Abscopal Effect of Ultra-Hypofractionated Radiation Plus Immunotherapy in Metastatic Renal Cell Carcinoma

Summary

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.

Eligibility

Inclusion Criteria:

1. Patients aged 18 years and above with metastatic renal cell carcinoma
2. Patients currently receiving immune checkpoint inhibitor (ICI) therapy who are assessed as having iCPD or iSD according to iRECIST
3. 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
4. Planned to undergo IGU to the target lesion
5. Provided written informed consent after receiving sufficient explanation of this study Note: Proxy signature is permitted if the patient is physically unable to sign

Exclusion Criteria:

1. Patients with active double cancers (synchronous double cancers or metachronous double cancers with a disease-free interval within 2 years).

   However, carcinoma in situ or intramucosal carcinoma considered cured by treatment, and the following tumors even if within 2 years of disease-free interval are not excluded: gastric cancer stage 0-II (UICC), prostate cancer stage I-III, colorectal cancer stage 0-II, esophageal cancer stage 0-I, breast cancer stage 0-II, endometrial cancer stage I-II, cervical cancer stage 0-II, and thyroid cancer stage I-III. In addition, any cancer with a disease-free interval greater than 2 years is not excluded regardless of stage.
2. Patients with serious comorbidities, such as:

   * severe cardiac disease
   * uncontrolled diabetes mellitus despite continuous insulin therapy
   * myocardial infarction within 6 months
   * uncontrolled hypertension
   * active infections (bacterial, viral, or fungal)
   * diarrhea (watery stool), paralytic ileus, or bowel obstruction
   * autoimmune disease
   * any other severe comorbid condition
3. Patients with clear evidence of idiopathic interstitial pneumonia (usual interstitial pneumonia pattern) on chest X-ray or CT
4. Patients with acute-phase pneumonia
5. Patients with psychiatric disorders or psychiatric symptoms judged to make study participation difficult

Conditions2

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