Total Body Irradiation Treatment Research Articles

Protection of Transplanted Hematopoietic Stem Cells from Inflammatory Recipient Marrow Environment through Specific TNF-α Signal Blockade

IntroductionHematopoietic stem cell (HSC) transplantation (HSCT) for hematological malignancy generally requires aggressive chemotherapy and irradiation, which exceed dose-limiting toxicity. These treatments are necessary to eradicate malignant cells and to create a niche for graft HSCs. However, as the intense preconditioning may also induce inflammation in recipient bone marrow (BM), transplanted HSCs thus should be inevitably exposed to this devastating environment. Whilst triggered inflammation within BM is hypothesized to deteriorate transplanted HSCs, how this BM environmental change affects graft HSCs remains largely unknown. We therefore sought to clarify how the pre-conditioned BM environment might affect donor HSCs, focusing especially on inflammatory effects and on developing protective measures against them.Methods & ResultsOur experiments revealed that total body irradiation (TBI) could induce local inflammation peaking around 2-3 days within marrow environment. In vivo exposure of HSCs to irradiated BM environment 2-3 days after TBI exhibited negative effects on HSC function.Then, we tested how the TBI-conditioned BM environment could affect donor HSCs. We first conducted comprehensive gene expression analysis on BM-resident stromal cells considered to constitute the HSC niche. We found that expression of 3 major inflammatory cytokines, IFN-γ, IL-1β, and TNF-α was induced after TBI treatments, thus we compared the effects of these cytokines by an in vitro HSC colony forming assay. Only TNF-α inhibited colony formation of HSCs in a dose dependent manner.We then sought to elucidate mechanisms by which TNF-α impaired HSCs' reconstitution abilities. Based on previous reports, TNF-α is a major stimulus of reactive oxygen species (ROS) through activating Nicotinamide Adenine Dinucleotidemono Phosphate Hydride (NADPH) oxidase. We therefore determined whether TNF-α stimulation produced excessive levels of ROS in highly purified murine HSPCs by culturing them with or without TNF-α for up to 48 hours and staining them with dichlorodihydrofluorescein (DCF) to quantify the accumulation of ROS. The addition of TNF-α was found to induce ROS production in HSPCs in a dose- and time-dependent manner. We next examined if overproduction of TNF-α-mediated ROS impaired reconstitution ability of HSCs; we compared reconstitution abilities of HSCs between groups, one exhibiting high levels of ROS and the other with low/medium levels of ROS. Transplantation experiments using flow-cytometry-sorted populations revealed the negative effect of high levels of ROS on HSCs, suggesting a causal role of elevated ROS levels in TNF-α-mediated impairment of stem cell ability.Accordingly we examined the hypothesis that specific inhibition of the TNF-α-ROS signaling could preserve graft HSCs' functions. The TNF receptor 1 (TNFR1) blocking peptide (PepTNFR1) that specifically blocks NADPH oxidase-mediated ROS production in cells after stimulation with TNF-α was evaluated for this purpose. Pre-incubation of murine HSPCs with PepTNFR1, but not with a scrambled control peptide, inhibited TNF-α-mediated ROS accumulation. Eventually, to determine if reduction of TNF-α-mediated ROS accumulation in graft-HSCs by PepTNFR1 could improve transplantation outcomes, we compared reconstitution kinetics of highly purified HSCs pre-incubated for 2 hours either with PepTNFR1 or a scrambled control peptide. Pre-treatment with PepTNFR1 successfully protected transplanted HSCs from an inflammatory BM environment, showing higher donor-cell chimerism in recipients of "protected" HSCs than in those of non-protected HSCs.ConclusionWe here provide a proof of concept that stem cell protection measures through specific TNF-α signal blockade in the context of HSCT will eventually lead to better engraftment and reconstitution kinetics in transplantation, thereby ameliorating outcomes of HSCT. DisclosuresNo relevant conflicts of interest to declare.

