Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in a murine model

2016 ◽  
Vol 119 (2) ◽  
pp. 342-348 ◽  
Author(s):  
James Liu ◽  
Caleb Abshire ◽  
Connor Carry ◽  
Andrew B. Sholl ◽  
Sree Harsha Mandava ◽  
...  
Author(s):  
L. M. Mittlmeier ◽  
M. Unterrainer ◽  
S. Rodler ◽  
A. Todica ◽  
N. L. Albert ◽  
...  

Abstract Introduction Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. Methods 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. Results Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. Conclusion On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.


Author(s):  
S. Lowell Kahn

Surgical resection of renal cell carcinoma (RCC) remains the standard of care given the excellent reported outcomes for early stage disease, with 5-year cancer-specific survival (CSS) rates of 97% for pT1a and 87% for pT1b tumors after nephrectomy. Outcomes after partial nephrectomy are equally encouraging, with 5- and 10-year CSS rates of 92% and 80%, respectively, across all stages and 96% and 90%, respectively, for tumors less than 4 cm. Transarterial embolization prior to thermal ablation for RCC is far less frequent, but it is described in the literature. To date, there are no randomized controlled studies that demonstrate a benefit of combined therapy over radiofrequency ablation (RFA) or cryoablation alone. However, lipiodol is profoundly radiopaque, and utilization prior to RFA or cryoablation may aid in the visualization of the tumor.


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