Advantages and implications of high dose rate (HDR) total skin electron irradiation (TSEI) for the management of Mycosis Fungoides. Indian experience

Background

Mycosis Fungoides (MF) is an indolent lymphoproliferative disorder affecting dermis caused by abnormal proliferation of CD4+ T-cells. Radiation therapy is the most effective modality of treatment for MF which offers cure in limited stage disease and desirable palliation in advance stage disease. Treating entire skin having many curved surfaces and folds with radiation is the real challenge for the radiation oncologist. Many techniques, dose schedules and modifications in total skin electron irradiation (TSEI) have been tried since 1950s. TSEI treatment is a very time consuming, inconvenient and physically challenging to both patient as well as oncologist.

Aim

At our center TSEI was performed since 1983 with conventional linear accelerator where the treatment time was prolonged beyond two hours, which was very difficult or the patient, oncologist, technical officer and eating away the machine time hampering the treatment of other patients. From 1998 we shifted to high dose rate (HDR) mode, in order to bring down the treatment time of a single patient every day from two and half hour to 15 min. The reduction of treatment time increases patient compliance and at the same time saved machine time.

Materials and methods

Between 1998 and 2003, eleven pathological diagnosed MF patients were treated using HDR TSEI. All the patients were male between 40 and 70 years of age, who had the history of having the disease for 7–22 months. Four patients had T2 and seven patients had T3 stage disease with more than 90% skin surface involvement. TSEI was performed with 4 MeV electrons with a daily fraction size of 120 cGy to a total dose of 36 Gy. At the end of 36 Gy, boost dose of 10 Gy was delivered to self shielding regions like sole, scalp and perineum. Considering the treatment related toxicities and consequent treatment interruptions, in the first seven patients, the last four patients were treated using similar HDR TSEI technique with modified treatment schedule, where the treatment was given on an alternate day basis following 2nd week of initiation of treatment.

Results

The patients were followed over a period of 144 months with a median of 72 months. Nine patients are alive without any evidence of disease, one patient relapsed and one died due to progression of disease. The most common radiation related morbidities are erythema, skin blisters, various degree of desquamations, swelling of joints (specially small joints) etc. which are controlled by treatment interruptions and conservative measures. By modifying the treatment schedule, the incidence of toxicity as well as treatment interruptions were brought down.

Conclusions

We can conclude that HDR-TSEI is an excellent and safe therapeutic modality for the patients with MF both curative as well as palliative without any added toxicity profile, provided patient positioning is done properly.     

The current management of mycosis fungoides and Sézary syndrome and the role of radiotherapy: Principles and indications

Aim

To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies.

Background

MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases.

Materials and methods

The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated.

Results

New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure “minimal stage” MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces.

Conclusions

New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces.     

Literature review of clinical results of total skin electron irradiation (TSEBT) of mycosis fungoides in adults

Background

Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin. Even with the establishment of MF staging, the initial treatment strategy often remains unclear.

Aim

The aim of this study was to review the clinical results of total skin electron beam therapy (TSEBT) for MF in adults published in English language scientific journals searched in Pubmed/Medline database until December 2012.

Results

MF is very sensitive to radiation therapy (RT) delivered either by photons or by electrons. In limited patches and/or plaques local electron beam irradiation results in good outcomes besides the fact of not being superior to other modalities. For extensive patches and/or plaques data suggest that TSEBT shows superior response rates. The cutaneous disease presentation is favorably managed with radiotherapy due to its ability to treat the full thickness of deeply infiltrated skin. For generalized erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For advanced disease, palliation, or recurrence after the first radiotherapy treatment course, TSEBT may still be beneficial, with acceptable toxicity. Recommended dose is 30–36 Gy delivered in 6–10 weeks.

Conclusion

TSEBT can be used to treat any stage of MF. It also presents good tumor response with symptoms of relief and a palliative effect on MF, either after previous irradiation or failure of other treatment strategies.     

Total skin electron beam (TSEB) therapy in pediatric patients: A review of the literature

Aim

A literature review was undertaken to identify current TSEB therapy in pediatric patients.

Background

Total skin electron beam (TSEB) therapy is a method of irradiation with low energy electron beam dedicated to patients who have superficial skin lesions all over their body. Such skin malignancies are sparse among adults and even more uncommon with pediatric population.

Materials and methods

In this study, all reported case reports were summed up with a special emphasis on techniques used, doses prescribed and special shielding of critical organs. Moreover, potential problems that were encountered during TSEB irradiation of very young patients were depicted.

