Tailoring CTV Displacement To Improve The Dosimetry Of Intensity-modulated Radiotherapy For Left-sided Breast Cancer After Modified Radical Mastectomy By Using 4DCT Combined With CBCT

Background and PurposeModified radical mastectomy remains the most widely accepted surgical operation for locally advanced stages of breast cancer in China,and adjuvant radiotherapy has been proved to improve local control and survival.Our previous work has demonstrated that 5-field intensity modulated radiotherapy（5F-IMRT）had significant dosimetrical advantage over 3DCRT-FIF and 2P-VMAT in left-sided breast cancer after modified radical mastectomy.We also firstly raised the hypothesis that individually quantifying and minimizing CTV displacement might improve the dosimetry of 5F-IMRT for left-sided breast cancer after modified radical mastectomy.To improve the dosimetry of post modified radical mastectomy intensity-modulated radiotherapy（PMRM-IMRT）for left-sided breast cancer patients,1)we tailored and minimized PTV expansion three-dimensionally utilizing four-dimensional computed tomography（4DCT）combined with on-board cone beam CT（CBCT）under natural breathing;2)verified the phase 0 having the best dosimetry over other phases during deep breathing and established the functional relation between left lung expansion amplitude and reduction of heart radiation exposure.3)We also compared the overall survival and radiation toxicity between patients using 5F-IMRT and those using 3-dimensional conformal field in field（3DCRT-FinF）.Methods（1）We enrolled a total of 10 consecutive left-sided breast cancer patients to undergo PMRM-IMRT.We measured the intra-fractional CTV displacement attributed to respiratory movement by defining 9 points on the left chest wall and quantifying their displacement by using the 4DCT,and measured the inter-fractional CTV displacement resulting from the integrated effect of respiratory movement,thoracic deformation and set up errors by using CBCT.We created 3 different PMRM-IMRT plans for each of the patients using PTV_t（tailored PTV expansion three-dimensionally）,PTV_0.5and PTV_0.7（isotropic 0.5-cm and isotropic 0.7-cm expanding margin of CTV）,respectively.Dosimetry was compared between the three IMRT plans.（2）We also conducted 4DCT scan for those patients during deep breathing after respiration training.The CT images of phase 0（end of deep inspiration）,phase 30%and phase 50%（end of deep expiration）were obtained and 3 different PMRM-IMRT plans for each of the phase,PTV-DB0（0%breathing phase）,PTV-DB30（30%breathing phase）,and PTV-DB50（50%breathing phase）were created,respectively.Dosimetry was compared between the three IMRT plans.The expansion of left lung volume（?V-Lung）,the percentage of increasement of left lung volume（?M-Lung）and reduction of the heart mean dose（?D-Heart）between IMRT plans（PTV-DB0）and（PTV-DB30）were calculated.The functional relationships between?V-Lung and?D-Heart,as well as?M-Lung and?D-Heart were established.（3）We also compared the overall survival and complexion radiation toxicity between patients using 5F-IMRT and those using 3-dimensional conformal field in field（3DCRT-FinF）.We performed Shapiro Wilk method and ANOVA to test the data.Paired sample t-test was used to analyze the difference of dosimetry and toxicity among different radiotherapy plans.Linear regression was used to establish the relationship between?V-Lung,?M-Lung and?D-Heart.P<0.05 was considered statistically significant.Results（1）The inter-fractional CTV displacement（2.6±2.2mm vertically,2.8±2.3mm longitudinally,and 1.7±1.2mm laterally）measured by CBCT was much larger than the intra-fractional one（0.5±0.5mm vertically,0.5±1.0mm longitudinally,and 0.3±0.3mm laterally,respectively）measured by 4DCT.Intensity-modulated radiotherapy with tailored PTV expansion based on inter-fractional CTV displacement had dosimetrical advantages over those with PTV _0.5or those with PTV_0.7owing to its perfect PTV dose coverage and better OARs sparing（especially of heart and left lung）.（2）Intensity-modulated radiotherapy with PTV-DB0 had dosimetrical advantages over those with PTV-DB30 or those with PTV-DB50 owing to its perfect PTV dose coverage and better heart sparing.There was a positive linear correlation between?V-Lung（x）and?D-Heart（y）,y=0.3497*x+43.77,r=0.8362,P=0.0004.There was also a positive linear correlation between?M-Lung（x）and?D-Heart（y）,y=3.729*x+41.81,r=0.8046,P=0.0004.With every 230 cm3or 22%of increasemnt of left lung volume,the heart mean dose can be reduced by 1.24Gy.（3）The median follow-up duration was 61 months of 5F-IMRT patients and 69months of 3DCRT-FinF patients.There was no significant difference in the 3-year cumulative survival rate between the two groups（84%vs 90%,P=0.22）.There was no difference in grade I and grade II complexion toxicity between the two groups.No grade III or IV skin toxicity developed in either group（P>0.05）.Conclusion（1）The CTV displacement in PMRM-IMRT predominantly arises from inter-fraction rather than from intra-fraction during natural respiration and differs in 3 coordinate axes either inter-fractionally or intra-fractionally.Therefore,respiratory gating technique is not suitable for PMRM-IMRT during natural respiration.However,tailoring and minimizing PTV expansion three-dimensionally significantly improves the dosimetry of PMRM-IMRT for left-sided breast cancer patients.（2）The end of inspiration has the best dosimetry over other phases during deep breathing in PMRM-IMRT for left-sided breast cancer patients.The degree of left lung volume expansion is positively correlated with the degree of reduction of heart radiation exposure.We might screen out the subgroup of those who might benefit from PMRM-IMRT during deep breathing using respiratory gating technique.（3）The breast cancer patients using PMRM-IMRT had no significant less 3-year OS,and had slight complexion radiation toxicity comparing with those using3DCRT-FinF.