Functional imaging biomarkers for assessing response to treatment in liver and lung metastases

Abstract

Management of patients with metastatic cancer and development of new treatments rely on imaging to provide non-invasive biomarkers of tumour response and progression. The widely used size-based criteria have increasingly become inadequate where early measures of response are required to avoid toxicity of ineffective treatments, as biological, physiologic, and molecular modifications in tumours occur before changes in gross tumour size. A multiparametric approach with the current range of imaging techniques allows functional aspects of tumours to be simultaneously interrogated. Appropriate use of these imaging techniques and their timing in relation to the treatment schedule, particularly in the context of clinical trials, is fundamental. There is a lack of consensus regarding which imaging parameters are most informative for a particular disease site and the best time to image so that, despite an increasing body of literature, open questions on these aspects remain. In addition, standardization of these new parameters is required. This review summarizes the published literature over the last decade on functional and molecular imaging techniques in assessing treatment response in liver and lung metastases.

Figure 1

Metastatic non-small cell lung cancer (NSCLC) on crizotinib. Baseline axial CT (venous phase, A) demonstrates multiple bilobar liver metastases. At 45 days (B), the disease has progressed by size (RECIST) criteria, although lower attenuation of metastases suggests an early response to treatment. Subsequent follow-up images (C, D) at 5 months from baseline confirm a partial response to treatment.

Figure 2

Metastatic breast cancer treated with lapatinib–capecitabine: axial T1-weighted image 20 minutes after injection of a hepatospecific contrast agent (A), 900 b value DWI (B), and corresponding ADC map (C) before treatment. Metastatic deposits in segment V/VI of the liver show restricted diffusion (ADC value = 0.85 × 10⁻³/mm²/s). After 3 months of treatment, no significant change in size is demonstrated on the delayed postcontrast T1-weighted image (E), whereas the ADC value has increased to 1.08 × 10⁻³/mm²/s as demonstrated qualitatively (F, G) and by histogram analysis before and after treatment, respectively (D, H), suggesting a response to treatment.

Figure 3

Volumetric assessment of lung metastasis. CT (A) and segmented volume (B) in a right upper lobe target lesion with corresponding images (C, D) after 2 cycles of carboplatin. Although the disease is stable by RECIST criteria (<20% increase of the maximum diameter in the interval), the volumetric assessment of the same target lesion indicates that the lesion has doubled in volume (B vs D) in the interval, suggesting disease progression.

Figure 4

DW-MRI in lung metastases. Axial CT image shows multiple small bilateral lung metastases (≤13 mm) (A). These lesions are identified on a high b value DW image (b800, B) and have a low ADC value (0.4–0.7 × 10⁻³/mm²/s) compared with muscle (1.3 × 10⁻³/mm²/s) on the ADC map (C).

Figure 5

Quantification of ADC in lung metastases. Axial T2 HASTE image (A), DWI (b800, B), and ADC map (C) showing a dominant 16-mm right lung metastasis. Pixel-by-pixel quantification of the ADC is performed by drawing a region of interest (ROI) around the lesion and determining the rate of decay of signal using a monoexponential fit of the data (ADEPT in-house software; ICR, UK). A minimum, maximum, and mean value of ADC can be derived for the ROI as well as a histogram plot of the ADC distribution in the lesion (D).

Figure 6

Metabolic response assessment of lung metastasis on FDG-PET/CT. CT (A) and fused FDG-PET/CT (B) in NSCLC before treatment with corresponding images (C and D) post treatment showing that concomitant atelectasis makes it difficult to assess response to treatment on CT alone (black arrow, C). Following treatment there is almost complete metabolic activity shutdown within the lesion (white arrow, D) indicating treatment response.