Gene expression signature for early prediction of late occurring pancytopenia in irradiated baboons.

Based on gene expression changes measured in the peripheral blood within the first 2 days after irradiation, we predicted a pancytopenia in a baboon model. Eighteen baboons were irradiated with 2.5 or 5 Gy. According to changes in blood cell counts, the surviving baboons (n = 17) exhibited a hematological acute radiation syndrome (HARS) either with or without a pancytopenia. We used a two stage study design where stage I was a whole genome screen (microarrays) for mRNA combined with a qRT-PCR platform for simultaneous detection of 667 miRNAs using a part of the samples. Candidate mRNAs and miRNAs differentially upregulated or downregulated (>2-fold, p < 0.05) during the first 2 days after irradiation were chosen for validation in stage II using the remaining samples and using throughout more sensitive qRT-PCR. We detected about twice as many upregulated (mean 2128) than downregulated genes (mean 789) in baboons developing an HARS either with or without a pancytopenia. From 51 candidate mRNAs altogether, 11 mRNAs were validated using qRT-PCR. These mRNAs showed only significant differences between HARS groups and H0, but not between HARS groups with and without pancytopenia. Six miRNA species (e.g., miR-574-3p, p = 0.009, ROC = 0.94) revealed significant gene expression differences between HARS groups with and without pancytopenia and are known to sensitize irradiated cells. Hence, in particular, the newly identified miRNA species for prediction of pancytopenia will support the medical management decision making.

Pharmacokinetics of doxycycline in tilapia (Oreochromis aureus × Oreochromis niloticus) after intravenous and oral administration.

The pharmacokinetics of doxycycline was studied in plasma after a single dose (20 mg/kg) of intravenous or oral administration to tilapia (Oreochromis aureus × Oreochromis niloticus) reared in fresh water at 24 °C. Plasma samples were collected from six fish per sampling point. Doxycycline concentrations were determined by high-performance liquid chromatography with a 0.005 µg/mL limit of detection, then were subjected to noncompartmental analysis. Following oral administration, the double-peak phenomenon was observed, and the first (Cmax1 ) and second (Cmax2) peaks were 1.99 ± 0.43 µg/mL at 2.0 h and 2.27 ± 0.38 µg/mL at 24.0 h, respectively. After the intravenous injection, a Cmax2 (12.12 ± 1.97 µg/mL) was also observed, and initial concentration of 45.76 µg/mL, apparent elimination rate constant (λz) of 0.018 per h, apparent elimination half-life (t1/2λz) of 39.0 h, systemic total body clearance (Cl) of 41.28 mL/h/kg, volume of distribution (Vz) of 2323.21 mL/kg, and volume of distribution at steady-state (Vss) of 1356.69 mL/kg were determined, respectively. While after oral administration, the λz, t1/2λz, and bioavailability of doxycycline were 0.009 per h, 77.2 h, and 23.41%, respectively. It was shown that doxycycline was relatively slowly and incompletely absorbed, extensively distributed, and slowly eliminated in tilapia, in addition, doxycycline might undergo enterohepatic recycling in tilapia.

Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice.

Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.

Long-term remission and survival in dogs with high-grade, B cell lymphoma treated with chemotherapy with or without sequential low-dose rate half-body irradiation.

BACKGROUND: Standard of care for dogs with high-grade lymphoma, multiagent chemotherapy, achieves good initial responses but long-term remissions are infrequent; previous studies using half-body irradiation suggest improved long-term outcomes. HYPOTHESIS: The addition of low-dose rate half-body irradiation would improve outcomes in dogs with B-cell lymphoma. ANIMALS: Client-owned dogs with stage III or higher, substage a, B-cell lymphoma that achieved complete remission after 4 doses of multiagent chemotherapy. METHODS: A case-controlled design comparing 2-year remission and survival rates between dogs treated with CHOP-based chemotherapy and those treated with chemotherapy and sequential low-dose rate half-body irradiation. RESULTS: Thirty-eight dogs were enrolled with 18 included in final analysis, 9 prospectively-enrolled dogs and 9 case-matched historical controls. The irradiation cohort's 2-year disease-free rate was 56% whereas median duration exceeded the 730-day study period compared with 0% and 261 days in the chemotherapy only group. Remission duration significantly differed between cohorts (P < .01), hazard ratio 0.218 (95% CI: 0.06-0.77). The irradiation cohort's 2-year survival rate was 78% with median overall survival duration exceeding the 730 day study period compared with 11% and 286 days in the chemotherapy only group. Overall survival time significantly differed between cohorts (P < .02), hazard ratio 0.173 (95% CI: 0.03-0.839). CONCLUSIONS AND CLINICAL IMPORTANCE: The improved long-term outcome achieved by dogs administered sequential low-dose rate half-body irradiation in this study is similar to previous observational studies. Where long-term remission is sought in dogs with B-cell lymphoma low-dose rate half-body irradiation could be considered in addition to standard chemotherapy.

