| Background and Purpose:At present,the Non-small-cell lung cancer (NSCLC) especially with local advancedand advanced stage requires comprehensive treatment of the various means has cometo a consensus, Induction chemotherapy followed by radiotherapy or concomitantchemo-radiotherapy is a more commonly used pattern, but the most appropriateinduction chemotherapy cycles is still lack of sufficient evidence-based medicalevidence to support now, and also has not be one and all completely yet. Nowpretherapeutic tumor volume have been seen as a factor that influence clinicaloutcomes，but the study of the tumor volume variation in NSCLC after multi-cyclechemotherapy have not been reported. This study was to investigate the regularpattern variation of tumor volume after chemotherapy and to provide a theoreticalbasis of selecting the optimal number of cycles of induction chemotherapy andperforming radiotherapy. And analyze the possible factors which influnce the changeof tumor volume after chemotherapy. Then according to the findings to study thedifferences of the volume-dose parameter of OAR between different inductionchemotherapy cycles.Materials and Methods:1. Non-small-cell lung cancer patients with multi-cycle induction chemotherapywhich were firstly diagnosed from October2008until December2011were enrolledin this study. To utilize volume measurement software of TPS and ImageJ imageprocessing software to measure tumor volume, and to retrospective analyze thechange of tumor volume after each chemotherapy cycle.2. To set the original size before chemotherapy as1, calculate the relative volumeof the tumor after the first, second, third, fourth, fifth, sixth cycles of chemotherapyrespectively, and compare the differernces of tumor absolute volume and relativevolume between pre-chemotherapy and the first, and between other adjacent cyclesafter chemotherapy respectively.3. Analyzed the possible influencing factors which may affect tumor relativevolume shrinking rate(Grouped according to30%of tumor relative volume shrinking rate).The possible influencing factors included gender, Age（Grouped by medianage）, the general classification（1:central type，2:peripheral type），tumor location（1:upper lobe group:2:lower lobes+right median lobe group），pathological types（1:squamous cell carcinoma，2:adenocarcinoma，3:other type），T stage（1: T1-2，2:T3-4），the original volume size（Grouped by124000mm~3）.4. Nine consecutive NSCLC pitients treated with3D-CRT from December2011toFebruary2012were enrolled in the dosimetric study，assumed GTV was tumorvolume of pre-chemotherapy and named it as GTV0，according to the recession rateof post-chemotherapy of one cycle,two cycles……N cycles of the previous results,tocompute the simulative tumor volume and named them as GTV1and GTV2……GTVn,respectively.to expand them as PTV at equal condition， then designdradiotherapy treament planning and named it as Plan0，Plan1，Plan2……Plan-n,respectively.To compare the difference of OAR like lung V20、lung V5、lungV30、mean lung dose（MLD）、esophagusV45、heartV40among these plans.5. To utilize paired t-test to analyze the differentces of gross tumor volume betweenconsecutive chemotherapy cycles, to Analysis possible influencing factors whichinfluence the tumor relative volume changes after chemotherapy by Chi-square test.Performed multivariate analysis to study possible influencing factors which influencethe tumor relative volume changes by Logistic regression. Performed stratificationanalysis according to independent prognostic factors by logistic regression analysisrespectively. Compared differernt radiotherapy theatment plans in sparing thevolume-dose parameter of OAR by Analysis of Variance(ANOVA)，To set P≤0.05isof statistically significant.Results:1. Primary tumor volume before treatment is (85747.79±93281.41)mm~3.Thetumor absolute volumes after the first, second, third, fourth, fifth, and the sixthchemotherapy cycle were (62669.65±61373.10) mm~3,(71222.24±81366.22) mm~3,(68883.12±98207.61) mm~3,(61312.82±83212.36) mm~3,(58952.34±78131.99)mm~3,(68207.07±113,976.98) mm~3respectively. The tumor relative volumes (basedthe volume as1before chemotherapy)after first, second, third, fourth, fifth, and thesixth chemotherapy cycle were(0.8201±0.3405),(0.8647±0.5678),(0.9524±1.0282),(0.9058±0.8502),(0.9640±0.9937)，(1.0343±0.9908) respectively.The differences of absolute volume are compared with Paired t-test are as follows:pre-chemotherapy and post-chemotherapy of first cycle (t=5.402,P<0.001), fourthcycle and after fifth cycle(t=-2.023,P=0.049), but the differences between otherconsecutive cycles have not statistical significance.The differences of relative volumeare compared with Paired t-test are as follows: pre-chemotherapy andpost-chemotherapy of first cycle (t=5.640, P<0.001), but the differences betweenother consecutive cycles have not statistical significance.2. Univariate analysis demonstrates the original tumor volume is the influencingfactor which influence the tumor relative volume changes after the first cyclechemotherapy (χ~2=4.640， P=0.031),but other factors are not of statisticallysignificant.3.Logistic regression analysis demonstrates that T staging(χ~2=3.901，P=0.048,OR=2.410) and the original tumor volume (χ~2=6.478, P=0.011, OR=0.538) areindependent prognostic factors of tumor relative volume changes after the first cyclechemotherapy.4. According to T staging and original tumor volume, stratification analysisdemonstrates that the differences of tumor volume all have statistical significancesbetween pre-chemotherapy and post-chemotherapy of the first cycle:absolute volumeof original tumor volume<124000mm~3group(t=3.177, P=0.002),≥124000mm~3group(t=6.093，P<0.001), T1-2group(t=3.091，P=0.003), T3-4group(t=4.613，P<0.001). Relative volume of original tumor volume <124000mm~3group(t=3.756，P<0.001),≥124000mm~3group(t=5.908，P<0.001), T1-2group(t=3.167，P=0.003),T3-4group(t=4.938，P<0.001).But the differences between other consecutive cycleshave not statistical significance by paired t-test.5. The results of Plan0，Plan1，Plan2in sparing OAR by Analysis of Variance(ANOVA) are as follow: V5of lung (F=25.037,P＜0.001)，V20of lung (F=23.452,P＜0.001)，V30of lung (F=34.205,P＜0.001)，MLD (F=29.247,P＜0.001)，V40ofheart(F=4.378,P＜0.001)， V45of esophagus (F=3.934,P＜0.001).Comparisonbetween two blocks after ANOVA is as follow：Plan0vs Plan1: V5of lung (P＜0.001)， V20of lung (P＜0.001)，V30of lung (P＜0.001)，MLD(P＜0.001)，V40of heart (P=0.015)，V45of esophagus (P=0.020)；Plan1vs Plan2:V5of lung(P=0.297)，V20of lung (P=0.204),V30of lung (P=0.069), MLD (P=0.178), V40of heart (P=0.696)，V45of esophagus (P=0.676).Conclusions:1. The NSCLC primary tumor volume changes of multiple cycles inductionchemotherapy present a certain regularity from the first, second, third, fourth, fifth tosixth cycle of chemotherapy. The average original tumor volume change is obviousafter first cycle chemotherapy,are not significant after second, third,fourth cycle, mayrebound after fivth cycle compared with fourth cycle.By using the inductionchemotherapy for NSCLC, maybe one cycle is optimal,had better not up to fourcycles.2. T stage and original tumor volume are the independent influencing factors ofrelative tumor volume changes after first cycle chemotherapy.The effect ofchemotherapy in original tumor volume≥124000mm~3group is better than originaltumor volume <124000mm~3group, and the effect in T1-2group is better than T3-4group.3. Stratification analysis demonstrates tumor absolute volume and relative volumechanges after first cycle in different variable level are at equal pace on the whole.4. Radiotherapy after one cycle induction chemotherapy can spare OAR effectively,There is no advantage of induction chemotherapy of two cycle comparing with onecycle in sparing OAR. |
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