Supplementary Figure 1. Example of cluster image using the CellSearch ® system. Composite DAPI Cytokeratin-FITC M30-PE CD45-APC

Supplementary Figure 2. REMARK diagram of the 19 patients who had elevated CTC (Group B/C) at baseline that were used to study “CTC-response”. Group B/C at day 15: N=17 Group C 15 : ≥5CTC/7.5 ml N=12 Group B 15 : <5CTC/7.5 ml N=5 N=3 had no blood at day 15 N=1 had blood at BL, but no day 15 Group B/C at DAY 29: N=15 Group C 29 : ≥5CTC/7.5 ml N=10 Group B 29 : <5CTC/7.5 ml N=5 Group B/C at Baseline (BL): ≥5CTC/7.5 ml N=19 N=2 day had no day 15 Legend: Group B/C: ≥5CTC/7.5 ml whole blood at BL; BL=baseline; B 15 and B 29 : patients that cleared their CTC from ≥5CTC/7.5 ml at BL (Group B/C) to <5CTC at day 15(B 15 ) and 29 (B 29 ), respectively; C 15 and C 29 : patients that maintained ≥5CTC/7.5 ml from BL (Group B/C) to day 15 (C 15 ) and 29 (C 29 ), respectively.

N=33 P= 0.63 mPFS=3.0 mo mPFS=3.8 mo mPFS= 1.9 mo mPFS=3.1 mo N=19 P= 0.07 Supplementary Figure 3. PFS for TIG-treated patients versus the control group according to baseline CTC levels: CTC <5 (S2A) vs. ≥5 /7.5 ml WB (S2B) (note difference in time scale on y-axis). S2A S2B

CTC Response Yes No Yes No Yes No Yes No Type of Clinical Response ORR CBR ORR CBR Time Day 15 Day 29 P=0.54 P=0.10 P=0.24 P=0.09 Supplementary Figure 4. Association of CTC-response level with RECIST response: ORR and CBR for group B and C as stated above. (Clinical response= either overall response rate (ORR) or clinical benefit response (CBR), as defined in method).

CTC Apoptotic No Yes No Yes No Yes No Yes No Yes No Yes Type of Clinical Response ORR CBR ORR CBR ORR CBR Time Baseline Day 15 Day 29 Supplementary Figure 5. Association of CTC-apoptosis and response with RECIST response ORR and CBR. (Clinical response= either overall response rate (ORR) or clinical benefit response (CBR), as defined in method).