Total Body Irradiation Technique Research Articles

A novel AP/PA total body irradiation technique using abutting IMRT fields at extended SSD.

To develop a Total Body Irradiation (TBI) technique using IMRT at extended SSD that can be performed in any size Linac room. Patients studied were placed on a platform close to the floor, directly under the gantry with cranial-caudal axis parallel to the gantry rotation plane and at SSD ∼200cm. Two abutting fields with the same external isocenter at gantry angles of±21˚, collimator angle of 90˚, and field size of 25×40 cm2 are employed for both supine and prone positions. An iterative optimization algorithm was developed to generate a uniform dose at the patient mid-plane with adequate shielding to critical organs such as lungs and kidneys. The technique was validated in both phantom and patient CT images for treatment planning, and dose measurement and QA were performed in phantom. A uniform dose distribution in the mid-plane within±5% of the prescription dose was reached after a few iterations. This was confirmed with ion-chamber measurements in phantom. The mean dose to lungs and kidneys can be adjusted according to clinical requirements and can be as low as ∼25% of the prescription dose. For a typical prescription dose of 200 cGy/fraction, the total MU was ∼2400/1200 for the superior/inferior field. The overall treatment time for both supine/prone positions was ∼54 min to meet the maximum absorbed dose rate criteria of 15 cGy/min. IMRT QA with portal dosimetry shows excellent agreement. We have developed a promising TBI technique using abutting IMRT fields at extended SSD. The patient is in a comfortable recumbent position with good reproducibility and less motion during treatment. An additional benefit of this technique is that full 3D dose distribution is available from the TPS with a DVH summary for organs of interest. The technique allows precise sparing of lungs and kidneys and can be executed in any linac room.

VMAT TBI Technique Using Autoplanning Scripts

Evident by the Children's Oncology Group (COG) survey of pediatric total body irradiation (TBI) practice, 100% of physicians were open to refining the conventional TBI technique to lower the lung dose and 75% of respondents were interested in implementing VMAT or a 3-D CRT and IMRT system TBI. Unfortunately, only a handful of COG institutions have implemented VMAT or Tomo TBI. We created the autoplanning scripts and shared them with the public to make the VMAT TBI more wide-spread. Here, we report on our initial experience of treating Stanford VMAT TBI technique using the scripts. From October 2019 to February 2023, 75 patients were treated with VMAT TBI at our institution. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses); non-myeloablative (lungs, kidneys, lenses, gonads, brain, and thyroid). Treatment planning was performed using Eclipse Scripting Application Programming Interface (ESAPI) auto-planning scripts. Data on patient, treatment details, and dosimetric indices were collected. Treatment was delivered using IGRT for every isocenter and every fraction. In-vivo measurements were performed on the matchline between the VMAT and AP/PA fields and on the testes for the first fraction. Median patient age was 13 years (range, 1 - 64). The patient height and width range were 83.6-197.3 cm and 24.9-60.3 cm, respectively. Forty-eight percent of patients were treated using myeloablative and 52% nonmyeloablative regimens. For all patients the lungs, lungs-1cm, and kidneys Dmean were consistently spared to 59.8±4.7%, 43.0±6.5%, and 70.9±7.7% of the prescription dose, respectively. Gonadal sparing (Dmean = 31.5±5.9%) was achieved for all patients with benign disease. In addition, brain and thyroid was spared for these patients. For nine patients, VMAT TBI offered additional organ sparing (liver, heart, and previously irradiated areas) and possibility to perform the simultaneously integrated boost. The average PTV D1cc was 120.3±6.6% for all patients. PTV D1cc correlated with patient height and width (R2 = 0.62 and 0.53). Sixteen patients (21.3%) with height <116cm were treated with 3-isocenter VMAT only plans, 59 patients (78.6%) were treated with 3-4 isocenter VMAT plans in head-first-supine position and 1-3 AP/PA plan in feet-first-supine position. Rotational platform was used to change the patient orientation. The average matchline dose measurement indicated patient setup was reproducible (96.1±4.5% relative to planned dose). For the first 35 patients, treatment time, including patient setup and beam-on, was 47.5±9.5 min. VMAT TBI is a modern alternative to conventional 2D TBI treatment offering the possibility of organ sparing, dose painting, and accurate treatment using IGRT. The automated scripts enable streamline planning with consistent plan quality.

Improved organ sparing using auto-planned Stanford volumetric modulated arc therapy for total body irradiation technique.

