Number Of Radiation Fractions Research Articles

Abstract 11603: Reexamining the Incidence and Predictors of Radiation Induced Cardiac Implantable Electronic Device Malfunction in Cancer Patients and Streamlining Management

Background: Historically, the reported incidence of Cardiac Implantable Electronic Device (CIED) malfunction during Radiotherapy (RT) is estimated to range from 3% to 20%. However, most of these studies had small sample sizes and may have overestimated the clinical impact of this problem. In this retrospective study, we examined the incidence of device reset and transient signal interference due to RT in a large cohort of patients. In addition, we studied the feasibility of a novel method of monitoring CIEDs during RT: pulse check method (PCM). Methods: From 1/2015 to 4/2023, patients with CIEDs requiring RT at a tertiary cancer center were identified. CIEDs were checked prior to RT. Candidate patients were managed with PCM, which involves programming the lower pacing rate at 75 bpm (slightly faster than lower rate of pacing during reset mode). Pulse checks were performed after each fraction of RT. Patients with heart rate less than 75 bpm had immediate device interrogation to assess for reset. After completion of RT, devices were interrogated and CIED programming returned to original settings. Results: Our study reviewed 720 patients with CIEDs undergoing 837 courses (560 pacemakers and 277 defibrillators) of RT, of which the majority (85%) were managed with PCM. Neutron producing RT (proton and photon with >10MV beam energy) was used in 189 (22.6%) cases, and 9 (1.1%) devices experienced reset. All resets were recoverable and occurred in the setting of neutron-producing radiation, especially proton therapy [OR 12.06 (3.37 - 43.10), p-value 0.0001]. Site of radiation, type of device, and number of RT fractions did not predict reset. No transient signal interference or oversensing events occurred during RT. Conclusions: CIED malfunction is a rare complication of RT, occurring in the setting of neutron producing radiation, with no serious clinical consequence. Transient signal interference and oversensing during RT was not observed to be a clinical concern in contemporary devices. Thus, asynchronous pacing in pacer dependent patients and deactivation of defibrillator tachy-therapy during RT is not necessary. PCM is a practical and cost-effective way to monitor CIEDs during RT.

Higher radiation dose on immune cells is associated with radiation-induced lymphopenia and worse prognosis in patients with locally advanced esophageal squamous cell carcinoma.

To explore the effective dose to immune cells (EDIC) for better prognosis while avoiding radiation-induced lymphopenia (RIL) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Overall, 381 patients with locally advanced ESCC receiving definitive radiotherapy with or without chemotherapy (dRT ± CT) between 2014 and 2020 were included in this study. The EDIC model was calculated by radiation fraction number and mean doses to the heart, lung, and integral body. The correlation between EDIC and clinical outcomes was analyzed using Cox proportional hazards regression, and risk factors for RIL were determined by logistic regression analysis. The median EDIC was 4.38 Gy. Multivariate analysis revealed that low-EDIC significantly improved the OS of patients when compared with high-EDIC (HR = 1.614, P = 0.003) and PFS (HR = 1.401, P = 0.022). Moreover, high-EDIC was associated with a higher incidence of grade 4 RIL (OR = 2.053, P = 0.007) than low-EDIC. In addition, we identified body mass index (BMI), tumor thickness, and nodal stage as independent prognostic factors of OS and PFS, while BMI (OR = 0.576, P = 0.046) and weight loss (OR = 2.214, P = 0.005) as independent risk factors of grade 4 RIL. In subgroup analyses, the good group had better clinical outcomes than the remaining two groups (P< 0.001). This study demonstrated that EDIC significantly correlates with poor clinical outcomes and severe RIL. Optimizing treatment plans to decrease the radiation doses to immune cells is critical for improving the outcomes.

PO-0951 Effects of COVID-19 during radio(chemo)therapy in head and neck cancer patients

