Abstract
Purpose:
The aim of this study was to examine current practice patterns in pediatric total body irradiation (TBI) techniques among COG member institutions.
Methods and Materials:
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.
Results:
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.
Conclusions:
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.
Introduction
Total body irradiation (TBI) using megavoltage radiation has an important role in the management of a number of hematological malignancies.1,2 Unlike standard external beam radiation therapy that is used for curative or palliative reasons, TBI is primarily used as a conditioning regimen to eliminate cancer cells and for immunosuppression before hematopoietic stem cell transplantation to prevent graft rejection.3 For specific diseases, TBI delivers a specific dose to sanctuary sites including the central nervous system and testes, where chemotherapy may be less effective.
Since its introduction in the 1950s, TBI continues to be a challenging procedure owing to its unique inherent technical, practical, and clinical requirements.4 The challenges include treatment volume coverage, including both homogeneity and selective normal-tissue dose reduction; definition of the optimal dose rate, fraction size, and interfraction intervals; and the availability of systems to support treament planning, delivery, and reporting. The American Association of Physicists in Medicine guidelines in Report No. 17 recommends that the entire body receive a homogeneous radiation dose to within 10%.5 This can be achieved to some degree by using tissue compensation in the form of a water-equivalent bolus, plastic slabs, rice bags, or other materials. Conventional linear accelerators are usually designed with a maximum field size of 40 × 40 cm2 at iso-center, which is too small even for pediatric patients receiving TBI without extending the source-to-skin distance. Treatment at extended distance introduces changes in beam dosimetry that must be considered for each patient. Beam modifiers in the form of beam spoilers, tissue compensation, and blocking, with various levels of attenuation, may be introduced to achieve the desired dose uniformity. TBI also requires confirmation of patient treatment position and verification of the shielding of organs at risk (eg, lungs). Owing to the extended treatment distances, standard electronic portal imaging devices are not usable, necessitating other solutions such as implementation of a computed radiography system. In addition, computed tomography (CT) simulation and treatment planning systems for dose calculation, considered standard for most clinical scenarios, are rarely used for TBI treatment planning. This is primarily owed to the inability to simulate the patient with CT in a geometry that is compatible with the patient’s treatment position (standing, partially sitting up, etc). For simple TBI treatments without lung blocks, CT simulation and computerized treatment planning are generally not performed owing to the perceived added complexity and time requirements compared with performing caliper thickness measurements and hand calculations for monitor units. However, the incorporation of computerized treatment planning for TBI has been reported for patients treated in the supine or decubitus position.6
Since its inception in 2000, COG has strived to improve cures and quality of life for children with cancer.7,8 A recent trial examined the correlation between lung dose and survival outcomes in children receiving TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) as part of 3 hematopoietic stem cell transplantation preparative regimens for acute lymphocytic leukemia on a prospective COG trial COG ASCT0431.9 Analysis of the treatment planning information from that trial showed that the variability in TBI resulted in uncertainty in reported lung doses and that patients with lung exposures estimated to be 800 cGy or greater had inferior outcomes measured by event-free and overall survival. Those treated using lateral beams had the highest lung doses.9 To understand current practices and variability in treatment approaches, the COG Radiation Oncology Discipline conducted a survey of COG member institutions. The results of the survey will increase understanding of contemporary pediatric TBI practice in COG institutions and provide a foundation for standardization to reduce complications and improve toxicity assessment.
Methods and Materials
The physicist survey questions used in the questionnaire for this study were generated by a group of 12 medical physicists from 11 member institutions who designed different technical aspects of the TBI questionnaire. All questions were then reviewed and revised by this group. The main focus during this stage was to create a thorough survey that might help the radiation oncology community understand how pediatric TBI is being performed at different institutions. The questions were then created in Survey Monkey and shared with the group members for testing. Both the questions and answer structures were critically examined at this point to minimize subjective interpretation. Once the physics group was satisfied with the set of questions, it was sent to the physician group for review.
Similarly, the radiation oncologist survey was generated and vetted by a panel of radiation oncologists in the COG Radiation Oncology Discipline. After both surveys were completed, they were independently reviewed by 9 senior radiation oncologists who composed the steering committee of the COG Radiation Oncology Discipline. This survey was then reviewed and approved by the COG leadership before it was sent out.
