Robustness of response: A new measure of response assessment: Its impact on metricies of response in colorectal cancer

Abstract

3569 Background: To illustrate a new method of quantifying and comparing response assessment techniques known as robustness of response (ROR) and to evaluate unidimensional measurement (RECIST criteria) versus bidimensional measurement (WHO criteria) with respect to their impact on assessment including response classification, time to tumor progression (TTP) and time to best overall response (BOR) in patients with colorectal cancer. Methods: 68 patients with metastatic colorectal cancer on clinical trials of HAI Floxuridine and Dexamethasone with systemic oxaliplatin with 5FU/LV and/or Irinotecan were retrospectively reviewed. The studies of a total of 2735 measurements included 68 baselines and 200 follow-up CT examinations of the chest, abdomen and pelvis. Response assessment and progression-free survival were calculated with RECIST and WHO. ROR was determined and compared among and between discordant and concordant cases. Results: There was a 92.6% agreement rate and a 7.4% disagreement rate in BOR between RECIST and WHO. The median TTP assessed by RECIST was 5.83 months compared to 5.40 months assessed by WHO (P=0.006). Time to BOR was not significantly different comparing RECIST and WHO (P=0.82). Mean percentage decrease in tumor size among the 27 unidimensional responders and 28 bidimensional responders was 65.0% and 79.7%, respectively. Mean increase in size among the 36 unidimensional progressors and 48 bidimensional progressors was 61.8% and 139.1%, respectively. The average robustness value was -35.3% by RECIST and 53.9% by WHO among the 17 discordant pairs and -25.9% by RECIST and 78.9% by WHO among the 51 concordant pairs. A comparison of ROR in time to BOR found an average robustness value of 35.7% by RECIST versus 24.8% by WHO among the 10 discordant cases, and 5.3% by RECIST versus 60.6% by WHO among the 58 concordant cases. Conclusions: In colorectal cancer, time to tumor progression was different between WHO and RECIST. This may impact clinical trials whose results are interpreted with RECIST and WHO. A new method of measuring “ROR” may indicate disease sites or therapies that are affected by measurement technique, and help to define the degree of response or progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Byrne Foundation and NIH Cancer Chemotherapy Program Project (CA05826-35), Experimental Therapeutic Center