To evaluate dosimetric differences between auto-planned volumetric modulated arc therapy (VMAT) total body irradiation (TBI) technique and two-dimensional radiotherapy using anterior-posterial/posterio-anterial beams (2D AP/PA) TBI technique. Ten pediatric patients treated with VMAT-TBI on Varian c-arm linac were included in this study. VMAT-TBI plans were generated using our in-house developed and publicly shared auto-planning scripts. For each VMAT-TBI plan, a 2D AP/PA plan was created replicating the institution's clinical setup with the patient positioned at extended source to skin distance (SSD) with a compensator to account for differences in patient thickness, 50% transmission daily lung blocks, and electron chest wall boosts prescribed to 50% of the photon prescription. Clinically relevant metrics were analyzed and compared between the VMAT and 2D plans. All VMAT-TBI plans achieved planned target volume (PTV) D90%≥100% of prescription. VMAT-TBI PTV D90% significantly increased (7.1%±2.9%, p<.001) compared to the 2D technique, whereas no differences were observed in global Dmax (p<.2) and PTV V110% (p<.4). Compared to the 2D plans, significant decreases in the Dmean to the lungs (-25.6%±11.5%, p<.001) and lungs-1cm (-34.1%±10.1%, p<.001) were observed with the VMAT plans. The VMAT technique also enabled decrease of dose to other organs: kidneys Dmean (-32.5%±5.0%, p<.001) and lenses Dmax (-5.3%±8.1%, p=.03); and in addition, for 2Gy prescription: testes/ovaries Dmean (-41.5%±11.5%, p<.001), brain Dmean (-22.6%±5.4%, p=.002), and thyroid Dmean (-18.2%±16.0%, p=.03). Superior lung sparing with improved target coverage and similar global Dmax were observed with the VMAT plans as compared to 2D plans. In addition, VMAT-TBI plans provided greater dose reductions in gonads, kidneys, brain, thyroid, and lenses.

Autologous Stem Cell Transplantation With Intensity Modulated Total Body Irradiation Conditioning for Systemic Sclerosis

Autologous stem cell transplantation (HSCT) using myeloablative total body irradiation (TBI) and anti-thymocyte globulin (ATG) as a conditioning regimen has become a standard treatment option for certain patients with systemic sclerosis (SSc). Normal organs are more radiosensitive and prone to compromised function in SSc, and therefore lungs and kidneys require dose reduction. We evaluated the role of intensity modulated radiation therapy (IMRT) TBI compared to standard anteroposterior (AP)/posteroanterior (PA) TBI technique. Patients with SSc who underwent HSCT with TBI between 2017 and 2022 were eligible. All patients underwent conditioning with equine ATG, cyclophosphamide 120 mg/kg, and IMRT TBI to a total dose of 800 cGy in 200 cGy fractions. Patients were replanned using an AP/PA technique for dosimetric comparison. Patients were evaluated for outcomes including event-free survival (EFS), overall survival (OS), disease-modifying antirheumatic drug-free survival (DMARD-FS), and treatment related mortality (TRM). 14 patients were eligible for our analysis. Median follow-up was 34.6 months (1.0-51.7 months). There was one case of TRM secondary to respiratory failure. The 24-month OS, EFS, and DMARD-FS estimates were 92.9%, 74.3%, and 70.0%, respectively. Three patients experienced adverse events, which included respiratory failure (n=1), renal failure (n=1), and death (n=1). Five patients subsequently initiated DMARDs, but three did so due to worsening skin symptoms without other major organ dysfunction. On dosimetric analysis, the mean dose to the planning target volume (PTV) was significantly higher on the IMRT compared to the AP/PA plans (809.4 cGy versus 728.5 cGy, p<0.001). The mean dose to the lungs (239.5 cGy versus 443.9 cGy, p<0.001) and kidneys (204.9cGy versus 281.2 cGy, p<0.001) was significantly lower. Use of IMRT TBI as part of the conditioning regimen for HSCT for SSc yields improved dosimetry with efficacy and toxicity outcomes comparable with published data.