Purpose or Objective To evaluate effects of COVID-19 during (chemo)radiation (RT) or quarantine on overall treatment time and outcome, as well as to determine prognostic parameters for COVID-19 related death in patients with head and neck cancer (HNC). Materials and Methods We have performed a retrospective review and identified patients with confirmed SARS-CoV-2 or quarantine during RT of HNC, who were treated in 3 radiotherapy departments from March 2020 till February 2021. The quarantine was imposed due to a close contact with COVID-19 positive person e.g. after hospitalisation in the same patient's room. Univariate analysis was performed using a Cox proportional hazards model for COVID-19 positive patients. The covariates included were age, co-morbidities, smoking, white blood cell (WBC) ratio measured on the day of positive COVID-19 test result divided by WBC count taken one week before, C-reactive protein (CRP) ratio, which was obtained analogically to WBC ratio. WBC-ratio and CRP-ratio were chosen to reflect dynamics of possible changes in inflammatory parameters. Results 36 patients (pts) were included in the analysis. Mean age yield 66 years (Range: 25-87). 92% of pts, were treated with curative intent. Two patients had induction chemotherapy and 9 pts got simultaneous chemoradiation. The median follow-up was 3.4 month (Range: 1-5.6). In total 7 patients died, 5 of them were categorised as COVID-19 related death. The time lapsed from a COVID-19 positive test result to death varied in these 5 pts from 8 to 17 days. 26 (72%) pts had SARS-CoV-2 infection confirmed and in the case of 10 pts RT was interrupted due to imposed quarantine. The median interruption time of RT yield 20 days (13-65) and 14 days (10-19) due to COVID-19 and quarantine, respectively. 36% patients did not continue RT due to various reasons including death (5 pts) and deterioration of performance status (3 pts). We did not observe a significant correlation between age, hypertension, performance status, intention to treat (primary vs adjuvant vs palliative), smoking, number of RT fractions before COVID-19 infection, ischaemic heart disease, pulmonary disease, uncontrolled diabetes and risk of COVID-19 related death on univariate Cox analysis. However, in a subgroup of patients (n=17) with available regular blood analysis data WBC-ratio correlated significantly with risk of COVID-19 related death (p=0.02). CRP-ratio did not show significance for risk of COVID-19 related death (p=0.12). By the time of 3 month follow-up one patient treated with palliative intention progressed and died. Conclusion COVID-19 infection extended overall treatment time in median for 20 days. From radiobiological point of view this is a substantial prolongation, thus these patients are at higher risk of recurrence and demand careful follow-up. In our subgroup of patients WBC-ratio was prognostic for risk of COVID-19 related death. Due to low number of patients this observation should be validated in a larger cohort of patients.

Dilemma and Strategies Amidst Nationwide Covid-19 Lockdown for Lung Cancer Management

The whole world is affected due to pandemic caused by SARS Cov 2. Imposition of nationwide lockdown to curb viral transmission has impacted various healthcare services including cancer care services. Most important concern is the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV 2) and its effect on patients with cancer. Alteration in lung cancer care services including number of chemotherapy sessions, dosages of chemotherapy, number of radiotherapy fractions and duration, about maintenance therapy and immunotherapy etc., could maintain the continuity of care without affecting quality of cancer care. In this review, we have discussed challenges and counter measures for lung cancer management amidst COVID-19 pandemic.

Radiation Induced Lymphopenia is Associated with the Effective Dose to the Circulating Immune Cells (EDIC) for Breast Cancer

Radiation induced lymphopenia (RIL) has been reported to associate with treatment outcome in many types of solid cancers, including breast cancer of small series. In this study, we hypothesized that effective dose to circulating immune cells (EDIC) impacts the severity of radiation-induced lymphopenia in breast cancer. Breast cancer patients who received adjuvant radiation were enrolled in this study. Radiation dosimetric factors such as RT fields, RT fractionation schema, use of electron, mean cardiac dose, mean ipsilateral/bilateral lung dose, integral dose of the total body was collected retrospectively. A previously published EDIC model, which considered that the exposure of circulating immune cells as the proportion of blood flow into blood containing organs including lung, heart, and the volume of the exposed area of the total body, were used for this study. The model is expressed as EDIC = 0.12*MLD+0.08*MHD+0.45+0.35*0.85*n451/2*ITD61.8*103, where MLD, MHD, and ITD is the mean lung dose, mean heart dose and integral dose, n is the number of radiation fractions. The post- and pre-radiation lymphocyte ratio was calculated as the end point to predict lymphopenia. Linear regression between the lymphocyte ratio and EDIC was used for the analysis. The lymphocyte ratios were also compared by dividing patients into 3 EDIC groups. T-test was used for the comparison. Between March 2015 to February 2020, a total of 1288 breast cancers patients received radiation in clinical oncology of Hong Kong University Shenzhen Hospital and 735 patients with complete CBC results were included in this study. The lymphocyte ratio decreased linearly with increasing EDIC (R2 = 0.23, p<0.0001). The median lymphocyte ratio was 73.1%, 62.2% and 36.4% respectively, when EDIC was ≤ 0.75Gy, >0.75Gy but ≤1.25Gy, and >1.25Gy. The average EDIC was 75%±21%, 64%±19%, and 41%±23% correspondingly for the 3 EDIC groups (p<0.0001). EDIC is significantly associated with lymphocyte count changes and NCI defined lymphopenia after radiation. EDIC may be used to predict radiation induced lymphopenia and guide radiation plan optimization for breast cancer patients treated with radiotherapy.

