Using Active Breathing Control (ABC) In 3-dimensional Conformal Radiation Therapy And Intensity-modulated Radiation Therapy For Hepatocellular Carcinoma

Partâ… : Applying active breathing control (ABC) for 3-dimensional conformal radiationtherapy (3DCRT) in hepatocellular carcinoma (HCC): feasibility and dosimetriccomparisons.Objective: To evaluate the feasibility of applying active breathing control (ABC) for3-dimentional conformal radiation therapy (3DCRT) in hepatocellular carcinoma (HCC),and to compare its dosimetric parameters to flee-breathing (FB) radiotherapy plans.Material and Methods: After learnt how to use ABC, HCC patients underwent CTsimulation with ABC or FB. Two treatment plans were generated, and one with ABC wasactually implemented and the anther was for the dosimetric study. Setup errors and liverlocation reproducibility were evaluated. The dosimetric parameters that were comparedbetween ABC plans and FB plans included planning target volume (PTV), mean dose tonormal liver (MDTNL) and the percentage of liver volume, which received radiation doseno less than 23Gy (V₂₃) and normal tissue complication probability (NTCP) ofradiation-induced liver disease (RILD).Results: 28 HCC were eligible for this study. All patients tolerated ABC technique andno one discontinued radiotherapy because of breath holding problem. Fluoroscopy revealedthat the flee breathing range of these patients was 1.5 cm (range, 1.0 cm-2.2 cm), and theaverage maximal liver motion during breathing-hold was 1.3 mm (range, 0.0 mm-2.9 mm).The average intrafraction and interfraction cranial-caudal reproducibility (standarddeviation) of liver position relative to the vertebral bodies was 1.6 mm and 6.7 mm, inanterior-posterior direction the reproducibility was 0.9 mm and 4.4 mm, and in left-rightdirection that was 0.7 mm and 5.4 mm, respectively. PTV decreased from 781 cm³Â±527cm³in FB situation to 529 cm³Â±320 cm³ using ABC (P=0.000). MDTNL was 14.3 Cry±3.7 Gyand 16.9 Gy±4.6 Gy (P=0.000) for ABC and FB patients, respectively. V₂₃ were 30% and41%, and NTCP, 1.0 % and 2.5%(P=0.009) in ABC and FB patients, respectively. Thesystematic and random errors in ABC were 4.7 mm and 1.2 mm (cranial-caudal), 3.5 mmand 1.6 mm (anterior-posterior), and 2.7 mm and 1.8 mm (left-right). The average time needed in ABC radiotherapy was 6.5 minutes (range, 5 min -14 min).Conclusions: Application of ABC for 3DCRT in HCC has been demonstrated feasiblewith good setup accuracy and reproducibility. Interfracion reproducibility is worse thanintrafraction reproducibility. It is rational to take the liver position reproducibility intoaccount and apply image guidance when considering decreasing the planning target marginsafely. Use of ABC could decrease irradiated liver volume, MDTNL, and probably wouldreduce incidence of RILD. Partâ…¡: Comparison of dosimetric parameters of 3D-CRT and IMRT for treatment ofprimary hepatocellular carcinoma and investigation of optimal beam arrangement for IMRTplansObjective: To investigate whether IMRT has the potential benefit for treating primaryhepatocellular carcinoma by comparing the dosimetric parameters between IMRT and3D-CRT. The other objective was to investigate the optimal beam arrangement for IMRTplans.Material and Methods: Planning CT data were selected form eighteen patients withprimary hepatocelluler carcinoma enrolled in a phaseâ… /â…¡dose escalation clinical trail, whopreviously received radiotherapy with active breathing control (ABC) technique. 3D-CRTwas the plan has the ability to treat the patients with maximum tumor dose. Two differentIMRT plans were designed: the first one was IMRT3d, which was a reproduction of the3D-CRT gantry angles; the second called optimal individual IMRT (IMRTin), which wasselected from at least three IMRT plans designed for each patient, according to the criteriathat plan should have the ability to maximize the dose to PTV and has the minimum beamnumber. Dosimetric parameters of PTV and organs at risk between IMRT3d and 3D-CRTplans were compared, and IMRTin plans were evaluated. Hierarchical Clustering analysis(Ward Method) was used to investigate the difference of beam arrangements among 18IMRTin plans with different liver tumor locations (expressed in terms of involved liversegments).Results: All treatment plans resulted in more than 99% of PTV receiving 95% of theprescription dose. The mean EUD(equivalent uniform dose) (mean±standard deviation)across PTV of 3D-CRT and IMRT3d plan was 50.3 Gy±5.4 Gy and 50.1 Gy±6.2 Cry,respectively, and the difference was not statistically significant (p=0.630). IMRTin resultedin increasing EUD value about 10 Gy compared to 3D-CRT, the mean EUD of IMRTin was60.5 Gy±4.7 Gy, comparison of EUDs obtained from 3D-CR.T and IMKT3d demonstrateda statistically significant difference (p＜0.05). The mean MDTNL (mean dose to normal liver)(mean±standard deviation) resulted from 3D-CR.T and IMRT3d plan was 13.9 Gy±3.2 Gyand 12.3 Gy±3.0 Gy (P=0.000), respectively. Compared to 3D-CR.T plan, the IMRT3dplan produced smaller mean liver V₂₃ (the percent of normal liver received no less than23Gy radiation