Example of measurement of a single computed tomography scan slice. ( A) Lines represent possible interpretations of ‘longest tumour diameter’ according to current RECIST criteria. ( B) Lines represent suggested measurement sites perpendicular to fixed structures, chest wall and vertebral column, according to Modified RECIST criteria. by guest on October 28, 2011 http://annonc.oxfordjournals.org/ Downloaded from Aduro Biotech, Inc. Protocol ADU-CL-02-v8 CRS-207 with Pemetrexed and Cisplatin Version 8, 08 March 2018 Page 78A B 259 Validation of modified criteria The response status of all 73 patients was re-assessed at each trial time point according to these Modified RECIST criteri a. Patients were assigned to one of two groups: responding patients (‘responders’) and patients with SD or PD (‘non-responders’). Overall su rvival from the start of treatment and serial changes in FVC were analysed for these two groups as a surrogate measure ofpatient benefit. Results Tumour measurements from a total of 236 CT scans from 73 patients were reassessed for response status at each time point inthe trials according to the modified criteria. In general there was a close correlation between the origi nal response criteria and the Modified RECIST. Of 81 time points originally showing PR, 72remained classified as PR, five became SD and four became PD.Of 105 time points originally showing SD, 93 remained as SD, 11became PR and one became PD. Of 50 time points originallyshowing PD, 47 remained PD, two became SD and one becamePR (Table 1). The overall confir med response rate as assessed by the two systems did not differ, as two patients classified as SDbecame PR and two patients classifi ed as PR became SD (Table 2). Median survival was plotted as a Kaplan–Meier curve for the responding and non-responding patients (Figure 2). There was a statistically significant difference in survival between thetwo patient groups (log rank test P = 0.03). Median survival was 15.1 months for responding patients and 8.9 months for non-responding patients. FVC was plotted as a percentage of starting FVC for the responding and non-responding patients (Figure 3). FVC improvedsignificantly over the course of treatment for responding patientsas compared with non-responding patients ( P = 0.0001). The change in FVC against change in linear tumour measure- ment was plotted for each patient (Figure 4); a significant cor- relation was seen ( R = 0.63, P = 0.001). Discussion The response criteria used in our previous two trials of chemo-therapy in mesothelioma inc orporated bidimensional measure- ments, as the WHO response criteria were widely used when thefirst of these trials began accrua l. These response criteria were not altered for the second trial, which sought to broaden theapplicability of our findings in the first single-centre study into aTable 1. Comparison of response at individual time point observations between original response criteria and Modified RECIST criteria RECIST, response evaluation criteria in solid tumours; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.Original response criteria Modified RECIST criteria CR PR SD PD Total CR 0 0 0 0 0 P R 07 2 5 48 1 SD 0 11 93 1 105 PD 0 1 2 47 50 Total 0 84 100 52 236 Table 2. Comparison of response rates for original response criteria versus Modified RECIST criteria RECIST, response evaluation criteria in solid tumours; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.CR PR SD PD Overall response (%) Original response criteria02 7 4 0 63 7 Modified RECIST criteria02 7 4 0 63 7 Figure 2. Kaplan–Meier survival curve of overall survival (days) from start of treatment for 73 patients treated with cisplatin and gemcitabine. Responding (dashed line) versus non-responding (solid line) patients as per Modified RECIST criteria. P value represents results of log rank test.