Comprehensive analysis of lymphocyte loss kinetics in patients treated with focal fractionated radiation therapy.

e14191 Background: Radiation (RT)-induced lymphopenia (RIL) is associated with worse survival in patients with solid tumors as well as lower response rates to checkpoint inhibitors. This analysis aimed to model the kinetics of lymphocyte depletion during RT to assist in predicting RIL risk. Methods: This registry-based study included 419 patients who received either total body irradiation (TBI; n = 30), stereotactic body RT (SBRT; n = 73), or conventional chemoradiation (CRT; n = 316). For each patient, serial absolute lymphocyte counts (ALCs) were plotted against RT fraction number. The initial 3 weeks of treatment for conventionally irradiated patients and the entirety of treatment for SBRT and TBI patients were fit to exponential decay in the form ALC(x) = ae-bx. From those fits, percent per fraction loss in ALC (PFLAC) was calculated as PFLAC = (1 – e-b)*100, and multivariable regression was performed to find its significant predictors. Results: Curves were well fitted by exponential decay for all RT techniques (median linearized R2 0.98, 0.93, and 0.97 for patients treated with TBI, SBRT, and CRT, respectively). In CRT patients, apparent ALC loss rate slowed after week 3, potentially due to lymphocyte repopulation or other factors. TBI and SBRT patients completed RT before the end of the exponential decay phase, and their ALC loss rates remained unchanged throughout RT. Initial PFLAC varied significantly with treatment technique. Mean PFLAC was 35.5%, 24.3%, and 10.77% for patients treated with TBI, SBRT, and CRT, respectively (p &lt; 0.001). Significant predictors of PFLAC varied by site and included field size, dose per fraction, mean spleen dose, chemotherapy backbone, and age. In pancreas cancer patients, gemcitabine was associated with a higher PFLAC (mean = 10.7) than 5-FU (mean = 8.3) after adjustment for covariates (p &lt; 0.001). Finally, total % ALC loss during RT was highly correlated with PFLAC (p &lt; 0.001). Conclusions: Lymphocyte depletion kinetics during the initial phase of fractionated RT are characterized by pure exponential decay. Initial PFLAC is strongly correlated with RT planning parameters and predicts total % ALC loss. The highest ALC loss rates were associated with RT-only regimens, implying that concurrent chemotherapy is not solely responsible for lymphopenia in patients receiving CRT. This work may also assist in selecting patients for adaptive RT approaches to mitigate RIL risk.

Intermediate-risk prostate cancer: A Medicare-based cost comparison of five radiotherapy regimens.

108 Background: Patients with intermediate risk prostate cancer choosing radiotherapy may be treated with a number of regimens. The current study compares the direct treatment cost for five therapeutic options based on Fiscal Year 2014 Medicare allowable reimbursements. Methods: Hypothetical charge sheets were generated along with the expected Medicare allowable reimbursements (based on global billing where applicable) for the following regimens: 1.) Image Guided Intensity Modulated Radiotherapy (IGIMRT) to a dose of 78Gy in 39 fractions with one field reduction (IGIMRT); 2.) Dose escalated IGIMRT to 84.60Gy in 47 fractions with one field reduction (MSKCC-IGIMRT); 3.)IGIMRT to a dose of 45Gy in 25 fractions followed by a 90 seed I125 prostate implant (IGIMRT-BTX); 4.) Image Guided Proton Therapy to a dose of 78Gy(RBE) in 39 fractions with one field reduction (SFPT); 5.) Image Guided Hypofractionated Proton Therapy to a dose of 72.50Gy(RBE) in 29 fractions with one field reduction (HFPT). Results: Based on Fiscal Year 2014 Medicare allowable reimbursements, the direct cost for each of these interventions including professional fees, technical fees, isotope costs and facility fees is shown in the Table. Conclusions: This data presents a framework for evaluating the cost effectiveness of proton therapy as compared to competing therapeutic options. Under current Medicare allowable reimbursements, the cost of proton therapy relative to the cost of other therapeutic options is highly dependent on the number of radiotherapy fractions delivered. The feasibility of delivering hypofractionated proton therapy for patients with localized prostate cancer is being investigated at a number of institutions as well as within the framework of a multicenter protocol. Ultimately the cost of proton therapy will need to be weighed against tumor control probabilities as well as the economic and quality of life benefits associated with reduced normal tissue exposure. [Table: see text]

