The goal of this multicenter observational study is to elucidate the clinical and immunological characteristics of the abscopal effect in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitors (ICI) combined with image-guided ultra-hypofractionated radiotherapy (IGU).
The main questions this study aims to answer are:
What is the abscopal response rate (ARR) at one year after IGU in patients continuing ICI treatment?
What clinical and immunological factors are associated with the occurrence and timing of the abscopal effect?
Participants are patients with mRCC who have experienced immune-confirmed stable or progressive disease during ICI therapy and are scheduled to receive IGU to a selected lesion. Researchers will observe tumor responses at irradiated and non-irradiated sites using standard imaging (CT/MRI) and collect clinical and laboratory data at baseline, 3, 6, 9, and 12 months after IGU. Optional exploratory blood samples will be obtained for cytokine analysis (e.g., IFN-β, IFN-γ, TNF-α, IL-6).
The primary outcome is the abscopal response rate (ARR) at one year after IGU. Secondary outcomes include tumor shrinkage rate of irradiated and non-irradiated lesions, 1-year overall survival, disease-specific survival, and progression-free survival.
This study seeks to establish a foundation for developing combined immunotherapy and ultra-hypofractionated radiotherapy strategies for metastatic renal cell carcinoma.
\*This study is led by Prof. Hiroshi Onishi (University of Yamanashi). The registry entry is managed by Dr. Zhe Chen on behalf of the study group.
Patients aged 18 years and above with metastatic renal cell carcinoma
Patients currently receiving immune checkpoint inhibitor (ICI) therapy who are assessed as having iCPD or iSD according to iRECIST
Presence of two or more clinically measurable lesions (assessed by CT, MRI, physical examination, or visual inspection) Note: Osteosclerotic lesions without measurable soft-tissue components are excluded
Planned to undergo IGU to the target lesion
Patients with active double cancers (synchronous double cancers or metachronous double cancers with a disease-free interval within 2 years).
severe cardiac disease
uncontrolled diabetes mellitus despite continuous insulin therapy
myocardial infarction within 6 months
Adult patients (≥18 years) with histologically confirmed metastatic renal cell carcinoma (mRCC) who are receiving ICIs and are candidates for IGU to one or more metastatic lesions. Eligible patients must have immune-confirmed stable disease or progression during ongoing ICI therapy. Enrollment will include patients treated at participating centers of the AURICRE multicenter registry.
Cohort
Prospective
Not listed
Abscopal Response Rate (ARR) at 1 Year After IGU
The proportion of patients showing an abscopal response, defined as a ≥30% reduction in the sum of diameters of non-irradiated target lesions without new lesion appearance, evaluated according to RECIST 1.1 criteria. Tumor response will be assessed by radiological imaging (CT or MRI) at each follow-up visit and confirmed by central review.
Tumor Shrinkage Rate of Irradiated and Non-Irradiated Lesions
The percentage change in the sum of diameters of irradiated and non-irradiated lesions from baseline, assessed by RECIST 1.1 at each follow-up (3, 6, 9, and 12 months).
One-Year Overall Survival (OS)
Overall survival defined as the time from initiation of IGU to death from any cause. Patients alive at the end of follow-up will be censored at the date of last contact.
One-Year Disease-Specific Survival (DSS)
Disease-specific survival defined as the time from IGU to death due to renal cell carcinoma. Deaths from other causes will be censored at the date of death.
One-Year Progression-Free Survival (PFS)
Progression-free survival defined as the time from IGU to disease progression or death, whichever occurs first, based on RECIST 1.1 criteria.
Temporal Changes and Correlation of Serum Cytokine Profiles With Abscopal Response
Quantitative changes in circulating cytokines (IFN-β, IFN-γ, TNF-α, IL-6) measured by enzyme-linked immunosorbent assay (ELISA) at baseline and 3 and 12 months after IGU. Statistical correlations between cytokine dynamics and abscopal response rate will be analyzed using logistic regression and receiver operating characteristic (ROC) analysis.
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Zhe Chen
Lead sponsor
University of Yamanashi
Sponsor institution
Participating institutions of the AURICRE Study Group
Collaborator