Idiopathic Pneumonitis Syndrome After Total Body Irradiation in Pediatric Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation: A PENTEC Comprehensive Review

Pulmonary complications, especially idiopathic pneumonitis syndrome (IPS), are potentially life altering or fatal sequelae of hematopoietic cell transplantation (HCT). Total body irradiation (TBI) as part of the conditioning regimen has been implicated in IPS. A comprehensive PENTEC (Pediatric Normal Tissues in the Clinic) review was performed to increase our understanding of the role of TBI in the development of acute, noninfectious IPS. A systematic literature search was conducted using the MEDLINE, PubMed, and Cochrane library databases for articles describing pulmonary toxicity in children treated with HCT. Data pertaining to TBI and pulmonary endpoints were extracted. Risk of IPS was analyzed in relation to patient age, TBI dose, fractionation, dose rate, lung shielding, timing, and type of transplant, with the goal to better understand factors associated with this complication in children undergoing HCT. A logistic regression model was developed using a subset of studies with comparable transplant regimens and sufficient TBI data. Six studies met criteria for modeling of the correlation of TBI parameters with IPS; all consisted of pediatric patients undergoing allogeneic HCT with a cyclophosphamide-based chemotherapy regimen. IPS was variably defined, but all studies that reported IPS were included in this analysis. The mean incidence of post-HCT IPS was 16% (range, 4%-41%). Mortality from IPS, when it occurred, was high (median, 50%; range, 45%-100%). Fractionated TBI prescription doses encompassed a narrow range of 9 to 14 Gy. Many differing TBI methods were reported, and there was an absence of 3-dimensional dose analysis of lung blocking techniques. Thus, a univariate correlation between IPS and total TBI dose, dose fractionation, dose rate, or TBI technique could not be made. However, a model, built from these studies based on prescribed dose using a normalized dose parameter of equivalent dose in 2-Gy fractions (EQD2), adjusted for dose rate, suggested correlation with the development of IPS (P=.0004). The model-predicted odds ratio for IPS was 24.3 Gy-1 (95% confidence interval, 7.0-84.3). Use of TBI lung dose metrics (eg, midlung point dose) could not be successfully modeled, potentially because of dosimetric uncertainties in the actual delivered volumetric lung dose and imperfections in our modeling process. This PENTEC report is a comprehensive review of IPS in pediatric patients receiving fractionated TBI regimens for allogenic HCT. IPS was not clearly associated with 1 single TBI factor. Modeling using dose-rate adjusted EQD2 showed a response with IPS for allogeneic HCT using a cyclophosphamide-based chemotherapy regimen. Therefore, this model suggests IPS mitigation strategies can focus on not just the dose and dose per fraction but also the dose rate used in TBI. More data are needed to confirm this model and to determine the influence of chemotherapy regimens and contribution from graft-versus-host disease. The presence of confounding variables (eg, systemic chemotherapies) that affect risk, the narrow range of fractionated TBI doses found in the literature, and limitations of other reported data (eg, lung point dose) may have prevented a more straightforward link between IPS and total dose from being observed.

A Phantom Study on Feasibility of Manual Field-in-Field Clinical Implementation for Total Body Irradiation and Comparison of Midplane Dose with Different Bilateral TBI Techniques.

The aim of this study is to implement a new treatment technique in total body irradiation (TBI) using the manual field-in-field-TBI (MFIF-TBI) technique and dosimetrically verifying its results with respect to compensator-based TBI (CB-TBI) and open field TBI technique. A rice flour phantom (RFP) was placed on TBI couch with knee bent position at 385 cm source to surface distance. Midplane depth (MPD) was calculated for skull, umbilicus, and calf regions by measuring separations. Three subfields were opened manually for different regions using the multi-leaf collimator and jaws. The treatment Monitor unit (MU) was calculated based on each subfield size. In the CB-TBI technique, Perspex was used as a compensator. Treatment MU was calculated using MPD of umbilicus region and the required compensator thickness was calculated. For open field TBI, treatment MU was calculated using MPD of umbilicus region, and the treatment was executed without placing compensator. The diodes were placed on the surface of RFP to measure the delivered dose and the results were compared. The MFIF-TBI results showed that the deviation was within ± 3.0% for the different regions, except for the neck for which the deviation was 8.72%. In the CB-TBI delivery, the dose deviation was ± 3.0% for different regions in the RFP. The open field TBI results showed that the dose deviation was not within the limit ± 10.0%. The MFIF-TBI technique can be implemented for TBI treatment as no TPS is required, and laborious process of making a compensator can be avoided while ensuring that the dose uniformity in all the regions within the tolerance limit.

Feasibility and Toxicity of Full-Body Volumetric Modulated Arc Therapy Technique for High-Dose Total Body Irradiation.

Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

Robustness of a multi-isocenter VMAT Total Body Irradiation (TBI) dose distribution against daily patient setup errors

<h3>Objectives</h3> A VMAT technique using a rotatable tabletop for TBI in supine position is newly applied at UMC Utrecht. We aimed to assess the dose distribution robustness against daily isocenter shifts. <h3>Methods</h3> The tabletop enables rotation from head-first (HF) to feet-first (FF) supine position while the patient remains immobilized in an individualized whole-body vacuum matrass and a thermoplastic facemask. The treatment plan was optimized on the HF and FF CT-scans, co-registered on the overlapping anatomical region (20 cm longitudinal). Depending on patient-length, 4 to 6 isocenters with overlapping arcs (4 cm longitudinal) were used. Prescription dose (PD) was 12Gy in 6 fractions with mean dose constraints for lungs/kidneys <10Gy and lenses <8Gy. Daily patient-position verification procedure (PV) comprised: pelvic HF-iso3 (CBCT + online corrected); thoracic HF-iso2 (CBCT only, no correction); knee region FF-iso (CBCT + online corrected). Brain HF-iso1 and FF-iso4 or -iso5 (patient length dependent) not imaged. HF (FF) radiation delivery followed HF (FF)-PV. After each fraction, the dose distribution of the first 3 treated patients (length range 110-195 cm) was recalculated applying the registered isocenter corrections/shifts. Then, the 6-fraction rigidly accumulated dose distribution was compared to the original. <h3>Results</h3> The maximum shift for HF-iso2 was 0.4 cm lateral, 0.8 cm longitudinal and 0.9 vertical and for the knee region FF-iso 0.7 cm lateral, 0.4 cm longitudinal and 0.5 cm vertical over all patients/fractions. Over all patients, the differences in PTV volume receiving 80%, 90% and 120% PD between accumulated and original dose distribution were <1%, while a +3% V110% PD maximum difference was found. The maximum mean dose difference for lenses, lungs and kidneys between accumulated and original dose distributions was +1.0 Gy, +0.2 Gy and +0.6 Gy, respectively. <h3>Conclusion</h3> The dose distribution of the described VMAT technique for TBI, is proven to be robust against daily observed isocenter shifts.

Full Body Surface Coverage with Water-Equivalent Bolus as Novel Technique for Total Body Irradiation before Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoid Leukemia.

Total body irradiation (TBI) 2 × 2 Gy for 3 consecutive days followed by chemotherapy for conditioning pediatric patients with acute lymphoid leukemia (ALL) before bone marrow transplantation is superior to chemo-conditioning alone. The globally used anterior-posterior/posterior-anterior (AP/PA) technique is the most referable method, but volumetric modulated arc therapy (VMAT) with modern linear accelerators is more precise in terms of ensuring better dose distribution, especially for skin, and higher protection of organs at risk, resulting in less side effects. For TBI, a modern VMAT technique was used. Whole-body immobilization in the supine position was performed using a vacuum mattress with a full body coverage, with a water-equivalent bolus of 1 cm thickness. The design goal was to achieve dose inhomogeneity of less than ±10%. From 2020 to 2022, we performed TBI for five pediatric patients with ALL, with full body bolus and VMAT, who later received hematopoietic stem cell transplantation. No acute complications related to TBI were observed during the treatment period with a median follow-up of 1.27 (0.43-2.11) years. Using full body water-equivalent bolus with VMAT for TBI provides a safe method for children with a better organ sparing in the short term follow-up.

Planning and dosimetric evaluation of three total body irradiation techniques: Standard SSD VMAT, Extended SSD VMAT and Extended SSD Field-in-Field.

The aim of this study was to dosimetrically compare three total body irradiation (TBI) techniques which can be delivered by a standard linear accelerator, and to deduce which one is preferable. Specifically, Extended Source to Surface Distance (SSD) Field-in-Field (FiF), Extended SSD Volumetric Modulated Arc Therapy (VMAT), and Standard SSD VMAT TBI techniques were dosimetrically evaluated. Percent depth dose and dose profile measurements were made under treatment conditions for each specified technique. After having generated treatment plans with a treatment planning system (TPS), dose homogeneity and critical organ doses were investigated on a Rando phantom using radiochromic films and optically stimulated luminescence dosimeters (OSLDs). TBI dose of 12Gy in six fractions was prescribed for each technique. The gamma index (5%/5mm) was used for the analysis of radiochromic films. Passing rates for Extended SSD FiF, Extended SSD VMAT and Standard SSD VMAT techniques were found to be 90%, 87% and 94%, respectively. OSLD measurements were within ± 5% agreement with TPS calculations for the first two techniques whereas the agreement was found to be within ± 3% for the Standard SSD VMAT technique. TPS calculations demonstrated that mean lung doses in the first two techniques were around 8.5Gy while it was kept around 7Gy in Standard SSD VMAT. It is concluded that Standard SSD VMAT is superior in sparing the lung tissue while all three TBI techniques are feasible in clinical practice with acceptable dose homogeneity. In the absence of VMAT-based treatment planning, Extended SSD FiF would be a reasonable choice compared to other conventional techniques.

