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A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma

BACKGROUND: Cytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative. METHODS: In this dose-escalation trial, inoperable mRCC patients underwent SABR ta...

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Autores principales: Correa, Rohann J. M., Ahmad, Belal, Warner, Andrew, Johnson, Craig, MacKenzie, Mary J., Pautler, Stephen E., Bauman, Glenn S., Rodrigues, George B., Louie, Alexander V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859400/
https://www.ncbi.nlm.nih.gov/pubmed/29558966
http://dx.doi.org/10.1186/s13014-018-0992-3
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author Correa, Rohann J. M.
Ahmad, Belal
Warner, Andrew
Johnson, Craig
MacKenzie, Mary J.
Pautler, Stephen E.
Bauman, Glenn S.
Rodrigues, George B.
Louie, Alexander V.
author_facet Correa, Rohann J. M.
Ahmad, Belal
Warner, Andrew
Johnson, Craig
MacKenzie, Mary J.
Pautler, Stephen E.
Bauman, Glenn S.
Rodrigues, George B.
Louie, Alexander V.
author_sort Correa, Rohann J. M.
collection PubMed
description BACKGROUND: Cytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative. METHODS: In this dose-escalation trial, inoperable mRCC patients underwent SABR targeting the entire affected kidney. Toxicity (CTCAE v3.0), quality of life (QoL), renal function, and tumour response (RECIST v1.0) were assessed. RESULTS: Twelve patients of mostly intermediate (67%) or poor (25%) International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class, median KPS of 70%, and median tumour size of 8.7 cm (range: 4.8–13.8) were enrolled in successive dose cohorts of 25 (n = 3), 30 (n = 6), and 35 Gy (n = 3) in 5 fractions. SABR was well tolerated with 3 grade 3 events: fatigue (2) and bone pain (1). QoL decreased for physical well-being (p = 0.016), but remained unchanged in other domains. SABR achieved a median tumour size reduction of − 17.3% (range: + 5.3 to − 54.4) at 5.3 months. All patients progressed systemically and median OS was 6.7 months. Crude median follow-up was 5.8 months. CONCLUSIONS: In non-operable mRCC patients, renal-ablative SABR to 35 Gy in 5 fractions yielded acceptable toxicity, renal function preservation, and stable QoL. SABR merits further prospective investigation as an alternative to cytoreductive nephrectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02264548. Registered July 22 2014 – Retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT02264548 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13014-018-0992-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-58594002018-03-20 A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma Correa, Rohann J. M. Ahmad, Belal Warner, Andrew Johnson, Craig MacKenzie, Mary J. Pautler, Stephen E. Bauman, Glenn S. Rodrigues, George B. Louie, Alexander V. Radiat Oncol Research BACKGROUND: Cytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative. METHODS: In this dose-escalation trial, inoperable mRCC patients underwent SABR targeting the entire affected kidney. Toxicity (CTCAE v3.0), quality of life (QoL), renal function, and tumour response (RECIST v1.0) were assessed. RESULTS: Twelve patients of mostly intermediate (67%) or poor (25%) International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class, median KPS of 70%, and median tumour size of 8.7 cm (range: 4.8–13.8) were enrolled in successive dose cohorts of 25 (n = 3), 30 (n = 6), and 35 Gy (n = 3) in 5 fractions. SABR was well tolerated with 3 grade 3 events: fatigue (2) and bone pain (1). QoL decreased for physical well-being (p = 0.016), but remained unchanged in other domains. SABR achieved a median tumour size reduction of − 17.3% (range: + 5.3 to − 54.4) at 5.3 months. All patients progressed systemically and median OS was 6.7 months. Crude median follow-up was 5.8 months. CONCLUSIONS: In non-operable mRCC patients, renal-ablative SABR to 35 Gy in 5 fractions yielded acceptable toxicity, renal function preservation, and stable QoL. SABR merits further prospective investigation as an alternative to cytoreductive nephrectomy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02264548. Registered July 22 2014 – Retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT02264548 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13014-018-0992-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-20 /pmc/articles/PMC5859400/ /pubmed/29558966 http://dx.doi.org/10.1186/s13014-018-0992-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Correa, Rohann J. M.
Ahmad, Belal
Warner, Andrew
Johnson, Craig
MacKenzie, Mary J.
Pautler, Stephen E.
Bauman, Glenn S.
Rodrigues, George B.
Louie, Alexander V.
A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
title A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
title_full A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
title_fullStr A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
title_full_unstemmed A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
title_short A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
title_sort prospective phase i dose-escalation trial of stereotactic ablative radiotherapy (sabr) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859400/
https://www.ncbi.nlm.nih.gov/pubmed/29558966
http://dx.doi.org/10.1186/s13014-018-0992-3
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