Prevention and treatment of vitamin D deficiency in Dutch psychogeriatric nursing home residents by weekly half-body UVB exposure after showering: a pilot study.

BACKGROUND: in older people, induction of cutaneous vitamin D production by ultraviolet B (UVB) exposure may be preferable to oral supplementation: it cannot cause toxic levels, it helps to prevent polypharmacy and, moreover, there are indications that UVB exposure has beneficial effects on health and well being by mechanisms other than the vitamin D pathway alone. OBJECTIVE: the aim of this pilot study is to investigate whether weekly, half-body, UVB irradiation after showering can increase serum 25-hydroxyvitamin D (25(OH)D) to sufficient levels, in a Dutch psychogeriatric nursing home population. METHOD: subjects were eight psychogeriatric nursing home patients, mean age: 79 ± 8. Exclusion criteria were going outdoors into the sun more than once a week, the presence of actinic or cancer skin lesions and known resistance to body contact. The intervention consisted of weekly half-body UVB irradiation, after showering, over 8 weeks, with 0.5 minimal erythemal dose (MED). Main outcome measures were change in fasting serum levels of 25(OH)D and parathyroid hormone (PTH) at 0, 2, 4 and 8 weeks. RESULTS: at baseline, mean serum 25(OH)D was 28.5 nmol/l. Mean serum 25(OH)D levels increased to 46.5 nmol/l. Median serum PTH levels decreased by 20% after 8 weeks of treatment. CONCLUSION: an 8 week course of weekly, frontal half-body irradiation with UVB, at 0.5 MED, leads to an significant increase in 25(OH)D serum levels, but this period is too short to reach vitamin D sufficiency.

Densities of glutamatergic and GABAergic presynaptic terminals are altered in experimental cortical dysplasia.

PURPOSE: Cortical dysplasia (CD) is a major cause of epilepsy in children and adults, but underlying mechanisms of epileptogenesis in this disorder are poorly understood. We have utilized the irradiated rat model to study an injury-based form of diffuse CD in rats. Prior studies in this model have shown reduced numbers of γ-aminobutyric acid (GABA)ergic interneurons and reduced inhibitory synaptic currents in pyramidal cells in CD. We analyzed the number of excitatory and inhibitory presynaptic terminals in the neocortex of irradiated rats to better characterize altered connectivity in experimental CD. METHODS: Antibodies to vesicular glutamate transporter 1 (VGLUT1), vesicular glutamate transporter 2 (VGLUT2), vesicular GABA transporter (VGAT), and parvalbumin (PV) were used to quantify glutamatergic and GABAergic presynaptic terminals in control and dysplastic cortex. RESULTS: We found that the density of VGLUT1 terminals was increased in CD in comparison to layers IV, V, and VI in control cortex. VGLUT2 terminals were increased in CD compared to layers IV and VI. VGAT terminals were reduced in CD compared to layers II/III, IV, and V in controls as were PV-immunoreactive somata and terminals. DISCUSSION: These findings suggest an overall increase in excitatory synaptic connectivity and decrease in inhibitory synaptic connectivity in CD in irradiated rat. We propose that these changes contribute to hyperexcitability in these animals and may contribute to epileptogenicity in some forms of human CD.

Clinical tolerance in large field radiotherapy--the knowledge gained over the last ten years.

