal fees from Novocure outside the submitted work. S. Adebahr reports personal fees from the German Consortium of Translational Cancer Research (DKTK), during the conduct of the study. K. H. Kahl reports personal fees from Bristol Myers Squibb, MSD, Merck, AstraZeneca, Varian, Elekta and Zeiss Meditec, outside the submitted work. J. J. C. Verhoeff, O. Blanck, M. Guckenberger, J. Schaule, F. Roeder, F. Eckert and C. Fritz declare no conflicts of interest. Funding Information: N. Sundahl reports non-financial support from Bayer, MSD, Bristol-Myers Squibb and Astellas, outside the submitted work. S. Siva reports personal fees from the National Health and Medical Research Council and Cancer Council Victoria Colebatch Fellowship outside the submitted work. G. Skazikis reports grants from the University of Zurich, during the conduct of the study. M. Geier reports personal fees from Roche and Bristol-Myers Squibb outside the submitted work. D. Kaul reports personal fees from Novocure outside the submitted work. S. Adebahr reports personal fees from the German Consortium of Translational Cancer Research (DKTK), during the conduct of the study. K. H. Kahl reports personal fees from Bristol Myers Squibb, MSD, Merck, AstraZeneca, Varian, Elekta and Zeiss Meditec, outside the submitted work. J. J. C. Verhoeff, O. Blanck, M. Guckenberger, J. Schaule, F. Roeder, F. Eckert and C. Fritz declare no conflicts of interest. This work was financially supported by Varian Medical Systems. Varian Medical Systems was not involved in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication. Funding Information: This work was financially supported by Varian Medical Systems. Varian Medical Systems was not involved in the study design, collection, analysis and interpretation of data, the writing of the report or in the decision to submit the article for publication. Publisher Copyright: © 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd

PY - 2021/6

Y1 - 2021/6

N2 - OBJECTIVES: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy.PATIENTS AND METHODS: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03.RESULTS: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed.CONCLUSION: Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.

AB - OBJECTIVES: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy.PATIENTS AND METHODS: Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30 days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03.RESULTS: Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1 year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1 year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed.CONCLUSION: Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.

KW - #KidneyCancer

KW - #kcsm

KW - #uroonc

KW - concurrent

KW - immunotherapy

KW - oligometastases

KW - renal cell carcinoma

KW - stereotactic

KW - targeted therapy

UR - https://www.scopus.com/pages/publications/85096721054

U2 - 10.1111/bju.15284

DO - 10.1111/bju.15284

M3 - Article

C2 - 33113260

SN - 1464-4096

VL - 127

SP - 703

EP - 711

JO - BJU International

JF - BJU International

IS - 6

ER -

Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma

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