Improving The Accuracy Of Breast Cancer, Regional Lymph Node Radiation Therapy And Image Guided Radiation Therapy In The Treatment Of Early Breast Cancer

Part I: Delineation of the regional lymph nodes in the treatment position for breast cancer patients receiving radiotherapy.Purpose: To review the literature about the definition of the regional lymph nodes for breast cancer in CT images and to establish a practical guideline of lymph nodes delineation as to apply to the total local-regional treatment planning of radiotherapy.Material and methods: A practical guideline based on plain CT scan in the treatment position was established regarding the delineation of level I, II, III, interpectoral nodes, supraclavicular nodes and internal mammary nodes. A total of 10 patients with infiltrative breast cancer treated with lumpectomy and level I and II axillary dissection were then delineated with this guideline and anatomical comparison was made with regard to the bilateral axillary nodes was made.Results: Median delineation time for total regional nodes of ipsilateral side was 50 minutes(40-90). The median volume of ipsilateral level I, II and III axillary nodes was 60.2mL (37.3-119.8), 17.5 mL (11.4-28.3) and 12.6 mL (6.0-20.0) respectively. The median volume of interpectoral nodes and supraclavicular nodes was 7.0 mL (4.6-18.0 )and 22.5mL( 18.4-32.1)respectively. No statistically significant difference was found between the depths of different levels of axillary nodes in both sides. Only on level I of axillary nodes a statistical significant difference in volume was found between the dissected and undissected side(p<0.001). The median total volume of axillary nodes below the level of axillary vein was 48.2mL (32.9-110.1) on the dissected side and 116.7mL (77.6-221.4) on the contralateral side, (p<0.001). No statistically significant difference between both sides was found in the volume of axillary nodes above the level axillary vein.Conclusion: Delineation of regional lymph nodes after breast cancer surgery on plain CT in treatment position is feasible. The significant difference of volume between the dissected and undissed sides was found below the level of axillary vein, which confirms the limit of axillary dissection. Regional nodes above axillary vein should be the primary target of post-operative radiotherapy in high-risk patients. Part II Axillary lymph nodes dose for three-dimensional conformal radiotherapy with field in field technique of the whole breast.Purpose: To evaluate the dose distribution of axillary lymph nodes with a field in field technique for whole breast in patients with breast cancer treated with breast conservative surgery, and to analysis the factors influencing the dose to the axillary nodes.Material and methods: Twenty-one consecutive patients receiving breast conservative surgery with level I and II axillary dissection or sentinel node biopsy and lumpectomy only were evaluated. All patients underwent CT-based three-dimensional treatment planning with a field in field technique designed to treat the whole breast without regional lymph nodes. Delineation of level I-III and interpectoral lymph nodes was made on CT images, and a dosimetric analysis was made.Results: A linear correlation between the maximum depth of axillary vein and anterior/posterior(A/P)diameter was found. At least ninety percent of the breast PTV received dose of 50Gy/25F. The 95% isodose line of the prescribed dose encompass an average the volume of level I, II, III and interpectoral nodes by 35.5%, 5%, 0 and 37.7% respectively. The mean dose to the level I, II, III and interpectoral nodes were 32.4 Gy, 12.9Gy, 0 and 28.4Gy respectively. The average percent of the lymph nodes encompassed by 95% isodose line below and above the axillary lymph nodes was 44.9% and 0.1% respectively, with average mean dose of 38.8Gy and 6.6Gy respectively. The distance between the upper limit of the radiation field and the humeral head was the only statistically significant factor influencing mean dose of axillary nodes below the level of axillary vein, with the average mean dose of 36.7Gy and 40.6Gy respectively in patients with distance >2cm and with distance≤2cm, (p=0.006).Conclusion: Actual dose received by axillary lymph nodes below the level of axillary vein should not be neglected, an average of 44% of the volume received dose of 95% of the prescribed dose, and should be taken into consideration when local control of the axilla is analyzed after "breast only" irradiation. However, radiation field designed to treat the breast cannot deliver complete irradiation of the axilla. Part III: Anatomical variability of regional lymph nodes of the breast on CT images in treatment position in patients with breast cancer receiving radiotherapy.Purpose: To analyze the individual variability of regional lymph nodes of the breast in Chinese patients with breast cancer receiving radiotherapy and to explore the dosimetric consequence with traditional two-dimensional radiotherapeutic technique based on bony structure.Material and methods: In consecutive 50 infiltrative breast cancer patients treated with breast conservative surgery with level I and II dissection or modified mastectomy, anatomical structure of the regional lymph nodes was measured on CT images in treatment position, including the maximum depth of level I, II, III, interpectoral nodes and supraclavicular nodes. The maximum depth of internal mammary vessel(IMV) and the distance between the center of the IMV to the mid-sternum was measured at the levels of sterno-clavicular articulation, first, second and third intercostals spaces. The maximum depth of the axillary vein and A/P diameter at the level of axillary vein and supraclavilar node was also measured.Results: The average results of the maximum depth of the level I to III axillary lymph nodes were 75mm, 44mm and 31mm respectively. The average depth of the axillary vein was 47mm, and average A/P diameter at this level was 146mm. The average results of the maximum depth of the supraclavicular depth was 35mm, and average A/P diameter at this level was 150mm. A linear correlation between supraclavicular nodes