Malignant disorders are still far from being successfully managed in spite of the apparent progress achieved by surgical treatment, high energy radiotherapy (RT) and chemotherapy (CHT). They keep being the second most frequent cause of lethal outcomes both in Bulgaria and in most countries of the world. One of the promising approaches to increasing the efficaciousness of treatment is development and use of methods that are in full accord with the modern requirements of a complex therapy. Over the last fifty years, large field radiation techniques, applied as systemic therapy in oncology, have been investigated and established. These techniques show the transition in oncology to using actively various variants of large field radiotherapy (LFR), the "heavy artillery" of oncoradiologic practice, as an alternative or adjunct therapy to chemotherapy (CHT). In the present paper we review the current knowledge in the field and present the clinical experience accumulated over the last ten years with respect to clinical tolerance in the major large-field radiotherapy techniques--total body irradiation, half body irradiation, whole abdominal irradiation, total and partial lymphoid irradiation. Described in detail are the contemporary knowledge about clinical and hematologic tolerance in total body irradiation as part of the myelo- and nonmyeloablative conditioning regimens as well as in half body irradiation as a systemic therapy in oncology. We also present the amassed experience in clinical tolerance in partial body irradiation in the form of whole abdominal and total or partial lymphoid irradiation. Another point worth noting based again on the experience gained over the last ten years is that for LFR we need to develop a radiotherapy technique that is designed carefully to achieve an optimal therapeutic effect that should include the disease control, good clinical tolerance and reduction of post-radiotherapy sequelae.

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.

Effects of irradiation on cytokine production in a mouse model of Behçet's disease.

OBJECTIVE: Low-dose whole-body irradiation is known to have anti-inflammatory effects. The objectives of this study were to verify that cytokine augmentation is induced by irradiation in vivo, and to assess the effectiveness of radiation in treating Behçet's disease (BD). METHODS: Whole-body and half-body irradiation with single doses of 10cGy, 2Gy and 10Gy were delivered to normal mice, and cytokine and chemokine levels were analyzed in PBMC and sera. BD-like mice were treated with low-dose, half-body 10cGy irradiation. RESULTS: In normal mice, PBMC cytokine mRNA levels peaked four days after irradiation. Of the cytokines and chemokines examined, the levels of IL-4, IL-6, IL-12p40, TNF-alpha, TGF-b, MIP-1alpha and IL-18 were all influenced by radiation treatment. Of these, IL-4, an ameliorating factor for BD, was the most elevated following low-dose irradiation (10cGy group). FACS analysis showed intracellular IL-4-staining of 7.24+/-0.92% of PBMC from irradiated mice compared to 1.3+/-0.1% from non-irradiated, normal mice (p<0.005). Serum IL-4 levels were also significantly increased (6.08+/-1.7 pg/ml) relative to control (1.83+/-0.8; p<0.005). CONCLUSION: Augmentation of cytokine production may contribute to the anti-inflammatory effects of low dose irradiation and amelioration of BD symptoms in this mouse model.

Half body irradiation of patients with multiple bone metastases: a phase II trial.

AIM OF STUDY: The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. PATIENTS AND METHODS: A total of 44 patients received lower (n = 37), upper (n = 5), or sequential HBI (n = 2). The dose for lower HBI was 8 Gy in one fraction and for upper HBI 7 Gy in one fraction, with reduction of the lung dose to 6 Gy in one fraction by partial shielding. The majority of patients (n = 41) were males with prostate cancers (93%). Outcome and side effects were measured by the EORTC Quality of Life Questionnaire C30 (QLQ-C30), and by the doctors' toxicity scores in the medical record. Pain relief was defined as a reduction of more than 10 points on the QLQ-C30 scale. Evaluations were performed before and 2, 4, 8, 16, and 24 weeks after treatment. RESULTS: Relief of pain was observed in 76% of the patients receiving HBI with 8.8% of the patients experiencing complete pain relief with no residual pain in the treated field. For most patients, the pain relief was lasting throughout the follow-up period. About one third of the patients were able to reduce their intake of analgesics. Grade 1-2 diarrhoea was the most common side effect observed in 49% of the patients two weeks after treatment. Mild pulmonary symptoms (grade 1-2) were observed in four of seven patients receiving upper HBI. No clear effect was observed on the patients' global quality of life. CONCLUSION: Single fraction HBI is safe and effective providing long lasting pain reduction in 76% of patients with multiple bone metastases.

