AUA 2018: Safety Lead-in of a Phase II Trial of Neo-Adjuvant SAbR for IVC tumor Thrombus in RCC

San Francisco, CA (UroToday.com) Patients with advanced renal cell carcinoma (RCC) may be present with extension into the renal vein or into the inferior vena cava (IVC). It is evident in up to 10% of patients presenting with advanced RCC, and necessitates more urgent management. Traditionally, the standard of care has been nephrectomy and tumor thrombectomy – though this can be an extensive operation depending on the extent of the thrombus. Poor long-term outcomes are expected in patients who present with tumor thrombus, as many often present with metastatic disease.

The authors of this paper note that Stereotactic ablative radiation therapy (SAbR) has been increasingly utilized in the management of renal cell carcinoma – either to treat small volume metastatic disease or even the primary tumor in patients who are not surgical candidates. In the hepatocellular carcinoma literature, it has been directed at portal or IVC thrombi – albeit with moderate success. This group has previously published their small experience of SAbR in 2 elderly patients with tumor thrombus who were not surgical candidates.1 These 2 patients had 18-32 month survival without systemic therapy. 

SAbR, also sometimes referred to as SBRT, has the ability to be very focused and precise. It, therefore, enables high dose delivery with minimal effect on surrounding tissues. It causes rapid endothelial cell death, direct cell necrosis, and induces an immune response. 

Based on this, they have initiated a phase II trial of neo-adjuvant SAbR for IVC tumor thrombus prior to planned nephrectomy and tumor thrombectomy. Newly diagnosed patients with RCC and IVC-TT received 40 Gy in 5 fractions of neo-adjuvant SAbR specifically to the IVC-TT, followed by radical nephrectomy and thrombectomy. 

At this time, they are just presenting safety results of the lead-in phase II trial. Primary endpoints for the safety lead-in phase were feasibility and safety defined as the absence of grade 4-5 adverse events within 90 days of surgery. The study design is below:

UroToday AUA2018 Neo Adjuvant SABR for IVC tumor Thrombus in RCC

To date, 6 patients (3 male, 3 female) have been enrolled as part of the lead-in; an additional 28 patients will be treated. Patients primarily had level II thrombus (5/6) or level III thrombus (1/6), clear cell histology (4/6), stage III-IV disease (all), and ECOG 0-1 (5/6). 

One additional patient was withdrawn from the trial because of extensive liver metastasis found during surgery which was subsequently aborted – hence he never received nephrectomy. Median follow-up was 20 months (~1.5 years).  SAbR was administered over 9-16 days. During the SAbR treatment, seven immediate adverse events (grade 1-2) were reported in 4 patients – prior to surgery.  Surgery was performed within 4-14 days from the completion of SAbR. The estimated blood loss range was 10-1200cc and 3 patients (50%) received blood transfusions. No intraoperative complications were reported. 

Post-operatively, length of hospital stay was 3-10 days. No readmissions or mortality related to surgery were observed.  Overall, 56 post-operative adverse events were reported within 90 days, none of which were greater than grade 3; of those, 23 (41%) and 7 (12%) were considered to be related to surgery or SAbR, respectively.

In terms of oncologic outcomes, all patients are still alive. In terms of MFS – 1 immediately progressed after surgery, 1 developed lung mets after 12 months, and 1 developed breast angiosarcoma and was treated appropriately. They did not an abscopal effect in some patients, particularly in pre-op lung metastases – either complete or partial resolution.  This trial is ongoing and still recruiting. Further patient data will help confirm early results that suggest that adding SAbR in the neoadjuvant setting may be safe. Oncologic outcomes are still pending. 


References:
1. Hannan R, Margulis V, Chun SG, Cannon N, Kim DW, Abdulrahman RE, Sagalowsky A, Pedrosa I, Choy H, Brugarolas J, Timmerman RD. Stereotactic radiation therapy of renal cancer inferior vena cava tumor thrombus. Cancer Biol Ther. 2015;16(5):657-61. doi: 10.1080/15384047.2015.1026506.

Presented by: Yuval Freifeld, MD, UT Southwestern, Dallas, Texas
Co-Author: Raquibul Hannan, Solomon Woldu, Aditya Bagrodia, Jeffry Gahan, Robert Timmerman, Osama Mohamad, Aaron Laine, Neil Desai, James Brugarolas, Vitaly Margulis, Dallas, TX

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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