Total lymphoid irradiation in the Wistar rat: technique and dosimetry

The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization of lymph nodes, thymus and spleen. A practical advantage was found in the simultaneous irradiation through two portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetry, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments.     

Total body irradiation in France in the past twenty years]

A review of the activity and techniques of total body irradiation (TBI) in France in the last 20 years is presented. In order to have on overall view of the activity and techniques of total body irradiation in France, the group of cancer centre radiation oncologists sent a questionnaire to all the cancer centres or public hospitals radiotherapy departments dealing with this treatment. Thirty-six questionnaires were sent and thirty-one departments answered. Three departments do not offer this treatment. Five departments did not answer. Results, therefore, concern the activity of the 28 departments that agreed to give detailed and clear answers. A total of 10 630 TBIs have been documented, 850 to 900 TBI have been done each year since 1995. Single fraction TBIs are used in only five centres and are being progressively abandoned. For multiple-fraction TBIs, the techniques described here are the ones used in 1999, at the time the questionnaires were sent. A majority (98%) of the teams used linear accelerators. The collected data are synthesised in tables. Nowadays, single fraction TBIs are only indicated in exceptional cases. Most of the TBIs are fractionated in six twice-daily fractions with pulmonary shielding to limit the dose between 6 and 11 Gy depending on departments' protocols and pathologies.     

The dosimetry of 60Co total body irradiation.

The dosimetry characteristics of a single source ⁶⁰Co total body irradiation (TBI) facility have been studied. The dose distribution for AP-PA irradiation in an adult size and an infant size phantom was measured in detail using thermoluminescent dosimeters. A 10% homogeneity relative to the midline dose was found over most of the body. An increase of 10% relative to midline dose was noted in the thoracic region because of lower density lung tissue. A relative decrease of more than 10% was found in the head region because of the reduced beam intensity away from the central axis and reduced scatter volume. Dose in the abdomen was homogeneous to ± 5%.     

Total body irradiation in non-Hodgkin's lymphoma.

Between October 1972 and August 1977, low-dose fractionated total body irradiation (TBI), 150–300 rad, was selected for 48 patients with previously untreated non-Hodgkin's lymphoma staged II, III and IV. In 63% of the patients the disease had a nodular pattern; there were no patients with diffuse histiocytic lymphoma.All but 2 patients responded to TBI. The 4-year actuarial survival was 71% for the nodular group and 57% for the diffuse group.There were no acute symptoms during the course of treatment and no mortality associated with the treatment. Seventeen per cent of the patients developed transient platelet counts less than 30,000/mm³. Four required hospitalization for correction of thrombocytopenia and/or infection.The majority of patients who failed more than 3 months after initial complete remission were placed back in remission with either chemotherapy, TBI, or local irradiation. Patients with persistent disease after TBI showed a less favorable response with chemotherapy.A selected group of 15 patients in relapse after chemotherapy or localized radiotherapy were treated with TBI. Eleven responded to treatment, while 4 showed no useful response. The median survival for this group was slightly over 2 years. Twenty per cent developed transient platelet counts less than 30,000/mm³.     

Total body irradiation with a sweeping beam

A technique for total body irradiation, in which the patient lies in the prone or supine position in the beam of a conventional column mounted 4 MV linear accelerator, is described. A sufficiently large radiation field is obtained by rotating the beam in a vertical plane about the source (i.e., sweeping beam) at a source-to-skin distance of 190 cm on the vertical axis. The variation of the midplane dose is less than +/- 5% in parallel-opposed beams, when attenuators are placed over the region containing the lungs and bolus is employed around the head and legs. The percentage depth dose for the sweeping beam is identical to that of a stationary beam for the same collimator setting and source-to-skin distance. A method for monitoring the dose to the patient by means of a thimble ionization chamber located on the vertical beam axis is outlined. The average dose rates used are between 5 and 10 cGy/min. The design and placement of lung attenuators is simple. The treatment technique with the sweeping beam requires minimal modification of a treatment unit and can be applied on any unit which has a head swivel option.     

Total body irradiation in chronic myeloid leukemia

Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following busulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.     

Total body irradiation and pneumonitis risk: a review of outcomes

A review was undertaken of all patients treated at Royal Adelaide Hospital, South Australia with total body irradiation (TBI) for the purpose of assessing the incidence of interstitial pneumonitis (IP) and possible prognostic factors for its development. The aim was also to assess the impact of IP and other prognostic factors on long-term survival outcome following bone marrow transplantation. A total of 84 patients received TBI, with 12 Gy in six fractions delivered using two different instantaneous dose rates of 7.5 and 15 cGy min(-1). This series included 26 cases of acute lymphoblastic leukaemia, 26 of multiple myeloma and 15 of acute myelogenous leukaemia. On multivariate analysis, a higher dose rate was independently significant for an increased risk of IP.     