Half-body irradiation: a safe and acceptable treatment.

BACKGROUND: The aim of this study was an evaluation of the acute toxicity of single-fraction half-body irradiation (HBI). MATERIAL/METHODS: The material comprised 92 patients. Upper, lower, and middle HBI (UHBI, LHBI, MHBI) were performed in 34, 49, and 9 cases, respectively, with 6 Gy delivered for UHBI, 8 Gy for LHBI, and 6 or 8 Gy for MHBI. The patients' weights were measured on the HBI day. Two weeks later their weights and blood parameters were checked and diarrhea, skin toxicity (scale: 0-4), and nausea and vomiting intensity (scale: 0-3) were evaluated using WHO Toxicity Criteria. Items of all the evaluated symptoms were summarized and the means of the sums were calculated. RESULTS: Mean weight loss after HBI was 0.7 kg. One patient had grade 4 toxicity (thrombopenia). Grade 3 toxicity appeared in 9 cases (nausea and vomiting in 5, leukopenia in 1, and thrombopenia in 3). None had radiation pneumonitis. The means of the summarized items were 1.9 for UHBI than 1.4 for LHBI. The means of the summarized items were 1.6 for 8 Gy and 1.8 for 6 Gy. UHBI provoked a higher incidence and intensity of nausea and vomiting and LHBI caused a higher incidence and intensity of diarrhea. The remaining evaluated symptoms of toxicity were similar for irradiations of both halves of the body. CONCLUSIONS: From these results one can conclude that single-dose (6-8 Gy) HBI is a safe treatment, causing a low percentage of low-level, patient-acceptable adverse radiation sequels.

Sequential low-dose rate half-body irradiation and chemotherapy for the treatment of canine multicentric lymphoma.

BACKGROUND: Sequential half-body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2-week interradiation interval is possible in most dogs receiving low-dose rate irradiation (LDRI) protocols at 6 Gy dose levels. HYPOTHESIS: LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)-based chemotherapy protocol is effective for the treatment of lymphoma in dogs. ANIMALS: Thirty-eight client-owned animals diagnosed with multicentric lymphoma. METHODS: Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy. RESULTS: The median 1st remission was 410 days (95% confidence interval [CI] 241-803 days). The 1-, 2-, and 3-year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334-1,223 days). The 1-, 2-, and 3-year survival rates were 66, 47, and 44%. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggest that treatment intensification by a 2-week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.

Comparison of serum iohexol clearance and plasma creatinine clearance in clinically normal horses.

Objective-To determine whether a limited sampling time method based on serum iohexol clearance (Cl(iohexol)) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Cl(creatinine)). Animals-10 clinically normal adult horses. Procedures-A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cl(iohexol) and plasma Cl(creatinine) was compared with limits of agreement plots. Results-Values obtained for plasma Cl(creatinine) ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cl(iohexol) was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods. Conclusions and Clinical Relevance-Use of serum Cl(iohexol) yielded estimates of GFR in clinically normal adult horses similar to those for plasma Cl(creatinine). This study was the first step in the evaluation of the use of serum Cl(iohexol) for estimating GFR in adult horses.

Accuracy of Dose Calculation for Hemibody Treatments at Extended Distance Using a Commercial Treatment Planning System.