ESTRO ACROP and SIOPE recommendations for myeloablative Total Body Irradiation in children

Background and purposeMyeloablative Total Body Irradiation (TBI) is an important modality in conditioning for allogeneic hematopoietic stem cell transplantation (HSCT), especially in children with high-risk acute lymphoblastic leukemia (ALL). TBI practices are heterogeneous and institution-specific. Since TBI is associated with multiple late adverse effects, recommendations may help to standardize practices and improve the outcome versus toxicity ratio for children. Material and methodsThe European Society for Paediatric Oncology (SIOPE) Radiotherapy TBI Working Group together with ESTRO experts conducted a literature search and evaluation regarding myeloablative TBI techniques and toxicities in children. Findings were discussed in bimonthly virtual meetings and consensus recommendations were established. ResultsMyeloablative TBI in HSCT conditioning is mostly performed for high-risk ALL patients or patients with recurring hematologic malignancies. TBI is discouraged in children <3–4 years old because of increased toxicity risk. Publications regarding TBI are mostly retrospective studies with level III–IV evidence. Preferential TBI dose in children is 12–14.4 Gy in 1.6–2 Gy fractions b.i.d. Dose reduction should be considered for the lungs to <8 Gy, for the kidneys to ≤10 Gy, and for the lenses to <12 Gy, for dose rates ≥6 cGy/min. Highly conformal techniques i.e. TomoTherapy and VMAT TBI or Total Marrow (and/or Lymphoid) Irradiation as implemented in several centers, improve dose homogeneity and organ sparing, and should be evaluated in studies. ConclusionsThese ESTRO ACROP SIOPE recommendations provide expert consensus for conventional and highly conformal myeloablative TBI in children, as well as a supporting literature overview of TBI techniques and toxicities.

Total body irradiation for standard treatment rooms: a robust sweeping beam technique with respect to the body shape.

BackgroundThe purpose of this work is to improve a sweeping beam technique for total body irradiation (TBI) on a low flat couch using a varying patient thickness model. We designed a flat couch for total body irradiation in supine and prone position. Three generic arcs with rectangular segments for a patient torso thickness of 16, 22 and 28 cm were generated with respect to varying patient thickness of four particular parts of the body: head, torso, thighs and calves.Materials and methodsLongitudinal and transversal dose profiles were measured using an ionization chamber and the EBT3 gafchromic film in a solid water slab phantom. The robustness of the method was examined in phantoms of different thicknesses.ResultsMeasured dose homogeneity stays within ±10% of prescribed dose for all of the three patient thickness models. The robustness of the method was evaluated as the increase in dose in the phantom center of 0.7% per 1 cm reduction in phantom thickness.ConclusionThe method is applicable for the broad range of patient sizes, comfortable for patients, robust and suitable for standard treatment rooms with a standard linear accelerator. It requires minimal investments into equipment.

The Stanford Volumetric Modulated Arc Therapy Total Body Irradiation Technique

PurposeIn this article, we describe the technical aspects of the Stanford volumetric modulated arc therapy (VMAT) total body irradiation (TBI) technique, compare it with other VMAT-TBI techniques, and share our initial experience. Methods and MaterialsFrom September 2019 to August 2021, 35 patients were treated with VMAT-TBI at our institution. Treatment planning was performed using in-house developed automated planning scripts. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses) and nonmyeloablative with benign disease (lungs, kidneys, lenses, gonads, brain, and thyroid). Quality assurance was performed using electronic portal imaging device portal dosimetry and Mobius3D. Robustness was evaluated for the first 10 patients by performing local and global isocenter shifts of 5 mm. Treatment was delivered using image-guided radiation therapy for every isocenter and every fraction. In vivo measurements were performed on the match line between the VMAT and anterior-posterior/posterior-anterior fields and on the testes for the first fraction. ResultsThe lungs, lungs – 1 cm, and kidneys Dmean were consistently spared to 57.6% ± 4.4%, 40.7% ± 5.5%, and 70.0% ± 9.9% of the prescription dose, respectively. Gonadal sparing (Dmean = 0.69 ± 0.13 Gy) was performed for all patients with benign disease. The average planning target volume (PTV) maximum dose to 1 cubic centimeter (D1cc) was 120.7% ± 6.4% for all patients. The average Gamma passing rate for the VMAT plans was 98.1% ± 1.6% (criterion of 3%/2 mm). Minimal differences were observed between Mobius3D- and Eclipse AAA-calculated PTV Dmean (0.0% ± 0.3%) and lungs Dmean (–2.5% ± 1.2%). Robustness evaluation showed that the PTV Dmax and lungs Dmean were insensitive to small positioning deviations between the VMAT isocenters (1.1% ± 2.4% and 1.2% ± 1.0%, respectively). The average match-line dose measurement indicated patient setup was reproducible (96.1% ± 4.5% relative to prescription dose). Treatment time, including patient setup and beam-on, was 47.5 ± 9.5 min. ConclusionsThe Stanford VMAT-TBI technique, from simulation to treatment delivery, was presented and compared with other VMAT-TBI techniques. Together with publicly shared autoplanning scripts, our technique may provide the gateway for wider adaptation of this technology and the possibility of multi-institutional studies in the cooperative group setting.