Long-term complications of total body irradiation in adults

PURPOSE: To report long-term pulmonary, thyroid, and ocular complications in patients who had conditioning regimens including total body irradiation (TBI) before bone marrow transplantation (BMT). METHODS AND MATERIALS: Between June 1986 and December 1995, 478 patients received TBI in our institution. The present study includes 186 adult patients who had complete remission lasting one year or more after BMT. There were 108 males and 78 females. Median age was 36.5 years (range 15-60). Initial diagnoses were lymphomas (50%), acute lymphoid leukemias (16%), acute myeloid leukemias (16%), chronic myeloid leukemia (13%), aplastic anemia (3%), and myelodysplasia (2%). At the time of BMT, 43.5% of patients were in complete response and 56.5% in partial response. Treatment consisted of a single dose TBI at 10 Gy in 9% and fractionated TBI delivering 12 to 13.5 Gy in 6 fractions in 91%. From 1986 to October 1991, TBI was performed in lateral position with 9 MV energy (57% of patients) and thereafter in alternate prone and supine positions with 15 MV energy (43%). Chemical conditioning regimen was cyclophosphamide (60 mg/kg at D-4 and D-3) in 69% and CBV (cyclophosphamide 1500 mg/m(2) from D-6 to D-3, BCNU 300 mg/m(2) at D-6, VP-16 200 mg/m(2) from D-6 to D-4) in 25%. Fifty eight percent of patients received autologous and 42% allogeneic BMT. All patients had clinical, biologic, and functional examinations at one-year intervals. RESULTS: Median follow-up from BMT was 49 months (range 12-136). Late pulmonary effects were observed only in functional explorations, without clinical effect, including restrictive syndrome in 8% and alteration in the diffusing capacity of carbon monoxide in 12%. No patient showed clinical thyroid symptoms, and 10% developed biologic dysfunction: hypothyroidism (6.5%), thyroiditis (3%), and Basedow disease (0.5%). Ocular complications occurred in 29.5%, including cataract (15%), dry syndrome (13%), and keratitis (1.5%). In univariate and multivariate analysis, pulmonary complications were statistically increased by chronicle graft vs. host disease (GVHD) vs. no (p = 0.02), prone and supine vs. lateral TBI position (p = 0.02), and with 15 MV vs. 9 MV beam energy (p = 0.02). Cataract occurred less frequently with fractionated than with single-dose TBI (p = 0.000002). No differences were observed regarding age, sex, initial diagnosis, status at the time of BMT, conditioning chemotherapy regimen, and total dose of TBI. CONCLUSION: From this retrospective study it was shown that long-term complications of TBI were not symptomatic in most patients. The role of parameters of irradiation and especially position of treatment and beam energy should be emphasized and assessed with a longer follow-up.     

Cobalt-60 total body irradiation dosimetry at 220 cm source-axis distance

Adults with acute leukemia are treated with cyclophosphamide and total body irradiation (TBI) followed by autologous marrow transplants. For TBI, patients seated in a stand angled 45° above the floor are treated for about 2 hours at 220 cm source-axis distance (SAD) with sequential right and left lateral 87 cm × 87 cm fields to a 900 rad mid-pelvic dose at about 8 rad/min using a 5000 Ci cobalt unit. Maximum (lateral) to minimum (mid-plane) dose ratios are: hips—1.15, shoulders—1.30, and head—1.05, which is shielded by a compensator filter. Organ doses are small intestine, liver and kidneys—1100 rad, lung—1100–1200 rad, and heart-1300 rad. Verification dosimetry reveals the prescribed dose is delivered to within ± 5%. Details of the dosimetry of this treatment are presented.     

Total body irradiation for treatment of haematological diseases

The present status of total body irradiation (TBI) as a part of the treatment of haematological diseases was discussed during a separate symposium at the 5th Annual ESTRO meeting at Baden-Baden. The experimental techniques applied in Europe, the dosimetry for TBI, the radiobiological aspects and the late effects after TBI have been reviewed. For specific geometries, precautions have to be taken to avoid increased dose contributions at the skin due to electrons scattered from the wall behind the patient. CT data can be useful for the individualization of the exposure regimen of patients with extreme variations in lung anatomy or lung density. An appreciable number of centres apply in vivo dosimetry, however, special care is needed for the correct interpretation of the dosimeter readings. A number of late effects, including induction of cataract and secondary tumours has been observed after TBI. The techniques applied for TBI at the various centres and the temporal administration of the dose show wide variations. At present, the patient material is too heterogeneous to draw any conclusion about an optimum schedule for a TBI regimen. Further cooperation between clinicians, radiobiologists and radiation physicists has to be established to achieve consistency and further improvement of the results after TBI.     

Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up

Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.     

