Fig. 4. Treatment monitoring of individual patients using iCTCs and serum CA125.

Patients were designated using specific numbers and numeric stages. iCTCs (upper plot, data shown in red) and CA125 (lower plot, data shown in red) were plotted against same clinical status (both upper and lower plots, data shown in blue) that was expressed as either progressive disease (PD) or no evidence of disease (NED). Treatments were shown by specific patterned boxes on the top line of plots – red boxes indicate surgery; black boxes the first line treatment (Taxol/Carbo and/or Avastin); blank boxes the second line treatment (Topotecan, Taxol/Carbo or Avastin); patterned boxes the third line treatment (Taxol/Pazopancb). Red arrows indicate changes in iCTCs or CA125 relative to the positive response during the primary therapy (from PD to NED), while red arrows with marks (?) indicate failure of detecting response. Blue arrows indicate changes in iCTCs or CA125 relative to relapse (from NED to PD), while blue arrows with marks (?) indicate failure of detecting relapse. Green arrows indicate changes in iCTCs or CA125 relative to the positive response during the second and/or third lines of therapy (from PD to NED), while green arrows with marks (?) indicate failure of detecting response.

(A) Changes in iCTCs (upper plot) and CA125 (lower plot) of SB407 patient with stage III EOC treated with two lines of therapy as indicated. iCTCs at visit prior to the second cycle of the first line of therapy (75 days prior to the clinical status NED; red arrow) detected positive response from PD to NED, whereas CA125 failed detecting response. Similarly, iCTCs, but not CA125, detected relapse approximately 100 days earlier than it was revealed with radiographic imaging (blue arrows). During the second line of chemotherapy, both iCTCs (upper plot, green arrows) and CA125 (lower plot, green arrows) detected positive response from PD to NED. (B) Changes in iCTCs (upper plot) and CA125 (lower plot) of SB406 patient with stage III EOC treated with therapy as indicated. iCTCs, but not CA125, at visit prior to the second cycle of therapy (red arrow) detected positive response from PD to NED. (C) Changes in iCTCs (upper plot) and CA125 (lower plot) of SB405 patient with stage IC EOC treated with a therapy as indicated. iCTCs, but not CA125, at visit prior to the second cycle of therapy (red arrow) detected positive response from PD to NED. (D) Changes in iCTCs (upper plot) and CA125 (lower plot) of SB414 patient with stage IIIC EOC treated with two lines of therapy as indicated. In this case, bot h iCTCs and CA125 detected positive response in the first line of therapy (red arrows), relapse (blue arrows), and positive response from PD to NED in the second line of chemotherapy (green arrows). (E) Changes in iCTCs (upper plot) and CA125 (lower plot) of SB419 patient with stage IV EOC treated with three lines of therapy as indicated. In this case, decrease in iCTCs, but not CA125, detected positive response in the first line of therapy (red arrows); increase in iCTCs, but not CA125, identified relapse and non-responsiveness of the second line of chemotherapy (blue arrows) and the third line of chemotherapy (green arrows). (F) Changes in iCTCs (upper plot) and CA125 (lower plot) of SB445 patient with stage IV EOC treated with therapy as indicated. Decrease in both iCTCs and CA125 detected positive response from PD to NED during therapy (red arrows).