Whole-tumour CT-perfusion of unresectable lung cancer for the monitoring of anti-angiogenetic chemotherapy effects

Objective: To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate. Methods: 55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST. Results: Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2 +/- 34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9 +/- 22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (221.5 +/- 18.5%). A significant difference between the three histological sub-types was demonstrated only for BV (p<0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18 +/- 9.6%) and BV (12.6 +/- 9.2%) were observed; TTP increased in 3 (37.5%) cases, and PS decreased in 6 (75%) cases. SD patients showed an increase of BF, BV, TTP and PS in 6 (15%), 21 (52.5%), 23 (57.5%) and 2 (5%) cases, respectively. PD patients demonstrated an increase of BF (26 +/- 0.2%), BV (2.7 +/- 0.1%) and TTP (3.1 +/- 0.8%) while only PS decreased (23 +/- 0.2%). Conclusion: CT-p can adequately evaluate therapy-induced alterations in NSCLC, and perfusion parameters correlate with therapy response assessment performed with RECIST criteria. Advances in knowledge: Evaluating perfusional parameters, CT-p can demonstrate therapy-induced changes in patients with different types of lung cancer and identify response to treatment with excellent agreement to RECIST measurements.