Results

The literature has described only seven case reports of children undergoing TSEB therapy. Most of them were infants; however, two adolescents were also treated. For all infants, general anesthesia was provided to allow safe and accurate TSEB irradiation. The prescribed dose varied from 16 Gy to 28 Gy depending on the irradiation schedule and patient condition. Usually, boost fields were applied to the scalp and perineum. Typical shields for fingernails, toenails and lenses were usually used.

Conclusion

This paper revealed that TSEB therapy may be considered as a palliative treatment for pediatric patients with leukemia cutis. However, its role is still unclear and should be further investigated.     

Diagnostics in mycosis fungoides and Sezary syndrome

Aim

The aim of this paper was to present diagnostic methods helping in the recognition of mycosis fungoides (MF) and Sezary syndrome (SS).

Background

Mycosis fungoides is the most common form of primary cutaneous T-cell lymphomas. It is characterized by a distinctive long-term course and malignant T-cell proliferation. MF diagnosis is not easy, mainly due to the atypical clinical presentation of the disease at an early stage.

Materials and methods

Low specific changes, which can be observed at the histopathological examination. Initially, the skin lesions may resemble psoriasis, atopic dermatitis or chronic eczema. Patients are qualified according to the available, and generally accepted WHO-EORTC classification, based on a combination of clinical and histopathological markers. From a clinical point of view, it is also important to carry out the qualification according to the TNMB assessment, which allows to specify the stage of the disease, and is helpful in the monitoring of the course of disease and therapeutic effects.

Results

In this paper we try to present currently available diagnostic methods.

Conclusion

Diagnosis of MF and SS still causes many problems due to less characteristic changes in the early stage of disease and requires wide interdisciplinary knowledge.     

Integral dose: Comparison between four techniques for prostate radiotherapy

Aim

Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate.

Background

Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient.

Materials and methods

We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body.

Results

Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient''s body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body.

Conclusions

The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods.     

Prospective study on dosimetric comparison of helical tomotherapy and 3DCRT for craniospinal irradiation – A single institution experience

Aim

This prospective study aims to assess feasibility of helical tomotherapy (HT) for craniospinal irradiation (CSI) and perform dosimetric comparison of treatment plans for both HT and 3D conformal radiotherapy (3DCRT).

Background

CSI is a challenging procedure. Large PTV size requires field matching due to technical limitations of standard linear accelerators, which cannot irradiate such volumes as a single field. HT could help to avoid these limitations as irradiation of long fields is possible without field matching.

Materials and methods

Three adults were enrolled from 2009 to 2010. All patients received radiochemotherapy. Treatment plans in prone position for 3DCRT and in supine position for HT were generated. The superior plan was used for patients’ irradiation. Plans were compared with the application of DVH, Dx parameters – where x represents a percentage of the structure volume receiving a normalized dose and homogeneity index (HI).

Results

All patients received HT irradiation. The treatment was well tolerated. The HT plans resulted in a better dose coverage and uniformity in the PTV: HI were 5.4, 7.8, 6.8 for HT vs. 10.3, 6.6, 10.4 for 3DCRT. For most organs at risk (OARs), the D(V80) was higher for HT than for 3DCRT, whereas D(V5) was lower for HT.

Conclusions

HT is feasible for CSI, and in comparison with 3DCRT it improves PTV coverage. HT reduces high dose volumes of OARs, but larger volumes of normal tissue receive low radiation dose. HT requires further study to establish correlations between dosimetrical findings and clinical outcomes, especially with regard to late sequelae of treatment.     

Adjuvance in refractory keloids using electron beams with a spoiler: Recent results

Aim

To present clinical results of adjuvant irradiation of excised refractory keloid wounds using a novel bolus-free technique developed within our group to irradiate the skin surface with a linear accelerator.

Background

The use of a bolus to increase surface dose over a newly excised keloid presents several problems. Previous solutions are unsatisfactory. Our technique is promising but needs to be evaluated in practice.

Materials and methods

Twenty refractory skin keloids in 19 patients were excised and irradiated in Hospital Plató (Barcelona, Spain) using a 6 MeV electron beam with a 4-mm aluminium spoiler. 15 Gy in fractions of 3 Gy were delivered to the excision site plus a safety margin. All patients were examined during the follow-up (median: 40 months, interval: 12–68 months) and toxicities were recovered.

Results

At the end of the follow-up period, 76% of the cases had not recurred, while the complete response rate amounted to 53%. Residual hypertrophic scars were classified as partial responses. After therapy, itching and pain were observed in 30% of the patients, as well as one telangiectasia and two hyperchromatic scars.

