| Purpose: To quantitatively analyze vascular microenvironment of lung cancer and thechange of pulmonary blood flow around the tumor using iodine-based images and byaccurately measuring the effective iodine content (eIC) of tumor with spectral CTimaging. On the one hand, to quantitatively investigate the pulmonary blood flowaround the tumor and to analyze the related factors affecting the perfusion of thepulmonary parenchyma. On the other hand, to quantitatively analyze and monitor thevascular microenvironment changes of advanced lung cancer after chemotherapy, and toexplore the application value of eIC value changes on therapeutic effect evaluation afterchemotherapy.Method and material:(1)In the first part,58patients with lung cancer (21cases central lung cancer,37casesperipheral lung cancer), confirmed by pathology and underwent spectral CT imagingwith a standard injection protocol (including three scanning stage,25s,55s and140s),were enrolled in this study. The largest diameter of lung cancer was measured in plainCT scan image. The eIC values of the tumor tissue, pulmonary parenchyma around thetumor within three centimeters in diameter and the corresponding area in thecontra-lateral normal lung parenchyma were measured on iodine-based images inarterial phase. To compare the difference of eIC values between pulmonary parenchymaaround the tumor and the corresponding area in the other side in all patents, central lungcancer and peripheral lung cancer respectively. And to compare the difference of eICvalues in pulmonary parenchyma around the tumor between central lung cancer and peripheral lung cancer. At the same time, to analyze the correlation among the tumorsize, tumor eIC value and lung eIC value for the pulmonary parenchyma in the distalend of lung cancers.(2)In the second part,12patients with advanced non-small cell lung cancer (NSCLC),underwent chemotherapy and regular re-examination in department of oncology, wereenrolled in this study. All patients underwent spectral CT imaging with a standardinjection protocol before and after chemotherapy within interval time from34to165days (the median interval time for47days). The scanning conditions were same as thefirst part. The largest diameter of tumor was measured in plain CT scan image. The eICvalues of tumor were measured by three round region of interests (ROI) being same size(about50mm2) on the edge of the tumor on iodine-based images in venous phase. Thenwe calculated the average eIC value. The datum before and after each follow-up duringchemotherapy were composed as a group. We calculated the change of the largestdiameter, the difference of eIC value (DeIC) and the ratio of eIC value (ReIC，ReIC=DeIC/previous time eIC value×100%) for each group. We performed therapeuticevaluation according to RECIST1.1criteria, and classified complete response (CR),partial response (PR) and stable disease (SD) as the effective group and progressivedisease (PD) as the ineffective group. According to Choi criteria, we defined thechanges of eIC value: ReIC value decreasing more than15%was defined as PR, ReICvalue increasing more than15%was defined as PD, and the change of ReIC betweenPR and PD was defined as SD. We would compare the difference of DeIC and ReICvalues between effective group and ineffective group. Meanwhile, we also wouldcompare the difference of the eIC values before and after chemotherapy for effectivegroup or ineffective group, and analyze the correlation between DeIC value, ReIC valueand RECIST1.1criteria (including this time and next time evaluation results)respectively.Results:(1)In all cases, mean lung eIC value (10.26±5.96100ug/cm3) for the pulmonaryparenchyma in the distal end of lung cancers was significantly lower than that in the corresponding area in the contra-lateral normal lung (14.23±6.86100ug/cm3)(t=-5.72,P=0.00). And there was the same result in central lung cancer and peripheral cancerrespectively (8.31±3.83100ug/cm3,12.83±5.43100ug/cm3, t1=-4.84, P1=0.00;11.36±6.69100ug/cm3,15.03±7.50100ug/cm3, t2=-3.83, P2=0.00; P＜0.05).(2)We also found that the lung eIC value for the pulmonary parenchyma in the distalend of peripheral lung cancers (11.36±6.69100ug/cm3) was significantly higher thancentral lung cancer (8.31±3.83100ug/cm3)(t=-2.21, P=0.03).(3)There was a positive correlation between tumor eIC value and lung eIC value forpulmonary parenchyma in the distal end of lung cancers (r=0.49, P=0.00), but anegative correlation between the tumor size and lung eIC value for the pulmonaryparenchyma in the distal end of lung cancers (r=-0.34, P=0.01). And there was also anegative correlation between tumor eIC value and the tumor size (r=-0.38，P=0.00).(4)12patients with advanced NSCLC performed regular re-examination for38times,including33times spectral CT scanning and5times traditional Multislice SpiralComputed Tomography (MSCT) scanning on the last check. According to theRECIST1.1criteria, the results of therapeutic evaluation in all cases included3groupsPR,11groups SD and12groups PD. Among these groups, there were3groups PR,10groups SD and8groups PD, which were performed using spectral CT scanning beforeand after chemotherapy. That was to say, there were13effective groups and8ineffective groups.(5)There was no difference for the tumor mean eIC value between effective groups andineffective groups whether before or after chemotherapy (t1=0.62, P1=0.54; t2=-1.01,P2=0.33, P＞0.05). While, the DeIC value of effective groups (-0.64±3.60100ug/cm3)was obviously lower than ineffective groups (3.98±5.71100ug/cm3)(P=0.03, P＜0.05).And there was the same result in tumor ReIC value (P=0.04, P＜0.05).(6)In the effective groups, there was no difference for tumor eIC value between beforeand after chemotherapy (t=0.64, P=0.53). But, in ineffective groups, tumor eIC valueafter chemotherapy had an increasing trend than that before chemotherapy (t=-1.92,P=0.09). (7)There was no correlation between DeIC value, ReIC value and this time therapeuticevaluation results (r1=0.36, P1=0.11, r2=0.36, P2=0.11, respectively). But we found apositive correlation between DeIC value, ReIC value and next time evaluation results(r1=0.98, P1=0.00, r2=0.98, P=0.00, P＜0.05, respectively).(8) Comparing with RECIST1.1criteria, the therapeutic evaluation results of iodinevalues changes showed:38.46%(5/13) was uniformity,30.77%(4/13) was over-valuedand30.77%(4/13) was under-valued in the effective group, while, the uniformity andunder-evaluation were50%(4/8) respectively in the ineffective group. In the effectivegroup, when the therapeutic evaluation result of iodine value was PD, the therapeuticevaluation result of the next RECIST1.1criteria was PD too. And, when the therapeuticevaluation result of RECIST1.1criteria was PD, although the therapeutic evaluationresult of iodine value was SD, the therapeutic evaluation result of the next RECIST1.1criteria was still PD.Conclusion:(1)Iodine-based analysis with spectral CT imaging could be used to quantitativelyevaluate the pulmonary blood flow and its change induced by lung cancer. And weobserved the variously decreasing perfusion condition for pulmonary parenchyma in thedistal end of lung cancer, providing some valuable information for choosing lung canceroperation method and formulating the radiotherapy scope.(2)Iodine-based analysis with spectral CT imaging could quantitatively monitor thevascular microenvironment changes of advanced lung cancer during chemotherapy andprovide some supplementary information for RECIST1.1criteria. We could observe thevariously changes inside the tumors during chemotherapy and found DeIC value was abetter indicator for therapeutic evaluation. Although morphological evaluation resultshinted relatively stable or better, significantly increasing iodine content could indicatethe progress of lung cancer. The further research of curative effect evaluation wasneeded. |
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