Patient-specific compensation for Co-60 TBI treatments based on Monte Carlo design: A feasibility study

PurposeTo develop an AP–PA treatment technique for the delivery of total body irradiation (TBI) at extended SSD using a modified Co-60 unit equipped with flattening filter and patient-specific compensators supported by Monte Carlo (MC) simulations and measurements. MethodsAn existing Eldorado-78 Co-60 teletherapy unit was stripped of its original collimator and equipped with two beam-defining cerrobend blocks. An acrylic flattening filter was numerically designed based on detailed mapping of the dose distribution of the large open field at a 10 cm depth in water using a primary radiation attenuation calculation. An EGSnrc/BEAMnrc MC model of the resulting unit was developed and experimentally validated and was used to calculate MC dose distributions in whole-body supine and prone CT images of a patient. AP–PA patient-specific compensators were designed based on the supine and prone mid-plane dose distributions. ResultsThe designed flattening filter flattens the beam to within ±2% over a 200 cm × 70 cm area at 10 cm depth in water. Experimental validation of the calculated dose profiles in the open and flattened beams shows agreement of better than 2% and 1%, respectively. Patient MC dose calculations in the flattened, uncompensated beam showed dose deviations from prescription dose most notably in lung, neck and extremities ranging from −5% to +25%. The use of patient-specific compensators reduced inhomogeneities to within −5% to +10%. ConclusionsThis work demonstrates that a Co-60 TBI setup upgraded with patient-specific compensators, numerically designed using MC patient dose calculations, is feasible and considerably improves the dose homogeneity.

Some folded issues related to over-shielded and unplanned rooms for medical linear accelerators - A case study

A medical linear accelerator (LINAC) room must be properly shielded to limit the outside radiation exposure to an acceptable safe level defined by individual state and international regulations. However, along with this prime objective, some additional issues are also important. The current case-study was designed to unfold the issues related to over-shielded and unplanned treatment rooms for LINACs. In this connection, an apparently unplanned and over-shielded treatment room of 610 × 610 cm2 in size was compared with a properly designed treatment room of 762 × 762 cm2 in size (i.e., by following the procedures and recommendations of the IAEA Safety Reports Series No. 47 and NCRP 151). Evaluation of the unplanned room indicated that it was over-shielded and that its size was not suitable for total body irradiation (TBI), although the license for such a treatment facility had been acquired for the installed machine. An overall 14.96% reduction in the total shielding volume (i.e., concrete) for an optimally planned room as compared to a non-planned room was estimated. Furthermore, the inner room’s dimensions were increased by 25%, in order to accommodate TBI patients. These results show that planning and design of the treatment rooms are imperative to avoid extra financial burden to the hospitals and to provide enough space for easy and safe handling of the patients. A spacious room is ideal for storing treatment accessories and facilitates TBI treatment.

SU‐C‐213‐04: Application of Depth Sensing and 3D‐Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

Purpose:To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication.Methods:A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off‐axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs).Results:The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end‐to‐end test showed the overall dose difference was within 3%.Conclusion:Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.

SU-E-T-275: Dose Build Up and Bolusing Characteristics for Total Body Irradiation Dosimetry

Purpose: Total Body Irradiation (TBI) treatments are mainly used in a preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. Our standard regimen is a 12 Gy / 6 fraction bi-daily technique. To evaluate the delivered dose homogeneity to the patient, EBT3 Gafchromic film is positioned at the head, neck, chest, pelvis and groin for all fractions. This work investigates and quantifies the build-up dose characteristics at TBI distances and requirements for in-vivo dosimetry bolusing. Methods: Percentage dose build up characteristics of photon beams have been investigated at large extended SSD's using parallel plate ionisations chambers (Attix) and EBT3 Gafchromic film. Measurements were made to open fields at different field sizes as well as large 40cm × 40cm fields with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point. Results: Percentage surface dose measured values for open fields at 300 cm SSD were found to range from 20 % up to 65.5 % for fields of 5 cm × 5 cm to 40 cm × 40 cm. With the introduction of 1cm Perspex scattering plates used in TBI treatments the surface dose values increased up to 83% to 90%, depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 3mm water equivalent bolus / scatter material should be placed over the EBT3 for accurate dose assessment for TBI treatments. Conclusion: Build up dose characteristics exist at long (300cm) SSD's including treatments using Perspex scattering plates placed at various distances form the patient during TBI treatment. Top accurately assess the applied dose during treatment, in-vivo dosimeters such as Gafchromic EBT3 should have at least 3mm bolus / scatter material placed over them to measure actual applied doses.

