Total Body Irradiation Treatment Research Articles

SU-GG-T-118: Investigation of Intensity Modulated Compensator-Based TBI for Small Children

Purpose: A study was performed to determine the feasibility of using inversely optimized solid modulators designed on a commercial treatment planning system for the purpose of total body irradiation (TBI) of small children. It is suggested that solid modulators will provide improved dose distributions relative to traditional TBI techniques as well as reduce errors in the setup of blocks since only a single device needs to be placed per field. Method and Materials: A brass compensator model for a clinical 18 MV photon therapy beam was constructed for the purposes of intensity modulated radiation therapy. Using this model, two TBI treatment plans were constructed to deliver a single, AP beam to a small anthropomorphic phantom, representative of a six to twelve month old child. A third treatment plan was constructed using opposed AP/PA fields. Phantom irradiations proceeded according to these plans. TLD measurements were obtained at several anatomical positions for comparison to planned values, and traditional TBI plans were created for comparison to the intensity modulated plans. All plans used extended treatment distances. Results: The TLD results indicate that dose delivery within +/− 5% of the planned value is achievable to all anatomical sites with the exception of the mediastinum and neck. This is attributed to the difficulty of providing full dose to the mediastinum, while reducing lungdose to acceptable levels. However, the compensator‐based results are still clinically superior to the expected dose of standard TBI techniques. Conclusion: Solid modulator‐based TBI in small children can be successfully implemented using commercially available planning systems in either a single or dual field technique. Compared to traditional techniques, modulator‐based TBI results in greater dose homogeneity, reduced hot spots, and the ability to more accurately reduce dose to selected anatomical areas while reducing the number of blocks required to uniformly deliver dose.

SU-GG-T-485: A Statistical and Radiobiological Analysis of Circulating Blood Heterogeneity in Conformal TBI

Purpose: Improvements in delivery techniques of Total Body Irradiation (TBI) using Tomotherapy® and intensity modulated radiation therapy (IMRT) have been proven feasible. Despite the promise of improved dose conformality, application of these “sequential” techniques has been hampered by concerns over dose heterogeneity to circulating blood. The present study was conducted to provide quantitative evidence regarding the potential clinical impact of this heterogeneity. Method and Materials: Blood perfusion was modeled analytically as possessing linear, sinusoidal motion in the cranio-caudal dimension. The average perfusion period for human circulation was estimated to be 50 s. Sequential treatment delivery was modeled as a Gaussian-shaped dose cloud with a 10 cm length that traversed a 183 cm patient length at a uniform speed. Total dose to circulating blood voxels was calculated via numerical integration and normalized to 2 Gy per fraction. Dose statistics and equivalent uniform dose (EUD) were calculated for relevant treatment times, radiobiological parameters, blood perfusion rates and fractionation schemes. Results: The dose received by individual blood voxels exhibited asymmetric behavior that depended on coherence between the blood velocity, circulation phase and beam velocity. Heterogeneity increased with perfusion period and decreased with treatment time. Notwithstanding, heterogeneity was less than +/− 10% for perfusion periods less than 150 s. The EUD was compromised for radiosensitive cells, long perfusion periods and short treatment times. However, the EUD was unaffected (within 10%) for perfusion periods of less than 150 s or treatment times of 20 minutes or greater. Treatment over 6 fractions improved the EUD per fraction such that all parametric combinations resulted in unaffected EUD. Conclusion: Dose heterogeneity in circulating blood cells is clinically acceptable for typical treatment times, perfusion rates and cell types. Development of conformal, sequential TBI treatment techniques should not be withheld based on concerns over circulating blood dose heterogeneity.

鉄過剰負荷ならびにＸ線全身照射が低タンパク質食摂取マウスの骨髄と肝臓の酸化障害に及ぼす影響

We examined whether excess iron supplementation to a low-protein diet (7% casein) caused oxidative damage, and whether an additional treatment of total body irradiation (TBI) enhanced this oxidative damage. A preliminary study showed that more than 1 week of feeding a low protein diet decreased plasma iron, increased liver non-heme iron, and also enhanced TBI-induced chromosomal damage in bone marrow. Based on these findings, mice were fed on the low-protein diet for 1 week and then on the same diet with and without excess iron (2.5% carbonyl iron) for an additional week, before being exposed to TBI (0.5Gy) or not. Iron supplementation significantly increased the non-heme iron and lipid peroxidation in the liver, but did not increase chromosomal damage in the bone marrow. Simultaneous treatment with TBI and iron supplementation did not influence the degree of chromosomal damage or lipid peroxidation due to each treatment. These findings indicate that excess iron supplementation with a low-protein diet did not induce chromosomal damage in the bone marrow, but did induce marked lipid peroxidation in the liver.