The physicist survey consisted of 52 questions that covered the 2 main TBI delivery techniques—anterior-poste-rior/posterior-anterior (AP/PA) and lateral beam. The survey covered a range of technical aspects of pediatric TBI treatment including patient position, beam arrangement, beam energy, lung blocking, treatment planning and dose verification.
The radiation oncologist survey consisted of 9 questions addressing key clinical aspects such as concerns about lung dose and dose rate, desired delivery techniques, and outcome tracking. The radiation oncologist survey questions are shown in Appendix E1. The surveys were conducted with SurveyMonkey, a web-based survey application.
Both the physicist and the radiation oncologist questionnaires were sent to 152 COG institutions that enrolled patients in a recent COG study, AALL 1331, that involved the use of TBI. The institutions that did not respond were identified, and follow-up emails were sent to both representative physicians and physicists. The list of survey questions is shown in Appendix E2. The surveys remained open from November 2019 through February 2020.
Results
Of the 152 institutions to which the survey was sent, physicists and physicians at 12 institutions communicated that TBI was not performed at their institutions, despite their participation in AALL 1331. Therefore, the surveys were administered to the remaining 140 eligible institutions. A total of 96 radiation oncologists from 96 institutions completed the clinical survey (69% response rate). A total of 88 physicists representing 88 institutions completed the technical survey (63% response rate). These 88 institutions accounted for 74% of the total AALL 1331 accrual.
Of the 88 institutions that completed the technical survey, 50 (57%) treated more than 5 TBI patients annually and 18 (20%) treated more than 20 patients annually. Some institutions did not answer all 52 questions, likely owing to the fact that some questions were not applicable to every center.
Dose and fractionation
The reported dose per fraction ranged from 1.2 Gy to 2 Gy and the total dose ranged from 2 Gy to 16.2 Gy. For all dose schemes, if multiple fractions in a day were used, they were at least 6 hours apart. Institutions reported practicing 16 different dose fractionation schemes, with the most common being 12 Gy in 6 fractions (41 institutions [68%]), which is similar to the most common dose regimen as reported by a European survey.10,11 Other common dose schemes used were 2 Gy in 1 fraction (low dose scheme) (33% of institutions), 13.2 Gy in 8 fractions (22% of institutions), and 12 Gy in 8 fractions (17% of institutions). All other dose schemes were used by less than 10% of the institutions.
Among the 18 institutions that treated more than 20 patients annually, only 8 different dose schemes were used, as opposed to the 16 total different schemes reported among all institutions. In 9 (50%) of these 18 institutions, the most common fractionation scheme was 12 Gy in 6 fractions. However, none of these 18 institutions delivered TBI in the exact same manner in terms of technique, beam energy, dose rate, lung dose reporting, and determination.
The spread of total dose and fractions for both low- and high-dose schemes is shown in Figure 1. The low-dose regimens (typically 2–4 Gy) are given to patients who cannot tolerate myeloablative regimens (eg, patients previously treated with a myeloablative regimen).12 In myeloablative conditioning regimens, a total of 10 to 16 Gy is typically delivered.
Fig. 1.
Total body irradiation dose fractionation schemes used in COG member institutions. The area of each circle is proportional to the number of institutions using the dose scheme. The number of institutions using a certain dose scheme is denoted in the middle of each circle. Sixteen different total body irradiation dose schemes were used.
Treatment technique
A total of 49 institutions (56%) used an AP/PA technique for TBI, whereas 44 institutions (50%) used a lateral technique, making AP/PA and lateral beam arrangements the most common techniques currently used to treat pediatric TBI among the institutions in this study, as shown in Figure 2. Volumetric modulated arc therapy (VMAT) or tomotherapy was practiced at 14 institutions (16%).
Fig. 2.
Total body irradiation techniques used in COG member institutions.