Evaluation of Surface Dose and Commissioning of Compensator-Based Total Body Irradiation.

Purpose:The aim of the current study is to commission compensator-based total body irradiation (TBI) and to compare surface dose using percentage depth dose (PDD) while varying the distance between beam spoiler and phantom surface.Materials and Methods:TBI commissioning was performed on Elekta Synergy® Platform linear accelerator for bilateral extended source to surface distance treatment technique. The PDD was measured by varying the distance (10 cm, 20 cm, 30 cm, and 40 cm) between the beam spoiler and the phantom surface. Beam profile and half-value layer (HVL) measurement were carried out using the FC65 ion-chamber. Quality assurance (QA) was performed using an in-house rice-flour phantom (RFP). In-vivo diodes (IVD) were placed on the RFP at various regions to measure the delivered dose, and it was compared to the calculated dose.Results:An increase in Dmax and surface dose was observed when beam spoiler was moved away from the phantom surface. The flatness and symmetry of the beam profile were calculated. The HVL of Perspex and aluminum is 17 cm and 8 cm, respectively. The calculated dose of each region was compared to the measured dose on the RFP with IVD, and the findings showed that the variation was <4.7% for both Perspex and Aluminum compensators.Conclusion:The commissioning of the compensator-based TBI technique was performed and its QA measurements were carried out. The Mayneord factor corrected PDD and measured PDD values were compared. The results are well within the clinical tolerance limit. This study concludes that 10 cm −20 cm is the optimal distance from the beam spoiler to phantom surface to achieve prescribed dose to the skin.

Total Body Irradiation in Haematopoietic Stem Cell Transplantation for Paediatric Acute Lymphoblastic Leukaemia: Review of the Literature and Future Directions.

Total body irradiation (TBI) has been a pivotal component of the conditioning regimen for allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) in very-high-risk acute lymphoblastic leukaemia (ALL) for decades, especially in children and young adults. The myeloablative conditioning regimen has two aims: (1) to eradicate leukaemic cells, and (2) to prevent rejection of the graft through suppression of the recipient's immune system. Radiotherapy has the advantage of achieving an adequate dose effect in sanctuary sites and in areas with poor blood supply. However, radiotherapy is subject to radiobiological trade-offs between ALL cell destruction, immune and haematopoietic stem cell survival, and various adverse effects in normal tissue. To diminish toxicity, a shift from single-fraction to fractionated TBI has taken place. However, HSCT and TBI are still associated with multiple late sequelae, leaving room for improvement. This review discusses the past developments of TBI and considerations for dose, fractionation and dose-rate, as well as issues regarding TBI setup performance, limitations and possibilities for improvement. TBI is typically delivered using conventional irradiation techniques and centres have locally developed heterogeneous treatment methods and ways to achieve reduced doses in several organs. There are, however, limitations in options to shield organs at risk without compromising the anti-leukaemic and immunosuppressive effects of conventional TBI. Technological improvements in radiotherapy planning and delivery with highly conformal TBI or total marrow irradiation (TMI), and total marrow and lymphoid irradiation (TMLI) have opened the way to investigate the potential reduction of radiotherapy-related toxicities without jeopardising efficacy. The demonstration of the superiority of TBI compared with chemotherapy-only conditioning regimens for event-free and overall survival in the randomised For Omitting Radiation Under Majority age (FORUM) trial in children with high-risk ALL makes exploration of the optimal use of TBI delivery mandatory. Standardisation and comprehensive reporting of conventional TBI techniques as well as cooperation between radiotherapy centres may help to increase the ratio between treatment outcomes and toxicity, and future studies must determine potential added benefit of innovative conformal techniques to ultimately improve quality of life for paediatric ALL patients receiving TBI-conditioned HSCT.

