Computed tomography (CT) perfusion as an early predictive marker for treatment response to neoadjuvant chemotherapy in gastroesophageal junction cancer and gastric cancer--a prospective study

Abstract

Objectives: To evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for gastroesophageal junction (GEJ) and gastric cancer.

Materials and methods: Twenty-eight patients with adenocarcinoma of the gastro-esophageal junction (GEJ) and stomach were included. Patients received three series of chemotherapy before surgery, each consisting of a 3-week cycle of intravenous epirubicin, cisplatin or oxaliplatin, concomitant with capecitabine peroral. The patients were evaluated with a CT perfusion scan prior to, after the first series of, and after three series of chemotherapy. The CT perfusion scans were performed using a 320-detector row scanner. Tumour volume and perfusion parameters (arterial flow, blood volume and permeability) were computed on a dedicated workstation with a consensus between two radiologists. Response to chemotherapy was evaluated by two measures. Clinical response was defined as a tumour size reduction of more than 50%. Histological response was evaluated based on residual tumour cells in the surgical specimen using the standardized Mandard Score 1 to 5, in which values of 1 and 2 were classified as responders, and 3 to 5 were classified as nonresponders.

Results: A decrease in tumour permeability after one series of chemotherapy was positively correlated with clinical response after three series of chemotherapy. Significant changes in permeability and tumour volume were apparent after three series of chemotherapy in both clinical and histological responders. A cut-off value of more than 25% reduction in tumour permeability yielded a sensitivity of 69% and a specificity of 58% for predicting clinical response.

Conclusion: Early decrease in permeability is correlated with the likelihood of clinical response to pre-operative chemotherapy in GEJ and gastric cancer. As a single diagnostic test, CT Perfusion only has moderate sensitivity and specificity in response assessment of pre-operative chemotherapy making it insufficient for clinical decision purposes.

Figure 1. Illustration of histological response evaluation using Mandard score.

A) Tumour regression grade 2 (Mandard). Few, scattered residual cancer areas (arrows) separated by fibrosis (*). One tumour area is surrounding a vessel (V) and another tumour area is seen to the left. This patient was a histological responder. B) Tumour regression grade 4 (Mandard). Residual cancer areas (arrows) outgrowing fibrosis (*). This patient was a histological nonresponder.

Figure 2. CT perfusion images of a clinical responder.

Permeability k^trans parametric map in a clinical responder with a reduction in permeability between baseline and the first series of chemotherapy. A+B) Before chemotherapy (k^trans = 32.1 mL⋅min⁻¹⋅100 g⁻¹) C+D) After first series of chemotherapy (k^trans = 23.9 mL⋅min⁻¹⋅100 g⁻¹). Perfusion measures are averages from the entire tumor volume. The image illustrates perfusion measured in a reconstructed coronal plane which is possible with volume perfusion.

Figure 3. CT Perfusion images of a clinical nonresponder.

Permeability k^trans in a clinical nonresponder. An increase in k^trans is observed. E+F) Before chemotherapy (k^trans = 13.7 mL⋅min⁻¹⋅100 g⁻¹) and G+H) After first series of chemotherapy (k^trans = 21.0 mL⋅min⁻¹⋅100 g⁻¹). Perfusion measures are averages from the entire tumor volume.

Figure 4. Early changes in perfusion parameters and tumour volume in clinical responders.

Changes from baseline to first follow-up scan after first series of chemotherapy for the 27 cases available for early follow up evaluation. Each case is illustrated with a line between the baseline and the second scan. All values are in absolute numbers.

Figure 5. ROC analysis.

ROC curve with a cut-off value of 25% reduction in permeability between baseline and early follow up scan. Area under curve is 0.74 (Confidence interval 0.55–0.93).

Figure 6. Pre-operative scan and histological response based on Mandard Score.

Correlation between perfusion parameters pre-operatively and histological response. n = 27.