The most common energy used was 6 MV for both AP/PA techniques (reported by 79% of institutions) and lateral techniques (reported by 51% of institutions). Higher photon energies, 15 MV and 18 MV, were more commonly used with a lateral technique compared with AP/PA, as shown in Table 1. Patients were typically positioned lying supine or prone (42%), positioned decubitus (40%), or standing with support (33%) for AP/PA. The most common methods of positioning patients for a lateral technique were supine only (67%) and sitting up or partially sitting up (31%). Treatment distance for AP/PA setups was more varied compared with lateral setups, with a source-to-skin distance ranging from 180 to 600 cm; however, the most common source-to-skin distance for both techniques was 401 to 500 cm. Mid-plane dose rates between 6 and 15 cGy/min were most commonly used for both AP/PA and lateral techniques.
Table 1.
Treatment technique parameters for both AP/PA and lateral TBI techniques
| Treatment technique parameters | Institutions No. (%) |
||||
|---|---|---|---|---|---|
| AP/PA | Lateral | ||||
|
| |||||
| Energy, MV | 6 | 38 | (79) | 22 | (51) |
| 10 | 7 | (15) | 5 | (12) | |
| 15 | 6 | (13) | 10 | (23) | |
| 18 | 3 | (7) | 7 | (16) | |
| Other (Cobalt 60, 20, 25 MV, etc) | 2 | (5) | 2 | (5) | |
| Positioning | Standing with seat/support | 14 | (33) | 0 | (0) |
| Supine only | 3 | (6) | 30 | (67) | |
| Supine and prone | 21 | (42) | 0 | (0) | |
| Decubitus | 20 | (40) | 2 | (4) | |
| Sitting up or partially sitting up | 2 | (5) | 14 | (31) | |
| Other | 0 | (0) | 0 | (0) | |
| Treatment distance, cm | 100 | 1 | (2) | 0 | (0) |
| 101–200 | 10 | (20) | 0 | (0) | |
| 201–300 | 10 | (20) | 3 | (7) | |
| 301–400 | 9 | (21) | 14 | (33) | |
| 401–500 | 19 | (39) | 20 | (47) | |
| 501–600 | 6 | (12) | 6 | (14) | |
| Other (>600 cm) | 1 | (2) | 0 | (0) | |
| Dose rate, cGy/min | 0–5 | 2 | (4) | 4 | (8) |
| 6–10 | 28 | (58) | 20 | (40) | |
| 11–15 | 22 | (45) | 20 | (40) | |
| 16–20 | 9 | (19) | 6 | (12) | |
| >20 | 3 | (6) | 1 | (2) | |
Abbreviations: AP/PA = anterior-posterior/posterior-anterior; TBI = total body irradiation.
If an institution offered both AP/PA and lateral techniques, the lateral technique was typically used only for patients who were unable to be positioned and immobilized for AP/PA techniques. Young children who could not be immobilized in the lateral decubitus position for AP/PA TBI or who required sedation were generally treated using lateral TBI techniques with or without lung blocks. Because the thickness of body tissues traversed tends to be greater in the lateral direction, the lateral technique may yield a greater dose variation throughout the body compared with the AP/PA technique.5
Compensators and blocks
Beam spoilers, predominantly with thickness ranging from 0.6 to 1.5 cm and located 15 to 30 cm from the patient, were used for both AP/PA and lateral techniques, as shown in Table 2.
Table 2.
