Abstract 3972: Total lesion glycolysis (TLG) as an imaging biomarker of regorafenib treatment in metastatic colorectal cancer (mCRC)
Authors: Lim Yoojoo , Bang Ji-In , Han Sae-Won , Paeng Jin Chul , Yoon Jeong Hee , Lee Jeong Min , Won Jae-Kyung , Kang Gyeong Hoon , Jeong Seung-Yong , Park Kyu Joo , Lee Kyung-Hun , Kim Jee Hyun , Kim Tae-You 
Published: July 2016

Introduction: Regorafenib is an oral multikinase inhibitor with anti-angiogenic activity. Decrease in tumor density without significant decrease in tumor volume is often observed after treatment with the drug, suggesting the necessity of further means of response evaluation in addition to size criteria. This study was planned to evaluate whether metabolic imaging with 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict outcome in mCRC patient treated with regorafenib.

Methods: Patients were enrolled into a main study entitled Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer: A Prospective Explorative Study (NCT01996969). mCRC patients (N = 117) were treated with regorafenib, 160mg orally once daily, on days 1-21 of a 28-day cycle, and treatment outcome was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. For this imaging sub-study, the results of 18-FDG PET scans obtained at baseline and after 2 cycles of treatment were analyzed. Total lesion glycolysis (TLG) of each patient was calculated by multiplying the volume exceeding the threshold of 40% of maximum standardized uptake value (SUV) by the mean SUV of the lesion, and the percentage changes of TLG after treatment were calculated. The association between the changes of the metabolic imaging and treatment outcome was analyzed.

Results: A total of 44 patients were evaluable for 18-FDG PET scan results. The best overall response in the 44 patients were, partial response in 3 (6.8%), stable disease in 23 (52.3%) and progressive disease in 18 (40.9%). The median progression-free survival (PFS) and the median overall survival (OS) were 5.4 and 14.1 months, respectively. The median of TLG at baseline was 187.4 (range 18.3 to 8893.2). After 2 cycles of regorafenib, 50.0% of patients had a decrease in TLG. Median change in TLG was 1.7% (range, -75.7 to 251.6%). Changes in TLG were modestly associated with size changes (Pearson's r = 0.51, p = 0.001). Patients with lower baseline TLG (&lt; 324.49) showed significantly longer OS (1 year survival rate 75.6 vs. 33.5%, p = 0.008). Moreover, patients showing higher decrease in TLG (change &lt; 1.7%) showed significantly longer PFS (median 8.4 vs. 1.9 months, p&lt;0.001) and trend towards longer OS (1 year survival rate 67.6% vs. 50.9%, p = 0.068).

Conclusions: Lower baseline TLG is associated with better OS and higher decrease in TLG after treatment predicted better PFS in mCRC patients treated with regorafenib.

Citation Format: Yoojoo Lim, Ji-In Bang, Sae-Won Han, Jin Chul Paeng, Jeong Hee Yoon, Jeong Min Lee, Jae-Kyung Won, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Kyung-Hun Lee, Jee Hyun Kim, Tae-You Kim. Total lesion glycolysis (TLG) as an imaging biomarker of regorafenib treatment in metastatic colorectal cancer (mCRC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3972.