TU‐F‐CAMPUS‐T‐01: Dose and Energy Spectra From Neutron Induced Radioactivity in Medical Linear Accelerators Following High Energy Total Body Irradiation

Purpose:To assess the risk posed by neutron induced activation of components in medical linear accelerators (linacs) following the delivery of high monitor unit 18 MV photon beams such as used in TBI.Methods:Gamma spectroscopy was used to identify radioisotopes produced in components of a Varian 21EX and an Elekta Synergy following delivery of photon beams. Dose and risk estimates for TBI were assessed using dose deliveries from an actual patient treatment. A 1 litre spherical ion chamber (PTW, Germany) has been used to measure the dose at the beam exit window and at the total body irradiation (TBI) treatment couch following large and small field beams with long beam‐on times. Measurements were also made outside of the closed jaws to quantify the benefit of the attenuation provided by the jaws.Results:The radioisotopes produced in the linac head have been identified as 18⁷W, ⁵⁶Mn, 2⁴Na and 2⁸Al, which have half‐lives from between 2.3 min to 24 hours. The dose at the beam exit window following an 18 MV 2197 MU TBI beam delivery was 12.6 µSv in ten minutes. The dose rate at the TBI treatment couch 4.8 m away is a factor of ten lower. For a typical TBI delivered in six fractions each consisting of four beams and an annual patient load of 24, the annual dose estimate for a staff member at the treatment couch for ten minutes is 750 µSv. This can be further reduced by a factor of about twelve if the jaws are closed before entering the room, resulting in a dose estimate of 65 µSv.Conclusion:The dose resulting from the activation products for a representative TBI workload at our clinic of 24 patients per year is 750 µSv, which can be further reduced to 65 µSv by closing the jaws.

TU‐CD‐304‐04: Scanning Field Total Body Irradiation Using Dynamic Arc with Variable Dose Rate and Gantry Speed

Purpose:Enable a scanning field total body irradiation (TBI) technique, using dynamic arcs, which is biologically equivalent to a moving couch TBI.Methods:Patient is treated slightly above the floor and the treatment field scans across the patient by a moving gantry. MLC positions change during gantry motion to keep same field opening at the level of the treatment plane (170 cm). This is done to mimic the same geometry as the moving couch TBI technique which has been used in our institution for over 10 years. The dose rate and the gantry speed are determined considering a constant speed of the moving field, variations in SSD and slanted depths resulting from oblique gantry angles. An Eclipse (Varian) planning system is commissioned to accommodate the extended SSD. The dosimetric foundations of the technique have been thoroughly investigated using phantom measurements.Results:Dose uniformity better than 2% across 180 cm length at 10cm depth is achieved by moving the gantry from −55 to +55 deg. Treatment range can be extended by increasing gantry range. No device such as a gravity‐oriented compensator is needed to achieve a uniform dose. It is feasible to modify the dose distribution by adjusting the dose rate at each gantry angle to compensate for body thickness differences. Total treatment time for 2 Gy AP/PA fields is 40–50 minutes excluding patient set up time, at the machine dose rate of 100 MU/min.Conclusion:This novel yet transportable moving field technique enables TBI treatment in a small treatment room with less program development preparation than other techniques. Treatment length can be extended per need, and. MLC‐based thickness compensation and partial lung blocking are also possible.

SU‐E‐T‐485: In Vivo Dosimetry with EBT3 Radiochromic Films for TBI Treatments

Purpose:Total body irradiation (TBI) is a technique that requires special equipment to control “in vivo” the dose to the patient because it is a complex technique performed in extraordinary conditions. There are several devices to perform this task (diodes, TLDs, ionization chambers, MOSFET). In this paper we study the possibility of performing these measurements with radiochromic films EBT3 properly calibrated. This method has been compared to the PTW diodes system for TBI.Methods:Once made the TC to the patients, we measured different thicknesses of the relevant areas of the body (head, neck, chest with or without arms, umbilicus area, knees and ankles); for each of these thicknesses we measured dose rate (cGy / UM) in RW3 phantom, in TBI conditions, with ionization chamber in the center; in turn, the input diode and the output of each configuration is placed to assign dose to each set of diodes. Movie calibration is performed according to manufacturer's recommendations but TBI conditions. The dose at the center of each thickness compared to a linear interpolation of the dose at the entrance and exit, resulting in an adequate approximation. Finally in each session for each patient put a piece of film (2×2 cm2) at the entrance and another at the exit in each area, obtaining these readings and interpolating the estimated center dose, as with the diodes.Results:These results show a greater homogeneity in the distribution for use with film and validate the use of the same for this task and, if necessary, to avoid purchasing diode group if they have not.Conclusion:By using radiochromic films for this technique gives us a proper calculation of the dose received by the patient in the absence of other methods, or gives us a second additional track that already used normally.