Compensator and block parameters for both AP/PA and lateral TBI techniques
| Compensator or block parameters | Institutions, No. (%) |
||||
|---|---|---|---|---|---|
| AP/PA | Lateral | ||||
|
| |||||
| Spoiler thickness, cm | 0–0.5 | 5 | (11) | 2 | (5) |
| 0.6–1.0 | 21 | (47) | 16 | (39) | |
| 1.1–1.5 | 11 | (24) | 11 | (27) | |
| 1.6–2.0 | 4 | (9) | 8 | (20) | |
| Other (no spoiler used; bolus) | 6 | (13) | 4 | (10) | |
| Spoiler distance from patient, cm | <15 | 12 | (26) | 9 | (21) |
| 15–30 | 24 | (52) | 25 | (60) | |
| >30 | 6 | (9) | 4 | (10) | |
| No spoiler used | 7 | (15) | 7 | (17) | |
| Lung block frequency | Lung blocks not used | 7 | (15) | 33 | (77) |
| Every fraction | 27 | (56) | 12 | (28) | |
| Every other fraction | 4 | (8) | 0 | (0) | |
| After lung reaches dose threshold | 6 | (13) | 1 | (2) | |
| Varying fractionation | 5 | (10) | 1 | (2) | |
| Other (MLC) | 8 | (17) | 2 | (5) | |
| Block mounting | On accessory tray in machine head | 2 | (5) | 5 | (38) |
| Directly on patient | 8 | (20) | 3 | (23) | |
| On beam spoiler | 17 | (42) | 2 | (13) | |
| Block support near patient | 16 | (39) | 3 | (20) | |
| Block support far from patient | 1 | (2) | 0 | (0) | |
| Other (MLC) | 3 | (7) | 2 | (13) | |
| Patient-specific lung blocks | Yes | 39 | (98) | 13 | (100) |
| No | 1 | (2) | 0 | (0) | |
| Blocks of other organs | Lens | 1 | (2) | 2 | (4) |
| Kidney | 6 | (14) | 1 | (2) | |
| Thyroid | 0 | (0) | 1 | (2) | |
| Thymus | 0 | (0) | 0 | (0) | |
| Liver | 2 | (5) | 0 | (0) | |
| Head | 0 | (0) | 1 | (3) | |
| No routine blocks | 37 | (84) | 38 | (91) | |
| Compensator | Head | 23 | (53) | 39 | (93) |
| Neck | 23 | (53) | 33 | (79) | |
| Chest | 12 | (28) | 17 | (40) | |
| Arms | 8 | (19) | 11 | (26) | |
| Legs | 21 | (49) | 34 | (81) | |
| Feet, knees, ankles | 0 | (3) | 4 | (10) | |
| Abdomen, pelvis | 0 | (0) | 2 | (5) | |
| Whole body | 0 | (0) | 1 | (3) | |
| None | 15 | (35) | 3 | (8) | |
| None if within 10% dose difference | 1 | (3) | 2 | (5) | |
| Compensator material | Bolus | 5 | (11) | 4 | (8) |
| Brass | 1 | (2) | 3 | (7) | |
| Aluminum | 1 | (3) | 2 | (5) | |
| Copper | 1 | (3) | 0 | (0) | |
| Plastic | 5 | (11) | 6 | (15) | |
| Lead | 16 | (35) | 19 | (46) | |
| Rice | 3 | (7) | 8 | (20) | |
| No compensators used | 16 | (35) | 3 | (7) | |
| Other (MLC, varying jaw sizes, gantry adjustment, saline, etc) | 5 | (11) | 5 | (12) | |
Abbreviations: AP/PA = anterior-posterior/posterior-anterior; MLC = multileaf collimator; TBI = total body irradiation.
Seven institutions (15%) did not use any lung blocks for AP/PA treatments, whereas 33 institutions (77%) did not use lung blocks for lateral treatments. Responses indicating that no lung blocks were used for AP/PA treatments presumably correlated with low-dose regimens that typically do not use lung blocks. Of the 49 centers using AP/PA treatments, 27 (55%) used lung blocks for every fraction. When lung blocks were used, the thickness of the blocks varied to achieve 25% to 85% transmission.
Of the institutions that used lung blocks, 39 institutions (98%) and 13 institutions (100%) used patient-specific lung blocks for AP/PA and lateral techniques, respectively. When blocks were used for AP/PA techniques, 17 institutions (42%) mounted them on the beam spoiler, 16 (39%) mounted them on the block support near the patient, and 8 (20%) placed them directly on the patient. For the lateral technique, 5 institutions (38%) mounted blocks on the accessory tray, 3 (23%) mounted them directly on the patient, and 3 (23%) mounted them on a block support near the patient.
Of the institutions that used lung blocks, 37 (99%) and 16 institutions (100%) verified the position of the lung blocks for both AP/PA and lateral techniques respectively (Table 3). The use of compensators was more prevalent in the lateral technique compared with AP/PA, with a variety of materials used for compensation.
Table 3.
