This report aimed to standardize the methodology for simulation, target delineation, treatment planning, optimization, patient-specific quality assurance, in-vivo dosimetry, pre-treatment image verification, setup and treatment. Patients were considered for this procedure after due discussions in the multi-disciplinary tumor board in close co-ordination with the haemato-oncology team. Feasibility for TMLI in these patients was based on the ability and willingness to lie down on the treatment couch for at least 1.5 hours. All patients signed an informed consent document before the procedure. Our experience of treating the first five consecutive adult patients (age >18 years) has been used in this practical implementation report.
Simulation
Simulation was done after the insertion of all catheters or venous access as deemed fit by the hemato-oncology team. Patients were positioned supine in a large vacuum bag encompassing the entire body in a neutral position and a 3-clamp thermoplastic mask on a standard neck support was made to immobilize the head and shoulder. The arm, forearm and hands were placed closely touching the lateral aspect of the body. The knees were placed in a comfortable position and the height was adjusted on the vacuum bag. In males, the scrotum was strapped to the lower abdomen and marked. The firm impression of heel and toes on the vacuum bag was captured. Before acquiring CT imaging, a thin copper wire was placed over the mid-thigh bilaterally. Lines were drawn horizontally over upper and lower limbs with corresponding lines over the vacuum bag to aid reproducibility.
As HT unit can treat till a maximum length of 135cm, two sets of CT scans (on AcquillonLB, Toshiba, Japan) of 5mm slice thickness in free breathing were acquired for each patient. The first scan was acquired from vertex to distal thigh (at least 5cm beyond the wire placed over mid-thigh) in the headfirst supine (HFS) position. Then the patient along with the immobilization was rotated by 180° and a second CT scan was acquired from toes (entire vacuum bag to be included) to the upper thigh (at least 5cm beyond the wire placed over mid-thigh) in feet first supine (FFS) position. Both scans encompassed the entire thigh to aid in registration for the evaluation of the summated plan. For the HFS scan the CT reference point was marked over the chin and for the FFS scan over the knee.
Target Delineation:
CT images were transferred to RayStation Treatment Planning System (TPS, V7.0, RaySearch labs, Stockholm), which is the preferred system for target delineation in our department. Clinical target volume (CTV) included entire bony skeleton, brain, testes spleen and major lymphatics. CTV defined on HFS and FFS scan included bones auto-segmented based on grey level (Hounsfield units-HU) thresholding ranging between 250-1700 HU and edited appropriately. Bony CTV was split into multiple segments (skull, chest, upper/lower limbs, vertebra, and pelvis) to enable differential planning target volume (PTV) margins. Mandible, hyoid bone, patella and larynx were excluded from CTV. PTV margin of 3mm, 5mm, 7mm, 10mm, 5mm were given to CTV skull, vertebra, chest/spleen, upper limb (and lower limb for FFS scan), and pelvis (and scrotum) respectively. For patients with maximum lateral separation exceeding 45cm, an additional margin was created for PTV upper limbs since the field of view (FOV) of megavoltage CT (MVCT) was limited to 40cm. Lymphatics delineated included cervical, supraclavicular, mediastinal, axillary, entire para-aortic chain, external and internal iliac, and inguinal nodes. A uniform PTV margin of 5mm was applied to generate lymph nodal PTV. Individual PTV’s generated were summated to create PTV. Organs at risk (OAR) delineated were eyes, lens, midline mucosa (oral, pharyngeal, laryngeal, tracheal and esophageal mucosa), lungs, heart, liver, bowel, kidneys, parotids, thyroid, breast, and ovaries. Dose Prescription and dose constraints have been summarized in table-1.
Treatment planning, plan evaluation and patient-specific quality assurance (PSQA):
We used the Precision planning system (iDMS version 1.1.1.1, Accuray Inc, USA) for optimization and dose calculation purposes. For planning and optimization, the entire target volume contoured in HFS & FFS images series was divided into three parts namely PTV-upper, PTV-lower and PTV-Junction [Fig-1]. The length of the junction volume was kept at 10cm (typically located between the upper thigh corresponding to the distal end of the fingers and knee) and it was divided into five sub-volumes in each CT image series to create a dose gradient. They were labeled as PhyUG2Gy, PhyUG4Gy, PhyUG6Gy, PhyUG8Gy, PhyUG10Gy, PhyLG2Gy, PhyLG4Gy, PhyLG6Gy, PhyLG8Gy, and PhyLG10Gy. The copper wires placed on the left and right mid-thigh were used as common reference markers to correlate the axial positions from both HFS & FFS CT image series. Using this common reference marker the extension and location of the three PTV’s were verified in both the CT image series.
As a standard protocol CT tabletop in the image series was replaced by the Radixact couch model. The patient position was set using a green laser in such a way that the entire body was fit within the field of view. Two separate treatment plans were generated on each of the scans (HFS and FFS) to cover the entire target including the junction between the two plans [Fig-2a and 2b].
Plan setup parameters were chosen to meet the clinical goals of the target. Pitch from 0.3 – 0.43, field width of 5cm, modulation factor of 2.5 – 3.5 for HFS orientation and 2.15- 2.5 for FFS were used. A higher heterogeneity was accepted near the upper limbs especially near the forearm and hands. Pitch values were optimized to have minimal thread effect and good target coverage. Higher modulation factors were used for initial iterations and subsequently modified to have efficient beam delivery time. The final plans generated on both the CT’s were summated [Fig-3a] and the dose profile across the junction [Fig-3b] was evaluated on RayStation TPS (due to limitation in summating plans generated on two differently referenced CT’s on Precision TPS). As part of the PSQA, we measured the dose using a cylindrical cheese phantom (Accuray Inc, USA) with the A1SL ion chamber (Sun Nuclear, USA). Since the target volume exceeded 120cm, multiple point doses (3 for HFS plan and 2 for FFS plan) were measured to cover the entire target. Each point dose measurement was associated with a specific QA plan and a laser position co-ordinate for phantom placement. Before each measurement phantom position was verified using MVCT image registration with planning CT.
Treatment delivery and In-vivo dosimetry:
Pre-treatment imaging and treatment delivery were divided as the patient was treated in both HFS and FFS positions as described in the pictogram [Fig-4]. Treatment was interrupted each time after a pre-specified time. In HFS treatment, the first MVCT scan was obtained from mid-chest to upper abdomen level to correct any significant longitudinal and yaw errors manually. The 2nd MVCT was acquired from the vertex to the mid-chest level. After applying the necessary lateral and vertical corrections, patient was treated up to the upper abdomen. The third MVCT scan was obtained encompassing the entire abdomen up to mid-thigh, the position of scrotum was verified and the rest of the patient treatment was completed for HFS plan. Subsequently, the patient was rotated by 180 degrees (in yaw plane) with the same immobilization and alignment in place for FFS treatment plan. The fourth MVCT was acquired from ankle to thigh, couch corrections were applied (including the longitudinal corrections since the patient was moved manually) and treatment was delivered with FFS plan. The dosimetric accuracy of the junction was verified using GafChromic ebt3 film placed over the junction during the first treatment fraction.