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Albumin, corticosteroid use and Karnofsky performance status predict outcome of single-fraction gamma knife radiosurgery in clear cell renal cell carcinoma patients with brain metastases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. (Magnus Lindskog)
Department of Medical Radiation Physics and Nuclear Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Department of Neurosurgery, Bezmialem Vakif University Medical School, Istanbul, Turkey.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background and Purpose: To evaluate the effects of single fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA).

Material and Methods: Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n=43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60-100%.  Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE).

Results: One hundred and ninety-four targets were irradiated. Median number of targets at first sf-GKRS were two. The median prescription dose was 22 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC at 12 and 18 months were 97% and 90%. Median OS from first sf-GKRS was 15.7 months. Serum albumin (HR 5.3), corticosteroids pre sf-GKRS (HR 5.8) and KPS (HR 9.1) were independent prognostic factors. MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases provided no additional prognostic information. Other prognostic scores for BM radiosurgery, including DS-GPA, Renal-GPA, LLV-SIR and CITV-SIR, did not add prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within one month of sf-GKRS.

Conclusions: We identified three independent prognostic factors with potential impact on clinical decision making in patients with clear cell RCC BM.

Keywords [en]
renal cell carcinoma, kidney cancer, stereotactic radiotherapy, stereotactic radiosurgery, radiosurgery, SRS, gamma knife, overall survival, prognostic factors, gkrs, rcc
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-390135OAI: oai:DiVA.org:uu-390135DiVA, id: diva2:1340481
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-20
In thesis
1. Treatment selection in metastatic renal cell carcinoma: Towards an individualised approach
Open this publication in new window or tab >>Treatment selection in metastatic renal cell carcinoma: Towards an individualised approach
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Renal cell carcinoma (RCC), a common malignancy worldwide, affects 1200 new patients yearly in Sweden. Metastatic RCC (mRCC) develops in one in three and is commonly incurable. Clear cell histology dominates followed by papillary histology. The mainstay of mRCC treatment is targeted agents (TA) against aberrantly signalling pro-angiogenic tyrosine kinase receptors, and recently also immune checkpoint inhibitors. Local metastatic therapy with stereotactic radiotherapy (SRT) or surgical metastasectomy may be considered for oligometastatic disease.

The aims of this thesis were (1) to identify clinically relevant factors useful for prognostication in real-world patients with mRCC treated in the TA era, (2) to deepen the understanding of papillary mRCC, and (3) to evaluate local metastatic therapy in mRCC. The papers of this thesis were based on retrospective data from regional databases or patient records from 2005 and onwards to reflect the contemporary therapeutic landscape.

Paper I was a single-centre study analysing inflammatory blood and clinical parameters in relation to overall survival (OS) in mRCC (n=84). Median OS (mOS) was 20 months. Hypoalbuminemia was a negative prognostic factor (HR 2.7), independently of patient performance status (PS) or Memorial Sloan Kettering Cancer Center risk criteria.

Paper II included solely patients with papillary mRCC (n=86) treated at three centres. mOS was 11 months. Age ≥60 years (HR 2.2), ≥3 metastatic sites (HR 2.7), and Eastern Cooperative Oncology Group (ECOG) PS ≥2 vs 1 (HR 3.0) were independently associated with worse OS.

Paper III included mRCC patients treated with local metastatic therapy (n=117). Survival was similar irrespective of SRT or surgical metastasectomy with a mOS of 51 months. Treatment with TA in close proximity to local therapy was well tolerated. ECOG PS 1 vs 0 (HR 2.9), intracranial treatment (HR 1.8), and watchful waiting ≥18 months prior to treatment (HR 0.3) were independently prognostic.  

Paper IV was a follow-up of patients with ccRCC brain metastases treated with single fraction gamma knife radiosurgery (sf-GKRS) at three European centres (n=43). 1- and 3-year local control rates were 97% and 90%, and mOS was 16 months. Hypoalbuminemia (HR=5.3), corticosteroids prior to sf-GKRS (HR=5.8), and Karnofsky PS <80% (HR=9.1) were independently associated with worse OS, whereas previously described prognostic scores were not. Adverse radiation effects (ARE) were uncommon and associated with large target volumes and pre-treatment oedema.

In conclusion, this thesis identifies several factors potentially useful for prognostication in mRCC, and indicates the usefulness of local metastatic therapy, in particular SRT, in selected patients. The results should be validated prospectively.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 88
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1590
Keywords
rcc, renal cell carcinoma, kidney cancer, stereotactic radiotherapy, srt, stereotactic body radiotherapy, sbrt, gamma knife radiosurgery, gkrs, stereotactic radiosurgery, srs, radiotherapy, overall survival, prognostic factor, papillary
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-390138 (URN)978-91-513-0724-4 (ISBN)
Public defence
2019-10-07, Rudbeckssalen, Rudbecklaboratoriet, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2019-09-16 Created: 2019-08-20 Last updated: 2019-10-15Bibliographically approved

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