A bi-institutional multi-disciplinary failure mode and effects analysis (FMEA) for a Co-60 based total body irradiation technique

BackgroundWe aim to assess the risks associated with total body irradiation (TBI) delivered using a commercial dedicated Co-60 irradiator, and to evaluate inter-institutional and inter-professional variations in the estimation of these risks.MethodsA failure mode and effects analysis (FMEA) was generated using guidance from the AAPM TG-100 report for quantitative estimation of prospective risk metrics. Thirteen radiation oncology professionals from two institutions rated possible failure modes (FMs) for occurrence (O), severity (S), and detectability (D) indices to generate a risk priority number (RPN). The FMs were ranked by descending RPN value. Absolute gross differences (AGD) in resulting RPN values and Jaccard Index (JI; for the top 20 FMs) were calculated. The results were compared between professions and institutions.ResultsA total of 87 potential FMs (57, 15, 10, 3, and 2 for treatment, quality assurance, planning, simulation, and logistics respectively) were identified and ranked, with individual RPN ranging between 1–420 and mean RPN values ranging between 6 and 74. The two institutions shared 6 of their respective top 20 FMs. For various institutional and professional comparison pairs, the number of common FMs in the top 20 FMs ranged from 6 to 13, with JI values of 18–48%. For the top 20 FMs, the trend in inter-professional variability was institution-specific. The mean AGD values ranged between 12.5 and 74.5 for various comparison pairs. AGD values differed the most for medical physicists (MPs) in comparison to other specialties i.e. radiation oncologists (ROs) and radiation therapists (RTs) [MPs-vs-ROs: 36.3 (standard deviation SD = 34.1); MPs-vs-RTs: 41.2 (SD = 37.9); ROs-vs-RTs: 12.5 (SD = 10.8)]. Trends in inter-professional AGD values were similar for both institutions.ConclusionThis inter-institutional comparison provides prospective risk analysis for a new treatment delivery unit and illustrates the institution-specific nature of FM prioritization, primarily due to operational differences. Despite being subjective in nature, the FMEA is a valuable tool to ensure the identification of the most significant risks, particularly when implementing a novel treatment modality. The creation of a bi-institutional, multidisciplinary FMEA for this unique TBI technique has not only helped identify potential risks but also served as an opportunity to evaluate clinical and safety practices from the perspective of both multiple professional roles and different institutions.

Image Guided Volumetrically Modulated Total Body Irradiation (TBI): Progress on Single Institution Phase 2 Clinical Trial

<h3>Purpose/Objective(s)</h3> TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. <h3>Materials/Methods</h3> Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% ≥ 90%, D98% ≥ 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant. <h3>Results</h3> Patients were treated to 12 Gy in 8 BID fractions (n = 6) or 13.2 Gy in 8 BID fractions (n = 3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D_2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2). <h3>Conclusion</h3> Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.

Improved Organ Sparing with Autoplanned VMAT TBI

To evaluate dosimetric differences between Volumetric Modulated Arc Therapy (VMAT) and conventional 2D AP/PA Total Body Irradiation (TBI) techniques.Ten pediatric patients treated with a VMAT TBI technique on a C-arm Linac from November 2019 to August 2020 were included in this study. The VMAT TBI plans were generated using an in-house developed autoplanning script using a treatment planning system. For each VMAT TBI plan a corresponding 2D plan was created replicating our institution's current conventional AP/PA technique with the patient positioned standing in a booth at extended SSD with custom compensators to account for patient thickness variations in 8 regions on central axis, lung blocks with 50%-transmission and electron chest-wall boosts. The clinically relevant metrics in this study, including plan global Dmax, PTV V110%, lungs, and lungs contracted by 1cm (lungs-1 cm) Dmean were analyzed and compared between the VMAT TBI plans and simulated 2D plans. All dosimetric comparisons between the VMAT and 2D plans were made with the dose expressed as a percentage of the prescription dose (2Gy or 12 Gy) and the volume expressed as a percentage of the PTV volume. Paired t-test was used to compare the dosimetric indices between VMAT and 2D TBI plans.All VMAT TBI plans achieved D90%≥100% of prescription. PTV coverage, D90%, was reduced significantly (-6.2% ± 2.4%, P < 0.001) with the 2D plans, whereas no significant differences were observed between the 2D and VMAT global Dmax (P < 0.226) and PTV V110% (P < 0.444). Compared to 2D plans, VMAT TBI plans produced a significant decrease in the Dmean to the lungs and lungs-1cm volumes of -25.6% ± 11.5% (P < 0.001) and -34.1% ± 10.1% (P < 0.001), respectively. In addition to lungs, VMAT TBI technique enabled sparing of other organs: for 12 Gy prescription, kidneys Dmean of 64.7% ± 3.3% of prescription dose; for 2 Gy prescription, testes/ovaries Dmean of 31.6% ± 10.7%, brain Dmean of 74.8% ± 1.6% and thyroid Dmean of 72.5 ± 3.5% of prescription dose. Kidneys, gonads, brain and thyroid received the full prescription dose with 2D plans.Improved lung sparing with superior target coverage and similar global Dmax were observed with the VMAT plans as compared to 2D plans. In addition, VMAT TBI plans provided dose reduction in gonads, kidneys, brain and thyroid. Furthermore, VMAT TBI treatments were tolerated well by the patients in more comfortable supine position.

