Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast-enhanced CT.

OBJECTIVE The aim of this study was to improve response assessment in patients with metastatic renal cell carcinoma (RCC) on antiangiogenic targeted therapy by evaluating changes in both tumor size and attenuation and by detecting unique patterns of contrast enhancement on contrast-enhanced CT (CECT). MATERIALS AND METHODS Tumor long-axis measurements and volumetric mean tumor attenuation of target lesions on CECT images were correlated with time to progression in 53 patients with metastatic clear cell RCC treated with first-line sorafenib or sunitinib. The frequencies of specific patterns of tumor progression were assessed. The data were used to develop new imaging criteria, the size and attenuation CT (SACT) criteria. CECT findings were evaluated using the SACT criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and modified Choi criteria, and the Kaplan-Meier method was used to estimate survival functions. RESULTS One or more target metastatic lesions had decreased attenuation of >or=40 HU in 59% of patients with progression-free survival of >250 days (n=44) after initiating targeted therapy; 0% of patients with earlier disease progression (n=9) had this finding. A favorable response based on SACT criteria had a sensitivity of 75% and specificity of 100% for identifying patients with progression-free survival of >250 days, versus 16% and 100%, respectively, for RECIST and 93% and 44% for the modified Choi criteria. CONCLUSION Objectively measuring changes in both tumor size and attenuation on the first CECT study after initiating targeted therapy for metastatic RCC markedly improves response assessment. Distinct patterns of disease recurrence are seen in patients with metastatic RCC on targeted therapy.

[1]  V. Sukhatme,et al.  Renal cancer: molecular mechanisms and newer therapeutic options , 2002, Current opinion in nephrology and hypertension.

[2]  J. Kolesar,et al.  Role of sunitinib and sorafenib in the treatment of metastatic renal cell carcinoma. , 2008, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[3]  Haesun Choi,et al.  We should desist using RECIST, at least in GIST. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  M. Gore,et al.  Imaging in metastatic renal cell carcinoma. , 2007, AJR. American journal of roentgenology.

[5]  Apurva A Desai,et al.  Sorafenib in advanced clear-cell renal-cell carcinoma. , 2007, The New England journal of medicine.

[6]  Kyung Soo Lee,et al.  New CT response criteria in non-small cell lung cancer: proposal and application in EGFR tyrosine kinase inhibitor therapy. , 2011, Lung cancer.

[7]  S Nahum Goldberg,et al.  Perfusion MDCT enables early detection of therapeutic response to antiangiogenic therapy. , 2008, AJR. American journal of roentgenology.

[8]  Ivan Pedrosa,et al.  Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. , 2011, European Urology.

[9]  B. Rini,et al.  Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. , 2008, The Journal of urology.

[10]  A. D. Van den Abbeele,et al.  Imaging in renal cell carcinoma. , 2011, Hematology/oncology clinics of North America.

[11]  Eric P Tamm,et al.  CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. , 2004, AJR. American journal of roentgenology.

[12]  U. Mueller-Lisse,et al.  Imaging of advanced renal cell carcinoma , 2010, World Journal of Urology.

[13]  A. Scott,et al.  Potential of imaging biomarkers for characterization of renal masses , 2010, Expert review of anticancer therapy.

[14]  V. Goh,et al.  Assessment of response to tyrosine kinase inhibitors in metastatic renal cell cancer: CT texture as a predictive biomarker. , 2011, Radiology.

[15]  I. Pedrosa,et al.  Evaluation of Treatment Response in Patients with Metastatic Renal Cell Carcinoma: Role of State-of-the-Art Cross-Sectional Imaging , 2012, Current Urology Reports.

[16]  N. Lawrentschuk,et al.  Imaging renal cell carcinoma with ultrasonography, CT and MRI , 2010, Nature Reviews Urology.

[17]  M Van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. , 2000, Journal of the National Cancer Institute.

[18]  E. Fishman,et al.  Application of CT in the investigation of angiogenesis in oncology. , 2000, Academic radiology.

[19]  R. Bechtold,et al.  Cystic changes in hepatic metastases from gastrointestinal stromal tumors (GISTs) treated with Gleevec (imatinib mesylate). , 2002, AJR. American journal of roentgenology.

