3 Key Takeaways
Plain English Summary- 01Core Finding
To evaluate the feasibility, safety, clinical outcomes, and exploratory biomarker (measurable biological signal) effects of neoadjuvant stereotactic ablative radiotherapy (SABR) targeting IVC tumor thrombus before nephrectomy and thrombectomy.
- 02Study Evidence
Tested in a early human trial (23 patients) at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
What This Means for You
In this nonrandomized clinical trial, neoadjuvant SABR before nephrectomy and IVC thrombectomy appeared feasible with an acceptable safety profile. RFS met the prespecified Phase 2 screening criterion but remains exploratory and warrants further evaluation.
The Discovery
Renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus is associated with substantial perioperative risk and frequent recurrence despite nephrectomy and thrombectomy. No established neoadjuvant local therapy exists for this high-risk population. To evaluate the feasibility, safety, clinical outcomes, and exploratory biomarker (measurable biological signal) effects of neoadjuvant stereotactic ablative radiotherapy (SABR) targeting IVC tumor thrombus before nephrectomy and thrombectomy. This single-center prospective Phase 2 nonrandomized clinical trial enrolled patients with newly diagnosed RCC and Mayo level II to IV IVC tumor thrombus eligible for neoadjuvant SABR and definitive surgery from July 2015 to January 2024. Data were analyzed from August 2025 to August 2026. Neoadjuvant SABR to the radiographically defined IVC tumor thrombus, delivered as 40 Gy in 5 fractions or 36 Gy in 3 fractions, followed by radical nephrectomy and IVC thrombectomy. The primary end point was 1-year recurrence-free survival (RFS) compared with a prespecified historical surgery-alone benchmark of a clinically meaningful level. Secondary outcomes included 90-day perioperative morbidity and mortality, adverse events, pulmonary embolism, overall survival, and cancer-specific survival. Exploratory analyses included Ki-67 immunohistochemistry and tumor-informed circulating tumor DNA. The primary end point was 1-year recurrence-free survival (RFS) compared with a prespecified historical surgery-alone benchmark of a clinically meaningful level. Secondary outcomes included 90-day perioperative morbidity and mortality, adverse events, pulmonary embolism, overall survival, and cancer-specific survival. Exploratory analyses included Ki-67 immunohistochemistry and tumor-informed circulating tumor DNA. Of 23 patients who received neoadjuvant SABR, 22 completed surgery, and 21 were included in the primary RFS analysis. Of 21 included patients, 12 (57%) were male, and the median (IQR) age was 62.5 (54.0-73.2) years. A total of 19 patients had clear-cell RCC; all tumors were grade 3 or 4, and 3 patients had metastatic disease at enrollment. At a median (range) follow-up of 108.6 (2.0-127.2) months, 1-year RFS was 71.4% (80% CI, 56.6-82.0; 95% CI, 47.2-86.0), meeting the prespecified Phase 2 screening criterion based on comparison with the historical surgery-alone benchmark (P =.09). One-year overall survival was 95.2% (80% CI, 83.9-98.7; 95% CI, 70.7-99.3) and cancer-specific survival was 95.2% (80% CI, 83.9-98.7; 95% CI, 70.7-99.3). No 90-day perioperative mortality occurred; 4 grade 4 treatment-attributed events occurred, but no grade 4/5 radiation-attributed toxic effects occurred. Ki-67 expression was reduced in patients with irradiated tumor thrombus compared with nonirradiated controls. Tumor-informed circulating tumor DNA was detected in all patients with available plasma and declined after treatment.
How It Works, Simply
This oncology research focuses on immune response · Blood biomarker (measurable biological signal) · Genetics. Researchers evaluated it using an early human trial (23 patients) at the Phase I/II stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
To evaluate the feasibility, safety, clinical outcomes, and exploratory biomarker effects of neoadjuvant stereotactic ablative radiotherapy (SABR) targeting IVC tumor thrombus before nephrectomy and thrombectomy.
