Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration-7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05-11.61), 7.40 ± 2.50 months (95% CI = 5.61-9.19) and 4.20 ± 1.99 months (95% CI = 2.78-5.62) accordingly (p < 0.05). There was no difference in change of main lesions' longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35-25.87) and by 7.66 ± 6.72% (95% CI = 2.86-12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.

• Klíčová slova
• Apparent diffusion coefficient, Diffusion-weighted imaging, Early response, Imaging biomarker, MRI, Prediction, Progress, Renal cell carcinoma, Systemic treatment, Targeted therapy, Tyrosine kinase inhibitor,
• MeSH
• difuzní magnetická rezonance metody   MeSH
• indazoly MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z renálních buněk diagnostické zobrazování   farmakoterapie   mortalita   patologie   MeSH
• ledviny diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin diagnostické zobrazování   farmakoterapie   mortalita   patologie   MeSH
• pyrimidiny terapeutické užití   MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři MeSH
• sulfonamidy terapeutické užití   MeSH
• výsledek terapie MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• indazoly MeSH
• inhibitory angiogeneze MeSH
• pazopanib MeSH Prohlížeč
• pyrimidiny MeSH
• sulfonamidy MeSH

INTRODUCTION: Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and more than 90% of neoplasms arising from the kidney. Uninformative percutaneous kidney biopsies vary from 10 to 23%. As a result, 7.5-33.6% of partial nephrectomies in patients with small renal masses (SRM) are performed on benign renal tumors. The aim of this study was to assess the feasibility of the apparent diffusion coefficient (ADC) of the diffusion-weighted imaging (DWI) of MRI, as RCC imaging biomarker for differentiation of SRM. METHOD: Adult patients (n = 158) with 170 SRM were enrolled into this study. The control group were healthy volunteers with normal clinical and radiologic findings (n = 15). All participants underwent MRI with DWI sequence included. RESULTS: Mean ADC values of solid RCC (1.65 ± 0.38 × 10-3 mm2/s) were lower than healthy renal parenchyma (2.47 ± 0.12 × 10-3 mm2/s, p < 0.05). There was no difference between mean ADC values of ccRCC, pRCC and chRCC (1.82 ± 0.22 × 10-3 vs 1.61 ± 0.07 × 10-3 vs 1.46 ± 0.09 × 10-3 mm2/s, respectively, p = ns). An inverse relationship between mean ADC values and Fuhrman grade of nuclear atypia of solid ccRCCs was observed: grade I-1.92 ± 0.11 × 10-3 mm2/s, grade II-1.84 ± 0.14 × 10-3 mm2/s, grade III-1.79 ± 0.10 × 10-3 mm2/s, grade IV-1.72 ± 0.06 × 10-3 mm2/s. This was significant (p < 0.05) only between tumors of I and IV grades. Significant difference (p < 0.05) between mean ADC values of solid RCCs, benign renal tumors and renal cysts was observed (1.65 ± 0.38 × 10-3 vs 2.23 ± 0.18 × 10-3 vs 3.15 ± 0.51 × 10-3 mm2/s, respectively). In addition, there was a significant difference (p < 0.05) in mean ADC values between benign cysts and cystic RCC (3.36 ± 0.35 × 10-3 vs 2.83 ± 0.21 × 10-3 mm2/s, respectively). CONCLUSION: ADC maps with b values of 0 and 800 s/mm2 can be used as an imaging biomarker, to differentiate benign SRM from malignant SRM. Using ADC value threshold of 1.75 × 10-3 mm2/s allows to differentiate solid RCC from solid benign kidney tumors with 91% sensitivity and 89% specificity; ADC value threshold of 2.96 × 10-3 mm2/s distinguishes cystic RCC from benign renal cysts with 90% sensitivity and 88% specificity. However, the possibility of differentiation between ccRCC histologic subtypes and grades, utilizing ADC values, is limited.

• Klíčová slova
• Apparent diffusion coefficient, Diffusion-weighted imaging, MRI, Renal cell carcinoma, Small renal masses,
• MeSH
• cystická onemocnění ledvin diagnóza   MeSH
• diferenciální diagnóza MeSH
• difuzní magnetická rezonance metody   MeSH
• dospělí MeSH
• karcinom z renálních buněk * diagnóza   patologie   chirurgie   MeSH
• léčba šetřící orgány metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * diagnóza   patologie   chirurgie   MeSH
• nefrektomie metody   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH