Oncotarget

Research Papers:

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma

Shogo Hosogoe, Shingo Hatakeyama _, Ayumu Kusaka, Itsuto Hamano, Yoshimi Tanaka, Kazuhisa Hagiwara, Hideaki Hirai, Satoko Morohashi, Hiroshi Kijima, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie and Chikara Ohyama

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Oncotarget. 2017; 8:49749-49756. https://doi.org/10.18632/oncotarget.17930

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Abstract

Shogo Hosogoe1, Shingo Hatakeyama1, Ayumu Kusaka1, Itsuto Hamano1, Yoshimi Tanaka1, Kazuhisa Hagiwara1, Hideaki Hirai2, Satoko Morohashi2, Hiroshi Kijima2, Hayato Yamamoto1, Yuki Tobisawa1, Tohru Yoneyama3, Takahiro Yoneyama1, Yasuhiro Hashimoto3, Takuya Koie1 and Chikara Ohyama1,3

1Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

2Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

3Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

Correspondence to:

Shingo Hatakeyama, email: [email protected]

Keywords: renal cell carcinoma, presurgical therapy, axitinib, radiological response

Received: March 29, 2017     Accepted: May 04, 2017     Published: May 17, 2017

ABSTRACT

Background and Objective: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy.

Results: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were −19%, −24%, and −49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST.

Materials and Methods: Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis.

Conclusions: CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.


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