Clinical application of GAFCHROMIC ® EBT film for in vivo dose measurements of total body irradiation radiotherapy

The GAFCHROMIC ® EBT film model is a fairly new film product designed for absorbed dose measurements of high-energy photon beams. In vivo dosimetry for total body irradiation (TBI) remains a challenging task due to the extended source-to-surface distance (SSD), low dose rates, and the use of beam spoilers. EBT film samples were used for dose measurements on an anthropomorphic phantom using a TBI setup. Additionally, in vivo measurements were obtained for two TBI patients. Phantom results verified the suitability of the EBT film for TBI treatment in terms of accuracy, reproducibility, and dose linearity. Doses measured were compared to conventional dosimeter measurements using thermoluminescent dosimeters (TLDs), resulting in an agreement of 4.1% and 6.7% for the phantom and patient measurements, respectively. Results obtained from the phantom and patients confirm that GAFCHROMIC ® EBT films are a suitable alternative to TLDs as an in vivo dosimeter in TBI radiotherapy.

Senescence-unrelated impediment of osteogenesis from Flk1+ bone marrow mesenchymal stem cells induced by total body irradiation and its contribution to long-term bone and hematopoietic injury

Ionizing irradiation is a common treatment for cancer patients and can result in adverse side effects affecting the bone and hematopoietic systems. Although some studies have demonstrated that ionizing radiation can induce apoptosis and senescence in hematopoietic stem cells, little is known about the effects of total body irradiation (TBI) on bone marrow (BM) mesenchymal stem cells (MSC). The objectives of this study were to determine the response of BM MSC to irradiation stress, such as cellular senescence and differentiation potential in BM MSC, and the clinical significance of these changes caused by TBI. At different time points after TBI, Flk1+ MSC were isolated from BM of male C57BL/6 mice and analyzed for colony forming units-fibroblast (CFU-F), cellular senescence-related indices and osteogenic potential. Bone histomorphometric analysis, immunohistochemical staining and bone mineral density (BMD) tests were performed to detect the effects of TBI on bone and the hematopoietic system. TBI reduced the pool of BM mesenchymal stem/progenitor cells, and altered osteoblast differentiation ability of BM MSC evidenced by changes in TAZ expression. These alterations, sustained up to 28 days post-irradiation, were independent of cellular senescence in BM MSC. Irradiated mice showed obvious bone loss and destruction of the hematopoietic osteoblastic niche, which is normally comprised of spindle-shaped N-cadherin-expressing osteoblasts. TBI treatment results in impairment in BM MSC, which might be responsible for bone loss and, at least partially, for impaired hematopoiesis.

Dosimetry and verification of 60Co total body irradiation with human phantom and semiconductor diodes

Total Body Irradiation (TBI) is a form of radiotherapy used for patients prior to bone marrow or stem cell transplant to destroy any undetectable cancer cells. The dosimetry characteristics of a 60Co unit for TBI were studied and a simple method for the calculation of the prescribed dose for TBI is presented. Dose homogeneity was verified in a human phantom. Dose measurements were made in water phantom (30 × 30 × 30 cm3), using farmer ionization chamber (0.6 cc, TM30010, PTW) and a parallel plate ionization chamber (TM23343, PTW). Point dose measurements for AP/PA irradiation were measured in a human phantom using silicon diodes (T60010L, PTW). The lung dose was measured with an ionization chamber (0.3 cc, TM31013). The validity of the proposed algorithm was checked at TBI distance using the human phantom. The accuracy of the proposed algorithm was within 3.5%. The dose delivered to the mid-lobe of the lung was 14.14 Gy and it has been reduced to 8.16 Gy by applying the proper shield. Dose homogeneity was within ±7% for all measured points. The results indicate that a good agreement between the total prescribed and calculated midplane doses can be achieved using this method. Therefore, it could be possible to use calculated data for TBI treatments.

Allogeneic Stem Cell Transplantation Should Be Performed in First Complete Remission in Adults with Acute Lymphoblastic Leukemia; Strong Antileukemic Activity of Chronic Graft-Versus-Host Disease.