Dose calculation, verification, and dose reporting parameters
| Dose calculation, verification, and reporting parameters | Institutions, No. (%) |
||||
|---|---|---|---|---|---|
| AP/PA | Lateral | ||||
|
| |||||
| Measurements | Caliper | 33 | (67) | 33 | (75) |
| CT | 18 | (37) | 16 | (37) | |
| Other (extended SSD tables, AP radiograph) | 5 | (10) | 2 | (5) | |
| MU calculation | Hand calculation or spreadsheet | 41 | (84) | 40 | (91) |
| Treatment planning system | 11 | (22) | 5 | (11) | |
| Lung dose determination | If partial transmission is used, multiply percentage transmission and prescribed dose (with or without other correction factors) to obtain midlung dose | 14 | (30) | 8 | (20) |
| CT simulate, then calculate midlung and/or mean lung doses | 12 | (25) | 5 | (13) | |
| Measure entrance and exit dose, then average with or without correction factor to obtain midlung dose | 8 | (17) | 7 | (18) | |
| Use CT or chest x-ray to correct depth to midline for lung density to obtain midlung dose | 5 | (11) | 8 | (20) | |
| Not determined | 3 | (6) | 10 | (25) | |
| Other (spreadsheet calculation, assume prescription dose) | 4 | (9) | 1 | (3) | |
| Dose verification | Head | 29 | (76) | 27 | (79) |
| Neck | 24 | (63) | 18 | (52) | |
| Lung | 22 | (57) | 21 | (62) | |
| Umbilicus | 37 | (97) | 30 | (88) | |
| Hip | 12 | (31) | 19 | (56) | |
| Legs | 25 | (65) | 23 | (67) | |
| Thighs | 2 | (5) | 1 | (3) | |
| Knees | 4 | (10) | 2 | (6) | |
| Ankles | 4 | (10) | 2 | (6) | |
| Arms | 2 | (5) | 1 | (3) | |
| Not verified | 5 | (13) | 2 | (6) | |
| Verified only as needed | 2 | (5) | 0 | (0) | |
| Other (axilla, at distance from midline) | 2 | (5) | 0 | (0) | |
| Dose verification detector | Thermoluminescent dosimeter | 2 | (5) | 3 | (8) |
| Metal oxide semiconductor field effect transistor | 7 | (16) | 5 | (13) | |
| Optically stimulated luminescent dosimeter | 26 | (59) | 17 | (45) | |
| Diode | 11 | (25) | 16 | (42) | |
| Film | 1 | (2) | 0 | (0) | |
| Not used | 4 | (9) | 4 | (11) | |
| Lung block verification | Radiographic film | 15 | (32) | 5 | (14) |
| Digital radiography | 19 | (40) | 3 | (8) | |
| Computer radiography | 8 | (17) | 8 | (22) | |
| Marks on the patient | 1 | (2) | 1 | (3) | |
| Setup verification | Treatment distance | 45 | (91) | 35 | (92) |
| Beam spoiler | 39 | (90) | 33 | (87) | |
| Lung block | 42 | (95) | 24 | (63) | |
| Flash | 39 | (80) | 30 | (79) | |
| Separation | 38 | (78) | 29 | (76) | |
| Securing of patient | Safety harness | 19 | (48) | 10 | (29) |
| Other (vac loc, patient lying on table) | 21 | (53) | 26 | (74) | |
Abbreviations: AP/PA = anterior-posterior/posterior-anterior; CT = computed tomography; MU = monitor unit; SSD = source-to-skin distance; TBI = total body irradiation.
Dose calculation, verification and reporting
A total of 33 of the 49 institutions (67%) using AP/PA techniques and 33 of the 44 institutions (75%) using lateral techniques used caliper measurements of the external body dimensions for monitor unit (MU) calculation, as shown in Table 3. Eleven institutions (22%) using AP/PA techniques used a treatment planning system (TPS) for MU calculation, compared with 5 institutions (11%) treating laterally, although 18 (38%) of institutions obtained a CT scan.
Midlung dose was the most common lung dose specification for both AP/PA and lateral techniques, as shown in Figure 3. Ten institutions (25%) using lateral techniques did not specify the lung dose. As shown in Table 3, the most common method of determining lung dose, used by 14 institutions (30%) using AP/PA techniques and 8 institutions (20%) treating laterally, was to multiply the prescribed dose by the percentage of transmission, with or without correction factors.
