11C-methyl-L-methionine PET measuring parameters for the diagnosis of tumour progression against radiation-induced changes in brain metastases

Abstract

Objectives: Radiation-induced changes (RIC) secondary to focal radiotherapy can imitate tumour progression in brain metastases and make follow-up clinical decision making unreliable. ¹¹C-methyl-L-methionine-PET (MET-PET) is widely used for the diagnosis of RIC in brain metastases, but minimal literature exists regarding the optimum PET measuring parameter to be used. We analysed the diagnostic performance of different MET-PET measuring parameters in distinguishing between RIC and tumour progression in a retrospective cohort of brain metastasis patients.

Methods: 26 patients with 31 metastatic lesions were included on the basis of having undergone a PET scan due to radiological uncertainty of disease progression. The PET images were analysed and methionine uptake quantified using standardised-uptake-values (SUV) and tumour-to-normal tissue (T/N) ratios, generated as SUV_mean, SUV_max, SUV_peak, T/N_mean, T/N_max-mean and T/N_peak-mean. Metabolic-tumour-volume and total-lesion methionine metabolism were also computed. A definitive diagnosis of either RIC or tumour progression was established by clinicoradiological follow-up of least 4 months subsequent to the investigative PET scan.

Results: All MET-PET parameters except metabolic-tumour-volume showed statistically significant differences between tumour progression and lesions with RIC. Receiver-operating-characteristic curve and area-under the-curve analysis demonstrated the highest value of 0.834 for SUV_max with a corresponding optimum threshold of 3.29. This associated with sensitivity, specificity, positive predictive and negative predictive values of 78.57, 70.59%, 74.32 and 75.25% respectively.

Conclusions: MET-PET is a useful modality for the diagnosis of RIC in brain metastases. SUV_max was the PET parameter with the greatest diagnostic performance.

Advances in knowledge: More robust comparisons between SUV_max and SUV_peak could enhance follow-up treatment planning.

Figure 1.

Imaging of a 53-year-old female (case number 6: Supplementary Material 1) with a right lower-lobe lung adenocarcinoma metastasised to the right frontal-lobe. The lesion was resected and subjected to 10.00 × 3.00 Gy whole brain radiotherapy postoperatively. One year later the lesion showed progression, for which 20.00 Gy was given through SRT. The T1W (contrast-enhanced) MRI (a) was made 12 months after the SRT and depicts contrast-enhancement suspect for progression (white arrow). The MET-PET image (b) was performed one month afterwards and shows slight comparative tracer uptake (SUV_mean = 2.29, SUV_max = 3.39 and SUV_peak = 2.61; black arrow). The T1W (contrast-enhanced) MRI (c), performed five months after the PET scan, depicts tumour shrinkage. This was considered sufficient for a diagnosis of RIC. MET-PET, ¹¹C-methyl-L-methionine PET; RIC, Radiation-induced changes; SRT, Stereotactic radiotherapy; SUV, Standardised-uptake-value.

Figure 2.

Imaging of a 72-year-old male with a left-lower lobe lung carcinoma (subtype not specified) (case number 26: Supplementary Material 1) metastasised to the right occipital lobe. This patient was treated with 20.00 Gy through SRT. The T1W (contrast-enhanced) MRI (a) was made 1 year and 10 months afterwards, with new enhancement (white arrow). This was followed one month after by a MET-PET scan (b), showing distinct uptake (SUV_mean = 3.75, SUV_{max =} 6.18, SUV_peak = 4.22; black arrow) suggestive of TP. The T1W (contrast-enhanced) MRI, made 10 days later, highlighted an increase in size both cranially and ventrally (white arrow). Other sequences showed a considerable increase in vasogenic peritumoural oedema. This, along with the deteriorating clinical situation and the follow up reirradiation with SRT (8 × 3.00 Gy), led to the definitive diagnosis of TP. MET-PET, ¹¹C-methyl-L-methionine PET; SRT, Stereotactic radiotherapy; SUV, Standardised-uptake-value; TP, Tumour progression.

Figure 3.

Box-and-whisker plots for the SUV, TLMM and MTV PET parameters (a) and the T/N PET parameters (b). The panels are split according to measuring parameters and the boxes patterned by definitive diagnosis, as confirmed by clinicoradiological follow-up. The horizontal lines represent the median values for each parameter, the boxes indicate the IQR (Q1–Q3) and the error bars outline the range. MTV: metabolic-tumour-volume; RIC, Radiation-induced changes; SUV, Standardised-uptake-value; TLMM: Total-lesion methionine metabolism; T/N, Tumour-to-normal tissue ratio; TP, Tumour progression.

Figure 4.

Receiver-operating-characteristic curves for the SUV PET parameters (a), the T/N PET parameters (b) and the MTV/TLMM PET parameters (c). The curves indicate the trade-off between true-positive (sensitivity) and false-positive (1-specificity) rates for the differentiation between TP and RIC using each parameter. The perfect diagonal line for each panel is the reference or ‘random-guess’ line. MTV, Metabolic-tumour-volume; RIC, Radiation-induced changes; SUV, Standardised-uptake-value; T/N, Tumour-to-normal tissue ratio; TLMM, Total-lesion methionine metabolism; TP, Tumour progression.