Purpose: The role of allogeneic stem cell transplantation (SCT) for adult acute lymphoblastic leukemia (ALL) remains unclear because interpretation of transplantation outcome is complicated by the criteria used to select patients for transplantation and by the relatively small number of patients studied. Moreover, whether SCT from an unrelated donor could be a treatment option of equal value in a case lacking a compatible related donor remains controversial. The aim of the present study was to determine the graft-versus-leukemia (GVL) effect and risk factors affecting outcome of 218 adults with ALL who received allogeneic SCT during the last 10 years (1995 to 2004).Patients and Methods: The study population was 218 consecutive adults receiving an allogeneic SCT from matched sibling (n=162) or unrelated (n=56; 40 matched, 16 mismatched) donors at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea. Their median age was 30 years (range, 15–61 years). One hundred eighty-three (83.9%) patients had high-risk criteria, and of these, 69 (31.7%) had t(9;22)/BCR-ABL and 7 (3.2%) had t(4;11)/MLL-AF4. One hundred sixty-five patients (75.7%) were transplanted in first complete remission (CR1); 23 (10.5%) in CR2; and 30 (13.8%) were resistant to chemotherapy before transplantation. Most patients (n=206, 94.5%) received a preparative treatment of total body irradiation (TBI)-containing regimen (TBI/cyclophosphamide for CR1, TBI/cytarabine/melphalan for >CR1). Graft-versus-host disease (GVHD) prophylaxis was attempted by administering calcineurin inhibitor (cyclosporine for sibling, tacrolimus for unrelated) plus methotrexate.Results: With a median follow-up of 52 months (range, 15+ to 130+ months) after SCT, the 5-year probability of disease-free survival (DFS) was 51.3%±3.5% for all patients; 62.4%±4.3% for patients in CR1; and 11.3%±4.4% for patients in >CR1 at transplantation. There was no difference in DFS for sibling and unrelated transplant patients in CR1 (65.2%±4.3% v 62.3%±8.0%). Multivariate Cox regression analysis showed that the most powerful predictive factor affecting relapse and DFS was disease status at transplantation (CR1 v >CR1, p<0.001). The presence of chronic GVHD was also found to be significantly associated with favorable outcome (p<0.001).Conclusion: Our data in combination with recent studies suggest that matched related or unrelated allogeneic SCT should be performed in CR1 in adults with ALL. Further studies to develop treatment strategies to reduce leukemic cell burden and to enhance GVL effect are needed. The indications for allogeneic SCT also should be continuously evaluated.

SU-FF-T-226: A Dosimetric Evaluation of a New MOSFET Radiation Dosimeter for Total Body Irradiation

Purpose: To evaluate the use of a new metal oxide semiconductor field effect transistor (MOSFET) as an in vivo dosimeter for patients receiving total body irradiation (TBI). Method and Materials: The dose responses of the MOSFET dosimeters are compared to that of thermoluminescent dosimeters (TLDs) during TBI treatments of 4 patients. Each patient is treated AP/PA with 60Co irradiation, a field size of 44 × 44 cm2 at isocenter, and an SAD of 338.2 cm. One MOSFET dosimeter and 4 TLD crystals are placed at the entrance and exit of five anatomical sites: head, chest, lung, umbilicus, and pelvis. Additionally, the dosimeters are positioned at a calibration point in air to normalize the dosimeter readings. The MOSFET dosimeters are read instantaneously with a digital hand held reader, and the TLDs are measured with a TLD reader. Results: The measured midline dose rates and calculated treatment times of the MOSFET dosimeters and TLDs are compared. The average deviations of the MOSFETs from the TLDs are 6% at the head, 7% at the chest, 3% at the lung, 1% at the umbilicus, and 4% at the pelvis. The maximum deviation of the MOSFETs from the TLDs is 11.5%, and the minimum deviation is 0.94%. The MOSFET calculated treatment times are within 5% of the TLD calculated treatment times. Three dosimeters failed during the treatments. Conclusion: These results show that the new MOSFET dosimeters are an adequate and efficient measurement system for TBI treatments. The cause of dosimeter failure has not been determined as further analysis and experience with the MOSFET dosimeters are necessary. It is recommended that more than one MOSFET dosimeter is used per site for TBI treatment in case of dosimeter failure.

In vivo thermoluminescence dosimetry for total body irradiation.

An improvement in the clinical results obtained using total body irradiation (TBI) with photon beams requires precise TBI treatment planning, reproducible irradiation, precise in vivo dosimetry, accurate documentation and careful evaluation. In vivo dosimetry using LiF Harshaw TLD-100 chips was used during the TBI treatments performed in our department. The results of in vivo thermoluminescence dosimetry (TLD) show that using TLD measurements and interactive adjustment of some treatment parameters based on these measurements, like monitor unit calculations, lung shielding thickness and patient positioning, it is possible to achieve high precision in absorbed dose delivery (less than 0.5%) as well as in homogeneity of irradiation (less than 6%).

