Delivery Of Total Body Irradiation Research Articles

Late effects following HSCT for childhood ALL: A national single‐center study using three different modalities of delivery of total body irradiation

Late effects following HSCT for childhood ALL: A national single‐center study using three different modalities of delivery of total body irradiation

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.

American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) Practice Guideline for the Performance of Total Body Irradiation (TBI)

Total body irradiation (TBI) is a specialized radiotherapy technique. It is frequently used as a component of treatment plans involving hematopoietic stem cell transplant for a variety of disorders, most commonly hematologic malignancies. A variety of treatment delivery techniques, doses, and fractionation schemes can be utilized. A collaborative effort of the American College of Radiology and American Society for Radiation Oncology has produced a practice guideline for delivery of TBI. The guideline defines the qualifications and responsibilities of the involved personnel, including the radiation oncologist, physicist, dosimetrist, and radiation therapist. Review of the typical indications for TBI is presented, and the importance of integrating TBI into the multimodality treatment plan is discussed. Procedures and special considerations related to the simulation, treatment planning, treatment delivery, and quality assurance for patients treated with TBI are reviewed. This practice guideline can be part of ensuring quality and safety in a successful TBI program.

Feasibility study of helical tomotherapy for total body or total marrow irradiationa)

Total body radiation (TBI) has been used for many years as a preconditioning agent before bone marrow transplantation. Many side effects still plague its use. We investigated the planning and delivery of total body irradiation (TBI) and selective total marrow irradiation (TMI) and a reduced radiation dose to sensitive structures using image-guided helical tomotherapy. To assess the feasibility of using helical tomotherapy, (A) we studied variations in pitch, field width, and modulation factor on total body and total marrow helical tomotherapy treatments. We varied these parameters to provide a uniform dose along with a treatment times similar to conventional TBI (15-30 min). (B) We also investigated limited (head, chest, and pelvis) megavoltage CT (MVCT) scanning for the dimensional pretreatment setup verification rather than total body MVCT scanning to shorten the overall treatment time per treatment fraction. (C) We placed thermoluminescent detectors (TLDs) inside a Rando phantom to measure the dose at seven anatomical sites, including the lungs. A simulated TBI treatment showed homogeneous dose coverage (+/-10%) to the whole body. Doses to the sensitive organs were reduced by 35%-70% of the target dose. TLD measurements on Rando showed an accurate dose delivery (+/-7%) to the target and critical organs. In the TMI study, the dose was delivered conformally to the bone marrow only. The TBI and TMI treatment delivery time was reduced (by 50%) by increasing the field width from 2.5 to 5.0 cm in the inferior-superior direction. A limited MVCT reduced the target localization time 60% compared to whole body MVCT. MVCT image-guided helical tomotherapy offers a novel method to deliver a precise, homogeneous radiation dose to the whole body target while reducing the dose significantly to all critical organs. A judicious selection of pitch, modulation factor, and field size is required to produce a homogeneous dose distribution along with an acceptable treatment time. In addition, conformal radiation to the bone marrow appears feasible in an external radiation treatment using image-guided helical tomotherapy.

Changes in the Activation and Reconstitution of Lymphocytes Resulting from Total-Body Irradiation Correlate with Slowed Tumor Growth

Alterations in cytokine secretion, activation marker expression, and immune cell concentrations were investigated at sequential time points following delivery of total-body irradiation (TBI) to C57BL/6 mice (n = 64) in the Lewis lung tumor model. Significantly slower tumor growth was observed when a 3-Gy dose of TBI was administered 2 h prior to tumor implantation (p < 0.05). The antitumor effect was correlated with an increased CD4:CD8 T cell ratio and heightened leukocyte blastogenesis. TBI was also found to induce an expansion of natural killer (NK) cells in the blood and spleen of tumor-bearing animals 10 days after irradiation (2.8 × 10⁶ NK cells/spleen in test mice compared to 8.9 × 10⁵ NK cells/spleen in normal control animals). However, no significant differences were found in NK cell levels within the tumor tissue. Enhanced production of interleukin (IL)-12 and IL-18 from spleen supernatants was consistent with an augmentation of the NK cell response. Significant reductions in transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor, both of which are associated with immune suppression, were also noted. Furthermore, TBI induced changes in expression of CD25 and CD71 activation markers, suggesting that radiation may alter tumor surveillance. Taken together, the relative percentages and activation status of immune cell compartments support the conclusion that these TBI-induced changes function to slow tumor progression.

