ctDNA-guided adjuvant treatment after radical-intent treatment of metastatic spread from colorectal cancer-the first interim results from the OPTIMISE study.

BACKGROUND: Patients with detectable ctDNA after radical-intent treatment of metastatic spread from colorectal cancer (mCRC) have a very high risk of recurrence, which may be prevented with intensified adjuvant chemotherapy (aCTh). In the OPTIMISE study, we investigate ctDNA-guided aCTh after radical-intent treatment of mCRC. Here we present results from the preplanned interim analysis. MATERIAL AND METHODS: The study is an open-label 1:1 randomized clinical trial comparing ctDNA-guided aCTh against standard of care (SOC), with a run-in phase investigating feasibility measures. Key inclusion criteria; radical-intent treatment for mCRC and clinically eligible for triple-agent chemotherapy. Patients underwent a PET-CT scan before randomization. ctDNA analyses of plasma samples were done by ddPCR, detecting CRC-specific mutations and methylation of the NPY gene. In the ctDNA-guided arm, ctDNA positivity led to an escalation strategy with triple-agent chemotherapy, and conversely ctDNA negativity led to a de-escalation strategy by shared-decision making. Patients randomized to the standard arm were treated according to SOC. Feasibility measures for the run-in phase were; the inclusion of 30 patients over 12 months in two Danish hospitals, compliance with randomization >80%, rate of PET-CT-positive findings <20%, and eligibility for triple-agent chemotherapy >80%. RESULTS: Thirty-two patients were included. The rate of PET-CT-positive cases was 22% (n = 7/32). Ninety-seven percent of the patients were randomized. Fourteen patients were randomly assigned to SOC and sixteen to ctDNA-guided adjuvant treatment and follow-up. All analyses of baseline plasma samples in the ctDNA-guided arm passed the quality control, and 19% were ctDNA positive. The median time to result was three working days. All ctDNA-positive patients were eligible for triple-agent chemotherapy. CONCLUSION: The study was proven to be feasible and continues in the planned large-scale phase II trial. Results from the OPTIMISE study will potentially optimize the adjuvant treatment of patients undergoing radical-intent treatment of mCRC, thereby improving survival and reducing chemotherapy-related toxicity.

[18 F]-Fluoro-2-deoxy-D-galactose positron emission tomography/computed tomography as complementary imaging tool in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Positron emission tomography (PET) with the liver-specific tracer [18 F]-fluoro-2-deoxy-D-galactose (18 F-FDGal) can be used for imaging of hepatocellular carcinoma (HCC). Curative intended and locoregional treatments of HCC require absence of extrahepatic disease. The aim of this prospective study was to determine whether adding 18 F-FDGal PET/CT to standard work-up changes the planned treatment in patients with HCC deemed suitable for curative or locoregional treatment. METHODS: Fifty patients with HCC were included at our tertiary liver centre. The primary study outcome was a change in treatment strategy. A subgroup of 29 patients was also examined with [18 F]-fluoro-2-deoxy-D-glucose (18 F-FDG) PET/CT for comparison. RESULTS: 18 F-FDGal PET/CT detected eight extrahepatic HCC metastases in six patients (12%), which were primarily not detected by ceCT or MRI. These findings led to a change in treatment in five patients (10%). One of the eight extrahepatic HCC foci was also detected by 18 F-FDG PET/CT. A total of 85 malignant intrahepatic foci were examined, 12 of these were new findings by 18 F-FDGal PET/CT which had a sensitivity of 71%, highest for large foci. None of the additional intrahepatic foci found by 18 F-FDGal PET changed the planned treatment. CONCLUSIONS: For the detection of extrahepatic HCC metastases, 18 F-FDGal PET/CT was superior both to standard clinical work-up with contrast-enhanced CT, and/or MRI, and to 18 F-FDG PET/CT in patients deemed suitable for locoregional treatment. 18 F-FDGal PET/CT led to a change in the planned treatment in 10% of the patients whereas 18 F-FDG PET/CT did not change the planned treatment in any patient.

Diagnostic accuracy of CE-CT, MRI and FDG PET/CT for detecting colorectal cancer liver metastases in patients considered eligible for hepatic resection and/or local ablation.

PURPOSE: To compare the diagnostic performance of contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI) and combined fluorodeoxyglucose/positron emission tomography/computed tomography (FDG-PET/CT) for detection of colorectal liver metastases (CRLM) in patients eligible for local treatment. MATERIALS AND METHODS: This health-research ethics-committee-approved prospective consecutive diagnostic accuracy study, with written informed consent, included 80 cases (76 patients, four participating twice) between 29 June 2015 and 7 February 2017. Prior chemotherapy or local treatment did not exclude participation. Combined FDG-PET/CT including CE-CT and MRI was performed within 0-3 days shortly before local treatment. CE-CT and MRI images were read independently by two readers for each modality. The combined FDG-PET/CT images were read independently by two pairs of readers. A composite reference standard was used. Sensitivities, specificities and area under the receiver operating characteristic curves (AUCROC) were calculated and compared. RESULTS: In total, 260 CRLMs were confirmed. The MRI readers had significantly higher per-lesion sensitivity (85.9% and 83.8%) than both CE-CT readers (69.1% and 62.3%) and both PET/CT reader pairs (72.0% and 72.1%) (p<0.001). There were no significant differences in per-lesion specificity. MRI readers had significantly higher AUCROC (0.92 and 0.88) than both CE-CT readers (0.80 and 0.82) (p≤0.001). AUCROC for MR reader 1 was higher than that of both PET/CT reader pairs (0.83 and 0.84) (p≤0.0001). CONCLUSION: MRI performed significantly better than both CE-CT and combined FDG-PET/CT for detection of CRLM in consecutive patients eligible for local treatment irrespective of prior chemotherapy or local treatment. KEY POINTS: • Patients eligible for local treatment of colorectal liver-metastases require optimal imaging. • In 80 consecutive patients, MRI had superior per lesion diagnostic performance. • Findings were independent of prior treatment and type of planned local treatment. • Equally, MRI had superior diagnostic performance on per segment basis.