PET/CT in the Evaluation of Response to Treatment of Liver Metastases from Colorectal Cancer with Bevacizumab and Irinotecan

Abstract

The present approach at our institution for the treatment of patients with colorectal (CRC) cancer and with liver metastases planned for metastasectomy is the neoadjuvant administration of Bevacizumab with Irinotecan based therapy. Metabolic imaging of tumor viability with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and simultaneous anatomic localization provided by low-dose non-enhanced computed tomography (CT), can be obtained in a combined modality FDG-PET/CT scan. The purpose of this study was to evaluate the possible contribution of FDG-PET/CT as a surrogate marker to evaluate treatment response of liver metastases in vivo. This is a retrospective evaluation of 18F-FDG PET and CT findings in the first seven consecutive patients. FDG-PET/CT scans were performed before the start of the neoadjuvant and after four cycles of therapy, just prior to surgery. Results were compared to concurrent contrast-enhanced CT, when required, and pathology. Response to treatment was determined according to RECIST size criteria obtained from data from thin (3-5mm) slice CT, and changes in uptake of 18F-FDG uptake on PET. A total of 20 liver lesions were evaluated in seven patients. Overall, 6/7 patients had favorable response to treatment, and only one had progression of disease. One patient was found to be inoperable at surgery. Biopsy was obtained in 1/4 lesions in this patient, while pathology was unable for the remaining three lesions. As such, pathologic validation of findings was available for 17/20 lesions. Complete response (CR) was evident on FDG-PET in 10/17 (58%) lesions, whereas only 4/17(23%) were deemed CR by CT. Similarly, only 1/17 (6%) lesion appeared stable by FDG-PET criteria, whereas three (18%) were termed stable disease (SD) according to size on CT. FDG-PET findings correlated better than CT with pathology, and were more indicative of pathology. Overall PET/CT correctly predicted necrosis at pathology in 70% vs. 35% by CT. Our results suggest that 18F-FDG PET may be instrumental for predicting the pathologic response to Bevacizumab based therapy.

Monitoring and Predicting Response to Therapy with 18F-FDG PET in Colorectal Cancer: A Systematic Review

“…An important observation is that chemotherapy-induced normalization of 18 F-FDG uptake in liver metastases of colorectal cancer does not indicate a complete pathologic response (15)(16)(17). Tan et al (16) found that, despite the absence of detectable metabolic activity above the background, viable tumor cells could still be found in 85% of lesions.…”

Monitoring Predominantly Cytostatic Treatment Response with 18F-FDG PET

“…In a study in which colorectal liver metastasis patients were treated with neoadjuvant bevacizumab and irinotecan and underwent PET/CT, complete PET responses were observed after 4 cycles of treatment (44). In addition, 18 F-FDG PET/CT correctly predicted necrosis at pathology for 70% of patients, whereas CT alone did so for 35% of patients (44).…”

“…In a study in which colorectal liver metastasis patients were treated with neoadjuvant bevacizumab and irinotecan and underwent PET/CT, complete PET responses were observed after 4 cycles of treatment (44). In addition, 18 F-FDG PET/CT correctly predicted necrosis at pathology for 70% of patients, whereas CT alone did so for 35% of patients (44). In an early clinical trial of recombinant human endostatin, tumor blood flow and 18 F-FDG uptake were determined by PET for 25 patients on days 28 and 56; both parameters generally decreased with increasing drug doses, but the effects were complex and, in some analyses, nonlinear (45).…”

Application of PET/CT in the Development of Novel Anticancer Drugs

“…Combined PET/CT is a powerful tool for the staging of various malignancies [26,27], surgery and radiotherapy planning [28 -30], and the assessment of response early in the course of treatment [31,32].…”