SU‐E‐T‐522: Investigation of Underdosage of Total Body Irradiation with Bilateral Irradiation Scheme

Purpose:Patient in‐vivo measurements report lower readings than those predicted from TMR‐based treatment planning on TBI patient knees and ankles where rice was placed to fill the gap between patient's legs. This study is to understand and correct the under dosage of Total Body Irradiation(TBI) with rice tissue equivalent bolus placement at TBI treatment patient setup.Methods:Bilateral TBI scheme was investigated with rice bags bolus placing between patient's two legs acting as missing tissue. In‐house TMR based treatment planning system was commissioned with measurements under TBI condition at 10MV, i.e. source‐to‐reference distance 383.4cm with 40×40cm field size with 1cm thickness Lucite. Predictions of patient specific dose points are reported at different sites with 200cGy prescription at patient umbilicus point. Solid water and rice bag phantoms are used at TBI conditions for the attenuation factor verification and CT scanned to verify the CT number and electron density.Results:We found that the rice bag bolus overall density is 11% lower than the water; however, the attenuation factor of rice bags could become 15% lower than that of water at TBI condition. This overestimate of rice bag electron density could cause the lack of lateral scatter and the lack of backscatter. This could Result in an overestimate of dose at in‐vivo dosimeter measurement points with TMR‐based treatment planning systems. Observations of patient specific optically stimulated luminescent dosimeters(OSLDs) were used to confirm this overestimation. Measurements of setups with increasing the rice bag filled patient leg separation were performed to demonstrate eliminating the overdose issue.Conclusion:Rice bolus has a lower electron density than water does(11%) but results in 15% lower in attenuation factor at TBI condition. This effect was observed in patient delivery with OSLD measurements and can be corrected by increasing the filling rice bolus thickness with 15% longer of separation.

EP-1376: Alanine and fiber-coupled luminescence dosimetry for commissioning of total body irradiation treatments

EP-1376: Alanine and fiber-coupled luminescence dosimetry for commissioning of total body irradiation treatments

Total Body Irradiation using VMAT (RapidArc): A Planning Study of a novel treatment delivery method

Purpose: To evaluate the feasibility of using volumetric modulated arc therapy (VMAT) using RapidArc to deliver total body irradiation (TBI) treatment. Methods: VMAT planning was performed a whole body computed tomography (CT) data set using Rapid Arc. The planning target volumes included entire body trimmed to 3 mm below the skin. The organs at risk included the lungs and kidneys. A dose of 12 Gy in 10 fractions was prescribed to the target volume. The VMAT-TBI technique consisted of three isocentres and three overlapping arcs: the head and neck, the chest, and the pelvis. The plans were prescribed to ensure, at a minimum, 95% planning target volume dose coverage with the prescription dose (percentage of volume receiving dose of 12 Gy was 95%) and maximum dose of 109.8%. Mean dose to lung was restricted at 8.6Gy. Results: The total body volume in the study was 15469cm 3 and the PTV volume was 11322cm 3 . The mean dose to PTV was 104%. The homogeneity index was 0.09. Sparing of normal tissues with adequate coverage of skeletal bones was shown to be feasible with Rapid Arc. The study demonstrates that VMAT is feasible for TBI treatment. Unlike conventional TBI chest wall boost with electrons was not required. Conclusion: The technique for total body irradiation using RapidArc VMAT was found feasible and is undergoing further studies prior to clinical use.