TBI treatment planning using the ADAC Pinnacle Treatment Planning System

The use of total-body irradiation (TBI) for the purpose of bone marrow transplant is an established procedure at many institutions. In our institution, the TBI monitor unit (MU) calculation starts with the calibration done at the same conditions of the treatment source-axis distance (SAD) = 350 cm for the field size of 40 × 40 cm at a depth of 10 cm). The dose rate in the central axis of the beam at this distance is measured in cGy/MU. A tissue phantom ratio table obtained in the condition of treatment together with off-axis factors is used in the MU calculation for each particular patient. The treatment is done with the patient lying on his/her back and the beam is delivered using right-to-left lateral beams. Due to different thickness’ of the patient, a lead compensator is built to compensate for the different parts of the body. Eighteen or 10-MV x-ray photons are used in the TBI treatment, and a 1-cm-thick lucite plate is placed near the patient to increase the dose to the surface. In vivo dosimetry using diodes is done to verify the calculations. The Rando-Phantom™ was computed-tomography scanned from the head to the abdomen with 1-cm-thick slices covering 70 cm of the phantom. This simulated the TBI treatment and correlated the calculations done by the ADAC treatment planning system to film measurements at the pelvis and lung levels. These results agreed within 5% of the measured dose. The use of the upper arms to reduce the dose to the lungs and optimization of dose using special compensators has been studied using the treatment planning system. Use of the multileaf collimator to compensate the dose received by the patient has been explored in this paper.

Changes in the size and location of kidneys from the supine to standing positions and the implications for block placement during total body irradiation

Purpose: The use of total body irradiation (TBI) as a conditioning regimen for bone marrow transplantation often calls for partial transmission kidney blocks. These blocks are frequently designed based on the location of the kidneys during the abdominal computerized tomography (CT) scan. At our institution, TBI patients are treated in the standing position. As the kidneys can shift with different patient positions, a study was undertaken to evaluate the magnitude of the changes in the size and location of the kidneys from the supine CT position to the upright treatment position.Methods and Materials: Intravenous contrast was administered to 15 patients. The patients were initially positioned supine on a simulator table and then positioned upright immediately in front of the image intensifier. PA radiographs were obtained with the patients in both positions. Changes in the size of the kidneys and their location relative to the vertebral bodies were noted.Results: In going from the supine to upright position, all the kidneys shifted inferiorly between 0.5 cm and 7.5 cm with an average of 3.6 cm. Most of the kidneys also shifted in the transverse dimension and incurred a change in width. The range of the transverse shift was from 0.9 cm in the lateral direction to 4.9 cm medially. The maximum width broadening was 1.2 cm and the maximum decrease in width was 1.8 cm.Conclusions: When compared to the supine position, patients in the upright position show a dramatic inferior shift of the kidneys with other obvious, but less predictable, changes. For TBI treatments delivered in the upright position, kidney blocks should not be designed on the basis of supine abdominal CT scans.

Amifostine (WR2721) for dose escalation in marrow-ablative treatment of leukaemia

The in vivo effect of the radiochemoprotectant Amifostine on the therapeutic efficacy of marrow ablative treatment with cyclophosphamide (CP) and total body irradiation (TBI) followed by bone marrow transplantation (BMT) was studied in normal rats as well as in the Brown Norway rat acute myelocytic leukaemia (BNML) model. In normal rats, when the dose of TBI was escalated and the CP dose was kept constant, pretreatment with Amifostine yielded a positive dose modification factor of 1.26. No significant improvement was found after Amifostine pretreatment when the TBI dose was kept constant and CP dose escalated. When leukaemic rats received CP as the only antileukaemia treatment, Amifostine pretreatment did not lead to a reduction in the antileukaemic efficacy of CP, although protection against treatment-related mortality was observed. In the CP only groups, 9 out of 40 animals died of treatment-related toxicity, compared with none of the 40 animals in the Amifostine pretreatment groups. When applying the maximum tolerated treatment of CP and TBI in various combinations to leukaemic rats, 25 out of 36 rats died from treatment-related toxicity, whilst pretreatment with Amifostine reduced this to 11 out of 36, ( P=0.002). Of those animals which survived the CP+TBI conditioning treatment, 10 out of 25 in the Amifostine pretreatment group were cured, versus 8/11 in the CP+TBI only control group ( P=0.146). In conclusion, incorporation of Amifostine as a radiochemoprotectant in a marrow-ablative conditioning regimen allows the use of escalated doses of chemoradiotherapy without reducing the antileukaemic efficacy.