NK cell depletion results in accelerated tumor growth and attenuates the antitumor effect of total body irradiation

Total body irradiation (TBI), given in low to moderate doses as a single modality, can enhance leukocyte populations and immune modifiers, resulting in slowed tumor progression. The aim of this study was to evaluate natural killer (NK) cell involvement in mediating the antitumor effect of TBI by depleting NK populations and monitoring tumor progression and immune status following exposure. C57BL/6 mice (n=54) were injected with anti-NK1.1, anti-asialo GM1, or rabbit serum prior to irradiation/tumor implantation. Selected animal groups were irradiated with a 3 Gy dose of gamma-rays and Lewis lung carcinoma (LLC) cells were subcutaneously implanted 2 h later. Tumor volumes, leukocyte populations, and cytokine levels in blood and spleen were measured up to 10 days post-irradiation/tumor implantation. Depletion of asialo GM1+ cells, but not NK1.1+ cells, led to significant acceleration of tumor growth (P<0.05). Challenge with exogenous antigens (rabbit antibodies or serum) when accompanied by administration of TBI resulted in: a) radioresistance of splenic lymphocytes, b) increased granulocyte and monocyte numbers, and c) enhanced production of IgG, IL-10, and IL-18 within plasma and tumor supernatants. Delivery of TBI to NK1.1+ depleted mice, did not show similar enhancement of leukocytes and/or their modulators. These data indicate that TBI, in conjunction with immune challenge, activates leukocyte parameters and redirects the immune system toward a T helper 2 (Th2) cell response. Additionally, NK cells are involved in mediating the antitumor effect of TBI, while challenge with exogenous protein attenuates the slowing of malignant growth that accompanies delivery of radiation. These findings also support the premise that radiation exposure can activate NK and some T cytotoxic lymphocytes, thereby leading to tumor suppression.

A variable speed translating couch technique for total body irradiation.

We have developed a variable speed translating patient couch system for the delivery of total body irradiation (TBI). For a whole body Rando-type phantom, dose variation at mid-plane relative to the prescription point (navel) can be as high as 15% (neck or legs) with a constant velocity. By taking into account variations in body thickness, the intensity modulation radiation therapy, resulting from variable velocities, effectively delivers a uniform dose distribution at mid plane. The couch control user interface, technical aspects and dose planning optimization procedure for determining velocity distribution are described.

In-vivo dosimetry by diode semiconductors in combination with portal films during TBI: reporting a 5-year clinical experience

