Background: With limitations of conventional imaging and biopsy, accurate, non-invasive techniques to detect clear-cell renal cell carcinoma in patients with renal masses remain an unmet need. Zr-labelled monoclonal antibody ([Zr]Zr-girentuximab) has high affinity for carbonic anhydrase 9, a tumour antigen highly expressed in clear-cell renal cell carcinoma. We aimed to evaluate [Zr]Zr-girentuximab PET-CT imaging for detection and characterisation of clear-cell renal cell carcinoma.
Methods: ZIRCON was a prospective, open-label, multicentre, phase 3 trial conducted at 36 research hospitals and practices across nine countries (the USA, Australia, Canada, the UK, Türkiye, Belgium, the Netherlands, Spain, and France). Patients aged 18 years or older with an indeterminate renal mass 7 cm or smaller (cT1) suspicious for clear-cell renal cell carcinoma and scheduled for nephrectomy received a single dose of [Zr]Zr-girentuximab (37 MBq ±10%; 10 mg girentuximab) intravenously followed by abdominal PET-CT imaging 5 days (±2 days) later. Surgery was performed no later than 90 days after administration of [Zr]Zr-girentuximab. Blinded central review, conducted by three independent readers, determined the histology from surgical samples. The coprimary endpoints, determined for each individual reader, were the sensitivity and specificity of [Zr]Zr-girentuximab PET-CT imaging to detect clear-cell renal cell carcinoma, with histopathological confirmation as standard of truth. Analyses were on the full analysis set of patients, defined as patients who had evaluable PET-CT imaging and a confirmed histopathological diagnosis. The trial is registered with ClinicalTrials.gov, NCT03849118, and EUDRA Clinical Trials Register, 2018-002773-21, and is closed to enrolment.
Findings: Between Aug 14, 2019, and July 8, 2022, 371 patients were screened for eligibility, 332 of whom were enrolled. 300 patients received [Zr]Zr-girentuximab (214 [71%] male and 86 [29%] female). 284 (95%) evaluable patients were included in the primary analysis. The mean sensitivity was 85·5% (95% CI 81·5-89·6) and mean specificity was 87·0% (81·0-93·1). No safety signals were observed. Most adverse events were not or were unlikely to be related to [Zr]Zr-girentuximab, with most (193 [74%] of 261 events) occurring during or after surgery. The most common grade 3 or worse adverse events were post-procedural haemorrhage (in six [2%] of 261 patients), urinary retention (three [1%]), and hypertension (three [1%]). In 25 (8%) of 300 patients, 52 serious adverse events were reported, of which 51 (98%) occurred after surgery. There were no treatment-related deaths.
Interpretation: Our results suggest that [Zr]Zr-girentuximab PET-CT has a favourable safety profile and is a highly accurate, non-invasive imaging modality for the detection and characterisation of clear-cell renal cell carcinoma, which has the potential to be practice changing.
Funding: Telix Pharmaceuticals.
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http://dx.doi.org/10.1016/S1470-2045(24)00402-9 | DOI Listing |
Transl Oncol
December 2024
Biotherapy Center, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China. Electronic address:
It has been well established that tumor-infiltrating lymphocytes (TILs) play a critical role in the pathogenesis and progression of clear cell renal cell carcinoma (ccRCC). However, the mechanism on the interactions between TILs and tumor cells in the tumor-immune microenvironment remains unclear. In the present study, the expression of Response Gene to Complement 32 (RGC-32) was evaluated using immunohistochemistry.
View Article and Find Full Text PDFBiol Direct
December 2024
Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 Qingchun Road, Hangzhou, 310016, China.
Background: Precision oncology's implementation in clinical practice faces significant constraints due to the inadequacies in tools for detailed patient stratification and personalized treatment methodologies. Dysregulated tryptophan metabolism has emerged as a crucial factor in tumor progression, encompassing immune suppression, proliferation, metastasis, and metabolic reprogramming. However, its precise role in clear cell renal cell carcinoma (ccRCC) remains unclear, and predictive models or signatures based on tryptophan metabolism are conspicuously lacking.
View Article and Find Full Text PDFBMC Pharmacol Toxicol
December 2024
Department of Critical Care Medicine, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, 250014, China.
Background: The belzutifan is a hypoxia inducible factor-2 alpha (HIF-2α) inhibitor for the treatment of advanced or metastatic clear cell renal cell carcinoma (mccRCC) and has exhibited good safety and efficacy in clinical trials. We conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of belzutifan for the treatment of mccRCC.
Methods: Multiple databases and abstracts from major scientific meetings were systematically reviewed for eligible articles published before June 1, 2024.
J Cell Mol Med
December 2024
Department of Nephrology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Clear cell renal cell carcinoma (ccRCC) characterised by its diversity and a tendency to defy standard therapeutic approaches. Amidst the advent of immunotherapy, it has become imperative to pinpoint prognostic indicators of the tumour microenvironment (TME) influence the efficacy of treatments. Employing single-cell RNA sequencing (scRNA-seq), this research delved into the diverse landscape of ccRCC, uncovering its complex underpinnings and pinpointing molecular avenues for therapeutic intervention.
View Article and Find Full Text PDFJCO Clin Cancer Inform
December 2024
Ontada, Boston, MA.
Purpose: Nivolumab plus ipilimumab (NIVO + IPI) is a first-in-class combination immunotherapy for the treatment of intermediate- or poor (I/P)-risk advanced or metastatic renal cell carcinoma (mRCC). Currently, there are limited real-world data regarding clinical effectiveness beyond 12-24 months from treatment initiation. In this real-world study, treatment patterns and clinical outcomes were evaluated for NIVO + IPI in a community oncology setting.
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