PURPOSE: The objective of this study was to assess the accuracy of monitor units (MUs) calculation for extended distance hemibody (HB) treatments in Pinnacle, a commercial treatment planning system. The agreement between planning and delivery of low-dose radiation therapy (LD-RT) was assessed with direct comparison to expected doses and tabulated total body irradiation (TBI) calculations. Studies over the past decades indicate that LD-RT has strong potential to be an effective treatment modality for cancer patients with minimal toxicities. This physics-based study aims to provide sufficient conclusions required for prospective clinical studies involving HB irradiation regimes. Specifically, this study may provide reassurance of MU calculation in the Pinnacle system for an upcoming trial regarding nontargeted LD-RT for recurrent prostate cancer. METHODS: Water phantom: A plan was created in Pinnacle to deliver 100 cGy to a water phantom with an ion chamber mount. A percent depth dose was obtained. Electrometer readings were recorded with each irradiation of 400 MUs at varying ion chamber depths at extended distance. A percent depth dose was created from tabulated data. Anthropomorphic phantom: A parallel opposed pair plan was created in Pinnacle to deliver 150 cGy over 10 fractions to the umbilicus of the phantom at 4 m extended source-to-surface distance. The MUs required to deliver 150 cGy, as per Pinnacle were delivered to the phantom using 6 MV photons. Thermoluminescent dosimeters (TLD), used to measure exposure using light-emitting crystals, were placed along six reference locations (lung, mid-T-spine, abdomen, mid-pelvis, thigh, and mid-abdomen) on the phantom. TLD measurements were then compared with the Pinnacle-derived ROI mean doses. For experiment 2, TBI calculation factors were used to determine the required MUs to deliver 150 cGy to the prescription (Rx) point. The calculated MUs were delivered, and TLD readings were recorded to compare the level of agreement of using TBI calculations for HB treatments. RESULTS: Water phantom: Pinnacle did not accurately estimate dmax at extended distance; however, it did accurately estimate the dose past dmax. Anthropomorphic phantom: A 10% variation to expected dose was deemed significant. Both Pinnacle and TBI calculations were accurate methods of planning HB LD-RT treatment, with insignificant difference. Pinnacle's overall average variation across ROIs was borderline significant at 12.1%. CONCLUSION: At extended source-to-surface distance, Pinnacle inaccurately estimated the entrance dose and dmax. Anthropomorphic phantom studies indicated borderline significant variation, as per the implemented 10% limit. TBI calculations presented similar conclusions. For purposes of HB LD-RT, a borderline 10% variation will have insignificant impact to the patient's ability to tolerate treatment. Trial-eligible prostate cancer patients are currently being treated for HB LD-RT at the Juravinski Cancer Centre.

Use of a modified hemi-body irradiation technique for metastatic carcinoma of the prostate: report of a 10-year experience.

AIMS: To determine whether patients receiving hemi-body irradiation required further treatment to painful bone sites out with the radiation field (skull or lower leg), whether patients required further treatment to areas within the treated radiation field for pain or new skeletal events, and whether the treatment outcome was successful in terms of pain control. Toxicities, the need for transfusions and survival were also analysed. MATERIALS AND METHODS: In our retrospective review, 103 men aged 50-87 years, with skeletal metastases from prostate cancer, received modified hemi-body irradiation (HBI) during a consecutive 10-year period, using the same radiotherapy technique and dose. The upper HBI field excluded the region above the ramus of the mandible and the lower HBI field excluded the lower limb below the knee. A successful outcome was determined by assessing the pain response in combination with a change in analgesic intake. RESULTS: Twenty patients received upper HBI; 17/20 (85%) had a successful outcome at the 6-week review, sustained in 94.1% at the final follow-up with no need for radiotherapy to the skull. Thirty-eight patients received lower HBI; 26/38 (68.4%) had a successful outcome at the 6-week review, sustained in 80.8% at the final follow-up with no need for radiotherapy to the lower leg. Forty-five patients received sequential HBI; 33/45 (73.3%) had a successful outcome at the 6-week review, sustained in 87.9% at the final follow-up, with three patients requiring further radiotherapy to the skull (2/45) or lower leg (1/45). Only 5/103 patients (4.8%) developed new skeletal events in the treated area. Toxicity and transfusion requirements were minimal. CONCLUSIONS: Modifying the field size for single-fraction HBI does not have a significant effect on the final outcome of treatment, namely pain control and a need for additional radiotherapy. In our experience, modified HBI should be considered in patients with multiple bone pain sites, especially if they will probably require several visits for localised radiotherapy to single painful bone sites within a short period of time.

An evaluation of half-body irradiation in the treatment of widespread, painful metastatic bone disease.

