Predicting tumor response and outcome of second-look surgery with 18F-FDG PET/CT: insights from the GINECO CHIVA phase II trial of neoadjuvant chemotherapy plus nintedanib in stage IIIc-IV FIGO ovarian cancer

Abstract

Background: This ancillary study aimed to evaluate 18F-FDG PET parameter changes after one cycle of treatment compared to baseline in patients receiving first-line neoadjuvant anti-angiogenic nintedanib combined to paclitaxel-carboplatin chemotherapy or chemotherapy plus placebo and to evaluate the ability of 18F-FDG PET parameters to predict progression-free survival (PFS), overall survival (OS), and success of second-look surgery.

Materials and methods: Central review was performed by two readers blinded to the received treatment and to the patients' outcome, in consensus, by computing percentage change in PET metrics within a volume of interest encompassing the entire tumor burden. EORTC and PERCIST criteria were applied to classify patients as responders (partial metabolic response and complete metabolic response) or non-responders (stable metabolic disease and progressive metabolic disease). Also analyzed was the percentage change in metabolic active tumor volume (MATV) and total lesion glycolysis (TLG).

Results: Twenty-four patients were included in this ancillary study: 10 received chemotherapy + placebo and 14 chemotherapy + nintedanib. PERCIST and EORTC criteria showed similar discriminative power in predicting PSF and OS. Variation in MATV/TLG did not predict PFS or OS, and no optimal threshold could be found for MATV/TLG for predicting survival. Complete cytoreductive surgery (no residual disease versus residual disease < 0.25 cm/0.25-2.5 cm/> 2.5 cm) was more frequent in responders versus non-responders (P = 0.002 for PERCIST and P = 0.02 for EORTC criteria). No correlation was observed between the variation of PET data and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET, but a statistically significant correlation was observed between ΔSULpeak and ΔCA-125 between baseline sample and that performed after the second cycle.

Conclusion: 18F-FDG PET using EORTC or PERCIST criteria appeared to be a useful tool in ovarian cancer trials to analyze early tumor response, and predict second-look surgery outcome and survival. An advantage of PERCIST is the correlation of ΔSULpeak and ΔCA-125, PET response preceding tumor markers response by 1 month. Neither MATV nor TLG was useful in predicting survival.

Trial registration: NCT01583322 ARCAGY/ GINECO GROUP GINECO-OV119, 24 April 2012.

Keywords: 18F-FDG; MATV; Ovarian cancer; PERCIST; PET.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1

Flowchart description of the study design

Fig. 2

Waterfall diagrams of percentage variation in 18F-FDG PET metrics between baseline and interim PET. Panels a and b display %change in SULmax and panel c displays %change in SULpeak. Red dotted lines represent threshold used to discriminate between responders and non-responders for EORTC PET response criteria and PERCIST. SMD, stable metabolic disease; PMR, partial metabolic response; CMR, complete metabolic response

Fig. 3

Kaplan-Meier survival curves for progression-free survival (PFS, left panels a–c) and overall survival (OS, right panels a–c) in responding (CMR, complete metabolic response or PMR, partial metabolic response) versus non-responding patients (SMD, stable metabolic disease or PMD, progressive metabolic disease) using SULmax (EORTC PET response criteria) and SULpeak (PERCIST). For metabolic active tumor volume (MATV) and total lesion glycolysis (TLG), the thresholds used to discriminate between responders and non-responders were the median values of the series (− 74.2% for MATV and − 78.3% for TLG). MATV and TLG being perfectly correlated, they produced similar results and only the Kaplan-Meier curves for MATV are displayed in panel d

Fig. 4

Outcome of surgery in responders and non-responders using EORCT PET response criteria (a) or PERCIST (b)

Fig. 5

Example of metabolic tumor volume contouring in a patient with bulky peritoneal disease, classified as partial metabolic responder according to EORCT PET response criteria and PERCIST. Note: the uptake visible in the right upper chest is related to a central venous catheter

Fig. 6

Correlation (Spearman’s coefficient) between the variation of 18F-FDG PET metrics (SULmax: a and b, SULpeak: c and d, MATV e and f or TLG: g and h) and the variation of CA-125 blood level between baseline sample and that performed contemporary to the interim PET (median of 2 days between PET examination and blood sample, left panels) and that performed after a median of 23 days following the interim PET examination (right panels)