A Prospective Phase Ⅱ Clinical Study Of CT Imaging Markers Predicting Hematological Toxicity Of Radical Concurrent Chemoradiotherapy In Patients With Cervical Squamous Cell Carcinoma

Objective:To observe the changes of CT image characteristics of pelvic bone marrow during external irradiation of cervical cancer patients undergoing radical concurrent chemoradiotherapy,and to explore the correlation between hematological toxicity and changes of CT image characteristics.Methods:Patients diagnosed with cervical squamous cell carcinoma stage IA-IVA(FIGO 2018 version)were enrolled.All patients received concurrent chemoradiotherapy.The patients received contrast-enhanced pelvic CT scans before concurrent chemoradiotherapy(0th),10 times of radiotherapy(10th),and 25 times of radiotherapy(25th).The researchers delineated intracortical hypodensity in the lumbar region(1-4 lumbar vertebrae),the sacrococcygeal region(5th lumbar vertebra+sacrum+coccyx),and the hip region(iliac+ischium+pubic bone)on each patient’s CT images area.The three-dimensional mean CT value(CT0,CTl0,CT25)and maximum value at different time points in the three regions in the CT images were automatically determined by MIM software.All patients were monitored weekly for blood routine,and hematological toxicity was assessed with reference to the hematological toxicity grading standard CTCAE 5.0.Changes in blood cell counts and CT value were assessed using analysis of variance and rank sum test.Correlations between CT value,blood counts,hematologic toxicity and mean dose were analyzed by Pearson correlation analysis or Spearman correlation analysis.Risk factors associated with hematologic toxicity were analyzed using binary logistic regression.ROC curve was used to investigate the predictive power of CT value for hematological toxicity.Results:A total of 33 patients were included from February 2021 to December 2021,with an average age of 57.24±7.5 years,BMI 24.58±2.76 kg/m2,and stage IB3-ⅢC1r.The average dose of pelvic external irradiation was 45.5±1.3 Gy,the intraluminal irradiation dose was 6 Gy×5 fractions in the high-risk clinical target area,and 5 Gy×5 fractions in the intermediate-risk clinical target area.All patients received concurrent platinum-based chemotherapy.Hematologic toxicities occurred during CCRT:G1 4(12.1%),G2 12(36.4%),G3 14(42.4%),and G4 3(9%).The mean CT value of the sacrococcygeal region and the hip region at 0th,10th and 25th of external irradiation decreased significantly(P<0.001).The mean CT value of the lumbar region decreased significantly after 25 external irradiations(P=0.007).There was no significant difference in the maximum CT value of the lumbar region,the sacrococcygeal region and the hip region(P=0.395,P=0.773,P=0.255).Correlation analysis showed that ΔCT10 and ΔCT25 in the sacrococcygeal region and the hip region were significantly positively correlated with the average dose(sacrococcygeal region:ΔCT10:r=0.29,P=0.024,ΔCT25:r=0.32,P=0.024;hip region ΔCT10:r=0.386,P=0.003,ΔCT25:r=0.516,P<0.001;).The average dose in the lumbar region was significantly positively correlated with ΔCT10 in the lumbar region(ΔCT10:r=0.632,P=0.001).And ΔCT10 in the sacrococcygeal area and ΔCT10 in the hip bone area were positively correlated with the change in white blood cells(ΔWBC10)after 10 fractions of radiotherapy(the sacrococcygeal region;r=0.483,P<0.001;the hip region:r=0.515,P<0.001).The sacrococcygeal region ΔCT25 and the hip region ΔCT25 were positively correlated with the white blood cell change value(ΔWBC25)after 25 fractions of radiotherapy(the sacrococcygeal region:r=0.414,P<0.001;the hip region:r=0.545,P<0.001).Multivariate analysis found that ΔCT10 in the sacrococcygeal region was an independent predictor of grade 3 or higher hematological toxicity after external irradiation(B=1.13,P=0.04).The ROC curve showed that ΔCT10 in the sacrococcygeal region could predict the occurrence of hematological toxicity in G3-4 after external irradiation,with an AUC of 0.734(P=0.027),a sensitivity of 83.3%,and a specificity of 71.4%.Conclusion:During the course of radiotherapy in patients with cervical squamous cell carcinoma undergoing radical concurrent chemoradiotherapy,with the increase of radiotherapy fractions,the average CT value of the sacrococcygeal region and the hip bone region decreased significantly,which was positively correlated with the reduction of the average dose and WBC.Sacrococcygeal ΔCT10 was an independent predictor of grade 3 or higher hematologic toxicity after the end of external beam irradiation.