AIMS: Evaluation of analgesic uptake, pain intensity, and quality-of-life changes after half-body irradiation of patients with bone metastases. MATERIAL AND METHODS: Ninety-five patients (97 irradiations) were treated with single half-body irradiation fraction (3-8 Gy). Thirty-three patients had upper-half-body irradiation, 55 lower-half-body irradiation and 9 middle-half-body irradiation. The patients were examined on the day of irradiation, 2 and 4 weeks later, and then once a month. The intake of analgesics, pain level (from 0 to 10), and the quality of life (EORTC QLQ-C30) were evaluated. The fluctuations of pain levels and the particular scaling values of QLQ-C30 during a one-year period were analyzed (Kendall tau correlation). RESULTS: Over the course of 5 months, the incidence of patients using strong opioids decreased from 43.8% to 33.3%, and the incidence of patients who did not need to resort to analgesics increased from 6.7% to 25%. The mean pain level decreased from 6.1 points (half-body irradiation) to 3.1 points 2 weeks later. An inverse correlation between pain level readings and time was statistically significant. An increase was observed in the values of the five functional scales as reflected on the EORTC QLQ-C30 questionnaire (four of which correlated significantly with the observation time). A similar situation prevailed with respect to global health status. A decrease was observed in most of the values on the symptoms scales; 6 saw a significant decrease, in correlation with the follow-up. Correlations were also found between pain intensity and functionality, and between symptoms scales readings and global health status. CONCLUSIONS: Half-body irradiation of cancer patients suffering from painful multiple bone dissemination is an effective and simple treatment modality that affords significant quality-of-life improvement and pain relief, thus allowing for a reduction in the use of strong analgesics.

A novel Hemi-Body Irradiation technique using electron beams (HBIe-).

PURPOSE: Certain radiation responsive skin diseases may develop symptoms on the upper or the lower half of the body. The concept of a novel Hemi-Body Electron Irradiation (HBIe-) technique, described in this work, provides a low cost, LINAC based, intermediate treatment option in between extremely localized and Total Skin irradiation techniques. MATERIALS AND METHODS: The HBIe- technique, developed in our department, incorporates a custom crafted treatment chamber equipped with adjustable Pb shielding and a single electron beam in extended Source-Skin Distance (SSD) setup. The patient is positioned in 'Stanford' technique positions. The geometrical setup provides both optimal dose homogeneity and dose deposition up to a depth of 2 cm. To confirm this, the following characteristics were measured and evaluated: a) percentage depth dose (PDD) on the treatment plane produced by a single electron beam at perpendicular incidence for six fields at 'Stanford' angles, b) 2D profile of the entrance dose on the treatment plane produced by a single field and c) the total surface dose on an anthropomorphic phantom delivered by all 6 fields. RESULTS: The resulting homogeneity of the surface dose in the treatment plane for an average patient was 5-6%, while surface dose homogeneity on the anthropomorphic phantom was 7% for both the upper and the lower HBIe- variants. The total PDD exhibits an almost linear decrease to a practical range of 2 g/cm2. CONCLUSION: In conclusion, HBIe- was proven effective in delivering the prescribed dose to the target area, while protecting the healthy skin.

Efficacy and safety of 3D-conformal half body irradiation in patients with multiple bone metastases.

Half-body irradiation (HBI) represented a standard treatment for multiple painful bone metastases (BMs). However, its use has progressively reduced due to the associated toxicity rates. The aim of this paper was to evaluate HBI delivered by conformal radiotherapy (RT) technique in a large patients population with widespread BMs. HBI was delivered in 3 Gy fractions, bid, ≥ 6 h apart, on 2 consecutive days (total dose: 12 Gy) using 3-dimensional conformal RT (3D-CRT) box technique. The target included pelvic bones, lumbar-sacral vertebrae and upper third of femurs. Acute and late toxicity was scored based on RTOG and EORTC-RTOG scales, respectively. Pain was evaluated using the Pain-Drug scores and the Visual Analog Scale (VAS). One hundred and eighty patients were eligible for inclusion in this retrospective analysis. Grade 3 and 4 acute toxicity rates were 1.1% and 0.0%, respectively. Mean VAS before and after HBI was 5.3 versus 2.7, respectively (p: 0.0001). Based on VAS, 37.5% of patients showed complete pain relief (VAS: 0) while 38.1% had partial response (≥ 2-point VAS reduction). Overall, Pain and Drug Score reduction was observed in 76.3% and 50.4% of patients, respectively. 1-, 2-, and 3-year pain progression free survival was 77.0%, 63.4%, and 52.7%, respectively. Thirty patients (16.7%) underwent RT retreatment on the same site with median 15.9 months interval (range 2-126 months). HBI delivered with 3D-CRT technique is safe and effective. It provides long lasting pain control in patients with multiple BMs with negligible rates of relevant toxicity.

