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 ΔSUL_peak 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 ΔSUL_peak 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.

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 SUL_max and panel c displays %change in SUL_peak. 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 SUL_max (EORTC PET response criteria) and SUL_peak (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 (SUL_max: a and b, SUL_peak: 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)