Integration of surgery and radiosurgery

Standing between neurosurgery and radiation oncology, radiosurgery has spearheaded advances in both specialties. Radiation oncologists rapidly integrated and enhanced the benefits of the stereotactic frame, as well as adopted the concepts of frameless stereotaxis, seeing a revolution in their practice. Better target definition and delivery of radiation with exquisite accuracy permitted decrease in number of radiation fractions with more focus on tumor kill, instead of relying strictly on the principles of radiobiology to avoid side effects. This has brought enthusiasm to the radiation oncologists witnessing excellent results with more patient comfort and economy of resources. They are progressively abandoning the term stereotactic for one more akin to their specialty. Image Guided Radiation Therapy (IGRT) has been the center of discussion in the major Radiation Oncology Congresses; radiosurgery concepts are now applied to the whole body, leaving the realm of neurosurgery.[1,2] Terms unfamiliar to neurosurgeons such as “gross tumor volume” (GTV), clinical tumor volume (CTV), dose volume histogram (DVH), complete response (CR), partial response (PR), and no response (NR) have invaded radiosurgery, making radiosurgery concepts far more distant from the neurosurgeon's day-to-day practice. Neurosurgery has lagged behind in this development. Although stereotactic radiosurgery has made a great impact in neurosurgery, representing 15–20% of the caseload in the major neurosurgery departments,[5] traditionally neurosurgeons insist on the use of the stereotactic frame to justify their participation in this rapidly evolving and exciting field. Radiosurgery lacks the familiarity with the operating room that characterizes the personality of the neurosurgeon. A small number of neurosurgeons dedicated to radiosurgery–usually stereotactic–oriented individuals with mathematical and minimally-invasive mind sets–have carried and maintained the field. There is, however, a threat for neurosurgeons not to be involved in radiosurgery, as the radiation oncologists become familiar with and adapt neurosurgery's navigation tools to their needs–tailoring them to linear accelerators, and improving their own knowledge of the nervous system anatomy. Radiation oncologists are also becoming very familiar with neurosurgery's benign diseases such as acoustic neuromas, trigeminal neuralgia, skull base meningiomas, and arteriovenous malformations–which are easier and more attractive to treat than the oncological pathologies they have struggled with over the years.[4] Now that the stereotactic frame is no longer necessary[3] and imaging is quasi–capable to define histology, surgical skills are becoming unnecessary in the management of pathologies previously thought to be the most challenging for neurosurgeons. Results of radiosurgery have in some instances surpassed what can be obtained with exquisite neurosurgical techniques, a concept that is difficult to accept by neurosurgeons with years of experience. With an early imaging diagnosis, before going through the hardship of neurological symptoms, patients are reluctant to accept surgery, and are enticed to embrace the benefits of radiosurgery; the same feeling is shared by their relatives and health care payers. For them, the specialist taking care of the disease is irrelevant, as long as the treatment offered is effective, with the fewest possible side effects, allows them to keep working, and is affordable. This issue of Surgical Neurology International Stereotactic focuses on this integration of radiosurgery, image guided surgery, operating room imaging, and novel applications of stereotactic surgery. Having the paradigm of traditional surgery threatened during the end of the last century with the trend persisting and following the fast pace of neuroimaging improvement, neurosurgeons need to rapidly adapt to this reality. MRI with functional and chemical analysis and molecular imaging progressing are rapidly obviating the need of histological confirmation for treatment of several neurosurgical diseases, i.e., acoustic neuromas, meningiomas, arteriovenous malformations, and others. While neurosurgery will always exist, neurosurgeons and those training the future generations have to bring these technological advances in to the training programs and assure that neurosurgery continues to participate as the main integrative specialty in the treatment of these traditionally neurosurgical diseases– while also extending the horizon toward the neurological degenerative diseases and recapturing leadership in the management of vascular disorders, which in large part passed to the realm of the interventional radiologist. Mass effect needs surgery; it must be dealt with a consciously planned and performed decompressive surgery, now possible with software dedicated to this approach. The neurosurgeon has to keep in mind intact neurologic function, avoiding the risks of radical surgery, relying on the advances of radiosurgery, stereotactic radiotherapy, and endovascular interventional techniques. Brainlab, Inc., dedicated to bridge imaging developments, radiosurgery and surgery, has generously supported the publication of this issue of SNI Stereotactic.