Fig. 3.
Methods of lung dose reporting during total body irradiation using anterior-posterior/posterior-anterior and lateral techniques.
The most common detectors used for dose verification were an optically stimulated luminescent dosimeter (approximately 52% of institutions) and diodes (approximately 33% of institutions) placed on the body surface. The majority of institutions verified treatment distance (91%-AP/PA, 92%-Lat), placement of beam spoiler (90%-AP/PA, 87%-Lat), and lung blocks (95%-AP/PA, 63%-Lat). Most institutions also verified flash—that is, ensuring that the light and radiation field adequately covers the patient (80%-AP/PA, 79%-Lat)—and patient separation (78%-AP/PA, 76%-Lat) before each treatment.
Radiation oncologist survey
A total of 96 radiation oncologists responded to the questionnaire, which contained 9 questions on clinical practice of TBI. Of these, 73% had no clinical concerns associated with uncertainties in how lung doses were measured in their institutions, and 78% had no difficulty in meeting current COG protocol guidelines of keeping midlung doses below 8 Gy.
Almost all the radiation oncologists (98%) desired further refinement of current TBI techniques. Most (79%) supported the investigation of new techniques to lower lung doses, and 83% supported the investigation of VMAT or helical tomotherapy. Fifty-three percent reported that they evaluated lung function before the administration of TBI. Many (56%) were concerned about delivering TBI at dose rates greater than 15 cGy/min. Less than half (41%) either followed up with or collected clinical outcome data on TBI patients after administration of TBI.
Discussion
For clinical trials that include TBI, an accurate report of the target dose and organ-at-risk doses by the participating institution is critical for the valid interpretation of trial outcomes. This survey aimed to determine the variations in treatment techniques and dosimetry for pediatric TBI to help elucidate potential dosimetric uncertainties in reported doses. The technical survey questions included the key determinants of TBI treatment: patient position, beam arrangement, treatment distance, determination of beam-on time, normal organ dose considerations including lung blocking or compensation, and quality assurance measures. The clinical survey questions aimed to assess the key clinical considerations for TBI. As shown by the results of this survey and those conducted by others,10,13,14 TBI delivery practices are varied, ranging from simple AP/PA open fields to complex modulated arcs at extended distances. Surveys in Australia and New Zealand14 and in Canada13 reported that no 2 institutions carried out TBI with the exact same method. A survey carried out by the European Society for Pediatric Oncology (SIOPE)11 indicated that although there was uniformity in dose schemes and lung shielding, practices varied in terms of implementation of advanced techniques and shielding of organs at risk. The SIOPE survey, however, did not provide technical details on the reporting of doses and implementation of TBI techniques. Variation in the practice of TBI presents significant challenges to the standardization of TBI delivery and an opportunity for improvement. Standardization and improvement in the accuracy of TBI dose reporting are even more urgent for improving interpretation of outcomes data and future techniques.
The primary dose-limiting factor for TBI is the lung dose and related toxicities including radiation pneumonitis and fibrosis. Early in the history of TBI, single 10-Gy fractions were used15 but were found to cause severe lung toxicity. Low dose rates (≤10 cGy/min) were unavoidable because the treatment machines (Co-60 or early linear accelerators) were incapable of delivering higher dose rates at the extended distances. Despite the use of low dose rates, the incidence of lung toxicity persisted.15 To mitigate lung toxicity, fractionation was introduced, which reduced the incidence of radiation pneumonitis. Dose rates of about 10 cGy/min continue to be used, but there are mixed data to support this in light of the use of fractionated TBI dose schemes.16 As the current survey indicated, TBI treatments among the participating institutions were generally performed with 1 of 2 beam arrangements: AP/PA or opposed laterals. Patients were treated in the supine, decubitus, or standing positions. To decrease the potential for pneumonitis, lung compensation or blocking has been part of the treatment paradigm for decades for many but not all centers. Lateral fields treated without lung blocks are typically delivering higher lung doses17 that could be a potential cause of higher toxicity.9 More recently, reducing the lung dose to 800 cGy has been mandated by COG protocols, necessitating the use of Cerrobend alloy or lead lung blocks. The heterogeneity of treatment methods and the inability to perform 3-dimensional treatment planning (most often, TBI MUs are calculated by hand from caliper measurements) result in large uncertainties in lung doses during TBI. In the majority of institutions in this study that used manual dose calculations, the lung dose was reported at the center of the lung block (ie, the midlung dose). The mean lung dose has been correlated with pneumonitis.18 Large uncertainties in lung doses from TBI are apparent, as most institutions report the lung dose as estimated from the percentage of lung block transmission or from using a manual calculation based on approximate lung density and thickness. These methods can result in an error of up to 20% in determining the midlung dose6,19 and do not account for the peripheral lung dose, which may be much higher than the midlung dose depending on the block shape and position. Taken together, we concluded that the current methods for reporting lung dose do not represent the mean lung dose and preclude accurate correlation between lung dose and treatment outcomes after TBI. Modern techniques using helical tomotherapy or VMAT have tremendous potential to improve organ dosimetry by considering the dose to lung volumes, not to a single point, and provide superior organ sparing during TBI.20–28 Another, more recent technique that offers some organ sparing and is delivered at an extended distance is step-and-shoot intensity modulated radiation therapy TBI.29 Of the 88 institutions that responded to this survey, only 14 had implemented either VMAT TBI or helical tomotherapy TBI.