Total body irradiation using helical tomotherapy: Set-up experience and in-vivo dosimetric evaluation

PurposeHelical Tomotherapy (HT) appears as a valuable technique for total body irradiation (TBI) to create highly homogeneous and conformal dose distributions with more precise repositioning than conventional TBI techniques. The aim of this work is to describe the technique implementation, including treatment preparation, planning and dosimetric monitoring of TBI delivered in our institution from October 2016 to March 2019.Material and methodPrior to patient care, irradiation protocol was set up using physical phantoms. Gafchromic films were used to assess dose distribution homogeneity and evaluate imprecise patient positioning impact. Sixteen patients’ irradiations with a prescribed dose of 12 Gy were delivered in 6 fractions of 2 Gy over 3 days. Pre-treatment quality assurance (QA) was performed for the verification of dose distributions at selected positions. In addition, in-vivo dosimetry was carried out using optically stimulated luminescence dosimeters (OSLD).ResultsPlanning evaluation, as well as results of pre-treatment verifications, are presented. In-vivo dosimetry showed the strong consistency of OSLD measured doses. OSLD mean relative dose differences between measurement and calculation were respectively +0,96% and ?2% for armpit and hands locations, suggesting better reliability for armpit OSLD positioning. Repercussion of both longitudinal and transversal positioning inaccuracies on phantoms is depicted up to 2 cm shifts.ConclusionThe full methodology to set up TBI protocol, as well as dosimetric evaluation and pre-treatment QA, were presented. Our investigations reveal strong correspondence between planned and delivered doses shedding light on the dose reliability of OSLD for HT based TBI in-vivo dosimetry.     

Comparative 60Co total body irradiation (220 cm SAD) and 25 MV total body irradiation (370 cm SAD) dosimetry

Adults with acute leukemia and malignant lymphoma in relapse after conventional therapy are treated with cyclophosphamide and total body irradiation (TBI) followed by autologous bone marrow transplants. For cobalt TBI, patients seated in a stand angled 45° above the floor are treated in a single fraction with sequential right and left lateral 87 cm ×87 cm fields at 220 cm source-axis distance (SAD) using a 5000 Ci cobalt unit. Typical lateral diameters, mid-plane dose rates, mid-plane doses, and maximum doses are: Hips, 34 cm, 8 rad/min, 900 rad, and 1050 rad; and shoulders, 38 cm, 7.7 rad/min, 800 rad, 1080 rad. The estimated lung dose is 1000 to 1100 rad. A compensator limits the dose to the head to 1000 rad. Estimated organ doses are: small intestine, liver and kidneys-1100 rad, and heart-1200 rad. Phantom dosimetry and dosimetry on patients treated reveals that these doses are delivered within 5 % accuracy. Patient tolerance of treatment, and some biological considerations of low dose rate therapy are reviewed. Certain dosimetry features of an alternate treatment at 370 cm SAD, using 25 MV photons are also presented.     

Biological basis of total body irradiation]

A comprehensive understanding of the radiobiological bases of total body irradiation (TBI) is made difficult by the large number of normal and malignant tissues that must be taken into account. In addition, tissue responses to irradiation are also sensitive to associated treatments, type of graft and a number of patient characteristics. Experimental studies have yielded a large body of data, the clinical relevance of which still requires definite validation through randomized trials. Fractionated TBI schemes are able to reduce late normal tissue toxicity, but the ultimate consequences of the fractional dose reduction do not appear to be equivocal. Thus, leukemia and lymphoma cells are probably more radiobiologically heterogeneous than previously thought, with several cell lines displaying relatively high radioresistance and repair capability patterns. The most primitive host-type hematopoietic stem cells are likely to be at least partly protected by TBI fractionation and may hamper late engraftment. Similarly, but with possibly conflicting consequences on the probability of engraftment, the persistence of a functional marrow stroma may also be fractionation-sensitive, while higher rejection rates have been reported after T-depletion grafts and fractionated TBI. In clinical practice (as for the performance of relevant clinical trials), the influence of these results are rather limited by the heavy logistic constraints created by a sophisticated and time-consuming procedure. Lastly, clinicians are now facing an increasing incidence of second cancers, at least partly induced by irradiation, which jeopardize the long-term prospects of otherwise cured patients.     

Biological dosimetry after total body irradiation (TBI) for hematologic malignancy patients

PURPOSE: Biological dosimetry based on scoring chromosomal aberrations in peripheral lymphocytes was compared to physical dosimetry done for total body irradiation (TBI) before bone marrow transplantation (BMT) in patients with hematologic malignancies. PATIENTS AND METHODS: Fifteen patients undergoing TBI were included in the study. A total dose of 12 Gy in 2.5 days was fractionated into 2 or 3 daily doses of 1.8 Gy delivered by a 18 MV linear accelerator (dose rate: 15.8 cGy x min(-1)). Blood samples were obtained from patients before irradiation and after the first fraction of 1.8 Gy. A standard dose-effect curve was established by in vitro irradiation of healthy volunteer lymphocytes. Chromosomal aberrations were scored by the conventional cytogenetics (CCG) method for unstable anomalies and by fluorescent in situ hybridization (FISH) for stable anomalies. RESULTS: Healthy donor lymphocytes before irradiation yielded 0.1% dicentrics and 0.3% translocations of chromosome 4 (Chr. 4), that is 2.5% for the whole genome. Patients before irradiation had 2% of dicentrics and 1.1% of chromosome 4 translocations. The biologically estimated dose of the 15 patients after exposure to 1.8 Gy was 1.93 Gy (95% CI: 1.85-2.05) according to CCG, and 2.06 Gy (95% CI: 1.75-2.15) by FISH. CONCLUSION: The dose estimated by biological dosimetry, in this case of homogeneously distributed radiation of TBI agrees well with the absorbed radiation dose calculated by physical dosimetry.