- 02Study Evidence
Tested in a early human trial (23 patients) at the Phase I/II stage.
- 03Practical Meaning
Early-stage human studies — dosing, durability, and rare side effects still require Phase III confirmation.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Early human trial
Early human trial (23 patients) · Phase I/II
Biological Pathway & Modality
Immune response · Blood biomarker · Genetics
Intervention: Neoadjuvant Stereotactic Ablative Radiotherapy Before Inferior Vena Cava
Experimental Findings & Endpoints
Renal cell carcinoma (RCC) with inferior vena cava (IVC) tumor thrombus is associated with substantial perioperative risk and frequent recurrence despite nephrectomy and thrombectomy.
No established neoadjuvant local therapy exists for this high-risk population. To evaluate the feasibility, safety, clinical outcomes, and exploratory biomarker effects of neoadjuvant stereotactic ablative radiotherapy (SABR) targeting IVC tumor thrombus before nephrectomy and thrombectomy.
This single-center prospective Phase 2 nonrandomized clinical trial enrolled patients with newly diagnosed RCC and Mayo level II to IV IVC tumor thrombus eligible for neoadjuvant SABR and definitive surgery from July 2015 to January 2024. Data were analyzed from August 2025 to August 2026.
Neoadjuvant SABR to the radiographically defined IVC tumor thrombus, delivered as 40 Gy in 5 fractions or 36 Gy in 3 fractions, followed by radical nephrectomy and IVC thrombectomy. The primary end point was 1-year recurrence-free survival (RFS) compared with a prespecified historical surgery-alone benchmark of a clinically meaningful level.
Secondary outcomes included 90-day perioperative morbidity and mortality, adverse events, pulmonary embolism, overall survival, and cancer-specific survival. Exploratory analyses included Ki-67 immunohistochemistry and tumor-informed circulating tumor DNA.
The primary end point was 1-year recurrence-free survival (RFS) compared with a prespecified historical surgery-alone benchmark of a clinically meaningful level. Secondary outcomes included 90-day perioperative morbidity and mortality, adverse events, pulmonary embolism, overall survival, and cancer-specific survival.
Exploratory analyses included Ki-67 immunohistochemistry and tumor-informed circulating tumor DNA. Of 23 patients who received neoadjuvant SABR, 22 completed surgery, and 21 were included in the primary RFS analysis.
Of 21 included patients, 12 (57%) were male, and the median (IQR) age was 62.5 (54.0-73.2) years. A total of 19 patients had clear-cell RCC; all tumors were grade 3 or 4, and 3 patients had metastatic disease at enrollment.
At a median (range) follow-up of 108.6 (2.0-127.2) months, 1-year RFS was 71.4% (80% CI, 56.6-82.0; 95% CI, 47.2-86.0), meeting the prespecified Phase 2 screening criterion based on comparison with the historical surgery-alone benchmark (P =.09). One-year overall survival was 95.2% (80% CI, 83.9-98.7; 95% CI, 70.7-99.3) and cancer-specific survival was 95.2% (80% CI, 83.9-98.7; 95% CI, 70.7-99.3).
No 90-day perioperative mortality occurred; 4 grade 4 treatment-attributed events occurred, but no grade 4/5 radiation-attributed toxic effects occurred. Ki-67 expression was reduced in patients with irradiated tumor thrombus compared with nonirradiated controls.
Tumor-informed circulating tumor DNA was detected in all patients with available plasma and declined after treatment.
Clinical Translation & Practice Context
In this nonrandomized clinical trial, neoadjuvant SABR before nephrectomy and IVC thrombectomy appeared feasible with an acceptable safety profile.
RFS met the prespecified Phase 2 screening criterion but remains exploratory and warrants further evaluation.
The Bottom Line · Clinical Pearl
“In this nonrandomized clinical trial, neoadjuvant SABR before nephrectomy and IVC thrombectomy appeared feasible with an acceptable safety profile.”
Published in JAMA Oncology · Current Stage: Phase I/II