Acute immunosuppression and syngeneic bone marrow transplantation in ocular autoimmunity abort disease, but do not result in induction of long-term protection

Acute immunosuppression induced by total body irradiation (TBI) or cyclophosphamide (Cy) treatment, followed by syngeneic bone marrow transplantation (SBMT), was reported to be effective in inducing long-term tolerance in some autoimmune disease models. We examined the efficacy of this approach in the mouse model of experimental auto-immune uveoretinitis (EAU). Development of EAU induced by the interphotoreceptor retinoid binding protein (IRBP) was abolished almost completely by either TBI or Cy treatment, followed by SBMT, instituted one week after priming. In parallel, IRBP-specific delayed-type hyper-sensitivity (DTH) responses and lymph node cell proliferation were strongly suppressed or abolished. However, when these IRBP-immunized, lympho-ablated and BM reconstituted mice were rechallenged with the immunizing antigen seven weeks after the primary immunization, they were not protected from developing disease, despite the fact that DTH and lymph node cell proliferation to the antigen were suppressed relative to controls. TBI treatment appeared somewhat more effective than Cy treatment as judged by its more profound effect on immunological responses. These results demonstrate the ability of acute immunosuppression followed by reconstitution of the immune system to inhibit the development of EAU, although long-term protection from disease was not achieved.

The radiobiological basis of total body irradiation.

Total body irradiation (TBI) is an all-pervasive systemic treatment modality which is well suited to the sterilization of small numbers of widely dispersed radiosensitive cells. This makes it attractive for the treatment of leukaemia or lymphoma in remission. It is unlikely that hypoxia or repopulation will be a problem in TBI treatment of leukaemia, and clonal resistance to radiation occurs less readily than to drugs. Leukaemic cells are often radiosensitive with poor repair capacities but considerable variation is seen in laboratory studies and leukaemias may be highly individual. It is possible that programmed cell death (apoptosis) contributes to leukaemic cell killing and variability of apoptosis may give rise to biological individuality. Molecular methodologies may now be used to monitor leukaemic cell populations and may enable semi-quantitative predictive assays of radiosensitivity. When the malignant cell population is not uniformly distributed throughout the body, as in lymphoma, non-uniform TBI is appropriate, e.g. by addition of local boosts or by the combination of TBI with radiolabelled antibody treatment. Major side-effects mostly relate to critical organs with late-responding characteristics (low alpha/beta ratio, high sensitivity to fraction size or dose rate). The radiobiological basis of developmental effects in children is not well understood. In future, improved selectivity of TBI may come from molecular biological strategies to sensitize malignant cells and to protect normal tissues.

Total body irradiation with an Arc and a gravity-oriented compensator

To deliver uniform dose distributions for total-body irradiation (TBI) with an arc field and a gravity-oriented compensator. This technique allows the patient to be treated lying on the floor in a small treatment room. Through the sweeping motion of the gantry, a continuous arc field can deliver a large field to a patient lying on the floor. The dose profile, however, would not be uniform if no compensator were used, due to the effects of inverse square variation of beam intensity with distance as well as the slanted depth in patient. To solve this problem, a gravity-oriented compensator made of cerrobend alloy was designed. This compensator has a cross-section of an inverted isosceles triangle, with the apex always pointing downward, due to gravity. By properly selecting the thickness of the compensator, the width of the base, and the distance between the pivots to the base, the difference in the path length through the compensator can be made just right to compensate the effects of inverse-square and slanted depth, thus producing a uniform dose profile. Arc fields with a gravity-oriented compensator were used for 6, 10, 15, and 18 MV photon beams. The arc field can cover a patient with a height up to 180 cm. The field width was chosen from 32 to 40 cm at the machine isocenter. The optimal thickness of the compensator was found to be 2.5 cm, and its base was 25 cm wide. The distance from the pivot points to the flat surface of the compensator proximal to the beam ranges from 13 to 14 cm for different beam energies. The dose uniformity at a depth of 10 cm is within +/-5% for all beam energies used in this study. Highly uniform dose profiles for TBI treatments can be delivered with an arc and a gravity-oriented compensator. The proposed technique is simple and versatile. A single compensator can be used for all energies, because the amount of compensation can be adjusted by changing the distance to the pivot and/or the field size.