A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy.

PURPOSE: Over 20,000 patients have been treated with partial breast irradiation (PBI) using the MammoSite balloon brachytherapy applicator (IBB). Recently, a new form of balloon-based PBI, Xoft Axxent electronic brachytherapy (KVB), which uses a 50-kV x-ray source, has been introduced. This analysis was undertaken to dosimetrically compare the results of treatment using these two methods of PBI. METHODS AND MATERIALS: The study population consisted of 15 patients previously treated with IBB. The planning CT scans from these 15 patients were used to construct hypothetical treatment plans using the source characteristics of the KVB device. The plans were then compared using the dosimetric parameters discussed below. RESULTS: The mean %V(90) was 99.6% vs. 99.0% (p=nonsignificant [ns]), the mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 41.8% vs. 59.4% (p<0.05), the mean %V(200) was 11.3% vs. 32.0% (p<0.05), and the mean %V(300) was 0.4% vs. 6.7% (p<0.05) for the IBB and KVB methods, respectively. The mean ipsilateral breast %V(50) was 19.8% vs. 13.0% (p<0.05), the mean ipsilateral lung %V(30) was 3.7% vs. 1.1% (p<0.05), and the mean heart %V(5) was 59.2% vs. 9.4% (p<0.05) for the IBB and KVB methods, respectively. CONCLUSIONS: The IBB and KVB methods of PBI offer comparable target volume coverage; however, the KVB method is associated with an increased volume of breast tissue in the high-dose regions and a decreased dose to the adjacent normal tissues.

High-dose-rate interstitial brachytherapy in recurrent and previously irradiated head and neck cancers--preliminary results.

PURPOSE: Although high-dose-rate brachytherapy (HDRBT) offers significant advantages over low dose rate brachytherapy, there are scant data on improved local control (LC) and treatment-related complications in patients with recurrent head and neck (H&N) cancers. We report our preliminary results in patients with recurrent H&N cancers treated with interstitial HDRBT. METHODS AND MATERIALS: Thirty patients with recurrent H&N cancers were treated with HDRBT between September 2003 and October 2005. Seventy-seven percent (23/30) of the patients had either local or regional recurrence in the area of previous external beam radiation therapy. The treatment sites were oral cavity/oropharynx (11/30), neck (10/30), face/nasal cavity (6/30), and parotid bed (3/30). Whereas 18 patients underwent surgical resection followed by HDRBT, 3 patients were treated with combined external beam radiation and HDRBT, and the remaining 9 were treated with HDRBT alone. The dose and fractionation schedules used were 3.4Gy twice per day (b.i.d.) to 34Gy for postoperative cases, 4Gy b.i.d. to 20Gy when combined with 40-50Gy external beam, and 4Gy b.i.d. to 40Gy for definitive treatment. HDRBT was initiated 5 days after catheter placement to allow for tissue healing. RESULTS: With a median followup of 12 months, 6 local recurrences were observed 1-10 months after the procedure. The 2-year LC and overall survival outcomes for the entire group were 71% and 63%, respectively. Patients treated with surgical resection and HDRBT had an improved 2-year LC compared to the patients treated with HDRBT+/-external beam radiation alone (88% vs. 40%, p=0.05). Six Grade II and four Grade III complications were noted in five patients, all observed in the postoperative HDRBT group. CONCLUSION: The preliminary results of HDRBT indicate an acceptable LC and morbidity in recurrent H&N cancers. A planned surgical resection followed by HDRBT is associated with improved tumor control in these high-risk patients. Based on these encouraging results, prospective clinical trials are warranted using HDRBT in recurrent H&N cancers to decrease late toxicity.