Conclusion

Our technique avoids using a bolus while combining the benefits of electron beam therapy in keloids (fewer secondary effects, and fewer and shorter treatments) with a dose deposition adequate for skin surface treatments. Our results are in line with the most successful therapies evaluated in the literature, as secondary effects are acceptable and recurrence rates are low.     

Craniospinal radiotherapy in children: Electron- or photon-based technique of spinal irradiation

Background

The prone position and electron-based technique for craniospinal irradiation (CSI) have been standard in our department for many years. But this immobilization is difficult for the anaesthesiologist to gain airway access. The increasing number of children treated under anaesthesia led us to reconsider our technique.

Aim

The purpose of this study is to report our new photon-based technique for CSI which could be applied in both the supine and the prone position and to compare this technique with our electron-based technique.

Materials and methods

Between November 2007 and May 2008, 11 children with brain tumours were treated in the prone position with CSI. For 9 patients two treatment plans were created: the first one using photons and the second one using electron beams for spinal irradiation. We prepared seven 3D-conformal photon plans and four forward planned segmented field plans. We compared 20 treatment plans in terms of target dose homogeneity and sparing of organs at risk.

Results

In segmented field plans better dose homogeneity in the thecal sac volume was achieved than in electron-based plans. Regarding doses in organs at risk, in photon-based plans we obtained a lower dose in the thyroid but a higher one in the heart and liver.

Conclusions

Our technique can be applied in both the supine and prone position and it seems to be more feasible and precise than the electron technique. However, more homogeneous target coverage and higher precision of dose delivery for photons are obtained at the cost of slightly higher doses to the heart and liver.     

Long term results of HDR brachytherapy in men older than 75 with localized carcinoma of the prostate

Background

Prostate cancer is an illness with a high incidence, especially among older men. The choice of a treatment option among men above 75 years is, however, not clear. Radical prostatectomy in this age group is connected with a relatively high morbidity. A further possibility of curative treatment is radiotherapy which can be administered in the form of external beam or in combination with high dose rate (HDR) brachytherapy.

Aim

The aim of our work was to evaluate how HDR brachytherapy is tolerated among men older than 75 and how associated diseases can influence the tolerance to this treatment. Of interest to us were the treatment results and mortality from other diseases.

Materials and methods

We analyzed a sample of 20 men above 75 years old (median 77 years) who were undergoing treatment by a combination of external radiotherapy and brachytherapy. Sixteen (80%) of them had prostate cancer with an intermediate and high risk of recurrence, four had low risk prostate cancer. Most patients, 14 (70%), had less than two comorbidities.

Results

The median observation period was 57 months. No perioperative complications were recorded. Acute genitourinary toxicity (GU) to a maximum grade of 1–2 manifested in 60% of cases. Acute gastrointestinal toxicity (GIT) was observed only at grade 1 and in 25% of cases. Late GU toxicity occurred in 35% of patients, with only one showing grade 3; late GIT toxicity was recorded at grade 1 only in 3 patients (15%). 70% of the men lived longer than 3 years after treatment, at present, 50% lived more than 5 years. Long-term biochemical remission was achieved in 18 patients (90%).

Conclusions

HDR BRT is possible and well-tolerated in older men above 75 years in good condition and without serious intercurrence.Well-selected older patients with higher-risk tumours and without serious comorbidities undoubtedly benefit from radical treatment when compared with watchful waiting.     

Empirical estimation of beam-on time for prostate cancer patients treated on Tomotherapy

Background and aim

This study proposed a method to estimate the beam-on time for prostate cancer patients treated on Tomotherapy when FW (field width), PF (pitch factor), modulation factor (MF) and treatment length (TL) were given.

Material and methods

The study was divided into two parts: building and verifying the model. To build a model, 160 treatment plans were created for 10 patients. The plans differed in combination of FW, PF and MF. For all plans a graph of beam-on time as a function of TL was created and a linear trend function was fitted. Equation for each trend line was determined and used in a correlation model. Finally, 62 plans verified the treatment time computation model – the real execution time was compared with our estimation and irradiation time calculated based on the equation provided by the manufacturer.

Results

A linear trend function was drawn and the coefficient of determination R² and the Pearson correlation coefficient r were calculated for each of the 8 trend lines corresponding to the adequate treatment plan. An equation to correct the model was determined to estimate more accurately the beam-on time for different MFs. From 62 verification treatment plans, only 5 disagreed by more than 60 s with the real time from the HT software. Whereas, for the equation provided by the manufacturer the discrepancy was observed in 16 cases.

Conclusions

Our study showed that the model can well predict the treatment time for a given TL, MF, FW and it can be used in clinical practice.     