Background and purpose: In-vivo dosimetry is vital to assure an accurate delivery of total body irradiation (TBI). In-vivo lung dosimetry is strongly recommended because of the risk of radiation-induced interstitial pneumonia (IP). Here we report on our 5-year experience with in-vivo dosimetry using diodes in combination with portal films and assessing the effectiveness of in-vivo dosimetry in improving the accuracy of the treatment. Moreover, we wished to investigate in detail the possibility of in-vivo portal dosimetry to yield individual information on the lung dose and to evaluate the impact of CT planning on the correspondence between stated and in-vivo measured doses. Materials and methods: From March 1994 to March 1999, 229 supine-positioned patients were treated at our Institute with TBI, using a 6 MV X-rays opposed lateral beam technique. 146 patients received 10 Gy given in three fractions, once a day (FTBI), shielding the lungs by the arms; 70 received 12–13.2 Gy, given in 6–11 fractions, 2–3 fractions per day (HFTBI): in this case about 2/3 of the lungs were shielded by moulded blocks (mean shielded lung dose equal to 9 or 9.5 Gy). Thirteen patients received 8 Gy given in a single fraction (SFTBI, lung dose: 7 Gy). For all HFTBI and FTBI patients, midline in-vivo dosimetry was performed at the first fraction by positioning two diodes pairs (one at entrance and one at the exit side) at the waist (umbilicus) and at the pelvis (ankles). If at least one of the two diodes doses (waist-pelvis) was outside ±5% from the prescribed dose, actions could be initiated, together with possible checks on the following fractions. Transit dosimetry by portal films was performed for most patients; for 165 of them (117 and 48, respectively for FTBI and HFTBI) the midline in-vivo dose distribution of the chest region was derived and mean lung dose assessed. As a CT plan was performed for all HFTBI patients, for these patients, the lung dose measured by portal in-vivo dosimetry was compared with the expected value. Results: Concerning all diodes data, 528 measurements were available: when excluding the data of the first fraction(s) of the patients undergoing corrections ( n=392), mean and SD were respectively 0.0% and 4.5% (FTBI: −0.3±4.8%; HFTBI: 0.4±3.9%). In total 105/229 patients had a change after the first fraction and 66/229 were controlled by in-vivo dosimetry for more than one fraction. Since January 1998 a CT plan is performed for FTBI patients too: when comparing the diodes data before and after this date, a significant improvement was found (i.e. rate of deviations larger than 5% respectively equal to 30.7% and 13.1%, P=0.007). When considering only the patients with a CT plan, the global SD reduced to 3.5%. Concerning transit dosimetry data, for FTBI, the mean (midline) lung dose was found to vary significantly from patient to patient (Average 9.13±0.81 Gy; range 7.4–11.4 Gy); for the HFTBI patients the mean deviation between measured and expected lung dose was 0.0% (1 SD=3.8%). Conclusions: In vivo dosimetry is an effective tool to improve the accuracy of TBI. The impact of CT planning for FTBI significantly improved the accuracy of the treatment delivery. Transit dosimetry data revealed a significant inter-patient variation of the mean lung dose among patients undergoing the same irradiation technique. For patients with partial lung shielding (HFTBI), an excellent agreement between measured and expected lung dose was verified.

Dose Rate-Dependent Sparing of the Gastrointestinal Tract by Fractionated Total Body Irradiation in Dogs Given Marrow Autografts

Purpose: We compared gastrointestinal toxicity of single vs. fractionated total body irradiation (TBI) administered at dose rates ranging from 0.021 to 0.75 Gy/min in a canine model of marrow transplantation. Methods and Materials: Dogs were given otherwise marrow-lethal single or fractionated TBI from dual 60Co sources at total doses ranging from 8–18 Gy and delivered at dose rates of 0.021, 0.05, 0.10, 0.20, 0.40, and 0.75 Gy/min, respectively. They were protected from marrow death by infusion of previously stored autologous marrow cells and they were given intensive supportive care posttransplant. The study endpoint was 10-day mortality from gastrointestinal toxicity. Logistic regression analyses were used to jointly evaluate the effects of dose rate, total dose, and delivery regimen on toxicity. Results and Conclusion: With increasing dose rates, mortality increased for either mode of delivery of TBI. With dose rates through 0.10 Gy/min, mortality among dogs given single vs. fractionated TBI appeared comparable. Beginning at 0.20 Gy/min, fractionation appeared protective for the gastrointestinal tract. Results in dogs given TBI at 0.40 and 0.75 Gy/min, respectively, were comparable, and dose fractionation permitted the administration of considerably higher total doses of TBI than were possible after single doses, an increment that was on the order of 4.00 Gy. The data indicate that the impact of fractionating the total dose at high dose rates differs from the effect of fractionation at low dose rates.