dose), V₁₀ and V₅, and lesser probability of developing radiation-inducedliver disease (RILD), the differences were all statistically significant. The IMRT3d plan didn't produce increased radiation dose to gastrointestinal tract (stomach, duodenum andascending colon). Absolute both lung volume which received no less than 20 Gy producedby IMRT3d plan was 363 cm³Â±297 cm³, and by 3D-CRT plan was 372 cm³Â±303 cm³,the difference between this two plans was not statistically significant (p=0.160). Only onepatient' left kidney received radiation dose more than 20 Cry, the V₂₀ of IMRT3d and3D-CRT plan both was 1%; the mean V₂₀ of right kidney of 3D-CRT and IMRT3d plan was23% and 21%, respectively (p=0.002). Both 3D-CRT and IMRT3d plan produced no morethan 45 Gy dose to spinal cord. The mean MDTNL (mean±standard deviation) resultedfrom IMRTin plan was 18.8 Gy±3.5 Gy, the mean probability of developing RILD was2.5%±1.6%, all dose constraints to other organs at risk (OARs) satisfied. TheHierarchical Clustering analysis illuminated the difference of beam arrangements fordifferent liver segments involved by tumors: for left liver lobe(Ⅰ—Ⅳsegment) typical beamarrangement was 5 beams with couch at 0°, and gantry angle of 0°, 35°, 70°, 290°and 325°;Forâ…¤andâ…¥segments of right liver lobe the gantry angle of 5 coplanar beams distributedin the range of 160°to 340°, while forâ…¦andâ…§segments, the typical beam arrangementwas 5 coplanar beams with gantry angle of 200°, 235°, 270°, 305°and 340°.Conclusions: Compare to 3D-CRT, IMRT has the ability of maintaining the same doseto tumor at the same time decreasing mean dose to normal liver, reducing the probability ofdeveloping RILD, and decreasing or at lest maintaining the radiation injury to other OARs.IMRT also has the potential ability of increasing dose to the tumor effectively, whilesatisfying dose constraints to organs at risk. Different beam arrangements should apply toliver tumor located in different part of liver. The recommended beam arrangement is around5 coplanar beams, predominantly anterior-side and deviated to left for left side tumor, andpredominantly right-side and deviated to posterior for right side tumor. Partâ…¢: Normal liver regeneration after partial liver radiation: an experimental study onrats.Objective: To verify whether unirradiated normal liver has the ability to regenerateafter partial liver irradiation, and to investigate the timing of liver regeneration and the rolesof participated cytokines through an experimental study on rats.Material and Methods: The rats were randomly divided into before radiation (0 day),14-day-post radiation, 30-day-post-radiation, 60-day-post-radiation, 90-day-post radiationand 120-day-post-radiation group, and each group had six rats. The right half liver wasirradiated with a dose of 25 Gy using ⁶⁰Co-γray single fraction. The rats were sacrificed atthe scheduled time in each post radiation group. The radiated liver sample was excised forH. E., trichrome and TGF-β1 immunohistochemical staining to detect radiation-induced liverinjury; unirradiated liver sample were used for mitotic cell counting and proliferation cellnuclear antigen (PCNA) immunohistochemical staining to verify liver regeneration. Theexpression of TGF-β1 in unirradiated liver were also determined withimmunohistochemistry. Hepatocyte growth factor (HGF), Alanine aminotranferease (ALT)and aspartate aminotransferase (AST) in blood serum were measured in each post radiationgroup.Results: Irradiated part of liver showed radiation-induced liver injury tested by H. E.,trichrome and TGF-β1 immunohistochemical staining. ALT and AST were escalated to theirpeak values in 60 days after irradiation, and were 1.56 and 1.53 folds of normal ALT andAST enzyme lever, respectively. The peak number of mitotic hepatocellular cells appearedin 60-day-post-radiation group, with the value of 4.50±0.43 (Mean±SD) out of 1,000cells, compare to before radiation (0 day), 14-day-post radiation, 30-day-post-radiation,90-day-post-radiation and 120-day-post-radiation group the differences were all significantwith P value less than 0.05. The peak number of cells with PCNA strongly positive nuclearappeared in 60-day-post-radiation group, with the value of 77.33±2. 11 (Mean±SD) out of1,000 cells, compare to before radiation (0 day), 14-day-post-radiation,30-day-post-radiation, 90-day-post-radiation and 120-day-post-radiation group thedifferences were all significant with P value less than 0.05. TGF-β1 was expressed aroundcentral vein of hepatic lobule in unirradated liver in 90-day-post radiation and120-day-post-radiation groups. Serum HGF began to increase 14 days after irradiation andreached its peak 30 days after irradiation, compare to before radiation (0 day), 90-day-postradiation and 120-day-post-radiation group the differences were all significant (P＜0.05).Conclusions: Normal liver regeneration exists in 25Gy partial irradiated liver of rats, remarkable regeneration develops around 60 days after irradiation. The roles of associatedcytokines involved in liver regeneration after partial liver radiation need further research.