Radiotherapy induced hip joint avascular necrosis—Two cases report

Background

Avascular necrosis (AVN) refers to the death of osteocytes and osteoblasts. Sites such as the femoral head, the head of the humerus and the mandibula with restricted access to local blood supply are particularly vulnerable to osteonecrosis.A combination of several factors is responsible for ischaemia and is associated with AVN: corticosteroids, alcohol abuse, Cushing''s syndrome, SLE, systemic vasculitis, RA, scleroderma, haemoglobinopathies, radiotherapy. Management is based on proper diagnosis and treatment – conservative, pharmacological or surgical.Radiotherapy has become an integral part of the therapeutic programme of cancer patients. However, early and late after-effects of irradiation still constitute a significant issue in clinical practice.

Aim

The aim of this report is to present two cases of acetabular protrusion and femoral head deformities after a therapeutic pelvic irradiation and draw physicians’ attention to that clinical problem which continues to be underestimated.

Materials and methods

This report documents two cases of acetabular protrusion and femoral head deformities after a therapeutic pelvic radiation.

Results

Avascular necrosis (AVN) constitutes a severe and challenging long-term complication in radiation oncology.

Conclusion

It is necessary to take into account bone structures among organ at risk (OAR) involved in irradiation fields. The detailed analysis of the dose distribution and the use of collimators allow to decrease the total dose to OAR.An adequate management, early diagnosis and prompt, proper treatment may protect patients from long-term morbidities.     

A Monte Carlo study on dose distribution validation of GZP6 60Co stepping source

Aim

Stepping source in brachytherapy systems is used to treat a target lesion longer than the effective treatment length of the source. Cancerous lesions in the cervix, esophagus and rectum are examples of such a target lesion.

Background

In this study, the stepping source of a GZP6 afterloading intracavitary brachytherapy unit was simulated using Monte Carlo (MC) simulation and the results were used for the validation of the GZP6 treatment planning system (TPS).

Materials and methods

The stepping source was simulated using MCNPX Monte Carlo code. Dose distributions in the longitudinal plane were obtained by using a matrix shift method for esophageal tumor lengths of 8 and 10 cm. A mesh tally has been employed for the absorbed dose calculation in a cylindrical water phantom. A total of 5 × 10⁸ photon histories were scored and the MC statistical error obtained was at the range of 0.008–3.5%, an average of 0.2%.

Results

The acquired MC and TPS isodose curves were compared and it was shown that the dose distributions in the longitudinal plane were relatively coincidental. In the transverse direction, a maximum dose difference of 7% and 5% was observed for tumor lengths of 8 and 10 cm, respectively.

Conclusion

Considering that the certified source activity is given with ±10% uncertainty, the obtained difference is reasonable. It can be concluded that the accuracy of the dose distributions produced by GZP6 TPS for the stepping source is acceptable for its clinical applications.     

Low Frequency Magnetic Fields Enhance Antitumor Immune Response against Mouse H22 Hepatocellular Carcinoma

Objective

Many studies have shown that magnetic fields (MF) inhibit tumor growth and influence the function of immune system. However, the effect of MF on mechanism of immunological function in tumor-bearing mice is still unclear.

Methods

In this study, tumor-bearing mice were prepared by subcutaneously inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor growth and the innate and adaptive immune parameters were measured.

Results

MF treatment could prolong survival time (n = 28, p<0.05) and inhibit tumor growth (n = 9, p<0.01) in tumor-bearing mice. Moreover, this MF suppressed tumor-induced production of cytokines including interleukin-6 (IL-6), granulocyte colony- stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) (n = 9–10, p<0.05 or 0.01). Furthermore, MF exposure was associated with activation of macrophages and dendritic cells, enhanced profiles of CD4⁺ T and CD8⁺ T lymphocytes, the balance of Th17/Treg and reduced inhibitory function of Treg cells (n = 9–10, p<0.05 or 0.01) in the mice model.

Conclusion

The inhibitory effect of MF on tumor growth was related to the improvement of immune function in the tumor-bearing mice.     

Extracranial stereotactic body radiotherapy. Review of main SBRT features and indications in primary tumors

Aim

Review of main SBRT features and indications in primary tumors.

Background

Stereotactic body radiotherapy has been developed in the last few years. SBRT allows the hypofractionated treatment of extra cranial tumors, using either a single or limited number of dose fractions, and resulting in the delivery of a high biological effective dose with low toxicity.