The influence of x-ray energy on lung dose uniformity in total-body irradiation

Purpose : In this study we examine the influence of x-ray energy on the uniformity of the dose within the lung in total-body irradiation treatments in which partial transmission blocks are used to control the lung dose. Methods and Materials : A solid water phantom with a cork insert to simulate a lung was irradiated by x-rays with energies of either 6, 10, or 18 MV. The source to phantom distance was 3.9 meters. The cork insert was either 10 cm wide or 6 cm wide. Partial transmission blocks with transmission factors of 50% were placed anterior to the cork insert. The blocks were either 8 or 4 cm in width. Kodak XV-2 film was placed in the midline of the phantom to record the dose. Midplane dose profiles were measured with a densitometer. Results : For the 10 cm wide cork insert the uniformity of the dose over 80% of the block width varied from 6.6% for the 6 MV x-rays to 12.2% for the 18 MV x-rays. For the 6 cm wide cork insert the uniformity was comparable for all three x-ray energies, but for 18 MV the central dose increased by 9.4% compared to the 10 cm wide insert. Conclusion : Many factors must be considered in optimizing the dose for total-body irradiation. This study suggests that for AP/PA techniques lung dose uniformity is superior with 6 MV irradiation. The blanket recommendation that the highest x-ray energy be used in TBI is not valid for all situations.

Lateral scatter correction algorithm for percentage depth dose in a large-field photon beam

Differences between the scatter conditions of dosimetry and treatment situation are more important in the case of large-field photon beams than in standard ones. In the former, the scattering volume is defined by the phantom cross section; in the latter, the radiation field size. Two factors should be considered: the thickness and the cross section of the phantom. Both of them have an effect on the Percentage Depth Dose (PDD) distribution. In a previous study we addressed the influence of backscatter thickness on dose delivered. The aim of this work is to measure the effect of cross section phantom on the PDD curves under our TBI treatment conditions. Results showed a strong dependence of the PDDs on this parameter. A semi-empirical expression has also been derived to calculate (within 0.5% uncertainty) the Lateral scatter Correction Factor (LCF). The model of LCF states a linear dependence on depth whilst slope of these curves depends exponentially on distance to the lateral surface. The algorithm is being applied to our practical Total Body Irradiation (TBI) procedure.

Eye shielding for patients treated with total body irradiation

The incidence of cataracts in patients who have received total body irradiation (TBI) is about 20% and increases to 40% if the patient is treated for graft-versus-host disease. At our institution, all TBI patients are treated with two lateral opposed 24 MV photon fields. No attempt is usually made to shield the eyes during the TBI treatment because of the amount of lead required to adequately attenuate megavoltage photon beams, the difficulty in properly positioning an eye shield and the possibility of compromising the effectiveness of the treatment. However, we were asked to treat a TBI patient who is a professional pilot, and thus his livelihood is contingent upon maintaining perfect vision. A custom eye shield was constructed out of lead and ionization chamber and film measurements were performed under TBI conditions to determine the thickness and location of the eye block to optimize the competing effects of increased scatter and attenuation from the lead. Phantom data were also obtained for 6 MV irradiation for comparison with 24 MV. In-vivo patient and phantom measurements with thermoluminescent dosimeters showed that with visual positioning of the eye block the dose was reduced from 16 to 20% across the orbits of both eyes.

Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma.

Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.

Breath ethane generation during clinical total body irradiation as a marker of oxygen-free-radical-mediated lipid peroxidation: A case study

Total body irradiation (TBI) is used therapeutically for treatment of leukemias and other malignancies of the hemopoietic system. Ionizing radiation produces oxygen free radicals that contribute to cytotoxicity. Breath collected from one patient undergoing therapeutic TBI showed measurable changes in levels of ethane during treatment. Breath ethane is a marker of lipid peroxidation of n-3 fatty acids. The TBI treatment involved 4 days of irradiation. The largest changes in breath ethane occured on Day 2. The increased levels of breath ethane on Day 2 were correlated to clinical manifestations of toxicity. The correlation of the onset of gastrointestinal side effects with higher levels of breath ethane suggests that breath ethane may be a clinically useful measure of the toxicity of various TBI fractionation treatment protocols currently in use at different medical centers. The levels of breath ehtane on the other days of treatment were lower, suggesting that the oxidative-antioxidative balance of the patient may be important in protection against free radical mediated injury. These results for a single patient suggest that breath ethane may be a promising approach to elucidate the role of antioxidants in clinical TBI and should be extended for verification to a larger volunteer patient population.