A Simplified Craniocaudal Modulated Arc Technique for Total Body Irradiation

A simplified modulated arc therapy is investigated for Total Body Irradiation (TBI) using dynamic delivery of radiation along the craniocaudal axis of the patient in prone and supine position. The proposed technique is a practical solution for TBI treatments in standard size treatment rooms with patient in a reliable and comfortable position stretched on a custom table close to the floor. Beam model of the extended Source-to-Skin-Distance (SSD) arcs is determined using Monte Carlo (MC) simulations and Gafchromic film.

Treatment verification and in vivo dosimetry for total body irradiation using thermoluminescent and semiconductor detectors

The objective of this work is the characterization of thermoluminescent and semiconductor detectors and their applications in treatment verification and in vivo dosimetry for total body irradiation (TBI) technique. Dose measurements of TBI treatment simulation performed with thermoluminescent detectors inserted in the holes of a “Rando anthropomorphic phantom” showed agreement with the prescribed dose. For regions of the upper and lower chest where thermoluminescent detectors received higher doses it was recommended the use of compensating dose in clinic. The results of in vivo entrance dose measurements for three patients are presented. The maximum percentual deviation between the measurements and the prescribed dose was 3.6%, which is consistent with the action level recommended by the International Commission on Radiation Units and Measurements (ICRU), i.e., ±5%. The present work to test the applicability of a thermoluminescent dosimetric system and of a semiconductor dosimetric system for performing treatment verification and in vivo dose measurements in TBI techniques demonstrated the value of these methods and the applicability as a part of a quality assurance program in TBI treatments.

SU-E-T-404: Simple Field-In-Field Technique for Total Body Irradiation in Large Patients

Purpose: A simple Field-in-Field technique for Total Body Irradiation (TBI) was developed for traditional AP/PA TBI treatments to improve dosimetric uniformity in patients with large separation. Methods: TBI at our institution currently utilizes an AP/PA technique at an extended source-to-surface distance (SSD) of 380cm with patients in left decubitus position during the AP beam and in right decubitus during the PA beam. Patients who have differences in thickness (separation) between the abdomen and head greater than 10cm undergo CT simulation in both left and right decubitus treatment positions. One plan for each CT is generated to evaluate dose to patient midline with both AP and PA fields, but only corresponding AP fields will be exported for treatment for patient left decubitus position and PA fields for patient right decubitus position. Subfields are added by collimating with the x-ray jaws according to separation changes at 5–7% steps to minimize hot regions to less than 10%. Finally, the monitor units (MUs) for the plans are verified with hand calculation and water phantom measurements. Results: Dose uniformity (+/−10%) is achieved with field-in-field using only asymmetric jaws. It is dosimetrically robust with respect to minor setup/patient variations inevitable due to patient conditions. MUs calculated with Pinnacle were verified in 3 clinical cases and only a 2% difference was found compared to homogeneous calculation. In-vivo dosimeters were also used to verify doses received by each patient with and confirmed dose variations less than 10%. Conclusion: We encountered several cases with separation differences that raised uniformity concerns — based on a 1% dose difference per cm separation difference assumption. This could Resultin an unintended hot spot, often in the head/neck, up to 25%. This method allows dose modulation without adding treatment complexity nor introducing radiobiological variations, providing a reasonable solution for this unique TBI situation.

