{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:45:23Z","timestamp":1792079123025,"version":"4.4.0"},"reference-count":15,"publisher":"American Medical Association (AMA)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was 1-year recurrence-free survival (RFS) compared with a prespecified historical surgery-alone benchmark of 55.7%. 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 of 55.7% (\n P<\/jats:italic>\n \u2009=\u2009.09). 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.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT02473536<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.4172","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:00:37Z","timestamp":1792076437000},"source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant Stereotactic Ablative Radiotherapy Before Inferior Vena Cava Thrombectomy for Renal Cell Carcinoma"],"prefix":"10.1001","author":[{"given":"Raquibul","family":"Hannan","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Assadi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurentiu M.","family":"Pop","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily","family":"Robles","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Mulvaney","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Health Data Science and Biostatistics, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Payal","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Department of Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Garant","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Health Data Science and Biostatistics, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wait","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Timmerman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Margulis","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"issue":"12","key":"cbr260012r1","doi-asserted-by":"publisher","first-page":"4140","DOI":"10.1038\/s41591-025-03966-3","article-title":"Macrovascular tumor infiltration and circulating tumor cell cluster dynamics in patients with cancer approaching the end of life.","volume":"31","author":"Newcomer","year":"2025","journal-title":"Nat 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