Material and methods

SBRT requires a high level of accuracy for all phases of the treatment process: effective patient immobilization, precise target localization, highly conformed dosimetry and image guided systems for treatment verification. The implementation of SBRT in routine requires a careful considering of organ motion. Gating and tracking are effective ways to do so, and less invasive technologies “fiducials free” have been developed. Due to the hypofractionated scheme, the physician must pay attention to new dosimetric constraints in organ at risk and new radiobiological models are needed to assess the optimal fractionation and dose schemes.

Results

Currently, SBRT is safe and effective to treat primary tumors, which are otherwise untreatable with conventional radiotherapy or surgery. SBRT has quickly developed because of its excellent results in terms of tolerance and its high locoregional control rates. SBRT indications in primary tumors, such as lung primary tumors, have become a standard of care for inoperable patients. SBRT seems to be effective in many others indications in curative or palliative intent such as liver primary tumors, and novel indications and strategies are currently emerging in prostate cancer, head and neck tumor recurrences or pelvis reirradiations.

Conclusion

Currently, SBRT is mainly used when there is no other therapeutic alternative for the patient. This is due to the lack of randomized trials in these settings. However, the results shown in retrospective studies let us hope to impose SBRT as a new standard of care for many patients in the next few years.     

Radiotherapy applications of patients with malignant mesothelioma: A single center experience

Background

In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms.

Aim

The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma.

Materials and methods

Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy.

Results

Prophylactic radiation was applied to 27 patients with 4–15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6–18 MV photon and/or 4–12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases.

Conclusion

Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes.     

Intraoperative radiation therapy as part of breast conserving therapy of early breast cancer—Results of one-year follow-up

Aim

The aim of this study was to assess the therapeutic effect of intraoperative radiotherapy, describe the method, and examine the occurrence of side effects and quality of life.

Background

Breast conserving therapy has recently become a standard treatment modality in patients with early invasive cancer. Radiotherapy, along with surgery, is an integral part of such treatment. The important thing of radiotherapy is to deliver a high dose to the tumour bed. One of the methods is the intraoperative radiotherapy.

Materials and methods

The analysis comprised sixty Tis-T2N0-1A breast cancer patients treated with breast conserving surgery. Patients’ mean age was 57 years (range: 32–73 years). Intraoperative radiation therapy was delivered in the operating theatre during surgery and involved a single dose of 10 Gy with an electron beam of 4, 6, 9 or 12 MeV. After that, all patients were treated with whole breast irradiation. During one year observation photos and side effects examination were made.

Results

Physical and imaging examinations performed during a one-year follow-up revealed no local or distant relapse and good tolerance of IORT. Acute mild responses to the radiotherapy occurred in 23.3% of patients. Based on the examination, a good and very good cosmetic effect was found in 78.3%, with 83.3% of patients evaluating their treatment effects in the same way.

Conclusions

Due to its exceptional physical and radiobiological properties, intraoperative radiation therapy can be a good alternative to other methods of boosting dose to the post-operative site in management of low stage breast cancer, enabling a precise therapy to the tumour bed.     

Correlation of Plasma FL Expression with Bone Marrow Irradiation Dose

Purpose

Ablative bone marrow irradiation is an integral part of hematopoietic stem cell transplantation. These treatment regimens are based on classically held models of radiation dose and the bone marrow response. Flt-3 ligand (FL) has been suggested as a marker of hematopoiesis and bone marrow status but the kinetics of its response to bone marrow irradiation has yet to be fully characterized. In the current study, we examine plasma FL response to total body and partial body irradiation in mice and its relationship with irradiation dose, time of collection and pattern of bone marrow exposure.

Materials/Methods

C57BL6 mice received a single whole body or partial body irradiation dose of 1–8 Gy. Plasma was collected by mandibular or cardiac puncture at 24, 48 and 72 hr post-irradiation as well as 1–3 weeks post-irradiation. FL levels were determined via ELISA assay and used to generate two models: a linear regression model and a gated values model correlating plasma FL levels with radiation dose.

Results

At all doses between 1–8 Gy, plasma FL levels were greater than control and the level of FL increased proportionally to the total body irradiation dose. Differences in FL levels were statistically significant at each dose and at all time points. Partial body irradiation of the trunk areas, encompassing the bulk of the hematopoietically active bone marrow, resulted in significantly increased FL levels over control but irradiation of only the head or extremities did not. FL levels were used to generate a dose prediction model for total body irradiation. In a blinded study, the model differentiated mice into dose received cohorts of 1, 4 or 8 Gy based on plasma FL levels at 24 or 72 hrs post-irradiation.

Conclusion

Our findings indicate that plasma FL levels might be used as a marker of hematopoietically active bone marrow and radiation exposure in mice.