Clinical Factors Associated With Seroma Volume Reduction in Breast-Conserving Therapy for Early-Stage Breast Cancer: A Multi-Institutional Analysis

To correlate clinical factors with seroma volume and reduction; and to determine whether cone-beam CT (CBCT) could be used clinically to monitor seroma reduction. This investigation included 102 women from five institutions with stage T1-2 breast cancer treated with breast-conserving therapy. Two CT scans were acquired: the planning CT (CT1) and a second CT (CT2) during radiotherapy (RT). Seroma was contoured on all scans, and correlations between seroma characteristics and clinical factors were investigated by univariate and multivariate analyses. In a substudy, 10 of the 102 patients received multiple CBCT scans during RT. Seroma were contoured by two observers in the substudy. Fifteen time points at which CT and CBCT were performed within 2 days were identified. The levels of correlation in seroma contours between CBCT and CT and between the two observers were examined. The mean relative seroma reduction from CT1 to CT2 was 54% (p < 0.001). A significant inverse relationship was found between relative seroma reduction per week and number of RT fractions given by univariate and multivariate analyses (p = 0.01, 0.03). The mean difference in contoured seroma volumes between CT and CBCT was 12% (3.3 cm(3)). When assessing the relative difference in seroma contours between Observer 1 and Observer 2, an interobserver difference of 12% was demonstrated. Neither discrepancy was clinically significant. Radiotherapy seems to hinder seroma reduction. Volume discrepancies between CBCT and CT were minor, with low interobserver variation, indicating that CBCT might be useful in monitoring seroma reduction.

Inclusion of molecular biotherapies with radical radiotherapy: modeling of combined modality treatment schedules

Purpose: The use of molecular biology based therapies concurrently with radical radiotherapy is likely to offer potential benefits, but there is relatively little use of classical radiobiology in the rationale for such applications. The biological mechanisms that govern the outcomes of radiotherapy need to be completely understood before rational application and optimization of such adjuvant biotherapies with radiotherapy. Methods and Materials: Existing biomathematical models of radiotherapy can be used to explore the possible impact of biotherapies that modify tumor proliferation rates and/or radiosensitivity parameters during radiotherapy. Equations that show how to incorporate biotherapies with the linear-quadratic model of radiation cell kill are presented. Also considered are changes in tumor physiology, such as improved blood flow with enhanced delivery of biotherapy to the tumor cells and accelerated clonogen repopulation during radiotherapy. Monte Carlo random sampling methods are used to simulate these effects in heterogenous tumor populations with variation in radiosensitivities, clonogen numbers, and doubling times, as well as variations in repopulation onset rates and in vascular perfusion rates with time. Results: The time onset and duration of exposure of each type of biotherapy during radical radiotherapy can influence the predicted tumor cure probabilities in subtle ways. In general, the efficacy of biotherapies that radiosensitize will depend upon the number of radiotherapy fractions that are sensitized and the change in blood flow with time during radiotherapy. Biotherapies that control repopulation will depend not only on the duration of exposure but also, where accelerated repopulation occurs, on the time at which biotherapy is initiated during radiotherapy. From the ranges of radiobiological parameters and biotherapy efficacies assumed for exploratory examples, large changes of tumor control probability (TCP) are encountered in individual tumors from the application of cytostatic therapy. There are predictions of smaller increments in TCP in heterogenous tumor populations from the application of cytostatic and radiosensitizing biotherapies in combination. Conclusions: The exercises show how the scheduling of biotherapies may critically influence tumor cure probabilities in subtle ways and give considerable insight into the interacting biological mechanisms that influence these changes. Future therapeutic developments should be guided by these principles.

