Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study

Abstract

Background: In patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC).

Methods: Suitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes.

Results: 62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43).

Conclusion: Changes in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC.

Trial registration: CICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/ .

Keywords: Dual energy CT; GCIG CA125; High grade serous ovarian cancer (HGSOC); Iodine concentration; Progression free survival (PFS); RECIST.

Fig. 1

CONSORT diagram of patients included in analysis

Fig. 2

DECT axial imaging with 120kv reconstruction (A/C) and iodine maps (B/D) obtained at 90kv and 150kv –soft tissue mass, posterior to bladder, pre- treatment: (A) Lesion measures 2.98 cm, (B) iodine concentration − 1.4 mg/mL and post-treatment: (C) Lesion measures 3.5 cm and (D) iodine concentration − 1.1 mg/mL. Iodine maps (E/F) obtained at 150 kV- peritoneal deposit adjacent to quadrate/left lobe of liver, pre-treatment (E) iodine concentration 1.1 mg/mL, mid-treatment (F) iodine concentration 0.9 mg/mL

Fig. 3

Fig. 3A changes in size and iodine concentration of cancer lesion from one patient over ~ 12 months during which this patient received three different lines of treatment. RECIST and CA125 GCIG (3B) evaluations suggested stable disease throughout but the iodine concentration changes aligned more closely with the patient’s clinical condition

Fig. 4

Percentage change as per RECIST/DECT-iodine concentration/CA125 criteria aligned with duration of response (months) for each relapsed patient. A) RECIST response, B) DECT- iodine concentration response, where 15% increase/reduction in concentration is designated a ‘response’ and C) GCIG CA125 response

Fig. 5

Progression Free Survival (PFS) according to response in n = 32 relapse patients. A: RECIST v1.1 median PFS 7 months (responder, n = 25) versus 5 months (non responders, n = 7) p = 0.43 HR 0.7 95% CI 0.24 to 2.05. B: DECT (iodine concentration) median PFS 7 months (responders, n = 22) versus 4 months (non responders, n = 10) p =  0.0001, HR 0.1 95% CI 0.03 to 0.33. C: GCIG CA125 Median PFS 11 months (responders, n = 17) versus 4 months (non responders, n = 15) p =  0.0028, HR 0.23 95% CI 0.09 to 0.6