A translating-bed technique for total-body irradiation

Total-body irradiation (TBI) is a therapy modality that is being used with increasing frequency, in conjunction with chemotherapy, for patients undergoing bone-marrow transplantation. At the Ottawa Regional Cancer centre a technique has been developed for the delivery of TBI to patients prior to bone-marrow transplantation. In this technique patients are treated on a mobile couch at approximately 195 cm SSD with a field size of 66.5 cm wide by 57 cm long. A computer-controlled stepping motor drives the patient couch at a user-selectable speed. The total dose delivered to the patient is a function of couch velocity, field size and patient separation. Treatment times are of the order of 10 min for each of the anterior and posterior fields for a 400 cGy fraction. It has been found that the conventional central axis tissue maximum ratio (TMR) and percentage depth dose (PDD) functions are not appropriate for describing dose delivered during dynamic treatment. To this end the authors have developed dynamic TMR and PDD functions. Extensive measurements have been performed in an anthropomorphic water phantom to determine the dose distributions in three dimensions and the efficacy of polymethyl methacrylate (PMMA) beam spoilers as a replacement for anterior and lateral bolus. It has been found that 2.4 cm PMMA spoilers do provide full skin dose and negate the requirement for lateral bolus. This TBI procedure is simple, rapid and appears to be well tolerated by the patients. 55 patients have been treated since the introduction of this technique in 1991.

Verification of lung attenuator positioning before total body irradiation using an electronic portal imaging device

Purpose : We report the first clinical experience with an electronic portal imaging device for lung attenuator positioning before delivery of total body irradiation. We demonstrate a technique for lung attenuator placement which reduces the dose to the patient during setup, reduces the patient setup time, and increases the accuracy of lung attenuator positioning. Methods and Materials : Patients are treated with total body irradiation using a dedicated dual source irradiation facility prior to receiving bone marrow transplantation. The dose rate to the patient's midline is limited to 0.10 Gy/min, and partial transmission lung blocks are used to minimize radiation induced pneumonitis while delivering adequate dose to the regions under the blocks. Lung blocks are placed on the patient's back and chest wall, and portal images are used to verify proper block placement before the remaining treatment dose is delivered. Results : We report the use of a liquid ionization chamber matrix electronic portal imaging device for imaging total body irradiation patient setups. Conclusion : The dose to the patient using the EPID for portal imaging is a factor of 7.5 lower than that needed for film. Image quality is superior to that of film due to digital processing. Since less time and dose are needed for imaging, it is demonstrated that better and more efficient final placement of the lung blocks can be achieved.

A technique for delivery of total body irradiation for bone marrow transplantation in adults and adolescents

With the increasing use of bone marrow transplantation for cancer, total body irradiation is becoming a more commonplace procedure in many of the larger centers across the country. The technical difficulties in delivering homogeneous doses of radiation to the whole body are significant and involve many factors such as creation of a homogeneous, “flat” beam of radiation, and dealing with variations in patient thickness and tissue homogeneity, particularly in the lung. In addition, techniques must be used to safely and efficiently deal with patients who are usually very ill and require long treatment times. Although there is often an advantage in terms of dosimetry to using an AP/PA treatment technique, many institutions use parallel opposed lateral beams because of equipment and facility limitations. A technique has been devised that enables total body irradiation to be given by an AP/PA technique using equipment available in many radiotherapy departments. Patients are supported in an upright position during treatment by means of a modified harness attached to the ceiling of the treatment room. Lung compensators are fixed to individually fitted “vests,” allowing the patient moderate amounts of movement during treatment while maintaining the position of the compensator relative to the lungs. Thermolumuniscent dosimeter (TLD) dose measurements in a phantom indicate that this system can deliver accurate and homogeneous doses to lung tissue, while allowing a good degree of patient comfort and safety during the long treatment times that are required.