Faculty, Staff and Student Publications
Language
English
Publication Date
9-1-2023
Journal
European Urology
DOI
10.1016/j.eururo.2023.02.016
PMID
36898872
PMCID
PMC10440291
PubMedCentral® Posted Date
9-1-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
Background: Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.
Objective: To investigate whether SAbR is effective in the management of primary RCCs.
Design, setting, and participants: Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.
Outcome measurements and statistical analysis: The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 mm/yr on active surveillance) and pathologic evidence of tumor response at 1 yr. Secondary endpoints included LC by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), safety, and preservation of kidney function. Exploratory tumor cell-enriched spatial protein and gene expression analysis were conducted on pre- and post-treatment biopsy samples.
Results and limitations: Target accrual was reached with the enrollment of 16 ethnically diverse patients. Radiographic LC at 1 yr was observed in 94% of patients (15/16; 95% confidence interval: 70, 100), and this was accompanied by pathologic evidence of tumor response (hyalinization, necrosis, and reduced tumor cellularity) in all patients. By RECIST, 100% of the sites remained without progression at 1 yr. The median pretreatment growth rate was 0.8 cm/yr (interquartile range [IQR]: 0.3, 1.4), and the median post-treatment growth rate was 0.0 cm/yr (IQR: -0.4, 0.1, p < 0.002). Tumor cell viability decreased from 4.6% to 0.7% at 1 yr (p = 0.004). With a median follow-up of 36 mo for censored patients, the disease control rate was 94%. SAbR was well tolerated with no grade ≥2 (acute or late) toxicities. The average glomerular filtration rate declined from a baseline of 65.6 to 55.4 ml/min at 1 yr (p = 0.003). Spatial protein and gene expression analyses were consistent with the induction of cellular senescence by radiation.
Conclusions: This clinical trial adds to the growing body of evidence suggesting that SAbR is effective for primary RCC supporting its evaluation in comparative phase 3 clinical trials.
Patient summary: In this clinical trial, we investigated a noninvasive treatment option of stereotactic radiation therapy for the treatment of primary kidney cancer and found that it was safe and effective.
Keywords
Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Radiosurgery, Prospective Studies, Response Evaluation Criteria in Solid Tumors, Treatment Outcome, Primary renal cell carcinoma, Renal cell carcinoma, Stereotactic ablative radiotherapy, Senescence
Published Open-Access
yes
Recommended Citation
Hannan, Raquibul; McLaughlin, Mark F; Pop, Laurentiu M; et al., "Phase 2 Trial of Stereotactic Ablative Radiotherapy for Patients with Primary Renal Cancer" (2023). Faculty, Staff and Student Publications. 6407.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6407
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