The standard criteria used to evaluate tumor response, the Response Evaluation Criteria in Solid Tumors (RECIST), were developed to assess tumor shrinkage after cytotoxic chemotherapy and may be limited in assessing response to biologic agents, which have a cytostatic mechanism of action..
To validate novel tumor response criteria based on morphologic changes observed on computed tomography (CT) in patients with colorectal liver metastases (CLM) treated with bevacizumab-containing chemotherapy regimens.
Design, Setting, and Patients
234 CLM were analyzed in 50 patients who underwent hepatic resection after preoperative chemotherapy that included bevacizumab at a comprehensive US cancer center from 2004 to 2007; date of last follow-up was March 2008. All patients underwent routine contrast-enhanced CT at the start and end of preoperative therapy. Three blinded, independent radiologists evaluated images for morphologic response, based upon metastases changing from heterogeneous masses with ill-defined margins into homogeneous lesions with sharp borders. These criteria were validated with a separate cohort of 82 patients with unresectable CLM treated with bevacizumab-containing chemotherapy.
Main Outcome Measures
Response determined using morphologic criteria and RECIST was correlated with pathologic response in resected liver specimens and with patient survival.
Interobserver agreement for scoring morphologic changes was good among three radiologists (κ=0.68–0.78; 95% confidence interval, 0.51–0.93). In resected tumor specimens with morphologic optimal, incomplete, and no response, the median percentages of residual tumor cells were 20% (interquartile range [IQR], 10%–30%), 50% (IQR, 30%–60%), and 70% (IQR, 60%–70%), respectively (P<.001). With RECIST partial response, stable disease, and progressive disease, the median percentages of residual tumor cells were 30% (IQR, 10%–60%), 50% (IQR, 20%–70%), and 70% (IQR, 65%–70%), respectively (P=.04). Among patients who underwent hepatic resection, median overall survival was not yet reached with optimal morphologic response and 35 months (95% CI, 20.2 to 29.8 months) with incomplete or no morphologic response (P=.03). In the validation cohort, patients with optimal morphologic response had median overall survival of 31 months (95% CI, 26.8 to 35.2 months) compared to 19 months (95% CI, 14.6 to 23.4 months) with incomplete or no morphologic response (P=.009). RECIST did not correlate with survival in neither the surgical nor validation cohort.
Among patients with CLM treated with bevacizumab-containing chemotherapy, CT-based morphologic criteria had a statistically significant association with pathologic response and overall survival.