A Clinical Dosimetry Analysis of Total Body Irradiation for Leukemia Patients

Background and Purpose: To perform a retrospective in vivo dosimetry study of 129 total body irradiation (TBI) on leukemia and bone marrow transplant patients treated in our clinic from 2008 to 2011 and to find out if there is any indication of the necessity of developing a new efficient TBI approach. Materials and Methods: The in vivo dosimetry data of 129 patients treated with TBI between 2008 and 2011 were retrieved from the database and analyzed. These patients were mostly treated with the regime of a single fraction or 6 fractions with some exceptions of 8-fraction or 2-fraction treatments depending on the protocols that were applied. For every fraction of treatment, 10 pairs of diode dosimeters were used to monitor the doses to the midline of head, neck, arms, mediastinum, left lung, right lung, umbilicus, thigh, knee, and ankle for both AP and PA fields. The doses to the midline of the above body parts were considered to be the average of the AP and PA readings of each diode pair. Dose deviation from the prescribed value for each body part was studied by plotting the histogram of the frequency versus deviation and comparing this with the dose delivered to the midline of the umbilicus to where the dose was prescribed. The correlation of dose deviation to body part thickness was also studied. By studying the dose deviations, we can find the uniformity of general dose distributions for conventional TBI treatments. Results: The retrospective dosimetry study of the 129 TBI patient treatments indicates that for most of the patients treated in our clinic, the doses received by different body parts monitored with in vivo dosimetry were within the window of 10% difference from the prescribed dose. The inhomogeneity of dose on different body parts could be manually improved by using compensators, but the method is cumbersome and time consuming. The dose deviation in many histograms ranging from about ?10% to 10% indicates some incongruity of dose distribution. This could be due to the method of using lead compensators for a manual dose adjustment which could not ideally compensate for different body thicknesses everywhere. Conclusions: The conventional TBI could give uniform dose to the major body parts under the online in vivo dosimetry monitoring at the level of 10%, but the treatment procedure is cumbersome and time consuming. This implies the importance of developing a new and efficient TBI method by adopting modern radiation therapy technique.

Acute ablation of DP thymocytes induces up-regulation of IL-22 and Foxn1 in TECs

Thymic epithelial cells (TECs) provide the basic architecture for the development of thymocytes. TEC is regenerative after impairment in thymus of young mice. However, how this regeneration program is governed remains unclear. Transcription factor Foxn1 is a central mediator of the differentiation and function of TEC. We examined the relation between thymic injury and Foxn1 in TEC. Total body irradiation (TBI) treatments induced up-regulation of Foxn1 in TEC, which was abolished when thymic function recovered. Specific depletion of double positive (DP) thymocytes triggered the up-regulation of Foxn1. On the other hand, extracellular IL-22 is a potential regulator of homeostasis of TEC. We demonstrated that TBI treatments also induced the up-regulation of intrathymic IL-22. Expression pattern of Foxn1 shares similar characteristics with IL-22. Furthermore, Foxn1 related genes that regulate the function of TEC were also up-regulated. Thus, our data reveal that TBI treatment triggers regeneration program of TEC.

Targeting Myeloid Cells to the Brain Using Non-Myeloablative Conditioning

Bone marrow-derived cells (BMDCs) are able to colonize the central nervous system (CNS) at sites of damage. This ability makes BMDCs an ideal cellular vehicle for transferring therapeutic genes/molecules to the CNS. However, conditioning is required for bone marrow-derived myeloid cells to engraft in the brain, which so far has been achieved by total body irradiation (TBI) and by chemotherapy (e.g. busulfan treatment). Unfortunately, both regimens massively disturb the host’s hematopoietic compartment. Here, we established a conditioning protocol to target myeloid cells to sites of brain damage in mice using non-myeloablative focal head irradiation (HI). This treatment was associated with comparatively low inflammatory responses in the CNS despite cranial radiation doses which are identical to TBI, as revealed by gene expression analysis of cytokines/chemokines such as CCL2, CXCL10, TNF-α and CCL5. HI prior to bone marrow transplantation resulted in much lower levels of blood chimerism defined as the percentage of donor-derived cells in peripheral blood (< 5%) compared with TBI (> 95%) or busulfan treatment (>50%). Nevertheless, HI effectively recruited myeloid cells to the area of motoneuron degeneration in the brainstem within 7 days after facial nerve axotomy. In contrast, no donor-derived cells were detected in the lesioned facial nucleus of busulfan-treated animals up to 2 weeks after transplantation. Our findings suggest that myeloid cells can be targeted to sites of brain damage even in the presence of very low levels of peripheral blood chimerism. We established a novel non-myeloablative conditioning protocol with minimal disturbance of the host’s hematopoietic system for targeting BMDCs specifically to areas of pathology in the brain.