[20]  A. D. Van den Abbeele,et al.  Gastrointestinal stromal tumor: new nodule-within-a-mass pattern of recurrence after partial response to imatinib mesylate. , 2005, Radiology.

[21]  R. Motzer,et al.  Sunitinib efficacy against advanced renal cell carcinoma. , 2007, The Journal of urology.

[22]  C. Wood,et al.  Renal cell carcinoma: what the surgeon and treating physician need to know. , 2011, AJR. American journal of roentgenology.

[23]  K. Miles,et al.  Tumour angiogenesis and its relation to contrast enhancement on computed tomography: a review. , 1999, European journal of radiology.

[24]  V. Dicken,et al.  Semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma stage III/IV-A feasibility study , 2008, European Radiology.

[25]  D. Petrylak,et al.  Cytotoxic chemotherapy for advanced renal cell carcinoma. , 1993, The Urologic clinics of North America.

[26]  M. Gordon,et al.  Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma , 2008 .

[27]  R. Figlin,et al.  Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  O. Akin,et al.  Imaging assessment of tumor response: past, present and future. , 2011, Future oncology.

[29]  Peter N. Burns,et al.  Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy. , 2011, Radiology.

[30]  P. Petrow,et al.  Hepatic tumors treated with percutaneous radio-frequency ablation: CT and MR imaging follow-up. , 2002, Radiology.

[31]  C. Blank,et al.  A phase II study of presurgical sunitinib in patients with metastatic clear-cell renal carcinoma and the primary tumor in situ. , 2011, Urology.

[32]  A. D. Van den Abbeele,et al.  CT and PET: early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor. , 2007, AJR. American journal of roentgenology.

[33]  Michael Sühling,et al.  Semi-automated measurement of hyperdense, hypodense and heterogeneous hepatic metastasis on standard MDCT slices. Comparison of semi-automated and manual measurement of RECIST and WHO criteria , 2008, European Radiology.

[34]  J. Kaouk,et al.  Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib , 2007, International journal of urology : official journal of the Japanese Urological Association.

[35]  Martijn R. Meijerink,et al.  Targeted therapies in renal cell cancer: recent developments in imaging , 2010, Targeted Oncology.

[36]  Joong-Won Park,et al.  Computed tomography findings of sorafenib‐treated hepatic tumors in patients with advanced hepatocellular carcinoma , 2011, Journal of gastroenterology and hepatology.

[37]  Vahid Yaghmai,et al.  Response to treatment series: part 2, tumor response assessment--using new and conventional criteria. , 2011, AJR. American journal of roentgenology.

[38]  Haesun Choi,et al.  Response evaluation of gastrointestinal stromal tumors. , 2008, The oncologist.

[39]  M. Leggas,et al.  Sunitinib malate for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. , 2007, Clinical therapeutics.

[40]  M. Haider,et al.  Hepatic perfusion imaging: concepts and application. , 2010, Magnetic resonance imaging clinics of North America.

[41]  Haesun Choi,et al.  Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  P. Tamboli,et al.  Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib. , 2011, European urology.

[43]  Shetal N Shah,et al.  Morphology, Attenuation, Size, and Structure (MASS) criteria: assessing response and predicting clinical outcome in metastatic renal cell carcinoma on antiangiogenic targeted therapy. , 2010, AJR. American journal of roentgenology.

[44]  Joaquim Bellmunt,et al.  Optimisation of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine. , 2012, European journal of cancer.

[45]  P. Tamboli,et al.  Primary tumor response to targeted agents in patients with metastatic renal cell carcinoma. , 2011, European urology.

[46]  E. Sacco,et al.  Imaging of Renal Cell Carcinoma: State of the Art and Recent Advances , 2010, Urologia Internationalis.

[47]  Chiun Hsu,et al.  Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil. , 2011, Journal of hepatology.

[48]  S. Fosså,et al.  Interferon in metastatic renal cell carcinoma. , 2000, Seminars in oncology.

[49]  M. Johannsen,et al.  Difference between clinical and pathologic renal tumor size, correlation with survival, and implications for patient counseling regarding nephron-sparing surgery. , 2011, AJR. American journal of roentgenology.

[50]  M. van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors , 2000, Journal of the National Cancer Institute.

[51]  M. Michaelson ASCO 2006 highlights: targeted therapy for renal cell carcinoma. , 2007, Cancer treatment reviews.