RADIOTHERAPY OF CANINE NON‐TONSILLAR SQUAMOUS CELL CARCINOMA

The records of 14 dogs treated with megavoltage radiation for non‐tonsillar oral squamous cell carcinoma were reviewed to determine the efficacy of this treatment modality. Total radiation dose was either 48 or 57 Gray (Gy), while dose per fraction was either 3.0 or 4.0 Gy. Median disease free interval and survival were 365 and 450 days, respectively. Median disease free interval was shorter in dogs older than nine years (210 days) as compared with dogs less than or equal to nine years old (470 days), (p &lt; .005). Median survival was shorter in dogs older than nine years (315 days) as compared with dogs less than or equal to nine years old (1080 days), (p &lt; 0.02). Weight, stage, anatomic subsite, intraoral location, duration of disease, prior surgery, and number of radiation fractions did not appear to influence disease free interval or survival. Data presented herein suggest that survival in dogs with non‐tonsillar squamous cell carcinoma receiving megavoltage radiation may be longer than that achieved with orthovoltage radiation or surgery. Megavoltage radiation appears to be an effective treatment for non‐tonsillar oral squamous cell carcinoma in dogs. Further study is needed to determine the optimal time‐dose sched‐ule.

Effects of fractionated radiation therapy on human brain tumor multicellular spheroids

We investigated the cytotoxic effects of fractionated radiation therapy on multicellular spheroids of human malignant glioma cell lines U-87 MG, U-251 MG, and U-373 MG. Graded doses of x-rays were administered in 1, 3, 8, 15, and30 fractions over 15 days. The isoeffect dose for a 1 log cell kill ranged from 4-4.5 Gy for a single fraction to 7–8 Gy for an 8-fraction protocol; no additional dose-sparing was achieved with more fractions. Therefore, the effects of individual doses (1.56 Gy) of the 8-fraction protocol were studied in U-251 MG spheroids. A cell survival assay showed that the first dose of radiation killed 30–50% of the cells; subsequent doses usually killed fewer cells. The cell kill after all 8 doses was about 1.0 log. No consistent relationship between the intracellular glutathione level and fraction number was observed. The 24-hour labeling index of the spheroids did not decrease until after the second fraction. Thus, the higher cell kill of the first dose does not seem to be related to cell cycle synchrony. Multinuclear and mononuclear giant cells were limited almost entirely to the periphery of the spheroids and increased with the number of radiation fractions. We conclude that multicellular spheroids can be used to study the biological effects of fractionated radiation therapy on human brain tumor cells. Although this model cannot be used to evaluate the effect of radiation on normal tissue, it may be useful in developing more effective radiation therapy protocols for human brain tumors.

Additivity versus repair inhibition in fractionated treatments combining drugs and X rays: a theoretical analysis.

Drugs which inhibit the repair of radiation damage could potentially be useful for enhancing the effects of radiotherapy. In pre-clinical combined modality studies, however, it is often difficult to state with certainty whether or not a drug has inhibited radiation damage repair. This paper shows that several commonly used parameters for assessing repair can give the wrong answer regarding the presence of drug-induced repair inhibition. These parameters are; the difference in radiation dose between 1 and n fractions to give the same effect, the fractional recovered dose per fraction interval, FR, and the related parameter FREC. A further parameter used for treatment comparisons is the enhancement ratio for the drug (D.E.R.; ratio of radiation doses, with and without drug, to cause a given effect). An increasing D.E.R. with increasing number of radiation fractions has been taken as an indication that the drug inhibited repair. The present report demonstrates that this, too, can be misleading. From an analysis based on a linear-quadratic survival curve for X rays, it is suggested that deriving and comparing alpha/beta ratios (ratio of the linea to quadratic coefficients) gives the best indication of drug-induced changes in survival curve shape which may reflect underlying changes in repair capacity.

Facilitation of allogeneic bone marrow engraftment in mice by total lymphoid irradiation combined with total-body irradiation.

Different groups of C57BL/Ka mice received daily fractions of 2 Gy total lymphoid irradiation (TLI) in a total dose of 34, 24, or 14 Gy. On the day after the last irradiation, 30 X 10(6) allogeneic (BALB/c) nucleated bone marrow cells were infused into the irradiated animals. When the last one or two fractions of the radiation schedule were given to the whole body (combined total lymphoid-total-body irradiation, TLBI): (1) stable bone marrow chimerism with a higher number of donor-type cells in the peripheral blood was induced in a higher percentage of mice that had received 34 Gy TLBI compared with mice that received 34 Gy TLI. (2) bone marrow chimerism could also be induced after 24 Gy or 14 Gy TLBI, whereas 24 and 14 Gy TLI alone were ineffective. The tolerance to the TLBI schedules was excellent and no clinical signs of graft-versus-host disease were noticed. It is concluded that the addition of TBI can facilitate bone marrow engraftment after TLI and drastically reduce the number of radiation fractions needed to obtain successful chimerism after allogeneic bone marrow transplantation in mice.