Dosimetric comparison of AP/PA and bilateral geometries for total body irradiation treatment.

Total body irradiation (TBI) is an external radiotherapy technique. Its aim is to deliver a therapeutic dose uniformly within ± 10% of the absorbed dose to the prescription point. In the present study, the TBI technique was implemented in anterior/posterior (AP/PA), and bilateral geometry with photons from a 6 [Formula: see text] and 18 [Formula: see text] accelerator. The TBI technique was implemented on an Alderson Rando phantom at 312 [Formula: see text] source surface distance. During bilateral fraction, rice bags were applied as tissue compensators. To reduce the lung's absorbed dose to the acceptance level, in AP/PA geometry lung blocks made of Cerrobend were used. The required monitor unit (MU) for each fraction was calculated regarding depending on the prescribed dose and beam output. Gafchromic EBT3 films were used for dosimetry between the phantom layers in eight selected points. It is demonstrated that dose uniformity for AP/PA geometry with 6 [Formula: see text] and 18 [Formula: see text] photons was within ± 10%. In contrast, for the bilateral geometry the dose uniformity was not acceptable for both studied energies; However, the results for 18 [Formula: see text] were better than those for 6 [Formula: see text]. Dose accuracy for all measurements was within ± 5 of the prescribed dose. The absorbed dose to the lungs was successfully reduced using the lung blocks. By combining different therapeutic geometries and energies over six fractions, the results of uniformity and accuracy of dose delivery could be improved. It is concluded that the introduced TBI method achieved good dose accuracy and acceptable dose uniformity. Lungs absorbed dose was lower than 10 [Formula: see text] using the lungs blocks. Based on these results, the TBI technique can now be implemented in radiotherapy at Tehran's Imam Hospital. The approach developed in the present study can be used and adapted to match with the conditions at other hospitals.

Practice Patterns of Pediatric Total Body Irradiation Techniques: A Children's Oncology Group Survey

The aim of this study was to examine current practice patterns in pediatric total body irradiation (TBI) techniques among COG member institutions. Between November 2019 and February 2020, a questionnaire containing 52 questions related to the technical aspects of TBI was sent to medical physicists at 152 COG institutions. The questions were designed to obtain technical information on commonly used TBI treatment techniques. Another set of 9 questions related to the clinical management of patients undergoing TBI was sent to 152 COG member radiation oncologists at the same institutions. Twelve institutions were excluded because TBI was not performed in their institutions. A total of 88 physicists from 88 institutions (63% response rate) and 96 radiation oncologists from 96 institutions (69% response rate) responded. The anterior-posterior/posterior-anterior (AP/PA) technique was the most common technique reported (49 institutions [56%]); 44 institutions (50%) used the lateral technique, and 14 (16%) used volumetric modulated arc therapy or tomotherapy. Midplane dose rates of 6 to 15 cGy/min were most commonly used. The most common specification for lung dose was the midlung dose for both AP/PA techniques (71%) and lateral techniques (63%). Almost all physician responders agreed with the need to refine current TBI techniques, and 79% supported the investigation of new TBI techniques to further lower the lung dose. There was no consistency in the practice patterns, methods for dose measurement, and reporting of TBI doses among COG institutions. The lack of standardization precludes meaningful correlation between TBI doses and clinical outcomes including disease control and normal tissue toxicity. The COG radiation oncology discipline is currently undertaking several steps to standardize the practice and dose reporting of pediatric TBI using detailed questionnaires and phantom-based credentialing for all COG centers.