Most COG radiation oncologist respondents expressed a strong interest in refining or changing TBI techniques to improve dosimetry and reduce lung dose during TBI. The radiation oncology discipline in COG has taken several steps to improve understanding of current practices and ensure better quality of TBI treatments. The Imaging and Radiation Oncology Core Houston (IROC-H) is conducting an audit of all COG TBI programs. A pediatric TBI phantom of a 10-year-old child with thermoluminescent dosimeters located in the brain, neck, lung, abdomen, umbilicus, and pelvis is being sent to COG centers with instructions to irradiate the phantom using standard institutional techniques. In a preliminary report from 20 institutions,17 the mean (standard deviation) blocked lung dose was 58% (27%) of the prescription dose, indicating significant variation in lung doses using current techniques. The IROC-H has proposed credentialing criteria of 5% agreement at the prescription point and a nonlung dose within 15% of the prescription dose.17 Furthermore, for the first time, a credentialing requirement has been set up for all COG institutions enrolling patients in a prospective clinical trial for AML (AAML1831) that opened in July 2020. Our committee is critically reviewing novel TBI techniques using VMAT or tomotherapy before their adoption groupwide for children receiving TBI.
In terms of treatment technique, there is no major difference between pediatric versus adult TBI treatments. The majority of centers do not use sedation in infants, especially if a twice-daily TBI regimen is used. Very young children can be safely and securely immobilized in Papoose boards with them lying in the supine position, and they are treated using lateral TBI techniques with or without lung blocks. If sedation is used in young children, a lateral TBI technique can be similarly used with or without lung blocks. As such, the conclusions drawn in this study can generally be applied to adult TBI as well.
This survey-based study of pediatric TBI methods has several strengths in comparison with other such reports.10,11,13,14 The 88 responding institutions treated approximately 74% of cases on the recent COG leukemia protocol AALL1331. This survey included detailed questions about AP/PA and lateral treatment methods to better understand important details regarding treatment techniques and dose reporting. Separate clinical and technical questionnaires permitted a more comprehensive review of current technical practice and physician preferences. One weakness of this survey was that respondents did not provide answers to all questions, presumably because some questions were not applicable to their practice of TBI.
Conclusion
There was no consistency in TBI practice patterns, dosimetry, and dose reporting among COG institutions. The lack of a standardized approach 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. We are also critically evaluating the introduction of modern techniques for TBI using VMAT.
Supplementary Material
Acknowledgments—
The authors thank Ms. Heidi M. Pusztay from COG Communications and Publications for her assistance with the survey distribution.
This research has been supported by grants U10CA180886 from the National Cancer Institute, National Institute of Health to the Children’s Oncology Group and U24CA180803 from the Imaging and Radiation Oncology Core Group.
Footnotes
Disclosures: none.
Research data are included in this published article and its supplementary information files.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ijrobp.2021.07.1715.
Poster presentation at the annual meeting of the American Society for Radiation Oncology, October 2020.
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