One eight years old girl diagnosed with acute lymphocytic leukemia underwent allogenic stem-cell transplantation following TBI and VP16 chemotherapy treatment at Hongkong university Shenzhen hospital in 2020. Patient was informed about the treatment and it`s possible adverse events and about necessary diagnostics prior to treatment. Written consent by the patient herself and parents was obtained.
Positioning, immobilization and simulation
Simulation occurs on a computed tomography scanner (Philip Brilliance CT Bigbore) with a setting of 120kVp, 3 mm slice. The scan length is limited to 1.15meters. Both upper limbs are placed at the bilateral sides of the body. Head & neck and shoulders thermoplastic mask, head rest and moldable head and neck support are used to fix the head and neck and shoulders. Whole body thermoplastic cast and whole body evacuated vacuum bags are used to fix thorax, abdomen, and limbs. The patient was positioned on a total body base board, in order to connect all above positioning devices as a whole unit as shown in Fig. 1. Prior to CT acquisition, radiopaque markers are placed near the umbilicus to serve as origin(Fig. 2) and a merge point of the two scans. The overlap area of two scanned images should be longer than 7cm(5 cm for minimized dose gradient at radiation fields junctions, 2 cm for scattered dose calculation at radiation fields edge). If the patient is taller than 1.15 meters, two scans will be performed, the first scan (upper body) goes from the top of the head to pelvis with head first position, the second scan (lower body) goes from the bottom of the feet to the pelvis with feet first position. Both scans include the above origin markers. To allow for quality assurance (QA) measurements during radiotherapy, total eight 0.5 cm bolus are also scanned along with the patient, eight metal oxide semi-conductor field effect transistor (MOSFET) will be placed under bolus for timely treatment dose monitoring as shown in Fig. 1.
Body was contoured using search body automatic tool, then manually modified to include all the outer body contour.
Even with a well-positioned devices, given the movement of the chest wall and ribs, The planning target volume (PTV) was contoured using the outer body contour minus bilateral lungs (except 3 mm margin of lung tissue adjacent to the ribs and chest wall to ensure full dose coverage of the ribs and chest wall). PTV_upper and PTV_lower were contoured on upper body and lower body scans respectively. PTV_total is equal to PTV_upper plus PTV_lower. PTV_crop was equal to PTV_total shrinks by 3 mm in the three-dimensional direction. The right, left and bilateral lungs were contoured using the pulmonary windows separately according to RTOG atlases for Organs at Risk (OARs) in Thoracic Radiation Therapy.
Due to protection of lung tissues and dose coverage of chest wall, helping structures PTV_chestwall_1 cm was defined as the extrapulmonary three-dimensional area within 1 cm. In order to ensure adequate skin dose coverage, the area with PTV_upper and PTV_lower expansion of 3 mm were named PTV_upper_3 mm and PTV_lower_3 mm respectively. At the same time, in order to reduce the actual dose coverage error caused by the positioning error, five sections of dose-drop transition zone were drawn continuously at the junction, the length of each section was 1 cm, five sections were named as Step_12Gy-10Gy, Step_10Gy-8Gy, Step_8Gy-6Gy, Step_6Gy-4Gy and Step_4Gy-2Gy respectively as shown in Fig. 2. The parts of PTV_total in the dose-drop region was named PTV_drop. However, for dose statistics and dose volume histograms(DVH), the anatomical lungs are the relevant structures. The right, left and bilateral kidneys were contoured if pre-existing renal insufficiency. Additional helping structures within the overlapping regions were contoured and used for steering the optimizer leading to an improved dose distribution in those areas. Other OARs were not routinely contoured and involved in dose optimization.
Treatment planning and irradiation
The full-body CT scan was imported into Eclipse treatment planning system, version 15.0. Isocenter was created for treatment planning of each scan. The total prescription dose was 12 Gy, 2 Gy per fraction, two fractions per day, the minimum interval was 6 h. Irradiation was delivered at linac (Triology, Varian) based photon energy of 6 MV over three consecutive days. The elevator and linear accelerator room were routinely disinfected before each fraction radiotherapy. The dose constraint is as follows: The minimum dose (Dmin) of PTV is more than or equal to 90% of prescription dose; The Dmax of PTV is less than or equal to 130% of prescription dose; The volume of PTV covered by 120% of the prescription dose should be less than 10%. The mean dose of both lungs is less than or equal to 10 Gy; The mean dose of both kidneys is less than or equal to 10 Gy if renal insufficiency, no special dose limitation for both kidneys if normal renal function.
As shown in Fig. 2, total sixteen ARC and four AP-PA from five isocenters were designed. For upper body treatment planning, total 12 ARCs were designed with three iso-centers because of the collimator field limitation is 40 cm X 40 cm. For lower body treatment planning, four AP-PA fields in fields were designed for bilateral shanks with a isocenter firstly. Then, another four ARCs with another isocenter were used to cover other parts of lower body. For the convenience of positioning, the coordinate values of each iso-center point are only different in the longitudinal direction. The connection between each rapid arc plan at each isocentric point was administrated by the function module of Base Dose Plan Compensation (BDPC).
Regarding the adjacent region dose distribution between upper and lower body radiotherapy, slight errors may cause significant hot and cold spots if conventional radiotherapy plans. Therefore, we designed a dose-drop scheme on both sides of adjacent region, which decreased from the prescribed dose (12 Gy) to 2 Gy within a length of 5 cm.
We can treat upper body first with head first position, but re-position was needed with feet first position due to the limitation of the length of the linear accelerator treatment bed. For image guidance, kilo-voltage on broad imaging was used to collect images at anterior and right lateral directions for head and neck, abdomen, pelvis and lower limbs, and right lateral oblique directions for thorax to avoid obstruction by the arms. Online matching of the images with digital reconstruction radiograph (DRR) from the planning CTs were performed. Radiotherapy was permitted only if the senior physician and senior therapist confirm that the position error in each direction was less than 2 mm. Treatment team will monitor the whole process with audio and video.
Before radiotherapy, dose verification was performed on each isocentric rapid arc or AP-PA plan and each radiation fields using ScandiDos Delta4PT 3D QA phantom. PTW Octavius 4D QA phantom was used for Gamma passing rate (3 mm/ 3% Gamma criteria) at intersection of each two isocentric rapid arc plans of upper body. Point dose deviation at bilateral lower limbs and the junction of upper body and lower body were verified by a 60 cm(length) X 30cm(width) X 10 cm(height) solid water phantom, PinPoint 0.015 cc and UNDOSE electrometer. During the process of each fraction radiotherapy, total eight interest point sites dose monitoring were needed using MOSFET. Points of interest include forehead, bilateral chest, navel, perineum, bilateral knee and unilateral foot.