Commissioning total body irradiation using a computerised treatment planning system

Total body irradiation (TBI) is frequently used as a component of hematopoietic stem cell transplant (HSCT). TBI in conjunction with chemotherapy has proven useful for eradicating residual malignant cells and for immunosuppression prior to HSCT. Treatment planning for TBI has traditionally been performed using a manual point dose calculation approach, with treatment delivered in a single fraction through multiple fields. Although this approach has given a good clinical outcome there are drawbacks: manual calculation of a homogenous dose distribution is an arduous, time-consuming task, treatment setup can be complex and the use of fractionated TBI would reduce toxicity without compromising clinical outcome. We are in the process of commissioning a new fractionated TBI process, this will utilise a CT-based computer treatment planning system to create TBI plans with two patient irradiations using a field-in-field approach. We have opted to validate our existing Eclipse AAA beam model for use at an extended SSD of 450cm. Validation of the algorithm involved measurements of percentage depth doses, beam profiles and also investigation of dose calculations beyond inhomogeneities at extended SSD. The project involved design and construction of a suitable combination of treatment couch, Perspex headbox and spoiler for TBI. Furthermore, a TBI treatment planning study has been carried out and an independent MU check program has been created. The presentation is a description of our validation measurements, treatment planning study and also an introduction of our independent TBI MU check program.

Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation

Childhood cancer survivors may develop a number of endocrine complications linked to organ failure, such as hypogonadism, diabetes and growth hormone deficiency. However, increasing evidence now suggests that total body irradiation treatment, specifically, is linked with future risk of insulin resistance, hepatic steatosis and dyslipidaemia, possibly because total body irradiation affects adipocyte differentiation and impairs subcutaneous adipose tissue depot expansion during times of positive energy balance. We describe a 20-year-old woman who developed pancreatitis with severe hypertriglyceridaemia (serum triglycerides > 300 mmol/l) that required plasmapheresis. She had received total body irradiation prior to her bone marrow transplant at age 6 years for relapsed acute lymphoblastic leukaemia. She developed ovarian failure at age 12 years. At age 15 years she was noted to have hyperglycaemia, increased blood pressure, hepatic steatosis and mild hypertriglyceridaemia. She presented with severe hypertriglyceridaemia and eruptive xanthoma, and developed pancreatitis 12 h after admission. She was treated with plasmapheresis and intravenous insulin and made an excellent recovery. We implicate and discuss total body irradiation as the major contributing factor to her severe hypertriglyceridaemia, compounded by worsening glycaemic control, oestrogen deficiency and a changing adult lifestyle. Children who have received total body irradiation are at risk of diabetes and an exaggerated form of the metabolic syndrome with hypertriglyceridaemia, which can be life-threatening. We suggest that survivors of total body irradiation treatment require careful lifelong monitoring of their metabolic status.

SU-E-T-322: Evaluation of Total Body Irradiation Technique Using 20 Diodes In-Vivo Dosimetry System

Purpose: To evaluate a new Total Body Irradiation (TBI) technique using CT planning by 20 diodes real time in‐vivo dosimetry system.Material and Methods: TBI treatment is typically performed at extended SSD ( 3 to 4 meters) under high energy x‐rays (6 MV). Lateral treatment results in a more convenient setup but less dose uniformity as compared with AP/PA treatment. This study evaluated a new TBI treatment which is performed at 2 meter distance, AP/PA. Matched oblique field plan was created by Eclipse TPS with CT simulated data from PIXY phantom; using MLC for lung blocking. Field in Field technique was applied to improve dose uniformity. A steel attenuator with transmission factor 0.55 for 6MV photon field is used to reduce dose rate to 5–20 cGy/min while a 5mm thick Lexan sheet is placed about 20 cm above patient to increase skin dose. Patients will lay supine and prone on a movable bed. Three AP and PA fields were used to deliver prescribed dose. A 20‐diodes SunNuclear in‐vivo dosimetry system was used for monitoring dose at different sites. Diodes were calibrated with attenuator to accommodate energy spectrum change. SSD, dose rate, angular dependence of diodes were measured. RadCalc MU verification software was also tested for agreement with TPS and measured data. Results: Attenuator could reduce the dose rate to about 13 cGy/min. By averaging the entrance and exit reading, the doses at patients anatomical mid‐line were measured and found to have good agreement with TPS (within 7% difference). Two dry‐runs have demonstrated that the TBI plan can achieve and intended dose uniformity better than 10%. The RadCalc verification program agreed with TPS on average within 3%. Conclusion: CT‐image based and TPS generated TBI plan is feasible. Diodes are suitable for both the TBI technique testing and dose monitoring.