and A/P diameter was found with approximation of depth of supraclavicular=0.28*A/P diameter-0.64(cm); also linear correlation between depth of axillary vein and A/P diameter was found which can be expressed as depth of axillary vein = 0.48*A/P diameter-2.23(cm). The maximum depth of IMV at the level of sterno-clavicular articulation, first, second and third intercostals space were 1.2mm, 21.2mm, 17.8mm and 18.3mm respectively. The distance between center of IMV to the mid-sternum at these levels were 31.9mm, 29.7mm, 24.5mm and 24.6mm respectively.Conclusion: Our data confirmed important individual variability of the different levels of axillary nodes, supraclavicular nodes and internal mammary vessels exists in Chinese patients with breast cancer. Variability also exists with regard of the depth and distance to the mid-sternum of the internal mammary vessels at different levels. Individual treatment planning for regional nodal irradiation is necessary. Part IV: Treatment optimization of the supraclavicular irradiation based on CT-delineated supraclavicular and level III of the axillary nodes.Purpose: To compare the dose distribution of the supraclavicular irradiation on three-dimensional treatment planning using conventional photon or photon mixed with electron and CT-based optimization, as to explore the dosimetric outcome of target coverage between conventional and optimized planning.Material and methods: Planning target volume of the supraclavicular and level III axillary lymph nodes was delineated on three-dimensional treatment planning CT in 20 patients treated with breast conservative surgery with axillary dissection or modified mastectomy. Dosimetric comparison was generated with 4 different treatment plans. Plan 1: 6MV photon prescribed to 3cm depth; plan 2: 6MV photon mixed with electron prescribed to 3cm depth; plan3: CT optimized field in field conformal technique, FIF with 6MV photon; plan 4: CT optimized FIF technique with 15-20% weight of electron, FIF+E. The optimization should reach 100% PTV received 90% or above of the prescribed dose, with no more than 2% of the PTV received dose inferior to 93% or superior to 110% of the prescribed dose.Results: Coverage of the PTV by 95% of the prescribed dose was reached by all the three plans except for plan 2, which resulted in 86.6% only, p<0.001. Both CT optimized plans lowered the percent of the volume received by 110% of the isodose, p=0.003. Plan 2 showed the maximum "cold area", with an average of 10% of the PTV received dose below 93% of the prescribed dose, while FIF technique got the minimal "cold percent" of 0.38%, p<0.001. No difference of the ipsilateral lung V20, V10 and V5. Compared with FIF, FIF+E increased the volume received by isodose 105% and 107% and showed no dosimetric advantage.Conclusion: Conventional field with photon or photon mixed with electron with fixed dose reference point resulted in inadequate coverage of the supraclavicular and level III axillary lymph nodes and an excess region of high dose. CT-based field in field technique can significantly improve the PTV coverage by 95% isodose, lower the percent of volume received above 110% or below 93% of the prescribed dose. Supraclavicular irradiation should be integrated into the treatment planning with breast/chest wall. Part V A phase I/II clinical trial of accelerated partial breast irradiation in early-stage breast cancer patients treated with breast conservative surgery with initial experience of image-guided-radiation therapyPurpose: This trial aims to evaluate the feasibility and acute skin toxicity of accelerated partial breast irradiation(APBI) in place of the whole breast irradiation in low-risk early-stage breast cancer patients treated with breast conservative surgery, and to explore the initial experience of image-guided radiation therapy(IGRT) in breast cancer irradiation.Material and methods: Inclusion criteria included age≥18 years-old-<70 years-old, T1N0, infiltrative carcinoma or ductal carcinoma in situ(DCIS) except for lobular carcinoma, treated with breast conservative surgery with negative margin(>2mm), and informed consent. Six patients were enrolled between June 2008 and September 2008. Clinical target volume(CTV) is defined by surgical clips plus 1-1.5 cm, another 1cm is added to form the planning target volume(PTV). Three-dimensional treatment planning or field in field technique based on modified tangential fields were generated with prescribed dose of 38.5Gy/10F, with 3.85Gy/F, twice daily with interval above 6 hours. After set-up according to skin marker , an online cone beam CT (CBCT) image was acquired prior to each fraction in 5 patients. Online image registration and correction of the position was conducted. Three different types of registration was used: bony anatomy, grey and manual. Actual treatment delivery was corrected by manual registration. Registration index, cost value was acquired after each grey registration.Conclusion: The ratio of APBI PTV/whole breast PTV was 20%-40% (median 29.3%). 6MV photon treatment with median fields of 3(3-6) was used in 5 patients, mixed electron of 6 MeV was applied in one patient. Grade II skin toxicity was found in all the 6 patients after 15-20(median 17) days of treatment. The average Cost value obtained in 4 patients were -0.71, -0.71, -0.75 and -0.86 respectively. A group of correction distance in the X, Y and Z axis with 3 different types of registration was obtained after each CBCT scan. An analysis of the average correction distance in each axis with each different type of registration showed no average correction distance exceed 0.6cm was found except for one patient with 0.8cm after bony registration in Y axis.Conclusion: Accelerated partial breast irradiation with three-conformal external beam is feasible on dosimetric outcome and initial follow-up. The correction distance with image-guided radiation therapy showed the set-up error does not exceed 0.8cm in either X, Y or Z axis. This resulted confirmed the safety of 1 cm margin from CTV to PTV. Optimized online registration type and the quantification of dose distribution with Cost value await further investigation.